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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.
Intensive ventilation precedes lesser pulmonary complications
Addition of 10 cm H2O to positive end-expiratory volume (PEEP) during mechanical ventilation was followed by significantly lessened pulmonary complications in hospitalized patients who developed hypoxemia after cardiac surgery, participating in a single-center, randomized trial.
This “intensive” alveolar recruitment strategy yielded a median pulmonary complications score of 1.7 (interquartile range, 1.0-2.0), compared with 2.0 (IQR, 1.5-3.0) among patients who underwent ventilation with a PEEP of 20 cm H2O, Alcino Costa Leme, RRT, PhD, said at the International Symposium on Intensive Care and Emergency Medicine. The report was published simultaneously online March 21 in JAMA.
Intensive alveolar recruitment nearly doubled the odds of a lower pulmonary complications score (common odds ratio, 1.9; 95% confidence interval, 1.2-2.8; P = .003), Dr. Leme and his associates reported.
The study comprised 320 adults who developed hypoxemia immediately after undergoing elective cardiac surgery at the Heart Institute (Incor) of the University of São Paulo. The median age of the patients was 62 years, and none had a history of lung disease. Pulmonary complications were scored between 0 (no signs or symptoms) and 5 (death), the investigators noted (JAMA. 2017 Mar 21. doi: 10.1001/jama.2017.2297).
The intensive alveolar recruitment strategy consisted of three 60-second cycles of lung inflation with a positive end-expiratory pressure (PEEP) of 30 cm H2O, pressure-controlled ventilation, driving pressure of 15 cm H2O, respiratory rate of 15/min, inspiratory time of 1.5 seconds, and FIO2 of 0.40. Between and after inflations, patients received assist-controlled or pressure-controlled ventilation, with driving pressures set to achieve a tidal volume of 6 mL/kg of predicted body weight, an inspiratory time of 1 second, PEEP of 13 cm H2O, and minimum respiratory rate to maintain PaCO2 between 35 and 45 mm Hg.
The “moderate strategy” consisted of three 30-second inflations under continuous positive airway pressure mode at 20 cm H2O and FIO2 of 0.60. Between and after inflations, patients received assist or control volume-controlled ventilation (decelerating-flow waveform), tidal volume of 6 mL/kg of predicted body weight, inspiratory time of 1 second, PEEP of 8 cm H2O, and FIO2 of 0.60, at a minimum respiratory rate that maintained PaCO2 at 35-45 mm Hg.
“[The] use of an intensive alveolar recruitment strategy compared with a moderate recruitment strategy resulted in less severe pulmonary complications during the hospital stay,” the investigators wrote. On average, intensively managed patients had shorter stays in the hospital (10.9 vs. 12.4 days; P = .04) and in the intensive care unit (3.8 vs. 4.8 days; P = .01) than did moderately managed patients. Intensive management also was associated with lower rates of hospital mortality and barotrauma, but the differences in these less common outcomes did not reach statistical significance.
“To our knowledge, this is the first study to show a significant effect of lung recruitment maneuvers on clinical outcomes, which objectively resulted in modest reductions in ICU and hospital length of stay,” the researchers wrote. “This is especially noteworthy considering that the control group was also receiving protective lung ventilation with low [tidal volume] and moderate PEEP levels. Thus, the major difference between treatment groups was the intensity of lung recruitment.”
FAPESP (Fundação de Amparo e Pesquisa do Estado de São Paulo) and FINEP (Financiadora de Estudos e Projetos) provided partial funding. Dr. Leme had no disclosures. Senior author Marcelo Britto Passos Amato, MD, PhD, disclosed research funding from Covidien/Medtronics, Dixtal Biomedica Ltd, and Timpel SA.
High PEEP “not only recruits collapsed lung tissue, but can also lead to lung overdistension. If lung collapse is extensive, as in patients with ARDS [acute respiratory distress syndrome], and maybe also in patients with postoperative ARDS, the balance between benefit (i.e., recruitment of lung tissue), and harm (i.e., lung overdistension), tips toward benefit. If there is very little lung collapse, as in critically ill patients without ARDS or patients during surgery, this balance could go in the other direction.”
The clinical trial by Leme and his colleagues “provides another brick in the evidence wall of lung protection. However, it remains unclear which patients benefit most from ventilation with a high [positive end-expiratory pressure] level.”
Ary Serpa Neto, MD, MSc, PhD, and Marcus J. Schultz, MD, PhD, are at the Academic Medical Center, Amsterdam. They reported having no conflicts of interest. These comments are from their editorial (JAMA. 2017 Mar 21. doi: 10.1001/jama.2017.2570).
High PEEP “not only recruits collapsed lung tissue, but can also lead to lung overdistension. If lung collapse is extensive, as in patients with ARDS [acute respiratory distress syndrome], and maybe also in patients with postoperative ARDS, the balance between benefit (i.e., recruitment of lung tissue), and harm (i.e., lung overdistension), tips toward benefit. If there is very little lung collapse, as in critically ill patients without ARDS or patients during surgery, this balance could go in the other direction.”
The clinical trial by Leme and his colleagues “provides another brick in the evidence wall of lung protection. However, it remains unclear which patients benefit most from ventilation with a high [positive end-expiratory pressure] level.”
Ary Serpa Neto, MD, MSc, PhD, and Marcus J. Schultz, MD, PhD, are at the Academic Medical Center, Amsterdam. They reported having no conflicts of interest. These comments are from their editorial (JAMA. 2017 Mar 21. doi: 10.1001/jama.2017.2570).
High PEEP “not only recruits collapsed lung tissue, but can also lead to lung overdistension. If lung collapse is extensive, as in patients with ARDS [acute respiratory distress syndrome], and maybe also in patients with postoperative ARDS, the balance between benefit (i.e., recruitment of lung tissue), and harm (i.e., lung overdistension), tips toward benefit. If there is very little lung collapse, as in critically ill patients without ARDS or patients during surgery, this balance could go in the other direction.”
The clinical trial by Leme and his colleagues “provides another brick in the evidence wall of lung protection. However, it remains unclear which patients benefit most from ventilation with a high [positive end-expiratory pressure] level.”
Ary Serpa Neto, MD, MSc, PhD, and Marcus J. Schultz, MD, PhD, are at the Academic Medical Center, Amsterdam. They reported having no conflicts of interest. These comments are from their editorial (JAMA. 2017 Mar 21. doi: 10.1001/jama.2017.2570).
Addition of 10 cm H2O to positive end-expiratory volume (PEEP) during mechanical ventilation was followed by significantly lessened pulmonary complications in hospitalized patients who developed hypoxemia after cardiac surgery, participating in a single-center, randomized trial.
