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No link between methylation, survival in ovarian cancer
NATIONAL HARBOR, MD. – Unlike mutation, methylation of homologous recombination DNA repair pathway genes was not linked to longer survival or platinum sensitivity in high-grade serous ovarian cancer, according to molecular and clinical analyses of 332 patients.
“Methylation may be more readily reversed than mutation, allowing more rapid development of platinum resistance and negating any impact on overall survival,” said Sarah Bernards, a second-year medical student at the University of Washington, Seattle, who presented the findings at the annual meeting of the Society of Gynecologic Oncology.
The homologous recombination (HR) DNA repair pathway is critical for repairing cross-linking and double-strand breaks, Ms. Bernards noted. Genes such as BRCA1, BRCA2, and RAD51C are important in this pathway, and inherited and sporadic mutations of these genes can lead to ovarian carcinoma. Importantly, ovarian cancers with HR gene mutations are more sensitive to platinum and radiation therapy and are associated with longer progression-free survival and overall survival compared with ovarian cancers without these mutations.
Methylation of the promoter regions of BRCA1 and RAD51C reduces expression of these genes and has been found to be associated with high-grade serous ovarian cancer, Ms. Bernards explained. One previous study found promoter methylations of BRCA1 and RAD51C in 11.5% and 3% of such tumors, respectively (Nature. 2011;474[7353]:609-15).
To further characterize HR gene methylations, Ms. Bernards and her associates used methylation-sensitive PCR to analyze ovarian carcinomas from patients who underwent primary debulking surgery and were enrolled in the University of Washington gynecologic oncology tissue bank. They also tested for damaging germline and somatic mutations in 16 HR DNA repair genes.
In all, 28% of cases had mutations in HR repair pathway genes, 7% had a BRCA1 methylation, and 3% had RAD51C methylation. BRCA1 and RAD51C methylation never overlapped with mutation (P = .001), and almost never overlapped with mutations in other HR DNA repair pathway genes, Ms. Bernards said.
Fully two-thirds of BRCA1 mutated cases were sensitive to chemotherapy, compared with 59% of BRCA1 methylated cases and 53% of wild-type BRCA1 cases (P = .03). Mutations of any HR DNA repair gene were associated with improved overall survival (hazard ratio, 0.7; 95% confidence interval, 0.5-0.9; P = .02), but methylation of RAD51C and BRCA1 was not (P = .3). Patients with HR gene mutations survived a median of 66 months after diagnosis, compared with 41 months for patients with RAD51C methylation and 43 months for patients with BRCA1 methylation.
Median age at diagnosis was 53 years for BRCA1 mutated cases (P less than .0001) and 55 years for BRCA1 methylated cases (P = .03), significantly lower than the 63-year median age for diagnosis of wild-type BRCA1 cases. High-grade histology characterized 71% of wild-type BRCA1 cases, compared with 82% of BRCA1 mutated cases (P = .001) and 91% of BRCA1 methylated cases (P = .05). Somatic TP53 mutations occurred in 67% of wild-type cases, 89% of mutated cases (P = .004), and 82% of methylated cases (P = .01).
To sum up, both methylation and mutation of BRCA1 were associated with younger age at diagnosis, high-grade histology, and TP53 mutations, but only BRCA1 mutation was tied to improved overall survival or platinum sensitivity, Ms. Bernards said.
The work was supported by a grant from the University of Washington School of Medicine Medical Student Research Training Program. Ms. Bernards conducted the work under Elizabeth Swisher, MD, a medical oncologist and head of the Swisher Lab at the University of Washington, Seattle. Ms. Bernards reported having no conflicts of interest.
NATIONAL HARBOR, MD. – Unlike mutation, methylation of homologous recombination DNA repair pathway genes was not linked to longer survival or platinum sensitivity in high-grade serous ovarian cancer, according to molecular and clinical analyses of 332 patients.
“Methylation may be more readily reversed than mutation, allowing more rapid development of platinum resistance and negating any impact on overall survival,” said Sarah Bernards, a second-year medical student at the University of Washington, Seattle, who presented the findings at the annual meeting of the Society of Gynecologic Oncology.
The homologous recombination (HR) DNA repair pathway is critical for repairing cross-linking and double-strand breaks, Ms. Bernards noted. Genes such as BRCA1, BRCA2, and RAD51C are important in this pathway, and inherited and sporadic mutations of these genes can lead to ovarian carcinoma. Importantly, ovarian cancers with HR gene mutations are more sensitive to platinum and radiation therapy and are associated with longer progression-free survival and overall survival compared with ovarian cancers without these mutations.
Methylation of the promoter regions of BRCA1 and RAD51C reduces expression of these genes and has been found to be associated with high-grade serous ovarian cancer, Ms. Bernards explained. One previous study found promoter methylations of BRCA1 and RAD51C in 11.5% and 3% of such tumors, respectively (Nature. 2011;474[7353]:609-15).
To further characterize HR gene methylations, Ms. Bernards and her associates used methylation-sensitive PCR to analyze ovarian carcinomas from patients who underwent primary debulking surgery and were enrolled in the University of Washington gynecologic oncology tissue bank. They also tested for damaging germline and somatic mutations in 16 HR DNA repair genes.
In all, 28% of cases had mutations in HR repair pathway genes, 7% had a BRCA1 methylation, and 3% had RAD51C methylation. BRCA1 and RAD51C methylation never overlapped with mutation (P = .001), and almost never overlapped with mutations in other HR DNA repair pathway genes, Ms. Bernards said.
Fully two-thirds of BRCA1 mutated cases were sensitive to chemotherapy, compared with 59% of BRCA1 methylated cases and 53% of wild-type BRCA1 cases (P = .03). Mutations of any HR DNA repair gene were associated with improved overall survival (hazard ratio, 0.7; 95% confidence interval, 0.5-0.9; P = .02), but methylation of RAD51C and BRCA1 was not (P = .3). Patients with HR gene mutations survived a median of 66 months after diagnosis, compared with 41 months for patients with RAD51C methylation and 43 months for patients with BRCA1 methylation.
Median age at diagnosis was 53 years for BRCA1 mutated cases (P less than .0001) and 55 years for BRCA1 methylated cases (P = .03), significantly lower than the 63-year median age for diagnosis of wild-type BRCA1 cases. High-grade histology characterized 71% of wild-type BRCA1 cases, compared with 82% of BRCA1 mutated cases (P = .001) and 91% of BRCA1 methylated cases (P = .05). Somatic TP53 mutations occurred in 67% of wild-type cases, 89% of mutated cases (P = .004), and 82% of methylated cases (P = .01).
To sum up, both methylation and mutation of BRCA1 were associated with younger age at diagnosis, high-grade histology, and TP53 mutations, but only BRCA1 mutation was tied to improved overall survival or platinum sensitivity, Ms. Bernards said.
The work was supported by a grant from the University of Washington School of Medicine Medical Student Research Training Program. Ms. Bernards conducted the work under Elizabeth Swisher, MD, a medical oncologist and head of the Swisher Lab at the University of Washington, Seattle. Ms. Bernards reported having no conflicts of interest.
NATIONAL HARBOR, MD. – Unlike mutation, methylation of homologous recombination DNA repair pathway genes was not linked to longer survival or platinum sensitivity in high-grade serous ovarian cancer, according to molecular and clinical analyses of 332 patients.
“Methylation may be more readily reversed than mutation, allowing more rapid development of platinum resistance and negating any impact on overall survival,” said Sarah Bernards, a second-year medical student at the University of Washington, Seattle, who presented the findings at the annual meeting of the Society of Gynecologic Oncology.
The homologous recombination (HR) DNA repair pathway is critical for repairing cross-linking and double-strand breaks, Ms. Bernards noted. Genes such as BRCA1, BRCA2, and RAD51C are important in this pathway, and inherited and sporadic mutations of these genes can lead to ovarian carcinoma. Importantly, ovarian cancers with HR gene mutations are more sensitive to platinum and radiation therapy and are associated with longer progression-free survival and overall survival compared with ovarian cancers without these mutations.
Methylation of the promoter regions of BRCA1 and RAD51C reduces expression of these genes and has been found to be associated with high-grade serous ovarian cancer, Ms. Bernards explained. One previous study found promoter methylations of BRCA1 and RAD51C in 11.5% and 3% of such tumors, respectively (Nature. 2011;474[7353]:609-15).
To further characterize HR gene methylations, Ms. Bernards and her associates used methylation-sensitive PCR to analyze ovarian carcinomas from patients who underwent primary debulking surgery and were enrolled in the University of Washington gynecologic oncology tissue bank. They also tested for damaging germline and somatic mutations in 16 HR DNA repair genes.
In all, 28% of cases had mutations in HR repair pathway genes, 7% had a BRCA1 methylation, and 3% had RAD51C methylation. BRCA1 and RAD51C methylation never overlapped with mutation (P = .001), and almost never overlapped with mutations in other HR DNA repair pathway genes, Ms. Bernards said.
Fully two-thirds of BRCA1 mutated cases were sensitive to chemotherapy, compared with 59% of BRCA1 methylated cases and 53% of wild-type BRCA1 cases (P = .03). Mutations of any HR DNA repair gene were associated with improved overall survival (hazard ratio, 0.7; 95% confidence interval, 0.5-0.9; P = .02), but methylation of RAD51C and BRCA1 was not (P = .3). Patients with HR gene mutations survived a median of 66 months after diagnosis, compared with 41 months for patients with RAD51C methylation and 43 months for patients with BRCA1 methylation.
Median age at diagnosis was 53 years for BRCA1 mutated cases (P less than .0001) and 55 years for BRCA1 methylated cases (P = .03), significantly lower than the 63-year median age for diagnosis of wild-type BRCA1 cases. High-grade histology characterized 71% of wild-type BRCA1 cases, compared with 82% of BRCA1 mutated cases (P = .001) and 91% of BRCA1 methylated cases (P = .05). Somatic TP53 mutations occurred in 67% of wild-type cases, 89% of mutated cases (P = .004), and 82% of methylated cases (P = .01).
To sum up, both methylation and mutation of BRCA1 were associated with younger age at diagnosis, high-grade histology, and TP53 mutations, but only BRCA1 mutation was tied to improved overall survival or platinum sensitivity, Ms. Bernards said.
The work was supported by a grant from the University of Washington School of Medicine Medical Student Research Training Program. Ms. Bernards conducted the work under Elizabeth Swisher, MD, a medical oncologist and head of the Swisher Lab at the University of Washington, Seattle. Ms. Bernards reported having no conflicts of interest.
AT THE ANNUAL MEETING ON WOMEN’S CANCER
Key clinical point: Unlike mutation, methylation of BRCA1 was not linked to longer survival or platinum sensitivity in high-grade serous ovarian cancer.
Major finding: Fully two-thirds of BRCA1 mutated cases were platinum-sensitive compared with 59% of BRCA1 methylated cases and 53% of wild-type BRCA1 cases (P = .03). Mutations of HR DNA repair genes were associated with improved overall survival (hazard ratio, 0.7; 95% confidence interval, 0.5-0.9; P = .02), but methylation of BRCA1 and RAD51C was not (P = .3).
Data source: Methylation-sensitive PCR and clinical assessment of 332 primary ovarian carcinomas.
Disclosures: The University of Washington School of Medicine Medical Student Research Training Program supported the work. Ms. Bernards reported having no conflicts of interest.
Experts warn against readmissions as sole quality measure in ovarian cancer
NATIONAL HARBOR, MD. – For patients with ovarian cancer, focusing solely on hospital readmission rates as a quality measure might worsen long-term outcomes while unfairly penalizing the best hospitals, suggest the results of two analyses of the National Cancer Database presented at the annual meeting of the Society of Gynecologic Oncology.
Hospitals with the highest ovarian cancer caseloads had the best rates of overall survival and postsurgical mortality, but also had the highest rates of readmission within 30 days after postsurgical discharge, reported Shitanshu Uppal, MBBS, of the obstetrics and gynecology department at the University of Michigan in Ann Arbor.
A separate analysis linked neoadjuvant chemotherapy with significantly fewer readmissions, but also with significantly worse overall survival compared with primary debulking surgery, reported Emma L. Barber, MD, of the University of North Carolina at Chapel Hill.
“Policies that prioritize decreased readmission rates inherently encourage neoadjuvant chemotherapy over primary debulking surgery,” Dr. Barber stressed. She recommended that policies and incentive programs incorporate both short- and long-term outcomes for patients with ovarian cancer.
Thirty-day hospital readmissions cost Medicare $17.4 billion in 2004 alone, noted Dr. Uppal. Research shows that almost one in seven patients is readmitted to the hospital within 30 days of discharge after major surgery, and that high-volume hospitals with low surgical mortality rates have lower surgical readmission rates than other hospitals do (N Engl J Med. 2013;369:1134-42).
