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Is additional treatment needed, pretransplant, for r/r AML?
This critically important question was debated at the annual meeting of the Society of Hematologic Oncology, held in Houston and online.
Johannes Schetelig, MD, argued in favor of proceeding to transplant, even without a complete remission.
“In the past, I’ve told many patients with relapsed or refractory AML that we do need to induce a [complete remission] prior to transplantation,” said Dr. Schetelig, from the Clinical Trials Unit at DKMS in Dresden, Germany. “But is it true?”
According to findings from a recent randomized trial, it may not be. The trial, led by Dr. Schetelig, found that patients with AML who received immediate allogeneic transplant without first having achieved a complete response following induction therapy did just as well as those who received intensive salvage induction therapy to establish remission before transplant.
If this finding holds, it “completely upends” how experts have traditionally approached patients with AML, Mikkael A. Sekeres, MD, of the University of Miami said at a conference press briefing last year.
The phase 3 ASAP trial, presented at last year’s American Society of Hematology meeting, included patients with AML who had had a poor response or who had experienced a relapse after first induction therapy. Patients were randomly assigned to a remission-induction strategy prior to allogeneic stem cell transplant (alloHCT) or a disease-control approach of watchful waiting followed by sequential conditioning and alloHCT. The primary endpoint was treatment success, defined as a complete response at day 56 following alloHCT.
In an intention-to-treat analysis, 83.5% of patients in the disease-control group and 81% in the remission-induction group achieved treatment success. Similarly, in the per-protocol analysis, 84.1% and 81.3%, respectively, achieved a complete response at day 56 after alloHCT. After a median follow-up of 4 years, there were no differences in leukemia-free survival or overall survival between the two groups.
Another advantage to forgoing an intensive salvage induction regimen: Patients in the disease-control arm experienced significantly fewer severe adverse events (23% vs. 64% in the remission induction arm) and spent a mean of 27 fewer days in the hospital prior to transplantation.
At last year’s press briefing, Dr. Schetelig said his team did not expect that a complete response on day 56 after transplantation would translate into “equal long-term benefit” for these groups. “This is what I was really astonished about,” he said.
Delving further into the findings, Dr. Schetelig explained that in the remission-induction arm patients who had had a complete response prior to transplantation demonstrated significantly better overall survival at 4 years than those who had not had a complete response at that point: 60% vs. 40%.
The study also revealed that in the disease-control arm, for patients under watchful waiting who did not need low-dose cytarabine and mitoxantrone for disease control, overall survival outcomes were similar to those of patients in the remission-induction arm who achieved a complete response.
These findings suggest that patients who can be bridged with watchful waiting may have a more favorable disease biology, and chemosensitivity could just be a biomarker for disease biology. In other words, “AML biology matters for transplant outcome and not tumor load,” Dr. Schetelig explained.
A recent study that found that having minimal residual disease (MRD) prior to transplant “had no independent effect on leukemia-free survival” supports this idea, he added.
Overall, Dr. Schetelig concluded that data from the ASAP trial suggest that watchful waiting prior to alloHCT represents “an alternative” for some patients.
Counterpoint: Aim for complete remission
Ronald B. Walter, MD, PhD, argued the counterpoint: that residual disease before transplantation is associated with worse posttransplant outcomes and represents a meaningful pretransplant therapeutic target.
The goal of intensifying treatment for patients with residual disease is to erase disease vestiges prior to transplantation.
“The idea is that by doing so you might optimize the benefit-to-risk ratio and ultimately improve outcomes,” said Dr. Walter, of the translational science and therapeutics division at the Fred Hutchinson Cancer Research Center in Seattle.
Several reports support this view that patients who are MRD negative at the time of transplant have significantly better survival outcomes than patients with residual disease who undergo transplant.
A 2016 study from Dr. Walter and colleagues at Fred Hutchinson, for instance, found that 3-year overall survival was significantly higher among patients with no MRD who underwent myeloablative alloHCT: 73% vs. 26% of those in MRD-positive morphologic remission and 23% of patients with active AML.
Another study, published the year before by a different research team, also revealed that “adult patients with AML in morphologic [complete remission] but with detectable MRD who undergo alloHCT have poor outcomes, which approximates those who undergo transplantation with active disease,” the authors of the 2015 study wrote in a commentary highlighting findings from both studies.
Still, providing intensive therapy prior to transplant comes with drawbacks, Dr. Walter noted. These downsides include potential toxicity from more intense therapy, which may prevent further therapy with curative intent, as well as the possibility that deintensifying therapy could lead to difficult-to-treat relapse.
It may, however, be possible to reduce the intensity of therapy before transplant and still achieve good outcomes after transplant, though the data remain mixed.
One trial found that a reduced-intensity conditioning regimen was associated with a greater risk of relapse post transplant and worse overall survival, compared with standard myeloablative conditioning.
However, another recent trial in which patients with AML or high-risk myelodysplastic syndrome were randomly assigned to either a reduced-intensity conditioning regimen or an intensified version of that regimen prior to transplant demonstrated no difference in relapse rates and overall survival, regardless of patients’ MRD status prior to transplant.
“To me, it’s still key to go into transplant with as little disease as possible,” Dr. Walter said. How much value there is in targeted treatment to further reduce disease burden prior to transplant “will really require further careful study,” he said.
The ASAP trial was sponsored by DKMS. Dr. Schetelig has received honoraria from BeiGene, BMS, Janssen, AstraZeneca, AbbVie, and DKMS. Dr. Walter reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
This critically important question was debated at the annual meeting of the Society of Hematologic Oncology, held in Houston and online.
Johannes Schetelig, MD, argued in favor of proceeding to transplant, even without a complete remission.
“In the past, I’ve told many patients with relapsed or refractory AML that we do need to induce a [complete remission] prior to transplantation,” said Dr. Schetelig, from the Clinical Trials Unit at DKMS in Dresden, Germany. “But is it true?”
According to findings from a recent randomized trial, it may not be. The trial, led by Dr. Schetelig, found that patients with AML who received immediate allogeneic transplant without first having achieved a complete response following induction therapy did just as well as those who received intensive salvage induction therapy to establish remission before transplant.
If this finding holds, it “completely upends” how experts have traditionally approached patients with AML, Mikkael A. Sekeres, MD, of the University of Miami said at a conference press briefing last year.
The phase 3 ASAP trial, presented at last year’s American Society of Hematology meeting, included patients with AML who had had a poor response or who had experienced a relapse after first induction therapy. Patients were randomly assigned to a remission-induction strategy prior to allogeneic stem cell transplant (alloHCT) or a disease-control approach of watchful waiting followed by sequential conditioning and alloHCT. The primary endpoint was treatment success, defined as a complete response at day 56 following alloHCT.
In an intention-to-treat analysis, 83.5% of patients in the disease-control group and 81% in the remission-induction group achieved treatment success. Similarly, in the per-protocol analysis, 84.1% and 81.3%, respectively, achieved a complete response at day 56 after alloHCT. After a median follow-up of 4 years, there were no differences in leukemia-free survival or overall survival between the two groups.
Another advantage to forgoing an intensive salvage induction regimen: Patients in the disease-control arm experienced significantly fewer severe adverse events (23% vs. 64% in the remission induction arm) and spent a mean of 27 fewer days in the hospital prior to transplantation.
At last year’s press briefing, Dr. Schetelig said his team did not expect that a complete response on day 56 after transplantation would translate into “equal long-term benefit” for these groups. “This is what I was really astonished about,” he said.
Delving further into the findings, Dr. Schetelig explained that in the remission-induction arm patients who had had a complete response prior to transplantation demonstrated significantly better overall survival at 4 years than those who had not had a complete response at that point: 60% vs. 40%.
The study also revealed that in the disease-control arm, for patients under watchful waiting who did not need low-dose cytarabine and mitoxantrone for disease control, overall survival outcomes were similar to those of patients in the remission-induction arm who achieved a complete response.
These findings suggest that patients who can be bridged with watchful waiting may have a more favorable disease biology, and chemosensitivity could just be a biomarker for disease biology. In other words, “AML biology matters for transplant outcome and not tumor load,” Dr. Schetelig explained.
A recent study that found that having minimal residual disease (MRD) prior to transplant “had no independent effect on leukemia-free survival” supports this idea, he added.
Overall, Dr. Schetelig concluded that data from the ASAP trial suggest that watchful waiting prior to alloHCT represents “an alternative” for some patients.
Counterpoint: Aim for complete remission
Ronald B. Walter, MD, PhD, argued the counterpoint: that residual disease before transplantation is associated with worse posttransplant outcomes and represents a meaningful pretransplant therapeutic target.
The goal of intensifying treatment for patients with residual disease is to erase disease vestiges prior to transplantation.
“The idea is that by doing so you might optimize the benefit-to-risk ratio and ultimately improve outcomes,” said Dr. Walter, of the translational science and therapeutics division at the Fred Hutchinson Cancer Research Center in Seattle.
Several reports support this view that patients who are MRD negative at the time of transplant have significantly better survival outcomes than patients with residual disease who undergo transplant.
A 2016 study from Dr. Walter and colleagues at Fred Hutchinson, for instance, found that 3-year overall survival was significantly higher among patients with no MRD who underwent myeloablative alloHCT: 73% vs. 26% of those in MRD-positive morphologic remission and 23% of patients with active AML.
Another study, published the year before by a different research team, also revealed that “adult patients with AML in morphologic [complete remission] but with detectable MRD who undergo alloHCT have poor outcomes, which approximates those who undergo transplantation with active disease,” the authors of the 2015 study wrote in a commentary highlighting findings from both studies.
Still, providing intensive therapy prior to transplant comes with drawbacks, Dr. Walter noted. These downsides include potential toxicity from more intense therapy, which may prevent further therapy with curative intent, as well as the possibility that deintensifying therapy could lead to difficult-to-treat relapse.
It may, however, be possible to reduce the intensity of therapy before transplant and still achieve good outcomes after transplant, though the data remain mixed.
One trial found that a reduced-intensity conditioning regimen was associated with a greater risk of relapse post transplant and worse overall survival, compared with standard myeloablative conditioning.
However, another recent trial in which patients with AML or high-risk myelodysplastic syndrome were randomly assigned to either a reduced-intensity conditioning regimen or an intensified version of that regimen prior to transplant demonstrated no difference in relapse rates and overall survival, regardless of patients’ MRD status prior to transplant.
“To me, it’s still key to go into transplant with as little disease as possible,” Dr. Walter said. How much value there is in targeted treatment to further reduce disease burden prior to transplant “will really require further careful study,” he said.
The ASAP trial was sponsored by DKMS. Dr. Schetelig has received honoraria from BeiGene, BMS, Janssen, AstraZeneca, AbbVie, and DKMS. Dr. Walter reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
This critically important question was debated at the annual meeting of the Society of Hematologic Oncology, held in Houston and online.
Johannes Schetelig, MD, argued in favor of proceeding to transplant, even without a complete remission.
“In the past, I’ve told many patients with relapsed or refractory AML that we do need to induce a [complete remission] prior to transplantation,” said Dr. Schetelig, from the Clinical Trials Unit at DKMS in Dresden, Germany. “But is it true?”
According to findings from a recent randomized trial, it may not be. The trial, led by Dr. Schetelig, found that patients with AML who received immediate allogeneic transplant without first having achieved a complete response following induction therapy did just as well as those who received intensive salvage induction therapy to establish remission before transplant.
If this finding holds, it “completely upends” how experts have traditionally approached patients with AML, Mikkael A. Sekeres, MD, of the University of Miami said at a conference press briefing last year.
The phase 3 ASAP trial, presented at last year’s American Society of Hematology meeting, included patients with AML who had had a poor response or who had experienced a relapse after first induction therapy. Patients were randomly assigned to a remission-induction strategy prior to allogeneic stem cell transplant (alloHCT) or a disease-control approach of watchful waiting followed by sequential conditioning and alloHCT. The primary endpoint was treatment success, defined as a complete response at day 56 following alloHCT.
In an intention-to-treat analysis, 83.5% of patients in the disease-control group and 81% in the remission-induction group achieved treatment success. Similarly, in the per-protocol analysis, 84.1% and 81.3%, respectively, achieved a complete response at day 56 after alloHCT. After a median follow-up of 4 years, there were no differences in leukemia-free survival or overall survival between the two groups.
Another advantage to forgoing an intensive salvage induction regimen: Patients in the disease-control arm experienced significantly fewer severe adverse events (23% vs. 64% in the remission induction arm) and spent a mean of 27 fewer days in the hospital prior to transplantation.
At last year’s press briefing, Dr. Schetelig said his team did not expect that a complete response on day 56 after transplantation would translate into “equal long-term benefit” for these groups. “This is what I was really astonished about,” he said.
Delving further into the findings, Dr. Schetelig explained that in the remission-induction arm patients who had had a complete response prior to transplantation demonstrated significantly better overall survival at 4 years than those who had not had a complete response at that point: 60% vs. 40%.
The study also revealed that in the disease-control arm, for patients under watchful waiting who did not need low-dose cytarabine and mitoxantrone for disease control, overall survival outcomes were similar to those of patients in the remission-induction arm who achieved a complete response.
These findings suggest that patients who can be bridged with watchful waiting may have a more favorable disease biology, and chemosensitivity could just be a biomarker for disease biology. In other words, “AML biology matters for transplant outcome and not tumor load,” Dr. Schetelig explained.
A recent study that found that having minimal residual disease (MRD) prior to transplant “had no independent effect on leukemia-free survival” supports this idea, he added.
Overall, Dr. Schetelig concluded that data from the ASAP trial suggest that watchful waiting prior to alloHCT represents “an alternative” for some patients.
Counterpoint: Aim for complete remission
Ronald B. Walter, MD, PhD, argued the counterpoint: that residual disease before transplantation is associated with worse posttransplant outcomes and represents a meaningful pretransplant therapeutic target.
The goal of intensifying treatment for patients with residual disease is to erase disease vestiges prior to transplantation.
“The idea is that by doing so you might optimize the benefit-to-risk ratio and ultimately improve outcomes,” said Dr. Walter, of the translational science and therapeutics division at the Fred Hutchinson Cancer Research Center in Seattle.
Several reports support this view that patients who are MRD negative at the time of transplant have significantly better survival outcomes than patients with residual disease who undergo transplant.
A 2016 study from Dr. Walter and colleagues at Fred Hutchinson, for instance, found that 3-year overall survival was significantly higher among patients with no MRD who underwent myeloablative alloHCT: 73% vs. 26% of those in MRD-positive morphologic remission and 23% of patients with active AML.
Another study, published the year before by a different research team, also revealed that “adult patients with AML in morphologic [complete remission] but with detectable MRD who undergo alloHCT have poor outcomes, which approximates those who undergo transplantation with active disease,” the authors of the 2015 study wrote in a commentary highlighting findings from both studies.
Still, providing intensive therapy prior to transplant comes with drawbacks, Dr. Walter noted. These downsides include potential toxicity from more intense therapy, which may prevent further therapy with curative intent, as well as the possibility that deintensifying therapy could lead to difficult-to-treat relapse.
It may, however, be possible to reduce the intensity of therapy before transplant and still achieve good outcomes after transplant, though the data remain mixed.
One trial found that a reduced-intensity conditioning regimen was associated with a greater risk of relapse post transplant and worse overall survival, compared with standard myeloablative conditioning.
However, another recent trial in which patients with AML or high-risk myelodysplastic syndrome were randomly assigned to either a reduced-intensity conditioning regimen or an intensified version of that regimen prior to transplant demonstrated no difference in relapse rates and overall survival, regardless of patients’ MRD status prior to transplant.
“To me, it’s still key to go into transplant with as little disease as possible,” Dr. Walter said. How much value there is in targeted treatment to further reduce disease burden prior to transplant “will really require further careful study,” he said.
The ASAP trial was sponsored by DKMS. Dr. Schetelig has received honoraria from BeiGene, BMS, Janssen, AstraZeneca, AbbVie, and DKMS. Dr. Walter reported no relevant financial relationships.
A version of this article appeared on Medscape.com.
FROM SOHO 2023
Hemostatic powder superior in controlling tumor bleeding
The findings, published online in Gastroenterology (2023 Jun 3. doi: 10.1053/j.gastro.2023.05.042), come from the largest randomized trial to date of TC-325 (Hemospray, Cook Medical), compared with standard endoscopic hemostatic interventions for tumor bleeding.
For their research, Rapat Pittayanon, MD, of Chulalongkorn University in Bangkok and her colleagues, randomized patients (60% male, mean age 63) with active malignant upper or lower GI bleeding and low disability levels related to their cancers (ECOG score 0-2). The study was conducted at nine hospitals in Thailand.
The 106 patients who passed screening underwent either TC-325 or standard endoscopic hemostasis, which could involve use of thermal or mechanical methods or adrenaline injection, alone or combined with another modality, at the endoscopist’s discretion. Crossover between treatment allocations was permitted if hemostasis was not achieved. Investigators assessed rates of immediate hemostasis and rebleeding at 30 days.
Dr. Pittayanon and colleagues found rebleeding to be significantly lower among TC-325 treated patients, at 2.1%, compared with 21.3% for standard care (odds ratio, 0.09; 95% confidence interval, 0.01-0.80; P = .03). Rates of immediate hemostasis were 100% for TC-325–treated subjects, compared with 68.6% in the conventional-treatment group (OR, 1.45; 95% CI, 0.93-2.29; P < .001).
None of the 55 patients in the TC-325 group underwent crossover treatment, but 15 patients in the standard care group were crossed over to TC-325 after their endoscopic treatment was deemed to have failed. One-fifth of patients who got TC-325 as a crossover treatment developed rebleeding at 30 days, which the investigators surmised was related to mucosal damage incurred during the endoscopic procedure.
The study was not powered to adequately assess survival outcomes. Seven patients in the TC-325 group and four in the conventional care group died before 30 days’ follow-up, and no death was directly related to recurrent tumor bleeding.
