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Low response rate with trofosfamide for advanced STS in elderly
CHICAGO – In elderly patients with previously untreated metastatic soft-tissue sarcomas (STSs), the oral alkylating agent trofosfamide was associated with a lower overall response rate but long-lasting remissions among patients who had complete responses, investigators reported.
In a randomized phase 2 trial that compared trofosfamide with doxorubicin (Adriamycin), the 6-month progression-free survival (PFS) rate with trofosfamide, the primary endpoint, was 27. 6% versus 35.9% in the doxorubicin arm, said Joerg Thomas Hartmann, MD, from Franziskus Hospital in Bielefeld, Germany.
“Median age was 70 years, which means that the population included [patients] 10-15 years older as compared to other trials in metastatic adult sarcoma. The trial met its predefined endpoint, demonstrating that patients treated with trofosfamide attained a 6-month progression-free rate of more than 20%,” he said at the annual meeting of the American Society of Clinical Oncology.
Trofosfamide is an oral alkylating agent chemically related to cyclophosphamide and ifosfamide. It has been evaluated in a variety of hematologic and solid malignancies and has shown particular activity in patients with chemotherapy-naive and treatment-refractory adult STSs.
Dr. Hartmann and his colleagues conducted the phase 2 study to determine whether oral continuous or “metronomic” therapy with trofosfamide could produce a 6-month PFS rate of at least 20% in patients older than 60 years with previously untreated STSs. They selected this rate of 20% or higher based on the European Organisation for Research and Treatment of Cancer (EORTC) target criterion for doxorubicin of 25%.
They also compared grade 3 or greater toxicities of the two regimens, as well as overall response rate according to Response Evaluation Criteria in Solid Tumors (RECIST) 1,0, and overall survival.
A total of 120 patients with histologically confirmed STSs with no prior first-line chemotherapy and with adequate bone marrow, renal, and liver function were enrolled. The histologies included pleomorphic sarcoma not otherwise specified, leiomyosarcoma, liposarcoma, and others not specified by Dr. Hartmann.
The patients were randomly assigned on a 1:2 basis to receive either intravenous doxorubicin 60 mg/m2 on day 1 of each 21-day cycle for a total of 6 cycles (40 patients) or oral trofosfamide 300 mg/day for days 1 through 7 followed by 150 mg/day until disease progression or unacceptable toxicities (80 patients).
The median patient age in each arm was 70 years.
After a median follow-up of 18.4 months, the trial met its primary endpoint of a 6-months PFS with trofosfamide exceeding 20% (27.6%).
Overall response rates were 7.7% in the doxorubicin arm and 6.6% in the trofosfamide arm.
All three responses in the doxorubicin arm were partial. In the trofosfamide arm there were five responses, including two complete responses and three PR.
The duration of responses in the patients treated with trofosfamide who achieved a complete response were 8.8 and 46.6 months (median, 27.7 months). The median duration of response for trofosfamide-treated patients with a partial response was 8.2 months (range, 1.4-14.9 months).
In contrast, the median duration of response in the patients treated with doxorubicin who achieved a partial response was 4.3 months (range, 2.2-5.6 months).
Grade 3 or 4 adverse events occurred in significantly more patients treated with doxorubicin than they did in patients treated with trofosfamide (61.5% vs. 38.2%, respectively; P = .01). However, deaths within 30 or 60 days of starting on the assigned study drug were higher in the trofosfamide arm (zero vs. two and three vs. six, respectively).
Rates of anemia, leukocytopenia, nausea, and asthenia were similar between the groups, but trofosfamide was significantly associated with higher rates of dyspnea (P = .0148) and fatigue (P = .0264) and with lower rates of neutropenia (P less than .0001) and mucositis (P = .0008).
The trial was supported by Baxter Oncology of Germany. Dr. Hartmann reported having no conflicts of interest to disclose.
SOURCE: Hartman JT et al. ASCO 2018, Abstract 11507.
CHICAGO – In elderly patients with previously untreated metastatic soft-tissue sarcomas (STSs), the oral alkylating agent trofosfamide was associated with a lower overall response rate but long-lasting remissions among patients who had complete responses, investigators reported.
In a randomized phase 2 trial that compared trofosfamide with doxorubicin (Adriamycin), the 6-month progression-free survival (PFS) rate with trofosfamide, the primary endpoint, was 27. 6% versus 35.9% in the doxorubicin arm, said Joerg Thomas Hartmann, MD, from Franziskus Hospital in Bielefeld, Germany.
“Median age was 70 years, which means that the population included [patients] 10-15 years older as compared to other trials in metastatic adult sarcoma. The trial met its predefined endpoint, demonstrating that patients treated with trofosfamide attained a 6-month progression-free rate of more than 20%,” he said at the annual meeting of the American Society of Clinical Oncology.
Trofosfamide is an oral alkylating agent chemically related to cyclophosphamide and ifosfamide. It has been evaluated in a variety of hematologic and solid malignancies and has shown particular activity in patients with chemotherapy-naive and treatment-refractory adult STSs.
Dr. Hartmann and his colleagues conducted the phase 2 study to determine whether oral continuous or “metronomic” therapy with trofosfamide could produce a 6-month PFS rate of at least 20% in patients older than 60 years with previously untreated STSs. They selected this rate of 20% or higher based on the European Organisation for Research and Treatment of Cancer (EORTC) target criterion for doxorubicin of 25%.
They also compared grade 3 or greater toxicities of the two regimens, as well as overall response rate according to Response Evaluation Criteria in Solid Tumors (RECIST) 1,0, and overall survival.
A total of 120 patients with histologically confirmed STSs with no prior first-line chemotherapy and with adequate bone marrow, renal, and liver function were enrolled. The histologies included pleomorphic sarcoma not otherwise specified, leiomyosarcoma, liposarcoma, and others not specified by Dr. Hartmann.
The patients were randomly assigned on a 1:2 basis to receive either intravenous doxorubicin 60 mg/m2 on day 1 of each 21-day cycle for a total of 6 cycles (40 patients) or oral trofosfamide 300 mg/day for days 1 through 7 followed by 150 mg/day until disease progression or unacceptable toxicities (80 patients).
The median patient age in each arm was 70 years.
After a median follow-up of 18.4 months, the trial met its primary endpoint of a 6-months PFS with trofosfamide exceeding 20% (27.6%).
Overall response rates were 7.7% in the doxorubicin arm and 6.6% in the trofosfamide arm.
All three responses in the doxorubicin arm were partial. In the trofosfamide arm there were five responses, including two complete responses and three PR.
The duration of responses in the patients treated with trofosfamide who achieved a complete response were 8.8 and 46.6 months (median, 27.7 months). The median duration of response for trofosfamide-treated patients with a partial response was 8.2 months (range, 1.4-14.9 months).
In contrast, the median duration of response in the patients treated with doxorubicin who achieved a partial response was 4.3 months (range, 2.2-5.6 months).
Grade 3 or 4 adverse events occurred in significantly more patients treated with doxorubicin than they did in patients treated with trofosfamide (61.5% vs. 38.2%, respectively; P = .01). However, deaths within 30 or 60 days of starting on the assigned study drug were higher in the trofosfamide arm (zero vs. two and three vs. six, respectively).
Rates of anemia, leukocytopenia, nausea, and asthenia were similar between the groups, but trofosfamide was significantly associated with higher rates of dyspnea (P = .0148) and fatigue (P = .0264) and with lower rates of neutropenia (P less than .0001) and mucositis (P = .0008).
The trial was supported by Baxter Oncology of Germany. Dr. Hartmann reported having no conflicts of interest to disclose.
SOURCE: Hartman JT et al. ASCO 2018, Abstract 11507.
CHICAGO – In elderly patients with previously untreated metastatic soft-tissue sarcomas (STSs), the oral alkylating agent trofosfamide was associated with a lower overall response rate but long-lasting remissions among patients who had complete responses, investigators reported.
In a randomized phase 2 trial that compared trofosfamide with doxorubicin (Adriamycin), the 6-month progression-free survival (PFS) rate with trofosfamide, the primary endpoint, was 27. 6% versus 35.9% in the doxorubicin arm, said Joerg Thomas Hartmann, MD, from Franziskus Hospital in Bielefeld, Germany.
“Median age was 70 years, which means that the population included [patients] 10-15 years older as compared to other trials in metastatic adult sarcoma. The trial met its predefined endpoint, demonstrating that patients treated with trofosfamide attained a 6-month progression-free rate of more than 20%,” he said at the annual meeting of the American Society of Clinical Oncology.
Trofosfamide is an oral alkylating agent chemically related to cyclophosphamide and ifosfamide. It has been evaluated in a variety of hematologic and solid malignancies and has shown particular activity in patients with chemotherapy-naive and treatment-refractory adult STSs.
Dr. Hartmann and his colleagues conducted the phase 2 study to determine whether oral continuous or “metronomic” therapy with trofosfamide could produce a 6-month PFS rate of at least 20% in patients older than 60 years with previously untreated STSs. They selected this rate of 20% or higher based on the European Organisation for Research and Treatment of Cancer (EORTC) target criterion for doxorubicin of 25%.
They also compared grade 3 or greater toxicities of the two regimens, as well as overall response rate according to Response Evaluation Criteria in Solid Tumors (RECIST) 1,0, and overall survival.
A total of 120 patients with histologically confirmed STSs with no prior first-line chemotherapy and with adequate bone marrow, renal, and liver function were enrolled. The histologies included pleomorphic sarcoma not otherwise specified, leiomyosarcoma, liposarcoma, and others not specified by Dr. Hartmann.
The patients were randomly assigned on a 1:2 basis to receive either intravenous doxorubicin 60 mg/m2 on day 1 of each 21-day cycle for a total of 6 cycles (40 patients) or oral trofosfamide 300 mg/day for days 1 through 7 followed by 150 mg/day until disease progression or unacceptable toxicities (80 patients).
The median patient age in each arm was 70 years.
After a median follow-up of 18.4 months, the trial met its primary endpoint of a 6-months PFS with trofosfamide exceeding 20% (27.6%).
Overall response rates were 7.7% in the doxorubicin arm and 6.6% in the trofosfamide arm.
All three responses in the doxorubicin arm were partial. In the trofosfamide arm there were five responses, including two complete responses and three PR.
The duration of responses in the patients treated with trofosfamide who achieved a complete response were 8.8 and 46.6 months (median, 27.7 months). The median duration of response for trofosfamide-treated patients with a partial response was 8.2 months (range, 1.4-14.9 months).
In contrast, the median duration of response in the patients treated with doxorubicin who achieved a partial response was 4.3 months (range, 2.2-5.6 months).
Grade 3 or 4 adverse events occurred in significantly more patients treated with doxorubicin than they did in patients treated with trofosfamide (61.5% vs. 38.2%, respectively; P = .01). However, deaths within 30 or 60 days of starting on the assigned study drug were higher in the trofosfamide arm (zero vs. two and three vs. six, respectively).
Rates of anemia, leukocytopenia, nausea, and asthenia were similar between the groups, but trofosfamide was significantly associated with higher rates of dyspnea (P = .0148) and fatigue (P = .0264) and with lower rates of neutropenia (P less than .0001) and mucositis (P = .0008).
The trial was supported by Baxter Oncology of Germany. Dr. Hartmann reported having no conflicts of interest to disclose.
SOURCE: Hartman JT et al. ASCO 2018, Abstract 11507.
PRESENTED AT ASCO 2018
Key clinical point: The oral alkylating agent trofosfamide showed efficacy in a small number of elderly patients with untreated metastatic soft-tissue sarcomas (STS).
Major finding: The trial met its primary endpoint with a 6-month progression-free survival with trofosfamide of 27.6%
Study details: Randomized phase 2 trial comparing trofosfamide with doxorubicin in elderly patients with previously untreated metastatic STS.
Disclosures: The trial was supported by Baxter Oncology of Germany. Dr. Hartmann reported having no conflicts of interest to disclose.
Source: Hartman JT et al. ASCO 2018, Abstract 11507.
Trabectedin bests supportive care in advanced soft-tissue sarcomas
CHICAGO – Trabectedin (Yondelis) was superior to best supportive care at prolonging progression-free survival in patients with heavily pretreated advanced leiomyosarcomas and liposarcomas, investigators in the randomized phase 3 T-SAR trial reported.
Among 103 patients with soft-tissue sarcomas that had progressed after two to four lines of standard chemotherapy, median progression-free survival (PFS) for patients randomized to trabectedin was 3.12 months, compared with 1.51 for patients randomized to best supportive care.
This difference translated into a hazard ratio (HR) favoring trabectedin of 0.39 (P less than .0001), Axel Le Cesne, MD, of Gustave Roussy Cancer Institute in Villejuif, France, reported on behalf of colleagues in the French Sarcoma Group.
All of the benefit was apparently among patients with what he termed “L-sarcomas” – leiomyosarcoma and liposarcoma – compared with other sarcoma histologies.
“The tumor control rate after six courses of trabectedin is similar to previous studies. As already reported, trabectedin is well-tolerated,” he said at the annual meeting of the American Society of Clinical Oncology.
Trabectedin was shown to be superior to best supportive care at delaying disease progression among patients with advanced translocation-related sarcomas in a randomized phase 2 trial in Japan, but had not been studied in this setting against other sarcoma histologies, Dr. Le Cesne said.
The investigators enrolled 103 patients and randomly assigned them to receive either best supportive care or trabectedin in a 1.5 mg/m2 infusion over 24 hours every 3 weeks. Patients in the best supportive care arm could be crossed over to the trabectedin arm at the time of progression.
Sarcoma histologies included liposarcoma, leiomyosarcoma, undifferentiated sarcomas, myxofibrosarcoma, synovial sarcoma, and others. The L-sarcomas accounted for 60.2% of the patient population.
