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EMA panel endorses two cancer drugs, one sickle cell drug
The drugs are enfortumab vedotin (Padcev, Astellas/Seagen) for urothelial cancer, tepotinib (Tepmetko, Merck) for non–small cell lung cancer (NSCLC), and voxelotor (Oxbryta, Global Blood Therapeutics) for sickle cell hemolytic anemia.
EMA’s Committee for Medicinal Products for Human Use gave the nod for marketing authorization on Dec. 16, 2021, and agency approval generally follows about 6 weeks later. All three products are already approved in the United States.
Enfortumab vedotin for urothelial cancer
The recommendation for Astellas’ antibody-drug conjugate infusion was based on the phase 3 EV-301 trial, which found about a 4-month median overall survival benefit with the antibody-drug conjugate versus investigator-chosen chemotherapy across 608 patients with locally advanced or metastatic urothelial carcinoma previously treated with platinum-based chemotherapy and a programmed death 1 or PD–ligand 1 inhibitor.
The planned European indication is for adults with locally advanced or metastatic disease who met the same criteria – previous platinum-based chemotherapy plus a PD-1 or PD-L1 inhibitor.
The Food and Drug Administration approval came in December 2019, and with the same indication as well as for patients ineligible for cisplatin-containing chemotherapy who have had one or more prior lines of therapy. The U.S. labeling carries a boxed warning of severe and fatal skin reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis.
Tepotinib for NSCLC
The recommendation for Merck’s tepotinib, a once-daily oral MET inhibitor, followed results from the phase 2 VISION study. The study found an investigator-assessed response rate of 56% across 152 patients with advanced or metastatic NSCLC with a confirmed MET exon 14 skipping mutation, regardless of previous therapy.
The planned European indication will be for monotherapy in adults with advanced disease harboring the mutation who require systemic therapy following prior treatment with immunotherapy and/or platinum-based chemotherapy.
The FDA approved the drug in February 2021, and carries the same indication, minus the prior therapy requirement.
Voxelotor for sickle cell disease
Voxelotor is an oral hemoglobin S polymerization inhibitor from Global Blood Therapeutics.
The European approval recommendation was based on a phase 3 trial in 274 patients with sickle cell disease that found a greater than 1 g/dL increase in hemoglobin levels at 24 weeks in 51.1% of patients versus 6.5% randomized to placebo, regardless of whether patients were on concomitant hydroxyurea.
The small molecule binds and stabilizes hemoglobin, preventing the hemoglobin polymerization that causes red blood cells to sickle.
“There is a high unmet need for medicines to treat hemolytic anemia” in sickle cell disease because available treatment options are limited to blood transfusions and allogenic hematopoietic stem cell transplantation,” the EMA explained in a press release announcing the approval recommendation.
The planned European indication is for treating hemolytic anemia in sickle cell disease in patients 12 years or older either alone or in combination with hydroxycarbamide (hydroxyurea).
The FDA approved the agent in November 2019 for the same indication, but can be given to children as young as 4 years old.
A version of this article first appeared on Medscape.com.
The drugs are enfortumab vedotin (Padcev, Astellas/Seagen) for urothelial cancer, tepotinib (Tepmetko, Merck) for non–small cell lung cancer (NSCLC), and voxelotor (Oxbryta, Global Blood Therapeutics) for sickle cell hemolytic anemia.
EMA’s Committee for Medicinal Products for Human Use gave the nod for marketing authorization on Dec. 16, 2021, and agency approval generally follows about 6 weeks later. All three products are already approved in the United States.
Enfortumab vedotin for urothelial cancer
The recommendation for Astellas’ antibody-drug conjugate infusion was based on the phase 3 EV-301 trial, which found about a 4-month median overall survival benefit with the antibody-drug conjugate versus investigator-chosen chemotherapy across 608 patients with locally advanced or metastatic urothelial carcinoma previously treated with platinum-based chemotherapy and a programmed death 1 or PD–ligand 1 inhibitor.
The planned European indication is for adults with locally advanced or metastatic disease who met the same criteria – previous platinum-based chemotherapy plus a PD-1 or PD-L1 inhibitor.
The Food and Drug Administration approval came in December 2019, and with the same indication as well as for patients ineligible for cisplatin-containing chemotherapy who have had one or more prior lines of therapy. The U.S. labeling carries a boxed warning of severe and fatal skin reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis.
Tepotinib for NSCLC
The recommendation for Merck’s tepotinib, a once-daily oral MET inhibitor, followed results from the phase 2 VISION study. The study found an investigator-assessed response rate of 56% across 152 patients with advanced or metastatic NSCLC with a confirmed MET exon 14 skipping mutation, regardless of previous therapy.
The planned European indication will be for monotherapy in adults with advanced disease harboring the mutation who require systemic therapy following prior treatment with immunotherapy and/or platinum-based chemotherapy.
The FDA approved the drug in February 2021, and carries the same indication, minus the prior therapy requirement.
Voxelotor for sickle cell disease
Voxelotor is an oral hemoglobin S polymerization inhibitor from Global Blood Therapeutics.
The European approval recommendation was based on a phase 3 trial in 274 patients with sickle cell disease that found a greater than 1 g/dL increase in hemoglobin levels at 24 weeks in 51.1% of patients versus 6.5% randomized to placebo, regardless of whether patients were on concomitant hydroxyurea.
The small molecule binds and stabilizes hemoglobin, preventing the hemoglobin polymerization that causes red blood cells to sickle.
“There is a high unmet need for medicines to treat hemolytic anemia” in sickle cell disease because available treatment options are limited to blood transfusions and allogenic hematopoietic stem cell transplantation,” the EMA explained in a press release announcing the approval recommendation.
The planned European indication is for treating hemolytic anemia in sickle cell disease in patients 12 years or older either alone or in combination with hydroxycarbamide (hydroxyurea).
The FDA approved the agent in November 2019 for the same indication, but can be given to children as young as 4 years old.
A version of this article first appeared on Medscape.com.
The drugs are enfortumab vedotin (Padcev, Astellas/Seagen) for urothelial cancer, tepotinib (Tepmetko, Merck) for non–small cell lung cancer (NSCLC), and voxelotor (Oxbryta, Global Blood Therapeutics) for sickle cell hemolytic anemia.
EMA’s Committee for Medicinal Products for Human Use gave the nod for marketing authorization on Dec. 16, 2021, and agency approval generally follows about 6 weeks later. All three products are already approved in the United States.
Enfortumab vedotin for urothelial cancer
The recommendation for Astellas’ antibody-drug conjugate infusion was based on the phase 3 EV-301 trial, which found about a 4-month median overall survival benefit with the antibody-drug conjugate versus investigator-chosen chemotherapy across 608 patients with locally advanced or metastatic urothelial carcinoma previously treated with platinum-based chemotherapy and a programmed death 1 or PD–ligand 1 inhibitor.
The planned European indication is for adults with locally advanced or metastatic disease who met the same criteria – previous platinum-based chemotherapy plus a PD-1 or PD-L1 inhibitor.
The Food and Drug Administration approval came in December 2019, and with the same indication as well as for patients ineligible for cisplatin-containing chemotherapy who have had one or more prior lines of therapy. The U.S. labeling carries a boxed warning of severe and fatal skin reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis.
Tepotinib for NSCLC
The recommendation for Merck’s tepotinib, a once-daily oral MET inhibitor, followed results from the phase 2 VISION study. The study found an investigator-assessed response rate of 56% across 152 patients with advanced or metastatic NSCLC with a confirmed MET exon 14 skipping mutation, regardless of previous therapy.
The planned European indication will be for monotherapy in adults with advanced disease harboring the mutation who require systemic therapy following prior treatment with immunotherapy and/or platinum-based chemotherapy.
The FDA approved the drug in February 2021, and carries the same indication, minus the prior therapy requirement.
Voxelotor for sickle cell disease
Voxelotor is an oral hemoglobin S polymerization inhibitor from Global Blood Therapeutics.
The European approval recommendation was based on a phase 3 trial in 274 patients with sickle cell disease that found a greater than 1 g/dL increase in hemoglobin levels at 24 weeks in 51.1% of patients versus 6.5% randomized to placebo, regardless of whether patients were on concomitant hydroxyurea.
The small molecule binds and stabilizes hemoglobin, preventing the hemoglobin polymerization that causes red blood cells to sickle.
“There is a high unmet need for medicines to treat hemolytic anemia” in sickle cell disease because available treatment options are limited to blood transfusions and allogenic hematopoietic stem cell transplantation,” the EMA explained in a press release announcing the approval recommendation.
The planned European indication is for treating hemolytic anemia in sickle cell disease in patients 12 years or older either alone or in combination with hydroxycarbamide (hydroxyurea).
The FDA approved the agent in November 2019 for the same indication, but can be given to children as young as 4 years old.
A version of this article first appeared on Medscape.com.
Voxelotor for sickle cell anemia now down to 4-year-olds
The indication had previously been for patients 12 years old and up, the FDA said in an announcement.
Voxelotor (Oxbryta) was originally approved for sickle cell disease in November 2019 and was described as the first drug that directly inhibits sickle hemoglobin polymerization, the root cause of the disease. It binds and stabilizes hemoglobin to prevent red blood cells from sickling and being destroyed.
Approval for the new indication of use in children down to age 4 was based on data from a phase 2 trial that involved 45 children aged 4-11 years; the results show that 36% had an increase in hemoglobin greater than 1 g/dL by week 24, the FDA said.
“Complications of [sickle cell disease] that can cause irreversible organ damage are known to begin in the first few years of life, which is why earlier intervention is critical,” commented Ted Love, MD, president and CEO of Global Blood Therapeutics, the manufacturer, in a press release.
The company is studying voxelotor in children as young as 9 months old.
The agent was granted an accelerated approval by the FDA, so continued approval depends on additional data to confirm that increases in hemoglobin have clinical benefit.
With the new approvals, voxelotor is now available in 500-mg tablets and the 300-mg tablets for oral suspension. Dosing for ages 12 years and up is 1,500 mg once daily. Dosing for children 4 to up to 12 years old is weight based.
The most common side effects are headache, vomiting, diarrhea, abdominal pain, nausea, rash, and fever.
A version of this article first appeared on Medscape.com.
The indication had previously been for patients 12 years old and up, the FDA said in an announcement.
Voxelotor (Oxbryta) was originally approved for sickle cell disease in November 2019 and was described as the first drug that directly inhibits sickle hemoglobin polymerization, the root cause of the disease. It binds and stabilizes hemoglobin to prevent red blood cells from sickling and being destroyed.
Approval for the new indication of use in children down to age 4 was based on data from a phase 2 trial that involved 45 children aged 4-11 years; the results show that 36% had an increase in hemoglobin greater than 1 g/dL by week 24, the FDA said.
“Complications of [sickle cell disease] that can cause irreversible organ damage are known to begin in the first few years of life, which is why earlier intervention is critical,” commented Ted Love, MD, president and CEO of Global Blood Therapeutics, the manufacturer, in a press release.
The company is studying voxelotor in children as young as 9 months old.
The agent was granted an accelerated approval by the FDA, so continued approval depends on additional data to confirm that increases in hemoglobin have clinical benefit.
With the new approvals, voxelotor is now available in 500-mg tablets and the 300-mg tablets for oral suspension. Dosing for ages 12 years and up is 1,500 mg once daily. Dosing for children 4 to up to 12 years old is weight based.
The most common side effects are headache, vomiting, diarrhea, abdominal pain, nausea, rash, and fever.