“To our knowledge, our trial is the first to show such significant findings in an RCT setting, which now provide a long-awaited efficacious hemostatic approach where one had been lacking when managing patients with malignant GI bleeding,” the investigators wrote in their analysis.
“Perhaps most importantly, this carefully controlled study also highlights the unreliable hemostatic effect of standard endoscopic modalities available for GI tumor hemostasis, with high 30-day rebleeding rates in our patient population.”
Dr. Pittayanon and colleagues noted several limitations of their study. These included the inability to blind patients to an endoscopist, which “may have influenced subsequent management decisions … including the decision to cross over.”
Only in 5 of 15 cases of crossover did the treating endoscopist provide photo evidence of treatment failure as required by the trial’s protocol. Also, the use of adrenaline injection alone was permitted in the study, in contrast to best practice guidelines for endoscopic hemostasis to treat peptic ulcer bleeding. Finally, the study was conducted in Thailand, potentially reducing the generalizability of the results.
The study was funded by King Chulalongkorn Memorial Hospital; the Thai Red Cross; and Chulalongkorn University. Cook Medical donated some of the TC-325 kits used in the study.
One study coauthor, Alan N. Barkun, disclosed consulting work for Medtronic and past paid work for Cook Medical. The remaining authors disclosed no conflicts of interest.
Gastrointestinal tumor bleeding is a challenging problem that can lead to prolonged hospitalization and interruption of curative or palliative oncologic interventions. Standard endoscopic hemostasis interventions, such as subepithelial epinephrine injection and mechanical and thermal treatments, can be limited because of the underlying tumor biology that alters angiogenesis, distorts the surrounding mucosa, and undermines the normal coagulation process. This randomized trial by Pittayanon et al. demonstrated that the hemostatic powder TC-325 (Hemospray, Cook Medical) was superior to standard endoscopic intervention in achieving immediate hemostasis (100% vs. 69%) and reducing 30-day rebleeding rate (2% vs. 21%).
As clinicians and endoscopists, our ultimate goals in treating GI tumor bleeding are to provide safe and efficient hemostasis, to decrease hospital stay and to minimize delay and interruption of oncologic or palliative treatments. This study advocates that TC-325 may be a better primary option than standard endoscopic treatments for GI tumor bleeding in the appropriate setting. Safety, efficacy, and feasibility studies comparing TC-325 to the other hemostatic powder products are needed.
Malorie K. Simons, MD, is an interventional endoscopist with Fox Chase Cancer Center, Temple University Health System, Philadelphia. She specializes in colorectal cancer, esophageal cancer, and gastric cancer. She has no conflicts of interest.
Gastrointestinal tumor bleeding is a challenging problem that can lead to prolonged hospitalization and interruption of curative or palliative oncologic interventions. Standard endoscopic hemostasis interventions, such as subepithelial epinephrine injection and mechanical and thermal treatments, can be limited because of the underlying tumor biology that alters angiogenesis, distorts the surrounding mucosa, and undermines the normal coagulation process. This randomized trial by Pittayanon et al. demonstrated that the hemostatic powder TC-325 (Hemospray, Cook Medical) was superior to standard endoscopic intervention in achieving immediate hemostasis (100% vs. 69%) and reducing 30-day rebleeding rate (2% vs. 21%).
As clinicians and endoscopists, our ultimate goals in treating GI tumor bleeding are to provide safe and efficient hemostasis, to decrease hospital stay and to minimize delay and interruption of oncologic or palliative treatments. This study advocates that TC-325 may be a better primary option than standard endoscopic treatments for GI tumor bleeding in the appropriate setting. Safety, efficacy, and feasibility studies comparing TC-325 to the other hemostatic powder products are needed.
Malorie K. Simons, MD, is an interventional endoscopist with Fox Chase Cancer Center, Temple University Health System, Philadelphia. She specializes in colorectal cancer, esophageal cancer, and gastric cancer. She has no conflicts of interest.
Gastrointestinal tumor bleeding is a challenging problem that can lead to prolonged hospitalization and interruption of curative or palliative oncologic interventions. Standard endoscopic hemostasis interventions, such as subepithelial epinephrine injection and mechanical and thermal treatments, can be limited because of the underlying tumor biology that alters angiogenesis, distorts the surrounding mucosa, and undermines the normal coagulation process. This randomized trial by Pittayanon et al. demonstrated that the hemostatic powder TC-325 (Hemospray, Cook Medical) was superior to standard endoscopic intervention in achieving immediate hemostasis (100% vs. 69%) and reducing 30-day rebleeding rate (2% vs. 21%).
As clinicians and endoscopists, our ultimate goals in treating GI tumor bleeding are to provide safe and efficient hemostasis, to decrease hospital stay and to minimize delay and interruption of oncologic or palliative treatments. This study advocates that TC-325 may be a better primary option than standard endoscopic treatments for GI tumor bleeding in the appropriate setting. Safety, efficacy, and feasibility studies comparing TC-325 to the other hemostatic powder products are needed.
Malorie K. Simons, MD, is an interventional endoscopist with Fox Chase Cancer Center, Temple University Health System, Philadelphia. She specializes in colorectal cancer, esophageal cancer, and gastric cancer. She has no conflicts of interest.
The findings, published online in Gastroenterology (2023 Jun 3. doi: 10.1053/j.gastro.2023.05.042), come from the largest randomized trial to date of TC-325 (Hemospray, Cook Medical), compared with standard endoscopic hemostatic interventions for tumor bleeding.
For their research, Rapat Pittayanon, MD, of Chulalongkorn University in Bangkok and her colleagues, randomized patients (60% male, mean age 63) with active malignant upper or lower GI bleeding and low disability levels related to their cancers (ECOG score 0-2). The study was conducted at nine hospitals in Thailand.
The 106 patients who passed screening underwent either TC-325 or standard endoscopic hemostasis, which could involve use of thermal or mechanical methods or adrenaline injection, alone or combined with another modality, at the endoscopist’s discretion. Crossover between treatment allocations was permitted if hemostasis was not achieved. Investigators assessed rates of immediate hemostasis and rebleeding at 30 days.
Dr. Pittayanon and colleagues found rebleeding to be significantly lower among TC-325 treated patients, at 2.1%, compared with 21.3% for standard care (odds ratio, 0.09; 95% confidence interval, 0.01-0.80; P = .03). Rates of immediate hemostasis were 100% for TC-325–treated subjects, compared with 68.6% in the conventional-treatment group (OR, 1.45; 95% CI, 0.93-2.29; P < .001).
None of the 55 patients in the TC-325 group underwent crossover treatment, but 15 patients in the standard care group were crossed over to TC-325 after their endoscopic treatment was deemed to have failed. One-fifth of patients who got TC-325 as a crossover treatment developed rebleeding at 30 days, which the investigators surmised was related to mucosal damage incurred during the endoscopic procedure.
The study was not powered to adequately assess survival outcomes. Seven patients in the TC-325 group and four in the conventional care group died before 30 days’ follow-up, and no death was directly related to recurrent tumor bleeding.
“To our knowledge, our trial is the first to show such significant findings in an RCT setting, which now provide a long-awaited efficacious hemostatic approach where one had been lacking when managing patients with malignant GI bleeding,” the investigators wrote in their analysis.
“Perhaps most importantly, this carefully controlled study also highlights the unreliable hemostatic effect of standard endoscopic modalities available for GI tumor hemostasis, with high 30-day rebleeding rates in our patient population.”
Dr. Pittayanon and colleagues noted several limitations of their study. These included the inability to blind patients to an endoscopist, which “may have influenced subsequent management decisions … including the decision to cross over.”
Only in 5 of 15 cases of crossover did the treating endoscopist provide photo evidence of treatment failure as required by the trial’s protocol. Also, the use of adrenaline injection alone was permitted in the study, in contrast to best practice guidelines for endoscopic hemostasis to treat peptic ulcer bleeding. Finally, the study was conducted in Thailand, potentially reducing the generalizability of the results.
The study was funded by King Chulalongkorn Memorial Hospital; the Thai Red Cross; and Chulalongkorn University. Cook Medical donated some of the TC-325 kits used in the study.
One study coauthor, Alan N. Barkun, disclosed consulting work for Medtronic and past paid work for Cook Medical. The remaining authors disclosed no conflicts of interest.
The findings, published online in Gastroenterology (2023 Jun 3. doi: 10.1053/j.gastro.2023.05.042), come from the largest randomized trial to date of TC-325 (Hemospray, Cook Medical), compared with standard endoscopic hemostatic interventions for tumor bleeding.
For their research, Rapat Pittayanon, MD, of Chulalongkorn University in Bangkok and her colleagues, randomized patients (60% male, mean age 63) with active malignant upper or lower GI bleeding and low disability levels related to their cancers (ECOG score 0-2). The study was conducted at nine hospitals in Thailand.
The 106 patients who passed screening underwent either TC-325 or standard endoscopic hemostasis, which could involve use of thermal or mechanical methods or adrenaline injection, alone or combined with another modality, at the endoscopist’s discretion. Crossover between treatment allocations was permitted if hemostasis was not achieved. Investigators assessed rates of immediate hemostasis and rebleeding at 30 days.
Dr. Pittayanon and colleagues found rebleeding to be significantly lower among TC-325 treated patients, at 2.1%, compared with 21.3% for standard care (odds ratio, 0.09; 95% confidence interval, 0.01-0.80; P = .03). Rates of immediate hemostasis were 100% for TC-325–treated subjects, compared with 68.6% in the conventional-treatment group (OR, 1.45; 95% CI, 0.93-2.29; P < .001).
None of the 55 patients in the TC-325 group underwent crossover treatment, but 15 patients in the standard care group were crossed over to TC-325 after their endoscopic treatment was deemed to have failed. One-fifth of patients who got TC-325 as a crossover treatment developed rebleeding at 30 days, which the investigators surmised was related to mucosal damage incurred during the endoscopic procedure.
The study was not powered to adequately assess survival outcomes. Seven patients in the TC-325 group and four in the conventional care group died before 30 days’ follow-up, and no death was directly related to recurrent tumor bleeding.
“To our knowledge, our trial is the first to show such significant findings in an RCT setting, which now provide a long-awaited efficacious hemostatic approach where one had been lacking when managing patients with malignant GI bleeding,” the investigators wrote in their analysis.
“Perhaps most importantly, this carefully controlled study also highlights the unreliable hemostatic effect of standard endoscopic modalities available for GI tumor hemostasis, with high 30-day rebleeding rates in our patient population.”
Dr. Pittayanon and colleagues noted several limitations of their study. These included the inability to blind patients to an endoscopist, which “may have influenced subsequent management decisions … including the decision to cross over.”
Only in 5 of 15 cases of crossover did the treating endoscopist provide photo evidence of treatment failure as required by the trial’s protocol. Also, the use of adrenaline injection alone was permitted in the study, in contrast to best practice guidelines for endoscopic hemostasis to treat peptic ulcer bleeding. Finally, the study was conducted in Thailand, potentially reducing the generalizability of the results.
The study was funded by King Chulalongkorn Memorial Hospital; the Thai Red Cross; and Chulalongkorn University. Cook Medical donated some of the TC-325 kits used in the study.
One study coauthor, Alan N. Barkun, disclosed consulting work for Medtronic and past paid work for Cook Medical. The remaining authors disclosed no conflicts of interest.
FROM GASTROENTEROLOGY
Exercise tied to lower mortality risk across cancer types
TOPLINE:
Regular exercise can significantly reduce a cancer survivor’s mortality from cancer or other causes, a large analysis finds.
METHODOLOGY:
- Following a cancer diagnosis, the impact of exercise on all cause and cause-specific mortality among survivors, and whether the benefit of exercise differs by cancer site, remains unclear.
- To investigate, researchers leveraged data from 11,480 cancer survivors in the Prostate, Lung, Colorectal, and Ovarian cancer screening trial.
- Postdiagnosis exercise levels were quantified via a questionnaire. The primary outcome was all-cause mortality; secondary endpoints were deaths from cancer and other causes.
- Cox models estimated cause-specific hazard ratio for all-cause mortality as well as cancer and noncancer mortality based on whether survivors met or did not meet exercise guidelines.
- Meeting national exercise guidelines meant moderate-intensity exercise 4 or more days per week with sessions lasting, on average, 30 minutes or longer; and/or strenuous-intensity exercise 2 or more days per week with sessions lasting, on average, 20 minutes or longer.
TAKEAWAY:
- Overall, 62% of participants were deemed nonexercisers (no exercise or exercise below guidelines) and 38% were classified as exercisers (meeting or exceeding guidelines). After a median follow-up of 16 years from diagnosis, researchers documented 4,665 deaths – 1,940 from cancer and 2,725 from other causes.
- Exercise at recommended levels was associated with “near-universal” all-cause mortality benefit for most cancers represented, including prostate, breast, endometrial, renal, and head and neck cancers.
- In multivariate analysis, compared with nonexercisers, exercisers had a 25% reduced risk of all-cause mortality (HR, 0.75), with the benefit apparent within 5 years and persisting for at least 20 years after diagnosis.
- Exercise was associated with a 21% reduction in cancer mortality and a 28% reduction in mortality from other causes, with more exercise demonstrating a greater benefit on cancer-specific mortality risk.
IN PRACTICE:
Overall, “our findings show exercise is a holistic strategy that may complement contemporary management approaches to further reduce cancer mortality (in select sites) while simultaneously lowering risk of death from other competing causes, which combine to improve all-cause mortality,” the authors conclude. “This benefit was observed within a few years after diagnosis and sustained for at least 20 years.”
SOURCE:
The study, led by Jessica Lavery, MS, Memorial Sloan Kettering Cancer Center, New York, was published online in the Journal of Clinical Oncology.
LIMITATIONS:
Exercise habits were self-reported at one time point, not measured more objectively over time using wearable devices. The population studied was predominantly non-Hispanic White. The researchers could not determine whether exercise habits reflected lower disease and/or treatment-related toxicities as opposed to direct exercise-induced effects or better adherence to a healthy lifestyle.
DISCLOSURES:
Support for the study was provided by AKTIV Against Cancer and grants from Memorial Sloan Kettering Cancer Center and UCLA Jonsson Comprehensive Cancer Center. Disclosures for the study authors are available with the original article.
A version of this article first appeared on Medscape.com.
TOPLINE:
Regular exercise can significantly reduce a cancer survivor’s mortality from cancer or other causes, a large analysis finds.
METHODOLOGY:
- Following a cancer diagnosis, the impact of exercise on all cause and cause-specific mortality among survivors, and whether the benefit of exercise differs by cancer site, remains unclear.
- To investigate, researchers leveraged data from 11,480 cancer survivors in the Prostate, Lung, Colorectal, and Ovarian cancer screening trial.
- Postdiagnosis exercise levels were quantified via a questionnaire. The primary outcome was all-cause mortality; secondary endpoints were deaths from cancer and other causes.
- Cox models estimated cause-specific hazard ratio for all-cause mortality as well as cancer and noncancer mortality based on whether survivors met or did not meet exercise guidelines.
- Meeting national exercise guidelines meant moderate-intensity exercise 4 or more days per week with sessions lasting, on average, 30 minutes or longer; and/or strenuous-intensity exercise 2 or more days per week with sessions lasting, on average, 20 minutes or longer.
TAKEAWAY:
- Overall, 62% of participants were deemed nonexercisers (no exercise or exercise below guidelines) and 38% were classified as exercisers (meeting or exceeding guidelines). After a median follow-up of 16 years from diagnosis, researchers documented 4,665 deaths – 1,940 from cancer and 2,725 from other causes.
- Exercise at recommended levels was associated with “near-universal” all-cause mortality benefit for most cancers represented, including prostate, breast, endometrial, renal, and head and neck cancers.
- In multivariate analysis, compared with nonexercisers, exercisers had a 25% reduced risk of all-cause mortality (HR, 0.75), with the benefit apparent within 5 years and persisting for at least 20 years after diagnosis.
- Exercise was associated with a 21% reduction in cancer mortality and a 28% reduction in mortality from other causes, with more exercise demonstrating a greater benefit on cancer-specific mortality risk.
IN PRACTICE:
Overall, “our findings show exercise is a holistic strategy that may complement contemporary management approaches to further reduce cancer mortality (in select sites) while simultaneously lowering risk of death from other competing causes, which combine to improve all-cause mortality,” the authors conclude. “This benefit was observed within a few years after diagnosis and sustained for at least 20 years.”
SOURCE:
The study, led by Jessica Lavery, MS, Memorial Sloan Kettering Cancer Center, New York, was published online in the Journal of Clinical Oncology.
LIMITATIONS:
Exercise habits were self-reported at one time point, not measured more objectively over time using wearable devices. The population studied was predominantly non-Hispanic White. The researchers could not determine whether exercise habits reflected lower disease and/or treatment-related toxicities as opposed to direct exercise-induced effects or better adherence to a healthy lifestyle.
DISCLOSURES:
Support for the study was provided by AKTIV Against Cancer and grants from Memorial Sloan Kettering Cancer Center and UCLA Jonsson Comprehensive Cancer Center. Disclosures for the study authors are available with the original article.
A version of this article first appeared on Medscape.com.
TOPLINE:
Regular exercise can significantly reduce a cancer survivor’s mortality from cancer or other causes, a large analysis finds.
METHODOLOGY:
- Following a cancer diagnosis, the impact of exercise on all cause and cause-specific mortality among survivors, and whether the benefit of exercise differs by cancer site, remains unclear.
- To investigate, researchers leveraged data from 11,480 cancer survivors in the Prostate, Lung, Colorectal, and Ovarian cancer screening trial.
- Postdiagnosis exercise levels were quantified via a questionnaire. The primary outcome was all-cause mortality; secondary endpoints were deaths from cancer and other causes.
- Cox models estimated cause-specific hazard ratio for all-cause mortality as well as cancer and noncancer mortality based on whether survivors met or did not meet exercise guidelines.
