Maintenance with mirvetuximab soravtansine plus bevacizumab vs bevacizumab in FRα-high platinum-sensitive ovarian cancer.

At first recurrence, platinum-sensitive ovarian cancer (PSOC) is frequently treated with platinum-based chemotherapy doublets plus bevacizumab, then single-agent bevacizumab. Most patients' disease progresses within a year after chemotherapy, emphasizing the need for novel strategies. Mirvetuximab soravtansine-gynx (MIRV), an antibody-drug conjugate, comprises a folate receptor alpha (FRα)-binding antibody and tubulin-targeting payload (maytansinoid DM4). In FRα-high PSOC, MIRV plus bevacizumab previously showed promising efficacy (objective response rate, 69% [95% CI: 41-89]; median progression-free survival, 13.3 months [95% CI: 8.3-18.3]; median duration of response, 12.9 months [95% CI: 6.5-15.7]) and safety. The Phase III randomized GLORIOSA trial will evaluate MIRV plus bevacizumab vs. bevacizumab alone as maintenance therapy in patients with FRα-high PSOC who did not have disease progression following second-line platinum-based doublet chemotherapy plus bevacizumab.Clinical Trial Registration: ClinicalTrials.gov ID: NCT05445778; GOG.org ID: GOG-3078; ENGOT.ESGO.org ID: ENGOT-ov76.

Most patients with ovarian cancer are initially treated with platinum-based chemotherapy. If the cancer reappears/recurs after more than 6 months following this therapy, it is called platinum-sensitive ovarian cancer (PSOC). Patients with PSOC usually receive additional platinum-based chemotherapy along with bevacizumab, a drug that reduces tumor growth by decreasing its blood supply. If patients improve or are stable on this therapy, they are usually kept on bevacizumab alone for 'maintenance therapy'. Unfortunately, this maintenance therapy does not work long-term in all patients, so better long-term treatments are needed. The GLORIOSA (NCT05445778) clinical trial will compare maintenance therapy with bevacizumab alone to maintenance therapy with bevacizumab plus a drug called mirvetuximab soravtansine-gynx (MIRV) to determine which therapy leads to better results in patients with PSOC. MIRV is made up of an antibody that binds to a specific protein (folate receptor alpha [FRα]) on cancer cells to directly deliver a cancer-killing drug. MIRV received US FDA approval to be used as a therapy for patients with ovarian cancer who are resistant to platinum-based chemotherapy and express high levels of FRα. The GLORIOSA trial will study maintenance therapy with MIRV plus bevacizumab in patients with PSOC who have not had cancer progression after second-line platinum-based chemotherapy plus bevacizumab, and whose cancer expresses high amounts of FRα. The main purpose of this trial is to determine if MIRV plus bevacizumab leads to better patient survival and decreases cancer growth and spread when compared with bevacizumab alone.

Safety and tolerance of radical hysterectomy for cervical cancer in the elderly.

BACKGROUND: Despite institutional studies that suggest that radical hysterectomy for cervical cancer is well tolerated in the elderly, little population-level data are available on the procedure's outcomes in older women. We performed a population-based analysis to determine the morbidity, mortality, and resource utilization of radical hysterectomy in elderly women with cervical cancer. METHODS: Patients recorded in the Nationwide Inpatient Sample with invasive cervical cancer who underwent abdominal radical hysterectomy between 1998 and 2010 were analyzed. Patients were stratified by age: <50, 50-59, 60-69, and ≥70 years. We examined the association between age and the outcomes of interest using chi square tests and multivariable generalized estimating equations. RESULTS: A total of 8199 women were identified, including 768 (9.4%) women age 60-69 and 462 (5.6%) women ≥70 years of age. All cause morbidity increased from 22.1% in women <50, to 24.7% in those 50-59 years, 31.4% in patients 60-69 years and 34.9% in women >70years of age (P<0.0001). Compared to women<50, those >70 were more likely to have intraoperative complications (4.8% vs. 9.1%, P=0.0003), surgical site complications (10.9% vs. 17.5%, P<0.0001), and medical complications (9.9% vs. 19.5%, P<0.0001). The risk of non-routine discharge (to a nursing facility) was 0.5% in women <50 vs. 12.3% in women ≥70 (P<0.0001). Perioperative mortality women ≥70 years of age was 30 times greater than that of women <50 (P<0.0001). CONCLUSION: Perioperative morbidity and mortality are substantially greater in elderly women who undergo radical hysterectomy for cervical cancer. Non-surgical treatments should be considered in these patients.