Fifty-two patients were randomized to trabectedin and 51 to best supportive care, but 2 patients assigned to best supportive care dropped out soon after randomization, leaving 52 and 49 patients, respectively, for the as-treated analysis. All 103 patients were assessable for efficacy.
After a median follow-up of 26 months, median PFS for all patients, as noted before, was 3.12 months in the trabectedin arm and 1.51 months in the best supportive care arm.
The overall response rate in the trabectedin arm was 13.7%, composed of seven partial responses. There were no responses in the best supportive care arm. In all, 66.7% of patients in the trabectedin arm and 61.2% of patients in the best supportive care arm had stable disease, and 19.6% and 38.8%, respectively, had disease progression.
An analysis of PFS by sarcoma histology showed that all of the benefit appeared to be in patients with L-sarcomas, with a median PFS for trabectedin-treated patients of 5.13 months compared with 1.41 months for controls (HR 0.29, P less than .0001).
In contrast, there was no significant difference between the groups among patients with non–L sarcomas, with respective median PFS of 1.81 and 1.51 months (HR 0.60, P = .16). There were no treatment responses among patients in either treatment arm in this subgroup.
Not surprisingly, there were more grade 3 or 4 adverse events among patients in the trabectedin arm. Neutropenia was seen in 23 patients given trabectedin and 1 given best supportive care; leukopenia in 18 patients vs. 0, thrombocytopenia in 13 vs. 0, and elevated liver transaminases in 17 vs. 1, respectively.
In all, 45 of the 49 patients who were treated in the best supportive care arm were crossed over to trabectedin.
Median overall survival was 13.6 months in the trabectedin arm and 10.8 months in the best supportive care arm. This difference was not statistically significant.
Dr Le Cesne noted that the tumor control rate of 30% with trabectedin was similar to that seen in an earlier French trial (Lancet Oncol. 2015 Mar 1;16[3]:312-19).
Pharmamar supplied trabectedin for the study. Dr. Le Cesne disclosed honoraria from the company and from Amgen, Bayer, Lilly, Novartis, and Pfizer.
SOURCE: Le Cesne A et al. ASCO 2018. Abstract 11508.
CHICAGO – Trabectedin (Yondelis) was superior to best supportive care at prolonging progression-free survival in patients with heavily pretreated advanced leiomyosarcomas and liposarcomas, investigators in the randomized phase 3 T-SAR trial reported.
Among 103 patients with soft-tissue sarcomas that had progressed after two to four lines of standard chemotherapy, median progression-free survival (PFS) for patients randomized to trabectedin was 3.12 months, compared with 1.51 for patients randomized to best supportive care.
This difference translated into a hazard ratio (HR) favoring trabectedin of 0.39 (P less than .0001), Axel Le Cesne, MD, of Gustave Roussy Cancer Institute in Villejuif, France, reported on behalf of colleagues in the French Sarcoma Group.
All of the benefit was apparently among patients with what he termed “L-sarcomas” – leiomyosarcoma and liposarcoma – compared with other sarcoma histologies.
“The tumor control rate after six courses of trabectedin is similar to previous studies. As already reported, trabectedin is well-tolerated,” he said at the annual meeting of the American Society of Clinical Oncology.
Trabectedin was shown to be superior to best supportive care at delaying disease progression among patients with advanced translocation-related sarcomas in a randomized phase 2 trial in Japan, but had not been studied in this setting against other sarcoma histologies, Dr. Le Cesne said.
The investigators enrolled 103 patients and randomly assigned them to receive either best supportive care or trabectedin in a 1.5 mg/m2 infusion over 24 hours every 3 weeks. Patients in the best supportive care arm could be crossed over to the trabectedin arm at the time of progression.
Sarcoma histologies included liposarcoma, leiomyosarcoma, undifferentiated sarcomas, myxofibrosarcoma, synovial sarcoma, and others. The L-sarcomas accounted for 60.2% of the patient population.
Fifty-two patients were randomized to trabectedin and 51 to best supportive care, but 2 patients assigned to best supportive care dropped out soon after randomization, leaving 52 and 49 patients, respectively, for the as-treated analysis. All 103 patients were assessable for efficacy.
After a median follow-up of 26 months, median PFS for all patients, as noted before, was 3.12 months in the trabectedin arm and 1.51 months in the best supportive care arm.
The overall response rate in the trabectedin arm was 13.7%, composed of seven partial responses. There were no responses in the best supportive care arm. In all, 66.7% of patients in the trabectedin arm and 61.2% of patients in the best supportive care arm had stable disease, and 19.6% and 38.8%, respectively, had disease progression.
An analysis of PFS by sarcoma histology showed that all of the benefit appeared to be in patients with L-sarcomas, with a median PFS for trabectedin-treated patients of 5.13 months compared with 1.41 months for controls (HR 0.29, P less than .0001).
In contrast, there was no significant difference between the groups among patients with non–L sarcomas, with respective median PFS of 1.81 and 1.51 months (HR 0.60, P = .16). There were no treatment responses among patients in either treatment arm in this subgroup.
Not surprisingly, there were more grade 3 or 4 adverse events among patients in the trabectedin arm. Neutropenia was seen in 23 patients given trabectedin and 1 given best supportive care; leukopenia in 18 patients vs. 0, thrombocytopenia in 13 vs. 0, and elevated liver transaminases in 17 vs. 1, respectively.
In all, 45 of the 49 patients who were treated in the best supportive care arm were crossed over to trabectedin.
Median overall survival was 13.6 months in the trabectedin arm and 10.8 months in the best supportive care arm. This difference was not statistically significant.
Dr Le Cesne noted that the tumor control rate of 30% with trabectedin was similar to that seen in an earlier French trial (Lancet Oncol. 2015 Mar 1;16[3]:312-19).
Pharmamar supplied trabectedin for the study. Dr. Le Cesne disclosed honoraria from the company and from Amgen, Bayer, Lilly, Novartis, and Pfizer.
SOURCE: Le Cesne A et al. ASCO 2018. Abstract 11508.
CHICAGO – Trabectedin (Yondelis) was superior to best supportive care at prolonging progression-free survival in patients with heavily pretreated advanced leiomyosarcomas and liposarcomas, investigators in the randomized phase 3 T-SAR trial reported.
Among 103 patients with soft-tissue sarcomas that had progressed after two to four lines of standard chemotherapy, median progression-free survival (PFS) for patients randomized to trabectedin was 3.12 months, compared with 1.51 for patients randomized to best supportive care.
This difference translated into a hazard ratio (HR) favoring trabectedin of 0.39 (P less than .0001), Axel Le Cesne, MD, of Gustave Roussy Cancer Institute in Villejuif, France, reported on behalf of colleagues in the French Sarcoma Group.
All of the benefit was apparently among patients with what he termed “L-sarcomas” – leiomyosarcoma and liposarcoma – compared with other sarcoma histologies.
“The tumor control rate after six courses of trabectedin is similar to previous studies. As already reported, trabectedin is well-tolerated,” he said at the annual meeting of the American Society of Clinical Oncology.
Trabectedin was shown to be superior to best supportive care at delaying disease progression among patients with advanced translocation-related sarcomas in a randomized phase 2 trial in Japan, but had not been studied in this setting against other sarcoma histologies, Dr. Le Cesne said.
The investigators enrolled 103 patients and randomly assigned them to receive either best supportive care or trabectedin in a 1.5 mg/m2 infusion over 24 hours every 3 weeks. Patients in the best supportive care arm could be crossed over to the trabectedin arm at the time of progression.
Sarcoma histologies included liposarcoma, leiomyosarcoma, undifferentiated sarcomas, myxofibrosarcoma, synovial sarcoma, and others. The L-sarcomas accounted for 60.2% of the patient population.
Fifty-two patients were randomized to trabectedin and 51 to best supportive care, but 2 patients assigned to best supportive care dropped out soon after randomization, leaving 52 and 49 patients, respectively, for the as-treated analysis. All 103 patients were assessable for efficacy.
After a median follow-up of 26 months, median PFS for all patients, as noted before, was 3.12 months in the trabectedin arm and 1.51 months in the best supportive care arm.
The overall response rate in the trabectedin arm was 13.7%, composed of seven partial responses. There were no responses in the best supportive care arm. In all, 66.7% of patients in the trabectedin arm and 61.2% of patients in the best supportive care arm had stable disease, and 19.6% and 38.8%, respectively, had disease progression.
An analysis of PFS by sarcoma histology showed that all of the benefit appeared to be in patients with L-sarcomas, with a median PFS for trabectedin-treated patients of 5.13 months compared with 1.41 months for controls (HR 0.29, P less than .0001).
In contrast, there was no significant difference between the groups among patients with non–L sarcomas, with respective median PFS of 1.81 and 1.51 months (HR 0.60, P = .16). There were no treatment responses among patients in either treatment arm in this subgroup.
Not surprisingly, there were more grade 3 or 4 adverse events among patients in the trabectedin arm. Neutropenia was seen in 23 patients given trabectedin and 1 given best supportive care; leukopenia in 18 patients vs. 0, thrombocytopenia in 13 vs. 0, and elevated liver transaminases in 17 vs. 1, respectively.
In all, 45 of the 49 patients who were treated in the best supportive care arm were crossed over to trabectedin.
Median overall survival was 13.6 months in the trabectedin arm and 10.8 months in the best supportive care arm. This difference was not statistically significant.
Dr Le Cesne noted that the tumor control rate of 30% with trabectedin was similar to that seen in an earlier French trial (Lancet Oncol. 2015 Mar 1;16[3]:312-19).
Pharmamar supplied trabectedin for the study. Dr. Le Cesne disclosed honoraria from the company and from Amgen, Bayer, Lilly, Novartis, and Pfizer.
SOURCE: Le Cesne A et al. ASCO 2018. Abstract 11508.
REPORTING FROM ASCO 2018
Key clinical point: Trabectedin was superior to best supportive care in delaying disease progression among patients with advanced soft tissue sarcomas.
Major finding: Median progression-free survival for patients with leiomyosarcoma or liposarcoma treated with trabectedin was 5.13 months vs. 1.41 months for patients treated with best supportive care.
Study details: Randomized open-label trial of 103 patients with histologically proven advanced soft-tissue sarcoma who progressed after at least 1 anthracycline-containing regimen.
Disclosures: Pharmamar supplied trabectedin for the study. Dr. Le Cesne disclosed receiving honoraria from the company and from Amgen, Bayer, Lilly, Novartis, and Pfizer.
Source: Le Cesne A et al. ASCO 2018. Abstract 11508.
Rare clear cell papillary RCC has indolent course
Clear cell papillary renal cell carcinoma (CCPRCC), a recently identified, rare type of renal tumor, appears to have an indolent course with low risk of either local invasion or distant metastasis, results of a small retrospective study suggest.
Among 25 patients with CCPRCC followed for as long as 119 months, there were no cases of local recurrence or distant metastasis, reported Wei-Jen Chen, MD, of Tapei (Taiwan) Veterans General Hospital, and colleagues.
“Based on our findings, CCPRCC has an indolent behavior even if the patients are immunosuppressed or if they receive less invasive therapy. Microscopically, CCPRCC is considered to be a tumor of low malignant potential, as all tumors in our series were of low nuclear grade,” they wrote in a study published online in the Journal of the Chinese Medical Association.
“Whenever the diagnosis is made in a high grade renal tumor, it should be carefully re-confirmed by either cytogenetic or molecular genetic methods,” the authors reported.
CCPRCC was newly recognized as a distinct renal malignancy in the 2016 World Health Organization Classification of Tumors of the Urinary System and Male Genital Organs. The classification describes CCPRCC as “a renal epithelial neoplasm composed of low-grade clear epithelial cells arranged in tubules and papillae with a predominantly linear nuclear alignment away from the basement membrane.”
Although rare, these tumors account for up to 5% of all resected renal tumors, and arise sporadically in patients with end-stage renal disease (ESRD) and von Hippel-Lindau syndrome, the classification states, adding that “according to current knowledge, these tumors have indolent behavior.”
To see if they could verify that last statement, Dr. Chen and associates collected data on all patients diagnosed at their institution with CCPRCC from January 2008 through September 2016.
They identified a total of 25 patients (11 men and 14 women) with a mean age at diagnosis of 62.8 years. Of this group, three patients with poor general condition underwent cryotherapy after a biopsy-confirmed diagnosis of CCPRCC.
All of the remaining 22 patients underwent surgical resection. Of this group, four had ESRD; three of these patients had received a kidney transplant prior to diagnosis of CCPRCC in the native kidneys, and one had three tumors over both kidneys.
“Three patients had other types of synchronous RCC; one with acquired cystic kidney disease-associated RCC, and the others with ccRCC. All CCPRCCs were localized and low grade (pT1a- pT1b, Fuhrman grade 2), and all of the patients are currently alive with no evidence of disease,” the investigators wrote.
Mean follow-up was 49.7 months (range 12 to 119 months).
One additional patient who was not included in the series was initially diagnosed with CCPRCC with lung metastasis. This patient, who died 3 years and 8 months after cytoreductive nephrectomy, had a clinical course distinct from that of all the other patients, leading the investigators to reexamine his kidney specimen with whole-exome sequencing. The sequencing led to a revision of the diagnosis to clear cell RCC.
The investigators noted that clear cell RCC, papillary RCC, and translocation RCC are three RCC subtypes that should be considered in the differential diagnosis of CCPRCC.
The investigators did not report a study funding source. They reported having no conflicts of interest relevant to the subject matter or materials discussed in the article.
SOURCE: Chen W-J et al. J Chinese Med Assoc. 2018 July 20. doi: 10.1016/j.jcma.2018.04.005.