This “intensive” alveolar recruitment strategy yielded a median pulmonary complications score of 1.7 (interquartile range, 1.0-2.0), compared with 2.0 (IQR, 1.5-3.0) among patients who underwent ventilation with a PEEP of 20 cm H2O, Alcino Costa Leme, RRT, PhD, said at the International Symposium on Intensive Care and Emergency Medicine. The report was published simultaneously online March 21 in JAMA.
Intensive alveolar recruitment nearly doubled the odds of a lower pulmonary complications score (common odds ratio, 1.9; 95% confidence interval, 1.2-2.8; P = .003), Dr. Leme and his associates reported.
The study comprised 320 adults who developed hypoxemia immediately after undergoing elective cardiac surgery at the Heart Institute (Incor) of the University of São Paulo. The median age of the patients was 62 years, and none had a history of lung disease. Pulmonary complications were scored between 0 (no signs or symptoms) and 5 (death), the investigators noted (JAMA. 2017 Mar 21. doi: 10.1001/jama.2017.2297).
The intensive alveolar recruitment strategy consisted of three 60-second cycles of lung inflation with a positive end-expiratory pressure (PEEP) of 30 cm H2O, pressure-controlled ventilation, driving pressure of 15 cm H2O, respiratory rate of 15/min, inspiratory time of 1.5 seconds, and FIO2 of 0.40. Between and after inflations, patients received assist-controlled or pressure-controlled ventilation, with driving pressures set to achieve a tidal volume of 6 mL/kg of predicted body weight, an inspiratory time of 1 second, PEEP of 13 cm H2O, and minimum respiratory rate to maintain PaCO2 between 35 and 45 mm Hg.
The “moderate strategy” consisted of three 30-second inflations under continuous positive airway pressure mode at 20 cm H2O and FIO2 of 0.60. Between and after inflations, patients received assist or control volume-controlled ventilation (decelerating-flow waveform), tidal volume of 6 mL/kg of predicted body weight, inspiratory time of 1 second, PEEP of 8 cm H2O, and FIO2 of 0.60, at a minimum respiratory rate that maintained PaCO2 at 35-45 mm Hg.
“[The] use of an intensive alveolar recruitment strategy compared with a moderate recruitment strategy resulted in less severe pulmonary complications during the hospital stay,” the investigators wrote. On average, intensively managed patients had shorter stays in the hospital (10.9 vs. 12.4 days; P = .04) and in the intensive care unit (3.8 vs. 4.8 days; P = .01) than did moderately managed patients. Intensive management also was associated with lower rates of hospital mortality and barotrauma, but the differences in these less common outcomes did not reach statistical significance.
“To our knowledge, this is the first study to show a significant effect of lung recruitment maneuvers on clinical outcomes, which objectively resulted in modest reductions in ICU and hospital length of stay,” the researchers wrote. “This is especially noteworthy considering that the control group was also receiving protective lung ventilation with low [tidal volume] and moderate PEEP levels. Thus, the major difference between treatment groups was the intensity of lung recruitment.”
FAPESP (Fundação de Amparo e Pesquisa do Estado de São Paulo) and FINEP (Financiadora de Estudos e Projetos) provided partial funding. Dr. Leme had no disclosures. Senior author Marcelo Britto Passos Amato, MD, PhD, disclosed research funding from Covidien/Medtronics, Dixtal Biomedica Ltd, and Timpel SA.
Addition of 10 cm H2O to positive end-expiratory volume (PEEP) during mechanical ventilation was followed by significantly lessened pulmonary complications in hospitalized patients who developed hypoxemia after cardiac surgery, participating in a single-center, randomized trial.
This “intensive” alveolar recruitment strategy yielded a median pulmonary complications score of 1.7 (interquartile range, 1.0-2.0), compared with 2.0 (IQR, 1.5-3.0) among patients who underwent ventilation with a PEEP of 20 cm H2O, Alcino Costa Leme, RRT, PhD, said at the International Symposium on Intensive Care and Emergency Medicine. The report was published simultaneously online March 21 in JAMA.
Intensive alveolar recruitment nearly doubled the odds of a lower pulmonary complications score (common odds ratio, 1.9; 95% confidence interval, 1.2-2.8; P = .003), Dr. Leme and his associates reported.
The study comprised 320 adults who developed hypoxemia immediately after undergoing elective cardiac surgery at the Heart Institute (Incor) of the University of São Paulo. The median age of the patients was 62 years, and none had a history of lung disease. Pulmonary complications were scored between 0 (no signs or symptoms) and 5 (death), the investigators noted (JAMA. 2017 Mar 21. doi: 10.1001/jama.2017.2297).
The intensive alveolar recruitment strategy consisted of three 60-second cycles of lung inflation with a positive end-expiratory pressure (PEEP) of 30 cm H2O, pressure-controlled ventilation, driving pressure of 15 cm H2O, respiratory rate of 15/min, inspiratory time of 1.5 seconds, and FIO2 of 0.40. Between and after inflations, patients received assist-controlled or pressure-controlled ventilation, with driving pressures set to achieve a tidal volume of 6 mL/kg of predicted body weight, an inspiratory time of 1 second, PEEP of 13 cm H2O, and minimum respiratory rate to maintain PaCO2 between 35 and 45 mm Hg.
The “moderate strategy” consisted of three 30-second inflations under continuous positive airway pressure mode at 20 cm H2O and FIO2 of 0.60. Between and after inflations, patients received assist or control volume-controlled ventilation (decelerating-flow waveform), tidal volume of 6 mL/kg of predicted body weight, inspiratory time of 1 second, PEEP of 8 cm H2O, and FIO2 of 0.60, at a minimum respiratory rate that maintained PaCO2 at 35-45 mm Hg.
“[The] use of an intensive alveolar recruitment strategy compared with a moderate recruitment strategy resulted in less severe pulmonary complications during the hospital stay,” the investigators wrote. On average, intensively managed patients had shorter stays in the hospital (10.9 vs. 12.4 days; P = .04) and in the intensive care unit (3.8 vs. 4.8 days; P = .01) than did moderately managed patients. Intensive management also was associated with lower rates of hospital mortality and barotrauma, but the differences in these less common outcomes did not reach statistical significance.
“To our knowledge, this is the first study to show a significant effect of lung recruitment maneuvers on clinical outcomes, which objectively resulted in modest reductions in ICU and hospital length of stay,” the researchers wrote. “This is especially noteworthy considering that the control group was also receiving protective lung ventilation with low [tidal volume] and moderate PEEP levels. Thus, the major difference between treatment groups was the intensity of lung recruitment.”