- Meeting national exercise guidelines meant moderate-intensity exercise 4 or more days per week with sessions lasting, on average, 30 minutes or longer; and/or strenuous-intensity exercise 2 or more days per week with sessions lasting, on average, 20 minutes or longer.
TAKEAWAY:
- Overall, 62% of participants were deemed nonexercisers (no exercise or exercise below guidelines) and 38% were classified as exercisers (meeting or exceeding guidelines). After a median follow-up of 16 years from diagnosis, researchers documented 4,665 deaths – 1,940 from cancer and 2,725 from other causes.
- Exercise at recommended levels was associated with “near-universal” all-cause mortality benefit for most cancers represented, including prostate, breast, endometrial, renal, and head and neck cancers.
- In multivariate analysis, compared with nonexercisers, exercisers had a 25% reduced risk of all-cause mortality (HR, 0.75), with the benefit apparent within 5 years and persisting for at least 20 years after diagnosis.
- Exercise was associated with a 21% reduction in cancer mortality and a 28% reduction in mortality from other causes, with more exercise demonstrating a greater benefit on cancer-specific mortality risk.
IN PRACTICE:
Overall, “our findings show exercise is a holistic strategy that may complement contemporary management approaches to further reduce cancer mortality (in select sites) while simultaneously lowering risk of death from other competing causes, which combine to improve all-cause mortality,” the authors conclude. “This benefit was observed within a few years after diagnosis and sustained for at least 20 years.”
SOURCE:
The study, led by Jessica Lavery, MS, Memorial Sloan Kettering Cancer Center, New York, was published online in the Journal of Clinical Oncology.
LIMITATIONS:
Exercise habits were self-reported at one time point, not measured more objectively over time using wearable devices. The population studied was predominantly non-Hispanic White. The researchers could not determine whether exercise habits reflected lower disease and/or treatment-related toxicities as opposed to direct exercise-induced effects or better adherence to a healthy lifestyle.
DISCLOSURES:
Support for the study was provided by AKTIV Against Cancer and grants from Memorial Sloan Kettering Cancer Center and UCLA Jonsson Comprehensive Cancer Center. Disclosures for the study authors are available with the original article.
A version of this article first appeared on Medscape.com.
Seeking help for burnout may be a gamble for doctors
By the end of 2021, Anuj Peddada, MD, had hit a wall. He couldn’t sleep, couldn’t concentrate, erupted in anger, and felt isolated personally and professionally. To temper pandemic-driven pressures, the Colorado radiation oncologist took an 8-week stress management and resiliency course, but the feelings kept creeping back.
Still, Dr. Peddada, in his own private practice, pushed through, working 60-hour weeks and carrying the workload of two physicians. It wasn’t until he caught himself making uncharacteristic medical errors, including radiation planning for the wrong site, that he knew he needed help – and possibly a temporary break from medicine.
There was just one hitch: He was closing his private practice to start a new in-house job with Centura Health, the Colorado Springs hospital he’d contracted with for over 20 years.
Given the long-standing relationship – Dr. Peddada’s image graced some of the company’s marketing billboards – he expected Centura would understand when, on his doctor’s recommendation, he requested a short-term medical leave that would delay his start date by 1 month.
Instead, Centura abruptly rescinded the employment offer, leaving Dr. Peddada jobless and with no recourse but to sue.
“I was blindsided. The hospital had a physician resiliency program that claimed to encourage physicians to seek help, [so] I thought they would be completely supportive and understanding,” Dr. Peddada said.
He told this news organization that he was naive to have been so honest with the hospital he’d long served as a contractor, including the decade-plus he›d spent directing its radiation oncology department.
“It is exceedingly painful to see hospital leadership use me in their advertisement[s] ... trying to profit off my reputation and work after devastating my career.”
The lawsuit Dr. Peddada filed in July in Colorado federal district court may offer a rare glimpse of the potential career ramifications of seeking help for physician burnout. Despite employers’ oft-stated support for physician wellness, Dr. Peddada’s experience may serve as a cautionary tale for doctors who are open about their struggles.
Centura Health did not respond to requests for comment. In court documents, the health system’s attorneys asked for more time to respond to Dr. Peddada’s complaint.
A plea for help
In the complaint, Dr. Peddada and his attorneys claim that Centura violated the state’s Anti-Discrimination Act and the Americans with Disabilities Act (ADA) when it failed to offer reasonable accommodations after he began experiencing “physiological and psychological symptoms corresponding to burnout.”
Since 1999, Dr. Peddada had contracted exclusively with Centura to provide oncology services at its hospital, Penrose Cancer Center, and began covering a second Centura location in 2021. As medical director of Penrose’s radiation oncology department, he helped establish a community nurse navigator program and accounted for 75% of Centura’s radiation oncology referrals, according to the complaint.
But when his symptoms and fear for the safety of his patients became unbearable, Dr. Peddada requested an urgent evaluation from his primary care physician, who diagnosed him with “physician burnout” and recommended medical leave.
Shortly after presenting the leave request to Centura, rumors began circulating that he was having a “nervous breakdown,” the complaint noted. Dr. Peddada worried that perhaps his private health information was being shared with hospital employees.
After meeting with the hospital’s head of physician resiliency and agreeing to undergo a peer review evaluation by the Colorado Physician Health Program, which would decide the reinstatement timeline and if further therapy was necessary, Dr. Peddada was assured his leave would be approved.
Five days later, his job offer was revoked.
In an email from hospital leadership, the oncologist was informed that he had “declined employment” by failing to sign a revised employment contract sent to him 2 weeks prior when he was out of state on a preapproved vacation, according to the lawsuit.
The lawsuit alleges that Dr. Peddada was wrongfully discharged due to his disability after Centura “exploited [his] extensive patient base, referral network, and reputation to generate growth and profit.”
Colorado employment law attorney Deborah Yim, Esq., who is not involved in Peddada’s case, told this news organization that the ADA requires employers to provide reasonable accommodations for physical or mental impairments that substantially limit at least one major life activity, except when the request imposes an undue hardship on the employer.
“Depression and related mental health conditions would qualify, depending on the circumstances, and courts have certainly found them to be qualifying disabilities entitled to ADA protection in the past,” she said.
Not all employers are receptive to doctors’ needs, says the leadership team at Physicians Just Equity, an organization providing peer support to doctors experiencing workplace conflicts like discrimination and retaliation. They say that Dr. Peddada’s experience, where disclosing burnout results in being “ostracized, penalized, and ultimately ousted,” is the rule rather than the exception.
“Dr. Peddada’s case represents the unfortunate reality faced by many physicians in today’s clinical landscape,” the organization’s board of directors said in a written statement. “The imbalance of unreasonable professional demands, the lack of autonomy, moral injury, and disintegrating practice rewards is unsustainable for the medical professional.”
“Retaliation by employers after speaking up against this imbalance [and] requesting support and time to rejuvenate is a grave failure of health care systems that prioritize the business of delivering health care over the health, well-being, and satisfaction of their most valuable resource – the physician,” the board added in their statement.
Dr. Peddada has since closed his private practice and works as an independent contractor and consultant, his attorney, Iris Halpern, JD, said in an interview. She says Centura could have honored the accommodation request or suggested another option that met his needs, but “not only were they unsupportive, they terminated him.”
Ms. Yim says the parties will have opportunities to reach a settlement and resolve the dispute as the case works through the court system. Otherwise, Dr. Peddada and Centura may eventually head to trial.
Current state of physician burnout
The state of physician burnout is certainly a concerning one. More than half (53%) of physicians responding to this year’s Medscape Physician Burnout & Depression Report said they are burned out. Nearly one-quarter reported feeling depressed. Some of the top reasons they cited were too many bureaucratic tasks (61%), too many work hours (37%), and lack of autonomy (31%).
A 2022 study by the Mayo Clinic found a substantial increase in physician burnout in the first 2 years of the pandemic, with doctors reporting rising emotional exhaustion and depersonalization.
Although burnout affects many physicians and is a priority focus of the National Academy of Medicine’s plan to restore workforce well-being, admitting it is often seen as taboo and can imperil a doctor’s career. In the Medscape report, for example, 39% of physicians said they would not even consider professional treatment for burnout, with many commenting that they would just deal with it themselves.
“Many physicians are frightened to take time out for self-care because [they] fear losing their job, being stigmatized, and potentially ending their careers,” said Dr. Peddada, adding that physicians are commonly asked questions about their mental health when applying for hospital privileges. He says this dynamic forces them to choose between getting help or ignoring their true feelings, leading to poor quality of care and patient safety risks.
Medical licensing boards probe physicians’ mental health, too. As part of its #FightingForDocs campaign, the American Medical Association hopes to remove the stigma around burnout and depression and advocates for licensing boards to revise questions that may discourage physicians from seeking assistance. The AMA recommends that physicians only disclose current physical or mental conditions affecting their ability to practice.
Pringl Miller, MD, founder and executive director of Physician Just Equity, told Medscape that improving physician wellness requires structural change.
“Physicians (who) experience burnout without the proper accommodations run the risk of personal harm, because most physicians will prioritize the health and well-being of their patients over themselves ... [resulting in] suboptimal and unsafe patient care,” she said.
Helping doctors regain a sense of purpose
One change involves reframing how the health care industry thinks about and approaches burnout, says Steven Siegel, MD, chief mental health and wellness officer with Keck Medicine of USC. He told this news organization that these discussions should enhance the physician’s sense of purpose.
“Some people treat burnout as a concrete disorder like cancer, instead of saying, ‘I’m feeling exhausted, demoralized, and don’t enjoy my job anymore. What can we do to restore my enthusiasm for work?’ ”
Dr. Siegel recognizes that these issues existed before the pandemic and have only worsened as physicians feel less connected to and satisfied with their profession – a byproduct, he says, of the commercialization of medicine.
“We’ve moved from practices to systems, then from small to large systems, where it seems the path to survival is cutting costs and increasing margins, even among nonprofits.”
The road ahead
Making headway on these problems will take time. Last year, Keck Medicine received a $2 million grant to launch a 3-year randomized clinical trial to help reconnect physicians and other clinicians with their work. Dr. Siegel says the trial may serve as a national pilot program and will eventually grow to include 400 volunteers.
The trial will investigate the effectiveness of three possible interventions: (1) teaching people how to regulate their internal narratives and emotions through techniques like cognitive behavioral therapy and acceptance and commitment therapy; (2) providing customized EHR training to reduce the burden of navigating the system; and (3) allowing physicians to weigh in on workflow changes.
“We put physicians on teams that make the decisions about workflows,” said Dr. Siegel. The arrangement can give people the agency they desire and help them understand why an idea might not be plausible, which enriches future suggestions and discussions, he says.
A version of this article first appeared on Medscape.com.
By the end of 2021, Anuj Peddada, MD, had hit a wall. He couldn’t sleep, couldn’t concentrate, erupted in anger, and felt isolated personally and professionally. To temper pandemic-driven pressures, the Colorado radiation oncologist took an 8-week stress management and resiliency course, but the feelings kept creeping back.
Still, Dr. Peddada, in his own private practice, pushed through, working 60-hour weeks and carrying the workload of two physicians. It wasn’t until he caught himself making uncharacteristic medical errors, including radiation planning for the wrong site, that he knew he needed help – and possibly a temporary break from medicine.
There was just one hitch: He was closing his private practice to start a new in-house job with Centura Health, the Colorado Springs hospital he’d contracted with for over 20 years.
Given the long-standing relationship – Dr. Peddada’s image graced some of the company’s marketing billboards – he expected Centura would understand when, on his doctor’s recommendation, he requested a short-term medical leave that would delay his start date by 1 month.
Instead, Centura abruptly rescinded the employment offer, leaving Dr. Peddada jobless and with no recourse but to sue.
“I was blindsided. The hospital had a physician resiliency program that claimed to encourage physicians to seek help, [so] I thought they would be completely supportive and understanding,” Dr. Peddada said.
He told this news organization that he was naive to have been so honest with the hospital he’d long served as a contractor, including the decade-plus he›d spent directing its radiation oncology department.
“It is exceedingly painful to see hospital leadership use me in their advertisement[s] ... trying to profit off my reputation and work after devastating my career.”
The lawsuit Dr. Peddada filed in July in Colorado federal district court may offer a rare glimpse of the potential career ramifications of seeking help for physician burnout. Despite employers’ oft-stated support for physician wellness, Dr. Peddada’s experience may serve as a cautionary tale for doctors who are open about their struggles.
Centura Health did not respond to requests for comment. In court documents, the health system’s attorneys asked for more time to respond to Dr. Peddada’s complaint.
A plea for help
In the complaint, Dr. Peddada and his attorneys claim that Centura violated the state’s Anti-Discrimination Act and the Americans with Disabilities Act (ADA) when it failed to offer reasonable accommodations after he began experiencing “physiological and psychological symptoms corresponding to burnout.”
Since 1999, Dr. Peddada had contracted exclusively with Centura to provide oncology services at its hospital, Penrose Cancer Center, and began covering a second Centura location in 2021. As medical director of Penrose’s radiation oncology department, he helped establish a community nurse navigator program and accounted for 75% of Centura’s radiation oncology referrals, according to the complaint.
But when his symptoms and fear for the safety of his patients became unbearable, Dr. Peddada requested an urgent evaluation from his primary care physician, who diagnosed him with “physician burnout” and recommended medical leave.
Shortly after presenting the leave request to Centura, rumors began circulating that he was having a “nervous breakdown,” the complaint noted. Dr. Peddada worried that perhaps his private health information was being shared with hospital employees.
After meeting with the hospital’s head of physician resiliency and agreeing to undergo a peer review evaluation by the Colorado Physician Health Program, which would decide the reinstatement timeline and if further therapy was necessary, Dr. Peddada was assured his leave would be approved.
Five days later, his job offer was revoked.
In an email from hospital leadership, the oncologist was informed that he had “declined employment” by failing to sign a revised employment contract sent to him 2 weeks prior when he was out of state on a preapproved vacation, according to the lawsuit.
The lawsuit alleges that Dr. Peddada was wrongfully discharged due to his disability after Centura “exploited [his] extensive patient base, referral network, and reputation to generate growth and profit.”
Colorado employment law attorney Deborah Yim, Esq., who is not involved in Peddada’s case, told this news organization that the ADA requires employers to provide reasonable accommodations for physical or mental impairments that substantially limit at least one major life activity, except when the request imposes an undue hardship on the employer.
“Depression and related mental health conditions would qualify, depending on the circumstances, and courts have certainly found them to be qualifying disabilities entitled to ADA protection in the past,” she said.
Not all employers are receptive to doctors’ needs, says the leadership team at Physicians Just Equity, an organization providing peer support to doctors experiencing workplace conflicts like discrimination and retaliation. They say that Dr. Peddada’s experience, where disclosing burnout results in being “ostracized, penalized, and ultimately ousted,” is the rule rather than the exception.
“Dr. Peddada’s case represents the unfortunate reality faced by many physicians in today’s clinical landscape,” the organization’s board of directors said in a written statement. “The imbalance of unreasonable professional demands, the lack of autonomy, moral injury, and disintegrating practice rewards is unsustainable for the medical professional.”
“Retaliation by employers after speaking up against this imbalance [and] requesting support and time to rejuvenate is a grave failure of health care systems that prioritize the business of delivering health care over the health, well-being, and satisfaction of their most valuable resource – the physician,” the board added in their statement.
Dr. Peddada has since closed his private practice and works as an independent contractor and consultant, his attorney, Iris Halpern, JD, said in an interview. She says Centura could have honored the accommodation request or suggested another option that met his needs, but “not only were they unsupportive, they terminated him.”
Ms. Yim says the parties will have opportunities to reach a settlement and resolve the dispute as the case works through the court system. Otherwise, Dr. Peddada and Centura may eventually head to trial.
Current state of physician burnout
The state of physician burnout is certainly a concerning one. More than half (53%) of physicians responding to this year’s Medscape Physician Burnout & Depression Report said they are burned out. Nearly one-quarter reported feeling depressed. Some of the top reasons they cited were too many bureaucratic tasks (61%), too many work hours (37%), and lack of autonomy (31%).
A 2022 study by the Mayo Clinic found a substantial increase in physician burnout in the first 2 years of the pandemic, with doctors reporting rising emotional exhaustion and depersonalization.
Although burnout affects many physicians and is a priority focus of the National Academy of Medicine’s plan to restore workforce well-being, admitting it is often seen as taboo and can imperil a doctor’s career. In the Medscape report, for example, 39% of physicians said they would not even consider professional treatment for burnout, with many commenting that they would just deal with it themselves.
“Many physicians are frightened to take time out for self-care because [they] fear losing their job, being stigmatized, and potentially ending their careers,” said Dr. Peddada, adding that physicians are commonly asked questions about their mental health when applying for hospital privileges. He says this dynamic forces them to choose between getting help or ignoring their true feelings, leading to poor quality of care and patient safety risks.
Medical licensing boards probe physicians’ mental health, too. As part of its #FightingForDocs campaign, the American Medical Association hopes to remove the stigma around burnout and depression and advocates for licensing boards to revise questions that may discourage physicians from seeking assistance. The AMA recommends that physicians only disclose current physical or mental conditions affecting their ability to practice.
Pringl Miller, MD, founder and executive director of Physician Just Equity, told Medscape that improving physician wellness requires structural change.
“Physicians (who) experience burnout without the proper accommodations run the risk of personal harm, because most physicians will prioritize the health and well-being of their patients over themselves ... [resulting in] suboptimal and unsafe patient care,” she said.
Helping doctors regain a sense of purpose
One change involves reframing how the health care industry thinks about and approaches burnout, says Steven Siegel, MD, chief mental health and wellness officer with Keck Medicine of USC. He told this news organization that these discussions should enhance the physician’s sense of purpose.
“Some people treat burnout as a concrete disorder like cancer, instead of saying, ‘I’m feeling exhausted, demoralized, and don’t enjoy my job anymore. What can we do to restore my enthusiasm for work?’ ”
Dr. Siegel recognizes that these issues existed before the pandemic and have only worsened as physicians feel less connected to and satisfied with their profession – a byproduct, he says, of the commercialization of medicine.