Accordingly, the Centers for Medicare and Medicaid Services limits reimbursements if hospitals exceed 30-day readmission thresholds after surgeries for certain conditions, including acute myocardial infarction, heart failure, pneumonia, chronic obstructive pulmonary disease, coronary artery disease, and total hip and total knee arthroplasty. For now, these procedures do not include primary or interval debulking, but hospitals do monitor readmission rates, in general, as part of the Hospital Readmission Reduction Program, Dr. Barber noted.
Studies of ovarian cancer have shown postsurgical readmission rates of 10%-20%, Dr. Uppal said. To evaluate readmissions as a quality metric in this setting, he and his associates identified patients diagnosed with stage III or stage IV high-grade serous carcinoma between 2004 and 2013 who underwent cytoreductive surgery as primary treatment. More than 44,000 patients meeting these criteria were treated at hospitals that handled anywhere from under 10 to more than 30 cases annually.
The overall rate of unplanned readmissions was 6.2% (95% confidence interval, 5.2%-6.4%), and patients resembled each other clinically and demographically, irrespective of hospital caseload, Dr. Uppal said. After adjustment for other risk factors for readmission, including higher-stage disease, hospitals that treated more than 30 cases of ovarian cancer per year had significantly higher 30-day readmission rates than did the lowest-volume hospitals – nearly 10%, compared with about 7.5% (adjusted odd ratio, 1.25; 95% CI, 1.1-1.5; P less than .05). However, high-volume hospitals had the lowest 30-day and 90-day mortality rates (P less than .05), the highest rate of 5-year overall survival (adjusted hazard ratio, 0.83; 95% CI, 0.78-0.88; P less than .05), and a significantly higher frequency of adherence to NCCN guidelines compared with low-volume hospitals.
“Not all readmissions reflect a failed discharge,” Dr. Uppal emphasized. “Certain readmissions may be appropriate and necessary, and some surgeries merit appropriate aggression and result in a high readmission rate.”
The study by Dr. Barber included data from nearly 27,000 patients who underwent chemotherapy and surgery for stage IIIC epithelial ovarian cancer at Commission on Cancer–accredited institutions between 2006 and 2012. The overall 30-day readmission rate was 11%, and 57% of readmissions were unplanned. About 16% of patients received neoadjuvant chemotherapy followed by interval debulking surgery, and the rest underwent primary debulking surgery, Dr. Barber said.
Rates of 30-day readmissions were 6.5% after neoadjuvant chemotherapy with interval debulking, compared with 12% after primary debulking. Neoadjuvant chemotherapy was associated with a 48% drop in the risk of readmission and with a 37% decrease in the chances of unplanned readmission after the researchers controlled for age, race, insurance status, comorbidities, and histology, Dr. Barber said. However, primary debulking significantly increased the chances of survival at next follow-up (HR, 1.36; 95% CI, 1.29-1.42; P less than .001). Median overall survival was 47 months with primary debulking surgery and 37 months with neoadjuvant chemotherapy (P less than .001).
These findings show how broad health policies that are not designed for specific patient subgroups can create unique, unintended, and undesirable incentives and consequences, Dr. Barber said. Unfairly penalizing high-volume hospitals by concentrating solely on readmissions, rather than taking a more holistic view of cancer care, could inadvertently encourage the use of less aggressive debulking surgeries and increase the use of neoadjuvant therapies in cases where primary debulking is more appropriate, Dr. Uppal added.
Dr. Barber and Dr. Uppal acknowledged no external funding sources and reported having no conflicts of interest.
NATIONAL HARBOR, MD. – For patients with ovarian cancer, focusing solely on hospital readmission rates as a quality measure might worsen long-term outcomes while unfairly penalizing the best hospitals, suggest the results of two analyses of the National Cancer Database presented at the annual meeting of the Society of Gynecologic Oncology.
Hospitals with the highest ovarian cancer caseloads had the best rates of overall survival and postsurgical mortality, but also had the highest rates of readmission within 30 days after postsurgical discharge, reported Shitanshu Uppal, MBBS, of the obstetrics and gynecology department at the University of Michigan in Ann Arbor.
A separate analysis linked neoadjuvant chemotherapy with significantly fewer readmissions, but also with significantly worse overall survival compared with primary debulking surgery, reported Emma L. Barber, MD, of the University of North Carolina at Chapel Hill.
“Policies that prioritize decreased readmission rates inherently encourage neoadjuvant chemotherapy over primary debulking surgery,” Dr. Barber stressed. She recommended that policies and incentive programs incorporate both short- and long-term outcomes for patients with ovarian cancer.
Thirty-day hospital readmissions cost Medicare $17.4 billion in 2004 alone, noted Dr. Uppal. Research shows that almost one in seven patients is readmitted to the hospital within 30 days of discharge after major surgery, and that high-volume hospitals with low surgical mortality rates have lower surgical readmission rates than other hospitals do (N Engl J Med. 2013;369:1134-42).
Accordingly, the Centers for Medicare and Medicaid Services limits reimbursements if hospitals exceed 30-day readmission thresholds after surgeries for certain conditions, including acute myocardial infarction, heart failure, pneumonia, chronic obstructive pulmonary disease, coronary artery disease, and total hip and total knee arthroplasty. For now, these procedures do not include primary or interval debulking, but hospitals do monitor readmission rates, in general, as part of the Hospital Readmission Reduction Program, Dr. Barber noted.
Studies of ovarian cancer have shown postsurgical readmission rates of 10%-20%, Dr. Uppal said. To evaluate readmissions as a quality metric in this setting, he and his associates identified patients diagnosed with stage III or stage IV high-grade serous carcinoma between 2004 and 2013 who underwent cytoreductive surgery as primary treatment. More than 44,000 patients meeting these criteria were treated at hospitals that handled anywhere from under 10 to more than 30 cases annually.
The overall rate of unplanned readmissions was 6.2% (95% confidence interval, 5.2%-6.4%), and patients resembled each other clinically and demographically, irrespective of hospital caseload, Dr. Uppal said. After adjustment for other risk factors for readmission, including higher-stage disease, hospitals that treated more than 30 cases of ovarian cancer per year had significantly higher 30-day readmission rates than did the lowest-volume hospitals – nearly 10%, compared with about 7.5% (adjusted odd ratio, 1.25; 95% CI, 1.1-1.5; P less than .05). However, high-volume hospitals had the lowest 30-day and 90-day mortality rates (P less than .05), the highest rate of 5-year overall survival (adjusted hazard ratio, 0.83; 95% CI, 0.78-0.88; P less than .05), and a significantly higher frequency of adherence to NCCN guidelines compared with low-volume hospitals.
“Not all readmissions reflect a failed discharge,” Dr. Uppal emphasized. “Certain readmissions may be appropriate and necessary, and some surgeries merit appropriate aggression and result in a high readmission rate.”
The study by Dr. Barber included data from nearly 27,000 patients who underwent chemotherapy and surgery for stage IIIC epithelial ovarian cancer at Commission on Cancer–accredited institutions between 2006 and 2012. The overall 30-day readmission rate was 11%, and 57% of readmissions were unplanned. About 16% of patients received neoadjuvant chemotherapy followed by interval debulking surgery, and the rest underwent primary debulking surgery, Dr. Barber said.
Rates of 30-day readmissions were 6.5% after neoadjuvant chemotherapy with interval debulking, compared with 12% after primary debulking. Neoadjuvant chemotherapy was associated with a 48% drop in the risk of readmission and with a 37% decrease in the chances of unplanned readmission after the researchers controlled for age, race, insurance status, comorbidities, and histology, Dr. Barber said. However, primary debulking significantly increased the chances of survival at next follow-up (HR, 1.36; 95% CI, 1.29-1.42; P less than .001). Median overall survival was 47 months with primary debulking surgery and 37 months with neoadjuvant chemotherapy (P less than .001).
These findings show how broad health policies that are not designed for specific patient subgroups can create unique, unintended, and undesirable incentives and consequences, Dr. Barber said. Unfairly penalizing high-volume hospitals by concentrating solely on readmissions, rather than taking a more holistic view of cancer care, could inadvertently encourage the use of less aggressive debulking surgeries and increase the use of neoadjuvant therapies in cases where primary debulking is more appropriate, Dr. Uppal added.
Dr. Barber and Dr. Uppal acknowledged no external funding sources and reported having no conflicts of interest.
NATIONAL HARBOR, MD. – For patients with ovarian cancer, focusing solely on hospital readmission rates as a quality measure might worsen long-term outcomes while unfairly penalizing the best hospitals, suggest the results of two analyses of the National Cancer Database presented at the annual meeting of the Society of Gynecologic Oncology.
Hospitals with the highest ovarian cancer caseloads had the best rates of overall survival and postsurgical mortality, but also had the highest rates of readmission within 30 days after postsurgical discharge, reported Shitanshu Uppal, MBBS, of the obstetrics and gynecology department at the University of Michigan in Ann Arbor.
A separate analysis linked neoadjuvant chemotherapy with significantly fewer readmissions, but also with significantly worse overall survival compared with primary debulking surgery, reported Emma L. Barber, MD, of the University of North Carolina at Chapel Hill.
“Policies that prioritize decreased readmission rates inherently encourage neoadjuvant chemotherapy over primary debulking surgery,” Dr. Barber stressed. She recommended that policies and incentive programs incorporate both short- and long-term outcomes for patients with ovarian cancer.
Thirty-day hospital readmissions cost Medicare $17.4 billion in 2004 alone, noted Dr. Uppal. Research shows that almost one in seven patients is readmitted to the hospital within 30 days of discharge after major surgery, and that high-volume hospitals with low surgical mortality rates have lower surgical readmission rates than other hospitals do (N Engl J Med. 2013;369:1134-42).
Accordingly, the Centers for Medicare and Medicaid Services limits reimbursements if hospitals exceed 30-day readmission thresholds after surgeries for certain conditions, including acute myocardial infarction, heart failure, pneumonia, chronic obstructive pulmonary disease, coronary artery disease, and total hip and total knee arthroplasty. For now, these procedures do not include primary or interval debulking, but hospitals do monitor readmission rates, in general, as part of the Hospital Readmission Reduction Program, Dr. Barber noted.
Studies of ovarian cancer have shown postsurgical readmission rates of 10%-20%, Dr. Uppal said. To evaluate readmissions as a quality metric in this setting, he and his associates identified patients diagnosed with stage III or stage IV high-grade serous carcinoma between 2004 and 2013 who underwent cytoreductive surgery as primary treatment. More than 44,000 patients meeting these criteria were treated at hospitals that handled anywhere from under 10 to more than 30 cases annually.
The overall rate of unplanned readmissions was 6.2% (95% confidence interval, 5.2%-6.4%), and patients resembled each other clinically and demographically, irrespective of hospital caseload, Dr. Uppal said. After adjustment for other risk factors for readmission, including higher-stage disease, hospitals that treated more than 30 cases of ovarian cancer per year had significantly higher 30-day readmission rates than did the lowest-volume hospitals – nearly 10%, compared with about 7.5% (adjusted odd ratio, 1.25; 95% CI, 1.1-1.5; P less than .05). However, high-volume hospitals had the lowest 30-day and 90-day mortality rates (P less than .05), the highest rate of 5-year overall survival (adjusted hazard ratio, 0.83; 95% CI, 0.78-0.88; P less than .05), and a significantly higher frequency of adherence to NCCN guidelines compared with low-volume hospitals.
“Not all readmissions reflect a failed discharge,” Dr. Uppal emphasized. “Certain readmissions may be appropriate and necessary, and some surgeries merit appropriate aggression and result in a high readmission rate.”
The study by Dr. Barber included data from nearly 27,000 patients who underwent chemotherapy and surgery for stage IIIC epithelial ovarian cancer at Commission on Cancer–accredited institutions between 2006 and 2012. The overall 30-day readmission rate was 11%, and 57% of readmissions were unplanned. About 16% of patients received neoadjuvant chemotherapy followed by interval debulking surgery, and the rest underwent primary debulking surgery, Dr. Barber said.
Rates of 30-day readmissions were 6.5% after neoadjuvant chemotherapy with interval debulking, compared with 12% after primary debulking. Neoadjuvant chemotherapy was associated with a 48% drop in the risk of readmission and with a 37% decrease in the chances of unplanned readmission after the researchers controlled for age, race, insurance status, comorbidities, and histology, Dr. Barber said. However, primary debulking significantly increased the chances of survival at next follow-up (HR, 1.36; 95% CI, 1.29-1.42; P less than .001). Median overall survival was 47 months with primary debulking surgery and 37 months with neoadjuvant chemotherapy (P less than .001).
These findings show how broad health policies that are not designed for specific patient subgroups can create unique, unintended, and undesirable incentives and consequences, Dr. Barber said. Unfairly penalizing high-volume hospitals by concentrating solely on readmissions, rather than taking a more holistic view of cancer care, could inadvertently encourage the use of less aggressive debulking surgeries and increase the use of neoadjuvant therapies in cases where primary debulking is more appropriate, Dr. Uppal added.