Clear cell papillary renal cell carcinoma (CCPRCC), a recently identified, rare type of renal tumor, appears to have an indolent course with low risk of either local invasion or distant metastasis, results of a small retrospective study suggest.
Among 25 patients with CCPRCC followed for as long as 119 months, there were no cases of local recurrence or distant metastasis, reported Wei-Jen Chen, MD, of Tapei (Taiwan) Veterans General Hospital, and colleagues.
“Based on our findings, CCPRCC has an indolent behavior even if the patients are immunosuppressed or if they receive less invasive therapy. Microscopically, CCPRCC is considered to be a tumor of low malignant potential, as all tumors in our series were of low nuclear grade,” they wrote in a study published online in the Journal of the Chinese Medical Association.
“Whenever the diagnosis is made in a high grade renal tumor, it should be carefully re-confirmed by either cytogenetic or molecular genetic methods,” the authors reported.
CCPRCC was newly recognized as a distinct renal malignancy in the 2016 World Health Organization Classification of Tumors of the Urinary System and Male Genital Organs. The classification describes CCPRCC as “a renal epithelial neoplasm composed of low-grade clear epithelial cells arranged in tubules and papillae with a predominantly linear nuclear alignment away from the basement membrane.”
Although rare, these tumors account for up to 5% of all resected renal tumors, and arise sporadically in patients with end-stage renal disease (ESRD) and von Hippel-Lindau syndrome, the classification states, adding that “according to current knowledge, these tumors have indolent behavior.”
To see if they could verify that last statement, Dr. Chen and associates collected data on all patients diagnosed at their institution with CCPRCC from January 2008 through September 2016.
They identified a total of 25 patients (11 men and 14 women) with a mean age at diagnosis of 62.8 years. Of this group, three patients with poor general condition underwent cryotherapy after a biopsy-confirmed diagnosis of CCPRCC.
All of the remaining 22 patients underwent surgical resection. Of this group, four had ESRD; three of these patients had received a kidney transplant prior to diagnosis of CCPRCC in the native kidneys, and one had three tumors over both kidneys.
“Three patients had other types of synchronous RCC; one with acquired cystic kidney disease-associated RCC, and the others with ccRCC. All CCPRCCs were localized and low grade (pT1a- pT1b, Fuhrman grade 2), and all of the patients are currently alive with no evidence of disease,” the investigators wrote.
Mean follow-up was 49.7 months (range 12 to 119 months).
One additional patient who was not included in the series was initially diagnosed with CCPRCC with lung metastasis. This patient, who died 3 years and 8 months after cytoreductive nephrectomy, had a clinical course distinct from that of all the other patients, leading the investigators to reexamine his kidney specimen with whole-exome sequencing. The sequencing led to a revision of the diagnosis to clear cell RCC.
The investigators noted that clear cell RCC, papillary RCC, and translocation RCC are three RCC subtypes that should be considered in the differential diagnosis of CCPRCC.
The investigators did not report a study funding source. They reported having no conflicts of interest relevant to the subject matter or materials discussed in the article.
SOURCE: Chen W-J et al. J Chinese Med Assoc. 2018 July 20. doi: 10.1016/j.jcma.2018.04.005.
Clear cell papillary renal cell carcinoma (CCPRCC), a recently identified, rare type of renal tumor, appears to have an indolent course with low risk of either local invasion or distant metastasis, results of a small retrospective study suggest.
Among 25 patients with CCPRCC followed for as long as 119 months, there were no cases of local recurrence or distant metastasis, reported Wei-Jen Chen, MD, of Tapei (Taiwan) Veterans General Hospital, and colleagues.
“Based on our findings, CCPRCC has an indolent behavior even if the patients are immunosuppressed or if they receive less invasive therapy. Microscopically, CCPRCC is considered to be a tumor of low malignant potential, as all tumors in our series were of low nuclear grade,” they wrote in a study published online in the Journal of the Chinese Medical Association.
“Whenever the diagnosis is made in a high grade renal tumor, it should be carefully re-confirmed by either cytogenetic or molecular genetic methods,” the authors reported.
CCPRCC was newly recognized as a distinct renal malignancy in the 2016 World Health Organization Classification of Tumors of the Urinary System and Male Genital Organs. The classification describes CCPRCC as “a renal epithelial neoplasm composed of low-grade clear epithelial cells arranged in tubules and papillae with a predominantly linear nuclear alignment away from the basement membrane.”
Although rare, these tumors account for up to 5% of all resected renal tumors, and arise sporadically in patients with end-stage renal disease (ESRD) and von Hippel-Lindau syndrome, the classification states, adding that “according to current knowledge, these tumors have indolent behavior.”
To see if they could verify that last statement, Dr. Chen and associates collected data on all patients diagnosed at their institution with CCPRCC from January 2008 through September 2016.
They identified a total of 25 patients (11 men and 14 women) with a mean age at diagnosis of 62.8 years. Of this group, three patients with poor general condition underwent cryotherapy after a biopsy-confirmed diagnosis of CCPRCC.
All of the remaining 22 patients underwent surgical resection. Of this group, four had ESRD; three of these patients had received a kidney transplant prior to diagnosis of CCPRCC in the native kidneys, and one had three tumors over both kidneys.
“Three patients had other types of synchronous RCC; one with acquired cystic kidney disease-associated RCC, and the others with ccRCC. All CCPRCCs were localized and low grade (pT1a- pT1b, Fuhrman grade 2), and all of the patients are currently alive with no evidence of disease,” the investigators wrote.
Mean follow-up was 49.7 months (range 12 to 119 months).
One additional patient who was not included in the series was initially diagnosed with CCPRCC with lung metastasis. This patient, who died 3 years and 8 months after cytoreductive nephrectomy, had a clinical course distinct from that of all the other patients, leading the investigators to reexamine his kidney specimen with whole-exome sequencing. The sequencing led to a revision of the diagnosis to clear cell RCC.
The investigators noted that clear cell RCC, papillary RCC, and translocation RCC are three RCC subtypes that should be considered in the differential diagnosis of CCPRCC.
The investigators did not report a study funding source. They reported having no conflicts of interest relevant to the subject matter or materials discussed in the article.
SOURCE: Chen W-J et al. J Chinese Med Assoc. 2018 July 20. doi: 10.1016/j.jcma.2018.04.005.
FROM JOURNAL OF THE CHINESE MEDICAL SOCIETY
Key clinical point: Clear cell papillary renal cell carcinoma (CCPRCC) is a distinct renal tumor type with an apparently indolent clinical course.
Major finding: There were no cases of local recurrence or distant metastasis of CCPRCC after a mean of 49.7 months of follow-up (range 12-119 months).
Study details: Retrospective case study of 25 patients diagnosed and treated at a single center.
Disclosures: The investigators did not report a study funding source. They reported having no conflicts of interest relevant to the subject matter or materials discussed in the article.
Source: Chen W-J et al. J Chinese Med Assoc. 2018 July 20 doi: 10.1016/j.jcma.2018.04.005.
Insurance is a matter of life or death for lymphoma patients
Having health insurance can mean the difference between life and death for patients with follicular lymphoma, suggest results of a study showing that patients with private health insurance had nearly twofold better survival outcomes than patients without insurance or those who were covered by Medicare or Medicaid.
A review of records on more than 43,000 patients with follicular lymphoma (FL) in a national cancer registry showed that, compared with patients under age 65 with private insurance, the hazard ratios (HR) for death among patients in the same age bracket with either no insurance, Medicaid, or Medicare were, respectively, 1.96, 1.83, and 1.96 (P less than .0001 for each comparison).
“Our study finds that insurance status contributes to survival disparities in FL. Future studies on outcomes in FL should include insurance status as an important predictor,” Christopher R. Flowers, MD, of Emory University in Atlanta and his colleagues wrote in Blood.
“Further research on prognosis for FL should examine the impact of public policy, such as the passage of the [Affordable Care Act], on FL outcomes, as well as examine other factors that influence access to care, such as individual-level socioeconomic status, regular primary care visits, access to prescription medications, and care affordability,” they added.
The investigators noted that earlier research found that patients with Medicaid or no insurance were more likely than privately-insured patients to be diagnosed with cancers at advanced stages, and that some patients with aggressive non-Hodgkin lymphomas have been shown to have insurance-related disparities in treatments and outcomes.
To see whether the same could be true for patients with indolent-histology lymphomas such as FL, they extracted data from the National Cancer Database, a nationwide hospital-based cancer registry sponsored jointly by the American College of Surgeons and the American Cancer Society.
They identified a total of 43,648 patients aged 18 years or older who were diagnosed with FL from 2004 through 2014. They looked at both patients 18-64 years and those 65 years and older to account for changes in insurance with Medicare eligibility.
Overall survival among patients younger than age 65 was significantly worse for patients with public insurance (Medicaid or Medicare) or no insurance in Cox proportional hazard models controlling for available data on sociodemographic factors and prognostic indicators.
However, compared with patients aged 65 and older with private insurance, only patients with Medicare as their sole source of insurance had significantly worse overall survival (HR, 1.28; P less than .0001).
Patients who were uninsured or had Medicaid were more likely than others to have lower socioeconomic status, present with advanced-stage disease, have systemic symptoms, and have multiple comorbidities that persisted after controlling for known sociodemographic and prognostic factors.
The investigators found that, among patients under age 65, those with a comorbidity score of 1 had an HR for death of 1.71, compared with patients with no comorbidities, and that patients with a score of 2 or greater had a HR of 3.1 (P less than .0001 for each comparison).
“The findings of the study indicate that improving access to affordable, quality health care may reduce disparities in survival for those currently lacking coverage,” the investigators wrote.
The study was supported by Emory University, the National Institutes of Health, and the National Center for Advancing Translational Sciences. Dr. Flowers reported financial relationships with AbbVie, Spectrum, Celgene, and several other companies. The other authors reported having nothing to disclose.
SOURCE: Goldstein JS et al. Blood. 2018 Jul 24. doi: 10.1182/blood-2018-03-839035.
Having health insurance can mean the difference between life and death for patients with follicular lymphoma, suggest results of a study showing that patients with private health insurance had nearly twofold better survival outcomes than patients without insurance or those who were covered by Medicare or Medicaid.
A review of records on more than 43,000 patients with follicular lymphoma (FL) in a national cancer registry showed that, compared with patients under age 65 with private insurance, the hazard ratios (HR) for death among patients in the same age bracket with either no insurance, Medicaid, or Medicare were, respectively, 1.96, 1.83, and 1.96 (P less than .0001 for each comparison).
“Our study finds that insurance status contributes to survival disparities in FL. Future studies on outcomes in FL should include insurance status as an important predictor,” Christopher R. Flowers, MD, of Emory University in Atlanta and his colleagues wrote in Blood.
“Further research on prognosis for FL should examine the impact of public policy, such as the passage of the [Affordable Care Act], on FL outcomes, as well as examine other factors that influence access to care, such as individual-level socioeconomic status, regular primary care visits, access to prescription medications, and care affordability,” they added.
The investigators noted that earlier research found that patients with Medicaid or no insurance were more likely than privately-insured patients to be diagnosed with cancers at advanced stages, and that some patients with aggressive non-Hodgkin lymphomas have been shown to have insurance-related disparities in treatments and outcomes.
To see whether the same could be true for patients with indolent-histology lymphomas such as FL, they extracted data from the National Cancer Database, a nationwide hospital-based cancer registry sponsored jointly by the American College of Surgeons and the American Cancer Society.
They identified a total of 43,648 patients aged 18 years or older who were diagnosed with FL from 2004 through 2014. They looked at both patients 18-64 years and those 65 years and older to account for changes in insurance with Medicare eligibility.
Overall survival among patients younger than age 65 was significantly worse for patients with public insurance (Medicaid or Medicare) or no insurance in Cox proportional hazard models controlling for available data on sociodemographic factors and prognostic indicators.
However, compared with patients aged 65 and older with private insurance, only patients with Medicare as their sole source of insurance had significantly worse overall survival (HR, 1.28; P less than .0001).
Patients who were uninsured or had Medicaid were more likely than others to have lower socioeconomic status, present with advanced-stage disease, have systemic symptoms, and have multiple comorbidities that persisted after controlling for known sociodemographic and prognostic factors.
The investigators found that, among patients under age 65, those with a comorbidity score of 1 had an HR for death of 1.71, compared with patients with no comorbidities, and that patients with a score of 2 or greater had a HR of 3.1 (P less than .0001 for each comparison).
“The findings of the study indicate that improving access to affordable, quality health care may reduce disparities in survival for those currently lacking coverage,” the investigators wrote.
The study was supported by Emory University, the National Institutes of Health, and the National Center for Advancing Translational Sciences. Dr. Flowers reported financial relationships with AbbVie, Spectrum, Celgene, and several other companies. The other authors reported having nothing to disclose.
SOURCE: Goldstein JS et al. Blood. 2018 Jul 24. doi: 10.1182/blood-2018-03-839035.
Having health insurance can mean the difference between life and death for patients with follicular lymphoma, suggest results of a study showing that patients with private health insurance had nearly twofold better survival outcomes than patients without insurance or those who were covered by Medicare or Medicaid.
A review of records on more than 43,000 patients with follicular lymphoma (FL) in a national cancer registry showed that, compared with patients under age 65 with private insurance, the hazard ratios (HR) for death among patients in the same age bracket with either no insurance, Medicaid, or Medicare were, respectively, 1.96, 1.83, and 1.96 (P less than .0001 for each comparison).
“Our study finds that insurance status contributes to survival disparities in FL. Future studies on outcomes in FL should include insurance status as an important predictor,” Christopher R. Flowers, MD, of Emory University in Atlanta and his colleagues wrote in Blood.