FAPESP (Fundação de Amparo e Pesquisa do Estado de São Paulo) and FINEP (Financiadora de Estudos e Projetos) provided partial funding. Dr. Leme had no disclosures. Senior author Marcelo Britto Passos Amato, MD, PhD, disclosed research funding from Covidien/Medtronics, Dixtal Biomedica Ltd, and Timpel SA.
FROM ISICEM
Key clinical point: Intensive lung recruitment during mechanical ventilation of hypoxemic cardiac surgery patients was followed by less severe pulmonary complications, compared with moderate lung recruitment.
Major finding: Compared with moderate alveolar recruitment, intensive recruitment nearly doubled the odds that patients had a lower pulmonary complications score (odds ratio, 1.9; 95% confidence interval, 1.2 to 2.8; P = .003).
Data source: A single-center randomized trial of 320 adults with no history of pulmonary disease who developed hypoxemia after undergoing elective cardiac surgery.
Disclosures: FAPESP (Fundação de Amparo e Pesquisa do Estado de São Paulo) and FINEP (Financiadora de Estudos e Projetos) provided partial funding. Dr. Leme had no disclosures. Senior author Marcelo Britto Passos Amato, MD, PhD, disclosed research funding from Covidien/Medtronics, Dixtal Biomedica Ltd, and Timpel SA.
Dexmedetomidine improves sedation in sepsis
Use of dexmedetomidine improved sedation among ventilated patients with sepsis, but did not significantly cut mortality rates or increase ventilator-free days in a multicenter, open-label randomized controlled trial.
Twenty-eight days after the start of mechanical ventilation, cumulative mortality rates were 23% among patients who received dexmedetomidine and 31% among those who did not (hazard ratio, 0.7; 95% confidence interval, 0.4 to 1.2; P = .2), Yu Kawazoe, MD, PhD, and his associates reported at the International Symposium on Intensive Care and Emergency Medicine. The report was simultaneously published in JAMA.
“The study may have identified a clinically important benefit of dexmedetomidine – an 8% reduction in 28-day mortality – that did not demonstrate statistical significance ... ” wrote Dr. Kawazoe of Tohoku University Graduate School of Medicine, Sendai, Japan. “Physicians may consider an 8% difference in 28-day mortality to be clinically significant, but this study was underpowered to detect this difference.” 
Dexmedetomidine often is used for sedation during ventilation, but its effects on mortality and ventilator weaning are poorly understood, the researchers noted. However, this highly selective alpha2-adrenergic agonist has been found to suppress inflammation and to protect organs, and “can improve patients’ ability to communicate pain compared with midazolam and propofol,” the researchers wrote. Therefore, they randomly assigned 201 patients with sepsis at eight intensive care units in Japan to receive sedation with or without dexmedetomidine. Both arms received fentanyl, propofol, and midazolam, dosed to achieve Richmond Agitation-Sedation Scale (RASS) scores of 0 (calm) during the day and –2 (lightly sedated) at night (JAMA. 2017 March 21. doi: 10.1001/jama.2017.2088).
The dexmedetomidine group spent a median of 20 days off the ventilator, compared with 18 days for controls (P = .20), the investigators reported. However, dexmedetomidine led to significantly higher rates of well-controlled sedation. The highest rate of well-controlled sedation (defined as having a RASS scores between –3 and 1 throughout 1 day in the ICU) in treated patients was 58%, while the highest rate of well-controlled sedation in the control group was 39% (P = .01).
Rates of adverse events did not significantly differ between groups. Bradycardia was most common, affecting 7% of the intervention group and 2% of controls (P = .1) the researchers said.
Hospira Japan provided partial funding with a grant to Wakayama Medical University, and helped design the study but was otherwise not involved in the research project. Dr. Kawazoe disclosed ties to Hospira Japan and Pfizer Japan. Three coinvestigators disclosed ties to Pfizer Japan, AbbVie, AstraZeneca, Daiichi Sankyo, and several other pharmaceutical companies. The other coinvestigators had no disclosures.
Use of dexmedetomidine improved sedation among ventilated patients with sepsis, but did not significantly cut mortality rates or increase ventilator-free days in a multicenter, open-label randomized controlled trial.
Twenty-eight days after the start of mechanical ventilation, cumulative mortality rates were 23% among patients who received dexmedetomidine and 31% among those who did not (hazard ratio, 0.7; 95% confidence interval, 0.4 to 1.2; P = .2), Yu Kawazoe, MD, PhD, and his associates reported at the International Symposium on Intensive Care and Emergency Medicine. The report was simultaneously published in JAMA.
“The study may have identified a clinically important benefit of dexmedetomidine – an 8% reduction in 28-day mortality – that did not demonstrate statistical significance ... ” wrote Dr. Kawazoe of Tohoku University Graduate School of Medicine, Sendai, Japan. “Physicians may consider an 8% difference in 28-day mortality to be clinically significant, but this study was underpowered to detect this difference.”
Dexmedetomidine often is used for sedation during ventilation, but its effects on mortality and ventilator weaning are poorly understood, the researchers noted. However, this highly selective alpha2-adrenergic agonist has been found to suppress inflammation and to protect organs, and “can improve patients’ ability to communicate pain compared with midazolam and propofol,” the researchers wrote. Therefore, they randomly assigned 201 patients with sepsis at eight intensive care units in Japan to receive sedation with or without dexmedetomidine. Both arms received fentanyl, propofol, and midazolam, dosed to achieve Richmond Agitation-Sedation Scale (RASS) scores of 0 (calm) during the day and –2 (lightly sedated) at night (JAMA. 2017 March 21. doi: 10.1001/jama.2017.2088).
The dexmedetomidine group spent a median of 20 days off the ventilator, compared with 18 days for controls (P = .20), the investigators reported. However, dexmedetomidine led to significantly higher rates of well-controlled sedation. The highest rate of well-controlled sedation (defined as having a RASS scores between –3 and 1 throughout 1 day in the ICU) in treated patients was 58%, while the highest rate of well-controlled sedation in the control group was 39% (P = .01).
Rates of adverse events did not significantly differ between groups. Bradycardia was most common, affecting 7% of the intervention group and 2% of controls (P = .1) the researchers said.
Hospira Japan provided partial funding with a grant to Wakayama Medical University, and helped design the study but was otherwise not involved in the research project. Dr. Kawazoe disclosed ties to Hospira Japan and Pfizer Japan. Three coinvestigators disclosed ties to Pfizer Japan, AbbVie, AstraZeneca, Daiichi Sankyo, and several other pharmaceutical companies. The other coinvestigators had no disclosures.
Use of dexmedetomidine improved sedation among ventilated patients with sepsis, but did not significantly cut mortality rates or increase ventilator-free days in a multicenter, open-label randomized controlled trial.