A version of this article first appeared on Medscape.com.
The indication had previously been for patients 12 years old and up, the FDA said in an announcement.
Voxelotor (Oxbryta) was originally approved for sickle cell disease in November 2019 and was described as the first drug that directly inhibits sickle hemoglobin polymerization, the root cause of the disease. It binds and stabilizes hemoglobin to prevent red blood cells from sickling and being destroyed.
Approval for the new indication of use in children down to age 4 was based on data from a phase 2 trial that involved 45 children aged 4-11 years; the results show that 36% had an increase in hemoglobin greater than 1 g/dL by week 24, the FDA said.
“Complications of [sickle cell disease] that can cause irreversible organ damage are known to begin in the first few years of life, which is why earlier intervention is critical,” commented Ted Love, MD, president and CEO of Global Blood Therapeutics, the manufacturer, in a press release.
The company is studying voxelotor in children as young as 9 months old.
The agent was granted an accelerated approval by the FDA, so continued approval depends on additional data to confirm that increases in hemoglobin have clinical benefit.
With the new approvals, voxelotor is now available in 500-mg tablets and the 300-mg tablets for oral suspension. Dosing for ages 12 years and up is 1,500 mg once daily. Dosing for children 4 to up to 12 years old is weight based.
The most common side effects are headache, vomiting, diarrhea, abdominal pain, nausea, rash, and fever.
A version of this article first appeared on Medscape.com.
Risk for breast cancer recurrence persists past 30 years
The data come from a Danish study involving 20,315 women who were treated for early operable breast cancer between 1987 and 2004, all of whom were disease-free at 10 years.
Further follow-up showed that 2,595 women had a breast cancer recurrence more than 10 years after their primary diagnosis.
The cumulative incidence of recurrence was 8.5% at 15 years; 12.5% at 20 years; 15.2% at 25 years, and 16.6% at 32 years.
Recurrence risk was greatest early in the study period.
Women who had primary tumors larger than 20 mm, lymph node-positive disease, and estrogen receptor-positive tumors were at higher risk for late recurrence.
“Such patients may warrant extended surveillance, more aggressive treatment, or new therapy approaches,” said the investigators, led by Rikke Pedersen, MD, a PhD candidate in epidemiology at Aarhus University Hospital, Denmark.
“Our observed high cumulative incidence of late breast cancer recurrence is a concern given the increasing prevalence of long-term survivors.” Among other things, a new model to better select women for prolonged surveillance is needed, they said.
The new findings were published online Nov. 8 in the Journal of the National Cancer Institute (NCI).
This study confirms previous investigations, but it is the first to report that breast cancer can recur more than 30 years after diagnosis, note the authors of an accompanying editorial, Serban Negoita, MD, DrPH, and Esmeralda Ramirez-Peña, PhD, MPH, both from the National Cancer Institute.
The caveat is that treatment has evolved considerably since the women in the study were diagnosed, so the prognostic value of the findings with current treatment regimens is uncertain, they note. Some studies haven’t found a recurrence benefit for aggressive upfront treatment, but those studies had shorter follow-ups.
Research into the issue is “increasingly important” to guide clinical management and counsel women who are living longer after their primary diagnosis, they comment.
Further details from the study
Data for the study came from the Danish Breast Cancer Group clinical database and other national databases. The researchers focused on women who were disease-free at 10 years after their primary diagnosis, which was stage I or II disease. Median age was 55 years.
Cumulative incidence for breast cancer recurrence was highest for grade 1 tumors with four or more positive lymph nodes (37.9% 10-25 years after the primary diagnosis) and was lowest for patients with grade 3 disease and no involved lymph nodes (7.5%).
The finding of higher recurrence incidence with lower grade tumors goes against some previous reports, the researchers commented. It may be that some tumors considered lower risk decades ago, and treated accordingly, would be considered higher risk in more recent times.
The cumulative incidence of late recurrence was also higher in younger patients and those treated with breast-conserving surgery instead of mastectomy, the team reported.
Adjusted hazard ratios followed the incidence trends, with higher hazards of recurrence for women diagnosed before age 40 as well as those who had breast-conserving surgery, four or more positive lymph nodes, and primary tumors 20 mm or more across.
The work was funded by the Danish Cancer Society and Aarhus University. Lead author Dr. Pedersen reports no disclosures, but coauthors report ties to Amgen, Novo Nordisk, Roche, and other companies. The editorialists have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The data come from a Danish study involving 20,315 women who were treated for early operable breast cancer between 1987 and 2004, all of whom were disease-free at 10 years.
Further follow-up showed that 2,595 women had a breast cancer recurrence more than 10 years after their primary diagnosis.
The cumulative incidence of recurrence was 8.5% at 15 years; 12.5% at 20 years; 15.2% at 25 years, and 16.6% at 32 years.
Recurrence risk was greatest early in the study period.
Women who had primary tumors larger than 20 mm, lymph node-positive disease, and estrogen receptor-positive tumors were at higher risk for late recurrence.
“Such patients may warrant extended surveillance, more aggressive treatment, or new therapy approaches,” said the investigators, led by Rikke Pedersen, MD, a PhD candidate in epidemiology at Aarhus University Hospital, Denmark.
“Our observed high cumulative incidence of late breast cancer recurrence is a concern given the increasing prevalence of long-term survivors.” Among other things, a new model to better select women for prolonged surveillance is needed, they said.
The new findings were published online Nov. 8 in the Journal of the National Cancer Institute (NCI).
This study confirms previous investigations, but it is the first to report that breast cancer can recur more than 30 years after diagnosis, note the authors of an accompanying editorial, Serban Negoita, MD, DrPH, and Esmeralda Ramirez-Peña, PhD, MPH, both from the National Cancer Institute.
The caveat is that treatment has evolved considerably since the women in the study were diagnosed, so the prognostic value of the findings with current treatment regimens is uncertain, they note. Some studies haven’t found a recurrence benefit for aggressive upfront treatment, but those studies had shorter follow-ups.
Research into the issue is “increasingly important” to guide clinical management and counsel women who are living longer after their primary diagnosis, they comment.
Further details from the study
Data for the study came from the Danish Breast Cancer Group clinical database and other national databases. The researchers focused on women who were disease-free at 10 years after their primary diagnosis, which was stage I or II disease. Median age was 55 years.
Cumulative incidence for breast cancer recurrence was highest for grade 1 tumors with four or more positive lymph nodes (37.9% 10-25 years after the primary diagnosis) and was lowest for patients with grade 3 disease and no involved lymph nodes (7.5%).
The finding of higher recurrence incidence with lower grade tumors goes against some previous reports, the researchers commented. It may be that some tumors considered lower risk decades ago, and treated accordingly, would be considered higher risk in more recent times.
The cumulative incidence of late recurrence was also higher in younger patients and those treated with breast-conserving surgery instead of mastectomy, the team reported.
Adjusted hazard ratios followed the incidence trends, with higher hazards of recurrence for women diagnosed before age 40 as well as those who had breast-conserving surgery, four or more positive lymph nodes, and primary tumors 20 mm or more across.
The work was funded by the Danish Cancer Society and Aarhus University. Lead author Dr. Pedersen reports no disclosures, but coauthors report ties to Amgen, Novo Nordisk, Roche, and other companies. The editorialists have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
The data come from a Danish study involving 20,315 women who were treated for early operable breast cancer between 1987 and 2004, all of whom were disease-free at 10 years.
Further follow-up showed that 2,595 women had a breast cancer recurrence more than 10 years after their primary diagnosis.
The cumulative incidence of recurrence was 8.5% at 15 years; 12.5% at 20 years; 15.2% at 25 years, and 16.6% at 32 years.
Recurrence risk was greatest early in the study period.
Women who had primary tumors larger than 20 mm, lymph node-positive disease, and estrogen receptor-positive tumors were at higher risk for late recurrence.
“Such patients may warrant extended surveillance, more aggressive treatment, or new therapy approaches,” said the investigators, led by Rikke Pedersen, MD, a PhD candidate in epidemiology at Aarhus University Hospital, Denmark.
“Our observed high cumulative incidence of late breast cancer recurrence is a concern given the increasing prevalence of long-term survivors.” Among other things, a new model to better select women for prolonged surveillance is needed, they said.
The new findings were published online Nov. 8 in the Journal of the National Cancer Institute (NCI).
This study confirms previous investigations, but it is the first to report that breast cancer can recur more than 30 years after diagnosis, note the authors of an accompanying editorial, Serban Negoita, MD, DrPH, and Esmeralda Ramirez-Peña, PhD, MPH, both from the National Cancer Institute.
The caveat is that treatment has evolved considerably since the women in the study were diagnosed, so the prognostic value of the findings with current treatment regimens is uncertain, they note. Some studies haven’t found a recurrence benefit for aggressive upfront treatment, but those studies had shorter follow-ups.
Research into the issue is “increasingly important” to guide clinical management and counsel women who are living longer after their primary diagnosis, they comment.
Further details from the study
Data for the study came from the Danish Breast Cancer Group clinical database and other national databases. The researchers focused on women who were disease-free at 10 years after their primary diagnosis, which was stage I or II disease. Median age was 55 years.
Cumulative incidence for breast cancer recurrence was highest for grade 1 tumors with four or more positive lymph nodes (37.9% 10-25 years after the primary diagnosis) and was lowest for patients with grade 3 disease and no involved lymph nodes (7.5%).
The finding of higher recurrence incidence with lower grade tumors goes against some previous reports, the researchers commented. It may be that some tumors considered lower risk decades ago, and treated accordingly, would be considered higher risk in more recent times.
The cumulative incidence of late recurrence was also higher in younger patients and those treated with breast-conserving surgery instead of mastectomy, the team reported.
Adjusted hazard ratios followed the incidence trends, with higher hazards of recurrence for women diagnosed before age 40 as well as those who had breast-conserving surgery, four or more positive lymph nodes, and primary tumors 20 mm or more across.
The work was funded by the Danish Cancer Society and Aarhus University. Lead author Dr. Pedersen reports no disclosures, but coauthors report ties to Amgen, Novo Nordisk, Roche, and other companies. The editorialists have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
‘First reliable estimate’ of breast cancer metastasis
The data come from a massive meta-analysis of more than 400 studies conducted around the world, involving tens of thousands of women.
It found that the overall risk of metastasis is between 6% and 22%, with younger women having a higher risk.
While women aged 50 years or older when they were diagnosed with breast cancer have a risk of developing metastasis that ranged from 3.7% to 28.6%, women diagnosed with breast cancer before age 35 had a higher risk – 12.7% to 38%. The investigators speculate that this may be because younger women have a more aggressive form of breast cancer or because they are diagnosed at a later stage.
The risk of metastasis also varies by tumor type, with luminal B cancers having a 4.2% to 35.5% risk of metastasis versus a 2.3% to 11.8% risk with luminal A tumors.
“The quantification of recurrence and disease progression is important to assess the effectiveness of treatment, evaluate prognosis, and allocate resources,” commented lead investigator Eileen Morgan, PhD, of the International Agency for Research on Cancer.
Dr. Morgan and colleagues presented the new meta-analysis at the virtual Advanced Breast Cancer Sixth International Consensus Conference.
She added that this information has not been available until now “because cancer registries have not been routinely collecting this data.”
In fact, the U.S. National Cancer Institute began a project earlier this year to track this information, after 48 years of not doing so.