“Further research on prognosis for FL should examine the impact of public policy, such as the passage of the [Affordable Care Act], on FL outcomes, as well as examine other factors that influence access to care, such as individual-level socioeconomic status, regular primary care visits, access to prescription medications, and care affordability,” they added.
The investigators noted that earlier research found that patients with Medicaid or no insurance were more likely than privately-insured patients to be diagnosed with cancers at advanced stages, and that some patients with aggressive non-Hodgkin lymphomas have been shown to have insurance-related disparities in treatments and outcomes.
To see whether the same could be true for patients with indolent-histology lymphomas such as FL, they extracted data from the National Cancer Database, a nationwide hospital-based cancer registry sponsored jointly by the American College of Surgeons and the American Cancer Society.
They identified a total of 43,648 patients aged 18 years or older who were diagnosed with FL from 2004 through 2014. They looked at both patients 18-64 years and those 65 years and older to account for changes in insurance with Medicare eligibility.
Overall survival among patients younger than age 65 was significantly worse for patients with public insurance (Medicaid or Medicare) or no insurance in Cox proportional hazard models controlling for available data on sociodemographic factors and prognostic indicators.
However, compared with patients aged 65 and older with private insurance, only patients with Medicare as their sole source of insurance had significantly worse overall survival (HR, 1.28; P less than .0001).
Patients who were uninsured or had Medicaid were more likely than others to have lower socioeconomic status, present with advanced-stage disease, have systemic symptoms, and have multiple comorbidities that persisted after controlling for known sociodemographic and prognostic factors.
The investigators found that, among patients under age 65, those with a comorbidity score of 1 had an HR for death of 1.71, compared with patients with no comorbidities, and that patients with a score of 2 or greater had a HR of 3.1 (P less than .0001 for each comparison).
“The findings of the study indicate that improving access to affordable, quality health care may reduce disparities in survival for those currently lacking coverage,” the investigators wrote.
The study was supported by Emory University, the National Institutes of Health, and the National Center for Advancing Translational Sciences. Dr. Flowers reported financial relationships with AbbVie, Spectrum, Celgene, and several other companies. The other authors reported having nothing to disclose.
SOURCE: Goldstein JS et al. Blood. 2018 Jul 24. doi: 10.1182/blood-2018-03-839035.
FROM BLOOD
Key clinical point:
Major finding: The risk for death among patients under age 65 with no insurance, Medicaid, or Medicare was nearly twice that of similar patients with private health insurance.
Study details: Review of data on 43,648 patients with follicular lymphoma in the National Cancer Database.
Disclosures: The study was supported by Emory University, the National Institutes of Health, and the National Center for Advancing Translational Sciences. Dr. Flowers reported financial relationships with AbbVie, Spectrum, Celgene, and several other companies. The other authors reported having nothing to disclose.
Source: Goldstein JS et al. Blood. 2018 Jul 24. doi: 10.1182/blood-2018-03-839035.
Conditional OS estimates show upfront TKI benefit in mRCC
An analysis of conditional survival outcomes for patients with metastatic renal cell carcinoma (mRCC) has suggested that first-line therapy with a tyrosine kinase inhibitor (TKI) can result in improved survival odds over time.
Patients with mRCC treated with a TKI upfront had gradual increases over time in conditional overall survival estimates when compared with baseline survival predictions, a retrospective review has indicated.
Patients who survived at least 36 months after the start of therapy had an estimated 36-month conditional overall survival (OS) rate that was 7.3% higher than the predicted survival at the initiation of therapy, reported Seong Il Seo, MD, PhD, from Samsung Medical Center in Seoul, North Korea, and his colleagues.
The investigators also found that, while predictors of survival changed over time, previous metastasectomy was a key prognosticator of conditional overall survival throughout 36 months of follow-up, they reported in The Journal of Urology.
“To our knowledge, our data are the first to reveal the beneficial role of metastasectomy on conditional OS probabilities with time since an initial survival estimation, particularly in patients at intermediate and poor risk. [Conditional survival] estimates can be beneficial to counsel patients with mRCC about more practical prognoses and helpful to continuously adjust surveillance planning in these patients,” they wrote.
Conditional survival is an analytical method for providing more accurate estimates of how prognoses change over time when patients with aggressive metastatic disease, such as mRCC, are exposed to therapies such as nephrectomy or TKIs.
The investigators retrospectively reviewed records for 1,131 patients with mRCC in the Korean Renal Cancer Study Group database. They calculated conditional OS using a nomogram that indicated the likelihood that a patient would survive an additional number of years given that he or she had already survived a certain number of years. They also created a multivariate regression model to identify predictors of conditional survival over time.
They found that, at all survival times after the start of TKI therapy (6, 12, 18, 24, and 36 months), conditional overall survival gradually increased when compared with baseline survival estimates.
“While the actual overall survival rate decreased with time, the 36-month conditional overall survival rate was calculated as 7.3% higher in patients who had already survived 36 months compared to baseline estimations at the time of initial tyrosine kinase inhibitor treatment,” they wrote.
In the multivariate model, prognostic factors such as gender, pathologic T stage, and Heng risk classification became nonsignificant over time, but previous metastasectomy remained a significant independent predictor of survival after TKI therapy at all time points except for 18 months.
“This study largely corroborates previous data from the IMDC (International Metastatic Renal Cell Carcinoma Database Consortium), and it provides useful information on prognostication,” commented Adam B. Weiner, MD, of Northwestern University in Chicago, in a brief accompanying editorial.
The study was supported by a National Research Foundation of Korea research grant funded by the Ministry of Science and Information and Communications Technology and by a Korea Health Technology R&D Project grant through the Korea Health Industry Development Institute funded by the Ministry of Health and Welfare in South Korea. No conflicts of interest were reported.
SOURCE: Kang M et al. J Urol. 2018 June 22. doi: 10.1016/j.juro.2018.06.030.
An analysis of conditional survival outcomes for patients with metastatic renal cell carcinoma (mRCC) has suggested that first-line therapy with a tyrosine kinase inhibitor (TKI) can result in improved survival odds over time.
Patients with mRCC treated with a TKI upfront had gradual increases over time in conditional overall survival estimates when compared with baseline survival predictions, a retrospective review has indicated.
Patients who survived at least 36 months after the start of therapy had an estimated 36-month conditional overall survival (OS) rate that was 7.3% higher than the predicted survival at the initiation of therapy, reported Seong Il Seo, MD, PhD, from Samsung Medical Center in Seoul, North Korea, and his colleagues.
The investigators also found that, while predictors of survival changed over time, previous metastasectomy was a key prognosticator of conditional overall survival throughout 36 months of follow-up, they reported in The Journal of Urology.
“To our knowledge, our data are the first to reveal the beneficial role of metastasectomy on conditional OS probabilities with time since an initial survival estimation, particularly in patients at intermediate and poor risk. [Conditional survival] estimates can be beneficial to counsel patients with mRCC about more practical prognoses and helpful to continuously adjust surveillance planning in these patients,” they wrote.
Conditional survival is an analytical method for providing more accurate estimates of how prognoses change over time when patients with aggressive metastatic disease, such as mRCC, are exposed to therapies such as nephrectomy or TKIs.
The investigators retrospectively reviewed records for 1,131 patients with mRCC in the Korean Renal Cancer Study Group database. They calculated conditional OS using a nomogram that indicated the likelihood that a patient would survive an additional number of years given that he or she had already survived a certain number of years. They also created a multivariate regression model to identify predictors of conditional survival over time.
They found that, at all survival times after the start of TKI therapy (6, 12, 18, 24, and 36 months), conditional overall survival gradually increased when compared with baseline survival estimates.
“While the actual overall survival rate decreased with time, the 36-month conditional overall survival rate was calculated as 7.3% higher in patients who had already survived 36 months compared to baseline estimations at the time of initial tyrosine kinase inhibitor treatment,” they wrote.
In the multivariate model, prognostic factors such as gender, pathologic T stage, and Heng risk classification became nonsignificant over time, but previous metastasectomy remained a significant independent predictor of survival after TKI therapy at all time points except for 18 months.
“This study largely corroborates previous data from the IMDC (International Metastatic Renal Cell Carcinoma Database Consortium), and it provides useful information on prognostication,” commented Adam B. Weiner, MD, of Northwestern University in Chicago, in a brief accompanying editorial.
The study was supported by a National Research Foundation of Korea research grant funded by the Ministry of Science and Information and Communications Technology and by a Korea Health Technology R&D Project grant through the Korea Health Industry Development Institute funded by the Ministry of Health and Welfare in South Korea. No conflicts of interest were reported.
SOURCE: Kang M et al. J Urol. 2018 June 22. doi: 10.1016/j.juro.2018.06.030.
An analysis of conditional survival outcomes for patients with metastatic renal cell carcinoma (mRCC) has suggested that first-line therapy with a tyrosine kinase inhibitor (TKI) can result in improved survival odds over time.
Patients with mRCC treated with a TKI upfront had gradual increases over time in conditional overall survival estimates when compared with baseline survival predictions, a retrospective review has indicated.
Patients who survived at least 36 months after the start of therapy had an estimated 36-month conditional overall survival (OS) rate that was 7.3% higher than the predicted survival at the initiation of therapy, reported Seong Il Seo, MD, PhD, from Samsung Medical Center in Seoul, North Korea, and his colleagues.
The investigators also found that, while predictors of survival changed over time, previous metastasectomy was a key prognosticator of conditional overall survival throughout 36 months of follow-up, they reported in The Journal of Urology.
“To our knowledge, our data are the first to reveal the beneficial role of metastasectomy on conditional OS probabilities with time since an initial survival estimation, particularly in patients at intermediate and poor risk. [Conditional survival] estimates can be beneficial to counsel patients with mRCC about more practical prognoses and helpful to continuously adjust surveillance planning in these patients,” they wrote.
Conditional survival is an analytical method for providing more accurate estimates of how prognoses change over time when patients with aggressive metastatic disease, such as mRCC, are exposed to therapies such as nephrectomy or TKIs.
The investigators retrospectively reviewed records for 1,131 patients with mRCC in the Korean Renal Cancer Study Group database. They calculated conditional OS using a nomogram that indicated the likelihood that a patient would survive an additional number of years given that he or she had already survived a certain number of years. They also created a multivariate regression model to identify predictors of conditional survival over time.
They found that, at all survival times after the start of TKI therapy (6, 12, 18, 24, and 36 months), conditional overall survival gradually increased when compared with baseline survival estimates.
“While the actual overall survival rate decreased with time, the 36-month conditional overall survival rate was calculated as 7.3% higher in patients who had already survived 36 months compared to baseline estimations at the time of initial tyrosine kinase inhibitor treatment,” they wrote.
In the multivariate model, prognostic factors such as gender, pathologic T stage, and Heng risk classification became nonsignificant over time, but previous metastasectomy remained a significant independent predictor of survival after TKI therapy at all time points except for 18 months.
“This study largely corroborates previous data from the IMDC (International Metastatic Renal Cell Carcinoma Database Consortium), and it provides useful information on prognostication,” commented Adam B. Weiner, MD, of Northwestern University in Chicago, in a brief accompanying editorial.
The study was supported by a National Research Foundation of Korea research grant funded by the Ministry of Science and Information and Communications Technology and by a Korea Health Technology R&D Project grant through the Korea Health Industry Development Institute funded by the Ministry of Health and Welfare in South Korea. No conflicts of interest were reported.
SOURCE: Kang M et al. J Urol. 2018 June 22. doi: 10.1016/j.juro.2018.06.030.
FROM THE JOURNAL OF UROLOGY
Key clinical point: Conditional overall survival estimates may help clinicians adjust surveillance planning in patients with mRCC.
Major finding: At all survival times after the start of TKI therapy, conditional overall survival gradually increased when compared with baseline survival estimates.
Study details: Retrospective review of records on 1,131 patients with mRCC.
Disclosures: The study was supported by a National Research Foundation of Korea research grant funded by the Ministry of Science and Information and Communications Technology and by a Korea Health Technology R&D Project grant through the Korea Health Industry Development Institute funded by the Ministry of Health and Welfare in South Korea. No conflicts of interest were reported.
Source: Kang M et al. J Urol. 2018 June 22. doi: 10.1016/j.juro.2018.06.030.
HPV positivity associated with good esophageal adenocarcinoma outcomes
Patients with Barrett high-grade dysplasia or esophageal adenocarcinoma who are positive for human papillomavirus (HPV) infection have significantly better outcomes than patients with the same diseases who are negative for HPV, investigators report.
Among patients with Barrett high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC), mean disease-free survival (DFS) was 40.3 months for HPV-positive patients, compared with 24.1 months for HPV-negative patients (P = .003). Mean overall survival was also significantly better in HPV-positive patients, at 43.7 months versus 29.8 months (P =.009) respectively, reported Shanmugarajah Rajendra, MD, from Bankstown-Lincombe Hospital in Sydney and colleagues.
“If these findings of a favorable prognosis of HPV-positive HGD and EAC are confirmed in larger cohorts with more advanced disease, it presents an opportunity for treatment de-escalation in the hope of reducing toxic effects without deleteriously affecting survival,” they wrote in JAMA Network Open.
The findings support those of earlier studies suggesting that HPV infection is associated with better prognosis among patients with other cancers of the head and neck. For example, a retrospective analysis of data from two clinical trials reported in 2014 found that, 2 years after a diagnosis of recurrent oropharyngeal cancer, 54.6% of HPV-positive patients were alive, compared with 27.6% of HPV-negative patients (P less than .001).