“We’ve moved from practices to systems, then from small to large systems, where it seems the path to survival is cutting costs and increasing margins, even among nonprofits.”
The road ahead
Making headway on these problems will take time. Last year, Keck Medicine received a $2 million grant to launch a 3-year randomized clinical trial to help reconnect physicians and other clinicians with their work. Dr. Siegel says the trial may serve as a national pilot program and will eventually grow to include 400 volunteers.
The trial will investigate the effectiveness of three possible interventions: (1) teaching people how to regulate their internal narratives and emotions through techniques like cognitive behavioral therapy and acceptance and commitment therapy; (2) providing customized EHR training to reduce the burden of navigating the system; and (3) allowing physicians to weigh in on workflow changes.
“We put physicians on teams that make the decisions about workflows,” said Dr. Siegel. The arrangement can give people the agency they desire and help them understand why an idea might not be plausible, which enriches future suggestions and discussions, he says.
A version of this article first appeared on Medscape.com.
By the end of 2021, Anuj Peddada, MD, had hit a wall. He couldn’t sleep, couldn’t concentrate, erupted in anger, and felt isolated personally and professionally. To temper pandemic-driven pressures, the Colorado radiation oncologist took an 8-week stress management and resiliency course, but the feelings kept creeping back.
Still, Dr. Peddada, in his own private practice, pushed through, working 60-hour weeks and carrying the workload of two physicians. It wasn’t until he caught himself making uncharacteristic medical errors, including radiation planning for the wrong site, that he knew he needed help – and possibly a temporary break from medicine.
There was just one hitch: He was closing his private practice to start a new in-house job with Centura Health, the Colorado Springs hospital he’d contracted with for over 20 years.
Given the long-standing relationship – Dr. Peddada’s image graced some of the company’s marketing billboards – he expected Centura would understand when, on his doctor’s recommendation, he requested a short-term medical leave that would delay his start date by 1 month.
Instead, Centura abruptly rescinded the employment offer, leaving Dr. Peddada jobless and with no recourse but to sue.
“I was blindsided. The hospital had a physician resiliency program that claimed to encourage physicians to seek help, [so] I thought they would be completely supportive and understanding,” Dr. Peddada said.
He told this news organization that he was naive to have been so honest with the hospital he’d long served as a contractor, including the decade-plus he›d spent directing its radiation oncology department.
“It is exceedingly painful to see hospital leadership use me in their advertisement[s] ... trying to profit off my reputation and work after devastating my career.”
The lawsuit Dr. Peddada filed in July in Colorado federal district court may offer a rare glimpse of the potential career ramifications of seeking help for physician burnout. Despite employers’ oft-stated support for physician wellness, Dr. Peddada’s experience may serve as a cautionary tale for doctors who are open about their struggles.
Centura Health did not respond to requests for comment. In court documents, the health system’s attorneys asked for more time to respond to Dr. Peddada’s complaint.
A plea for help
In the complaint, Dr. Peddada and his attorneys claim that Centura violated the state’s Anti-Discrimination Act and the Americans with Disabilities Act (ADA) when it failed to offer reasonable accommodations after he began experiencing “physiological and psychological symptoms corresponding to burnout.”
Since 1999, Dr. Peddada had contracted exclusively with Centura to provide oncology services at its hospital, Penrose Cancer Center, and began covering a second Centura location in 2021. As medical director of Penrose’s radiation oncology department, he helped establish a community nurse navigator program and accounted for 75% of Centura’s radiation oncology referrals, according to the complaint.
But when his symptoms and fear for the safety of his patients became unbearable, Dr. Peddada requested an urgent evaluation from his primary care physician, who diagnosed him with “physician burnout” and recommended medical leave.
Shortly after presenting the leave request to Centura, rumors began circulating that he was having a “nervous breakdown,” the complaint noted. Dr. Peddada worried that perhaps his private health information was being shared with hospital employees.
After meeting with the hospital’s head of physician resiliency and agreeing to undergo a peer review evaluation by the Colorado Physician Health Program, which would decide the reinstatement timeline and if further therapy was necessary, Dr. Peddada was assured his leave would be approved.
Five days later, his job offer was revoked.
In an email from hospital leadership, the oncologist was informed that he had “declined employment” by failing to sign a revised employment contract sent to him 2 weeks prior when he was out of state on a preapproved vacation, according to the lawsuit.
The lawsuit alleges that Dr. Peddada was wrongfully discharged due to his disability after Centura “exploited [his] extensive patient base, referral network, and reputation to generate growth and profit.”
Colorado employment law attorney Deborah Yim, Esq., who is not involved in Peddada’s case, told this news organization that the ADA requires employers to provide reasonable accommodations for physical or mental impairments that substantially limit at least one major life activity, except when the request imposes an undue hardship on the employer.
“Depression and related mental health conditions would qualify, depending on the circumstances, and courts have certainly found them to be qualifying disabilities entitled to ADA protection in the past,” she said.
Not all employers are receptive to doctors’ needs, says the leadership team at Physicians Just Equity, an organization providing peer support to doctors experiencing workplace conflicts like discrimination and retaliation. They say that Dr. Peddada’s experience, where disclosing burnout results in being “ostracized, penalized, and ultimately ousted,” is the rule rather than the exception.
“Dr. Peddada’s case represents the unfortunate reality faced by many physicians in today’s clinical landscape,” the organization’s board of directors said in a written statement. “The imbalance of unreasonable professional demands, the lack of autonomy, moral injury, and disintegrating practice rewards is unsustainable for the medical professional.”
“Retaliation by employers after speaking up against this imbalance [and] requesting support and time to rejuvenate is a grave failure of health care systems that prioritize the business of delivering health care over the health, well-being, and satisfaction of their most valuable resource – the physician,” the board added in their statement.
Dr. Peddada has since closed his private practice and works as an independent contractor and consultant, his attorney, Iris Halpern, JD, said in an interview. She says Centura could have honored the accommodation request or suggested another option that met his needs, but “not only were they unsupportive, they terminated him.”
Ms. Yim says the parties will have opportunities to reach a settlement and resolve the dispute as the case works through the court system. Otherwise, Dr. Peddada and Centura may eventually head to trial.
Current state of physician burnout
The state of physician burnout is certainly a concerning one. More than half (53%) of physicians responding to this year’s Medscape Physician Burnout & Depression Report said they are burned out. Nearly one-quarter reported feeling depressed. Some of the top reasons they cited were too many bureaucratic tasks (61%), too many work hours (37%), and lack of autonomy (31%).
A 2022 study by the Mayo Clinic found a substantial increase in physician burnout in the first 2 years of the pandemic, with doctors reporting rising emotional exhaustion and depersonalization.
Although burnout affects many physicians and is a priority focus of the National Academy of Medicine’s plan to restore workforce well-being, admitting it is often seen as taboo and can imperil a doctor’s career. In the Medscape report, for example, 39% of physicians said they would not even consider professional treatment for burnout, with many commenting that they would just deal with it themselves.
“Many physicians are frightened to take time out for self-care because [they] fear losing their job, being stigmatized, and potentially ending their careers,” said Dr. Peddada, adding that physicians are commonly asked questions about their mental health when applying for hospital privileges. He says this dynamic forces them to choose between getting help or ignoring their true feelings, leading to poor quality of care and patient safety risks.
Medical licensing boards probe physicians’ mental health, too. As part of its #FightingForDocs campaign, the American Medical Association hopes to remove the stigma around burnout and depression and advocates for licensing boards to revise questions that may discourage physicians from seeking assistance. The AMA recommends that physicians only disclose current physical or mental conditions affecting their ability to practice.
Pringl Miller, MD, founder and executive director of Physician Just Equity, told Medscape that improving physician wellness requires structural change.
“Physicians (who) experience burnout without the proper accommodations run the risk of personal harm, because most physicians will prioritize the health and well-being of their patients over themselves ... [resulting in] suboptimal and unsafe patient care,” she said.
Helping doctors regain a sense of purpose
One change involves reframing how the health care industry thinks about and approaches burnout, says Steven Siegel, MD, chief mental health and wellness officer with Keck Medicine of USC. He told this news organization that these discussions should enhance the physician’s sense of purpose.
“Some people treat burnout as a concrete disorder like cancer, instead of saying, ‘I’m feeling exhausted, demoralized, and don’t enjoy my job anymore. What can we do to restore my enthusiasm for work?’ ”
Dr. Siegel recognizes that these issues existed before the pandemic and have only worsened as physicians feel less connected to and satisfied with their profession – a byproduct, he says, of the commercialization of medicine.
“We’ve moved from practices to systems, then from small to large systems, where it seems the path to survival is cutting costs and increasing margins, even among nonprofits.”
The road ahead
Making headway on these problems will take time. Last year, Keck Medicine received a $2 million grant to launch a 3-year randomized clinical trial to help reconnect physicians and other clinicians with their work. Dr. Siegel says the trial may serve as a national pilot program and will eventually grow to include 400 volunteers.
The trial will investigate the effectiveness of three possible interventions: (1) teaching people how to regulate their internal narratives and emotions through techniques like cognitive behavioral therapy and acceptance and commitment therapy; (2) providing customized EHR training to reduce the burden of navigating the system; and (3) allowing physicians to weigh in on workflow changes.
“We put physicians on teams that make the decisions about workflows,” said Dr. Siegel. The arrangement can give people the agency they desire and help them understand why an idea might not be plausible, which enriches future suggestions and discussions, he says.
A version of this article first appeared on Medscape.com.
Can this device take on enlarged prostates?
Inflating a drug-coated balloon in the prostate is the latest approach to treating a common cause of frequent or difficult urination in older men.
As the prostate naturally grows with age, the gland can obstruct the flow of urine – leading to frequent trips to the bathroom and disrupted nights. An estimated 50% of men aged 60 years and older have benign prostatic hyperplasia (BPH). That figure rises to more than 80% by age 70 and to 90% by age 80.
Transurethral resection of the prostate was the main surgical treatment for symptomatic BPH for much of the 20th century.
More recently, researchers have developed various minimally invasive surgical therapy (MIST) devices to treat the obstruction while limiting effects on sexual function. Some newer devices use lasers or water vapor to remove prostate tissue. Another approach uses implants to move and hold prostate tissue out of the way.
Now drug-coated balloons have entered the picture.
, paclitaxel – best known as a chemotherapy medication – to limit further growth and keep the lobes apart.
The Food and Drug Administration approved Optilume BPH in June. The results from a randomized controlled trial of the device were published in The Journal of Urology.
Uptake of MIST devices for BPH “has been variable due to a host of factors including mixed results, complexity of equipment, and costs,” the journal’s editor, D. Robert Siemens, MD, noted in the issue.
The developer of the device, Urotronic, said it expects that the newest treatment will be commercially available in the near future. Discussions about cost, insurance coverage, and how to train urologists to use it are ongoing, said Ian Schorn, the company’s vice president of clinical affairs.
Raevti Bole, MD, a urologic surgeon at Cleveland Clinic’s Glickman Urological and Kidney Institute, said BPH treatments ideally benefit patients for years, so she is eager to see how patients are doing 5 and 10 years after the Optilume BPH procedure. Studies should also examine its effects on fertility.
But given the safety and efficacy results reported 1 year after treatment, “I think this is something that a lot of people are going to be able to use in their practice and that their patients are going to benefit from,” Dr. Bole told this news organization.
She said she expects most urologists will be able to master the technology. The procedure’s minimal effect on sexual issues and the relatively short time needed to perform it are other advantages.
“All of those things are very positive in terms of whether patients are going to want to consider it and also whether surgeons are going to be able to realistically learn it and offer it at their centers,” Dr. Bole said.
In choosing a particular treatment, Dr. Bole discusses options with patients and takes into account factors such as trial data, the nature and severity of symptoms, treatment goals, comorbidities, and the size of the prostate.
Available MIST devices can vary by institution, and urologists can have different levels of experience with each device. If a patient is interested in an approach a surgeon does not offer, the surgeon can refer the patient to a colleague who does.
Active vs. sham treatment
Urologists may be familiar with another Optilume device, the Optilume urethral drug-coated balloon, that is used for urethral strictures.
The devices have similar names, and the underlying technology is similar, but there are major differences, Mr. Schorn said.
The BPH device expands between the lobes of the prostate, creating an anterior commissurotomy. A double-lobe balloon locks the device in place during inflation.
For the PINNACLE trial of the BPH device, which was conducted at 18 sites in the United States and Canada, Steven A. Kaplan, MD, of the Icahn School of Medicine at Mount Sinai, New York, and colleagues enrolled 148 men with symptomatic BPH who were experiencing urinary flow obstruction.
The average age of the patients was 65 years; 100 of them were assigned to undergo active treatment with Optilume BPH. The rest received a sham procedure that mimicked active treatment.
At 3 months, men who received active treatment had an average improvement in the International Prostate Symptom Score of about 11 points. This improvement was maintained at 1 year. Those who received sham treatment experienced an 8-point improvement at 3 months that dissipated over time.
The rate of urine flow increased dramatically with Optilume BPH, the researchers reported.
Five serious adverse events were considered to be possibly related to the device. There were four cases of postprocedural hematuria that required cystoscopic management or extended observation, and one case of urethral false passage that required extended catheterization.
Nonserious adverse events in the men who underwent the Optilume procedure typically resolved in about a month and included hematuria (40%), urinary tract infection (14%), dysuria (9.2%), urge or mixed incontinence (8.2%), mild stress incontinence (7.1%), bladder spasms (6.1%), elevated prostate-specific antigen levels (6.1%), and urinary urgency (6.1%), according to the researchers.
In a subset of participants for whom pharmacokinetic data were available, systemic exposure to paclitaxel was minimal.
Four participants in the Optilume BPH arm (4.1%) reported ejaculatory dysfunction, compared with one man in the sham treatment arm (2.1%). There were no cases of treatment-related erectile dysfunction.
Most patients were treated under deep sedation or general anesthesia, and the average procedure time was 26 minutes.
After the procedure, patients received a Foley catheter, which remained in place for about 2 days, “which is not significantly different from water vapor thermal therapy, holmium laser enucleation of the prostate, or laser photovaporization in similar gland sizes,” Dr. Bole and Petar Bajic, MD, also with Cleveland Clinic, noted in a commentary accompanying the article in The Journal of Urology.
MIST devices can be ideal for patients who prioritize sexual function, but the need for a temporary catheter after the procedure can be a “major postoperative source of patient dissatisfaction,” they acknowledged.
“Consistent with other minimally invasive technologies, the Optilume BPH procedure is a straightforward procedure that can be conducted in an ambulatory or office outpatient setting with pain management at physician and patient discretion,” Dr. Kaplan and his coauthors wrote.
The study was featured on the cover of the journal, which the research team saw as an unusual but welcome spotlight for a treatment for BPH.
“We were thrilled that we got on the cover of The Journal of Urology, which is not a common thing for BPH technology,” Mr. Schorn said.
Urotronic funded the PINNACLE study. Dr. Bole has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Inflating a drug-coated balloon in the prostate is the latest approach to treating a common cause of frequent or difficult urination in older men.
As the prostate naturally grows with age, the gland can obstruct the flow of urine – leading to frequent trips to the bathroom and disrupted nights. An estimated 50% of men aged 60 years and older have benign prostatic hyperplasia (BPH). That figure rises to more than 80% by age 70 and to 90% by age 80.
Transurethral resection of the prostate was the main surgical treatment for symptomatic BPH for much of the 20th century.
More recently, researchers have developed various minimally invasive surgical therapy (MIST) devices to treat the obstruction while limiting effects on sexual function. Some newer devices use lasers or water vapor to remove prostate tissue. Another approach uses implants to move and hold prostate tissue out of the way.
Now drug-coated balloons have entered the picture.
, paclitaxel – best known as a chemotherapy medication – to limit further growth and keep the lobes apart.
The Food and Drug Administration approved Optilume BPH in June. The results from a randomized controlled trial of the device were published in The Journal of Urology.
Uptake of MIST devices for BPH “has been variable due to a host of factors including mixed results, complexity of equipment, and costs,” the journal’s editor, D. Robert Siemens, MD, noted in the issue.
The developer of the device, Urotronic, said it expects that the newest treatment will be commercially available in the near future. Discussions about cost, insurance coverage, and how to train urologists to use it are ongoing, said Ian Schorn, the company’s vice president of clinical affairs.
Raevti Bole, MD, a urologic surgeon at Cleveland Clinic’s Glickman Urological and Kidney Institute, said BPH treatments ideally benefit patients for years, so she is eager to see how patients are doing 5 and 10 years after the Optilume BPH procedure. Studies should also examine its effects on fertility.
But given the safety and efficacy results reported 1 year after treatment, “I think this is something that a lot of people are going to be able to use in their practice and that their patients are going to benefit from,” Dr. Bole told this news organization.
She said she expects most urologists will be able to master the technology. The procedure’s minimal effect on sexual issues and the relatively short time needed to perform it are other advantages.
“All of those things are very positive in terms of whether patients are going to want to consider it and also whether surgeons are going to be able to realistically learn it and offer it at their centers,” Dr. Bole said.
In choosing a particular treatment, Dr. Bole discusses options with patients and takes into account factors such as trial data, the nature and severity of symptoms, treatment goals, comorbidities, and the size of the prostate.
Available MIST devices can vary by institution, and urologists can have different levels of experience with each device. If a patient is interested in an approach a surgeon does not offer, the surgeon can refer the patient to a colleague who does.
Active vs. sham treatment
Urologists may be familiar with another Optilume device, the Optilume urethral drug-coated balloon, that is used for urethral strictures.
The devices have similar names, and the underlying technology is similar, but there are major differences, Mr. Schorn said.
The BPH device expands between the lobes of the prostate, creating an anterior commissurotomy. A double-lobe balloon locks the device in place during inflation.