Reacting to the findings, Shani Paluch-Shimon, MBBS, director of the Breast Unit at Hadassah University Hospital, Jerusalem, commented that this work “provides the first reliable estimate of how many breast cancer patients go on to develop advanced disease in contemporary cohorts.”
“This information is, of course, important for patients who want to understand their prognosis,” she continued.
“But it’s also vital at a public health level for those of us working to treat and prevent advanced breast cancer, to help us understand the scale of the disease around the world,” she said. “It will help us identify at-risk groups across different populations and demonstrate how disease course is changing with contemporary treatments.”
“It will also help us understand what resources are needed and where, to ensure we can collect and analyze quality data in real-time as this is key for resource allocation and planning future studies.”
The work was funded by a grant from the Susan G. Komen Foundation.
A version of this article first appeared on Medscape.com.
The data come from a massive meta-analysis of more than 400 studies conducted around the world, involving tens of thousands of women.
It found that the overall risk of metastasis is between 6% and 22%, with younger women having a higher risk.
While women aged 50 years or older when they were diagnosed with breast cancer have a risk of developing metastasis that ranged from 3.7% to 28.6%, women diagnosed with breast cancer before age 35 had a higher risk – 12.7% to 38%. The investigators speculate that this may be because younger women have a more aggressive form of breast cancer or because they are diagnosed at a later stage.
The risk of metastasis also varies by tumor type, with luminal B cancers having a 4.2% to 35.5% risk of metastasis versus a 2.3% to 11.8% risk with luminal A tumors.
“The quantification of recurrence and disease progression is important to assess the effectiveness of treatment, evaluate prognosis, and allocate resources,” commented lead investigator Eileen Morgan, PhD, of the International Agency for Research on Cancer.
Dr. Morgan and colleagues presented the new meta-analysis at the virtual Advanced Breast Cancer Sixth International Consensus Conference.
She added that this information has not been available until now “because cancer registries have not been routinely collecting this data.”
In fact, the U.S. National Cancer Institute began a project earlier this year to track this information, after 48 years of not doing so.
Reacting to the findings, Shani Paluch-Shimon, MBBS, director of the Breast Unit at Hadassah University Hospital, Jerusalem, commented that this work “provides the first reliable estimate of how many breast cancer patients go on to develop advanced disease in contemporary cohorts.”
“This information is, of course, important for patients who want to understand their prognosis,” she continued.
“But it’s also vital at a public health level for those of us working to treat and prevent advanced breast cancer, to help us understand the scale of the disease around the world,” she said. “It will help us identify at-risk groups across different populations and demonstrate how disease course is changing with contemporary treatments.”
“It will also help us understand what resources are needed and where, to ensure we can collect and analyze quality data in real-time as this is key for resource allocation and planning future studies.”
The work was funded by a grant from the Susan G. Komen Foundation.
A version of this article first appeared on Medscape.com.
The data come from a massive meta-analysis of more than 400 studies conducted around the world, involving tens of thousands of women.
It found that the overall risk of metastasis is between 6% and 22%, with younger women having a higher risk.
While women aged 50 years or older when they were diagnosed with breast cancer have a risk of developing metastasis that ranged from 3.7% to 28.6%, women diagnosed with breast cancer before age 35 had a higher risk – 12.7% to 38%. The investigators speculate that this may be because younger women have a more aggressive form of breast cancer or because they are diagnosed at a later stage.
The risk of metastasis also varies by tumor type, with luminal B cancers having a 4.2% to 35.5% risk of metastasis versus a 2.3% to 11.8% risk with luminal A tumors.
“The quantification of recurrence and disease progression is important to assess the effectiveness of treatment, evaluate prognosis, and allocate resources,” commented lead investigator Eileen Morgan, PhD, of the International Agency for Research on Cancer.
Dr. Morgan and colleagues presented the new meta-analysis at the virtual Advanced Breast Cancer Sixth International Consensus Conference.
She added that this information has not been available until now “because cancer registries have not been routinely collecting this data.”
In fact, the U.S. National Cancer Institute began a project earlier this year to track this information, after 48 years of not doing so.
Reacting to the findings, Shani Paluch-Shimon, MBBS, director of the Breast Unit at Hadassah University Hospital, Jerusalem, commented that this work “provides the first reliable estimate of how many breast cancer patients go on to develop advanced disease in contemporary cohorts.”
“This information is, of course, important for patients who want to understand their prognosis,” she continued.
“But it’s also vital at a public health level for those of us working to treat and prevent advanced breast cancer, to help us understand the scale of the disease around the world,” she said. “It will help us identify at-risk groups across different populations and demonstrate how disease course is changing with contemporary treatments.”
“It will also help us understand what resources are needed and where, to ensure we can collect and analyze quality data in real-time as this is key for resource allocation and planning future studies.”
The work was funded by a grant from the Susan G. Komen Foundation.
A version of this article first appeared on Medscape.com.
Luminal, basal groupings could change metastatic prostate cancer treatment
.
Furthermore, the classification is “an important step toward better personalizing therapy for men with mCRPC,” write investigators led by Rahul Aggarwal, MD, a genitourinary oncologist at the University of California, San Francisco.
The classification is already of clinical importance in localized disease for prognosis and guides treatment, but has not until now been examined in mCRPC, they point out.
That’s probably because of the difficulty of biopsying prostate metastases, which often reside in the bone, the team adds.
The team retrospectively reviewed genetic and clinical information from 634 men in four clinical trial cohorts; 45% had tumors classified as luminal and 55% were classified as basal, based on increased or decreased expression of luminal and basal gene signatures. Treatment in the cohorts was at physicians’ discretion.
Much of what the team found is similar to what’s been reported for localized disease. Namely, “that patients with luminal tumors should be considered for androgen-signaling inhibitor [ASI] therapy, and those with basal tumors could be considered for chemotherapeutic approaches given the similarity to small cell/neuroendocrine prostate cancer and the diminished benefit of androgen-signaling inhibitors,” Dr. Aggarwal and colleagues write.
Stunningly and consistent with dependence on oncogenic androgen-receptor signaling in luminal tumors, luminal patients had significantly better survival when they were treated with ASIs instead of chemotherapy, with a median overall survival of 32 vs. 8.7 months (hazard ratio, 0.27; P < .001).
Notably, luminal tumors demonstrated an increased expression of androgen-signaling genes and obtained preferential benefit for ASI therapy, compared with basal tumors.
The basal subtype included but was not exclusive to small cell/neuroendocrine prostate cancer (SCNC), “which raises the potential that non-SCNC basal tumors (the majority) may share enough similarity with their SCNC counterparts that similar chemotherapy-based treatment strategies may be effective, especially given the diminished benefit of ASI therapy,” the team writes.
Overall, the investigators say the findings “warrant further validation in larger prospective cohorts and clinical trials.”
Possibly practice changing
Rodwell Mabaera, MD, PhD, a medical oncologist at Dartmouth-Hitchcock Medical Center in Lebanon, N.H., agreed with investigators about the potential impact of the basal/luminal classifications in an accompanying editorial.
“These subtypes represent a potentially powerful tool for personalized therapeutic decision-making that may improve outcomes in mCRPC,” he writes.
Dr. Mabaera notes that “the worst survival outcome was seen among patients with luminal tumors treated with chemotherapy, suggesting a potential negative effect of chemotherapy in this subgroup.”
The authors “appropriately concluded that use of ASI would be recommended in this population. ... If confirmed, these results would be practice changing for choice of treatment in [the] luminal subtype of mCRPC.”
In basal tumors, the investigators identified genetic changes for resistance to androgen-receptor antagonists and increased dependence on DNA damage-repair pathways. That opens “the prospect that PARP inhibitors,” which block cancer cells from repairing DNA, “may be effective in this subgroup of patients,” Dr. Mabaera said.
The basal/luminal treatment duality may not completely apply, however.
That’s because there was a trend toward improved survival with ASI treatment in basal tumors (HR, 0.62; P = .07), which suggests there may still be a subset of basal tumors that are dependent on androgen pathway signaling and would benefit from ASI therapy, he said.
Regarding the difficulty of biopsying mCRPC metastases, the investigators noted that the limited intraindividual variability in biopsy results supports “the feasibility of classifying patients on [the] basis of a single biopsy of a metastatic tumor.”
The work was supported by the U.S. Department of Defense Prostate Cancer Research Program, the National Cancer Institute, and others. Dr. Aggarwal has served as a paid consultant to and/or has received research funding from a number of companies, including Janssen, Merck, and AstraZeneca. Dr. Mabaera has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
.
Furthermore, the classification is “an important step toward better personalizing therapy for men with mCRPC,” write investigators led by Rahul Aggarwal, MD, a genitourinary oncologist at the University of California, San Francisco.
The classification is already of clinical importance in localized disease for prognosis and guides treatment, but has not until now been examined in mCRPC, they point out.
That’s probably because of the difficulty of biopsying prostate metastases, which often reside in the bone, the team adds.
The team retrospectively reviewed genetic and clinical information from 634 men in four clinical trial cohorts; 45% had tumors classified as luminal and 55% were classified as basal, based on increased or decreased expression of luminal and basal gene signatures. Treatment in the cohorts was at physicians’ discretion.
Much of what the team found is similar to what’s been reported for localized disease. Namely, “that patients with luminal tumors should be considered for androgen-signaling inhibitor [ASI] therapy, and those with basal tumors could be considered for chemotherapeutic approaches given the similarity to small cell/neuroendocrine prostate cancer and the diminished benefit of androgen-signaling inhibitors,” Dr. Aggarwal and colleagues write.
Stunningly and consistent with dependence on oncogenic androgen-receptor signaling in luminal tumors, luminal patients had significantly better survival when they were treated with ASIs instead of chemotherapy, with a median overall survival of 32 vs. 8.7 months (hazard ratio, 0.27; P < .001).
Notably, luminal tumors demonstrated an increased expression of androgen-signaling genes and obtained preferential benefit for ASI therapy, compared with basal tumors.
The basal subtype included but was not exclusive to small cell/neuroendocrine prostate cancer (SCNC), “which raises the potential that non-SCNC basal tumors (the majority) may share enough similarity with their SCNC counterparts that similar chemotherapy-based treatment strategies may be effective, especially given the diminished benefit of ASI therapy,” the team writes.
Overall, the investigators say the findings “warrant further validation in larger prospective cohorts and clinical trials.”
Possibly practice changing
Rodwell Mabaera, MD, PhD, a medical oncologist at Dartmouth-Hitchcock Medical Center in Lebanon, N.H., agreed with investigators about the potential impact of the basal/luminal classifications in an accompanying editorial.
“These subtypes represent a potentially powerful tool for personalized therapeutic decision-making that may improve outcomes in mCRPC,” he writes.
Dr. Mabaera notes that “the worst survival outcome was seen among patients with luminal tumors treated with chemotherapy, suggesting a potential negative effect of chemotherapy in this subgroup.”
The authors “appropriately concluded that use of ASI would be recommended in this population. ... If confirmed, these results would be practice changing for choice of treatment in [the] luminal subtype of mCRPC.”
In basal tumors, the investigators identified genetic changes for resistance to androgen-receptor antagonists and increased dependence on DNA damage-repair pathways. That opens “the prospect that PARP inhibitors,” which block cancer cells from repairing DNA, “may be effective in this subgroup of patients,” Dr. Mabaera said.
The basal/luminal treatment duality may not completely apply, however.
That’s because there was a trend toward improved survival with ASI treatment in basal tumors (HR, 0.62; P = .07), which suggests there may still be a subset of basal tumors that are dependent on androgen pathway signaling and would benefit from ASI therapy, he said.