Utility of cell salvage in women undergoing abdominal myomectomy.

OBJECTIVE: We examined the use and cost of autologous blood cell salvage in women who undergo abdominal myomectomy. STUDY DESIGN: Patients who underwent abdominal myomectomy from 2007-2011 were identified. Use of the cell salvage system and reinfusion of autologous blood in women who had the system set-up were analyzed. Cost was examined by directly reported data. RESULTS: We identified 607 patients who underwent abdominal myomectomy. Four hundred twenty-five women (70%) had the set-up of the cell salvage system. Cell-salvaged blood was processed and reinfused into 85 of these subjects (20%). In a multivariable model, performance of myomectomy by a gynecologic-specific surgeon (odds ratio [OR], 2.14; 95% confidence interval [CI], 1.28-3.59), >5 myomas (OR, 2.49; 95% CI, 1.27-4.89), and larger uterine size statistically were associated significantly with cell-salvage device set-up. Conversely, having a reproductive-endocrinology-infertility specialist as the surgeon was associated with a significant reduction in cell-salvage system set-up (OR, 0.37; 95% CI, 0.21-0.66). For the women who had cell-salvage system set-up, uterine size of >15-19 weeks of gestation (OR, 3.22; 95% CI, 1.56-8.95) or ≥20 weeks of gestation (OR, 4.62; 95% CI, 1.45-14.73), operating time of >120 minutes (OR, 3.98; 95% CI, 1.70-9.29), and intraoperative blood loss of >1000 mL (OR, 26.31; 95% CI, 10.49-65.99) were associated significantly with a higher incidence of reinfusion of cell-salvaged blood. CONCLUSION: The routine use of cell salvage in women who undergo abdominal myomectomy does not appear to be warranted. Cell-salvage set-up appears to be cost-effective only when reinfused, but clinical characteristics cannot predict accurately which women will require reinfusion of cell-salvaged blood.

Patterns of use of hemostatic agents in patients undergoing major surgery.

BACKGROUND: Although a number of prohemostatic agents that are applied intraoperatively have been introduced to minimize bleeding, little is known about the patterns of use and the factors that influence use. We examined the use of hemostatic agents in patients undergoing major surgery. METHODS: All patients who underwent major general, gynecologic, urologic, cardiothoracic, or orthopedic surgery from 2000-2010 who were recorded in the Perspective database were analyzed. RESULTS: Among 3,633,799 patients, hemostatic agents were used in 30.3% (n = 1,102,267). The use of hemostatic agents increased from 28.5% in 2000 to 35.2% in 2010. Over the same period, the rates of transfusion declined for pancreatectomy (-14.4%), liver resection (-15.0%), gastrectomy (-11.7%), prostatectomy (-6.6%), nephrectomy (-4.6%), hip arthroplasty (-10.4%), and knee arthroplasty (-6.6%). Over the same time period, the transfusion rate increased for colectomy (6.0%), hysterectomy (3.7%), coronary artery bypass graft (8.4%), valvuloplasty (4.2%), lung resection (1.9%), and spine surgery (1.6%). Transfusion remained relatively stable for thyroidectomy (0.2%). CONCLUSIONS: The use of hemostatic agents has increased rapidly even for surgeries associated with a small risk of transfusion and bleeding complications. In addition to patient characteristics, surgeon and hospital factors exerted substantial influence on the allocation of hemostatic agents.

Body surface area predicts plasma oxaliplatin and pharmacokinetic advantage in hyperthermic intraoperative intraperitoneal chemotherapy.

