Society of Gynecologic Oncology Clinical Outcomes Registry: From small beginnings come great things.

OBJECTIVE: Clinical registries within medical societies have demonstrated the capacity to promote quality improvement. Opportunities for well-designed data repositories could yield reliable national standards for informing reimbursement, determining adherence to care guidelines, maintaining board certification, and developing bundled payment models. Looking to the future, we set out to develop a gynecologic cancer registry serving the members of the Society of Gynecologic Oncology (SGO). METHODS: The SGO Clinical Outcomes Registry (COR) initiated a web-based data entry platform as a foray into developing a functional registry, compiling data elements specific to gynecologic oncology. Endometrial and ovarian cancer patients began enrollment in early 2014. Within one year, 19 sites were participating with the addition of cervical cancer patients in January 2015. RESULTS: To date, >6500 patients are currently entered from 29 sites, and the COR is being queried to address topics of quality improvement, disparities, and cancer outcomes. CONCLUSIONS: The SGO COR has proven the feasibility of developing a functional gynecologic cancer registry, with high uptake, rapid accrual, and ability to investigate topics of quality and outcome using the COR.

Disparities in treatment and survival for women with endometrial cancer: A contemporary national cancer database registry analysis.

PURPOSE: The study aim was to identify contemporary socioeconomic, racial, ethnic, and facility-related factors associated with stage at diagnosis, receipt of cancer treatment, and survival in women with endometrial cancer (EC). PATIENTS AND METHODS: Women diagnosed with EC between 1998 and 2010 were identified from the National Cancer Database. Variables associated with the outcomes of interest were assessed using multivariable Cox proportional hazards and logistic regression. RESULTS: Among 228,511 women identified, the percentage of blacks with stage IIIC/IV disease at diagnosis was nearly twice that of non-Hispanic whites (17.8% vs 9.8%; P<0.001). Patients with advanced disease who were insured with Medicare were less likely to receive standard-of-care postoperative radiotherapy and/or chemotherapy than those with private insurance (odds ratio: OR 0.80, P<0.001), as were those residing in the South (reference) in comparison to the Northeast, Atlantic, Great Lakes, and Midwest regions (OR 1.3-1.7, all P<0.001). Those residing in the Mountain region were even less likely to receive appropriate treatment (OR 0.7, P<0.001). Five-year stage IIIC/IV survival was 42.8% for non-Hispanic whites vs 24.6% for blacks (hazard ratio 1.3, P<0.001). Other factors associated with inferior 5-year survival included payer status (not insured, Medicaid, Medicare, vs private, ORs 1.2-1.3, all P<0.01), and treatment at low-volume centers (<5 vs ≥30cases/year, HR 1.3, P<0.001). CONCLUSIONS AND RELEVANCE: Socioeconomic, geographic and facility-related factors predict advanced endometrial cancer stage, failure to receive cancer care, and shorter survival. Black women had especially poor survival. Nationwide standardization and concentration of treatment at high-volume centers may improve outcomes.

In vitro chemoresponse in metachronous pairs of ovarian cancers.

BACKGROUND/AIM: An in vitro chemoresponse assay may aid effective therapy selection in epithelial ovarian cancer (EOC). This study explores changes in chemoresponse between paired primary and recurrent EOC tumors. PATIENTS AND METHODS: RESULTS from metachronous tumors were examined in 242 patients. Changes in in vitro chemoresponse, measured by the area under the dose response curve (AUC) between paired tumors were assessed. RESULTS: A significant increase in AUC was identified in most first-line therapies over time. No significant difference was observed in most recurrent therapies. When the elapsed time between occurrences was <17 months, no difference was observed for any recurrent therapies, and half of first-line therapies exhibited significant increases in AUC. When ≥17 months, all 7 therapies showed significant increases. CONCLUSION: These results suggest an increase in chemoresistance over time, which is more pronounced for first-line therapies. This is consistent with clinical observations and suggests the biologic concordance between assay results and response to chemotherapy.

Tolerability, efficacy, and safety of pegylated liposomal Doxorubicin in combination with Carboplatin versus gemcitabine-Carboplatin for the treatment of platinum-sensitive recurrent ovarian cancer: a systematic review.