Regarding the difficulty of biopsying mCRPC metastases, the investigators noted that the limited intraindividual variability in biopsy results supports “the feasibility of classifying patients on [the] basis of a single biopsy of a metastatic tumor.”
The work was supported by the U.S. Department of Defense Prostate Cancer Research Program, the National Cancer Institute, and others. Dr. Aggarwal has served as a paid consultant to and/or has received research funding from a number of companies, including Janssen, Merck, and AstraZeneca. Dr. Mabaera has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
.
Furthermore, the classification is “an important step toward better personalizing therapy for men with mCRPC,” write investigators led by Rahul Aggarwal, MD, a genitourinary oncologist at the University of California, San Francisco.
The classification is already of clinical importance in localized disease for prognosis and guides treatment, but has not until now been examined in mCRPC, they point out.
That’s probably because of the difficulty of biopsying prostate metastases, which often reside in the bone, the team adds.
The team retrospectively reviewed genetic and clinical information from 634 men in four clinical trial cohorts; 45% had tumors classified as luminal and 55% were classified as basal, based on increased or decreased expression of luminal and basal gene signatures. Treatment in the cohorts was at physicians’ discretion.
Much of what the team found is similar to what’s been reported for localized disease. Namely, “that patients with luminal tumors should be considered for androgen-signaling inhibitor [ASI] therapy, and those with basal tumors could be considered for chemotherapeutic approaches given the similarity to small cell/neuroendocrine prostate cancer and the diminished benefit of androgen-signaling inhibitors,” Dr. Aggarwal and colleagues write.
Stunningly and consistent with dependence on oncogenic androgen-receptor signaling in luminal tumors, luminal patients had significantly better survival when they were treated with ASIs instead of chemotherapy, with a median overall survival of 32 vs. 8.7 months (hazard ratio, 0.27; P < .001).
Notably, luminal tumors demonstrated an increased expression of androgen-signaling genes and obtained preferential benefit for ASI therapy, compared with basal tumors.
The basal subtype included but was not exclusive to small cell/neuroendocrine prostate cancer (SCNC), “which raises the potential that non-SCNC basal tumors (the majority) may share enough similarity with their SCNC counterparts that similar chemotherapy-based treatment strategies may be effective, especially given the diminished benefit of ASI therapy,” the team writes.
Overall, the investigators say the findings “warrant further validation in larger prospective cohorts and clinical trials.”
Possibly practice changing
Rodwell Mabaera, MD, PhD, a medical oncologist at Dartmouth-Hitchcock Medical Center in Lebanon, N.H., agreed with investigators about the potential impact of the basal/luminal classifications in an accompanying editorial.
“These subtypes represent a potentially powerful tool for personalized therapeutic decision-making that may improve outcomes in mCRPC,” he writes.
Dr. Mabaera notes that “the worst survival outcome was seen among patients with luminal tumors treated with chemotherapy, suggesting a potential negative effect of chemotherapy in this subgroup.”
The authors “appropriately concluded that use of ASI would be recommended in this population. ... If confirmed, these results would be practice changing for choice of treatment in [the] luminal subtype of mCRPC.”
In basal tumors, the investigators identified genetic changes for resistance to androgen-receptor antagonists and increased dependence on DNA damage-repair pathways. That opens “the prospect that PARP inhibitors,” which block cancer cells from repairing DNA, “may be effective in this subgroup of patients,” Dr. Mabaera said.
The basal/luminal treatment duality may not completely apply, however.
That’s because there was a trend toward improved survival with ASI treatment in basal tumors (HR, 0.62; P = .07), which suggests there may still be a subset of basal tumors that are dependent on androgen pathway signaling and would benefit from ASI therapy, he said.
Regarding the difficulty of biopsying mCRPC metastases, the investigators noted that the limited intraindividual variability in biopsy results supports “the feasibility of classifying patients on [the] basis of a single biopsy of a metastatic tumor.”
The work was supported by the U.S. Department of Defense Prostate Cancer Research Program, the National Cancer Institute, and others. Dr. Aggarwal has served as a paid consultant to and/or has received research funding from a number of companies, including Janssen, Merck, and AstraZeneca. Dr. Mabaera has disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Watchful waiting in BCC: Which patients can benefit?
Basal cell carcinomas (BCCs), the most common form of skin cancer, are generally slow-growing tumors that occur in older patients.
Given the low rates of metastasis and mortality associated with BCC, some patients do not require treatment. However, there have been no evidence-based recommendations on who may benefit from a watch-and-wait approach.
.
The investigators found that, for older people with low-grade BCCs and limited life expectancy, the risks associated with surgery – bleeding, infection, and wound dehiscence – appeared to outweigh the advantages. According to the authors, these patients “might not live long enough to benefit from treatment.”
This finding mirrors oncologists’ observations regarding low-risk prostate cancer, for which watchful waiting is now the standard of care.
“At present, however, procedure rates [for patients with BCC] increase with age, and many basal cell carcinomas are treated surgically regardless of a patient’s life expectancy,” Eleni Linos, MD, PhD, professor of dermatology at Stanford (Calif.) University, and Mary-Margaret Chren, MD, chair of dermatology at Vanderbilt University, Nashville, Tenn., write in a viewpoint article published in August in JAMA Internal Medicine.
Considering the current treatment patterns for BCC, patients would “benefit from the existence of an evidence-based standard of care that includes active surveillance,” Mackenzie Wehner, MD, assistant professor at MD Anderson Cancer Center, Houston, Tex., writes in an editorial that accompanies the article in JAMA Dermatology.
Insights from the Dutch study
The article in JAMA Dermatology presents a cohort study conducted at Radboud University Medical Center in Nijmegen, the Netherlands. The study included 89 patients who were managed with watchful waiting. The patients received no treatment for at least 3 months following their diagnoses.
The median age of the patients was 83 years. The patients had a total of 280 BCCs. The median initial diameter of the BCCs was 9.5 mm. Just over half of the patients were men, and about half of the BCCs were in the head and neck region.
The median follow-up was 9 months; the maximum follow-up was 6.5 years. Remarkably, the investigators say, more than half the tumors (53.2%) did not grow, and some even shrank. The majority of patients were asymptomatic at presentation, and fewer than 10% developed new symptoms, such as bleeding and itching, during follow-up.
Among the tumors that did grow, 70% were low-risk superficial/nodular tumors, which only increased in size by an estimated 1.06 mm over a year. Thirty percent were higher-risk micronodular/infiltrative tumors, which grew an estimated 4.46 mm over a 12-month period.
About two-thirds of patients eventually chose to have at least one of their BCCs removed after a median of about 7 months. Only three BCCs (2.8%) needed more extensive surgery – reconstructive surgery, rather than primary closure, for instance – than would have been necessary with an earlier excision.
No deaths from BCC were reported in the study.
The investigators tracked the reasons patients opted for watchful waiting. Many understood that their tumors likely would not cause problems in their remaining years. Others prioritized dealing with more pressing health or family problems. Logistics came into play for some, such as not having reliable transportation for hospital visits.
“In patients with [limited life expectancy] and asymptomatic low-risk tumors, [watchful waiting] should be discussed as a potentially appropriate approach,” the investigators, led by Marieke E. C. van Winden, MD, a dermatology resident at Radboud University, conclude.
For patients who wish to pursue a watchful waiting approach, the Dutch team recommends conducting follow-up visits every 3-6 months to see whether patients wish to continue with watchful waiting and to determine whether the risk-to-benefit ratio has shifted.
These recommendations are in line with criteria Dr. Linos and Dr. Chren propose in their viewpoint article in JAMA Internal Medicine. They characterize low-risk BCCs as asymptomatic, smaller than 1 cm in diameter, and located on the trunk or extremities in immunocompetent patients. They note that details regarding active surveillance for BCCs need to be worked out.
“Active surveillance should be studied as a management option because it is supported by the available evidence, congruent with the care of other low-risk cancers, and in accord with principles of shared decision-making,” Dr. Linos and Dr. Chren write.
No funding source was reported. Dr. Wehner, Dr. van Winden, Dr. Linos, and Dr. Chren have disclosed no relevant financial relationships. Two of Dr. van Winden’s coauthors report ties to several companies, including Sanofi Genzyme, AbbVie, Novartis, and Janssen.
A version of this article first appeared on Medscape.com.
Basal cell carcinomas (BCCs), the most common form of skin cancer, are generally slow-growing tumors that occur in older patients.
Given the low rates of metastasis and mortality associated with BCC, some patients do not require treatment. However, there have been no evidence-based recommendations on who may benefit from a watch-and-wait approach.
.
The investigators found that, for older people with low-grade BCCs and limited life expectancy, the risks associated with surgery – bleeding, infection, and wound dehiscence – appeared to outweigh the advantages. According to the authors, these patients “might not live long enough to benefit from treatment.”
This finding mirrors oncologists’ observations regarding low-risk prostate cancer, for which watchful waiting is now the standard of care.
“At present, however, procedure rates [for patients with BCC] increase with age, and many basal cell carcinomas are treated surgically regardless of a patient’s life expectancy,” Eleni Linos, MD, PhD, professor of dermatology at Stanford (Calif.) University, and Mary-Margaret Chren, MD, chair of dermatology at Vanderbilt University, Nashville, Tenn., write in a viewpoint article published in August in JAMA Internal Medicine.
Considering the current treatment patterns for BCC, patients would “benefit from the existence of an evidence-based standard of care that includes active surveillance,” Mackenzie Wehner, MD, assistant professor at MD Anderson Cancer Center, Houston, Tex., writes in an editorial that accompanies the article in JAMA Dermatology.
Insights from the Dutch study
The article in JAMA Dermatology presents a cohort study conducted at Radboud University Medical Center in Nijmegen, the Netherlands. The study included 89 patients who were managed with watchful waiting. The patients received no treatment for at least 3 months following their diagnoses.
The median age of the patients was 83 years. The patients had a total of 280 BCCs. The median initial diameter of the BCCs was 9.5 mm. Just over half of the patients were men, and about half of the BCCs were in the head and neck region.
The median follow-up was 9 months; the maximum follow-up was 6.5 years. Remarkably, the investigators say, more than half the tumors (53.2%) did not grow, and some even shrank. The majority of patients were asymptomatic at presentation, and fewer than 10% developed new symptoms, such as bleeding and itching, during follow-up.
Among the tumors that did grow, 70% were low-risk superficial/nodular tumors, which only increased in size by an estimated 1.06 mm over a year. Thirty percent were higher-risk micronodular/infiltrative tumors, which grew an estimated 4.46 mm over a 12-month period.
About two-thirds of patients eventually chose to have at least one of their BCCs removed after a median of about 7 months. Only three BCCs (2.8%) needed more extensive surgery – reconstructive surgery, rather than primary closure, for instance – than would have been necessary with an earlier excision.
No deaths from BCC were reported in the study.
The investigators tracked the reasons patients opted for watchful waiting. Many understood that their tumors likely would not cause problems in their remaining years. Others prioritized dealing with more pressing health or family problems. Logistics came into play for some, such as not having reliable transportation for hospital visits.
“In patients with [limited life expectancy] and asymptomatic low-risk tumors, [watchful waiting] should be discussed as a potentially appropriate approach,” the investigators, led by Marieke E. C. van Winden, MD, a dermatology resident at Radboud University, conclude.