BACKGROUND: Hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) is used to treat peritoneal surface-spreading malignancies to maximize local drug concentrations while minimizing systemic effects. The pharmacokinetic advantage of HIPEC is defined as the intraperitoneal to intravascular ratio of drug concentrations. We hypothesized that body surface area (BSA) would correlate with the pharmacokinetic advantage of HIPEC. Because oxaliplatin is administered in 5 % dextrose, we hypothesized that BSA would correlate with glycemia. METHODS: We collected blood and peritoneal perfusate samples from ten patients undergoing HIPEC with a BSA-based dose of 250 mg/m(2) oxaliplatin, and measured drug concentrations by inductively coupled plasma mass spectrophotometry. We monitored blood glucose for 24 h postoperatively. Areas under concentration-time curves (AUC) were calculated by trapezoidal rule. Pharmacokinetic advantage was calculated by (AUC[peritoneal fluid]/AUC[plasma]). We used linear regression to test for statistical significance. RESULTS: Higher BSA was associated with lower plasma oxaliplatin AUC (p = 0.0075) and with a greater pharmacokinetic advantage (p = 0.0198) over the 60-minute duration of HIPEC. No statistically significant relationships were found between BSA and blood glucose AUC or peak blood glucose levels. CONCLUSIONS: Higher BSA is correlated with lower plasma drug levels and greater pharmacokinetic advantage in HIPEC, likely because of increased circulating blood volume with inadequate time for equilibration. Plasma glucose levels after oxaliplatin HIPEC were not clearly related to BSA.

Quantitative X-ray computed tomography peritoneography in malignant peritoneal mesothelioma patients receiving intraperitoneal chemotherapy.

BACKGROUND: Intraperitoneal chemotherapy is used to treat peritoneal surface-spreading malignancies. We sought to determine whether volume and surface area of the intraperitoneal chemotherapy compartments are associated with overall survival and posttreatment glomerular filtration rate (GFR) in malignant peritoneal mesothelioma (MPM) patients. METHODS: Thirty-eight MPM patients underwent X-ray computed tomography peritoneograms during outpatient intraperitoneal chemotherapy. We calculated volume and surface area of contrast-filled compartments by semiautomated computer algorithm. We tested whether these were associated with overall survival and posttreatment GFR. RESULTS: Decreased likelihood of mortality was associated with larger surface areas (p = 0.0201) and smaller contrast-filled compartment volumes (p = 0.0341), controlling for age, sex, histologic subtype, and presence of residual disease >0.5 cm postoperatively. Larger volumes were associated with higher posttreatment GFR, controlling for pretreatment GFR, body surface area, surface area, and the interaction between body surface area and volume (p = 0.0167). DISCUSSION: Computed tomography peritoneography is an appropriate modality to assess for maldistribution of intraperitoneal chemotherapy. In addition to identifying catheter failure and frank loculation, quantitative analysis of the contrast-filled compartment's surface area and volume may predict overall survival and cisplatin-induced nephrotoxicity. Prospective studies should be undertaken to confirm and extend these findings to other diseases, including advanced ovarian carcinoma.

Prognostic significance of mucinous differentiation of endometrioid adenocarcinoma of the endometrium.

Using Surveillance, Epidemiology, and End Results database we identified 43,882 (97.0%) women with endometrioid adenocarcinomas and 1,374 (3.0%) with mucinous adenocarcinomas. Women with mucinous tumors were older (P < .0001), more often white (P = .04), and more often to present at advanced stage (P = .001). Survival was similar for both histologies; the hazard ratio for cancer-specific survival for mucinous compared to endometrioid tumors was 0.90 (95% CI, 0.74-1.09) while the hazard ratio for overall survival was 0.95 (95% CI, 0.85-1.07). Five-year survival for stage I mucinous tumors was 89.9% (95% CI, 87.6-91.9%) compared to 89.0% (95% CI, 88.6-89.4%) for endometrioid tumors.

Carcinosarcoma of the ovary: natural history, patterns of treatment, and outcome.