To determine whether there was a similar association between HPV infection and better prognosis of Barrett HGD or EAC, Dr. Rajendra and associates conducted a retrospective case-control study of 142 patients with HGD or EAC treated at secondary or tertiary referral centers in Australia. The patients, all of whom were white, included 126 men. The mean age was 66 years, and in all, 37 patients were positive for HPV.
As noted before, both DFS and overall survival were significantly better for HPV-infected patients, with mean differences of 16.2 months and 13.9 months, respectively. HPV-positive patients also had lower rates of progression or recurrence (24.3% vs. 58.1%; P less than .001), distant metastases (8.1% vs. 27.6%; P = .02), and death from EAC (13.5% vs. 36.2%; P = .02).
In multivariate analysis, superior DFS was associated with HPV positivity, (hazard ratio, 0.39; P = .02), biologically active virus (HR, 0.36; P = .02), E6 and E7 messenger RNA (HR, 0.36; P = .04), and with high p16 expression (HR, 0.49; P = .02).
The study was supported by the South Western Sydney Clinical School; the University of New South Wales, Sydney; and the Oesophageal Cancer Research Fund. Dr. Rajendra reported grants from the University of New South Wales and the Oesophageal Cancer Research Fund during the conduct of the study. No other disclosures were reported.
SOURCE: Rajendra S et al. JAMA Network Open. 2018 Aug 3. doi:10.1001/jamanetworkopen.2018.1054.
The study by Rajendra et al highlights the potential role of human papillomavirus (HPV) status in the prognosis of esophageal adenocarcinoma (EAC). However, the use of HPV as a predictive marker for treatment remains unproven, and many questions abound. Important considerations for studies of de-escalation of treatment in HPV-positive EAC include how best to select patients for less intensive treatment: Should trials be restricted to nonsmoking patients with better prognosis pathology characteristics, including lower T stage and lack of lymph node involvement? What is the best method to assess HPV status in a cost-effective and easily available assay for broad international use? Should there be a de-escalation of chemotherapy, radiation, or both? Is there potentially a role for de-escalation of surgery? Are these trials that patients would consider participation in given the lethality of these cancers?
Finally, the presence of a vaccine for HPV may affect the incidence of cervical, oropharyngeal, and other cancers. If HPV is an important risk factor for EAC, we may see a reduction in the rates of this highly lethal cancer over time. These benefits may take some time to bear out and are highly dependent on vaccination rates. Nonetheless, primary prevention of HPV infection may result in a significant reduction in the global burden of this disease. In the meantime, larger-scale studies of the role of HPV in the pathogenesis of EAC are warranted, particularly before moving toward trials of less intensive therapy. While the results of this small cohort study are impressive, they are preliminary, and the study requires confirmation in a larger, prospective trial.
Sukhbinder Dhesy-Thind, MD, FRCPC is from McMaster University, Hamilton, Ontario. Her remarks are excerpted from an editorial accompanying the study. She reported personal fees from Teva Canada Innovation and Novartis Pharmaceuticals Canada outside the submitted work.
The study by Rajendra et al highlights the potential role of human papillomavirus (HPV) status in the prognosis of esophageal adenocarcinoma (EAC). However, the use of HPV as a predictive marker for treatment remains unproven, and many questions abound. Important considerations for studies of de-escalation of treatment in HPV-positive EAC include how best to select patients for less intensive treatment: Should trials be restricted to nonsmoking patients with better prognosis pathology characteristics, including lower T stage and lack of lymph node involvement? What is the best method to assess HPV status in a cost-effective and easily available assay for broad international use? Should there be a de-escalation of chemotherapy, radiation, or both? Is there potentially a role for de-escalation of surgery? Are these trials that patients would consider participation in given the lethality of these cancers?
Finally, the presence of a vaccine for HPV may affect the incidence of cervical, oropharyngeal, and other cancers. If HPV is an important risk factor for EAC, we may see a reduction in the rates of this highly lethal cancer over time. These benefits may take some time to bear out and are highly dependent on vaccination rates. Nonetheless, primary prevention of HPV infection may result in a significant reduction in the global burden of this disease. In the meantime, larger-scale studies of the role of HPV in the pathogenesis of EAC are warranted, particularly before moving toward trials of less intensive therapy. While the results of this small cohort study are impressive, they are preliminary, and the study requires confirmation in a larger, prospective trial.
Sukhbinder Dhesy-Thind, MD, FRCPC is from McMaster University, Hamilton, Ontario. Her remarks are excerpted from an editorial accompanying the study. She reported personal fees from Teva Canada Innovation and Novartis Pharmaceuticals Canada outside the submitted work.
The study by Rajendra et al highlights the potential role of human papillomavirus (HPV) status in the prognosis of esophageal adenocarcinoma (EAC). However, the use of HPV as a predictive marker for treatment remains unproven, and many questions abound. Important considerations for studies of de-escalation of treatment in HPV-positive EAC include how best to select patients for less intensive treatment: Should trials be restricted to nonsmoking patients with better prognosis pathology characteristics, including lower T stage and lack of lymph node involvement? What is the best method to assess HPV status in a cost-effective and easily available assay for broad international use? Should there be a de-escalation of chemotherapy, radiation, or both? Is there potentially a role for de-escalation of surgery? Are these trials that patients would consider participation in given the lethality of these cancers?
Finally, the presence of a vaccine for HPV may affect the incidence of cervical, oropharyngeal, and other cancers. If HPV is an important risk factor for EAC, we may see a reduction in the rates of this highly lethal cancer over time. These benefits may take some time to bear out and are highly dependent on vaccination rates. Nonetheless, primary prevention of HPV infection may result in a significant reduction in the global burden of this disease. In the meantime, larger-scale studies of the role of HPV in the pathogenesis of EAC are warranted, particularly before moving toward trials of less intensive therapy. While the results of this small cohort study are impressive, they are preliminary, and the study requires confirmation in a larger, prospective trial.
Sukhbinder Dhesy-Thind, MD, FRCPC is from McMaster University, Hamilton, Ontario. Her remarks are excerpted from an editorial accompanying the study. She reported personal fees from Teva Canada Innovation and Novartis Pharmaceuticals Canada outside the submitted work.
Patients with Barrett high-grade dysplasia or esophageal adenocarcinoma who are positive for human papillomavirus (HPV) infection have significantly better outcomes than patients with the same diseases who are negative for HPV, investigators report.
Among patients with Barrett high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC), mean disease-free survival (DFS) was 40.3 months for HPV-positive patients, compared with 24.1 months for HPV-negative patients (P = .003). Mean overall survival was also significantly better in HPV-positive patients, at 43.7 months versus 29.8 months (P =.009) respectively, reported Shanmugarajah Rajendra, MD, from Bankstown-Lincombe Hospital in Sydney and colleagues.
“If these findings of a favorable prognosis of HPV-positive HGD and EAC are confirmed in larger cohorts with more advanced disease, it presents an opportunity for treatment de-escalation in the hope of reducing toxic effects without deleteriously affecting survival,” they wrote in JAMA Network Open.
The findings support those of earlier studies suggesting that HPV infection is associated with better prognosis among patients with other cancers of the head and neck. For example, a retrospective analysis of data from two clinical trials reported in 2014 found that, 2 years after a diagnosis of recurrent oropharyngeal cancer, 54.6% of HPV-positive patients were alive, compared with 27.6% of HPV-negative patients (P less than .001).
To determine whether there was a similar association between HPV infection and better prognosis of Barrett HGD or EAC, Dr. Rajendra and associates conducted a retrospective case-control study of 142 patients with HGD or EAC treated at secondary or tertiary referral centers in Australia. The patients, all of whom were white, included 126 men. The mean age was 66 years, and in all, 37 patients were positive for HPV.
As noted before, both DFS and overall survival were significantly better for HPV-infected patients, with mean differences of 16.2 months and 13.9 months, respectively. HPV-positive patients also had lower rates of progression or recurrence (24.3% vs. 58.1%; P less than .001), distant metastases (8.1% vs. 27.6%; P = .02), and death from EAC (13.5% vs. 36.2%; P = .02).
In multivariate analysis, superior DFS was associated with HPV positivity, (hazard ratio, 0.39; P = .02), biologically active virus (HR, 0.36; P = .02), E6 and E7 messenger RNA (HR, 0.36; P = .04), and with high p16 expression (HR, 0.49; P = .02).
The study was supported by the South Western Sydney Clinical School; the University of New South Wales, Sydney; and the Oesophageal Cancer Research Fund. Dr. Rajendra reported grants from the University of New South Wales and the Oesophageal Cancer Research Fund during the conduct of the study. No other disclosures were reported.
SOURCE: Rajendra S et al. JAMA Network Open. 2018 Aug 3. doi:10.1001/jamanetworkopen.2018.1054.
Patients with Barrett high-grade dysplasia or esophageal adenocarcinoma who are positive for human papillomavirus (HPV) infection have significantly better outcomes than patients with the same diseases who are negative for HPV, investigators report.
Among patients with Barrett high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC), mean disease-free survival (DFS) was 40.3 months for HPV-positive patients, compared with 24.1 months for HPV-negative patients (P = .003). Mean overall survival was also significantly better in HPV-positive patients, at 43.7 months versus 29.8 months (P =.009) respectively, reported Shanmugarajah Rajendra, MD, from Bankstown-Lincombe Hospital in Sydney and colleagues.
“If these findings of a favorable prognosis of HPV-positive HGD and EAC are confirmed in larger cohorts with more advanced disease, it presents an opportunity for treatment de-escalation in the hope of reducing toxic effects without deleteriously affecting survival,” they wrote in JAMA Network Open.
The findings support those of earlier studies suggesting that HPV infection is associated with better prognosis among patients with other cancers of the head and neck. For example, a retrospective analysis of data from two clinical trials reported in 2014 found that, 2 years after a diagnosis of recurrent oropharyngeal cancer, 54.6% of HPV-positive patients were alive, compared with 27.6% of HPV-negative patients (P less than .001).
To determine whether there was a similar association between HPV infection and better prognosis of Barrett HGD or EAC, Dr. Rajendra and associates conducted a retrospective case-control study of 142 patients with HGD or EAC treated at secondary or tertiary referral centers in Australia. The patients, all of whom were white, included 126 men. The mean age was 66 years, and in all, 37 patients were positive for HPV.
As noted before, both DFS and overall survival were significantly better for HPV-infected patients, with mean differences of 16.2 months and 13.9 months, respectively. HPV-positive patients also had lower rates of progression or recurrence (24.3% vs. 58.1%; P less than .001), distant metastases (8.1% vs. 27.6%; P = .02), and death from EAC (13.5% vs. 36.2%; P = .02).
In multivariate analysis, superior DFS was associated with HPV positivity, (hazard ratio, 0.39; P = .02), biologically active virus (HR, 0.36; P = .02), E6 and E7 messenger RNA (HR, 0.36; P = .04), and with high p16 expression (HR, 0.49; P = .02).
The study was supported by the South Western Sydney Clinical School; the University of New South Wales, Sydney; and the Oesophageal Cancer Research Fund. Dr. Rajendra reported grants from the University of New South Wales and the Oesophageal Cancer Research Fund during the conduct of the study. No other disclosures were reported.
SOURCE: Rajendra S et al. JAMA Network Open. 2018 Aug 3. doi:10.1001/jamanetworkopen.2018.1054.
FROM JAMA NETWORK OPEN
Key clinical point: Human papillomavirus infection is associated with better outcomes for patients with esophageal adenocarcinoma and other head and neck cancers.
Major finding: Mean disease-free survival was 40.3 months for HPV-positive patients versus 24.1 months for HPV-negative patients (P = .003).
Study details: A retrospective case-control study of 142 patients with Barrett high-grade dysplasia or esophageal adenocarcinoma.
Disclosures: The study was supported by the South Western Sydney Clinical School; the University of New South Wales, Sydney; and the Oesophageal Cancer Research Fund. Dr. Rajendra reported grants from University of New South Wales and the Oesophageal Cancer Research Fund during the conduct of the study. No other disclosures were reported.
Source: Rajendra S et al. JAMA Network Open. 2018 Aug 3. doi: 10.1001/jamanetworkopen.2018.1054.
Melanoma diagnosis does not deter pregnancy
Women in the United States do not appear to be delaying pregnancy after a diagnosis of melanoma, despite general recommendations to wait at least 2 years to attempt pregnancy because it might increase the risk of recurrence or exacerbate disease, investigators reported in the Journal of Surgical Research.
A review of records from a large national health care database showed that women aged 18-40 years with melanoma who were not pregnant on the index date had a significantly higher rate of pregnancy within 2 years, compared with matched controls, reported Julie A. DiSano, MD, from Penn State University, Hershey.
“These results suggest that a diagnosis of melanoma may serve as an impetus for some families to begin childbearing or have additional children sooner than they otherwise would have,” they wrote.
The investigators also found, reassuringly, that women who became pregnant after a melanoma diagnosis were not at increased risk for requiring additional therapy for the malignancy, at least in the short term.
Although earlier studies suggested that women who were pregnant at the time of a melanoma diagnosis had worse prognoses when compared with women who were not pregnant at the time of diagnosis, more recent studies have indicated women who are pregnant when diagnosed have similar outcomes as nonpregnant women with the same disease stage, the investigators noted.
“What is unclear and difficult to study is the relationship between melanoma and subsequent pregnancy rates, and pregnancy on melanoma outcomes. Very little data exist to guide women and physicians as to the safety of pregnancy after a diagnosis of melanoma. As a result, there are no formal guidelines for physicians who wish to counsel their patients regarding pregnancy after melanoma, and it is unknown whether women receive any counseling at all,” they wrote.
To get a clearer picture of the link between melanoma and subsequent pregnancy, the investigators scanned the Truven Health MarketScan database and identified 11,801 women from 18-40 years with melanoma who were not pregnant on the index date, determined by the earliest claim for melanoma diagnosis or therapy.