Dr. Barber and Dr. Uppal acknowledged no external funding sources and reported having no conflicts of interest.
AT THE ANNUAL MEETING ON WOMEN’S CANCER
Key clinical point: For patients with ovarian cancer, focusing solely on postsurgical hospital readmissions as a quality measure could worsen outcomes and might penalize the best hospitals.
Major finding: Hospitals that treated the most cases of ovarian cancer annually had significantly better rates of overall survival and postsurgical mortality, as well as the highest 30-day readmission rates (P less than .05). A separate analysis linked neoadjuvant chemotherapy with significantly fewer readmissions, but also with significantly worse overall survival compared with primary debulking surgery.
Data source: Two large retrospective analyses of the National Cancer Database.
Disclosures: Dr. Barber and Dr. Uppal acknowledged no external funding sources and reported having no conflicts of interest.
Maintenance taxane therapy of no benefit in advanced ovarian cancer
NATIONAL HARBOR, MD. – Using either a polymerized formulation of paclitaxel or paclitaxel alone as maintenance therapy conferred no survival benefit for women with advanced ovarian, fallopian tube, or peritoneal cancer.
In a phase III randomized trial, patients survived a median 54.8 months with surveillance alone, 51.3 months with maintenance paclitaxel, and 60.0 months with maintenance paclitaxel poliglumex; these differences were not statistically significant.
In a presentation at the annual meeting of the Society of Gynecologic Oncology, Larry Copeland, MD, a professor of gynecologic oncology at Ohio State University, Columbus, said that treatment with surgery and chemotherapy yields a clinical complete response in many patients with these cancers. However, he said, recurrent progressive disease is still very common; the rationale behind maintenance chemotherapy is that it may “reduce the risk of recurrence and extend survival.”
There had been promising earlier data supporting this approach from a previous phase III comparison trial that evaluated the difference in clinical complete response between 3 or 12 cycles of paclitaxel, said Dr. Copeland. The results of a predefined interim analysis prompted the data monitoring committee to close that study (J Clin Oncol. 2003;21[13]:2460-5) since the 12-cycle, 7-month arm of the study had better progression-free survival. However, the 12-cycle protocol did not confer a benefit in overall survival, the investigators later reported (Gynecol Oncol 2009;114[2]:195-8).
The current stage III randomized trial enrolled women with stage III or IV ovarian, fallopian tube, or peritoneal cancer who had had five to eight cycles of chemotherapy and achieved clinical complete response. If patients had neuropathy, it could not exceed grade 1, and their cancer performance status scores could not exceed 2, Dr. Copeland said.
Patients were randomized 1:1:1 to a surveillance arm, to receive paclitaxel as a 3-hour infusion, or to receive paclitaxel poliglumex as a 10- to 20-minute infusion. Both study drugs were dosed at 35 mg/m2 every 28 days for 12 cycles.
The study ran from March 2005 to January 2014, enrolling 1,157 patients who were followed for a median of 71 months. Over 80% of patients in each study arm had ovarian cancer, and a similar number had stage III cancer and serous histology. Over 90% of patients in each arm had grade 2 or higher histology.
The study was designed as a superiority design, and patients were not to receive other cancer treatments until they had disease progression. Primary clinical endpoints for the study included overall survival, quality of life as measured by the Ovarian Specific Questionnaire Quality of Life–Cancer, and patient-reported neurotoxicity as reported on the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group/Neurotoxicity questionnaire.
The third scheduled interim analysis, in May 2016, examined the primary endpoint of overall survival, triggered when at least 200 deaths occurred in the surveillance group. The overall final analysis had been scheduled for the point at which at least 301 deaths happened in the surveillance group. In the abstract accompanying the presentation, Dr. Copeland wrote that the data at the point of this interim analysis indicated that “the relative death hazards passed the futility boundaries for both taxane regimens.”
“The log-rank statistic for each taxane regimen was below the interval specific in the study design, making it unlikely either of the taxane regimens has superior overall survival compared to surveillance,” said Dr. Copeland.
The hazard ratio for overall survival of the paclitaxel group compared to surveillance was 1.104, with a 97.5% confidence interval (CI) of 0.884-1.38. For the paclitaxel poliglumex group, the hazard ratio compared to surveillance alone was 0.979 (97.5% CI, 0.781-1.23).
Dr. Copeland and his colleagues also looked at progression-free survival, not a primary endpoint of the study. For the paclitaxel patients compared to surveillance, the HR for progression-free survival was 0.783 (95% CI, 0.666-0.921). For paclitaxel poliglumex, the HR was 0.847 (95% CI, 0.666-0.921).
Not unexpectedly, more patients who received taxane treatment than those in the surveillance arm experienced adverse events, said Dr. Copeland. The most common adverse events were hypersensitivity or allergic reactions, fatigue, alopecia, nausea, constipation, and sensory neuropathies. Grade 2 alopecia was experienced by about a quarter of the paclitaxel poliglumex cohort, and by a little less than half of the paclitaxel cohort. Neurologic adverse events were very common, reported by three quarters of the paclitaxel poliglumex cohort, four in five of the paclitaxel group, and by a little over half of the surveillance cohort.
Overall quality of life scores did not differ significantly among the treatment arms.
In an exploratory analysis, Dr. Copeland and his colleagues determined that patients with no residual disease (R0 patients) after initial cytoreductive surgery fared better, with a median 70 months of survival compared to a median 43.6 months for individuals with gross residual disease. When those patients were sorted out by treatment arm, there was no significant difference in OS for R0 patients who received any intervention or surveillance.
“Overall survival was not improved with taxane maintenance, though progression-free survival is slightly delayed,” Dr. Copeland concluded.
In discussion after the presentation, he said that he is not sure that further investigations will be pursued for paclitaxel poliglumex in the treatment of ovarian cancers.
Paclitaxel poliglumex (CT-2103; Opaxio) is paclitaxel conjugated to a polyglutamate polymer, a formulation that may enhance tumor penetration and retention, and that allows shorter infusion at a peripheral site. Previous work had shown that CT-2103’s structure enhanced pharmacokinetics and potentially decreased toxicity (Expert Opin Investig Drugs. 2004 Nov;13[11]:1501-8).
Dr. Copeland reported receiving consulting or honoraria fees from Clovis, Advaxis, Janssen, and Tesaro, and is a stockholder or shareholder in Merck, Eli Lilly, and Cardinal Health. The study was sponsored by the Cancer Therapy Evaluation Program of the National Cancer Institute and by Cell Therapeutics, which plans to market paclitaxel poliglumex.
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NATIONAL HARBOR, MD. – Using either a polymerized formulation of paclitaxel or paclitaxel alone as maintenance therapy conferred no survival benefit for women with advanced ovarian, fallopian tube, or peritoneal cancer.
In a phase III randomized trial, patients survived a median 54.8 months with surveillance alone, 51.3 months with maintenance paclitaxel, and 60.0 months with maintenance paclitaxel poliglumex; these differences were not statistically significant.
In a presentation at the annual meeting of the Society of Gynecologic Oncology, Larry Copeland, MD, a professor of gynecologic oncology at Ohio State University, Columbus, said that treatment with surgery and chemotherapy yields a clinical complete response in many patients with these cancers. However, he said, recurrent progressive disease is still very common; the rationale behind maintenance chemotherapy is that it may “reduce the risk of recurrence and extend survival.”
There had been promising earlier data supporting this approach from a previous phase III comparison trial that evaluated the difference in clinical complete response between 3 or 12 cycles of paclitaxel, said Dr. Copeland. The results of a predefined interim analysis prompted the data monitoring committee to close that study (J Clin Oncol. 2003;21[13]:2460-5) since the 12-cycle, 7-month arm of the study had better progression-free survival. However, the 12-cycle protocol did not confer a benefit in overall survival, the investigators later reported (Gynecol Oncol 2009;114[2]:195-8).
The current stage III randomized trial enrolled women with stage III or IV ovarian, fallopian tube, or peritoneal cancer who had had five to eight cycles of chemotherapy and achieved clinical complete response. If patients had neuropathy, it could not exceed grade 1, and their cancer performance status scores could not exceed 2, Dr. Copeland said.
Patients were randomized 1:1:1 to a surveillance arm, to receive paclitaxel as a 3-hour infusion, or to receive paclitaxel poliglumex as a 10- to 20-minute infusion. Both study drugs were dosed at 35 mg/m2 every 28 days for 12 cycles.
The study ran from March 2005 to January 2014, enrolling 1,157 patients who were followed for a median of 71 months. Over 80% of patients in each study arm had ovarian cancer, and a similar number had stage III cancer and serous histology. Over 90% of patients in each arm had grade 2 or higher histology.
The study was designed as a superiority design, and patients were not to receive other cancer treatments until they had disease progression. Primary clinical endpoints for the study included overall survival, quality of life as measured by the Ovarian Specific Questionnaire Quality of Life–Cancer, and patient-reported neurotoxicity as reported on the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group/Neurotoxicity questionnaire.
The third scheduled interim analysis, in May 2016, examined the primary endpoint of overall survival, triggered when at least 200 deaths occurred in the surveillance group. The overall final analysis had been scheduled for the point at which at least 301 deaths happened in the surveillance group. In the abstract accompanying the presentation, Dr. Copeland wrote that the data at the point of this interim analysis indicated that “the relative death hazards passed the futility boundaries for both taxane regimens.”
“The log-rank statistic for each taxane regimen was below the interval specific in the study design, making it unlikely either of the taxane regimens has superior overall survival compared to surveillance,” said Dr. Copeland.
The hazard ratio for overall survival of the paclitaxel group compared to surveillance was 1.104, with a 97.5% confidence interval (CI) of 0.884-1.38. For the paclitaxel poliglumex group, the hazard ratio compared to surveillance alone was 0.979 (97.5% CI, 0.781-1.23).
Dr. Copeland and his colleagues also looked at progression-free survival, not a primary endpoint of the study. For the paclitaxel patients compared to surveillance, the HR for progression-free survival was 0.783 (95% CI, 0.666-0.921). For paclitaxel poliglumex, the HR was 0.847 (95% CI, 0.666-0.921).
Not unexpectedly, more patients who received taxane treatment than those in the surveillance arm experienced adverse events, said Dr. Copeland. The most common adverse events were hypersensitivity or allergic reactions, fatigue, alopecia, nausea, constipation, and sensory neuropathies. Grade 2 alopecia was experienced by about a quarter of the paclitaxel poliglumex cohort, and by a little less than half of the paclitaxel cohort. Neurologic adverse events were very common, reported by three quarters of the paclitaxel poliglumex cohort, four in five of the paclitaxel group, and by a little over half of the surveillance cohort.
Overall quality of life scores did not differ significantly among the treatment arms.
In an exploratory analysis, Dr. Copeland and his colleagues determined that patients with no residual disease (R0 patients) after initial cytoreductive surgery fared better, with a median 70 months of survival compared to a median 43.6 months for individuals with gross residual disease. When those patients were sorted out by treatment arm, there was no significant difference in OS for R0 patients who received any intervention or surveillance.
“Overall survival was not improved with taxane maintenance, though progression-free survival is slightly delayed,” Dr. Copeland concluded.
In discussion after the presentation, he said that he is not sure that further investigations will be pursued for paclitaxel poliglumex in the treatment of ovarian cancers.
Paclitaxel poliglumex (CT-2103; Opaxio) is paclitaxel conjugated to a polyglutamate polymer, a formulation that may enhance tumor penetration and retention, and that allows shorter infusion at a peripheral site. Previous work had shown that CT-2103’s structure enhanced pharmacokinetics and potentially decreased toxicity (Expert Opin Investig Drugs. 2004 Nov;13[11]:1501-8).
Dr. Copeland reported receiving consulting or honoraria fees from Clovis, Advaxis, Janssen, and Tesaro, and is a stockholder or shareholder in Merck, Eli Lilly, and Cardinal Health. The study was sponsored by the Cancer Therapy Evaluation Program of the National Cancer Institute and by Cell Therapeutics, which plans to market paclitaxel poliglumex.
[email protected]
On Twitter @karioakes
NATIONAL HARBOR, MD. – Using either a polymerized formulation of paclitaxel or paclitaxel alone as maintenance therapy conferred no survival benefit for women with advanced ovarian, fallopian tube, or peritoneal cancer.
In a phase III randomized trial, patients survived a median 54.8 months with surveillance alone, 51.3 months with maintenance paclitaxel, and 60.0 months with maintenance paclitaxel poliglumex; these differences were not statistically significant.
In a presentation at the annual meeting of the Society of Gynecologic Oncology, Larry Copeland, MD, a professor of gynecologic oncology at Ohio State University, Columbus, said that treatment with surgery and chemotherapy yields a clinical complete response in many patients with these cancers. However, he said, recurrent progressive disease is still very common; the rationale behind maintenance chemotherapy is that it may “reduce the risk of recurrence and extend survival.”