For the PINNACLE trial of the BPH device, which was conducted at 18 sites in the United States and Canada, Steven A. Kaplan, MD, of the Icahn School of Medicine at Mount Sinai, New York, and colleagues enrolled 148 men with symptomatic BPH who were experiencing urinary flow obstruction.
The average age of the patients was 65 years; 100 of them were assigned to undergo active treatment with Optilume BPH. The rest received a sham procedure that mimicked active treatment.
At 3 months, men who received active treatment had an average improvement in the International Prostate Symptom Score of about 11 points. This improvement was maintained at 1 year. Those who received sham treatment experienced an 8-point improvement at 3 months that dissipated over time.
The rate of urine flow increased dramatically with Optilume BPH, the researchers reported.
Five serious adverse events were considered to be possibly related to the device. There were four cases of postprocedural hematuria that required cystoscopic management or extended observation, and one case of urethral false passage that required extended catheterization.
Nonserious adverse events in the men who underwent the Optilume procedure typically resolved in about a month and included hematuria (40%), urinary tract infection (14%), dysuria (9.2%), urge or mixed incontinence (8.2%), mild stress incontinence (7.1%), bladder spasms (6.1%), elevated prostate-specific antigen levels (6.1%), and urinary urgency (6.1%), according to the researchers.
In a subset of participants for whom pharmacokinetic data were available, systemic exposure to paclitaxel was minimal.
Four participants in the Optilume BPH arm (4.1%) reported ejaculatory dysfunction, compared with one man in the sham treatment arm (2.1%). There were no cases of treatment-related erectile dysfunction.
Most patients were treated under deep sedation or general anesthesia, and the average procedure time was 26 minutes.
After the procedure, patients received a Foley catheter, which remained in place for about 2 days, “which is not significantly different from water vapor thermal therapy, holmium laser enucleation of the prostate, or laser photovaporization in similar gland sizes,” Dr. Bole and Petar Bajic, MD, also with Cleveland Clinic, noted in a commentary accompanying the article in The Journal of Urology.
MIST devices can be ideal for patients who prioritize sexual function, but the need for a temporary catheter after the procedure can be a “major postoperative source of patient dissatisfaction,” they acknowledged.
“Consistent with other minimally invasive technologies, the Optilume BPH procedure is a straightforward procedure that can be conducted in an ambulatory or office outpatient setting with pain management at physician and patient discretion,” Dr. Kaplan and his coauthors wrote.
The study was featured on the cover of the journal, which the research team saw as an unusual but welcome spotlight for a treatment for BPH.
“We were thrilled that we got on the cover of The Journal of Urology, which is not a common thing for BPH technology,” Mr. Schorn said.
Urotronic funded the PINNACLE study. Dr. Bole has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Inflating a drug-coated balloon in the prostate is the latest approach to treating a common cause of frequent or difficult urination in older men.
As the prostate naturally grows with age, the gland can obstruct the flow of urine – leading to frequent trips to the bathroom and disrupted nights. An estimated 50% of men aged 60 years and older have benign prostatic hyperplasia (BPH). That figure rises to more than 80% by age 70 and to 90% by age 80.
Transurethral resection of the prostate was the main surgical treatment for symptomatic BPH for much of the 20th century.
More recently, researchers have developed various minimally invasive surgical therapy (MIST) devices to treat the obstruction while limiting effects on sexual function. Some newer devices use lasers or water vapor to remove prostate tissue. Another approach uses implants to move and hold prostate tissue out of the way.
Now drug-coated balloons have entered the picture.
, paclitaxel – best known as a chemotherapy medication – to limit further growth and keep the lobes apart.
The Food and Drug Administration approved Optilume BPH in June. The results from a randomized controlled trial of the device were published in The Journal of Urology.
Uptake of MIST devices for BPH “has been variable due to a host of factors including mixed results, complexity of equipment, and costs,” the journal’s editor, D. Robert Siemens, MD, noted in the issue.
The developer of the device, Urotronic, said it expects that the newest treatment will be commercially available in the near future. Discussions about cost, insurance coverage, and how to train urologists to use it are ongoing, said Ian Schorn, the company’s vice president of clinical affairs.
Raevti Bole, MD, a urologic surgeon at Cleveland Clinic’s Glickman Urological and Kidney Institute, said BPH treatments ideally benefit patients for years, so she is eager to see how patients are doing 5 and 10 years after the Optilume BPH procedure. Studies should also examine its effects on fertility.
But given the safety and efficacy results reported 1 year after treatment, “I think this is something that a lot of people are going to be able to use in their practice and that their patients are going to benefit from,” Dr. Bole told this news organization.
She said she expects most urologists will be able to master the technology. The procedure’s minimal effect on sexual issues and the relatively short time needed to perform it are other advantages.
“All of those things are very positive in terms of whether patients are going to want to consider it and also whether surgeons are going to be able to realistically learn it and offer it at their centers,” Dr. Bole said.
In choosing a particular treatment, Dr. Bole discusses options with patients and takes into account factors such as trial data, the nature and severity of symptoms, treatment goals, comorbidities, and the size of the prostate.
Available MIST devices can vary by institution, and urologists can have different levels of experience with each device. If a patient is interested in an approach a surgeon does not offer, the surgeon can refer the patient to a colleague who does.
Active vs. sham treatment
Urologists may be familiar with another Optilume device, the Optilume urethral drug-coated balloon, that is used for urethral strictures.
The devices have similar names, and the underlying technology is similar, but there are major differences, Mr. Schorn said.
The BPH device expands between the lobes of the prostate, creating an anterior commissurotomy. A double-lobe balloon locks the device in place during inflation.
For the PINNACLE trial of the BPH device, which was conducted at 18 sites in the United States and Canada, Steven A. Kaplan, MD, of the Icahn School of Medicine at Mount Sinai, New York, and colleagues enrolled 148 men with symptomatic BPH who were experiencing urinary flow obstruction.
The average age of the patients was 65 years; 100 of them were assigned to undergo active treatment with Optilume BPH. The rest received a sham procedure that mimicked active treatment.
At 3 months, men who received active treatment had an average improvement in the International Prostate Symptom Score of about 11 points. This improvement was maintained at 1 year. Those who received sham treatment experienced an 8-point improvement at 3 months that dissipated over time.
The rate of urine flow increased dramatically with Optilume BPH, the researchers reported.
Five serious adverse events were considered to be possibly related to the device. There were four cases of postprocedural hematuria that required cystoscopic management or extended observation, and one case of urethral false passage that required extended catheterization.
Nonserious adverse events in the men who underwent the Optilume procedure typically resolved in about a month and included hematuria (40%), urinary tract infection (14%), dysuria (9.2%), urge or mixed incontinence (8.2%), mild stress incontinence (7.1%), bladder spasms (6.1%), elevated prostate-specific antigen levels (6.1%), and urinary urgency (6.1%), according to the researchers.
In a subset of participants for whom pharmacokinetic data were available, systemic exposure to paclitaxel was minimal.
Four participants in the Optilume BPH arm (4.1%) reported ejaculatory dysfunction, compared with one man in the sham treatment arm (2.1%). There were no cases of treatment-related erectile dysfunction.
Most patients were treated under deep sedation or general anesthesia, and the average procedure time was 26 minutes.
After the procedure, patients received a Foley catheter, which remained in place for about 2 days, “which is not significantly different from water vapor thermal therapy, holmium laser enucleation of the prostate, or laser photovaporization in similar gland sizes,” Dr. Bole and Petar Bajic, MD, also with Cleveland Clinic, noted in a commentary accompanying the article in The Journal of Urology.
MIST devices can be ideal for patients who prioritize sexual function, but the need for a temporary catheter after the procedure can be a “major postoperative source of patient dissatisfaction,” they acknowledged.
“Consistent with other minimally invasive technologies, the Optilume BPH procedure is a straightforward procedure that can be conducted in an ambulatory or office outpatient setting with pain management at physician and patient discretion,” Dr. Kaplan and his coauthors wrote.
The study was featured on the cover of the journal, which the research team saw as an unusual but welcome spotlight for a treatment for BPH.
“We were thrilled that we got on the cover of The Journal of Urology, which is not a common thing for BPH technology,” Mr. Schorn said.
Urotronic funded the PINNACLE study. Dr. Bole has disclosed no relevant financial relationships.
A version of this article appeared on Medscape.com.
Is this the best screening test for prostate cancer?
In the ReIMAGINE study, a group of researchers from the United Kingdom found that half of men with apparently “safe” levels of prostate-specific antigen (PSA) below 3 ng/mL had clinically significant prostate cancers when multiparametric MRI was added to screening. The researchers, whose paper appeared in BMJ Oncology, also found that one in six screened men had a prostate lesion on MRI.
Meanwhile, a large Swedish population-based study, published in JAMA Network Open, showed that pre-biopsy MRIs combined with PSA testing after adoption of guidelines recommending MRIs led to a decrease in the proportion of men with negative biopsies (28% to 7%) and the number of Gleason score 6 cancers (24% to 6%), while the proportion of Gleason score 7-10 cancers rose from 49% to 86%.
Researchers compared prostate MRI uptake rates in the Jönköping Region in southern Sweden over 9 years – 2011 through 2018 before prostate MRIs were recommended nationally, and 2018-2020 when MRIs became commonly used.
David Robinson, MD, PhD, associate professor at Linköping University and leader of the Swedish study, told this news organization: “MRI is now standard for men before biopsy” in that country. In Sweden, which has a high rate of mortality from prostate cancer – about 50 deaths per 100,000 men vs. 12 and 8 per 100,000 in the United Kingdom and United States, respectively – PSA testing is not routine. “Most men that are diagnosed with prostate cancer have no symptoms. They have asked for a PSA when they have visited their general practitioner,” Dr. Robinson said. “To take a PSA test is not encouraged but it is not discouraged either. It is up to each man to decide.”
PSA screening is not common in the United Kingdom. Caroline Moore, MD, chair of urology at University College London and principal investigator on ReIMAGINE, said only 20% of UK men older than age 50 undergo PSA tests because doctors in the United Kingdom are concerned about the sort of overdiagnosis and overtreatment of prostate cancer that has occurred in the United States since the mid-1990s, when PSA screening was adopted here.
The rate of PSA screening in the United States has declined with controversies over recommendations for screening, though they remain above European rates: 37% in 2019, down from 47% in 2005, according to a 2022 Veterans Administration study published in JAMA Oncology.
In the UK study, Dr. Moore’s hospital-based group asked general practitioners to send letters to 2,096 men aged 50-75 years who had not been diagnosed with prostate cancer, inviting them to undergo prostate health checks combining screening with PSA and 10-minute prostate MRIs.
Of the 457 men who responded to the letters, 303 completed both screening tests. Older White men were more likely to respond, and Black men responded 20% less often.
Of the men who completed screening, 29 (9.6%) were diagnosed with clinically significant cancer and 3 were diagnosed with clinically insignificant cancer, the researchers reported.
Dr. Moore said the PSA and MRI-first approach spared men from biopsies as well as the downsides of active surveillance, which include close monitoring with urology visits and occasional MRIs or biopsies over many years. Biopsies are considered undesirable because of pain and the risk for sepsis and other infections associated with transrectal biopsies.
But urologists in America were less convinced by the international data. William J. Catalona, MD, a urologist at Northwestern University in Chicago, who developed the PSA screening test in the 1990s, said he wasn’t surprised so many men in ReIMAGINE with low PSAs had advanced cancers. “Some of the most aggressive prostate cancers occur in men with a low PSA level – not new news,” he said.
Dr. Catalona also disagreed with the UK researchers’ emphasis on MRIs because the readings often are incorrect. A 2021 study in Prostate Cancer and Prostatic Diseases reported that multiparametric MRI had a false-negative rate of between 10% and 20%.
“MRI alone should not be considered more reliable than PSA. Rather, it should be considered complementary,” he said.
Michael S. Leapman, MD, MHS, associate professor of urology at the Yale Cancer Center, New Haven, Conn., said the UK findings point to a role for MRI as a “triage tool” to help identify men with elevated PSAs who should have a prostate biopsy.
But he said the research to date doesn’t support the use of MRI as a stand-alone test for prostate cancer. “In my opinion, it would have to demonstrate some tangible benefit to patients other than finding a greater number of cancers, such as improvement in cancer control, lower burden from the disease overall, or cancer-specific survival,” he said.
Major U.S. guidelines recommend including MRIs before biopsies. Dr. Leapman also pointed out that 2023 recommendations from the National Comprehensive Cancer Network state that MRI is “strongly recommended if available.” Yet fewer than half of U.S. urologists use MRIs as a screening tool, he said.
“My sense is that MRI is not available everywhere. We have also seen that wait times are too long in some centers, leading physicians and patients to opt for biopsy – particularly in cases with higher suspicion,” he said.
The studies from Sweden and the United Kingdom “demonstrate the strides being made in reducing overdetection of low-grade prostate cancer will increase detection of clinically significant Gleason 3+4 or higher” tumors, Dr. Leapman said. “It is unclear whether such patients in whom their otherwise low-risk disease is recast as ‘intermediate risk’ meaningfully stand to benefit in the long term from this detection.”
Dr. Robinson reported no relevant financial conflicts of interest. The Swedish Cancer Society, the Swedish Research Council, Region Jönköping, Futurum, and Clinical Cancer Research Foundation in Jönköping supported the Swedish study. Members of the ReIMAGINE study team disclosed research support from the United Kingdom’s National Institute of Health Research and various industry/other sources. The Medical Research Council and Cancer Research UK funded the ReIMAGINE study.
A version of this article appeared on Medscape.com.
In the ReIMAGINE study, a group of researchers from the United Kingdom found that half of men with apparently “safe” levels of prostate-specific antigen (PSA) below 3 ng/mL had clinically significant prostate cancers when multiparametric MRI was added to screening. The researchers, whose paper appeared in BMJ Oncology, also found that one in six screened men had a prostate lesion on MRI.
Meanwhile, a large Swedish population-based study, published in JAMA Network Open, showed that pre-biopsy MRIs combined with PSA testing after adoption of guidelines recommending MRIs led to a decrease in the proportion of men with negative biopsies (28% to 7%) and the number of Gleason score 6 cancers (24% to 6%), while the proportion of Gleason score 7-10 cancers rose from 49% to 86%.
Researchers compared prostate MRI uptake rates in the Jönköping Region in southern Sweden over 9 years – 2011 through 2018 before prostate MRIs were recommended nationally, and 2018-2020 when MRIs became commonly used.
David Robinson, MD, PhD, associate professor at Linköping University and leader of the Swedish study, told this news organization: “MRI is now standard for men before biopsy” in that country. In Sweden, which has a high rate of mortality from prostate cancer – about 50 deaths per 100,000 men vs. 12 and 8 per 100,000 in the United Kingdom and United States, respectively – PSA testing is not routine. “Most men that are diagnosed with prostate cancer have no symptoms. They have asked for a PSA when they have visited their general practitioner,” Dr. Robinson said. “To take a PSA test is not encouraged but it is not discouraged either. It is up to each man to decide.”
PSA screening is not common in the United Kingdom. Caroline Moore, MD, chair of urology at University College London and principal investigator on ReIMAGINE, said only 20% of UK men older than age 50 undergo PSA tests because doctors in the United Kingdom are concerned about the sort of overdiagnosis and overtreatment of prostate cancer that has occurred in the United States since the mid-1990s, when PSA screening was adopted here.
The rate of PSA screening in the United States has declined with controversies over recommendations for screening, though they remain above European rates: 37% in 2019, down from 47% in 2005, according to a 2022 Veterans Administration study published in JAMA Oncology.
In the UK study, Dr. Moore’s hospital-based group asked general practitioners to send letters to 2,096 men aged 50-75 years who had not been diagnosed with prostate cancer, inviting them to undergo prostate health checks combining screening with PSA and 10-minute prostate MRIs.
Of the 457 men who responded to the letters, 303 completed both screening tests. Older White men were more likely to respond, and Black men responded 20% less often.
Of the men who completed screening, 29 (9.6%) were diagnosed with clinically significant cancer and 3 were diagnosed with clinically insignificant cancer, the researchers reported.
Dr. Moore said the PSA and MRI-first approach spared men from biopsies as well as the downsides of active surveillance, which include close monitoring with urology visits and occasional MRIs or biopsies over many years. Biopsies are considered undesirable because of pain and the risk for sepsis and other infections associated with transrectal biopsies.
But urologists in America were less convinced by the international data. William J. Catalona, MD, a urologist at Northwestern University in Chicago, who developed the PSA screening test in the 1990s, said he wasn’t surprised so many men in ReIMAGINE with low PSAs had advanced cancers. “Some of the most aggressive prostate cancers occur in men with a low PSA level – not new news,” he said.
Dr. Catalona also disagreed with the UK researchers’ emphasis on MRIs because the readings often are incorrect. A 2021 study in Prostate Cancer and Prostatic Diseases reported that multiparametric MRI had a false-negative rate of between 10% and 20%.
“MRI alone should not be considered more reliable than PSA. Rather, it should be considered complementary,” he said.
Michael S. Leapman, MD, MHS, associate professor of urology at the Yale Cancer Center, New Haven, Conn., said the UK findings point to a role for MRI as a “triage tool” to help identify men with elevated PSAs who should have a prostate biopsy.
But he said the research to date doesn’t support the use of MRI as a stand-alone test for prostate cancer. “In my opinion, it would have to demonstrate some tangible benefit to patients other than finding a greater number of cancers, such as improvement in cancer control, lower burden from the disease overall, or cancer-specific survival,” he said.
Major U.S. guidelines recommend including MRIs before biopsies. Dr. Leapman also pointed out that 2023 recommendations from the National Comprehensive Cancer Network state that MRI is “strongly recommended if available.” Yet fewer than half of U.S. urologists use MRIs as a screening tool, he said.
“My sense is that MRI is not available everywhere. We have also seen that wait times are too long in some centers, leading physicians and patients to opt for biopsy – particularly in cases with higher suspicion,” he said.