Each patient was matched on a 1:1 basis with women who did not have a melanoma claim at any time; cases were matched with controls on the basis of year of index date, age at index date, state of residence, and pregnancy status in the 90 days before the index date.
The authors found that the rate of pregnancy within 2 years of the index date was 15.8% for cases, compared with 13.6% for controls (P less than .001).
They also found, however, that women who required postsurgical therapy, suggesting more advanced disease stage or early recurrence, had a significantly lower probability of becoming pregnant within the first 9 months after the index date (hazard ratio, 0.26; P = .003).
There were no significant differences in the rate of postsurgical treatment by pregnancy status at either 3, 6, 9, or 12 months after surgery (P less than .05 for each), or in a Cox regression model for all time points (HR, 0.68, P = .23).
The authors offered several possible explanations for the higher pregnancy rates among women with melanoma, including the possibility that a cancer diagnosis could bring some couples closer together and “reorder” their priorities about starting a family.
“Another hypothesis is that families facing a melanoma diagnosis may decide to complete childbearing sooner in case the cancer recurs and subsequent treatment compromises fertility. Either way, the increased likelihood of pregnancy after melanoma diagnosis suggests an optimism about their future among families in the current childbearing generation in the United States,” they wrote.
The authors cautioned that the database does not include information about disease stage, and that “more detailed stage information is needed before revisiting recommendations.”
The study was supported by a Barsumian Trust grant; the authors reported having no conflicts of interest.
SOURCE: DiSano JA et al. J Surg Res. 2018 Jun 16. doi: 10.1016/j.jss.2018.05.026.
Women in the United States do not appear to be delaying pregnancy after a diagnosis of melanoma, despite general recommendations to wait at least 2 years to attempt pregnancy because it might increase the risk of recurrence or exacerbate disease, investigators reported in the Journal of Surgical Research.
A review of records from a large national health care database showed that women aged 18-40 years with melanoma who were not pregnant on the index date had a significantly higher rate of pregnancy within 2 years, compared with matched controls, reported Julie A. DiSano, MD, from Penn State University, Hershey.
“These results suggest that a diagnosis of melanoma may serve as an impetus for some families to begin childbearing or have additional children sooner than they otherwise would have,” they wrote.
The investigators also found, reassuringly, that women who became pregnant after a melanoma diagnosis were not at increased risk for requiring additional therapy for the malignancy, at least in the short term.
Although earlier studies suggested that women who were pregnant at the time of a melanoma diagnosis had worse prognoses when compared with women who were not pregnant at the time of diagnosis, more recent studies have indicated women who are pregnant when diagnosed have similar outcomes as nonpregnant women with the same disease stage, the investigators noted.
“What is unclear and difficult to study is the relationship between melanoma and subsequent pregnancy rates, and pregnancy on melanoma outcomes. Very little data exist to guide women and physicians as to the safety of pregnancy after a diagnosis of melanoma. As a result, there are no formal guidelines for physicians who wish to counsel their patients regarding pregnancy after melanoma, and it is unknown whether women receive any counseling at all,” they wrote.
To get a clearer picture of the link between melanoma and subsequent pregnancy, the investigators scanned the Truven Health MarketScan database and identified 11,801 women from 18-40 years with melanoma who were not pregnant on the index date, determined by the earliest claim for melanoma diagnosis or therapy.
Each patient was matched on a 1:1 basis with women who did not have a melanoma claim at any time; cases were matched with controls on the basis of year of index date, age at index date, state of residence, and pregnancy status in the 90 days before the index date.
The authors found that the rate of pregnancy within 2 years of the index date was 15.8% for cases, compared with 13.6% for controls (P less than .001).
They also found, however, that women who required postsurgical therapy, suggesting more advanced disease stage or early recurrence, had a significantly lower probability of becoming pregnant within the first 9 months after the index date (hazard ratio, 0.26; P = .003).
There were no significant differences in the rate of postsurgical treatment by pregnancy status at either 3, 6, 9, or 12 months after surgery (P less than .05 for each), or in a Cox regression model for all time points (HR, 0.68, P = .23).
The authors offered several possible explanations for the higher pregnancy rates among women with melanoma, including the possibility that a cancer diagnosis could bring some couples closer together and “reorder” their priorities about starting a family.
“Another hypothesis is that families facing a melanoma diagnosis may decide to complete childbearing sooner in case the cancer recurs and subsequent treatment compromises fertility. Either way, the increased likelihood of pregnancy after melanoma diagnosis suggests an optimism about their future among families in the current childbearing generation in the United States,” they wrote.
The authors cautioned that the database does not include information about disease stage, and that “more detailed stage information is needed before revisiting recommendations.”
The study was supported by a Barsumian Trust grant; the authors reported having no conflicts of interest.
SOURCE: DiSano JA et al. J Surg Res. 2018 Jun 16. doi: 10.1016/j.jss.2018.05.026.
Women in the United States do not appear to be delaying pregnancy after a diagnosis of melanoma, despite general recommendations to wait at least 2 years to attempt pregnancy because it might increase the risk of recurrence or exacerbate disease, investigators reported in the Journal of Surgical Research.
A review of records from a large national health care database showed that women aged 18-40 years with melanoma who were not pregnant on the index date had a significantly higher rate of pregnancy within 2 years, compared with matched controls, reported Julie A. DiSano, MD, from Penn State University, Hershey.
“These results suggest that a diagnosis of melanoma may serve as an impetus for some families to begin childbearing or have additional children sooner than they otherwise would have,” they wrote.
The investigators also found, reassuringly, that women who became pregnant after a melanoma diagnosis were not at increased risk for requiring additional therapy for the malignancy, at least in the short term.
Although earlier studies suggested that women who were pregnant at the time of a melanoma diagnosis had worse prognoses when compared with women who were not pregnant at the time of diagnosis, more recent studies have indicated women who are pregnant when diagnosed have similar outcomes as nonpregnant women with the same disease stage, the investigators noted.
“What is unclear and difficult to study is the relationship between melanoma and subsequent pregnancy rates, and pregnancy on melanoma outcomes. Very little data exist to guide women and physicians as to the safety of pregnancy after a diagnosis of melanoma. As a result, there are no formal guidelines for physicians who wish to counsel their patients regarding pregnancy after melanoma, and it is unknown whether women receive any counseling at all,” they wrote.
To get a clearer picture of the link between melanoma and subsequent pregnancy, the investigators scanned the Truven Health MarketScan database and identified 11,801 women from 18-40 years with melanoma who were not pregnant on the index date, determined by the earliest claim for melanoma diagnosis or therapy.
Each patient was matched on a 1:1 basis with women who did not have a melanoma claim at any time; cases were matched with controls on the basis of year of index date, age at index date, state of residence, and pregnancy status in the 90 days before the index date.
The authors found that the rate of pregnancy within 2 years of the index date was 15.8% for cases, compared with 13.6% for controls (P less than .001).
They also found, however, that women who required postsurgical therapy, suggesting more advanced disease stage or early recurrence, had a significantly lower probability of becoming pregnant within the first 9 months after the index date (hazard ratio, 0.26; P = .003).
There were no significant differences in the rate of postsurgical treatment by pregnancy status at either 3, 6, 9, or 12 months after surgery (P less than .05 for each), or in a Cox regression model for all time points (HR, 0.68, P = .23).
The authors offered several possible explanations for the higher pregnancy rates among women with melanoma, including the possibility that a cancer diagnosis could bring some couples closer together and “reorder” their priorities about starting a family.
“Another hypothesis is that families facing a melanoma diagnosis may decide to complete childbearing sooner in case the cancer recurs and subsequent treatment compromises fertility. Either way, the increased likelihood of pregnancy after melanoma diagnosis suggests an optimism about their future among families in the current childbearing generation in the United States,” they wrote.
The authors cautioned that the database does not include information about disease stage, and that “more detailed stage information is needed before revisiting recommendations.”
The study was supported by a Barsumian Trust grant; the authors reported having no conflicts of interest.
SOURCE: DiSano JA et al. J Surg Res. 2018 Jun 16. doi: 10.1016/j.jss.2018.05.026.
FROM THE JOURNAL OF SURGICAL RESEARCH
Key clinical point: Pregnancy after melanoma does not appear to increase risk for melanoma recurrence.
Major finding: The rate of pregnancy for women with melanoma was 15.8%, compared with 13.6% for controls (P less than .001).
Study details: A retrospective study of claims database records on 11,801 women with melanoma and an equal number of matched controls.
Disclosures: The study was supported by a Barsumian Trust grant; the authors reported having no conflicts of interest.
Source: DiSano JA et al. J Surg Res. 2018 Jun 16. doi: 10.1016/j.jss.2018.05.026.
Intrathecal methotrexate dosing in acute leukemia falls short
STOCKHOLM – Although intrathecal chemoprophylaxis for prevention of central nervous system involvement is an essential component of modern regimens to treat acute lymphoblastic leukemia (ALL), patients don’t always receive the recommended number of doses, potentially compromising remissions.
But as a large-scale audit of health care delivery in the United Kingdom has suggested, many of the possible causes for suboptimal delivery of intrathecal methotrexate (IT MTX) appear to be modifiable, reported Sven A. Sommerfeld, MD, and his colleagues from the Christie Hospital in Manchester, England.
“In our clinical observations, and confirmed in this audit, patients on intensive chemotherapy, including induction and consolidation protocols for acute lymphoblastic leukemia, can develop a number of issues and toxicities, which can interfere with the administration of IT MTX,” they wrote in a poster presented at the annual congress of the European Hematology Association.
Reasons for canceling or postponing scheduled doses of IT MTX range from “fairly compelling clinical reasons affecting patient safety or tolerance” to more mundane issues, such as scheduling and staffing problems, the investigators found.
“I think there are a number of factors that can improve compliance, including having your cancellation rate as low as possible. You have already prescribed the treatment, the patient is supposed to be attending [clinic], yet for some reason you cannot go ahead,” Dr. Sommerfeld said in an interview. “I think blood product support is important, but there are capacity issues. Organization of complex treatment protocols that involve systemic chemotherapy and concurrent intrathecal administration can be difficult as different people oversee both of these treatments.”
For example, protocols specify delivery of intrathecal chemoprophylaxis on specific days and induction chemotherapy on other days, and it may be difficult to coordinate the care so that the doses don’t overlap, he said.
Dr. Sommerfeld and his colleagues conducted an audit of standard of care for patients aged 16-60 years who were diagnosed with B-cell or T-cell ALL and received IT MTX under one of two clinical protocols: UKALL 2011 or UKALL 14.
The investigators examined data on IT MTX compliance and assigned each patient a compliance score calculated by the number of administered doses divided by protocol-defined number of doses. They also examined pharmacy records of cancellations of protocol-scheduled IT MTX from January 2016 through July 2017.
They found that the total number of IT MTX prescriptions delivered as a proportion of the number prescribed ranged from a low of 61.8% in 2009 to a high of 84.2% in 2007.
When the investigators looked at records for individual patients, including 29 adolescent and young adults receiving IT MTX under the UKALL 2011 protocol and 27 adults receiving it under the UKALL 14 protocol, they found that failure to maintain coagulation levels within parameters accounted for 23% of cancellations. The next most common reasons for cancellation were rescheduling for administrative or clinical reasons in 20% of canceled doses, low platelet levels in 19% of cases, and patient nonattendance or communication failure in 16% of cases. Other factors included problems with lumbar access, vincristine schedule for the same day, recent anticoagulation, and delay of blood results.
“Notable is the variable approach to IT MTX in patients requiring therapeutic dose anticoagulation, reflecting clinical decisions of different physicians on a case-by-case basis. Whilst a full discussion of this topic and management of asparaginase-associated [venous thromboembolism] is beyond the scope of this audit, we generally recognize today that many affected patients can be managed to continue therapy as per protocol,” the investigators wrote.
Integrating relevant prescriptions into a single information system, monitoring clinics for treatment backlogs, and improving clinical resources, such as staffing, could help to improve the efficacy of IT MTX therapy, they suggested.
The study was supported by the National Health Service Foundation Trust. Dr. Sommerfeld reported having no relevant financial disclosures.
SOURCE: Sommerfeld SA et al. EHA Congress, Abstract PS930.
STOCKHOLM – Although intrathecal chemoprophylaxis for prevention of central nervous system involvement is an essential component of modern regimens to treat acute lymphoblastic leukemia (ALL), patients don’t always receive the recommended number of doses, potentially compromising remissions.
But as a large-scale audit of health care delivery in the United Kingdom has suggested, many of the possible causes for suboptimal delivery of intrathecal methotrexate (IT MTX) appear to be modifiable, reported Sven A. Sommerfeld, MD, and his colleagues from the Christie Hospital in Manchester, England.
“In our clinical observations, and confirmed in this audit, patients on intensive chemotherapy, including induction and consolidation protocols for acute lymphoblastic leukemia, can develop a number of issues and toxicities, which can interfere with the administration of IT MTX,” they wrote in a poster presented at the annual congress of the European Hematology Association.
Reasons for canceling or postponing scheduled doses of IT MTX range from “fairly compelling clinical reasons affecting patient safety or tolerance” to more mundane issues, such as scheduling and staffing problems, the investigators found.
“I think there are a number of factors that can improve compliance, including having your cancellation rate as low as possible. You have already prescribed the treatment, the patient is supposed to be attending [clinic], yet for some reason you cannot go ahead,” Dr. Sommerfeld said in an interview. “I think blood product support is important, but there are capacity issues. Organization of complex treatment protocols that involve systemic chemotherapy and concurrent intrathecal administration can be difficult as different people oversee both of these treatments.”