Twenty-eight days after the start of mechanical ventilation, cumulative mortality rates were 23% among patients who received dexmedetomidine and 31% among those who did not (hazard ratio, 0.7; 95% confidence interval, 0.4 to 1.2; P = .2), Yu Kawazoe, MD, PhD, and his associates reported at the International Symposium on Intensive Care and Emergency Medicine. The report was simultaneously published in JAMA.
“The study may have identified a clinically important benefit of dexmedetomidine – an 8% reduction in 28-day mortality – that did not demonstrate statistical significance ... ” wrote Dr. Kawazoe of Tohoku University Graduate School of Medicine, Sendai, Japan. “Physicians may consider an 8% difference in 28-day mortality to be clinically significant, but this study was underpowered to detect this difference.”
Dexmedetomidine often is used for sedation during ventilation, but its effects on mortality and ventilator weaning are poorly understood, the researchers noted. However, this highly selective alpha2-adrenergic agonist has been found to suppress inflammation and to protect organs, and “can improve patients’ ability to communicate pain compared with midazolam and propofol,” the researchers wrote. Therefore, they randomly assigned 201 patients with sepsis at eight intensive care units in Japan to receive sedation with or without dexmedetomidine. Both arms received fentanyl, propofol, and midazolam, dosed to achieve Richmond Agitation-Sedation Scale (RASS) scores of 0 (calm) during the day and –2 (lightly sedated) at night (JAMA. 2017 March 21. doi: 10.1001/jama.2017.2088).
The dexmedetomidine group spent a median of 20 days off the ventilator, compared with 18 days for controls (P = .20), the investigators reported. However, dexmedetomidine led to significantly higher rates of well-controlled sedation. The highest rate of well-controlled sedation (defined as having a RASS scores between –3 and 1 throughout 1 day in the ICU) in treated patients was 58%, while the highest rate of well-controlled sedation in the control group was 39% (P = .01).
Rates of adverse events did not significantly differ between groups. Bradycardia was most common, affecting 7% of the intervention group and 2% of controls (P = .1) the researchers said.
Hospira Japan provided partial funding with a grant to Wakayama Medical University, and helped design the study but was otherwise not involved in the research project. Dr. Kawazoe disclosed ties to Hospira Japan and Pfizer Japan. Three coinvestigators disclosed ties to Pfizer Japan, AbbVie, AstraZeneca, Daiichi Sankyo, and several other pharmaceutical companies. The other coinvestigators had no disclosures.
Key clinical point. Use of dexmedetomidine improved sedation but did not significantly cut mortality rates or increase ventilator-free days among hospitalized patients with sepsis.
Major finding: Twenty-eight days after the start of mechanical ventilation, cumulative mortality rates were 23% among patients who received dexmedetomidine and 31% among those who did not (hazard ratio, 0.7; 95% confidence interval, 0.4 to 1.2; P = .2).
Data source: A multicenter, open-label randomized controlled trial of 201 ventilated patients with sepsis.
Disclosures: Hospira Japan provided partial funding with a grant to Wakayama Medical University, and helped design the study but was otherwise not involved. Dr. Kawazoe disclosed ties to Hospira Japan and Pfizer Japan. Three coinvestigators disclosed ties to Pfizer Japan, AbbVie, AstraZeneca, Daiichi Sankyo, and several other pharmaceutical companies. The other coinvestigators had no disclosures.
Norepinephrine shortage linked to mortality in patients with septic shock
A national shortage of norepinephrine in the United States was associated with higher rates of mortality among patients hospitalized with septic shock, investigators reported.
Rates of in-hospital mortality in 2011 were 40% during quarters when hospitals were facing shortages and 36% when they were not, Emily Vail, MD, and her associates said at the International Symposium on Intensive Care and Emergency Medicine. The report was published simultaneously in JAMA.
The link between norepinephrine shortage and death from septic shock persisted even after the researchers accounted for numerous clinical and demographic factors (adjusted odds ratio, 1.2; 95% confidence interval, 1.01 to 1.30; P = .03), wrote Dr. Vail of Columbia University, New York (JAMA. 2017 Mar 21. doi: 10.1001/jama.2017.2841).
Drug shortages are common in the United States, but few studies have explored their effects on patient outcomes. Investigators compared mortality rates among affected patients during 3-month intervals when hospitals were and were not using at least 20% less norepinephrine than baseline. The researchers used Premier Healthcare Database, which includes both standard claims and detailed, dated logs of all services billed to patients or insurance, with minimal missing data.
A total of 77% patients admitted with septic shock received norepinephrine before the shortage. During the lowest point of the shortage, 56% of patients received it, the researchers reported. Clinicians most often used phenylephrine instead, prescribing it to up to 54% of patients during the worst time of the shortage. The absolute increase in mortality during the quarters of shortage was 3.7% (95% CI, 1.5%-6.0%).
Several factors might explain the link between norepinephrine shortage and mortality, said the investigators. The vasopressors chosen to replace norepinephrine might result directly in worse outcomes, but a decrease in norepinephrine use also might be a proxy for relevant variables such as delayed use of vasopressors, lack of knowledge of how to optimally dose vasopressors besides norepinephrine, or the absence of a pharmacist dedicated to helping optimize the use of limited supplies.
The study did not uncover a dose-response association between greater decreases in norepinephrine use and increased mortality, the researchers noted. “This may be due to a threshold effect of vasopressor shortage on mortality, or lack of power due to relatively few hospital quarters at the extreme levels of vasopressor shortage,” they wrote.
Because the deaths captured included only those that occurred in-hospital, “the results may have underestimated mortality, particularly for hospitals that tend transfer patients early to other skilled care facilities,” the researchers noted.
The cohort of patients was limited to those who received vasopressors for 2 or more days and excluded patients who died on the first day of vasopressor treatment, the researchers said.
The Herbert and Florence Irving Scholars Program at Columbia University provided funding. One coinvestigator disclosed grant funding from the National Institutes of Health and personal fees from UpToDate. The other investigators reported having no conflicts of interest.
A national shortage of norepinephrine in the United States was associated with higher rates of mortality among patients hospitalized with septic shock, investigators reported.
Rates of in-hospital mortality in 2011 were 40% during quarters when hospitals were facing shortages and 36% when they were not, Emily Vail, MD, and her associates said at the International Symposium on Intensive Care and Emergency Medicine. The report was published simultaneously in JAMA.
The link between norepinephrine shortage and death from septic shock persisted even after the researchers accounted for numerous clinical and demographic factors (adjusted odds ratio, 1.2; 95% confidence interval, 1.01 to 1.30; P = .03), wrote Dr. Vail of Columbia University, New York (JAMA. 2017 Mar 21. doi: 10.1001/jama.2017.2841).