The studies from Sweden and the United Kingdom “demonstrate the strides being made in reducing overdetection of low-grade prostate cancer will increase detection of clinically significant Gleason 3+4 or higher” tumors, Dr. Leapman said. “It is unclear whether such patients in whom their otherwise low-risk disease is recast as ‘intermediate risk’ meaningfully stand to benefit in the long term from this detection.”
Dr. Robinson reported no relevant financial conflicts of interest. The Swedish Cancer Society, the Swedish Research Council, Region Jönköping, Futurum, and Clinical Cancer Research Foundation in Jönköping supported the Swedish study. Members of the ReIMAGINE study team disclosed research support from the United Kingdom’s National Institute of Health Research and various industry/other sources. The Medical Research Council and Cancer Research UK funded the ReIMAGINE study.
A version of this article appeared on Medscape.com.
In the ReIMAGINE study, a group of researchers from the United Kingdom found that half of men with apparently “safe” levels of prostate-specific antigen (PSA) below 3 ng/mL had clinically significant prostate cancers when multiparametric MRI was added to screening. The researchers, whose paper appeared in BMJ Oncology, also found that one in six screened men had a prostate lesion on MRI.
Meanwhile, a large Swedish population-based study, published in JAMA Network Open, showed that pre-biopsy MRIs combined with PSA testing after adoption of guidelines recommending MRIs led to a decrease in the proportion of men with negative biopsies (28% to 7%) and the number of Gleason score 6 cancers (24% to 6%), while the proportion of Gleason score 7-10 cancers rose from 49% to 86%.
Researchers compared prostate MRI uptake rates in the Jönköping Region in southern Sweden over 9 years – 2011 through 2018 before prostate MRIs were recommended nationally, and 2018-2020 when MRIs became commonly used.
David Robinson, MD, PhD, associate professor at Linköping University and leader of the Swedish study, told this news organization: “MRI is now standard for men before biopsy” in that country. In Sweden, which has a high rate of mortality from prostate cancer – about 50 deaths per 100,000 men vs. 12 and 8 per 100,000 in the United Kingdom and United States, respectively – PSA testing is not routine. “Most men that are diagnosed with prostate cancer have no symptoms. They have asked for a PSA when they have visited their general practitioner,” Dr. Robinson said. “To take a PSA test is not encouraged but it is not discouraged either. It is up to each man to decide.”
PSA screening is not common in the United Kingdom. Caroline Moore, MD, chair of urology at University College London and principal investigator on ReIMAGINE, said only 20% of UK men older than age 50 undergo PSA tests because doctors in the United Kingdom are concerned about the sort of overdiagnosis and overtreatment of prostate cancer that has occurred in the United States since the mid-1990s, when PSA screening was adopted here.
The rate of PSA screening in the United States has declined with controversies over recommendations for screening, though they remain above European rates: 37% in 2019, down from 47% in 2005, according to a 2022 Veterans Administration study published in JAMA Oncology.
In the UK study, Dr. Moore’s hospital-based group asked general practitioners to send letters to 2,096 men aged 50-75 years who had not been diagnosed with prostate cancer, inviting them to undergo prostate health checks combining screening with PSA and 10-minute prostate MRIs.
Of the 457 men who responded to the letters, 303 completed both screening tests. Older White men were more likely to respond, and Black men responded 20% less often.
Of the men who completed screening, 29 (9.6%) were diagnosed with clinically significant cancer and 3 were diagnosed with clinically insignificant cancer, the researchers reported.
Dr. Moore said the PSA and MRI-first approach spared men from biopsies as well as the downsides of active surveillance, which include close monitoring with urology visits and occasional MRIs or biopsies over many years. Biopsies are considered undesirable because of pain and the risk for sepsis and other infections associated with transrectal biopsies.
But urologists in America were less convinced by the international data. William J. Catalona, MD, a urologist at Northwestern University in Chicago, who developed the PSA screening test in the 1990s, said he wasn’t surprised so many men in ReIMAGINE with low PSAs had advanced cancers. “Some of the most aggressive prostate cancers occur in men with a low PSA level – not new news,” he said.
Dr. Catalona also disagreed with the UK researchers’ emphasis on MRIs because the readings often are incorrect. A 2021 study in Prostate Cancer and Prostatic Diseases reported that multiparametric MRI had a false-negative rate of between 10% and 20%.
“MRI alone should not be considered more reliable than PSA. Rather, it should be considered complementary,” he said.
Michael S. Leapman, MD, MHS, associate professor of urology at the Yale Cancer Center, New Haven, Conn., said the UK findings point to a role for MRI as a “triage tool” to help identify men with elevated PSAs who should have a prostate biopsy.
But he said the research to date doesn’t support the use of MRI as a stand-alone test for prostate cancer. “In my opinion, it would have to demonstrate some tangible benefit to patients other than finding a greater number of cancers, such as improvement in cancer control, lower burden from the disease overall, or cancer-specific survival,” he said.
Major U.S. guidelines recommend including MRIs before biopsies. Dr. Leapman also pointed out that 2023 recommendations from the National Comprehensive Cancer Network state that MRI is “strongly recommended if available.” Yet fewer than half of U.S. urologists use MRIs as a screening tool, he said.
“My sense is that MRI is not available everywhere. We have also seen that wait times are too long in some centers, leading physicians and patients to opt for biopsy – particularly in cases with higher suspicion,” he said.
The studies from Sweden and the United Kingdom “demonstrate the strides being made in reducing overdetection of low-grade prostate cancer will increase detection of clinically significant Gleason 3+4 or higher” tumors, Dr. Leapman said. “It is unclear whether such patients in whom their otherwise low-risk disease is recast as ‘intermediate risk’ meaningfully stand to benefit in the long term from this detection.”
Dr. Robinson reported no relevant financial conflicts of interest. The Swedish Cancer Society, the Swedish Research Council, Region Jönköping, Futurum, and Clinical Cancer Research Foundation in Jönköping supported the Swedish study. Members of the ReIMAGINE study team disclosed research support from the United Kingdom’s National Institute of Health Research and various industry/other sources. The Medical Research Council and Cancer Research UK funded the ReIMAGINE study.
A version of this article appeared on Medscape.com.
‘Promising’ new txs for most common adult leukemia
The rapid rise of chimeric antigen receptor T (CAR T-cell) therapy has allowed hematologists to make great strides in treating aggressive cases of multiple myeloma and several types of lymphoma and leukemia. But patients with chronic lymphocytic leukemia (CLL), the most common leukemia in adults, have been left out.
“These are the two immunotherapies that have the most potential right now,” said Ohio State University, Columbus, hematologist Kerry A. Rogers, MD, in an interview. She went on to say that these treatments could be a boon for patients with CLL who don’t respond well to targeted therapy drugs or are so young that those medications may not retain effectiveness throughout the patients’ lifespans.
As the American Cancer Society explains, CAR T therapy is a way to get T cells “to fight cancer by changing them in the lab so they can find and destroy cancer cells.” The cells are then returned to the patient.
As the National Cancer Institute says, “If all goes as planned, the CAR T cells will continue to multiply in the patient’s body and, with guidance from their engineered receptor, recognize and kill any cancer cells that harbor the target antigen on their surfaces.”
According to Dr. Rogers, CAR T therapy is less toxic than stem cell transplantation, a related treatment. That means older people can better tolerate it, including many CLL patients in their late 60s and beyond, she said. (Side effects of CAR T therapy include cytokine release syndrome, nervous system impairment, and weakening of the immune system.)
Thus far, CAR T therapy has been approved by the U.S. Food and Drug Administration to treat lymphomas, some forms of leukemia, and multiple myeloma. “Despite the excitement around these therapies, they lead to long-term survival in fewer than half of the patients treated,” cautions the National Cancer Institute, which also notes their high cost: more than $450,000 in one case.
CAR T therapy is not FDA-approved for CLL. “There are many reasons why CAR T is less effective in patients with CLL versus other lymphomas,” said Lee Greenberger, PhD, chief scientific officer of the Leukemia & Lymphoma Society, in an interview. “For one, many patients with heavily pretreated CLL – prior to any use of CAR T – have mutations that are known to be difficult to treat. Dysfunctional T cells are also common in patients with CLL, and there’s often a lower number of available T-cells to manufacture.”
The results of a phase 1/2 trial released in August 2023 offered new insight about CAR T for CLL. In the open-label trial reported in The Lancet, 117 U.S. patients with CLL or small lymphocytic lymphoma underwent a form of CAR T therapy called lisocabtagene maraleucel after failing treatment with two lines of therapy, including a Bruton´s tyrosine kinase inhibitor. Among 49 patients at a specific dose, “the rate of complete response or remission (including with incomplete marrow recovery) was statistically significant at 18%,” the researchers reported. A total of 51 patients in the entire study died.
The rate of undetectable minimal residual disease blood was 64%. That rate is impressive, said University of Texas MD Anderson Cancer Center leukemia specialist Nitin Jain, MD, in an interview. It’s not nearly as high as researchers have seen in other disease settings, but it’s “a good, good thing for these patients. We’ll have to see in the longer follow-up how these patients fare 2, 3, or 4 years down the line.”
Dr. Rogers, the Ohio physician, said doctors had hoped durable benefit in the Lancet study would be more impressive. An important factor limiting its value may be the aggressiveness of the disease in patients who have already failed several treatments, she said. “The efficacy of CAR T might be improved by giving it as an earlier line of therapy before the CLL has become this aggressive. But it’s difficult to propose that you should use this before a Bruton´s tyrosine kinase inhibitor or venetoclax because it’s expensive and difficult.”
What’s next for CART T research in CLL? Understanding the best timing for treatment will be key, Dr. Rogers said.
The Leukemia & Lymphoma Society’s Dr. Greenberger predicted that “we will begin to see CAR T explored in CLL patients whose disease has a high risk of failing approved agents, such as Bruton´s tyrosine kinase and B cell lymphoma 2 inhibitors. However, CLL patients may still receive prior therapy with more effective Bruton’s tyrosine kinase or B cell lymphoma 2 inhibitors in the future before using CAR T. This will likely be heightened as more Bruton´s tyrosine kinase inhibitors become generic in the next 5 to 10 years and, hopefully, less expensive than CAR T therapy.”
In the big picture, he said, “treatment of CLL with CAR T is possible, but still needs significant improvements if it is to become a mainline therapy in the future.”
CAR T therapy remains available via clinical trials, and Dr. Rogers said it is “currently an important option for patients whose CLL has become resistant to standard targeted agents. We can certainly expect to extend someone’s expected survival by years if they have a favorable response.” She acknowledged that the cost is quite high, but noted that targeted therapies are also expensive, especially over the long term. They can run to $10,000-$20,000 a month. Bispecific antibodies are also being explored as potential therapy for CLL. “They’re really exciting,” Dr. Rogers said, with the potential to spur responses similar to those from CAR T therapy.
A 2022 review described these drugs as “molecules that combine antibody-directed therapies with cellular mediated immunotherapy.” The FDA explains that “by targeting two antigens or epitopes, they can cause multiple physiological or antitumor responses, which may be independent or connected.”
According to Dr. Greenberger, many bispecifics are in clinical trials now. However, “in the context of CLL, actually, the data is actually very, very limited. The development is just starting, and there are phase 1 and phase 2 trials ongoing.”
But data from lymphoma trials are encouraging, he said, and bispecifics “are actually looking as good as CAR T in some settings.”
Regimens can be a challenge for patients taking bispecifics, Dr. Greenberger said. “Repeat dosing with a step-up dosing approach to start is typically required when treating lymphoma.”
On the other hand, Dr. Rogers noted that antibody treatment can be easier for hematologists to arrange than CAR T therapy and stem cell transplants. “From an administrative side, there’s not as many things you need to have set up. So it’s able to be administered in a wider variety of settings,” she said,
Bispecific side effects include cytokine release syndrome and neurotoxicity as well as infusion reactions, Dr. Greenberger said, adding that “I would not exclude cost as a challenge.”
According to Formulary Watch, the bispecific Columvi (glofitamab-gxbm), which recently gained FDA approval to treat diffuse large B-cell lymphoma, is estimated to cost $350,000 for an 8.5-month round of treatment. Reuters reported that the bispecific Talvey (talquetamab-tgvs), which just received FDA approval to treat multiple myeloma, is estimated to cost $270,000-$360,000 for 6-8 months of treatment.
For now, bispecific trials “are mostly now reserved for patients with CLL who become resistant to our current standard targeted agents,” Dr. Rogers said. “It’s a little unclear if you can do CAR T therapy first and then bispecifics, or bispecifics and then CAR T therapy.”
What’s coming next for bispecifics? “On the horizon is better ease of administration, which is already being addressed by subcutaneous dosing for some bispecifics in lymphomas,” Dr. Greenberger said. “There’s also the possibility of combining bispecifics with conventional therapy.”
Dr. Rogers discloses ties with Genentech, AbbVie, Novartis, AstraZeneca, Janssen, Pharmacyclics, Beigene, and LOXO@Lilly. Dr. Greenberger discloses employment with the Leukemia & Lymphoma Society, which supports academic grants and a venture philanthropy via the Therapy Acceleration Program.
Dr. Jain reports ties with Pharmacyclics, AbbVie, Genentech, AstraZeneca, Pfizer, and numerous other disclosures.
The rapid rise of chimeric antigen receptor T (CAR T-cell) therapy has allowed hematologists to make great strides in treating aggressive cases of multiple myeloma and several types of lymphoma and leukemia. But patients with chronic lymphocytic leukemia (CLL), the most common leukemia in adults, have been left out.
“These are the two immunotherapies that have the most potential right now,” said Ohio State University, Columbus, hematologist Kerry A. Rogers, MD, in an interview. She went on to say that these treatments could be a boon for patients with CLL who don’t respond well to targeted therapy drugs or are so young that those medications may not retain effectiveness throughout the patients’ lifespans.
As the American Cancer Society explains, CAR T therapy is a way to get T cells “to fight cancer by changing them in the lab so they can find and destroy cancer cells.” The cells are then returned to the patient.
As the National Cancer Institute says, “If all goes as planned, the CAR T cells will continue to multiply in the patient’s body and, with guidance from their engineered receptor, recognize and kill any cancer cells that harbor the target antigen on their surfaces.”
According to Dr. Rogers, CAR T therapy is less toxic than stem cell transplantation, a related treatment. That means older people can better tolerate it, including many CLL patients in their late 60s and beyond, she said. (Side effects of CAR T therapy include cytokine release syndrome, nervous system impairment, and weakening of the immune system.)
Thus far, CAR T therapy has been approved by the U.S. Food and Drug Administration to treat lymphomas, some forms of leukemia, and multiple myeloma. “Despite the excitement around these therapies, they lead to long-term survival in fewer than half of the patients treated,” cautions the National Cancer Institute, which also notes their high cost: more than $450,000 in one case.
CAR T therapy is not FDA-approved for CLL. “There are many reasons why CAR T is less effective in patients with CLL versus other lymphomas,” said Lee Greenberger, PhD, chief scientific officer of the Leukemia & Lymphoma Society, in an interview. “For one, many patients with heavily pretreated CLL – prior to any use of CAR T – have mutations that are known to be difficult to treat. Dysfunctional T cells are also common in patients with CLL, and there’s often a lower number of available T-cells to manufacture.”
The results of a phase 1/2 trial released in August 2023 offered new insight about CAR T for CLL. In the open-label trial reported in The Lancet, 117 U.S. patients with CLL or small lymphocytic lymphoma underwent a form of CAR T therapy called lisocabtagene maraleucel after failing treatment with two lines of therapy, including a Bruton´s tyrosine kinase inhibitor. Among 49 patients at a specific dose, “the rate of complete response or remission (including with incomplete marrow recovery) was statistically significant at 18%,” the researchers reported. A total of 51 patients in the entire study died.
The rate of undetectable minimal residual disease blood was 64%. That rate is impressive, said University of Texas MD Anderson Cancer Center leukemia specialist Nitin Jain, MD, in an interview. It’s not nearly as high as researchers have seen in other disease settings, but it’s “a good, good thing for these patients. We’ll have to see in the longer follow-up how these patients fare 2, 3, or 4 years down the line.”
Dr. Rogers, the Ohio physician, said doctors had hoped durable benefit in the Lancet study would be more impressive. An important factor limiting its value may be the aggressiveness of the disease in patients who have already failed several treatments, she said. “The efficacy of CAR T might be improved by giving it as an earlier line of therapy before the CLL has become this aggressive. But it’s difficult to propose that you should use this before a Bruton´s tyrosine kinase inhibitor or venetoclax because it’s expensive and difficult.”
What’s next for CART T research in CLL? Understanding the best timing for treatment will be key, Dr. Rogers said.
The Leukemia & Lymphoma Society’s Dr. Greenberger predicted that “we will begin to see CAR T explored in CLL patients whose disease has a high risk of failing approved agents, such as Bruton´s tyrosine kinase and B cell lymphoma 2 inhibitors. However, CLL patients may still receive prior therapy with more effective Bruton’s tyrosine kinase or B cell lymphoma 2 inhibitors in the future before using CAR T. This will likely be heightened as more Bruton´s tyrosine kinase inhibitors become generic in the next 5 to 10 years and, hopefully, less expensive than CAR T therapy.”
In the big picture, he said, “treatment of CLL with CAR T is possible, but still needs significant improvements if it is to become a mainline therapy in the future.”
CAR T therapy remains available via clinical trials, and Dr. Rogers said it is “currently an important option for patients whose CLL has become resistant to standard targeted agents. We can certainly expect to extend someone’s expected survival by years if they have a favorable response.” She acknowledged that the cost is quite high, but noted that targeted therapies are also expensive, especially over the long term. They can run to $10,000-$20,000 a month. Bispecific antibodies are also being explored as potential therapy for CLL. “They’re really exciting,” Dr. Rogers said, with the potential to spur responses similar to those from CAR T therapy.