For patients who wish to pursue a watchful waiting approach, the Dutch team recommends conducting follow-up visits every 3-6 months to see whether patients wish to continue with watchful waiting and to determine whether the risk-to-benefit ratio has shifted.
These recommendations are in line with criteria Dr. Linos and Dr. Chren propose in their viewpoint article in JAMA Internal Medicine. They characterize low-risk BCCs as asymptomatic, smaller than 1 cm in diameter, and located on the trunk or extremities in immunocompetent patients. They note that details regarding active surveillance for BCCs need to be worked out.
“Active surveillance should be studied as a management option because it is supported by the available evidence, congruent with the care of other low-risk cancers, and in accord with principles of shared decision-making,” Dr. Linos and Dr. Chren write.
No funding source was reported. Dr. Wehner, Dr. van Winden, Dr. Linos, and Dr. Chren have disclosed no relevant financial relationships. Two of Dr. van Winden’s coauthors report ties to several companies, including Sanofi Genzyme, AbbVie, Novartis, and Janssen.
A version of this article first appeared on Medscape.com.
Basal cell carcinomas (BCCs), the most common form of skin cancer, are generally slow-growing tumors that occur in older patients.
Given the low rates of metastasis and mortality associated with BCC, some patients do not require treatment. However, there have been no evidence-based recommendations on who may benefit from a watch-and-wait approach.
.
The investigators found that, for older people with low-grade BCCs and limited life expectancy, the risks associated with surgery – bleeding, infection, and wound dehiscence – appeared to outweigh the advantages. According to the authors, these patients “might not live long enough to benefit from treatment.”
This finding mirrors oncologists’ observations regarding low-risk prostate cancer, for which watchful waiting is now the standard of care.
“At present, however, procedure rates [for patients with BCC] increase with age, and many basal cell carcinomas are treated surgically regardless of a patient’s life expectancy,” Eleni Linos, MD, PhD, professor of dermatology at Stanford (Calif.) University, and Mary-Margaret Chren, MD, chair of dermatology at Vanderbilt University, Nashville, Tenn., write in a viewpoint article published in August in JAMA Internal Medicine.
Considering the current treatment patterns for BCC, patients would “benefit from the existence of an evidence-based standard of care that includes active surveillance,” Mackenzie Wehner, MD, assistant professor at MD Anderson Cancer Center, Houston, Tex., writes in an editorial that accompanies the article in JAMA Dermatology.
Insights from the Dutch study
The article in JAMA Dermatology presents a cohort study conducted at Radboud University Medical Center in Nijmegen, the Netherlands. The study included 89 patients who were managed with watchful waiting. The patients received no treatment for at least 3 months following their diagnoses.
The median age of the patients was 83 years. The patients had a total of 280 BCCs. The median initial diameter of the BCCs was 9.5 mm. Just over half of the patients were men, and about half of the BCCs were in the head and neck region.
The median follow-up was 9 months; the maximum follow-up was 6.5 years. Remarkably, the investigators say, more than half the tumors (53.2%) did not grow, and some even shrank. The majority of patients were asymptomatic at presentation, and fewer than 10% developed new symptoms, such as bleeding and itching, during follow-up.
Among the tumors that did grow, 70% were low-risk superficial/nodular tumors, which only increased in size by an estimated 1.06 mm over a year. Thirty percent were higher-risk micronodular/infiltrative tumors, which grew an estimated 4.46 mm over a 12-month period.
About two-thirds of patients eventually chose to have at least one of their BCCs removed after a median of about 7 months. Only three BCCs (2.8%) needed more extensive surgery – reconstructive surgery, rather than primary closure, for instance – than would have been necessary with an earlier excision.
No deaths from BCC were reported in the study.
The investigators tracked the reasons patients opted for watchful waiting. Many understood that their tumors likely would not cause problems in their remaining years. Others prioritized dealing with more pressing health or family problems. Logistics came into play for some, such as not having reliable transportation for hospital visits.
“In patients with [limited life expectancy] and asymptomatic low-risk tumors, [watchful waiting] should be discussed as a potentially appropriate approach,” the investigators, led by Marieke E. C. van Winden, MD, a dermatology resident at Radboud University, conclude.
For patients who wish to pursue a watchful waiting approach, the Dutch team recommends conducting follow-up visits every 3-6 months to see whether patients wish to continue with watchful waiting and to determine whether the risk-to-benefit ratio has shifted.
These recommendations are in line with criteria Dr. Linos and Dr. Chren propose in their viewpoint article in JAMA Internal Medicine. They characterize low-risk BCCs as asymptomatic, smaller than 1 cm in diameter, and located on the trunk or extremities in immunocompetent patients. They note that details regarding active surveillance for BCCs need to be worked out.
“Active surveillance should be studied as a management option because it is supported by the available evidence, congruent with the care of other low-risk cancers, and in accord with principles of shared decision-making,” Dr. Linos and Dr. Chren write.
No funding source was reported. Dr. Wehner, Dr. van Winden, Dr. Linos, and Dr. Chren have disclosed no relevant financial relationships. Two of Dr. van Winden’s coauthors report ties to several companies, including Sanofi Genzyme, AbbVie, Novartis, and Janssen.
A version of this article first appeared on Medscape.com.
Internal mammary lymph node radiation safe over the long term
After a median follow-up of 15.7 years among almost 4,000 women, for half of patients who received postoperative internal mammary and medial supraclavicular (IM-MS) lymph node irradiation, the “absolute rates and differences” of heart and lung complications “were very low, with no increased non–breast cancer related mortality, even before introducing heart-sparing techniques,” say investigators.
The findings come from the European Organization for Research and Treatment of Cancer (EORTC) trial. The investigators were led by Philip Poortmans, MD, PhD, a radiation oncologist at the University of Antwerp, Belgium.
The team had previously reported lower breast cancer mortality and breast cancer recurrence rates in the radiation group.
Women in the trial were treated from 1996 to 2004. “We expect that with contemporary volume-based radiation therapy outcomes will be even better, by improved coverage of target volumes, more homogeneous dose delivery, and decreased doses to non-target tissues,” the team says.
In the end, “our findings ... have important – reassuring – consequences for decision-making concerning elective lymph node treatment in breast cancer,” the researchers comment.
The study was published online on July 28 in the Journal of the National Cancer Institute.
Resolving the debate
There’s been debate for decades on whether the long-term risk associated with nodal irradiation, particularly collateral heart and lung damage from internal mammary irradiation, outweighs the benefits of better disease control, noted Julia White, MD, a radiation oncologist at the Ohio State University Breast Center, Columbus, in an accompanying editorial.
Concerns stem originally from trials conducted from the 1950s to the 1970s. In those trials, higher doses of radiation were delivered to the internal mammary node with far less precision than today. Subsequent studies have not laid the worry to rest, and protocols vary across institutions, Dr. White explains. Some treat IM nodes in high-risk patients, but others only treat the axilla and the medial supraclavicular lymph nodes.
Dr. White says the new EORTC trial “moves us one step closer to resolving the debate about the value of internal mammary nodal (IMN) radiation.”
She notes that since 2014, advances in the field have led to an almost 50% reduction in cardiac radiation exposure during breast cancer treatment. Current guidelines recommend that internal mammary nodes “should generally be treated” as part of postmastectomy radiotherapy, but cardiopulmonary complications are still possible even with improved techniques, she writes.
Mostly grade 1 morbidity
Women in the study had stage I-III breast cancer with axillary node involvement and/or medially located primary tumors. The median age at study entry was 54 years. The patients were treated at 46 centers in 13 countries.
The group that received IM-MS irradiation after surgery received 50 Gy in 25 fractions over 5 weeks.
The cumulative 15-year incidence of lung fibrosis was 5.7% among treated women, versus 2.9% among control patients. The incidence of cardiac fibrosis was 1.9% with treatment, versus 1.1% without.
The incidence of any cardiac disease was 11.1% in the radiation arm, versus 9.4% in the control group.
Complications were mostly of grade 1. The only statistically significant difference in rates of events of grade 2 or higher was in the incidence of pulmonary morbidity, which was 0.8% with radiation versus 0.1% without. There were no differences in the incidence of second malignancies, contralateral breast cancer cases, or cardiovascular deaths with IMN irradiation.
The authors note that their results conflict with a 2013 study that found a relative increase in major coronary events of 7.4% per Gy mean heart dose. The women in that trial were treated in Sweden and Denmark between 1958 and 2001.
Dr. Poortmans and collegues note, however, that this 2013 study and others found a proportional and not an absolute increase in risk. With a baseline risk of 10%, for instance, a 7% increase per 1 Gy translates to a total risk of 10.07%.
Also, no increased risk has been reported in more recently published trials, and a meta-analysis found no increase in non–breast cancer related mortality with trials that began after 1988.
Still, “it seems logical to take the pre-existing cardiac comorbidity of patients into consideration,” the investigators conclude. For patients with higher baseline cardiopulmonary risk factors, lower mean heart doses should be used, and such patients should undergo longer-term follow-up, they write.
The study was funded by La Ligue Nationale Contre Le Cancer and the KWF Kanker Bestrijding from the Netherlands. The investigators and Dr. White have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
After a median follow-up of 15.7 years among almost 4,000 women, for half of patients who received postoperative internal mammary and medial supraclavicular (IM-MS) lymph node irradiation, the “absolute rates and differences” of heart and lung complications “were very low, with no increased non–breast cancer related mortality, even before introducing heart-sparing techniques,” say investigators.
The findings come from the European Organization for Research and Treatment of Cancer (EORTC) trial. The investigators were led by Philip Poortmans, MD, PhD, a radiation oncologist at the University of Antwerp, Belgium.
The team had previously reported lower breast cancer mortality and breast cancer recurrence rates in the radiation group.
Women in the trial were treated from 1996 to 2004. “We expect that with contemporary volume-based radiation therapy outcomes will be even better, by improved coverage of target volumes, more homogeneous dose delivery, and decreased doses to non-target tissues,” the team says.
In the end, “our findings ... have important – reassuring – consequences for decision-making concerning elective lymph node treatment in breast cancer,” the researchers comment.
The study was published online on July 28 in the Journal of the National Cancer Institute.
Resolving the debate
There’s been debate for decades on whether the long-term risk associated with nodal irradiation, particularly collateral heart and lung damage from internal mammary irradiation, outweighs the benefits of better disease control, noted Julia White, MD, a radiation oncologist at the Ohio State University Breast Center, Columbus, in an accompanying editorial.
Concerns stem originally from trials conducted from the 1950s to the 1970s. In those trials, higher doses of radiation were delivered to the internal mammary node with far less precision than today. Subsequent studies have not laid the worry to rest, and protocols vary across institutions, Dr. White explains. Some treat IM nodes in high-risk patients, but others only treat the axilla and the medial supraclavicular lymph nodes.
Dr. White says the new EORTC trial “moves us one step closer to resolving the debate about the value of internal mammary nodal (IMN) radiation.”
She notes that since 2014, advances in the field have led to an almost 50% reduction in cardiac radiation exposure during breast cancer treatment. Current guidelines recommend that internal mammary nodes “should generally be treated” as part of postmastectomy radiotherapy, but cardiopulmonary complications are still possible even with improved techniques, she writes.
Mostly grade 1 morbidity
Women in the study had stage I-III breast cancer with axillary node involvement and/or medially located primary tumors. The median age at study entry was 54 years. The patients were treated at 46 centers in 13 countries.
The group that received IM-MS irradiation after surgery received 50 Gy in 25 fractions over 5 weeks.