Drug shortages are common in the United States, but few studies have explored their effects on patient outcomes. Investigators compared mortality rates among affected patients during 3-month intervals when hospitals were and were not using at least 20% less norepinephrine than baseline. The researchers used Premier Healthcare Database, which includes both standard claims and detailed, dated logs of all services billed to patients or insurance, with minimal missing data.
A total of 77% patients admitted with septic shock received norepinephrine before the shortage. During the lowest point of the shortage, 56% of patients received it, the researchers reported. Clinicians most often used phenylephrine instead, prescribing it to up to 54% of patients during the worst time of the shortage. The absolute increase in mortality during the quarters of shortage was 3.7% (95% CI, 1.5%-6.0%).
Several factors might explain the link between norepinephrine shortage and mortality, said the investigators. The vasopressors chosen to replace norepinephrine might result directly in worse outcomes, but a decrease in norepinephrine use also might be a proxy for relevant variables such as delayed use of vasopressors, lack of knowledge of how to optimally dose vasopressors besides norepinephrine, or the absence of a pharmacist dedicated to helping optimize the use of limited supplies.
The study did not uncover a dose-response association between greater decreases in norepinephrine use and increased mortality, the researchers noted. “This may be due to a threshold effect of vasopressor shortage on mortality, or lack of power due to relatively few hospital quarters at the extreme levels of vasopressor shortage,” they wrote.
Because the deaths captured included only those that occurred in-hospital, “the results may have underestimated mortality, particularly for hospitals that tend transfer patients early to other skilled care facilities,” the researchers noted.
The cohort of patients was limited to those who received vasopressors for 2 or more days and excluded patients who died on the first day of vasopressor treatment, the researchers said.
The Herbert and Florence Irving Scholars Program at Columbia University provided funding. One coinvestigator disclosed grant funding from the National Institutes of Health and personal fees from UpToDate. The other investigators reported having no conflicts of interest.
A national shortage of norepinephrine in the United States was associated with higher rates of mortality among patients hospitalized with septic shock, investigators reported.
Rates of in-hospital mortality in 2011 were 40% during quarters when hospitals were facing shortages and 36% when they were not, Emily Vail, MD, and her associates said at the International Symposium on Intensive Care and Emergency Medicine. The report was published simultaneously in JAMA.
The link between norepinephrine shortage and death from septic shock persisted even after the researchers accounted for numerous clinical and demographic factors (adjusted odds ratio, 1.2; 95% confidence interval, 1.01 to 1.30; P = .03), wrote Dr. Vail of Columbia University, New York (JAMA. 2017 Mar 21. doi: 10.1001/jama.2017.2841).
Drug shortages are common in the United States, but few studies have explored their effects on patient outcomes. Investigators compared mortality rates among affected patients during 3-month intervals when hospitals were and were not using at least 20% less norepinephrine than baseline. The researchers used Premier Healthcare Database, which includes both standard claims and detailed, dated logs of all services billed to patients or insurance, with minimal missing data.
A total of 77% patients admitted with septic shock received norepinephrine before the shortage. During the lowest point of the shortage, 56% of patients received it, the researchers reported. Clinicians most often used phenylephrine instead, prescribing it to up to 54% of patients during the worst time of the shortage. The absolute increase in mortality during the quarters of shortage was 3.7% (95% CI, 1.5%-6.0%).
Several factors might explain the link between norepinephrine shortage and mortality, said the investigators. The vasopressors chosen to replace norepinephrine might result directly in worse outcomes, but a decrease in norepinephrine use also might be a proxy for relevant variables such as delayed use of vasopressors, lack of knowledge of how to optimally dose vasopressors besides norepinephrine, or the absence of a pharmacist dedicated to helping optimize the use of limited supplies.
The study did not uncover a dose-response association between greater decreases in norepinephrine use and increased mortality, the researchers noted. “This may be due to a threshold effect of vasopressor shortage on mortality, or lack of power due to relatively few hospital quarters at the extreme levels of vasopressor shortage,” they wrote.
Because the deaths captured included only those that occurred in-hospital, “the results may have underestimated mortality, particularly for hospitals that tend transfer patients early to other skilled care facilities,” the researchers noted.
The cohort of patients was limited to those who received vasopressors for 2 or more days and excluded patients who died on the first day of vasopressor treatment, the researchers said.
The Herbert and Florence Irving Scholars Program at Columbia University provided funding. One coinvestigator disclosed grant funding from the National Institutes of Health and personal fees from UpToDate. The other investigators reported having no conflicts of interest.
FROM ISICEM
Key clinical point. The 2011 norepinephrine shortage was associated with mortality among patients hospitalized with septic shock.
Major finding: Rates of in-hospital mortality were 36% during quarters of normal norepinephrine use and 40% during quarters of decreased use (adjusted odds ratio, 1.2; P = .03).
Data source: A retrospective cohort study of 27,835 patients at 26 hospitals in the United States that were affected by the shortage.
Disclosures: The Herbert and Florence Irving Scholars Program at Columbia University provided funding. One coinvestigator disclosed grant funding from the National Institutes of Health and personal fees from UpToDate. The other investigators reported having no conflicts of interest.
Trial supports FFR-guided complete revascularization during PCI for STEMI
WASHINGTON – Using fractional flow reserve (FFR) to revascularize noninfarct coronary arteries during percutaneous coronary intervention (PCI) significantly reduced the subsequent 1-year risk of major adverse cardiovascular events among patients with ST-segment myocardial infarction and multivessel disease, according to the results of a randomized, multicenter trial.
Only 23 patients (8%) who underwent complete FFR-guided revascularization died or had a nonfatal myocardial infarction, cerebrovascular event, or repeat revascularization within a year of treatment, compared with 121 (20.5%) patients who underwent infarct-only treatment (hazard ratio, 0.35; 95% confidence interval, 0.22-0.55; P less than .001), Pieter C. Smits, MD, PhD, reported during a late-breaker session at the annual meeting of the American College of Cardiology.
Importantly, coronary angiography overestimated the physiological significance of noninfart lesions in the study, the researchers wrote. About half of noninfarct lesions that were considered significant on angiography had FFR values above 0.80, meaning that they were not physiologically significant.
Some 50% of patients with acute ST-segment elevation myocardial infarction (STEMI) have severe stenotic lesions of noninfarct coronary arteries. These lesions often are managed conservatively, but two recent randomized trials have challenged this approach, tying preventive stent placement to lower rates of subsequent adverse events. However, both studies based the decision to use stents on angiographic appearance, not symptoms or ischemia, even though angiography can fail to accurately estimate the functional severity of a lesion, the investigators wrote. For stable patients, using FFR to guide revascularization instead can prevent adverse events compared with angiography or conservative management, they added.