OBJECTIVE: To compare the tolerability, efficacy, and safety profiles of pegylated liposomal doxorubicin in combination with carboplatin (PLD-Carbo) with those of gemcitabine-carboplatin (Gem-Carbo) for the treatment of patients with platinum-sensitive recurrent ovarian cancer (PSROC) by reviewing the published literature. METHODS: Using the PubMed database, a systematic review of peer-reviewed literature published between January 2000 and September 2009 was undertaken to identify studies related to the treatment of patients with PSROC with PLD-Carbo or Gem-Carbo. Studies reporting either response rate, progression-free survival (PFS), and/or overall survival (OS) were included. Treatment regimens, efficacy endpoints, and safety profiles were compared between the two combination therapies. RESULTS: Ten studies evaluating 608 patients (PLD-Carbo: 5 studies, 278 patients; Gem-Carbo: 5 studies, 330 patients) were identified. The mean planned doses were: PLD, 34.8 mg/m(2) and Gem, 993 mg/m(2). The dose intensity reported in Gem trials was lower (75% of the planned dose) than the dose intensity reported in PLD trials (93.7% of the planned dose), suggesting better tolerability for the PLD-Carbo regimen. Among patients receiving PLD-Carbo, 60.2% achieved a response (complete, 27.0%; partial, 33.2%), versus 51.4% of patients treated with Gem-Carbo (complete, 19.2%; partial, 32.2%). The median PFS times were 10.6 months and 8.9 months in the PLD-Carbo and the Gem-Carbo populations, respectively. The median OS was longer for the PLD-Carbo regimen (27.1 months) than for the Gem-Carbo regimen (19.7 months). The hematological safety profiles were comparable in the two groups, although grade III or IV anemia (PLD-Carbo, 13.6%; Gem-Carbo, 24.5%) and neutropenia (PLD-Carbo, 45.5%; Gem-Carbo, 62.9%) were more common in patients receiving Gem-Carbo. CONCLUSION: Results from this systematic analysis of peer-reviewed literature suggest that PLD-Carbo therapy is a rational alternative to Gem-Carbo for the treatment of patients with PSROC.

Weekly topotecan for recurrent platinum resistant ovarian cancer.

OBJECTIVE: To evaluate toxicity, response and progression-free survival of weekly topotecan chemotherapy in women with primary and secondary platinum-resistant epithelial ovarian cancer. METHODS: A retrospective analysis of 69 patients who received weekly topotecan with a median dose of 3.75 on days 1, 8 and 15 of a 28-day cycle treated between November 2002 and May 2005. All patients had recurrent epithelial ovarian, primary peritoneal or tubal cancer with primary or secondary resistance to platinum. Disease response was evaluated by CA-125 levels, physical exam, and when appropriate, imaging studies. Toxicity was evaluated using the NCI Common Toxicity Criteria. RESULTS: Response to topotecan therapy was noted in 14 of 69 patients (20.3%); (complete response 7.3%, and partial response 13%). Stable disease was noted in 23 patients (33.3%) and progression of disease occurred in 31 patients (44.9%). Two patients (2.8%) had significant side effects that warranted discontinuation of therapy. There was no significant difference in response to therapy between patients with primary or secondary platinum resistance. A total of 229 cycles was given with a median of 3 (range 1-12) cycles per patient. Grades 3 and 4 myelosuppression was rare: 1 cycle (0.4%) with grade 3 leukopenia, 16 cycles (7%) with grade 3 or 4 neutropenia, 1 cycle (0.4%) with grade 3 anemia, and 2 cycles (0.9%) with grade 3 thrombocytopenia. No patient was admitted with neutropenic fever. The median progression-free survival for responders was 5.7 months (2-16.75). CONCLUSIONS: Weekly topotecan is a well-tolerated and effective regimen for platinum-resistant ovarian cancer with considerable less hematological toxicity when compared with historical data for the 5-day regimen.

Subcutaneous management of vertical incisions with 3 or more centimeters of subcutaneous fat.