The cumulative 15-year incidence of lung fibrosis was 5.7% among treated women, versus 2.9% among control patients. The incidence of cardiac fibrosis was 1.9% with treatment, versus 1.1% without.
The incidence of any cardiac disease was 11.1% in the radiation arm, versus 9.4% in the control group.
Complications were mostly of grade 1. The only statistically significant difference in rates of events of grade 2 or higher was in the incidence of pulmonary morbidity, which was 0.8% with radiation versus 0.1% without. There were no differences in the incidence of second malignancies, contralateral breast cancer cases, or cardiovascular deaths with IMN irradiation.
The authors note that their results conflict with a 2013 study that found a relative increase in major coronary events of 7.4% per Gy mean heart dose. The women in that trial were treated in Sweden and Denmark between 1958 and 2001.
Dr. Poortmans and collegues note, however, that this 2013 study and others found a proportional and not an absolute increase in risk. With a baseline risk of 10%, for instance, a 7% increase per 1 Gy translates to a total risk of 10.07%.
Also, no increased risk has been reported in more recently published trials, and a meta-analysis found no increase in non–breast cancer related mortality with trials that began after 1988.
Still, “it seems logical to take the pre-existing cardiac comorbidity of patients into consideration,” the investigators conclude. For patients with higher baseline cardiopulmonary risk factors, lower mean heart doses should be used, and such patients should undergo longer-term follow-up, they write.
The study was funded by La Ligue Nationale Contre Le Cancer and the KWF Kanker Bestrijding from the Netherlands. The investigators and Dr. White have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
After a median follow-up of 15.7 years among almost 4,000 women, for half of patients who received postoperative internal mammary and medial supraclavicular (IM-MS) lymph node irradiation, the “absolute rates and differences” of heart and lung complications “were very low, with no increased non–breast cancer related mortality, even before introducing heart-sparing techniques,” say investigators.
The findings come from the European Organization for Research and Treatment of Cancer (EORTC) trial. The investigators were led by Philip Poortmans, MD, PhD, a radiation oncologist at the University of Antwerp, Belgium.
The team had previously reported lower breast cancer mortality and breast cancer recurrence rates in the radiation group.
Women in the trial were treated from 1996 to 2004. “We expect that with contemporary volume-based radiation therapy outcomes will be even better, by improved coverage of target volumes, more homogeneous dose delivery, and decreased doses to non-target tissues,” the team says.
In the end, “our findings ... have important – reassuring – consequences for decision-making concerning elective lymph node treatment in breast cancer,” the researchers comment.
The study was published online on July 28 in the Journal of the National Cancer Institute.
Resolving the debate
There’s been debate for decades on whether the long-term risk associated with nodal irradiation, particularly collateral heart and lung damage from internal mammary irradiation, outweighs the benefits of better disease control, noted Julia White, MD, a radiation oncologist at the Ohio State University Breast Center, Columbus, in an accompanying editorial.
Concerns stem originally from trials conducted from the 1950s to the 1970s. In those trials, higher doses of radiation were delivered to the internal mammary node with far less precision than today. Subsequent studies have not laid the worry to rest, and protocols vary across institutions, Dr. White explains. Some treat IM nodes in high-risk patients, but others only treat the axilla and the medial supraclavicular lymph nodes.
Dr. White says the new EORTC trial “moves us one step closer to resolving the debate about the value of internal mammary nodal (IMN) radiation.”
She notes that since 2014, advances in the field have led to an almost 50% reduction in cardiac radiation exposure during breast cancer treatment. Current guidelines recommend that internal mammary nodes “should generally be treated” as part of postmastectomy radiotherapy, but cardiopulmonary complications are still possible even with improved techniques, she writes.
Mostly grade 1 morbidity
Women in the study had stage I-III breast cancer with axillary node involvement and/or medially located primary tumors. The median age at study entry was 54 years. The patients were treated at 46 centers in 13 countries.
The group that received IM-MS irradiation after surgery received 50 Gy in 25 fractions over 5 weeks.
The cumulative 15-year incidence of lung fibrosis was 5.7% among treated women, versus 2.9% among control patients. The incidence of cardiac fibrosis was 1.9% with treatment, versus 1.1% without.
The incidence of any cardiac disease was 11.1% in the radiation arm, versus 9.4% in the control group.
Complications were mostly of grade 1. The only statistically significant difference in rates of events of grade 2 or higher was in the incidence of pulmonary morbidity, which was 0.8% with radiation versus 0.1% without. There were no differences in the incidence of second malignancies, contralateral breast cancer cases, or cardiovascular deaths with IMN irradiation.
The authors note that their results conflict with a 2013 study that found a relative increase in major coronary events of 7.4% per Gy mean heart dose. The women in that trial were treated in Sweden and Denmark between 1958 and 2001.
Dr. Poortmans and collegues note, however, that this 2013 study and others found a proportional and not an absolute increase in risk. With a baseline risk of 10%, for instance, a 7% increase per 1 Gy translates to a total risk of 10.07%.
Also, no increased risk has been reported in more recently published trials, and a meta-analysis found no increase in non–breast cancer related mortality with trials that began after 1988.
Still, “it seems logical to take the pre-existing cardiac comorbidity of patients into consideration,” the investigators conclude. For patients with higher baseline cardiopulmonary risk factors, lower mean heart doses should be used, and such patients should undergo longer-term follow-up, they write.
The study was funded by La Ligue Nationale Contre Le Cancer and the KWF Kanker Bestrijding from the Netherlands. The investigators and Dr. White have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Better CNS control in children with ALL: ‘Goldilocks’ approach
Treatment of central nervous system involvement in pediatric acute lymphoblastic leukemia (ALL) needs to be based on risk, and should no longer be applied in a one-size-fits all approach, say experts writing in an editorial published July 29 in the journal Blood.
“Because cure rates now exceed 90%, using neurotoxic drugs in non–risk-adapted protocols is unacceptable and a paradigm shift in treating CNS ALL is required,” write pediatric leukemia researchers Christina Halsey, PhD, of the University of Glasgow and Gabriele Escherich, MD, of the University Medical Center Hamburg-Eppendorf (Germany).
“We want to reach a Goldilocks point: not too much, not too little, but just right for every child,” they write.
The problem is that “the absence of clinically useful biomarkers prevents accurate risk stratification, resulting in universal use of intensive CNS-directed therapy. This therapy is likely to overtreat many children, exposing them to an unnecessary risk of toxicity,” including long-term cognitive deficits in 20%-40% of them, they point out.
The editorial accompanied a new study in which investigators in China focused on improving CNS control in children with ALL, which the editorialists said was step in the right direction.
In the Chinese Children’s Cancer Group ALL-2015 trial, investigators found that prephase dexamethasone, delayed intrathecal therapy, intravenous anesthesia to reduce traumatic lumbar punctures, and flow cytometry to accurately ascertain initial CNS involvement may improve CNS control.
The trial included 7,640 consecutive children up to age 18 treated from 2015 to 2019 across 20 major medical centers in China. Children received conventional remission induction and subsequent risk-directed therapy, including 16-22 triple intrathecal treatments. Prophylactic cranial irradiation was not used.
The 5-year event-free survival was 80.3% and overall survival 91.1%. The cumulative risk of isolated CNS relapse was 1.9% and of any CNS relapse 2.7%, comparable to reports from other major study groups, both with and without cranial radiation.
“We attributed our relatively good CNS control to the prephase treatment with dexamethasone, which reduced leukemia cells in blood and the CNS, and to the delayed intrathecal therapy until all (or a large proportion) of circulating leukemic blasts were cleared, thus reducing the consequence of traumatic lumbar puncture with blasts,” said the investigators, led by Jingyan Tang, MD, a hematologist/oncologist at the Shanghai (China) Children’s Medical Center.
“This approach of delayed administration of initial intrathecal therapy after prephase steroid treatment, if confirmed successful by additional studies, can be adopted readily,” they say.
The editorialists concur. The low rates of CNS relapse, despite omission of radiotherapy and inclusion of high-risk subgroups, “might suggest a potential protective effect of steroids before diagnostic lumbar puncture,” they said.
“However, flow cytometry is not sensitive enough to track disease response over time. In the bone marrow, minimal residual disease (MRD) is used to identify children at high or low risk of relapse and modify therapy accordingly. We desperately need a minimal residual disease equivalent for CNS leukemia to allow us to tailor therapy,” Dr. Halsey and Dr. Escherich say.
It’s not surprising that the use of anesthesia led to fewer traumatic lumbar punctures than in “frightened child[ren] undergoing such a painful procedure without anesthesia,” the study team notes. Its correlation with lower CNS relapses is probably because drug delivery was more accurate in sedated children, the editorialists add.
Female sex was also protective against relapse in cases where general anesthesia wasn’t used for lumbar puncture. “One could speculate that it is more difficult to restrict male patients than female patients for successful intrathecal therapy if they were not undergoing anesthesia during the procedure,” the investigators write.
“Unfortunately,” the editorialists add, rapid adoption of anesthesia for lumbar punctures “is tempered by the recent observation that repeated general anesthesia in children with ALL is associated with increased neurotoxicity.”
The work was supported by grants from the National Natural Science Foundation of China, National Cancer Institute, and others. The study authors and editorialists have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Treatment of central nervous system involvement in pediatric acute lymphoblastic leukemia (ALL) needs to be based on risk, and should no longer be applied in a one-size-fits all approach, say experts writing in an editorial published July 29 in the journal Blood.
“Because cure rates now exceed 90%, using neurotoxic drugs in non–risk-adapted protocols is unacceptable and a paradigm shift in treating CNS ALL is required,” write pediatric leukemia researchers Christina Halsey, PhD, of the University of Glasgow and Gabriele Escherich, MD, of the University Medical Center Hamburg-Eppendorf (Germany).
“We want to reach a Goldilocks point: not too much, not too little, but just right for every child,” they write.
The problem is that “the absence of clinically useful biomarkers prevents accurate risk stratification, resulting in universal use of intensive CNS-directed therapy. This therapy is likely to overtreat many children, exposing them to an unnecessary risk of toxicity,” including long-term cognitive deficits in 20%-40% of them, they point out.
The editorial accompanied a new study in which investigators in China focused on improving CNS control in children with ALL, which the editorialists said was step in the right direction.
In the Chinese Children’s Cancer Group ALL-2015 trial, investigators found that prephase dexamethasone, delayed intrathecal therapy, intravenous anesthesia to reduce traumatic lumbar punctures, and flow cytometry to accurately ascertain initial CNS involvement may improve CNS control.
The trial included 7,640 consecutive children up to age 18 treated from 2015 to 2019 across 20 major medical centers in China. Children received conventional remission induction and subsequent risk-directed therapy, including 16-22 triple intrathecal treatments. Prophylactic cranial irradiation was not used.
The 5-year event-free survival was 80.3% and overall survival 91.1%. The cumulative risk of isolated CNS relapse was 1.9% and of any CNS relapse 2.7%, comparable to reports from other major study groups, both with and without cranial radiation.
“We attributed our relatively good CNS control to the prephase treatment with dexamethasone, which reduced leukemia cells in blood and the CNS, and to the delayed intrathecal therapy until all (or a large proportion) of circulating leukemic blasts were cleared, thus reducing the consequence of traumatic lumbar puncture with blasts,” said the investigators, led by Jingyan Tang, MD, a hematologist/oncologist at the Shanghai (China) Children’s Medical Center.
“This approach of delayed administration of initial intrathecal therapy after prephase steroid treatment, if confirmed successful by additional studies, can be adopted readily,” they say.