To more rigorously compare FFR-guided revascularization of noninfarct coronary arteries with infarct-only treatment, the researchers randomly assigned 885 adults with acute STEMI and multivessel disease to one of these two approaches during primary PCI. A total of 295 patients underwent FFR-guided complete revascularization, and 590 underwent infarct-only treatment plus FFR evaluation of noninfarct-artery lesions.
Compared with infarct-only treatment, complete revascularization was associated with lower, but statistically similar, rates of mortality (1.7% vs. 1.4%; HR, 0.80; 95% CI, 0.25-2.6; P = .7), nonfatal myocardial infarction (4.7% vs. 2.4%; HR, 0.5; 95% CI, 0.2-1.1; P = .1), and cerebrovascular events (0.7% vs. 0%). The study lacked power to detect differences in rates of these uncommon events, the researchers noted.
In the infarct-only treatment group, stable or unstable angina accounted for most repeat revascularizations, about 80% of which were clinically indicated based on the study protocol, according to the researchers. Performing FFR-guided revascularization during primary PCI prevents sequential catheterizations and can potentially save costs by reducing predischarge stress tests, they commented. In their study, 12% of patients in the infarct-only group underwent stress tests, compared with 7% of those who underwent FFR-guided revascularization (P = .03).
Two patients experienced a serious adverse event related to FFR, the investigators noted. In one case, the FFR wire caused a dissection in the noninfarcted right coronary artery. The artery subsequently infarcted and the patient died in the hospital. Another patient developed an occlusion of the noninfarcted left anterior descending coronary artery. The patient developed ST-segment elevation and recurrent chest pain, but underwent successful PCI of the artery. There were no other adverse events except for brief episodes of atrioventricular conduction delay and episodes of moderate hypotension, they wrote.
This was an open-label study, and it is possible that patients and physicians in the infarct-only group were biased toward subsequent revascularizations because they knew the angiography results, the researchers also noted.
Maasstad Cardiovascular Research funded the study with unrestricted grants from Abbott Vascular and St. Jude Medical. Dr. Smits disclosed grant support from Abbott Vascular and St. Jude Medical, and grants support and personal fees from both entities outside the submitted work.
WASHINGTON – Using fractional flow reserve (FFR) to revascularize noninfarct coronary arteries during percutaneous coronary intervention (PCI) significantly reduced the subsequent 1-year risk of major adverse cardiovascular events among patients with ST-segment myocardial infarction and multivessel disease, according to the results of a randomized, multicenter trial.
Only 23 patients (8%) who underwent complete FFR-guided revascularization died or had a nonfatal myocardial infarction, cerebrovascular event, or repeat revascularization within a year of treatment, compared with 121 (20.5%) patients who underwent infarct-only treatment (hazard ratio, 0.35; 95% confidence interval, 0.22-0.55; P less than .001), Pieter C. Smits, MD, PhD, reported during a late-breaker session at the annual meeting of the American College of Cardiology.
Importantly, coronary angiography overestimated the physiological significance of noninfart lesions in the study, the researchers wrote. About half of noninfarct lesions that were considered significant on angiography had FFR values above 0.80, meaning that they were not physiologically significant.
Some 50% of patients with acute ST-segment elevation myocardial infarction (STEMI) have severe stenotic lesions of noninfarct coronary arteries. These lesions often are managed conservatively, but two recent randomized trials have challenged this approach, tying preventive stent placement to lower rates of subsequent adverse events. However, both studies based the decision to use stents on angiographic appearance, not symptoms or ischemia, even though angiography can fail to accurately estimate the functional severity of a lesion, the investigators wrote. For stable patients, using FFR to guide revascularization instead can prevent adverse events compared with angiography or conservative management, they added.
To more rigorously compare FFR-guided revascularization of noninfarct coronary arteries with infarct-only treatment, the researchers randomly assigned 885 adults with acute STEMI and multivessel disease to one of these two approaches during primary PCI. A total of 295 patients underwent FFR-guided complete revascularization, and 590 underwent infarct-only treatment plus FFR evaluation of noninfarct-artery lesions.
Compared with infarct-only treatment, complete revascularization was associated with lower, but statistically similar, rates of mortality (1.7% vs. 1.4%; HR, 0.80; 95% CI, 0.25-2.6; P = .7), nonfatal myocardial infarction (4.7% vs. 2.4%; HR, 0.5; 95% CI, 0.2-1.1; P = .1), and cerebrovascular events (0.7% vs. 0%). The study lacked power to detect differences in rates of these uncommon events, the researchers noted.
In the infarct-only treatment group, stable or unstable angina accounted for most repeat revascularizations, about 80% of which were clinically indicated based on the study protocol, according to the researchers. Performing FFR-guided revascularization during primary PCI prevents sequential catheterizations and can potentially save costs by reducing predischarge stress tests, they commented. In their study, 12% of patients in the infarct-only group underwent stress tests, compared with 7% of those who underwent FFR-guided revascularization (P = .03).
Two patients experienced a serious adverse event related to FFR, the investigators noted. In one case, the FFR wire caused a dissection in the noninfarcted right coronary artery. The artery subsequently infarcted and the patient died in the hospital. Another patient developed an occlusion of the noninfarcted left anterior descending coronary artery. The patient developed ST-segment elevation and recurrent chest pain, but underwent successful PCI of the artery. There were no other adverse events except for brief episodes of atrioventricular conduction delay and episodes of moderate hypotension, they wrote.
This was an open-label study, and it is possible that patients and physicians in the infarct-only group were biased toward subsequent revascularizations because they knew the angiography results, the researchers also noted.
Maasstad Cardiovascular Research funded the study with unrestricted grants from Abbott Vascular and St. Jude Medical. Dr. Smits disclosed grant support from Abbott Vascular and St. Jude Medical, and grants support and personal fees from both entities outside the submitted work.
WASHINGTON – Using fractional flow reserve (FFR) to revascularize noninfarct coronary arteries during percutaneous coronary intervention (PCI) significantly reduced the subsequent 1-year risk of major adverse cardiovascular events among patients with ST-segment myocardial infarction and multivessel disease, according to the results of a randomized, multicenter trial.
Only 23 patients (8%) who underwent complete FFR-guided revascularization died or had a nonfatal myocardial infarction, cerebrovascular event, or repeat revascularization within a year of treatment, compared with 121 (20.5%) patients who underwent infarct-only treatment (hazard ratio, 0.35; 95% confidence interval, 0.22-0.55; P less than .001), Pieter C. Smits, MD, PhD, reported during a late-breaker session at the annual meeting of the American College of Cardiology.