There had been promising earlier data supporting this approach from a previous phase III comparison trial that evaluated the difference in clinical complete response between 3 or 12 cycles of paclitaxel, said Dr. Copeland. The results of a predefined interim analysis prompted the data monitoring committee to close that study (J Clin Oncol. 2003;21[13]:2460-5) since the 12-cycle, 7-month arm of the study had better progression-free survival. However, the 12-cycle protocol did not confer a benefit in overall survival, the investigators later reported (Gynecol Oncol 2009;114[2]:195-8).
The current stage III randomized trial enrolled women with stage III or IV ovarian, fallopian tube, or peritoneal cancer who had had five to eight cycles of chemotherapy and achieved clinical complete response. If patients had neuropathy, it could not exceed grade 1, and their cancer performance status scores could not exceed 2, Dr. Copeland said.
Patients were randomized 1:1:1 to a surveillance arm, to receive paclitaxel as a 3-hour infusion, or to receive paclitaxel poliglumex as a 10- to 20-minute infusion. Both study drugs were dosed at 35 mg/m2 every 28 days for 12 cycles.
The study ran from March 2005 to January 2014, enrolling 1,157 patients who were followed for a median of 71 months. Over 80% of patients in each study arm had ovarian cancer, and a similar number had stage III cancer and serous histology. Over 90% of patients in each arm had grade 2 or higher histology.
The study was designed as a superiority design, and patients were not to receive other cancer treatments until they had disease progression. Primary clinical endpoints for the study included overall survival, quality of life as measured by the Ovarian Specific Questionnaire Quality of Life–Cancer, and patient-reported neurotoxicity as reported on the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group/Neurotoxicity questionnaire.
The third scheduled interim analysis, in May 2016, examined the primary endpoint of overall survival, triggered when at least 200 deaths occurred in the surveillance group. The overall final analysis had been scheduled for the point at which at least 301 deaths happened in the surveillance group. In the abstract accompanying the presentation, Dr. Copeland wrote that the data at the point of this interim analysis indicated that “the relative death hazards passed the futility boundaries for both taxane regimens.”
“The log-rank statistic for each taxane regimen was below the interval specific in the study design, making it unlikely either of the taxane regimens has superior overall survival compared to surveillance,” said Dr. Copeland.
The hazard ratio for overall survival of the paclitaxel group compared to surveillance was 1.104, with a 97.5% confidence interval (CI) of 0.884-1.38. For the paclitaxel poliglumex group, the hazard ratio compared to surveillance alone was 0.979 (97.5% CI, 0.781-1.23).
Dr. Copeland and his colleagues also looked at progression-free survival, not a primary endpoint of the study. For the paclitaxel patients compared to surveillance, the HR for progression-free survival was 0.783 (95% CI, 0.666-0.921). For paclitaxel poliglumex, the HR was 0.847 (95% CI, 0.666-0.921).
Not unexpectedly, more patients who received taxane treatment than those in the surveillance arm experienced adverse events, said Dr. Copeland. The most common adverse events were hypersensitivity or allergic reactions, fatigue, alopecia, nausea, constipation, and sensory neuropathies. Grade 2 alopecia was experienced by about a quarter of the paclitaxel poliglumex cohort, and by a little less than half of the paclitaxel cohort. Neurologic adverse events were very common, reported by three quarters of the paclitaxel poliglumex cohort, four in five of the paclitaxel group, and by a little over half of the surveillance cohort.
Overall quality of life scores did not differ significantly among the treatment arms.
In an exploratory analysis, Dr. Copeland and his colleagues determined that patients with no residual disease (R0 patients) after initial cytoreductive surgery fared better, with a median 70 months of survival compared to a median 43.6 months for individuals with gross residual disease. When those patients were sorted out by treatment arm, there was no significant difference in OS for R0 patients who received any intervention or surveillance.
“Overall survival was not improved with taxane maintenance, though progression-free survival is slightly delayed,” Dr. Copeland concluded.
In discussion after the presentation, he said that he is not sure that further investigations will be pursued for paclitaxel poliglumex in the treatment of ovarian cancers.
Paclitaxel poliglumex (CT-2103; Opaxio) is paclitaxel conjugated to a polyglutamate polymer, a formulation that may enhance tumor penetration and retention, and that allows shorter infusion at a peripheral site. Previous work had shown that CT-2103’s structure enhanced pharmacokinetics and potentially decreased toxicity (Expert Opin Investig Drugs. 2004 Nov;13[11]:1501-8).
Dr. Copeland reported receiving consulting or honoraria fees from Clovis, Advaxis, Janssen, and Tesaro, and is a stockholder or shareholder in Merck, Eli Lilly, and Cardinal Health. The study was sponsored by the Cancer Therapy Evaluation Program of the National Cancer Institute and by Cell Therapeutics, which plans to market paclitaxel poliglumex.
[email protected]
On Twitter @karioakes
AT THE ANNUAL MEETING ON WOMEN’S CANCER
Key clinical point:
Major finding: There was no statistically significant overall survival benefit of maintenance taxane therapy for advanced ovarian, fallopian tube, or peritoneal cancer, compared with surveillance.
Data source: Phase III randomized trial of 1,157 patients with advanced ovarian, fallopian tube, or peritoneal cancer.
Disclosures: Dr. Copeland reported receiving consulting or honoraria fees from Clovis, Advaxis, Janssen, and Tesaro, and is a stockholder or shareholder in Merck, Eli Lilly, and Cardinal Health. The study was sponsored by the Cancer Therapy Evaluation Program of the National Cancer Institute and by Cell Therapeutics, which plans to market paclitaxel poliglumex.
Immunotherapy boosts OS from metastatic cervical cancer in early trial
NATIONAL HARBOR, MD – An investigational targeted immunotherapy led to a 52% improvement in overall survival, compared with pooled historical data, among patients with previously treated metastatic cervical cancer.
Patients in the phase II trial who received axalimogene filolisbac (AXAL) had a 12-month overall survival (OS) rate of 38%, which significantly exceeded the predicted rate of 25% had they gone untreated (P = .02), Charles Leath, MD, said during a late-breaking presentation at the annual meeting of the Society of Gynecologic Oncology. Investigators are now recruiting for a placebo-controlled phase III trial of AXAL in the adjuvant setting, he said.
In a previous trial in India, therapy with AXAL was associated with a 12-month OS of 34% among patients with persistent or recurrent metastatic cervical cancer. For the current trial, 50 women with persistent or recurrent metastatic cervical cancer despite prior systemic therapy received intravenous AXAL (1 x 109 CFU) every 28 days for up to three doses or until disease progression. Patients had a median age of 46 years, and most had a Gynecologic Oncology Group (GOG) performance status of 0. Most patients had received at least two previous lines of treatment, more than half had received bevacizumab, and 86% had received pelvic radiation, Dr. Leath reported.
Median overall survival time was 6.2 months (95% confidence interval, 4.4-12.3 months), and 44% of patients progressed on therapy, while 30% had stable disease. The only complete response occurred in a patient with squamous cell carcinoma of the cervix who developed pelvic recurrence 7 years after undergoing radical hysterectomy. She received paclitaxel/carboplatin, bevacizumab, and pelvic radiation, and her cancer recurred 1 year later. She subsequently received three intravenous doses of AXAL and has survived 18.5 months so far, Dr. Leath said.
Treatment-related adverse events affected 96% of patients, and usually consisted of grade 1 or 2 fatigue, chills, anemia, nausea, and fever. A total of 36% of patients had grade 3 treatment-related adverse events, of which anemia was the most common. One patient developed grade 4 hypotension that was considered probably related to treatment, and one patient developed grade 4 Klebsiella pneumonia and sepsis deemed possibly related to treatment.
The survival curve dropped off steeply at first and then had a long tail, reflecting the delayed effects of immunotherapy, Dr. Leath commented. For the phase III trial, patients with high-risk cervical cancer will receive at least 3 weeks of cisplatin and external beam radiation therapy before being randomly assigned to either intravenous AXAL (1 x 109 CFU) or placebo for up to 1 year, he added.
The trial was funded by the Gynecologic Oncology Group, Advaxis, and the National Cancer Institute. Dr. Leath disclosed grant funding from Celsion, Novartis, Astra Zeneca, and Plexikkon, and disclosed honoraria or reimbursements from Celsion and Genentech/Roche.
NATIONAL HARBOR, MD – An investigational targeted immunotherapy led to a 52% improvement in overall survival, compared with pooled historical data, among patients with previously treated metastatic cervical cancer.
Patients in the phase II trial who received axalimogene filolisbac (AXAL) had a 12-month overall survival (OS) rate of 38%, which significantly exceeded the predicted rate of 25% had they gone untreated (P = .02), Charles Leath, MD, said during a late-breaking presentation at the annual meeting of the Society of Gynecologic Oncology. Investigators are now recruiting for a placebo-controlled phase III trial of AXAL in the adjuvant setting, he said.
In a previous trial in India, therapy with AXAL was associated with a 12-month OS of 34% among patients with persistent or recurrent metastatic cervical cancer. For the current trial, 50 women with persistent or recurrent metastatic cervical cancer despite prior systemic therapy received intravenous AXAL (1 x 109 CFU) every 28 days for up to three doses or until disease progression. Patients had a median age of 46 years, and most had a Gynecologic Oncology Group (GOG) performance status of 0. Most patients had received at least two previous lines of treatment, more than half had received bevacizumab, and 86% had received pelvic radiation, Dr. Leath reported.
Median overall survival time was 6.2 months (95% confidence interval, 4.4-12.3 months), and 44% of patients progressed on therapy, while 30% had stable disease. The only complete response occurred in a patient with squamous cell carcinoma of the cervix who developed pelvic recurrence 7 years after undergoing radical hysterectomy. She received paclitaxel/carboplatin, bevacizumab, and pelvic radiation, and her cancer recurred 1 year later. She subsequently received three intravenous doses of AXAL and has survived 18.5 months so far, Dr. Leath said.
Treatment-related adverse events affected 96% of patients, and usually consisted of grade 1 or 2 fatigue, chills, anemia, nausea, and fever. A total of 36% of patients had grade 3 treatment-related adverse events, of which anemia was the most common. One patient developed grade 4 hypotension that was considered probably related to treatment, and one patient developed grade 4 Klebsiella pneumonia and sepsis deemed possibly related to treatment.
The survival curve dropped off steeply at first and then had a long tail, reflecting the delayed effects of immunotherapy, Dr. Leath commented. For the phase III trial, patients with high-risk cervical cancer will receive at least 3 weeks of cisplatin and external beam radiation therapy before being randomly assigned to either intravenous AXAL (1 x 109 CFU) or placebo for up to 1 year, he added.
The trial was funded by the Gynecologic Oncology Group, Advaxis, and the National Cancer Institute. Dr. Leath disclosed grant funding from Celsion, Novartis, Astra Zeneca, and Plexikkon, and disclosed honoraria or reimbursements from Celsion and Genentech/Roche.
NATIONAL HARBOR, MD – An investigational targeted immunotherapy led to a 52% improvement in overall survival, compared with pooled historical data, among patients with previously treated metastatic cervical cancer.
Patients in the phase II trial who received axalimogene filolisbac (AXAL) had a 12-month overall survival (OS) rate of 38%, which significantly exceeded the predicted rate of 25% had they gone untreated (P = .02), Charles Leath, MD, said during a late-breaking presentation at the annual meeting of the Society of Gynecologic Oncology. Investigators are now recruiting for a placebo-controlled phase III trial of AXAL in the adjuvant setting, he said.
In a previous trial in India, therapy with AXAL was associated with a 12-month OS of 34% among patients with persistent or recurrent metastatic cervical cancer. For the current trial, 50 women with persistent or recurrent metastatic cervical cancer despite prior systemic therapy received intravenous AXAL (1 x 109 CFU) every 28 days for up to three doses or until disease progression. Patients had a median age of 46 years, and most had a Gynecologic Oncology Group (GOG) performance status of 0. Most patients had received at least two previous lines of treatment, more than half had received bevacizumab, and 86% had received pelvic radiation, Dr. Leath reported.
Median overall survival time was 6.2 months (95% confidence interval, 4.4-12.3 months), and 44% of patients progressed on therapy, while 30% had stable disease. The only complete response occurred in a patient with squamous cell carcinoma of the cervix who developed pelvic recurrence 7 years after undergoing radical hysterectomy. She received paclitaxel/carboplatin, bevacizumab, and pelvic radiation, and her cancer recurred 1 year later. She subsequently received three intravenous doses of AXAL and has survived 18.5 months so far, Dr. Leath said.
Treatment-related adverse events affected 96% of patients, and usually consisted of grade 1 or 2 fatigue, chills, anemia, nausea, and fever. A total of 36% of patients had grade 3 treatment-related adverse events, of which anemia was the most common. One patient developed grade 4 hypotension that was considered probably related to treatment, and one patient developed grade 4 Klebsiella pneumonia and sepsis deemed possibly related to treatment.