OBJECTIVE: This study was undertaken to determine the most appropriate management of the subcutaneous tissue of midline vertical incisions with 3 cm or more of subcutaneous fat. STUDY DESIGN: Patients undergoing surgery within the Division of Gynecologic Oncology at University of South Florida and East Tennessee State University with 3 cm or more of subcutaneous fat were randomly assigned to 1 of 3 groups: suture approximation of Camper's fascia, closed suction drainage of the subcutaneous space, or no intervention as a control group. Participants were evaluated daily during postoperative hospitalization and at 2 and 6 weeks postoperatively as an outpatient. Demographic information, perioperative data, and wound complications were recorded and then analyzed with chi2, t test, analysis of variance, and logistic regression where appropriate. RESULTS: Two hundred twenty-five patients were enrolled with 222 eligible for evaluation. Wound complications were observed in 34 (15.3%) patients, and 25 of these women also had wound disruption. Overall wound complication and wound disruption rates were not significantly different between groups: suture (12.8%, 7.7%), drain (17.9%, 14.9%), control (15.6%, 11.7%); P = .70 and P = .39, respectively. CONCLUSION: Suture approximation or drainage of the subcutaneous tissues of women with 3 cm or more subcutaneous fat measured in midline vertical incisions resulted in no significant change in the incidence of overall wound complications or superficial wound disruption.

Clinical results and quality of life analysis for the MVAC combination (methotrexate, vinblastine, doxorubicin, and cisplatin) in carcinoma of the uterine cervix: A Gynecologic Oncology Group study.

OBJECTIVES: The Gynecologic Oncology Group (GOG) compared methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) with topotecan and cisplatin (TC) or cisplatin alone (C) in advanced cervical cancer. The primary endpoint was overall survival (OS), with response rate, progression-free survival (PFS), and quality of life (QOL) as secondary objectives. METHODS: Eligible patients were randomly allocated to receive either cisplatin 50 mg/m2 q 3 weeks (C) or cisplatin 50 mg/m2 day 1 and topotecan 0.75 mg/m2 days 1-3 q 3 weeks (TC) or methotrexate 30 mg/m2 days 1, 15, and 22, vinblastine 3 mg/m2 days 2, 15, and 22, doxorubicin 30 mg/m2 day 2, and cisplatin 70 mg/m2 day 2 q 4 weeks (MVAC). QOL was assessed at four time points using the Functional Assessment of Cancer Therapy-Cervix (FACT-Cx), Neurotoxicity Subscale (FACT/GOG-NTX subscale), and Brief Pain Inventory (BPI). RESULTS: One hundred eighty-six patients (C = 60; TC = 63; MVAC = 63) were enrolled before MVAC was closed by the GOG Data Safety Monitoring Board after four treatment-related deaths occurred on that arm. MVAC produced a 22% overall response rate (95% CI: 0.13 to 0.34) and median PFS and OS of 4.4 months and 9.4 months, respectively. Compared with C and TC, there was more hematologic toxicity with MVAC. There were no appreciable differences in QOL scores after controlling for baseline scores. CONCLUSIONS: MVAC's clinical activity tended to be similar to that of TC but with an unacceptable risk of death from sepsis at this dose and schedule. Nevertheless, QOL, as measured by these instruments, was not substantially impaired by this regimen.

Sites of bowel resected to achieve optimal ovarian cancer cytoreduction: implications regarding surgical management.

OBJECTIVE: The purpose of this study was to 1) report on the distribution of bowel segments resected in a population of patients who underwent primary optimal cytoreductive surgery for epithelial ovarian cancer, and 2) discuss implications for surgical management regarding resection of these bowel segments. STUDY DESIGN: This was a retrospective study from 1995 to 2003 of 144 ovarian cancer patients who underwent primary optimal cytoreductive operations that included bowel resection. RESULTS: Bowel segments removed and major complications are presented in tabulated form. Eighty-one out of 144 resections were rectosigmoid only. Thirty-six percent had extensive involvement of colon segments separate from the rectosigmoid. Excluding hemorrhage, 9 patients (6%) experienced a major complication. CONCLUSION: The present study does suggest the necessity for a highly individualized approach to the surgical management of epithelial ovarian cancer patients who can be optimally cyto-reduced by resection of multifocal colonic involvement. Further study is needed to better assess the complications, function, and oncologic outcome of the different surgical approaches to these patients.