For example, protocols specify delivery of intrathecal chemoprophylaxis on specific days and induction chemotherapy on other days, and it may be difficult to coordinate the care so that the doses don’t overlap, he said.
Dr. Sommerfeld and his colleagues conducted an audit of standard of care for patients aged 16-60 years who were diagnosed with B-cell or T-cell ALL and received IT MTX under one of two clinical protocols: UKALL 2011 or UKALL 14.
The investigators examined data on IT MTX compliance and assigned each patient a compliance score calculated by the number of administered doses divided by protocol-defined number of doses. They also examined pharmacy records of cancellations of protocol-scheduled IT MTX from January 2016 through July 2017.
They found that the total number of IT MTX prescriptions delivered as a proportion of the number prescribed ranged from a low of 61.8% in 2009 to a high of 84.2% in 2007.
When the investigators looked at records for individual patients, including 29 adolescent and young adults receiving IT MTX under the UKALL 2011 protocol and 27 adults receiving it under the UKALL 14 protocol, they found that failure to maintain coagulation levels within parameters accounted for 23% of cancellations. The next most common reasons for cancellation were rescheduling for administrative or clinical reasons in 20% of canceled doses, low platelet levels in 19% of cases, and patient nonattendance or communication failure in 16% of cases. Other factors included problems with lumbar access, vincristine schedule for the same day, recent anticoagulation, and delay of blood results.
“Notable is the variable approach to IT MTX in patients requiring therapeutic dose anticoagulation, reflecting clinical decisions of different physicians on a case-by-case basis. Whilst a full discussion of this topic and management of asparaginase-associated [venous thromboembolism] is beyond the scope of this audit, we generally recognize today that many affected patients can be managed to continue therapy as per protocol,” the investigators wrote.
Integrating relevant prescriptions into a single information system, monitoring clinics for treatment backlogs, and improving clinical resources, such as staffing, could help to improve the efficacy of IT MTX therapy, they suggested.
The study was supported by the National Health Service Foundation Trust. Dr. Sommerfeld reported having no relevant financial disclosures.
SOURCE: Sommerfeld SA et al. EHA Congress, Abstract PS930.
STOCKHOLM – Although intrathecal chemoprophylaxis for prevention of central nervous system involvement is an essential component of modern regimens to treat acute lymphoblastic leukemia (ALL), patients don’t always receive the recommended number of doses, potentially compromising remissions.
But as a large-scale audit of health care delivery in the United Kingdom has suggested, many of the possible causes for suboptimal delivery of intrathecal methotrexate (IT MTX) appear to be modifiable, reported Sven A. Sommerfeld, MD, and his colleagues from the Christie Hospital in Manchester, England.
“In our clinical observations, and confirmed in this audit, patients on intensive chemotherapy, including induction and consolidation protocols for acute lymphoblastic leukemia, can develop a number of issues and toxicities, which can interfere with the administration of IT MTX,” they wrote in a poster presented at the annual congress of the European Hematology Association.
Reasons for canceling or postponing scheduled doses of IT MTX range from “fairly compelling clinical reasons affecting patient safety or tolerance” to more mundane issues, such as scheduling and staffing problems, the investigators found.
“I think there are a number of factors that can improve compliance, including having your cancellation rate as low as possible. You have already prescribed the treatment, the patient is supposed to be attending [clinic], yet for some reason you cannot go ahead,” Dr. Sommerfeld said in an interview. “I think blood product support is important, but there are capacity issues. Organization of complex treatment protocols that involve systemic chemotherapy and concurrent intrathecal administration can be difficult as different people oversee both of these treatments.”
For example, protocols specify delivery of intrathecal chemoprophylaxis on specific days and induction chemotherapy on other days, and it may be difficult to coordinate the care so that the doses don’t overlap, he said.
Dr. Sommerfeld and his colleagues conducted an audit of standard of care for patients aged 16-60 years who were diagnosed with B-cell or T-cell ALL and received IT MTX under one of two clinical protocols: UKALL 2011 or UKALL 14.
The investigators examined data on IT MTX compliance and assigned each patient a compliance score calculated by the number of administered doses divided by protocol-defined number of doses. They also examined pharmacy records of cancellations of protocol-scheduled IT MTX from January 2016 through July 2017.
They found that the total number of IT MTX prescriptions delivered as a proportion of the number prescribed ranged from a low of 61.8% in 2009 to a high of 84.2% in 2007.
When the investigators looked at records for individual patients, including 29 adolescent and young adults receiving IT MTX under the UKALL 2011 protocol and 27 adults receiving it under the UKALL 14 protocol, they found that failure to maintain coagulation levels within parameters accounted for 23% of cancellations. The next most common reasons for cancellation were rescheduling for administrative or clinical reasons in 20% of canceled doses, low platelet levels in 19% of cases, and patient nonattendance or communication failure in 16% of cases. Other factors included problems with lumbar access, vincristine schedule for the same day, recent anticoagulation, and delay of blood results.
“Notable is the variable approach to IT MTX in patients requiring therapeutic dose anticoagulation, reflecting clinical decisions of different physicians on a case-by-case basis. Whilst a full discussion of this topic and management of asparaginase-associated [venous thromboembolism] is beyond the scope of this audit, we generally recognize today that many affected patients can be managed to continue therapy as per protocol,” the investigators wrote.
Integrating relevant prescriptions into a single information system, monitoring clinics for treatment backlogs, and improving clinical resources, such as staffing, could help to improve the efficacy of IT MTX therapy, they suggested.
The study was supported by the National Health Service Foundation Trust. Dr. Sommerfeld reported having no relevant financial disclosures.
SOURCE: Sommerfeld SA et al. EHA Congress, Abstract PS930.
REPORTING FROM THE EHA CONGRESS
Key clinical point:
Major finding: The total number of intrathecal methotrexate prescriptions delivered as a proportion of the number prescribed ranged from a low of 61.8% in 2009 to a high of 84.2% in 2007.
Study details: Audit of standard of care delivery of intrathecal methotrexate in the United Kingdom.
Disclosures: The study was supported by the National Health Service Foundation Trust. Dr. Sommerfeld reported having no relevant financial disclosures.
Source: Sommerfeld SA et al. EHA Congress, Abstract PS930.
Gene assays reveal some ‘unknown primary’ cancers as RCC
Gene expression profiling and/or immunohistochemistry can identify occult renal cell carcinoma (RCC) in a subset of patients diagnosed with carcinoma of unknown primary (CUP), suggesting that these patients could benefit from RCC-specific targeted therapy or immunotherapy, investigators contend.
Of 539 patients presenting at a single center with CUP, a 92-gene reverse transcription polymerase chain reaction molecular cancer classifier assay (MCCA) performed on biopsy specimens identified 24 as having RCC. All of the patients had clinical characteristics typical of advanced RCC, but none had suspicious renal lesions on CT scans, reported F. Anthony Greco, MD and John D. Hainsworth, MD, of the Sarah Cannon Cancer Center and Research Institute in Nashville, Tenn.
“Although further experience is necessary, these patients responded to RCC-specific therapy in a manner consistent with advanced RCC. These patients are unlikely to benefit from treatment with empiric chemotherapy. The reliable identification of RCC patients within the heterogeneous CUP population is possible using MCCA, and has potentially important therapeutic implications,” they wrote. The report was published in Clinical Genitourinary Cancer.
They noted that previously the only therapeutic option for patients with CUP suspected of being renal in origin was ineffective systemic chemotherapy, making a specific diagnosis of more academic interest than clinical importance.
“This situation has now changed because of the introduction of several targeted agents and immune checkpoint blockers that improve survival in patients with advanced RCC. It is likely that these new RCC treatments are also more effective than empiric chemotherapy for patients with CUP who have an occult renal primary site. Therefore, recognition of the RCC subset of patients within the CUP population has practical therapeutic importance,” they wrote.
Dr. Greco and Dr. Hainsworth conducted a retrospective review of patients at their center with CUP from 2008 through 2013 who had RCC predicted by MCCA.
A total of 539 patients presented with CUP during the study period, and of this group, 24 (4.4%) had RCC identified by MCCA.
The patients, 18 men and 6 women, with a median age of 61 years, all had abdominal CT scans that failed to show renal lesions suggestive of a primary RCC. Nine of the 24 patients had baseline MCCA performed as part of a prospective phase 2 clinical trial; the other 15 were patients treated at the center who had MCCA performed later in the clinical course, usually during or after first-line empiric chemotherapy.
Sixteen patients had metastases in the retroperitoneum, 10 in the mediastinum, 6 in bone, 5 in the liver, and 5 in lungs and/or pleura.
Pathologic studies using light microscopy showed poorly differentiated carcinomas in eight patients, poorly differentiated adenocarcinomas in nine, and well or moderately differentiated adenocarcinomas in seven patients.
A pathologist identified RCC as the possible primary in only 4 of the 24 patients. Immunohistochemistry tests in these patients were consistent with a diagnosis of RCC. Only 5 of the 24 had focal features suggestive of RCC, including one clear-cell and four papillary histologies.
Sixteen of the 24 patients received first-line treatment for advanced RCC, including sunitinib, temsirolimus, bevacizumab, and/or interleukin 1. Four other patients received RCC-specific therapy following empiric chemotherapy (three patients who received RCC-specific therapies in the first line also received it in the second line).
Among the 16 patients who received first-line RCC-specific therapies there were 3 partial responses (PR), 10 cases of stable disease (SD), 2 of progressive disease (PD), and 1 patient was not evaluable. The median duration of both PR and SD was 8 months.
Of the eight patients who received first-line empiric chemotherapy, one had a PR, two had SD, and five had PD.
For the seven patients who received second-line RCC-specific therapy after either first-line chemotherapy or site-specific therapy, responses included one PR, two SD, two PD, and two not evaluable.
Median survival for all 24 patients was 12 months (range 2 to more than 43 months). Median survival of the 16 patients who received first-line RCC-specific treatment was 14 months (range 2-25 months).
Median survival for all 20 patients who received RCC-specific treatment at some time during their course was 16 months (range, 2 to more than 43 months).
The authors called for further prospective studies of this subset of patients with CUP.
SOURCE: Greco FA, Hainsworth JD. Clin Genitourin Cancer. 2018 Aug;16(4):e893-8.
Gene expression profiling and/or immunohistochemistry can identify occult renal cell carcinoma (RCC) in a subset of patients diagnosed with carcinoma of unknown primary (CUP), suggesting that these patients could benefit from RCC-specific targeted therapy or immunotherapy, investigators contend.
Of 539 patients presenting at a single center with CUP, a 92-gene reverse transcription polymerase chain reaction molecular cancer classifier assay (MCCA) performed on biopsy specimens identified 24 as having RCC. All of the patients had clinical characteristics typical of advanced RCC, but none had suspicious renal lesions on CT scans, reported F. Anthony Greco, MD and John D. Hainsworth, MD, of the Sarah Cannon Cancer Center and Research Institute in Nashville, Tenn.
“Although further experience is necessary, these patients responded to RCC-specific therapy in a manner consistent with advanced RCC. These patients are unlikely to benefit from treatment with empiric chemotherapy. The reliable identification of RCC patients within the heterogeneous CUP population is possible using MCCA, and has potentially important therapeutic implications,” they wrote. The report was published in Clinical Genitourinary Cancer.
They noted that previously the only therapeutic option for patients with CUP suspected of being renal in origin was ineffective systemic chemotherapy, making a specific diagnosis of more academic interest than clinical importance.
“This situation has now changed because of the introduction of several targeted agents and immune checkpoint blockers that improve survival in patients with advanced RCC. It is likely that these new RCC treatments are also more effective than empiric chemotherapy for patients with CUP who have an occult renal primary site. Therefore, recognition of the RCC subset of patients within the CUP population has practical therapeutic importance,” they wrote.
Dr. Greco and Dr. Hainsworth conducted a retrospective review of patients at their center with CUP from 2008 through 2013 who had RCC predicted by MCCA.
A total of 539 patients presented with CUP during the study period, and of this group, 24 (4.4%) had RCC identified by MCCA.
The patients, 18 men and 6 women, with a median age of 61 years, all had abdominal CT scans that failed to show renal lesions suggestive of a primary RCC. Nine of the 24 patients had baseline MCCA performed as part of a prospective phase 2 clinical trial; the other 15 were patients treated at the center who had MCCA performed later in the clinical course, usually during or after first-line empiric chemotherapy.
Sixteen patients had metastases in the retroperitoneum, 10 in the mediastinum, 6 in bone, 5 in the liver, and 5 in lungs and/or pleura.
Pathologic studies using light microscopy showed poorly differentiated carcinomas in eight patients, poorly differentiated adenocarcinomas in nine, and well or moderately differentiated adenocarcinomas in seven patients.
A pathologist identified RCC as the possible primary in only 4 of the 24 patients. Immunohistochemistry tests in these patients were consistent with a diagnosis of RCC. Only 5 of the 24 had focal features suggestive of RCC, including one clear-cell and four papillary histologies.
Sixteen of the 24 patients received first-line treatment for advanced RCC, including sunitinib, temsirolimus, bevacizumab, and/or interleukin 1. Four other patients received RCC-specific therapy following empiric chemotherapy (three patients who received RCC-specific therapies in the first line also received it in the second line).
Among the 16 patients who received first-line RCC-specific therapies there were 3 partial responses (PR), 10 cases of stable disease (SD), 2 of progressive disease (PD), and 1 patient was not evaluable. The median duration of both PR and SD was 8 months.
Of the eight patients who received first-line empiric chemotherapy, one had a PR, two had SD, and five had PD.
For the seven patients who received second-line RCC-specific therapy after either first-line chemotherapy or site-specific therapy, responses included one PR, two SD, two PD, and two not evaluable.