A 2022 review described these drugs as “molecules that combine antibody-directed therapies with cellular mediated immunotherapy.” The FDA explains that “by targeting two antigens or epitopes, they can cause multiple physiological or antitumor responses, which may be independent or connected.”
According to Dr. Greenberger, many bispecifics are in clinical trials now. However, “in the context of CLL, actually, the data is actually very, very limited. The development is just starting, and there are phase 1 and phase 2 trials ongoing.”
But data from lymphoma trials are encouraging, he said, and bispecifics “are actually looking as good as CAR T in some settings.”
Regimens can be a challenge for patients taking bispecifics, Dr. Greenberger said. “Repeat dosing with a step-up dosing approach to start is typically required when treating lymphoma.”
On the other hand, Dr. Rogers noted that antibody treatment can be easier for hematologists to arrange than CAR T therapy and stem cell transplants. “From an administrative side, there’s not as many things you need to have set up. So it’s able to be administered in a wider variety of settings,” she said,
Bispecific side effects include cytokine release syndrome and neurotoxicity as well as infusion reactions, Dr. Greenberger said, adding that “I would not exclude cost as a challenge.”
According to Formulary Watch, the bispecific Columvi (glofitamab-gxbm), which recently gained FDA approval to treat diffuse large B-cell lymphoma, is estimated to cost $350,000 for an 8.5-month round of treatment. Reuters reported that the bispecific Talvey (talquetamab-tgvs), which just received FDA approval to treat multiple myeloma, is estimated to cost $270,000-$360,000 for 6-8 months of treatment.
For now, bispecific trials “are mostly now reserved for patients with CLL who become resistant to our current standard targeted agents,” Dr. Rogers said. “It’s a little unclear if you can do CAR T therapy first and then bispecifics, or bispecifics and then CAR T therapy.”
What’s coming next for bispecifics? “On the horizon is better ease of administration, which is already being addressed by subcutaneous dosing for some bispecifics in lymphomas,” Dr. Greenberger said. “There’s also the possibility of combining bispecifics with conventional therapy.”
Dr. Rogers discloses ties with Genentech, AbbVie, Novartis, AstraZeneca, Janssen, Pharmacyclics, Beigene, and LOXO@Lilly. Dr. Greenberger discloses employment with the Leukemia & Lymphoma Society, which supports academic grants and a venture philanthropy via the Therapy Acceleration Program.
Dr. Jain reports ties with Pharmacyclics, AbbVie, Genentech, AstraZeneca, Pfizer, and numerous other disclosures.
The rapid rise of chimeric antigen receptor T (CAR T-cell) therapy has allowed hematologists to make great strides in treating aggressive cases of multiple myeloma and several types of lymphoma and leukemia. But patients with chronic lymphocytic leukemia (CLL), the most common leukemia in adults, have been left out.
“These are the two immunotherapies that have the most potential right now,” said Ohio State University, Columbus, hematologist Kerry A. Rogers, MD, in an interview. She went on to say that these treatments could be a boon for patients with CLL who don’t respond well to targeted therapy drugs or are so young that those medications may not retain effectiveness throughout the patients’ lifespans.
As the American Cancer Society explains, CAR T therapy is a way to get T cells “to fight cancer by changing them in the lab so they can find and destroy cancer cells.” The cells are then returned to the patient.
As the National Cancer Institute says, “If all goes as planned, the CAR T cells will continue to multiply in the patient’s body and, with guidance from their engineered receptor, recognize and kill any cancer cells that harbor the target antigen on their surfaces.”
According to Dr. Rogers, CAR T therapy is less toxic than stem cell transplantation, a related treatment. That means older people can better tolerate it, including many CLL patients in their late 60s and beyond, she said. (Side effects of CAR T therapy include cytokine release syndrome, nervous system impairment, and weakening of the immune system.)
Thus far, CAR T therapy has been approved by the U.S. Food and Drug Administration to treat lymphomas, some forms of leukemia, and multiple myeloma. “Despite the excitement around these therapies, they lead to long-term survival in fewer than half of the patients treated,” cautions the National Cancer Institute, which also notes their high cost: more than $450,000 in one case.
CAR T therapy is not FDA-approved for CLL. “There are many reasons why CAR T is less effective in patients with CLL versus other lymphomas,” said Lee Greenberger, PhD, chief scientific officer of the Leukemia & Lymphoma Society, in an interview. “For one, many patients with heavily pretreated CLL – prior to any use of CAR T – have mutations that are known to be difficult to treat. Dysfunctional T cells are also common in patients with CLL, and there’s often a lower number of available T-cells to manufacture.”
The results of a phase 1/2 trial released in August 2023 offered new insight about CAR T for CLL. In the open-label trial reported in The Lancet, 117 U.S. patients with CLL or small lymphocytic lymphoma underwent a form of CAR T therapy called lisocabtagene maraleucel after failing treatment with two lines of therapy, including a Bruton´s tyrosine kinase inhibitor. Among 49 patients at a specific dose, “the rate of complete response or remission (including with incomplete marrow recovery) was statistically significant at 18%,” the researchers reported. A total of 51 patients in the entire study died.
The rate of undetectable minimal residual disease blood was 64%. That rate is impressive, said University of Texas MD Anderson Cancer Center leukemia specialist Nitin Jain, MD, in an interview. It’s not nearly as high as researchers have seen in other disease settings, but it’s “a good, good thing for these patients. We’ll have to see in the longer follow-up how these patients fare 2, 3, or 4 years down the line.”
Dr. Rogers, the Ohio physician, said doctors had hoped durable benefit in the Lancet study would be more impressive. An important factor limiting its value may be the aggressiveness of the disease in patients who have already failed several treatments, she said. “The efficacy of CAR T might be improved by giving it as an earlier line of therapy before the CLL has become this aggressive. But it’s difficult to propose that you should use this before a Bruton´s tyrosine kinase inhibitor or venetoclax because it’s expensive and difficult.”
What’s next for CART T research in CLL? Understanding the best timing for treatment will be key, Dr. Rogers said.
The Leukemia & Lymphoma Society’s Dr. Greenberger predicted that “we will begin to see CAR T explored in CLL patients whose disease has a high risk of failing approved agents, such as Bruton´s tyrosine kinase and B cell lymphoma 2 inhibitors. However, CLL patients may still receive prior therapy with more effective Bruton’s tyrosine kinase or B cell lymphoma 2 inhibitors in the future before using CAR T. This will likely be heightened as more Bruton´s tyrosine kinase inhibitors become generic in the next 5 to 10 years and, hopefully, less expensive than CAR T therapy.”
In the big picture, he said, “treatment of CLL with CAR T is possible, but still needs significant improvements if it is to become a mainline therapy in the future.”
CAR T therapy remains available via clinical trials, and Dr. Rogers said it is “currently an important option for patients whose CLL has become resistant to standard targeted agents. We can certainly expect to extend someone’s expected survival by years if they have a favorable response.” She acknowledged that the cost is quite high, but noted that targeted therapies are also expensive, especially over the long term. They can run to $10,000-$20,000 a month. Bispecific antibodies are also being explored as potential therapy for CLL. “They’re really exciting,” Dr. Rogers said, with the potential to spur responses similar to those from CAR T therapy.
A 2022 review described these drugs as “molecules that combine antibody-directed therapies with cellular mediated immunotherapy.” The FDA explains that “by targeting two antigens or epitopes, they can cause multiple physiological or antitumor responses, which may be independent or connected.”
According to Dr. Greenberger, many bispecifics are in clinical trials now. However, “in the context of CLL, actually, the data is actually very, very limited. The development is just starting, and there are phase 1 and phase 2 trials ongoing.”
But data from lymphoma trials are encouraging, he said, and bispecifics “are actually looking as good as CAR T in some settings.”
Regimens can be a challenge for patients taking bispecifics, Dr. Greenberger said. “Repeat dosing with a step-up dosing approach to start is typically required when treating lymphoma.”
On the other hand, Dr. Rogers noted that antibody treatment can be easier for hematologists to arrange than CAR T therapy and stem cell transplants. “From an administrative side, there’s not as many things you need to have set up. So it’s able to be administered in a wider variety of settings,” she said,
Bispecific side effects include cytokine release syndrome and neurotoxicity as well as infusion reactions, Dr. Greenberger said, adding that “I would not exclude cost as a challenge.”
According to Formulary Watch, the bispecific Columvi (glofitamab-gxbm), which recently gained FDA approval to treat diffuse large B-cell lymphoma, is estimated to cost $350,000 for an 8.5-month round of treatment. Reuters reported that the bispecific Talvey (talquetamab-tgvs), which just received FDA approval to treat multiple myeloma, is estimated to cost $270,000-$360,000 for 6-8 months of treatment.
For now, bispecific trials “are mostly now reserved for patients with CLL who become resistant to our current standard targeted agents,” Dr. Rogers said. “It’s a little unclear if you can do CAR T therapy first and then bispecifics, or bispecifics and then CAR T therapy.”
What’s coming next for bispecifics? “On the horizon is better ease of administration, which is already being addressed by subcutaneous dosing for some bispecifics in lymphomas,” Dr. Greenberger said. “There’s also the possibility of combining bispecifics with conventional therapy.”
Dr. Rogers discloses ties with Genentech, AbbVie, Novartis, AstraZeneca, Janssen, Pharmacyclics, Beigene, and LOXO@Lilly. Dr. Greenberger discloses employment with the Leukemia & Lymphoma Society, which supports academic grants and a venture philanthropy via the Therapy Acceleration Program.
Dr. Jain reports ties with Pharmacyclics, AbbVie, Genentech, AstraZeneca, Pfizer, and numerous other disclosures.
AI mammogram screening is equivalent to human readers
, a radiology and biomedical imaging professor at Yale University in New Haven, Conn.
The reason is because AI is proving to be as good as humans in interpreting mammograms, at least in the research setting.
In one of the latest reports, published online in Radiology, British investigators found that the performance of a commercially available AI system (INSIGHT MMG version 1.1.7.1 – Lunit) was essentially equivalent to over 500 specialized readers. The results are in line with other recent AI studies.
Double reading – having mammograms read by two clinicians to increase cancer detection rates – is common in the United Kingdom and elsewhere in Europe.
The British team compared the performance of 552 readers with Lunit’s AI program on the Personal Performance in Mammographic Screening exam, a quality assurance test which mammogram readers in the United Kingdom are required to take twice a year. Readers assign a malignancy score to 60 challenging cases, a mix of normal breasts and breasts with benign and cancerous lesions. The study included two test sessions for a total of 120 breast screenings.
Fifty-seven percent of the readers in the study were board-certified radiologists, 37% were radiographers, and 6% were breast clinicians. Each read at least 5,000 mammograms a year.
There was no difference in overall performance between the AI program and the human readers (AUC 0.93 vs. 0.88, P = .15).
Commenting in an editorial published with the investigation, Dr. Philpotts said the results “suggest that AI could confidently act as a second reader to decrease workloads.”
As for the United States, where double reading is generally not done, she pointed out that “many U.S. radiologists interpreting mammograms are nonspecialized and do not read high volumes of mammograms. Thus, the AI system evaluated in the study “could be used as a supplemental tool to aid the performance of readers in the United States or in other countries where screening programs use a single reading.”
There was also no difference in sensitivity between AI and human readers (84% vs. 90%, P = .34), but the AI algorithm had a higher specificity (89% vs. 76%, P = .003).
Using AI recall scores that matched the average human reader performance (90% sensitivity, 76% specificity), there was no difference with AI in regard to sensitivity (91%, P = .73) or specificity (77%, P = .85), but the investigators noted the power of the analysis was limited.
Overall, “diagnostic performance of AI was comparable with that of the average human reader.” It seems “increasingly likely that AI will eventually play a part in the interpretation of screening mammograms,” said investigators led by Yan Chen, PhD, of the Nottingham Breast Institute in England.
“That the AI system was able to match the performance of the average reader in this specialized group of mammogram readers indicates the robustness of this AI algorithm,” Dr. Philpotts said.
However, there are some caveats.
For one, the system was designed for 2D mammography, the current standard of care in the United Kingdom, while digital breast tomosynthesis (DBT) is replacing 2D mammography in the United States.
In the United States, “AI algorithms specific to DBT are necessary and will need to be reliable and reproducible to be embraced by radiologists,” Dr. Philpotts said.
Also in the United Kingdom, screening is performed at 3-year intervals in women aged 50-70 years old, which means that the study population was enriched for older women with less-dense breasts. Screening generally starts earlier in the United States and includes premenopausal women with denser breasts.
A recent study from Korea, where many women have dense breasts, found that 2D mammography and supplementary ultrasound outperformed AI for cancer detection.
“This underscores the challenges of finding cancers in dense breasts, which plague both radiologists and AI alike, and provides evidence that breast density is an important factor to consider when evaluating AI performance,” Dr. Philpotts said.
The work was funded by Lunit, the maker of the AI program used in the study. The investigators and Dr. Philpotts had no disclosures.
, a radiology and biomedical imaging professor at Yale University in New Haven, Conn.
The reason is because AI is proving to be as good as humans in interpreting mammograms, at least in the research setting.
In one of the latest reports, published online in Radiology, British investigators found that the performance of a commercially available AI system (INSIGHT MMG version 1.1.7.1 – Lunit) was essentially equivalent to over 500 specialized readers. The results are in line with other recent AI studies.
Double reading – having mammograms read by two clinicians to increase cancer detection rates – is common in the United Kingdom and elsewhere in Europe.
The British team compared the performance of 552 readers with Lunit’s AI program on the Personal Performance in Mammographic Screening exam, a quality assurance test which mammogram readers in the United Kingdom are required to take twice a year. Readers assign a malignancy score to 60 challenging cases, a mix of normal breasts and breasts with benign and cancerous lesions. The study included two test sessions for a total of 120 breast screenings.
Fifty-seven percent of the readers in the study were board-certified radiologists, 37% were radiographers, and 6% were breast clinicians. Each read at least 5,000 mammograms a year.
There was no difference in overall performance between the AI program and the human readers (AUC 0.93 vs. 0.88, P = .15).
Commenting in an editorial published with the investigation, Dr. Philpotts said the results “suggest that AI could confidently act as a second reader to decrease workloads.”
As for the United States, where double reading is generally not done, she pointed out that “many U.S. radiologists interpreting mammograms are nonspecialized and do not read high volumes of mammograms. Thus, the AI system evaluated in the study “could be used as a supplemental tool to aid the performance of readers in the United States or in other countries where screening programs use a single reading.”
There was also no difference in sensitivity between AI and human readers (84% vs. 90%, P = .34), but the AI algorithm had a higher specificity (89% vs. 76%, P = .003).
Using AI recall scores that matched the average human reader performance (90% sensitivity, 76% specificity), there was no difference with AI in regard to sensitivity (91%, P = .73) or specificity (77%, P = .85), but the investigators noted the power of the analysis was limited.
Overall, “diagnostic performance of AI was comparable with that of the average human reader.” It seems “increasingly likely that AI will eventually play a part in the interpretation of screening mammograms,” said investigators led by Yan Chen, PhD, of the Nottingham Breast Institute in England.
“That the AI system was able to match the performance of the average reader in this specialized group of mammogram readers indicates the robustness of this AI algorithm,” Dr. Philpotts said.
However, there are some caveats.
For one, the system was designed for 2D mammography, the current standard of care in the United Kingdom, while digital breast tomosynthesis (DBT) is replacing 2D mammography in the United States.
In the United States, “AI algorithms specific to DBT are necessary and will need to be reliable and reproducible to be embraced by radiologists,” Dr. Philpotts said.
Also in the United Kingdom, screening is performed at 3-year intervals in women aged 50-70 years old, which means that the study population was enriched for older women with less-dense breasts. Screening generally starts earlier in the United States and includes premenopausal women with denser breasts.
A recent study from Korea, where many women have dense breasts, found that 2D mammography and supplementary ultrasound outperformed AI for cancer detection.
“This underscores the challenges of finding cancers in dense breasts, which plague both radiologists and AI alike, and provides evidence that breast density is an important factor to consider when evaluating AI performance,” Dr. Philpotts said.
The work was funded by Lunit, the maker of the AI program used in the study. The investigators and Dr. Philpotts had no disclosures.
, a radiology and biomedical imaging professor at Yale University in New Haven, Conn.
The reason is because AI is proving to be as good as humans in interpreting mammograms, at least in the research setting.
In one of the latest reports, published online in Radiology, British investigators found that the performance of a commercially available AI system (INSIGHT MMG version 1.1.7.1 – Lunit) was essentially equivalent to over 500 specialized readers. The results are in line with other recent AI studies.
Double reading – having mammograms read by two clinicians to increase cancer detection rates – is common in the United Kingdom and elsewhere in Europe.
The British team compared the performance of 552 readers with Lunit’s AI program on the Personal Performance in Mammographic Screening exam, a quality assurance test which mammogram readers in the United Kingdom are required to take twice a year. Readers assign a malignancy score to 60 challenging cases, a mix of normal breasts and breasts with benign and cancerous lesions. The study included two test sessions for a total of 120 breast screenings.
Fifty-seven percent of the readers in the study were board-certified radiologists, 37% were radiographers, and 6% were breast clinicians. Each read at least 5,000 mammograms a year.
There was no difference in overall performance between the AI program and the human readers (AUC 0.93 vs. 0.88, P = .15).
Commenting in an editorial published with the investigation, Dr. Philpotts said the results “suggest that AI could confidently act as a second reader to decrease workloads.”
As for the United States, where double reading is generally not done, she pointed out that “many U.S. radiologists interpreting mammograms are nonspecialized and do not read high volumes of mammograms. Thus, the AI system evaluated in the study “could be used as a supplemental tool to aid the performance of readers in the United States or in other countries where screening programs use a single reading.”
There was also no difference in sensitivity between AI and human readers (84% vs. 90%, P = .34), but the AI algorithm had a higher specificity (89% vs. 76%, P = .003).