Importantly, coronary angiography overestimated the physiological significance of noninfart lesions in the study, the researchers wrote. About half of noninfarct lesions that were considered significant on angiography had FFR values above 0.80, meaning that they were not physiologically significant.
Some 50% of patients with acute ST-segment elevation myocardial infarction (STEMI) have severe stenotic lesions of noninfarct coronary arteries. These lesions often are managed conservatively, but two recent randomized trials have challenged this approach, tying preventive stent placement to lower rates of subsequent adverse events. However, both studies based the decision to use stents on angiographic appearance, not symptoms or ischemia, even though angiography can fail to accurately estimate the functional severity of a lesion, the investigators wrote. For stable patients, using FFR to guide revascularization instead can prevent adverse events compared with angiography or conservative management, they added.
To more rigorously compare FFR-guided revascularization of noninfarct coronary arteries with infarct-only treatment, the researchers randomly assigned 885 adults with acute STEMI and multivessel disease to one of these two approaches during primary PCI. A total of 295 patients underwent FFR-guided complete revascularization, and 590 underwent infarct-only treatment plus FFR evaluation of noninfarct-artery lesions.
Compared with infarct-only treatment, complete revascularization was associated with lower, but statistically similar, rates of mortality (1.7% vs. 1.4%; HR, 0.80; 95% CI, 0.25-2.6; P = .7), nonfatal myocardial infarction (4.7% vs. 2.4%; HR, 0.5; 95% CI, 0.2-1.1; P = .1), and cerebrovascular events (0.7% vs. 0%). The study lacked power to detect differences in rates of these uncommon events, the researchers noted.
In the infarct-only treatment group, stable or unstable angina accounted for most repeat revascularizations, about 80% of which were clinically indicated based on the study protocol, according to the researchers. Performing FFR-guided revascularization during primary PCI prevents sequential catheterizations and can potentially save costs by reducing predischarge stress tests, they commented. In their study, 12% of patients in the infarct-only group underwent stress tests, compared with 7% of those who underwent FFR-guided revascularization (P = .03).
Two patients experienced a serious adverse event related to FFR, the investigators noted. In one case, the FFR wire caused a dissection in the noninfarcted right coronary artery. The artery subsequently infarcted and the patient died in the hospital. Another patient developed an occlusion of the noninfarcted left anterior descending coronary artery. The patient developed ST-segment elevation and recurrent chest pain, but underwent successful PCI of the artery. There were no other adverse events except for brief episodes of atrioventricular conduction delay and episodes of moderate hypotension, they wrote.
This was an open-label study, and it is possible that patients and physicians in the infarct-only group were biased toward subsequent revascularizations because they knew the angiography results, the researchers also noted.
Maasstad Cardiovascular Research funded the study with unrestricted grants from Abbott Vascular and St. Jude Medical. Dr. Smits disclosed grant support from Abbott Vascular and St. Jude Medical, and grants support and personal fees from both entities outside the submitted work.
FROM ACC 17
Key clinical point:
Major finding: Only 23 patients (8%) who underwent complete FFR-guided revascularization died or had a nonfatal myocardial infarction, cerebrovascular event, or repeat revascularization within a year of treatment, compared with 121 (20.5%) patients who underwent infarct-only treatment (HR, 0.35; 95% CI, 0.22-0.55; P less than .001).
Data source: A prospective, multicenter, open-label clinical trial of 885 adults with acute STEMI and multivessel disease.
Disclosures: Maasstad Cardiovascular Research funded the study with unrestricted grants from Abbott Vascular and St. Jude Medical. Dr. Smits disclosed grant support from Abbott Vascular and St. Jude Medical, and grant support and personal fees from both entities outside the submitted work.
New approach for monitoring minimum residual disease in multiple myeloma
Next-generation sequencing might be useful to monitor for minimum residual disease in multiple myeloma, based on the results of a pilot study of 27 patients.
Of study participants whose multiple myeloma at least partially remitted on therapy, 41% showed evidence of persistent circulating myeloma cells or cell-free myeloma DNA based on next-generation sequencing of the clonotypic V(D)J rearrangement, compared with 91% of nonresponders or progressors (P less than .001), reported Anna Oberle of University Medical Center Hamburg-Eppendorf, Hamburg, Germany, and her associates. The findings were published in Haematologica.
“Taken together, our pilot study gives valuable biological insights into the circulating cellular and cell-free compartments explorable by ‘liquid biopsy’ in multiple myeloma,” the investigators wrote. Levels of V(D)J-positive circulating myeloma cells and cell-free DNA might decline faster in response to effective therapy than the “relatively inert M-protein,” and might therefore be a better way to immediately estimate treatment efficacy or predict minimum residual disease negativity, they added (Haematologica. 2017 Feb 9. doi: 10.3324/haematol.2016.161414).
Novel multiple myeloma therapies are inducing deeper, longer responses, which highlights the need for minimum residual disease monitoring, the researchers said. Next-generation sequencing of the clonotypic V(D)J immunoglobulin rearrangement has shown promise but requires painful bone marrow sampling. A minimally invasive alternative is to monitor for circulating myeloma cells (cmc) or cell-free myeloma (cfm). To investigate the feasibility of this technique, the researchers used next-generation sequencing to define the myeloma V(D)J rearrangement in bone marrow and to track sequential peripheral blood samples from multiple myeloma patients before and during treatment. Next-generation sequencing was performed with an Illumina MiSeq sequencer with 500 or 600 cycle single-indexed, paired-end runs.
After treatment initiation, 47% of follow-up peripheral blood samples were positive for cmc-V(D)J, cfm-V(D)J, or both, the researchers said. They found a clear link between poor remission status assessed by M-protein based IMWG criteria and positive cmc-V(D)J sampling, with a regression coefficient of 1.60 (95% CI, 0.68 to 2.50; P = .002). Poor remission status was also associated with evidence of cfm-V(D)J (regression coefficient 1.49; 95% CI, 0.70 to 2.27; P = .001).
“About half of partial responders showed complete clearance of circulating myeloma cells-/cell-free myeloma DNA -V(D)J despite persistent M-protein, suggesting that these markers are less inert than the M-protein, rely more on cell turnover, and therefore decline more rapidly after initiation of effective treatment,” the researchers emphasized. Also, in 30% of cases, patients were positive for only one of the two V(D)J measures, suggesting that cfm-V(D)J might reflect overall tumor burden, not just circulating tumor cells, they added. “Prospective studies need to define the predictive potential of high-sensitivity determination of circulating myeloma cells and DNA in the monitoring of multiple myeloma,” they concluded.
Eppendorfer Krebs- und Leukämiehilfe e.V. and the Deutsche Krebshilfe funded the study. The researchers disclosed no conflicts of interest.