The survival curve dropped off steeply at first and then had a long tail, reflecting the delayed effects of immunotherapy, Dr. Leath commented. For the phase III trial, patients with high-risk cervical cancer will receive at least 3 weeks of cisplatin and external beam radiation therapy before being randomly assigned to either intravenous AXAL (1 x 109 CFU) or placebo for up to 1 year, he added.
The trial was funded by the Gynecologic Oncology Group, Advaxis, and the National Cancer Institute. Dr. Leath disclosed grant funding from Celsion, Novartis, Astra Zeneca, and Plexikkon, and disclosed honoraria or reimbursements from Celsion and Genentech/Roche.
Key clinical point. Treatment with axalimogene filolisbac led to a 52% improvement in overall survival, compared with pooled historical data, in previously treated patients with metastatic cervical cancer.
Major finding: Twelve-month overall survival was 38%, significantly greater than the modeled prediction of 25% had patients gone untreated (P = .02).
Data source: A multicenter phase II trial of 50 patients with previously treated metastatic cervical cancer.
Disclosures: The study was supported by the Gynecologic Oncology Group, Advaxis, and the National Cancer Institute. Dr. Leath disclosed grant funding from Celsion, Novartis, Astra Zeneca, and Plexikkon, and honoraria or reimbursements from Celsion and Genentech/Roche.
VIDEO: Striking improvement in PFS with olaparib for ovarian cancer
NATIONAL HARBOR, MD. – Maintenance therapy with the first-in-class PARP inhibitor olaparib was associated with a striking improvement in progression-free survival in patients with platinum-sensitive relapsed ovarian cancer and BRCA 1/2 mutation in the randomized, placebo-controlled phase III SOLO2 trial.
Compared with placebo, the tablet formulation of olaparib was associated with investigator-assessed PFS of 19.1 months in 196 patients, compared with 5.5 months in 99 patients who received placebo (hazard ratio, 0.30), Dr. Eric Pujade-Lauraine reported at the annual meeting of the Society of Gynecologic Oncology.
The SOLO2 results were both clinically meaningful and highly statistically significant, said Dr. Pujade-Lauraine of Hopital Hotel-Dieu, Paris.
Active treatment, which involved a twice-daily 300-mg oral dose of olaparib, was well tolerated; 75% of patients completed the study without dose reduction, he noted.
In this video interview, Dr. Pujade-Lauraine discussed the SOLO2 study and findings, which confirmed those of the phase II Study 19. Study 19 looked at olaparib in all-comers with platinum-sensitive relapsed ovarian cancer and involved a different formulation of the drug, which required that patients take 16 capsules each day to achieve a twice-daily dose of 400 mg. Patients with BRCA mutations were found in that study to derive the most benefit from olaparib.
The current findings are practice changing, Dr. Pujade-Lauraine said, concluding that “it is important to test BRCA, and if this test is positive, to offer olaparib in patients who are platinum sensitive.”
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
NATIONAL HARBOR, MD. – Maintenance therapy with the first-in-class PARP inhibitor olaparib was associated with a striking improvement in progression-free survival in patients with platinum-sensitive relapsed ovarian cancer and BRCA 1/2 mutation in the randomized, placebo-controlled phase III SOLO2 trial.
Compared with placebo, the tablet formulation of olaparib was associated with investigator-assessed PFS of 19.1 months in 196 patients, compared with 5.5 months in 99 patients who received placebo (hazard ratio, 0.30), Dr. Eric Pujade-Lauraine reported at the annual meeting of the Society of Gynecologic Oncology.
The SOLO2 results were both clinically meaningful and highly statistically significant, said Dr. Pujade-Lauraine of Hopital Hotel-Dieu, Paris.
Active treatment, which involved a twice-daily 300-mg oral dose of olaparib, was well tolerated; 75% of patients completed the study without dose reduction, he noted.
In this video interview, Dr. Pujade-Lauraine discussed the SOLO2 study and findings, which confirmed those of the phase II Study 19. Study 19 looked at olaparib in all-comers with platinum-sensitive relapsed ovarian cancer and involved a different formulation of the drug, which required that patients take 16 capsules each day to achieve a twice-daily dose of 400 mg. Patients with BRCA mutations were found in that study to derive the most benefit from olaparib.
The current findings are practice changing, Dr. Pujade-Lauraine said, concluding that “it is important to test BRCA, and if this test is positive, to offer olaparib in patients who are platinum sensitive.”
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
NATIONAL HARBOR, MD. – Maintenance therapy with the first-in-class PARP inhibitor olaparib was associated with a striking improvement in progression-free survival in patients with platinum-sensitive relapsed ovarian cancer and BRCA 1/2 mutation in the randomized, placebo-controlled phase III SOLO2 trial.
Compared with placebo, the tablet formulation of olaparib was associated with investigator-assessed PFS of 19.1 months in 196 patients, compared with 5.5 months in 99 patients who received placebo (hazard ratio, 0.30), Dr. Eric Pujade-Lauraine reported at the annual meeting of the Society of Gynecologic Oncology.
The SOLO2 results were both clinically meaningful and highly statistically significant, said Dr. Pujade-Lauraine of Hopital Hotel-Dieu, Paris.
Active treatment, which involved a twice-daily 300-mg oral dose of olaparib, was well tolerated; 75% of patients completed the study without dose reduction, he noted.
In this video interview, Dr. Pujade-Lauraine discussed the SOLO2 study and findings, which confirmed those of the phase II Study 19. Study 19 looked at olaparib in all-comers with platinum-sensitive relapsed ovarian cancer and involved a different formulation of the drug, which required that patients take 16 capsules each day to achieve a twice-daily dose of 400 mg. Patients with BRCA mutations were found in that study to derive the most benefit from olaparib.
The current findings are practice changing, Dr. Pujade-Lauraine said, concluding that “it is important to test BRCA, and if this test is positive, to offer olaparib in patients who are platinum sensitive.”
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT THE ANNUAL MEETING ON WOMEN'S CANCER
VIDEO: Vaginal brachytherapy linked with better survival in rare uterine cancer
NATIONAL HARBOR, MD. – A large retrospective database study linked the use of vaginal brachytherapy and chemotherapy with improved survival among patients with early-stage uterine papillary serous carcinoma.
The findings offer a degree of clinical guidance on the adjuvant treatment of this relatively rare, aggressive histologic cancer subtype, Stephanie Cham, MD, said during a video interview at the annual meeting of the Society of Gynecologic Oncology.
Large dataset analyses can be especially helpful for exploring the treatment of rare diseases for which clinical trials can be infeasible, said Dr. Cham of Columbia University College of Physicians and Surgeons in New York. To evaluate chemotherapy, vaginal brachytherapy, and whole beam pelvic radiation therapy in stage I and stage II uterine papillary serous carcinoma, she and her associates analyzed the National Cancer Database.
Among 7,325 patients treated between 1998 and 2012, 38% of patients had received chemotherapy, 18% had received external beam radiation, and 20% received brachytherapy, Dr. Cham said. The use of chemotherapy rose significantly over time, regardless of stage (P less than .0001), as did the use of brachytherapy, while the use of external beam radiation decreased.
After the researchers controlled for numerous demographic and clinical variables, chemotherapy was associated with a statistically significant decrease in the risk of death overall (hazard ratio, 0.78; 95% confidence interval, 0.69 to 0.88) and in patients with stage IB (HR, 0.58; 95% CI, 0.44-0.77) or stage II cancer (HR, 0.74; 95% CI, 0.60-0.90). The use of brachytherapy also was associated with significantly improved survival overall (HR, 0.67), in stage IA cancer (HR, 0.67), and in stage II cancer (HR, 0.64).
The survival effect of brachytherapy held up in additional subgroup analyses, Dr. Cham explained. In contrast, external beam radiation therapy was not associated with improved survival overall or in any subgroup, she said. The results highlight the potential use of vaginal brachytherapy in early-stage uterine papillary serous carcinoma, she emphasized.
Dr. Cham cited no funding sources and reported having no conflicts of interest.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
NATIONAL HARBOR, MD. – A large retrospective database study linked the use of vaginal brachytherapy and chemotherapy with improved survival among patients with early-stage uterine papillary serous carcinoma.
The findings offer a degree of clinical guidance on the adjuvant treatment of this relatively rare, aggressive histologic cancer subtype, Stephanie Cham, MD, said during a video interview at the annual meeting of the Society of Gynecologic Oncology.
Large dataset analyses can be especially helpful for exploring the treatment of rare diseases for which clinical trials can be infeasible, said Dr. Cham of Columbia University College of Physicians and Surgeons in New York. To evaluate chemotherapy, vaginal brachytherapy, and whole beam pelvic radiation therapy in stage I and stage II uterine papillary serous carcinoma, she and her associates analyzed the National Cancer Database.
Among 7,325 patients treated between 1998 and 2012, 38% of patients had received chemotherapy, 18% had received external beam radiation, and 20% received brachytherapy, Dr. Cham said. The use of chemotherapy rose significantly over time, regardless of stage (P less than .0001), as did the use of brachytherapy, while the use of external beam radiation decreased.
After the researchers controlled for numerous demographic and clinical variables, chemotherapy was associated with a statistically significant decrease in the risk of death overall (hazard ratio, 0.78; 95% confidence interval, 0.69 to 0.88) and in patients with stage IB (HR, 0.58; 95% CI, 0.44-0.77) or stage II cancer (HR, 0.74; 95% CI, 0.60-0.90). The use of brachytherapy also was associated with significantly improved survival overall (HR, 0.67), in stage IA cancer (HR, 0.67), and in stage II cancer (HR, 0.64).
The survival effect of brachytherapy held up in additional subgroup analyses, Dr. Cham explained. In contrast, external beam radiation therapy was not associated with improved survival overall or in any subgroup, she said. The results highlight the potential use of vaginal brachytherapy in early-stage uterine papillary serous carcinoma, she emphasized.
Dr. Cham cited no funding sources and reported having no conflicts of interest.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
NATIONAL HARBOR, MD. – A large retrospective database study linked the use of vaginal brachytherapy and chemotherapy with improved survival among patients with early-stage uterine papillary serous carcinoma.
The findings offer a degree of clinical guidance on the adjuvant treatment of this relatively rare, aggressive histologic cancer subtype, Stephanie Cham, MD, said during a video interview at the annual meeting of the Society of Gynecologic Oncology.
Large dataset analyses can be especially helpful for exploring the treatment of rare diseases for which clinical trials can be infeasible, said Dr. Cham of Columbia University College of Physicians and Surgeons in New York. To evaluate chemotherapy, vaginal brachytherapy, and whole beam pelvic radiation therapy in stage I and stage II uterine papillary serous carcinoma, she and her associates analyzed the National Cancer Database.
Among 7,325 patients treated between 1998 and 2012, 38% of patients had received chemotherapy, 18% had received external beam radiation, and 20% received brachytherapy, Dr. Cham said. The use of chemotherapy rose significantly over time, regardless of stage (P less than .0001), as did the use of brachytherapy, while the use of external beam radiation decreased.
After the researchers controlled for numerous demographic and clinical variables, chemotherapy was associated with a statistically significant decrease in the risk of death overall (hazard ratio, 0.78; 95% confidence interval, 0.69 to 0.88) and in patients with stage IB (HR, 0.58; 95% CI, 0.44-0.77) or stage II cancer (HR, 0.74; 95% CI, 0.60-0.90). The use of brachytherapy also was associated with significantly improved survival overall (HR, 0.67), in stage IA cancer (HR, 0.67), and in stage II cancer (HR, 0.64).
The survival effect of brachytherapy held up in additional subgroup analyses, Dr. Cham explained. In contrast, external beam radiation therapy was not associated with improved survival overall or in any subgroup, she said. The results highlight the potential use of vaginal brachytherapy in early-stage uterine papillary serous carcinoma, she emphasized.
Dr. Cham cited no funding sources and reported having no conflicts of interest.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT THE ANNUAL MEETING ON WOMEN’S CANCER
Key clinical point: Chemotherapy and brachytherapy were independently associated with survival in early-stage uterine papillary serous carcinoma.
Major finding: Multivariable analyses linked chemotherapy with a statistically significant decrease in the risk of death overall (hazard ratio, 0.78) and in stage IB (HR, 0.58; 95% CI, 0.44 to 0.77) and stage II cancer (HR, 0.74; 95% CI, 0.60 to 0.90). The use of brachytherapy also was associated with significantly improved survival in the entire cohort (HR, 0.67), in stage IA cancer (HR, 0.67), and in stage II cancer (HR, 0.64).
Data source: A retrospective analysis of patients with stage I or II uterine papillary serous carcinoma from the National Cancer Database.
Disclosures: Dr. Cham cited no funding sources and reported having no conflicts of interest.