A phase II evaluation of flavopiridol as second-line chemotherapy of endometrial carcinoma: a Gynecologic Oncology Group study.

OBJECTIVE: A phase II study was conducted to determine the efficacy of single agent flavopiridol therapy in patients with recurrent or persistent endometrial adenocarcinoma refractory to established treatments. METHODS: Eligible patients with measurable disease who failed primary therapy including one cytotoxic regimen were eligible for the trial. They were treated with single agent flavopiridol (50 mg/m(2)/day, IV bolus days 1, 2, 3). Treatment was repeated every 21 days with dose adjustments made for toxicity. Patients were treated until progression of disease or adverse side effects precluded further therapy. RESULTS: A total of 26 patients were enrolled in the study of whom, 23 patients were eligible. There were no objective responses. Five patients had stable disease (22%), 15 (65%) had increasing disease, and response could not be assessed in 3 (13%). The most frequent side effects included anemia, neutropenia, and diarrhea, all of which appeared manageable. CONCLUSION: Flavopiridol as a single agent in the above dosing schedule appears to have minimal activity as second-line chemotherapy of endometrial adenocarcinoma.

The administration of chemotherapy in a patient with Charcot-Marie-Tooth and ovarian cancer.

BACKGROUND: Standard adjuvant chemotherapy for epithelial ovarian carcinoma most commonly consists of a combination of carboplatin with a taxane derivative. However, treatment-related side effects such as peripheral neuropathy and neutropenia can be debilitating and in certain patient populations alterations may need to be considered. CASE: We describe a case of a patient with epithelial ovarian carcinoma who had pre-existing peripheral neuropathy secondary to Charcot-Marie-Tooth Disease (CMT). She developed a distal sensory and motor neuropathy after her first treatment with carboplatin and paclitaxel and was unable to walk, write, or drive. Upon transfer of care to our center, we changed her taxane to docetaxel and her symptoms improved dramatically. We discuss the outcome of her treatment and the effects of paclitaxel on her underlying peripheral neuropathy. CONCLUSION: Patients with Charcot-Marie-Tooth Disease who require chemotherapy may not be able to tolerate the neurotoxic side effects of paclitaxel-based chemotherapy. Consideration of alternative, less neurotoxic treatment regimens containing docetaxel may be considered.

Randomized phase III trial of cisplatin with or without topotecan in carcinoma of the uterine cervix: a Gynecologic Oncology Group Study.

PURPOSE: On the basis of reported activity of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) or topotecan plus cisplatin in advanced cervix cancer, we undertook a randomized trial comparing these combinations versus cisplatin alone, to determine whether survival is improved with either combination compared with cisplatin alone, and to compare toxicities and quality of life (QOL) among the regimens. PATIENTS AND METHODS: Eligible patients were randomly allocated to receive cisplatin 50 mg/m(2) every 3 weeks (CPT); cisplatin 50 mg/m(2) day 1 plus topotecan 0.75 mg/m(2) days 1 to 3 every 3 weeks (CT); or methotrexate 30 mg/m(2) days 1, 15, and 22, vinblastine 3 mg/m(2) days 2, 15, and 22, doxorubicin 30 mg/m(2) day 2, and cisplatin 70 mg/m(2) day 2 every 4 weeks (MVAC). Survival was the primary end point; response rate and progression-free survival (PFS) were secondary end points. QOL data are reported separately. RESULTS: The MVAC arm was closed by the Data Safety Monitoring Board after four treatment-related deaths occurred among 63 patients, and is not included in this analysis. Two hundred ninety-four patients enrolled onto the remaining regimens: 146 to CPT and 147 to CT. Grade 3 to 4 hematologic toxicity was more common with CT. Patients receiving CT had statistically superior outcomes to those receiving CPT, with median overall survival of 9.4 and 6.5 months (P = .017), median PFS of 4.6 and 2.9 months (P = .014), and response rates of 27% and 13%, respectively. CONCLUSION: This is the first randomized phase III trial to demonstrate a survival advantage for combination chemotherapy over cisplatin alone in advanced cervix cancer.