The editorialists concur. The low rates of CNS relapse, despite omission of radiotherapy and inclusion of high-risk subgroups, “might suggest a potential protective effect of steroids before diagnostic lumbar puncture,” they said.
“However, flow cytometry is not sensitive enough to track disease response over time. In the bone marrow, minimal residual disease (MRD) is used to identify children at high or low risk of relapse and modify therapy accordingly. We desperately need a minimal residual disease equivalent for CNS leukemia to allow us to tailor therapy,” Dr. Halsey and Dr. Escherich say.
It’s not surprising that the use of anesthesia led to fewer traumatic lumbar punctures than in “frightened child[ren] undergoing such a painful procedure without anesthesia,” the study team notes. Its correlation with lower CNS relapses is probably because drug delivery was more accurate in sedated children, the editorialists add.
Female sex was also protective against relapse in cases where general anesthesia wasn’t used for lumbar puncture. “One could speculate that it is more difficult to restrict male patients than female patients for successful intrathecal therapy if they were not undergoing anesthesia during the procedure,” the investigators write.
“Unfortunately,” the editorialists add, rapid adoption of anesthesia for lumbar punctures “is tempered by the recent observation that repeated general anesthesia in children with ALL is associated with increased neurotoxicity.”
The work was supported by grants from the National Natural Science Foundation of China, National Cancer Institute, and others. The study authors and editorialists have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Treatment of central nervous system involvement in pediatric acute lymphoblastic leukemia (ALL) needs to be based on risk, and should no longer be applied in a one-size-fits all approach, say experts writing in an editorial published July 29 in the journal Blood.
“Because cure rates now exceed 90%, using neurotoxic drugs in non–risk-adapted protocols is unacceptable and a paradigm shift in treating CNS ALL is required,” write pediatric leukemia researchers Christina Halsey, PhD, of the University of Glasgow and Gabriele Escherich, MD, of the University Medical Center Hamburg-Eppendorf (Germany).
“We want to reach a Goldilocks point: not too much, not too little, but just right for every child,” they write.
The problem is that “the absence of clinically useful biomarkers prevents accurate risk stratification, resulting in universal use of intensive CNS-directed therapy. This therapy is likely to overtreat many children, exposing them to an unnecessary risk of toxicity,” including long-term cognitive deficits in 20%-40% of them, they point out.
The editorial accompanied a new study in which investigators in China focused on improving CNS control in children with ALL, which the editorialists said was step in the right direction.
In the Chinese Children’s Cancer Group ALL-2015 trial, investigators found that prephase dexamethasone, delayed intrathecal therapy, intravenous anesthesia to reduce traumatic lumbar punctures, and flow cytometry to accurately ascertain initial CNS involvement may improve CNS control.
The trial included 7,640 consecutive children up to age 18 treated from 2015 to 2019 across 20 major medical centers in China. Children received conventional remission induction and subsequent risk-directed therapy, including 16-22 triple intrathecal treatments. Prophylactic cranial irradiation was not used.
The 5-year event-free survival was 80.3% and overall survival 91.1%. The cumulative risk of isolated CNS relapse was 1.9% and of any CNS relapse 2.7%, comparable to reports from other major study groups, both with and without cranial radiation.
“We attributed our relatively good CNS control to the prephase treatment with dexamethasone, which reduced leukemia cells in blood and the CNS, and to the delayed intrathecal therapy until all (or a large proportion) of circulating leukemic blasts were cleared, thus reducing the consequence of traumatic lumbar puncture with blasts,” said the investigators, led by Jingyan Tang, MD, a hematologist/oncologist at the Shanghai (China) Children’s Medical Center.
“This approach of delayed administration of initial intrathecal therapy after prephase steroid treatment, if confirmed successful by additional studies, can be adopted readily,” they say.
The editorialists concur. The low rates of CNS relapse, despite omission of radiotherapy and inclusion of high-risk subgroups, “might suggest a potential protective effect of steroids before diagnostic lumbar puncture,” they said.
“However, flow cytometry is not sensitive enough to track disease response over time. In the bone marrow, minimal residual disease (MRD) is used to identify children at high or low risk of relapse and modify therapy accordingly. We desperately need a minimal residual disease equivalent for CNS leukemia to allow us to tailor therapy,” Dr. Halsey and Dr. Escherich say.
It’s not surprising that the use of anesthesia led to fewer traumatic lumbar punctures than in “frightened child[ren] undergoing such a painful procedure without anesthesia,” the study team notes. Its correlation with lower CNS relapses is probably because drug delivery was more accurate in sedated children, the editorialists add.
Female sex was also protective against relapse in cases where general anesthesia wasn’t used for lumbar puncture. “One could speculate that it is more difficult to restrict male patients than female patients for successful intrathecal therapy if they were not undergoing anesthesia during the procedure,” the investigators write.
“Unfortunately,” the editorialists add, rapid adoption of anesthesia for lumbar punctures “is tempered by the recent observation that repeated general anesthesia in children with ALL is associated with increased neurotoxicity.”
The work was supported by grants from the National Natural Science Foundation of China, National Cancer Institute, and others. The study authors and editorialists have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Internal mammary lymph node radiation safe over the long term
After a median follow-up 15.7 years among almost 4,000 women, for half of patients who received postoperative internal mammary and medial supraclavicular (IM-MS) lymph node irradiation, the “absolute rates and differences” of heart and lung complications “were very low, with no increased non–breast cancer–related mortality, even before introducing heart-sparing techniques,” said the investigators.
The findings come from the European Organization for Research and Treatment of Cancer (EORTC) trial. The investigators were led by Philip Poortmans, MD, PhD, a radiation oncologist at the University of Antwerp (Belgium).
The team had previously reported lower breast cancer mortality and breast cancer recurrence rates in the radiation group.
Women in the trial were treated from 1996 to 2004. “We expect that with contemporary volume-based radiation therapy outcomes will be even better, by improved coverage of target volumes, more homogeneous dose delivery and decreased doses to nontarget tissues,” the team wrote.
In the end, “our findings ... have important – reassuring – consequences for decision-making concerning elective lymph node treatment in breast cancer,” the researchers commented.
The study was published online on July 28, 2021, in the Journal of the National Cancer Institute.
Resolving the debate
There’s been debate for decades on whether the long-term risk associated with nodal irradiation, particularly collateral heart and lung damage from internal mammary irradiation, outweigh the benefits of better disease control, Julia White, MD, a radiation oncologist at the Ohio State University Breast Center, Columbus, noted in an accompanying editorial.
Concerns stem originally from trials conducted from the 1950s to the 1970s. In those trials, higher doses of radiation were delivered to the internal mammary node with far less precision than today. Subsequent studies have not laid the worry to rest, and protocols vary across institutions, Dr. White explained. Some treat IM nodes in high-risk patients, but others only treat the axilla and the medial supraclavicular lymph nodes.
Dr. White said the new EORTC trial “moves us one step closer to resolving the debate about the value of internal mammary nodal [IMN] radiation.”
She noted that, since 2014, advances in the field have led to an almost 50% reduction in cardiac radiation exposure during breast cancer treatment. Current guidelines recommend that internal mammary nodes “should generally be treated” as part of postmastectomy radiotherapy but that cardiopulmonary complications are still possible even with improved techniques, she wrote.
Mostly grade 1 morbidity
Women in the study had stage I-III breast cancer with axillary node involvement and/or medially located primary tumors. The median age at study entry was 54 years. The patients were treated at 46 centers in 13 countries.
The group that received IM-MS irradiation after surgery received 50 Gy in 25 fractions over 5 weeks.
The cumulative 15-year incidence of lung fibrosis was 5.7% among treated women versus 2.9% among control patients. The incidence of cardiac fibrosis was 1.9% with treatment, versus 1.1%.
The incidence of any cardiac disease was 11.1% in the radiation arm versus 9.4% in the control group.
Complications were mostly of grade 1. The only statistically significant difference in rates of events of grade 2 or higher was in the incidence of pulmonary morbidity, which was 0.8% with radiation versus 0.1% without. There were no differences in the incidence of second malignancies, contralateral breast cancer cases, or cardiovascular deaths with IMN irradiation.
The authors noted that their results conflict with a 2013 study that found a relative increase in major coronary events of 7.4% per Gy mean heart dose. The women in that trial were treated in Sweden and Denmark between 1958 and 2001.
Dr. Poortmans and colleagues noted, however, that this 2013 study and others found a proportional and not an absolute increase in risk. With a baseline risk of 10%, for instance, a 7% increase per 1 Gy translates to a total risk of 10.07%.
Also, no increased risk has been reported in more recently published trials, and a meta-analysis found no increase in non–breast cancer–related mortality with trials that began after 1988.
Still, “it seems logical to take the preexisting cardiac comorbidity of patients into consideration,” the investigators concluded. For patients with higher baseline cardiopulmonary risk factors, lower mean heart doses should be used, and such patients should undergo longer-term follow-up.
The study was funded by La Ligue Nationale Contre Le Cancer and the KWF Kanker Bestrijding from the Netherlands. The investigators and Dr. White disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
After a median follow-up 15.7 years among almost 4,000 women, for half of patients who received postoperative internal mammary and medial supraclavicular (IM-MS) lymph node irradiation, the “absolute rates and differences” of heart and lung complications “were very low, with no increased non–breast cancer–related mortality, even before introducing heart-sparing techniques,” said the investigators.
The findings come from the European Organization for Research and Treatment of Cancer (EORTC) trial. The investigators were led by Philip Poortmans, MD, PhD, a radiation oncologist at the University of Antwerp (Belgium).
The team had previously reported lower breast cancer mortality and breast cancer recurrence rates in the radiation group.
Women in the trial were treated from 1996 to 2004. “We expect that with contemporary volume-based radiation therapy outcomes will be even better, by improved coverage of target volumes, more homogeneous dose delivery and decreased doses to nontarget tissues,” the team wrote.
In the end, “our findings ... have important – reassuring – consequences for decision-making concerning elective lymph node treatment in breast cancer,” the researchers commented.
The study was published online on July 28, 2021, in the Journal of the National Cancer Institute.
Resolving the debate
There’s been debate for decades on whether the long-term risk associated with nodal irradiation, particularly collateral heart and lung damage from internal mammary irradiation, outweigh the benefits of better disease control, Julia White, MD, a radiation oncologist at the Ohio State University Breast Center, Columbus, noted in an accompanying editorial.
Concerns stem originally from trials conducted from the 1950s to the 1970s. In those trials, higher doses of radiation were delivered to the internal mammary node with far less precision than today. Subsequent studies have not laid the worry to rest, and protocols vary across institutions, Dr. White explained. Some treat IM nodes in high-risk patients, but others only treat the axilla and the medial supraclavicular lymph nodes.
Dr. White said the new EORTC trial “moves us one step closer to resolving the debate about the value of internal mammary nodal [IMN] radiation.”
She noted that, since 2014, advances in the field have led to an almost 50% reduction in cardiac radiation exposure during breast cancer treatment. Current guidelines recommend that internal mammary nodes “should generally be treated” as part of postmastectomy radiotherapy but that cardiopulmonary complications are still possible even with improved techniques, she wrote.
Mostly grade 1 morbidity
Women in the study had stage I-III breast cancer with axillary node involvement and/or medially located primary tumors. The median age at study entry was 54 years. The patients were treated at 46 centers in 13 countries.