Isolated tumor cells did not predict progression in endometrial cancer
NATIONAL HARBOR, MD. – Patients with endometrial cancer should not receive adjuvant chemotherapy or radiotherapy solely because they have isolated tumor cells in their sentinel lymph nodes, Marie Plante, MD, said during an oral presentation at the annual meeting of the Society of Gynecologic Oncology.
In a single-center prospective cohort study, about 96% of patients with endometrial cancer were alive and progression free at 3 years, a rate which resembles those reported for node-negative patients, said Dr. Plante of Laval University, Quebec City. Moreover, all 10 patients who did not receive adjuvant therapy remained alive and progression free during follow-up, she said. “Patients with isolated tumor cells carry an excellent prognosis,” she added. “Adjuvant treatment should be tailored based on uterine factors and histology and not solely on the presence of isolated tumor cells in sentinel lymph nodes.”
Pathologic ultrastaging has boosted the detection of low-volume metastases, which comprise anywhere from 35% to 63% of nodal metastases in patients with endometrial cancer. Clinicians continue to debate management when this low-volume disease consists of isolated tumor cells (ITC), defined as fewer than 200 carcinoma cells found singly or in small clusters. Finding ITC in endometrial cancer is uncommon, and few studies have examined this subgroup, Dr. Plante noted.
She and her associates evaluated 519 patients who underwent hysterectomy, salpingo-oophorectomy, lymphadenectomy, or sentinel lymph node mapping for endometrial cancer at their center between 2010 and 2015. Pathologic ultrastaging identified 31 patients with ITC (6%), of whom 11 patients received adjuvant chemotherapy, 14 received pelvic radiation therapy, and 10 underwent only brachytherapy or observation, with some patients receiving more than one treatment. Another 54 patients in the cohort had metastatic disease, including 43 patients with macrometastasis and 11 with micrometastasis.
Stage, not treatment, predicted progression-free survival (PFS), Dr. Plante emphasized. After a median follow-up period of 29 months, the estimated 3-year rate of PFS was significantly better among patients with ITC (96%), node-negative disease (88%), or micrometastasis (86%) than among those with macrometastasis (59%; P = .001), even though macrometastasis patients received significantly more chemotherapy (P = .0001).
Rates of PFS did not statistically differ between the ITC and node-negative groups, Dr. Plante noted. The single recurrence in an ITC patient involved a 7 cm carcinosarcoma that recurred despite adjuvant chemotherapy and radiation therapy. There were no recurrences among patients with endometrioid histology.
Among ITC patients who received no adjuvant treatment, half had stage IA endometrial cancer and half were stage IB, half were grade 1 and half were grade 2, all had endometrioid histology, and seven (70%) had evidence of lymphovascular space invasion, Dr. Plante said. All remained alive and progression free at follow-up.
Ultrastaging should only be performed if a sentinel lymph node is negative on initial hematoxylin and eosin stain and if there is myoinvasion, commented Nadeem R. Abu-Rustum, MD, chief of the gynecology service at Memorial Sloan Kettering Cancer Center, New York, who was not involved in the study. “Ultrastaging increases positive-node detection by about 8%,” he said during the scientific plenary session at the conference. “Finding positive nodes can change management, and we have to be careful not to overtreat.”
Ongoing research is examining the topography and anatomic location of ITC in sentinel lymph nodes, Dr. Abu-Rustum said. In the meantime, he advised clinicians to consider any ultrastaging result of ITC in context. “When modeling the risk of ITCs, don’t look at them in isolation. Don’t be ‘node-centric,’ ” he advised. “Look at the uterine factors and the overall bigger picture.”
Dr. Plante did not acknowledge external funding sources. Dr. Plante and Dr. Abu-Rustum reported having no conflicts of interest.
NATIONAL HARBOR, MD. – Patients with endometrial cancer should not receive adjuvant chemotherapy or radiotherapy solely because they have isolated tumor cells in their sentinel lymph nodes, Marie Plante, MD, said during an oral presentation at the annual meeting of the Society of Gynecologic Oncology.
In a single-center prospective cohort study, about 96% of patients with endometrial cancer were alive and progression free at 3 years, a rate which resembles those reported for node-negative patients, said Dr. Plante of Laval University, Quebec City. Moreover, all 10 patients who did not receive adjuvant therapy remained alive and progression free during follow-up, she said. “Patients with isolated tumor cells carry an excellent prognosis,” she added. “Adjuvant treatment should be tailored based on uterine factors and histology and not solely on the presence of isolated tumor cells in sentinel lymph nodes.”
Pathologic ultrastaging has boosted the detection of low-volume metastases, which comprise anywhere from 35% to 63% of nodal metastases in patients with endometrial cancer. Clinicians continue to debate management when this low-volume disease consists of isolated tumor cells (ITC), defined as fewer than 200 carcinoma cells found singly or in small clusters. Finding ITC in endometrial cancer is uncommon, and few studies have examined this subgroup, Dr. Plante noted.
She and her associates evaluated 519 patients who underwent hysterectomy, salpingo-oophorectomy, lymphadenectomy, or sentinel lymph node mapping for endometrial cancer at their center between 2010 and 2015. Pathologic ultrastaging identified 31 patients with ITC (6%), of whom 11 patients received adjuvant chemotherapy, 14 received pelvic radiation therapy, and 10 underwent only brachytherapy or observation, with some patients receiving more than one treatment. Another 54 patients in the cohort had metastatic disease, including 43 patients with macrometastasis and 11 with micrometastasis.
Stage, not treatment, predicted progression-free survival (PFS), Dr. Plante emphasized. After a median follow-up period of 29 months, the estimated 3-year rate of PFS was significantly better among patients with ITC (96%), node-negative disease (88%), or micrometastasis (86%) than among those with macrometastasis (59%; P = .001), even though macrometastasis patients received significantly more chemotherapy (P = .0001).
Rates of PFS did not statistically differ between the ITC and node-negative groups, Dr. Plante noted. The single recurrence in an ITC patient involved a 7 cm carcinosarcoma that recurred despite adjuvant chemotherapy and radiation therapy. There were no recurrences among patients with endometrioid histology.
Among ITC patients who received no adjuvant treatment, half had stage IA endometrial cancer and half were stage IB, half were grade 1 and half were grade 2, all had endometrioid histology, and seven (70%) had evidence of lymphovascular space invasion, Dr. Plante said. All remained alive and progression free at follow-up.
Ultrastaging should only be performed if a sentinel lymph node is negative on initial hematoxylin and eosin stain and if there is myoinvasion, commented Nadeem R. Abu-Rustum, MD, chief of the gynecology service at Memorial Sloan Kettering Cancer Center, New York, who was not involved in the study. “Ultrastaging increases positive-node detection by about 8%,” he said during the scientific plenary session at the conference. “Finding positive nodes can change management, and we have to be careful not to overtreat.”
Ongoing research is examining the topography and anatomic location of ITC in sentinel lymph nodes, Dr. Abu-Rustum said. In the meantime, he advised clinicians to consider any ultrastaging result of ITC in context. “When modeling the risk of ITCs, don’t look at them in isolation. Don’t be ‘node-centric,’ ” he advised. “Look at the uterine factors and the overall bigger picture.”
Dr. Plante did not acknowledge external funding sources. Dr. Plante and Dr. Abu-Rustum reported having no conflicts of interest.
NATIONAL HARBOR, MD. – Patients with endometrial cancer should not receive adjuvant chemotherapy or radiotherapy solely because they have isolated tumor cells in their sentinel lymph nodes, Marie Plante, MD, said during an oral presentation at the annual meeting of the Society of Gynecologic Oncology.
In a single-center prospective cohort study, about 96% of patients with endometrial cancer were alive and progression free at 3 years, a rate which resembles those reported for node-negative patients, said Dr. Plante of Laval University, Quebec City. Moreover, all 10 patients who did not receive adjuvant therapy remained alive and progression free during follow-up, she said. “Patients with isolated tumor cells carry an excellent prognosis,” she added. “Adjuvant treatment should be tailored based on uterine factors and histology and not solely on the presence of isolated tumor cells in sentinel lymph nodes.”
Pathologic ultrastaging has boosted the detection of low-volume metastases, which comprise anywhere from 35% to 63% of nodal metastases in patients with endometrial cancer. Clinicians continue to debate management when this low-volume disease consists of isolated tumor cells (ITC), defined as fewer than 200 carcinoma cells found singly or in small clusters. Finding ITC in endometrial cancer is uncommon, and few studies have examined this subgroup, Dr. Plante noted.
She and her associates evaluated 519 patients who underwent hysterectomy, salpingo-oophorectomy, lymphadenectomy, or sentinel lymph node mapping for endometrial cancer at their center between 2010 and 2015. Pathologic ultrastaging identified 31 patients with ITC (6%), of whom 11 patients received adjuvant chemotherapy, 14 received pelvic radiation therapy, and 10 underwent only brachytherapy or observation, with some patients receiving more than one treatment. Another 54 patients in the cohort had metastatic disease, including 43 patients with macrometastasis and 11 with micrometastasis.
Stage, not treatment, predicted progression-free survival (PFS), Dr. Plante emphasized. After a median follow-up period of 29 months, the estimated 3-year rate of PFS was significantly better among patients with ITC (96%), node-negative disease (88%), or micrometastasis (86%) than among those with macrometastasis (59%; P = .001), even though macrometastasis patients received significantly more chemotherapy (P = .0001).
Rates of PFS did not statistically differ between the ITC and node-negative groups, Dr. Plante noted. The single recurrence in an ITC patient involved a 7 cm carcinosarcoma that recurred despite adjuvant chemotherapy and radiation therapy. There were no recurrences among patients with endometrioid histology.
Among ITC patients who received no adjuvant treatment, half had stage IA endometrial cancer and half were stage IB, half were grade 1 and half were grade 2, all had endometrioid histology, and seven (70%) had evidence of lymphovascular space invasion, Dr. Plante said. All remained alive and progression free at follow-up.
Ultrastaging should only be performed if a sentinel lymph node is negative on initial hematoxylin and eosin stain and if there is myoinvasion, commented Nadeem R. Abu-Rustum, MD, chief of the gynecology service at Memorial Sloan Kettering Cancer Center, New York, who was not involved in the study. “Ultrastaging increases positive-node detection by about 8%,” he said during the scientific plenary session at the conference. “Finding positive nodes can change management, and we have to be careful not to overtreat.”
Ongoing research is examining the topography and anatomic location of ITC in sentinel lymph nodes, Dr. Abu-Rustum said. In the meantime, he advised clinicians to consider any ultrastaging result of ITC in context. “When modeling the risk of ITCs, don’t look at them in isolation. Don’t be ‘node-centric,’ ” he advised. “Look at the uterine factors and the overall bigger picture.”
Dr. Plante did not acknowledge external funding sources. Dr. Plante and Dr. Abu-Rustum reported having no conflicts of interest.
AT THE ANNUAL MEETING ON WOMEN’S CANCER
Key clinical point: For patients with endometrial cancer, isolated tumor cells in sentinel lymph nodes did not lead to disease progression and were not an indication for adjuvant treatments.
Major finding: At 3 years, the estimated rate of progression-free survival was 100% among patients who underwent only pelvic brachytherapy or observation.
Data source: A single-center prospective study of 519 patients undergoing hysterectomy, salpingo-oophorectomy, lymphadenectomy, and sentinel lymph node mapping for endometrial cancer, including 31 patients with isolated tumor cells identified in sentinel lymph nodes.
Disclosures: Dr. Plante did not report having external funding sources. Dr. Plante and Dr. Abu-Rustum had no disclosures.
VIDEO: Cell-free DNA mutations linked with recurrence of ovarian cancer
NATIONAL HARBOR, MD. – Next-generation sequencing of high-grade serous ovarian tumor specimens taken during interval debulking identified several mutations that matched those in cell-free DNA (cfDNA), Rebecca C. Arend, MD, said at the annual meeting of the Society of Gynecologic Oncology.
Furthermore, three of four patients whose ovarian cancer recurred had mutations in cfDNA that were previously detected in tumors, said Dr. Arend of the University of Alabama at Birmingham.
Researchers continue to search for ways to spare patients with ovarian cancer from serial biopsies, Dr. Arend noted during a video interview. As part of that work, she and her associates performed longitudinal next-generation sequencing of 50 genes in tumor and plasma specimens from 14 patients with high-grade serous ovarian cancer.
Mutations found only in tumors were relatively consistent before and after neoadjuvant chemotherapy, while mutations found only in cell-free DNA varied substantially.
The researchers also sequenced plasma samples from four patients at cancer recurrence. Three patients had at least one mutation that was previously detected in their tumor sample. Implicated genes included PIK3CA, TP53, KIT, and KDR.
Many studies have sought circulating tumor markers that reliably predict tumor recurrence. When it comes to cfDNA, “we are not there yet,” but the work is worthwhile, Dr. Arend stressed. Sequencing tumor and cfDNA specimens from patients at multiple points during their journey might one day help pinpoint mutations that reliably predict cancer recurrence, sparing patients from repeated biopsies and helping them efficiently enter clinical trials that target their specific mutation, she added.