Using AI recall scores that matched the average human reader performance (90% sensitivity, 76% specificity), there was no difference with AI in regard to sensitivity (91%, P = .73) or specificity (77%, P = .85), but the investigators noted the power of the analysis was limited.
Overall, “diagnostic performance of AI was comparable with that of the average human reader.” It seems “increasingly likely that AI will eventually play a part in the interpretation of screening mammograms,” said investigators led by Yan Chen, PhD, of the Nottingham Breast Institute in England.
“That the AI system was able to match the performance of the average reader in this specialized group of mammogram readers indicates the robustness of this AI algorithm,” Dr. Philpotts said.
However, there are some caveats.
For one, the system was designed for 2D mammography, the current standard of care in the United Kingdom, while digital breast tomosynthesis (DBT) is replacing 2D mammography in the United States.
In the United States, “AI algorithms specific to DBT are necessary and will need to be reliable and reproducible to be embraced by radiologists,” Dr. Philpotts said.
Also in the United Kingdom, screening is performed at 3-year intervals in women aged 50-70 years old, which means that the study population was enriched for older women with less-dense breasts. Screening generally starts earlier in the United States and includes premenopausal women with denser breasts.
A recent study from Korea, where many women have dense breasts, found that 2D mammography and supplementary ultrasound outperformed AI for cancer detection.
“This underscores the challenges of finding cancers in dense breasts, which plague both radiologists and AI alike, and provides evidence that breast density is an important factor to consider when evaluating AI performance,” Dr. Philpotts said.
The work was funded by Lunit, the maker of the AI program used in the study. The investigators and Dr. Philpotts had no disclosures.
FROM RADIOLOGY
CHP/CCUS: Low blood cancer risk for most patients
The reason is that patients will inevitably “go online and see that [the conditions are] associated with lots of bad things; it can really cause patients psychosocial harm if there is no one to explain what their risk is and also provide risk-specific management,” Dr. Weeks said at the annual meeting of the Society of Hematologic Oncology in Houston.
CHIP and CCUS are precursors of myeloid malignancies but for most patients, the risk of progression is less than 1%. CHIPS and CCUS are also associated with cardiovascular, rheumatologic, hepatic, and other diseases.
CHIP is defined by somatic mutations in myeloid malignancy driver genes with a variant allele fraction of 2% or more; CCUS is when those molecular features are accompanied by an unexplained and persistent anemia, thrombocytopenia, or neutropenia.
A small 2017 study suggested that about a third of patients with otherwise unexplained cytopenias have CCUS.
With the increasing use of next generation sequencing for tissue and liquid biopsies and other uses, the incidental diagnosis of both conditions is increasing.
Fortunately, Dr. Weeks’ group recently published a tool for predicting the risk of progression to myeloid malignancy.
Their “clonal hematopoiesis risk score” (CHRS) was developed and validated in over 400,000 healthy volunteers in the UK Biobank, with additional validation in cohorts from Dana Farber and the University of Pavia, Italy.
The CHRS incorporates eight high-risk genetic and clinical prognostic factors, including the type and number of genetic mutations in blood cells, factors related to red blood cell volume, and age over 65. It’s available online.
“You just input the patient’s information and it spits out if the patient is low, intermediate, or high risk for progression to any myeloid malignancy,” Dr. Weeks told her audience.
High-risk patients have about a 50% 10-year cumulative incidence of myeloid malignancy. The large majority of patients are low risk, however, and have a 10-year cumulative incidence of less than 1%. Patients in the middle have a 10-year risk of about 8%.
The low-risk group “is the population of people who probably don’t need to see a specialist,” and can be followed with an annual CBC with their primary care doctors plus further workup with any clinical change. Patients should also be evaluated for cardiovascular and other comorbidity risks.
“It’s the high-risk group we worry most about,” Dr. Weeks said. “We see them more often and repeat the next-generation sequencing” annually with a CBC at least every 6 months and a bone marrow biopsy with any clinical change.
“This is the population we would shuttle towards a clinical trial, as this is the population most likely to benefit,” she said.
The overarching goal of the several ongoing studies in CHIP/CCUS is to find a way to prevent progression to blood cancer. They range from prospective cohorts and single arm pilot studies to randomized clinical trials. One trial is evaluating canakinumab to prevent progression. “Intervention in clonal hematopoiesis might have the dual benefit of both preventing hematologic malignancy as well as reducing [the] inflammatory comorbidities,” Dr. Weeks said.
The reason is that patients will inevitably “go online and see that [the conditions are] associated with lots of bad things; it can really cause patients psychosocial harm if there is no one to explain what their risk is and also provide risk-specific management,” Dr. Weeks said at the annual meeting of the Society of Hematologic Oncology in Houston.
CHIP and CCUS are precursors of myeloid malignancies but for most patients, the risk of progression is less than 1%. CHIPS and CCUS are also associated with cardiovascular, rheumatologic, hepatic, and other diseases.
CHIP is defined by somatic mutations in myeloid malignancy driver genes with a variant allele fraction of 2% or more; CCUS is when those molecular features are accompanied by an unexplained and persistent anemia, thrombocytopenia, or neutropenia.
A small 2017 study suggested that about a third of patients with otherwise unexplained cytopenias have CCUS.
With the increasing use of next generation sequencing for tissue and liquid biopsies and other uses, the incidental diagnosis of both conditions is increasing.
Fortunately, Dr. Weeks’ group recently published a tool for predicting the risk of progression to myeloid malignancy.
Their “clonal hematopoiesis risk score” (CHRS) was developed and validated in over 400,000 healthy volunteers in the UK Biobank, with additional validation in cohorts from Dana Farber and the University of Pavia, Italy.
The CHRS incorporates eight high-risk genetic and clinical prognostic factors, including the type and number of genetic mutations in blood cells, factors related to red blood cell volume, and age over 65. It’s available online.
“You just input the patient’s information and it spits out if the patient is low, intermediate, or high risk for progression to any myeloid malignancy,” Dr. Weeks told her audience.
High-risk patients have about a 50% 10-year cumulative incidence of myeloid malignancy. The large majority of patients are low risk, however, and have a 10-year cumulative incidence of less than 1%. Patients in the middle have a 10-year risk of about 8%.
The low-risk group “is the population of people who probably don’t need to see a specialist,” and can be followed with an annual CBC with their primary care doctors plus further workup with any clinical change. Patients should also be evaluated for cardiovascular and other comorbidity risks.
“It’s the high-risk group we worry most about,” Dr. Weeks said. “We see them more often and repeat the next-generation sequencing” annually with a CBC at least every 6 months and a bone marrow biopsy with any clinical change.
“This is the population we would shuttle towards a clinical trial, as this is the population most likely to benefit,” she said.
The overarching goal of the several ongoing studies in CHIP/CCUS is to find a way to prevent progression to blood cancer. They range from prospective cohorts and single arm pilot studies to randomized clinical trials. One trial is evaluating canakinumab to prevent progression. “Intervention in clonal hematopoiesis might have the dual benefit of both preventing hematologic malignancy as well as reducing [the] inflammatory comorbidities,” Dr. Weeks said.
The reason is that patients will inevitably “go online and see that [the conditions are] associated with lots of bad things; it can really cause patients psychosocial harm if there is no one to explain what their risk is and also provide risk-specific management,” Dr. Weeks said at the annual meeting of the Society of Hematologic Oncology in Houston.
CHIP and CCUS are precursors of myeloid malignancies but for most patients, the risk of progression is less than 1%. CHIPS and CCUS are also associated with cardiovascular, rheumatologic, hepatic, and other diseases.
CHIP is defined by somatic mutations in myeloid malignancy driver genes with a variant allele fraction of 2% or more; CCUS is when those molecular features are accompanied by an unexplained and persistent anemia, thrombocytopenia, or neutropenia.
A small 2017 study suggested that about a third of patients with otherwise unexplained cytopenias have CCUS.
With the increasing use of next generation sequencing for tissue and liquid biopsies and other uses, the incidental diagnosis of both conditions is increasing.
Fortunately, Dr. Weeks’ group recently published a tool for predicting the risk of progression to myeloid malignancy.
Their “clonal hematopoiesis risk score” (CHRS) was developed and validated in over 400,000 healthy volunteers in the UK Biobank, with additional validation in cohorts from Dana Farber and the University of Pavia, Italy.
The CHRS incorporates eight high-risk genetic and clinical prognostic factors, including the type and number of genetic mutations in blood cells, factors related to red blood cell volume, and age over 65. It’s available online.
“You just input the patient’s information and it spits out if the patient is low, intermediate, or high risk for progression to any myeloid malignancy,” Dr. Weeks told her audience.
High-risk patients have about a 50% 10-year cumulative incidence of myeloid malignancy. The large majority of patients are low risk, however, and have a 10-year cumulative incidence of less than 1%. Patients in the middle have a 10-year risk of about 8%.
The low-risk group “is the population of people who probably don’t need to see a specialist,” and can be followed with an annual CBC with their primary care doctors plus further workup with any clinical change. Patients should also be evaluated for cardiovascular and other comorbidity risks.
“It’s the high-risk group we worry most about,” Dr. Weeks said. “We see them more often and repeat the next-generation sequencing” annually with a CBC at least every 6 months and a bone marrow biopsy with any clinical change.
“This is the population we would shuttle towards a clinical trial, as this is the population most likely to benefit,” she said.
The overarching goal of the several ongoing studies in CHIP/CCUS is to find a way to prevent progression to blood cancer. They range from prospective cohorts and single arm pilot studies to randomized clinical trials. One trial is evaluating canakinumab to prevent progression. “Intervention in clonal hematopoiesis might have the dual benefit of both preventing hematologic malignancy as well as reducing [the] inflammatory comorbidities,” Dr. Weeks said.
FROM SOHO 2023
Growing public perception that cannabis is safer than tobacco
TOPLINE:
METHODOLOGY:
- While aggressive campaigns have led to a dramatic reduction in the prevalence of cigarette smoking and created safer smoke-free environments, regulation governing cannabis – which is associated with some health benefits but also many negative health outcomes – has been less restrictive.
- The study included a nationally representative sample of 5,035 mostly White U.S. adults, mean age 53.4 years, who completed three online surveys between 2017 and 2021 on the safety of tobacco and cannabis.
- In all three waves of the survey, respondents were asked to rate the safety of smoking one marijuana joint a day to smoking one cigarette a day, and of secondhand smoke from marijuana to that from tobacco.
- Respondents also expressed views on the safety of secondhand smoke exposure (of both marijuana and tobacco) on specific populations, including children, pregnant women, and adults (ratings were from “completely unsafe” to “completely safe”).
- Independent variables included age, sex, race, ethnicity, education level, annual income, employment status, marital status, and state of residence.
TAKEAWAY:
- There was a significant shift over time toward an increasingly favorable perception of cannabis; more respondents reported cannabis was “somewhat safer” or “much safer” than tobacco in 2021 than 2017 (44.3% vs. 36.7%; P < .001), and more believed secondhand smoke was somewhat or much safer for cannabis vs. tobacco in 2021 than in 2017 (40.2% vs. 35.1%; P < .001).
- More people endorsed the greater safety of secondhand smoke from cannabis vs. tobacco for children and pregnant women, and these perceptions remained similar over the study period.
- Younger and unmarried individuals were significantly more likely to move toward viewing smoking cannabis as safer than cigarettes, but legality of cannabis in respondents’ state of residence was not associated with change over time, suggesting the increasing perception of cannabis safety may be a national trend rather than a trend seen only in states with legalized cannabis.
IN PRACTICE:
“Understanding changing views on tobacco and cannabis risk is important given that increases in social acceptance and decreases in risk perception may be directly associated with public health and policies,” the investigators write.
SOURCE:
The study was conducted by Julia Chambers, MD, department of medicine, University of California, San Francisco, and colleagues. It was published online in JAMA Network Open.
LIMITATIONS:
The generalizability of the study may be limited by nonresponse and loss to follow-up over time. The wording of survey questions may have introduced bias in respondents. Participants were asked about safety of smoking cannabis joints vs. tobacco cigarettes and not to compare safety of other forms of smoked and vaped cannabis, tobacco, and nicotine.
DISCLOSURES:
The study received support from the California Tobacco-Related Disease Research Program. Dr. Chambers has no relevant conflicts of interest; author Katherine J. Hoggatt, PhD, MPH, department of medicine, UCSF, reported receiving grants from the Veterans Health Administration during the conduct of the study and grants from the National Institutes of Health, Rubin Family Foundation, and Veterans Health Administration outside the submitted work.
A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- While aggressive campaigns have led to a dramatic reduction in the prevalence of cigarette smoking and created safer smoke-free environments, regulation governing cannabis – which is associated with some health benefits but also many negative health outcomes – has been less restrictive.
- The study included a nationally representative sample of 5,035 mostly White U.S. adults, mean age 53.4 years, who completed three online surveys between 2017 and 2021 on the safety of tobacco and cannabis.
- In all three waves of the survey, respondents were asked to rate the safety of smoking one marijuana joint a day to smoking one cigarette a day, and of secondhand smoke from marijuana to that from tobacco.
- Respondents also expressed views on the safety of secondhand smoke exposure (of both marijuana and tobacco) on specific populations, including children, pregnant women, and adults (ratings were from “completely unsafe” to “completely safe”).
- Independent variables included age, sex, race, ethnicity, education level, annual income, employment status, marital status, and state of residence.
TAKEAWAY:
- There was a significant shift over time toward an increasingly favorable perception of cannabis; more respondents reported cannabis was “somewhat safer” or “much safer” than tobacco in 2021 than 2017 (44.3% vs. 36.7%; P < .001), and more believed secondhand smoke was somewhat or much safer for cannabis vs. tobacco in 2021 than in 2017 (40.2% vs. 35.1%; P < .001).
- More people endorsed the greater safety of secondhand smoke from cannabis vs. tobacco for children and pregnant women, and these perceptions remained similar over the study period.
- Younger and unmarried individuals were significantly more likely to move toward viewing smoking cannabis as safer than cigarettes, but legality of cannabis in respondents’ state of residence was not associated with change over time, suggesting the increasing perception of cannabis safety may be a national trend rather than a trend seen only in states with legalized cannabis.
IN PRACTICE:
“Understanding changing views on tobacco and cannabis risk is important given that increases in social acceptance and decreases in risk perception may be directly associated with public health and policies,” the investigators write.
SOURCE:
The study was conducted by Julia Chambers, MD, department of medicine, University of California, San Francisco, and colleagues. It was published online in JAMA Network Open.
LIMITATIONS:
The generalizability of the study may be limited by nonresponse and loss to follow-up over time. The wording of survey questions may have introduced bias in respondents. Participants were asked about safety of smoking cannabis joints vs. tobacco cigarettes and not to compare safety of other forms of smoked and vaped cannabis, tobacco, and nicotine.
DISCLOSURES:
The study received support from the California Tobacco-Related Disease Research Program. Dr. Chambers has no relevant conflicts of interest; author Katherine J. Hoggatt, PhD, MPH, department of medicine, UCSF, reported receiving grants from the Veterans Health Administration during the conduct of the study and grants from the National Institutes of Health, Rubin Family Foundation, and Veterans Health Administration outside the submitted work.
A version of this article first appeared on Medscape.com.
TOPLINE:
METHODOLOGY:
- While aggressive campaigns have led to a dramatic reduction in the prevalence of cigarette smoking and created safer smoke-free environments, regulation governing cannabis – which is associated with some health benefits but also many negative health outcomes – has been less restrictive.
- The study included a nationally representative sample of 5,035 mostly White U.S. adults, mean age 53.4 years, who completed three online surveys between 2017 and 2021 on the safety of tobacco and cannabis.
- In all three waves of the survey, respondents were asked to rate the safety of smoking one marijuana joint a day to smoking one cigarette a day, and of secondhand smoke from marijuana to that from tobacco.
- Respondents also expressed views on the safety of secondhand smoke exposure (of both marijuana and tobacco) on specific populations, including children, pregnant women, and adults (ratings were from “completely unsafe” to “completely safe”).
- Independent variables included age, sex, race, ethnicity, education level, annual income, employment status, marital status, and state of residence.
TAKEAWAY:
- There was a significant shift over time toward an increasingly favorable perception of cannabis; more respondents reported cannabis was “somewhat safer” or “much safer” than tobacco in 2021 than 2017 (44.3% vs. 36.7%; P < .001), and more believed secondhand smoke was somewhat or much safer for cannabis vs. tobacco in 2021 than in 2017 (40.2% vs. 35.1%; P < .001).
- More people endorsed the greater safety of secondhand smoke from cannabis vs. tobacco for children and pregnant women, and these perceptions remained similar over the study period.
- Younger and unmarried individuals were significantly more likely to move toward viewing smoking cannabis as safer than cigarettes, but legality of cannabis in respondents’ state of residence was not associated with change over time, suggesting the increasing perception of cannabis safety may be a national trend rather than a trend seen only in states with legalized cannabis.
IN PRACTICE:
“Understanding changing views on tobacco and cannabis risk is important given that increases in social acceptance and decreases in risk perception may be directly associated with public health and policies,” the investigators write.
SOURCE:
The study was conducted by Julia Chambers, MD, department of medicine, University of California, San Francisco, and colleagues. It was published online in JAMA Network Open.
LIMITATIONS:
The generalizability of the study may be limited by nonresponse and loss to follow-up over time. The wording of survey questions may have introduced bias in respondents. Participants were asked about safety of smoking cannabis joints vs. tobacco cigarettes and not to compare safety of other forms of smoked and vaped cannabis, tobacco, and nicotine.
DISCLOSURES:
The study received support from the California Tobacco-Related Disease Research Program. Dr. Chambers has no relevant conflicts of interest; author Katherine J. Hoggatt, PhD, MPH, department of medicine, UCSF, reported receiving grants from the Veterans Health Administration during the conduct of the study and grants from the National Institutes of Health, Rubin Family Foundation, and Veterans Health Administration outside the submitted work.
A version of this article first appeared on Medscape.com.