Median survival for all 24 patients was 12 months (range 2 to more than 43 months). Median survival of the 16 patients who received first-line RCC-specific treatment was 14 months (range 2-25 months).
Median survival for all 20 patients who received RCC-specific treatment at some time during their course was 16 months (range, 2 to more than 43 months).
The authors called for further prospective studies of this subset of patients with CUP.
SOURCE: Greco FA, Hainsworth JD. Clin Genitourin Cancer. 2018 Aug;16(4):e893-8.
Gene expression profiling and/or immunohistochemistry can identify occult renal cell carcinoma (RCC) in a subset of patients diagnosed with carcinoma of unknown primary (CUP), suggesting that these patients could benefit from RCC-specific targeted therapy or immunotherapy, investigators contend.
Of 539 patients presenting at a single center with CUP, a 92-gene reverse transcription polymerase chain reaction molecular cancer classifier assay (MCCA) performed on biopsy specimens identified 24 as having RCC. All of the patients had clinical characteristics typical of advanced RCC, but none had suspicious renal lesions on CT scans, reported F. Anthony Greco, MD and John D. Hainsworth, MD, of the Sarah Cannon Cancer Center and Research Institute in Nashville, Tenn.
“Although further experience is necessary, these patients responded to RCC-specific therapy in a manner consistent with advanced RCC. These patients are unlikely to benefit from treatment with empiric chemotherapy. The reliable identification of RCC patients within the heterogeneous CUP population is possible using MCCA, and has potentially important therapeutic implications,” they wrote. The report was published in Clinical Genitourinary Cancer.
They noted that previously the only therapeutic option for patients with CUP suspected of being renal in origin was ineffective systemic chemotherapy, making a specific diagnosis of more academic interest than clinical importance.
“This situation has now changed because of the introduction of several targeted agents and immune checkpoint blockers that improve survival in patients with advanced RCC. It is likely that these new RCC treatments are also more effective than empiric chemotherapy for patients with CUP who have an occult renal primary site. Therefore, recognition of the RCC subset of patients within the CUP population has practical therapeutic importance,” they wrote.
Dr. Greco and Dr. Hainsworth conducted a retrospective review of patients at their center with CUP from 2008 through 2013 who had RCC predicted by MCCA.
A total of 539 patients presented with CUP during the study period, and of this group, 24 (4.4%) had RCC identified by MCCA.
The patients, 18 men and 6 women, with a median age of 61 years, all had abdominal CT scans that failed to show renal lesions suggestive of a primary RCC. Nine of the 24 patients had baseline MCCA performed as part of a prospective phase 2 clinical trial; the other 15 were patients treated at the center who had MCCA performed later in the clinical course, usually during or after first-line empiric chemotherapy.
Sixteen patients had metastases in the retroperitoneum, 10 in the mediastinum, 6 in bone, 5 in the liver, and 5 in lungs and/or pleura.
Pathologic studies using light microscopy showed poorly differentiated carcinomas in eight patients, poorly differentiated adenocarcinomas in nine, and well or moderately differentiated adenocarcinomas in seven patients.
A pathologist identified RCC as the possible primary in only 4 of the 24 patients. Immunohistochemistry tests in these patients were consistent with a diagnosis of RCC. Only 5 of the 24 had focal features suggestive of RCC, including one clear-cell and four papillary histologies.
Sixteen of the 24 patients received first-line treatment for advanced RCC, including sunitinib, temsirolimus, bevacizumab, and/or interleukin 1. Four other patients received RCC-specific therapy following empiric chemotherapy (three patients who received RCC-specific therapies in the first line also received it in the second line).
Among the 16 patients who received first-line RCC-specific therapies there were 3 partial responses (PR), 10 cases of stable disease (SD), 2 of progressive disease (PD), and 1 patient was not evaluable. The median duration of both PR and SD was 8 months.
Of the eight patients who received first-line empiric chemotherapy, one had a PR, two had SD, and five had PD.
For the seven patients who received second-line RCC-specific therapy after either first-line chemotherapy or site-specific therapy, responses included one PR, two SD, two PD, and two not evaluable.
Median survival for all 24 patients was 12 months (range 2 to more than 43 months). Median survival of the 16 patients who received first-line RCC-specific treatment was 14 months (range 2-25 months).
Median survival for all 20 patients who received RCC-specific treatment at some time during their course was 16 months (range, 2 to more than 43 months).
The authors called for further prospective studies of this subset of patients with CUP.
SOURCE: Greco FA, Hainsworth JD. Clin Genitourin Cancer. 2018 Aug;16(4):e893-8.
FROM CLINICAL GENITOURINARY CANCER
Key clinical point: Some carcinomas of unknown primary (CUP) can be identified as renal in origin by molecular assays and treated accordingly.
Major finding: Molecular assays identified RCC as the primary in 24 of 539 patients with CUP.
Study details: Retrospective review of patients with CUP presenting at a single center from 2008 through 2013.
Disclosures: The Minnie Pearl Cancer Research Foundation supported the study. Dr. Greco disclosed a consultant role and speakers bureau activities for bioTheranostics.
Source: Greco FA, Hainsworth JD. Clinical Genitourinary Cancer 16(4): e893-8.
Rituximab reduces risk of follicular lymphoma transformation
Rituximab-based chemotherapy can significantly reduce the risk of transformation of follicular lymphoma (FL) from an indolent to an aggressive histology, such as diffuse large B-cell lymphoma, results of a retrospective pooled analysis have suggested.
“Despite the intrinsic limitations related to the retrospective nature of our study, we confirmed that the cumulative hazard of histological transformation as a first event in follicular lymphoma can be reduced significantly by introducing rituximab to a backbone therapy. Moreover, our data also confirm that histological transformation still has an adverse effect on patient outcome, although it is less catastrophic than the pre-rituximab regimens,” they wrote in the Lancet Haematology.
These investigators, from 11 cooperative groups or institutions across Europe, pooled data on patients aged 18 years and older who had a histologically confirmed diagnosis of grade 1, 2, or 3a FL between Jan. 2, 1997, and Dec. 20, 2013.
They defined histologic transformation as a biopsy-proven aggressive lymphoma that occurred as a first event after first-line therapy.
Data on a total of 8,116 patients were available for analysis; 509 of these patients had had histologic transformations. After a median follow-up of 87 months, the 10-year cumulative hazard for all patients was 7.7%. The 10-year cumulative hazard – one of two primary endpoints – was 5.2% for patients who had received any rituximab versus 8.7% for those who did not, which translated into a hazard ratio of 0.73 (P = .004).
Among patients who received rituximab during induction only, the 10-year cumulative hazard was 5.9%, and it was 3.6% among those who received rituximab during induction and maintenance phases of treatment. This difference translated into a HR of 0.55 (P = .003).
The benefit of rituximab induction and maintenance – compared with induction only – held up in a multivariate analysis controlling for age at diagnosis, sex, FLIPI (Follicular Lymphoma International Prognostic Index) score, active surveillance vs. treatment, and FL grade (HR, 0.55; P = .016).
There were 287 deaths among the 509 patients with transformation, resulting in a 10-year survival after transformation of 32%.
The 5-year survival after transformation was 38% for patients who were not exposed to rituximab, 42% for patients who received induction rituximab, and 43% for those who received both induction and maintenance rituximab, but the differences between the three groups were not statistically significant.
“More comprehensive knowledge of the biological risk factors for follicular lymphoma transformation and the molecular pathways involved is likely to help clinicians make more accurate prognostic assessments and also inform the potential usefulness of novel drugs for the treatment of follicular lymphoma,” the researchers wrote.
The study was funded by the European Lymphoma Institute and other research groups. The researchers reported having no financial disclosures.
SOURCE: Federico M et al. Lancet Haematol. 2018 Jul 4. doi: 10.1016/S2352-3026(18)30090-5.
Rituximab-based chemotherapy can significantly reduce the risk of transformation of follicular lymphoma (FL) from an indolent to an aggressive histology, such as diffuse large B-cell lymphoma, results of a retrospective pooled analysis have suggested.
“Despite the intrinsic limitations related to the retrospective nature of our study, we confirmed that the cumulative hazard of histological transformation as a first event in follicular lymphoma can be reduced significantly by introducing rituximab to a backbone therapy. Moreover, our data also confirm that histological transformation still has an adverse effect on patient outcome, although it is less catastrophic than the pre-rituximab regimens,” they wrote in the Lancet Haematology.
These investigators, from 11 cooperative groups or institutions across Europe, pooled data on patients aged 18 years and older who had a histologically confirmed diagnosis of grade 1, 2, or 3a FL between Jan. 2, 1997, and Dec. 20, 2013.
They defined histologic transformation as a biopsy-proven aggressive lymphoma that occurred as a first event after first-line therapy.
Data on a total of 8,116 patients were available for analysis; 509 of these patients had had histologic transformations. After a median follow-up of 87 months, the 10-year cumulative hazard for all patients was 7.7%. The 10-year cumulative hazard – one of two primary endpoints – was 5.2% for patients who had received any rituximab versus 8.7% for those who did not, which translated into a hazard ratio of 0.73 (P = .004).
Among patients who received rituximab during induction only, the 10-year cumulative hazard was 5.9%, and it was 3.6% among those who received rituximab during induction and maintenance phases of treatment. This difference translated into a HR of 0.55 (P = .003).
The benefit of rituximab induction and maintenance – compared with induction only – held up in a multivariate analysis controlling for age at diagnosis, sex, FLIPI (Follicular Lymphoma International Prognostic Index) score, active surveillance vs. treatment, and FL grade (HR, 0.55; P = .016).
There were 287 deaths among the 509 patients with transformation, resulting in a 10-year survival after transformation of 32%.
The 5-year survival after transformation was 38% for patients who were not exposed to rituximab, 42% for patients who received induction rituximab, and 43% for those who received both induction and maintenance rituximab, but the differences between the three groups were not statistically significant.
“More comprehensive knowledge of the biological risk factors for follicular lymphoma transformation and the molecular pathways involved is likely to help clinicians make more accurate prognostic assessments and also inform the potential usefulness of novel drugs for the treatment of follicular lymphoma,” the researchers wrote.
The study was funded by the European Lymphoma Institute and other research groups. The researchers reported having no financial disclosures.
SOURCE: Federico M et al. Lancet Haematol. 2018 Jul 4. doi: 10.1016/S2352-3026(18)30090-5.
Rituximab-based chemotherapy can significantly reduce the risk of transformation of follicular lymphoma (FL) from an indolent to an aggressive histology, such as diffuse large B-cell lymphoma, results of a retrospective pooled analysis have suggested.
“Despite the intrinsic limitations related to the retrospective nature of our study, we confirmed that the cumulative hazard of histological transformation as a first event in follicular lymphoma can be reduced significantly by introducing rituximab to a backbone therapy. Moreover, our data also confirm that histological transformation still has an adverse effect on patient outcome, although it is less catastrophic than the pre-rituximab regimens,” they wrote in the Lancet Haematology.
These investigators, from 11 cooperative groups or institutions across Europe, pooled data on patients aged 18 years and older who had a histologically confirmed diagnosis of grade 1, 2, or 3a FL between Jan. 2, 1997, and Dec. 20, 2013.
They defined histologic transformation as a biopsy-proven aggressive lymphoma that occurred as a first event after first-line therapy.
Data on a total of 8,116 patients were available for analysis; 509 of these patients had had histologic transformations. After a median follow-up of 87 months, the 10-year cumulative hazard for all patients was 7.7%. The 10-year cumulative hazard – one of two primary endpoints – was 5.2% for patients who had received any rituximab versus 8.7% for those who did not, which translated into a hazard ratio of 0.73 (P = .004).
Among patients who received rituximab during induction only, the 10-year cumulative hazard was 5.9%, and it was 3.6% among those who received rituximab during induction and maintenance phases of treatment. This difference translated into a HR of 0.55 (P = .003).
The benefit of rituximab induction and maintenance – compared with induction only – held up in a multivariate analysis controlling for age at diagnosis, sex, FLIPI (Follicular Lymphoma International Prognostic Index) score, active surveillance vs. treatment, and FL grade (HR, 0.55; P = .016).
There were 287 deaths among the 509 patients with transformation, resulting in a 10-year survival after transformation of 32%.
The 5-year survival after transformation was 38% for patients who were not exposed to rituximab, 42% for patients who received induction rituximab, and 43% for those who received both induction and maintenance rituximab, but the differences between the three groups were not statistically significant.
“More comprehensive knowledge of the biological risk factors for follicular lymphoma transformation and the molecular pathways involved is likely to help clinicians make more accurate prognostic assessments and also inform the potential usefulness of novel drugs for the treatment of follicular lymphoma,” the researchers wrote.
The study was funded by the European Lymphoma Institute and other research groups. The researchers reported having no financial disclosures.
SOURCE: Federico M et al. Lancet Haematol. 2018 Jul 4. doi: 10.1016/S2352-3026(18)30090-5.
FROM THE LANCET HAEMATOLOGY
Key clinical point:
Major finding: The 10-year cumulative hazard of histologic transformation was 5.2% for patients who had received rituximab and 8.7% for those who had not.
Study details: Retrospective pooled analysis of 8,116 patients with FL, 509 of whom had transformation over a 10-year period.
Disclosures: The study was funded by Associazione Angela Serra per la Ricerca sul Cancro, European Lymphoma Institute, European Hematology Association Lymphoma Group, Fondazione Italiana Linfomi, and the Spanish Group of Lymphoma and Bone Marrow Transplantation. The researchers reported having no financial disclosures.
Source: Federico M et al. Lancet Haematol. 2018 Jul 4. doi: 10.1016/S2352-3026(18)30090-5.