Dr. Arend cited no funding sources and reported having no conflicts of interest.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
NATIONAL HARBOR, MD. – Next-generation sequencing of high-grade serous ovarian tumor specimens taken during interval debulking identified several mutations that matched those in cell-free DNA (cfDNA), Rebecca C. Arend, MD, said at the annual meeting of the Society of Gynecologic Oncology.
Furthermore, three of four patients whose ovarian cancer recurred had mutations in cfDNA that were previously detected in tumors, said Dr. Arend of the University of Alabama at Birmingham.
Researchers continue to search for ways to spare patients with ovarian cancer from serial biopsies, Dr. Arend noted during a video interview. As part of that work, she and her associates performed longitudinal next-generation sequencing of 50 genes in tumor and plasma specimens from 14 patients with high-grade serous ovarian cancer.
Mutations found only in tumors were relatively consistent before and after neoadjuvant chemotherapy, while mutations found only in cell-free DNA varied substantially.
The researchers also sequenced plasma samples from four patients at cancer recurrence. Three patients had at least one mutation that was previously detected in their tumor sample. Implicated genes included PIK3CA, TP53, KIT, and KDR.
Many studies have sought circulating tumor markers that reliably predict tumor recurrence. When it comes to cfDNA, “we are not there yet,” but the work is worthwhile, Dr. Arend stressed. Sequencing tumor and cfDNA specimens from patients at multiple points during their journey might one day help pinpoint mutations that reliably predict cancer recurrence, sparing patients from repeated biopsies and helping them efficiently enter clinical trials that target their specific mutation, she added.
Dr. Arend cited no funding sources and reported having no conflicts of interest.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
NATIONAL HARBOR, MD. – Next-generation sequencing of high-grade serous ovarian tumor specimens taken during interval debulking identified several mutations that matched those in cell-free DNA (cfDNA), Rebecca C. Arend, MD, said at the annual meeting of the Society of Gynecologic Oncology.
Furthermore, three of four patients whose ovarian cancer recurred had mutations in cfDNA that were previously detected in tumors, said Dr. Arend of the University of Alabama at Birmingham.
Researchers continue to search for ways to spare patients with ovarian cancer from serial biopsies, Dr. Arend noted during a video interview. As part of that work, she and her associates performed longitudinal next-generation sequencing of 50 genes in tumor and plasma specimens from 14 patients with high-grade serous ovarian cancer.
Mutations found only in tumors were relatively consistent before and after neoadjuvant chemotherapy, while mutations found only in cell-free DNA varied substantially.
The researchers also sequenced plasma samples from four patients at cancer recurrence. Three patients had at least one mutation that was previously detected in their tumor sample. Implicated genes included PIK3CA, TP53, KIT, and KDR.
Many studies have sought circulating tumor markers that reliably predict tumor recurrence. When it comes to cfDNA, “we are not there yet,” but the work is worthwhile, Dr. Arend stressed. Sequencing tumor and cfDNA specimens from patients at multiple points during their journey might one day help pinpoint mutations that reliably predict cancer recurrence, sparing patients from repeated biopsies and helping them efficiently enter clinical trials that target their specific mutation, she added.
Dr. Arend cited no funding sources and reported having no conflicts of interest.
The video associated with this article is no longer available on this site. Please view all of our videos on the MDedge YouTube channel
AT THE ANNUAL MEETING ON WOMEN’S CANCER
Key clinical point: Next-generation sequencing of cell-free DNA specimens (liquid biopsies) might one day help identify tumor recurrence in patients with high-grade serous ovarian cancer.
Major finding: Three of four patients whose cancer recurred had mutations in cell-free DNA that were previously detected in tumor specimens collected during interval debulking.
Data source: Next-generation sequencing of tumor and cell-free (plasma) DNA from 14 patients with high-grade serous ovarian cancer before and after platinum-based neoadjuvant chemotherapy.
Disclosures: Dr. Arend cited no funding sources and reported having no conflicts of interest.
WPR may benefit patients with stage IVB cervical cancer
NATIONAL HARBOR, MD. – Whole pelvic radiation delivered in addition to chemotherapy in women who present with stage IVB cervical cancer confers significant 12-month overall and progression-free survival benefits, according to findings from a multi-institutional retrospective review.
Of 127 patients diagnosed during 2005-2015 at four academic high-volume centers, 31 received no treatment or elected hospice care and, of the remaining patients, 34 received whole pelvic radiation (WPR) in addition to chemotherapy, and 62 received chemotherapy alone, which is the standard of care. The median overall survival was 14.1 vs. 6.9 months with vs. without WPR, and the median progression-free survival was 10 vs. 5 months, respectively, Victoria B. Perkins, MD, said at the annual meeting of the Society of Gynecologic Oncology.
Of note, the rates of pelvic-related morbidity, including ureteral obstruction, vaginal or rectal bleeding, pelvic infection, pelvic pain, and fistula, did not differ significantly between the groups, said Dr. Perkins of the University of Oklahoma Health Sciences Center, Oklahoma City.
Study subjects were women with a median age of 54 years. A little more than a third (36%) were white, 35% were Hispanic, and 16% were black. Most (75%) had squamous cell carcinoma, and 95% were grade 2 or 3.
There were no significant differences in the demographics, location of [metastatic] disease, or distribution of chemotherapy type between the two groups, she said, noting that “interestingly, 26% of patients in the chemotherapy alone group received additional bevacizumab, compared to only 12% in the whole pelvic radiation with chemotherapy group.
“This could reflect the change in treatment strategy with the approval of bevacizumab during the treatment period,” Dr. Perkins noted.
About 5% of women have stage IVB cervical cancer at the time of diagnosis, but 5-year survival in these women is only about 15%.
“The mainstay of treatment is platinum and taxane with or without bevacizumab. In clinical practice, treatment of stage IVB disease varies,” Dr. Perkins said.
One strategy follows the guidance of phase III trials looking at chemotherapy with palliative radiation as needed.
“However, a significant number of patients experience morbidity and mortality directly related to their pelvic disease, such as vaginal bleeding, ureteral obstruction, fistulization, infections, and pain. Thus, an alternative approach is aimed at treating bulky pelvic disease with whole pelvic radiation followed by systemic chemotherapy with the goal to control symptoms and theoretically reduce recurrences in the pelvic field, which can be highly problematic in terms of symptomatic control,” she said, noting that this novel approach has not been formally studied.
The aim of the current review was to determine if WPR with chemotherapy would reduce pelvic morbidity and improve overall and progression-free survival.
“Survival in stage IVB disease remains extremely poor. Perhaps adding whole pelvic radiation to systemic chemotherapy has utility without increasing morbidity. However, the addition of whole pelvic radiation did not improve pelvic-related morbidity as previously hypothesized,” she said.
The study was limited by varied chemotherapy regimens in both groups and by changes in standard treatment practice during the span of study. It also was limited by the retrospective design, small sample size, and lack of quality of life data, but the findings support further study regarding subgroups of patients who could benefit the most from this treatment strategy, she concluded, noting, however, that such study is challenging because of the rarity of stage IVB disease.
Dr. Perkins reported having no disclosures.
NATIONAL HARBOR, MD. – Whole pelvic radiation delivered in addition to chemotherapy in women who present with stage IVB cervical cancer confers significant 12-month overall and progression-free survival benefits, according to findings from a multi-institutional retrospective review.
Of 127 patients diagnosed during 2005-2015 at four academic high-volume centers, 31 received no treatment or elected hospice care and, of the remaining patients, 34 received whole pelvic radiation (WPR) in addition to chemotherapy, and 62 received chemotherapy alone, which is the standard of care. The median overall survival was 14.1 vs. 6.9 months with vs. without WPR, and the median progression-free survival was 10 vs. 5 months, respectively, Victoria B. Perkins, MD, said at the annual meeting of the Society of Gynecologic Oncology.
Of note, the rates of pelvic-related morbidity, including ureteral obstruction, vaginal or rectal bleeding, pelvic infection, pelvic pain, and fistula, did not differ significantly between the groups, said Dr. Perkins of the University of Oklahoma Health Sciences Center, Oklahoma City.
Study subjects were women with a median age of 54 years. A little more than a third (36%) were white, 35% were Hispanic, and 16% were black. Most (75%) had squamous cell carcinoma, and 95% were grade 2 or 3.
There were no significant differences in the demographics, location of [metastatic] disease, or distribution of chemotherapy type between the two groups, she said, noting that “interestingly, 26% of patients in the chemotherapy alone group received additional bevacizumab, compared to only 12% in the whole pelvic radiation with chemotherapy group.
“This could reflect the change in treatment strategy with the approval of bevacizumab during the treatment period,” Dr. Perkins noted.
About 5% of women have stage IVB cervical cancer at the time of diagnosis, but 5-year survival in these women is only about 15%.
“The mainstay of treatment is platinum and taxane with or without bevacizumab. In clinical practice, treatment of stage IVB disease varies,” Dr. Perkins said.
One strategy follows the guidance of phase III trials looking at chemotherapy with palliative radiation as needed.
“However, a significant number of patients experience morbidity and mortality directly related to their pelvic disease, such as vaginal bleeding, ureteral obstruction, fistulization, infections, and pain. Thus, an alternative approach is aimed at treating bulky pelvic disease with whole pelvic radiation followed by systemic chemotherapy with the goal to control symptoms and theoretically reduce recurrences in the pelvic field, which can be highly problematic in terms of symptomatic control,” she said, noting that this novel approach has not been formally studied.
The aim of the current review was to determine if WPR with chemotherapy would reduce pelvic morbidity and improve overall and progression-free survival.
“Survival in stage IVB disease remains extremely poor. Perhaps adding whole pelvic radiation to systemic chemotherapy has utility without increasing morbidity. However, the addition of whole pelvic radiation did not improve pelvic-related morbidity as previously hypothesized,” she said.
The study was limited by varied chemotherapy regimens in both groups and by changes in standard treatment practice during the span of study. It also was limited by the retrospective design, small sample size, and lack of quality of life data, but the findings support further study regarding subgroups of patients who could benefit the most from this treatment strategy, she concluded, noting, however, that such study is challenging because of the rarity of stage IVB disease.
Dr. Perkins reported having no disclosures.
NATIONAL HARBOR, MD. – Whole pelvic radiation delivered in addition to chemotherapy in women who present with stage IVB cervical cancer confers significant 12-month overall and progression-free survival benefits, according to findings from a multi-institutional retrospective review.
Of 127 patients diagnosed during 2005-2015 at four academic high-volume centers, 31 received no treatment or elected hospice care and, of the remaining patients, 34 received whole pelvic radiation (WPR) in addition to chemotherapy, and 62 received chemotherapy alone, which is the standard of care. The median overall survival was 14.1 vs. 6.9 months with vs. without WPR, and the median progression-free survival was 10 vs. 5 months, respectively, Victoria B. Perkins, MD, said at the annual meeting of the Society of Gynecologic Oncology.
Of note, the rates of pelvic-related morbidity, including ureteral obstruction, vaginal or rectal bleeding, pelvic infection, pelvic pain, and fistula, did not differ significantly between the groups, said Dr. Perkins of the University of Oklahoma Health Sciences Center, Oklahoma City.
Study subjects were women with a median age of 54 years. A little more than a third (36%) were white, 35% were Hispanic, and 16% were black. Most (75%) had squamous cell carcinoma, and 95% were grade 2 or 3.
There were no significant differences in the demographics, location of [metastatic] disease, or distribution of chemotherapy type between the two groups, she said, noting that “interestingly, 26% of patients in the chemotherapy alone group received additional bevacizumab, compared to only 12% in the whole pelvic radiation with chemotherapy group.
“This could reflect the change in treatment strategy with the approval of bevacizumab during the treatment period,” Dr. Perkins noted.
About 5% of women have stage IVB cervical cancer at the time of diagnosis, but 5-year survival in these women is only about 15%.
“The mainstay of treatment is platinum and taxane with or without bevacizumab. In clinical practice, treatment of stage IVB disease varies,” Dr. Perkins said.
One strategy follows the guidance of phase III trials looking at chemotherapy with palliative radiation as needed.
“However, a significant number of patients experience morbidity and mortality directly related to their pelvic disease, such as vaginal bleeding, ureteral obstruction, fistulization, infections, and pain. Thus, an alternative approach is aimed at treating bulky pelvic disease with whole pelvic radiation followed by systemic chemotherapy with the goal to control symptoms and theoretically reduce recurrences in the pelvic field, which can be highly problematic in terms of symptomatic control,” she said, noting that this novel approach has not been formally studied.
The aim of the current review was to determine if WPR with chemotherapy would reduce pelvic morbidity and improve overall and progression-free survival.
“Survival in stage IVB disease remains extremely poor. Perhaps adding whole pelvic radiation to systemic chemotherapy has utility without increasing morbidity. However, the addition of whole pelvic radiation did not improve pelvic-related morbidity as previously hypothesized,” she said.