Lysophospholipids are potential biomarkers of ovarian cancer.

OBJECTIVE: To determine whether lysophosphatidic acid (LPA) and other lysophospholipids (LPL) are useful markers for diagnosis and/or prognosis of ovarian cancer in a controlled setting. METHOD: Plasma samples were collected from ovarian cancer patients and healthy control women in Hillsborough and Pinellas counties, Florida, and processed at the University of South Florida H. Lee Moffitt Cancer Center and Research Institute (Moffitt). Case patients with epithelial ovarian cancer (n = 117) and healthy control subjects (n = 27) participated in the study. Blinded LPL analysis, including 23 individual LPL species, was performed at the Cleveland Clinic Foundation using an electrospray ionization mass spectrometry-based method. LPL levels were transmitted to Moffitt, where clinical data were reviewed and statistical analyses were performed. RESULTS: There were statistically significant differences between preoperative case samples (n = 45) and control samples (n = 27) in the mean levels of total LPA, total lysophosphatidylinositol (LPI), sphingosine-1-phosphate (S1P), and individual LPA species as well as the combination of several LPL species. The combination of 16:0-LPA and 20:4-LPA yielded the best discrimination between preoperative case samples and control samples, with 93.1% correct classification, 91.1% sensitivity, and 96.3% specificity. In 22 cases with both preoperative and postoperative samples, the postoperative levels of several LPL, including S1P, total LPA, and lysophosphatidylcholine (LPC) levels and some individual species of LPA and LPC, were significantly different from preoperative levels. CONCLUSION: LPA, LPI, LPC, and S1P appear useful as diagnostic and prognostic biomarkers of ovarian cancer.

Accuracy of pelvic examination in the assessment of patients with operable cervical cancer.

OBJECTIVE: The purpose of this study was to determine whether pelvic examination identifies factors that suggest the need for radiotherapy after radical hysterectomy for cervical cancer. STUDY DESIGN: This was an observational study that was conducted from July 1, 2000 through December 31, 2002 that comprised 67 patients with stage 1B-2A cervical cancer who underwent primary surgical treatment. Assessments that were made on pelvic examination were compared with pathologic findings. Data were analyzed with the use of descriptive statistics, calculation of sensitivities, specificities, positive and negative predictive values, and determination of odds ratios. RESULTS: The overall spectrum of small to large tumors (<1-8 cm) and cervices (2.5-8 cm) correlated well with examination (r=0.77-0.88). The accuracy of examination was approximately 50% for tumor diameter (+/-25%), 85% for cervical diameter (+/-25%), 80% for outer-third invasion, 80% for endophytic growth, and 90% for vaginal involvement. The likelihood for adjuvant radiotherapy had a significant association with the number of at-risk examination variables that were present. CONCLUSION: For women who undergo radical hysterectomy for stage 1B to 2A cervical cancer, the presence of multiple high-risk factors that are found on pelvic examination is associated significantly with indications for adjuvant postoperative radiotherapy.

Infectious urinary tract morbidity with prolonged bladder catheterization after radical hysterectomy.

OBJECTIVE: This study was undertaken to determine the incidence of catheter-associated infection after radical hysterectomy and to evaluate the role of prophylactic antibiotics in these patients. STUDY DESIGN: A 4-year retrospective review of 102 women undergoing radical hysterectomy for cervical or endometrial cancer was performed. Clinical data were abstracted and analyzed with chi(2) and t tests. RESULTS: Catheter-associated infection was observed in 11% (12 of 102) and was not altered by the administration of prophylactic antibiotics (11.1% vs 11.8%, P=.95). Of the 12 women who had infection, 11 were treated as outpatients, and 1 patient required admission for pyelonephritis. Patient age, comorbid medical conditions, class of radical hysterectomy, perioperative complications, operative time, blood loss, catheter type, duration of catheterization, and length of hospitalization had no effect on the development of catheter-associated infection. CONCLUSION: The incidence of catheter-associated infection in women requiring prolonged catheterization after radical hysterectomy is relatively low. Withholding prophylactic antibiotics from these patients is a reasonable clinical option.