Next-generation sequencing might be useful to monitor for minimum residual disease in multiple myeloma, based on the results of a pilot study of 27 patients.
Of study participants whose multiple myeloma at least partially remitted on therapy, 41% showed evidence of persistent circulating myeloma cells or cell-free myeloma DNA based on next-generation sequencing of the clonotypic V(D)J rearrangement, compared with 91% of nonresponders or progressors (P less than .001), reported Anna Oberle of University Medical Center Hamburg-Eppendorf, Hamburg, Germany, and her associates. The findings were published in Haematologica.
“Taken together, our pilot study gives valuable biological insights into the circulating cellular and cell-free compartments explorable by ‘liquid biopsy’ in multiple myeloma,” the investigators wrote. Levels of V(D)J-positive circulating myeloma cells and cell-free DNA might decline faster in response to effective therapy than the “relatively inert M-protein,” and might therefore be a better way to immediately estimate treatment efficacy or predict minimum residual disease negativity, they added (Haematologica. 2017 Feb 9. doi: 10.3324/haematol.2016.161414).
Novel multiple myeloma therapies are inducing deeper, longer responses, which highlights the need for minimum residual disease monitoring, the researchers said. Next-generation sequencing of the clonotypic V(D)J immunoglobulin rearrangement has shown promise but requires painful bone marrow sampling. A minimally invasive alternative is to monitor for circulating myeloma cells (cmc) or cell-free myeloma (cfm). To investigate the feasibility of this technique, the researchers used next-generation sequencing to define the myeloma V(D)J rearrangement in bone marrow and to track sequential peripheral blood samples from multiple myeloma patients before and during treatment. Next-generation sequencing was performed with an Illumina MiSeq sequencer with 500 or 600 cycle single-indexed, paired-end runs.
After treatment initiation, 47% of follow-up peripheral blood samples were positive for cmc-V(D)J, cfm-V(D)J, or both, the researchers said. They found a clear link between poor remission status assessed by M-protein based IMWG criteria and positive cmc-V(D)J sampling, with a regression coefficient of 1.60 (95% CI, 0.68 to 2.50; P = .002). Poor remission status was also associated with evidence of cfm-V(D)J (regression coefficient 1.49; 95% CI, 0.70 to 2.27; P = .001).
“About half of partial responders showed complete clearance of circulating myeloma cells-/cell-free myeloma DNA -V(D)J despite persistent M-protein, suggesting that these markers are less inert than the M-protein, rely more on cell turnover, and therefore decline more rapidly after initiation of effective treatment,” the researchers emphasized. Also, in 30% of cases, patients were positive for only one of the two V(D)J measures, suggesting that cfm-V(D)J might reflect overall tumor burden, not just circulating tumor cells, they added. “Prospective studies need to define the predictive potential of high-sensitivity determination of circulating myeloma cells and DNA in the monitoring of multiple myeloma,” they concluded.
Eppendorfer Krebs- und Leukämiehilfe e.V. and the Deutsche Krebshilfe funded the study. The researchers disclosed no conflicts of interest.
Next-generation sequencing might be useful to monitor for minimum residual disease in multiple myeloma, based on the results of a pilot study of 27 patients.
Of study participants whose multiple myeloma at least partially remitted on therapy, 41% showed evidence of persistent circulating myeloma cells or cell-free myeloma DNA based on next-generation sequencing of the clonotypic V(D)J rearrangement, compared with 91% of nonresponders or progressors (P less than .001), reported Anna Oberle of University Medical Center Hamburg-Eppendorf, Hamburg, Germany, and her associates. The findings were published in Haematologica.
“Taken together, our pilot study gives valuable biological insights into the circulating cellular and cell-free compartments explorable by ‘liquid biopsy’ in multiple myeloma,” the investigators wrote. Levels of V(D)J-positive circulating myeloma cells and cell-free DNA might decline faster in response to effective therapy than the “relatively inert M-protein,” and might therefore be a better way to immediately estimate treatment efficacy or predict minimum residual disease negativity, they added (Haematologica. 2017 Feb 9. doi: 10.3324/haematol.2016.161414).
Novel multiple myeloma therapies are inducing deeper, longer responses, which highlights the need for minimum residual disease monitoring, the researchers said. Next-generation sequencing of the clonotypic V(D)J immunoglobulin rearrangement has shown promise but requires painful bone marrow sampling. A minimally invasive alternative is to monitor for circulating myeloma cells (cmc) or cell-free myeloma (cfm). To investigate the feasibility of this technique, the researchers used next-generation sequencing to define the myeloma V(D)J rearrangement in bone marrow and to track sequential peripheral blood samples from multiple myeloma patients before and during treatment. Next-generation sequencing was performed with an Illumina MiSeq sequencer with 500 or 600 cycle single-indexed, paired-end runs.
After treatment initiation, 47% of follow-up peripheral blood samples were positive for cmc-V(D)J, cfm-V(D)J, or both, the researchers said. They found a clear link between poor remission status assessed by M-protein based IMWG criteria and positive cmc-V(D)J sampling, with a regression coefficient of 1.60 (95% CI, 0.68 to 2.50; P = .002). Poor remission status was also associated with evidence of cfm-V(D)J (regression coefficient 1.49; 95% CI, 0.70 to 2.27; P = .001).
“About half of partial responders showed complete clearance of circulating myeloma cells-/cell-free myeloma DNA -V(D)J despite persistent M-protein, suggesting that these markers are less inert than the M-protein, rely more on cell turnover, and therefore decline more rapidly after initiation of effective treatment,” the researchers emphasized. Also, in 30% of cases, patients were positive for only one of the two V(D)J measures, suggesting that cfm-V(D)J might reflect overall tumor burden, not just circulating tumor cells, they added. “Prospective studies need to define the predictive potential of high-sensitivity determination of circulating myeloma cells and DNA in the monitoring of multiple myeloma,” they concluded.
Eppendorfer Krebs- und Leukämiehilfe e.V. and the Deutsche Krebshilfe funded the study. The researchers disclosed no conflicts of interest.
Key clinical point: Next-generation sequencing might be useful to monitor for minimum residual disease in multiple myeloma.
Major finding: Of patients who at least partially remitted on therapy, 41% showed evidence of persistent circulating myeloma cells or cell-free myeloma DNA based on next-generation sequencing of the clonotypic V(D)J rearrangement, compared with 91% of nonresponders or progressors (P less than .001).
Data source: A pilot study of 27 patients with multiple myeloma.
Disclosures: Eppendorfer Krebs- und Leukämiehilfe e.V. and the Deutsche Krebshilfe funded the study. The researchers disclosed no conflicts of interest.
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: 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.