The study was limited by varied chemotherapy regimens in both groups and by changes in standard treatment practice during the span of study. It also was limited by the retrospective design, small sample size, and lack of quality of life data, but the findings support further study regarding subgroups of patients who could benefit the most from this treatment strategy, she concluded, noting, however, that such study is challenging because of the rarity of stage IVB disease.
Dr. Perkins reported having no disclosures.
AT THE ANNUAL MEETING ON WOMEN’S CANCERS
Key clinical point:
Major finding: Median overall and progression-free survival with vs. without WPR: 14.1 vs. 6.9 months and 10 vs. 5 months, respectively, but no difference in pelvic-related morbidity.
Data source: A retrospective review of 127 cases.
Disclosures: Dr. Perkins reported having no disclosures.
Adjuvant chemotherapy alone may suffice for some high-risk early cervical cancers
National Harbor, MD. – Patients, even those with surgically-confirmed risk factors, fared well when they received adjuvant chemotherapy without radiotherapy for early-stage cervical cancer.
In a retrospective review of 101 patients, Kwang-Beom Lee, MD, and his associates found that patients with known surgical risk factors had a posttreatment disease-free survival rate of 94.6%, a 5-year overall survival rate of 90.6%. and a disease-specific 5-year survival rate of 96.2%. These figures compare with survival rates of 79.4%, 90.6%, and 90.6%, respectively, for early-stage cervical cancer patients with lymph node metastasis.
Dr. Lee, professor of obstetrics and gynecology at Gachon University School of Medicine, Incheon, South Korea, said that about 3,600 cases of cervical cancer are diagnosed each year in Korea, and a little more than half (58%) are early-stage cancers. Most Korean patients with International Federation of Gynecology and Obstetrics (FIGO) stage IA2-IIA cancer will receive a radical hysterectomy with lymphadenectomy, he said at the annual meeting of the Society of Gynecologic Oncology.
Dr. Lee and his colleagues sought to ascertain morbidity when patients with early cervical cancer received either adjuvant radiotherapy or concurrent chemoradiotherapy (CCRT), and to explore the potential role that chemotherapy alone might play in these patients.
Accordingly, one of the primary outcomes of the study was to determine outcomes of adjuvant chemotherapy alone for patients with FIGO stage IB-IIA cervical cancer who had surgically-confirmed risk factors, and who received radical surgery.
The surgically-confirmed factors included lymphovascular space invasion, depth of penetration, and tumor size.
Currently, Dr. Lee said, evidence indicates that CCRT for patients with high risk factors improves both progression-free survival and overall survival. For patients with intermediate risk factors, radiotherapy is associated with increased progression-free survival.
The researchers examined 101 patients in this category who were treated between March of 2006 and December of 2014 at two Korean academic medical centers, excluding patients who had positive tumor margins, who received neoadjuvant chemotherapy, or who had microscopic parametrium involvement.
The mean age of the patients was 47.1 years (range, 23-73 years). Their mean body mass index was 23.1, and two thirds of patients were premenopausal. Most patients (73.3%, n = 74) had stage IB1 cancer, while 23 (22.8%) had stage IB2 cancer, and 4 (3.9%) had stage IIA cancer. Most patients (74.3%, n = 75) had squamous cell cancer.
The radical procedure performed was a type C radical hysterectomy; patients underwent pelvic lymph node dissection, with or without para-aortic node dissection. Pelvic nodes included all of the common iliac nodes, the external and internal iliac chains, and the obturator nodes. Para-aortic node dissection included dissection up to the level of the inferior mesenteric artery.
A total of 50 patients received pelvic lymph node and para-aortic lymph node dissection, with a mean 54.5 tumors retrieved per patient. A mean of 4.58 pelvic nodes were assessed as metastatic. A mean of 11.2 para-aortic nodes were retrieved, and of these, a mean 5.3 were metastatic.
All together, 76 patients had a combination of three surgically-confirmed risk factors without positive lymph nodes; the remaining 25 patients had positive lymph nodes (4 with pelvic and para-aortic involvement, the remaining with pelvic involvement alone), and were included irrespective of whether they met other risk factor criteria.
Dr. Lee said that the protocol for chemotherapy paralelled Protocol 92 from the Gynecologic Oncology Group; patients received chemotherapy if the combination of tumor diameter, depth of stromal invasion, and lymphovascular space invasion met Protocol 92 criteria for treatment, or if more than one lymph node metastasis was found.
The chemotherapy regime for intermediate-risk patients called for six cycles of either platinum alone (n = 47), or platinum with paclitaxel (n = 54). High-risk patients received six cycles of paclitaxel and platinum.
Patients were followed for a median of 65 months, and a total of 14 patients had a recurrence.
Dr. Lee reported no conflicts of interest.
[email protected]
On Twitter @karioakes
National Harbor, MD. – Patients, even those with surgically-confirmed risk factors, fared well when they received adjuvant chemotherapy without radiotherapy for early-stage cervical cancer.
In a retrospective review of 101 patients, Kwang-Beom Lee, MD, and his associates found that patients with known surgical risk factors had a posttreatment disease-free survival rate of 94.6%, a 5-year overall survival rate of 90.6%. and a disease-specific 5-year survival rate of 96.2%. These figures compare with survival rates of 79.4%, 90.6%, and 90.6%, respectively, for early-stage cervical cancer patients with lymph node metastasis.
Dr. Lee, professor of obstetrics and gynecology at Gachon University School of Medicine, Incheon, South Korea, said that about 3,600 cases of cervical cancer are diagnosed each year in Korea, and a little more than half (58%) are early-stage cancers. Most Korean patients with International Federation of Gynecology and Obstetrics (FIGO) stage IA2-IIA cancer will receive a radical hysterectomy with lymphadenectomy, he said at the annual meeting of the Society of Gynecologic Oncology.
Dr. Lee and his colleagues sought to ascertain morbidity when patients with early cervical cancer received either adjuvant radiotherapy or concurrent chemoradiotherapy (CCRT), and to explore the potential role that chemotherapy alone might play in these patients.
Accordingly, one of the primary outcomes of the study was to determine outcomes of adjuvant chemotherapy alone for patients with FIGO stage IB-IIA cervical cancer who had surgically-confirmed risk factors, and who received radical surgery.
The surgically-confirmed factors included lymphovascular space invasion, depth of penetration, and tumor size.
Currently, Dr. Lee said, evidence indicates that CCRT for patients with high risk factors improves both progression-free survival and overall survival. For patients with intermediate risk factors, radiotherapy is associated with increased progression-free survival.
The researchers examined 101 patients in this category who were treated between March of 2006 and December of 2014 at two Korean academic medical centers, excluding patients who had positive tumor margins, who received neoadjuvant chemotherapy, or who had microscopic parametrium involvement.
The mean age of the patients was 47.1 years (range, 23-73 years). Their mean body mass index was 23.1, and two thirds of patients were premenopausal. Most patients (73.3%, n = 74) had stage IB1 cancer, while 23 (22.8%) had stage IB2 cancer, and 4 (3.9%) had stage IIA cancer. Most patients (74.3%, n = 75) had squamous cell cancer.
The radical procedure performed was a type C radical hysterectomy; patients underwent pelvic lymph node dissection, with or without para-aortic node dissection. Pelvic nodes included all of the common iliac nodes, the external and internal iliac chains, and the obturator nodes. Para-aortic node dissection included dissection up to the level of the inferior mesenteric artery.
A total of 50 patients received pelvic lymph node and para-aortic lymph node dissection, with a mean 54.5 tumors retrieved per patient. A mean of 4.58 pelvic nodes were assessed as metastatic. A mean of 11.2 para-aortic nodes were retrieved, and of these, a mean 5.3 were metastatic.
All together, 76 patients had a combination of three surgically-confirmed risk factors without positive lymph nodes; the remaining 25 patients had positive lymph nodes (4 with pelvic and para-aortic involvement, the remaining with pelvic involvement alone), and were included irrespective of whether they met other risk factor criteria.
Dr. Lee said that the protocol for chemotherapy paralelled Protocol 92 from the Gynecologic Oncology Group; patients received chemotherapy if the combination of tumor diameter, depth of stromal invasion, and lymphovascular space invasion met Protocol 92 criteria for treatment, or if more than one lymph node metastasis was found.
The chemotherapy regime for intermediate-risk patients called for six cycles of either platinum alone (n = 47), or platinum with paclitaxel (n = 54). High-risk patients received six cycles of paclitaxel and platinum.
Patients were followed for a median of 65 months, and a total of 14 patients had a recurrence.
Dr. Lee reported no conflicts of interest.
[email protected]
On Twitter @karioakes
National Harbor, MD. – Patients, even those with surgically-confirmed risk factors, fared well when they received adjuvant chemotherapy without radiotherapy for early-stage cervical cancer.
In a retrospective review of 101 patients, Kwang-Beom Lee, MD, and his associates found that patients with known surgical risk factors had a posttreatment disease-free survival rate of 94.6%, a 5-year overall survival rate of 90.6%. and a disease-specific 5-year survival rate of 96.2%. These figures compare with survival rates of 79.4%, 90.6%, and 90.6%, respectively, for early-stage cervical cancer patients with lymph node metastasis.
Dr. Lee, professor of obstetrics and gynecology at Gachon University School of Medicine, Incheon, South Korea, said that about 3,600 cases of cervical cancer are diagnosed each year in Korea, and a little more than half (58%) are early-stage cancers. Most Korean patients with International Federation of Gynecology and Obstetrics (FIGO) stage IA2-IIA cancer will receive a radical hysterectomy with lymphadenectomy, he said at the annual meeting of the Society of Gynecologic Oncology.
Dr. Lee and his colleagues sought to ascertain morbidity when patients with early cervical cancer received either adjuvant radiotherapy or concurrent chemoradiotherapy (CCRT), and to explore the potential role that chemotherapy alone might play in these patients.
Accordingly, one of the primary outcomes of the study was to determine outcomes of adjuvant chemotherapy alone for patients with FIGO stage IB-IIA cervical cancer who had surgically-confirmed risk factors, and who received radical surgery.
The surgically-confirmed factors included lymphovascular space invasion, depth of penetration, and tumor size.
Currently, Dr. Lee said, evidence indicates that CCRT for patients with high risk factors improves both progression-free survival and overall survival. For patients with intermediate risk factors, radiotherapy is associated with increased progression-free survival.
The researchers examined 101 patients in this category who were treated between March of 2006 and December of 2014 at two Korean academic medical centers, excluding patients who had positive tumor margins, who received neoadjuvant chemotherapy, or who had microscopic parametrium involvement.
The mean age of the patients was 47.1 years (range, 23-73 years). Their mean body mass index was 23.1, and two thirds of patients were premenopausal. Most patients (73.3%, n = 74) had stage IB1 cancer, while 23 (22.8%) had stage IB2 cancer, and 4 (3.9%) had stage IIA cancer. Most patients (74.3%, n = 75) had squamous cell cancer.
The radical procedure performed was a type C radical hysterectomy; patients underwent pelvic lymph node dissection, with or without para-aortic node dissection. Pelvic nodes included all of the common iliac nodes, the external and internal iliac chains, and the obturator nodes. Para-aortic node dissection included dissection up to the level of the inferior mesenteric artery.
A total of 50 patients received pelvic lymph node and para-aortic lymph node dissection, with a mean 54.5 tumors retrieved per patient. A mean of 4.58 pelvic nodes were assessed as metastatic. A mean of 11.2 para-aortic nodes were retrieved, and of these, a mean 5.3 were metastatic.
All together, 76 patients had a combination of three surgically-confirmed risk factors without positive lymph nodes; the remaining 25 patients had positive lymph nodes (4 with pelvic and para-aortic involvement, the remaining with pelvic involvement alone), and were included irrespective of whether they met other risk factor criteria.
Dr. Lee said that the protocol for chemotherapy paralelled Protocol 92 from the Gynecologic Oncology Group; patients received chemotherapy if the combination of tumor diameter, depth of stromal invasion, and lymphovascular space invasion met Protocol 92 criteria for treatment, or if more than one lymph node metastasis was found.
The chemotherapy regime for intermediate-risk patients called for six cycles of either platinum alone (n = 47), or platinum with paclitaxel (n = 54). High-risk patients received six cycles of paclitaxel and platinum.
Patients were followed for a median of 65 months, and a total of 14 patients had a recurrence.
Dr. Lee reported no conflicts of interest.
[email protected]
On Twitter @karioakes
AT THE ANNUAL MEETING ON WOMEN’S CANCERS
Key clinical point:
Major finding: Patients with known surgical risk factors had a posttreatment disease-free survival rate of 94.6%.
Data source: Retrospective, two-center review of patients with early cervical cancer and multiple risk factors or pelvic node involvement.
Disclosures: Dr. Lee reported no conflicts of interest.