OBJECTIVE: Ovarian carcinosarcomas (OCS) are rare tumors composed of both malignant epithelial and mesenchymal elements. We compared the natural history and outcomes of OCS to serous carcinoma of the ovary. METHODS: Patients with OCS and serous carcinomas registered in the Surveillance, Epidemiology, and End Results (SEER) database between 1988 and 2007 were analyzed. Demographic and clinical characteristics were compared using chi square tests while survival was analyzed using Cox proportional hazards models and the Kaplan-Meier method. RESULTS: A total of 27,737 women, including 1763 (6.4%) with OCS and 25,974 (93.6%) with serous carcinomas, were identified. Patients with carcinosarcomas tended to be older and have unstaged tumors (P<0.0001). After adjusting for other prognostic factors, women with carcinosarcomas were 72% more likely to die from their tumors (HR=1.72; 95% CI, 1.52-1.96). Five-year survival for stage I carcinosarcomas was 65.2% (95% CI, 58.0-71.4%) vs. 80.6% (95% CI, 78.9-82.2%) for serous tumors. Similarly, five-year survival for stage IIIC patients was 18.2% (95% CI, 14.5-22.4%) for carcinosarcomas compared to 33.3% (95% 32.1-34.5%) for serous carcinomas. CONCLUSIONS: Ovarian carcinosarcomas are aggressive tumors with a natural history that is distinct from serous cancers. The survival for both early and late stage carcinosarcoma is inferior to serous tumors.

Uptake and outcomes of intensity-modulated radiation therapy for uterine cancer.

OBJECTIVE: While intensity-modulated radiation therapy (IMRT) allows more precise radiation planning, the technology is substantially more costly than conformal radiation and, to date, the benefits of IMRT for uterine cancer are not well defined. We examined the use of IMRT and its effect on late toxicity for uterine cancer. METHODS: Women with uterine cancer treated from 2001 to 2007 and registered in the SEER-Medicare database were examined. We investigated the extent and predictors of IMRT administration. The incidence of acute and late-radiation toxicities was compared for IMRT and conformal radiation. RESULTS: We identified a total of 3555 patients including 328 (9.2%) who received IMRT. Use of IMRT increased rapidly and reached 23.2% by 2007. In a multivariable model, residence in the western U.S. and receipt of chemotherapy were associated with receipt of IMRT. Women who received IMRT had a higher rate of bowel obstruction (rate ratio=1.41; 95% CI, 1.03-1.93), but other late gastrointestinal and genitourinary toxicities as well as hip fracture rates were similar between the cohorts. After accounting for other characteristics, the cost of IMRT was $14,706 (95% CI, $12,073 to $17,339) greater than conformal radiation. CONCLUSION: The use of IMRT for uterine cancer is increasing rapidly. IMRT was not associated with a reduction in radiation toxicity, but was more costly.

Failure to rescue after major gynecologic surgery.

OBJECTIVE: There is growing recognition that, in addition to occurrence of perioperative complications, the treatment of patients with complications influences outcome. We examined complications, failure to rescue (death in patients with a complication), and mortality rates for women who underwent abdominal hysterectomy. STUDY DESIGN: Women who underwent abdominal hysterectomy from 1998-2010 and whose data were recorded in the Nationwide Inpatient Sample were identified. Hospitals were stratified based on risk-adjusted mortality rates into 5 quintiles, and rates of complications and failure to rescue were examined. RESULTS: A total of 664,229 women who had been treated at 741 hospitals were identified. The overall mortality rate for the cohort was 0.17%. The risk-adjusted, hospital-level mortality rate ranged from 0-1.12%. The complication rate was 6.5% at the hospitals with the lowest mortality rates, 9.9% at the second quintile hospitals, 9.5% at both the third and fourth quintile hospitals, and 7.9% at the hospitals with the highest mortality rates. In contrast to complications, the failure-to-rescue rate increased with each successive risk-adjusted mortality quintile. The failure-to-rescue rate was 0% at the hospitals with the lowest mortality rates and increased with each successive quintile to 1.1%, 2.1%, 2.7%, and 4.4% in the hospitals with the highest mortality rates (P < .0001). CONCLUSION: For women who underwent abdominal hysterectomy, hospital complication rates correlated poorly with mortality rates; failure-to-rescue is strongly associated with in-hospital mortality rates. The treatment of complications, not the actual development of a complication, is the most important factor to use to predict death after major gynecologic surgery.