The group that received IM-MS irradiation after surgery received 50 Gy in 25 fractions over 5 weeks.
The cumulative 15-year incidence of lung fibrosis was 5.7% among treated women versus 2.9% among control patients. The incidence of cardiac fibrosis was 1.9% with treatment, versus 1.1%.
The incidence of any cardiac disease was 11.1% in the radiation arm versus 9.4% in the control group.
Complications were mostly of grade 1. The only statistically significant difference in rates of events of grade 2 or higher was in the incidence of pulmonary morbidity, which was 0.8% with radiation versus 0.1% without. There were no differences in the incidence of second malignancies, contralateral breast cancer cases, or cardiovascular deaths with IMN irradiation.
The authors noted that their results conflict with a 2013 study that found a relative increase in major coronary events of 7.4% per Gy mean heart dose. The women in that trial were treated in Sweden and Denmark between 1958 and 2001.
Dr. Poortmans and colleagues noted, however, that this 2013 study and others found a proportional and not an absolute increase in risk. With a baseline risk of 10%, for instance, a 7% increase per 1 Gy translates to a total risk of 10.07%.
Also, no increased risk has been reported in more recently published trials, and a meta-analysis found no increase in non–breast cancer–related mortality with trials that began after 1988.
Still, “it seems logical to take the preexisting cardiac comorbidity of patients into consideration,” the investigators concluded. For patients with higher baseline cardiopulmonary risk factors, lower mean heart doses should be used, and such patients should undergo longer-term follow-up.
The study was funded by La Ligue Nationale Contre Le Cancer and the KWF Kanker Bestrijding from the Netherlands. The investigators and Dr. White disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
After a median follow-up 15.7 years among almost 4,000 women, for half of patients who received postoperative internal mammary and medial supraclavicular (IM-MS) lymph node irradiation, the “absolute rates and differences” of heart and lung complications “were very low, with no increased non–breast cancer–related mortality, even before introducing heart-sparing techniques,” said the investigators.
The findings come from the European Organization for Research and Treatment of Cancer (EORTC) trial. The investigators were led by Philip Poortmans, MD, PhD, a radiation oncologist at the University of Antwerp (Belgium).
The team had previously reported lower breast cancer mortality and breast cancer recurrence rates in the radiation group.
Women in the trial were treated from 1996 to 2004. “We expect that with contemporary volume-based radiation therapy outcomes will be even better, by improved coverage of target volumes, more homogeneous dose delivery and decreased doses to nontarget tissues,” the team wrote.
In the end, “our findings ... have important – reassuring – consequences for decision-making concerning elective lymph node treatment in breast cancer,” the researchers commented.
The study was published online on July 28, 2021, in the Journal of the National Cancer Institute.
Resolving the debate
There’s been debate for decades on whether the long-term risk associated with nodal irradiation, particularly collateral heart and lung damage from internal mammary irradiation, outweigh the benefits of better disease control, Julia White, MD, a radiation oncologist at the Ohio State University Breast Center, Columbus, noted in an accompanying editorial.
Concerns stem originally from trials conducted from the 1950s to the 1970s. In those trials, higher doses of radiation were delivered to the internal mammary node with far less precision than today. Subsequent studies have not laid the worry to rest, and protocols vary across institutions, Dr. White explained. Some treat IM nodes in high-risk patients, but others only treat the axilla and the medial supraclavicular lymph nodes.
Dr. White said the new EORTC trial “moves us one step closer to resolving the debate about the value of internal mammary nodal [IMN] radiation.”
She noted that, since 2014, advances in the field have led to an almost 50% reduction in cardiac radiation exposure during breast cancer treatment. Current guidelines recommend that internal mammary nodes “should generally be treated” as part of postmastectomy radiotherapy but that cardiopulmonary complications are still possible even with improved techniques, she wrote.
Mostly grade 1 morbidity
Women in the study had stage I-III breast cancer with axillary node involvement and/or medially located primary tumors. The median age at study entry was 54 years. The patients were treated at 46 centers in 13 countries.
The group that received IM-MS irradiation after surgery received 50 Gy in 25 fractions over 5 weeks.
The cumulative 15-year incidence of lung fibrosis was 5.7% among treated women versus 2.9% among control patients. The incidence of cardiac fibrosis was 1.9% with treatment, versus 1.1%.
The incidence of any cardiac disease was 11.1% in the radiation arm versus 9.4% in the control group.
Complications were mostly of grade 1. The only statistically significant difference in rates of events of grade 2 or higher was in the incidence of pulmonary morbidity, which was 0.8% with radiation versus 0.1% without. There were no differences in the incidence of second malignancies, contralateral breast cancer cases, or cardiovascular deaths with IMN irradiation.
The authors noted that their results conflict with a 2013 study that found a relative increase in major coronary events of 7.4% per Gy mean heart dose. The women in that trial were treated in Sweden and Denmark between 1958 and 2001.
Dr. Poortmans and colleagues noted, however, that this 2013 study and others found a proportional and not an absolute increase in risk. With a baseline risk of 10%, for instance, a 7% increase per 1 Gy translates to a total risk of 10.07%.
Also, no increased risk has been reported in more recently published trials, and a meta-analysis found no increase in non–breast cancer–related mortality with trials that began after 1988.
Still, “it seems logical to take the preexisting cardiac comorbidity of patients into consideration,” the investigators concluded. For patients with higher baseline cardiopulmonary risk factors, lower mean heart doses should be used, and such patients should undergo longer-term follow-up.
The study was funded by La Ligue Nationale Contre Le Cancer and the KWF Kanker Bestrijding from the Netherlands. The investigators and Dr. White disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FDA approves new asparaginase product for leukemia
The new product is Jazz Pharmaceutical’s Rylaze (asparaginase erwinia chrysanthemi [recombinant]-rywn), and it is approved for use in the treatment of acute lymphoblastic leukemia and lymphoblastic lymphoma.
Asparaginase, an enzyme that helps kill blood cancer cells, is a key component of chemotherapy for both conditions.
The problem is that about 20% of patients become allergic to the standard option, asparaginase derived from Escherichia coli.
The only alternative until now has been Erwinaze (also distributed by Jazz Pharmaceuticals), which, like Rylaze, is derived from Erwinia chrysanthemi, a plant pathogen related to Escherichia coli.
However, Erwinaze has been bedeviled by manufacturing problems and has been in short supply since 2016.
The situation has been “extremely disconcerting to patients, families and providers,” and the hope is that Rylaze will “provide a consistently sourced alternative,” Gregory Reaman, MD, the FDA’s associate director of pediatric oncology, said in a press release.
Rylaze will hit the U.S. market in mid-July. Jazz has been a distributor of Erwinaze as well, but it released its last batch in May, according to a spokesperson.
The key difference between the two products is that the asparaginase in Erwinaze is derived directly from Erwinia chrysanthemi, whereas the asparaginase in Rylaze is a recombinant product produced by different bacteria that have been genetically altered with Erwinia chrysanthemi DNA.
The approval for Rylaze was based on a study involving 102 patients (median age, 10 years) who developed hypersensitivity to Escherichia coli–derived enzyme or “silent inactivation” from neutralizing antibodies. In the study, almost 94% of patients achieved asparaginase target activity levels at the approved dosage of 25 mg/m2 IM every 48 hours. The study is ongoing, and investigators are currently evaluating intravenous dosing.
The most common side effects are hypersensitivity reactions, blood clots, hemorrhage, and pancreatic and liver toxicity. There is also a risk for fetal harm, so labeling advises women to use effective nonhormonal contraception during treatment and for 3 months afterward.
A version of this article first appeared on Medscape.com.
The new product is Jazz Pharmaceutical’s Rylaze (asparaginase erwinia chrysanthemi [recombinant]-rywn), and it is approved for use in the treatment of acute lymphoblastic leukemia and lymphoblastic lymphoma.
Asparaginase, an enzyme that helps kill blood cancer cells, is a key component of chemotherapy for both conditions.
The problem is that about 20% of patients become allergic to the standard option, asparaginase derived from Escherichia coli.
The only alternative until now has been Erwinaze (also distributed by Jazz Pharmaceuticals), which, like Rylaze, is derived from Erwinia chrysanthemi, a plant pathogen related to Escherichia coli.
However, Erwinaze has been bedeviled by manufacturing problems and has been in short supply since 2016.
The situation has been “extremely disconcerting to patients, families and providers,” and the hope is that Rylaze will “provide a consistently sourced alternative,” Gregory Reaman, MD, the FDA’s associate director of pediatric oncology, said in a press release.
Rylaze will hit the U.S. market in mid-July. Jazz has been a distributor of Erwinaze as well, but it released its last batch in May, according to a spokesperson.
The key difference between the two products is that the asparaginase in Erwinaze is derived directly from Erwinia chrysanthemi, whereas the asparaginase in Rylaze is a recombinant product produced by different bacteria that have been genetically altered with Erwinia chrysanthemi DNA.
The approval for Rylaze was based on a study involving 102 patients (median age, 10 years) who developed hypersensitivity to Escherichia coli–derived enzyme or “silent inactivation” from neutralizing antibodies. In the study, almost 94% of patients achieved asparaginase target activity levels at the approved dosage of 25 mg/m2 IM every 48 hours. The study is ongoing, and investigators are currently evaluating intravenous dosing.
The most common side effects are hypersensitivity reactions, blood clots, hemorrhage, and pancreatic and liver toxicity. There is also a risk for fetal harm, so labeling advises women to use effective nonhormonal contraception during treatment and for 3 months afterward.
A version of this article first appeared on Medscape.com.
The new product is Jazz Pharmaceutical’s Rylaze (asparaginase erwinia chrysanthemi [recombinant]-rywn), and it is approved for use in the treatment of acute lymphoblastic leukemia and lymphoblastic lymphoma.
Asparaginase, an enzyme that helps kill blood cancer cells, is a key component of chemotherapy for both conditions.
The problem is that about 20% of patients become allergic to the standard option, asparaginase derived from Escherichia coli.
The only alternative until now has been Erwinaze (also distributed by Jazz Pharmaceuticals), which, like Rylaze, is derived from Erwinia chrysanthemi, a plant pathogen related to Escherichia coli.
However, Erwinaze has been bedeviled by manufacturing problems and has been in short supply since 2016.
The situation has been “extremely disconcerting to patients, families and providers,” and the hope is that Rylaze will “provide a consistently sourced alternative,” Gregory Reaman, MD, the FDA’s associate director of pediatric oncology, said in a press release.
Rylaze will hit the U.S. market in mid-July. Jazz has been a distributor of Erwinaze as well, but it released its last batch in May, according to a spokesperson.
The key difference between the two products is that the asparaginase in Erwinaze is derived directly from Erwinia chrysanthemi, whereas the asparaginase in Rylaze is a recombinant product produced by different bacteria that have been genetically altered with Erwinia chrysanthemi DNA.
The approval for Rylaze was based on a study involving 102 patients (median age, 10 years) who developed hypersensitivity to Escherichia coli–derived enzyme or “silent inactivation” from neutralizing antibodies. In the study, almost 94% of patients achieved asparaginase target activity levels at the approved dosage of 25 mg/m2 IM every 48 hours. The study is ongoing, and investigators are currently evaluating intravenous dosing.
The most common side effects are hypersensitivity reactions, blood clots, hemorrhage, and pancreatic and liver toxicity. There is also a risk for fetal harm, so labeling advises women to use effective nonhormonal contraception during treatment and for 3 months afterward.
A version of this article first appeared on Medscape.com.