Clinical outcomes with utilization of high-potency topical steroids in patients with lichen sclerosus-associated vulvar cancer.

OBJECTIVES: To evaluate the impact of high-potency topical steroid use on risk of recurrence of lichen sclerosus-associated vulvar cancer. METHODS: This is a retrospective cohort study evaluating patients with lichen sclerosus (LS)- associated vulvar squamous cell cancer (VSCC). Demographic and clinical outcome data were compared between two comparison groups: patients who received steroids, mainly clobetasol, and patients who did not receive steroids following treatment of LS-related vulvar cancer. Categorical variables were compared using Fisher's exact test or chi-square test. Continuous variables were compared using a two-sided student's t-test. Time to recurrence (TTR) and overall survival (OS) were analyzed using Kaplan-Meier survival plot and compared using Mantel-Cox log rank test. Cox proportional hazard regression models were conducted to generate hazard ratios for both TTR and OS. A p value of <0.05 was considered statistically significant. RESULTS: A total of 49 patients were included, with 36 patients receiving steroid treatment and 13 patients in the expectant management group. The median age of diagnosis was 68. The average BMI was 31.7 +/- 7.0. The median length of follow up was 41 months. The majority of patients were diagnosed with stage I VSCC. There was no difference in demographics or oncologic management of vulvar cancer between the two cohorts. Overall recurrence was decreased among patients who received steroid treatment when compared to patients who did not, 12 patients (33.3%) versus 9 patients (69.2%) respectively (p = 0.048). CONCLUSIONS: High-potency topical steroid use following treatment of lichen sclerosus-associated vulvar squamous cell carcinoma is associated with decreased risk of recurrence and prolonged median time to recurrence.

OVARIO phase II trial of combination niraparib plus bevacizumab maintenance therapy in advanced ovarian cancer following first-line platinum-based chemotherapy with bevacizumab.

OBJECTIVE: To assess safety and efficacy of niraparib + bevacizumab as a first-line maintenance therapy for patients with newly diagnosed advanced ovarian cancer. METHODS: This multicenter, phase II, single-arm, open-label study enrolled adult patients with stage IIIB to IV ovarian, fallopian tube, or primary peritoneal cancer (NCT03326193). Patients were required to have an attempt at debulking surgery and have a complete response, partial response, or no evidence of disease following first-line, platinum-based chemotherapy with ≥3 cycles of bevacizumab. The primary endpoint was the progression-free survival (PFS) rate at 18 months. Secondary endpoints included PFS, overall survival, and safety. RESULTS: Among the 105 evaluable patients, the PFS rate at 18 months was 62% (95% CI 52-71%) in the overall population and 76% (95% CI 61-87) in the homologous recombination deficient (HRd), 47% (95% CI 31-64%) in the HR proficient (HRp), and 56% (95% CI 31-79%) in the HR not determined (HRnd) subgroups (December 24, 2020, cutoff). After a median follow-up time of 28.7 months (IQR, 23.9-32.5 months), median PFS was 19.6 months (95% CI 16.5-25.1) in the overall population (N = 105) and 28.3 months (95% CI 19.9-NE), 14.2 months (95% CI 8.6-16.8), and 12.1 months (95% CI 8.0-NE) in the HRd, HRp, and HRnd subgroups, respectively (June 16, 2021, cutoff). The most common any-grade treatment-related adverse events (related to niraparib and/or bevacizumab) were thrombocytopenia (74/105), fatigue (60/105), and anemia (55/105; December 24, 2020, cutoff). CONCLUSION: Niraparib + bevacizumab first-line maintenance therapy displayed promising PFS results. Safety was consistent with the known safety profiles of niraparib and bevacizumab as monotherapy.

Optimal overall treatment time for adjuvant therapy for women with completely resected, node-positive vulvar cancer.

INTRODUCTION: The optimal overall treatment time (OTT) from radical surgery to the end of adjuvant radiation therapy for some squamous cell carcinomas has been found to impact treatment outcomes. This study aims to identify the impact of OTT on overall survival (OS) for women with completely resected, node-positive squamous cell carcinomas of the vulva. MATERIALS AND METHODS: The National Cancer Data Base was queried for women with surgically resected, node-positive vulvar squamous cell carcinomas between 2004 and 2016 who were treated with adjuvant radiation therapy. Kaplan-Meier analysis with log-rank test and Cox proportional hazards tests were utilized for OS calculations. RESULTS: A total of 1500 women met inclusion criteria. The median OTT was 104 days. Shorter OTT was associated with age, facility volume, private insurance, and duration of post-operative hospitalization. Median OS with OTT ≤ 104 days was 56.1 months vs 45.4 months if ≥105 days (p = 0.015). On multivariable Cox analysis, OTT was independently associated with an increased risk of death of 0.4% per additional day (95%CI 1.001-1.007, p = 0.003), as were age at diagnosis (HR 1.031 [95%CI 1.024-1.037], p < 0.001), number of nodes positive (HR 1.031 [95%CI 1.024-1.037], p = 0.006), the use of concurrent chemotherapy (HR 0.815 [95%CI 0.693-0.960], p = 0.014) and increasing pT/pN stage. After propensity adjustment for factors predicting a shorter OTT, OTT continued to be associated with an increased risk of death per additional day (HR 1.004 [95%CI 1.001-1.007], p = 0.007). CONCLUSION: Overall treatment time is an independent risk factor for death in women being treated with adjuvant radiation therapy following complete resection of node-positive squamous cell carcinoma of the vulva.

Survival disparities in vulvar cancer patients in Commission on Cancer®-accredited facilities.

OBJECTIVES: To investigate survival disparities and prognostic factors in vulvar cancer by age at diagnosis. METHODS: Women who underwent surgery and were diagnosed with stage I-IV vulvar cancer from 2004 to 2014 in the National Cancer Database were eligible. Proportions were compared using Chi-Square test. Survival was evaluated using Cox analysis. RESULTS: There were 18,207 eligible women. Median age at diagnosis was 64 years, and 31% diagnosed ≥75 years old were categorized as elderly. Most vulvar cancers were diagnosed at stage I and with squamous histology. Diagnosis with higher stage or non-squamous histology was more common in elderly vs. non-elderly patients (P < 0.001). Survival was 3.5 times worse in the elderly than the non-elderly (P < 0.0001). Risk of death for each 5-year increment in age increased by 22% for non-elderly and 43% for elderly patients (P < 0.0001). The prognostic value of comorbidity score, stage, regional node assessment and histology was smaller in elderly vs. non-elderly women (each P < 0.05). Adjuvant chemoradiotherapy (CTRT) use in the elderly vs. non-elderly was rare for stage I-II disease (3% vs. 2%) and more common for stage III-IV disease (6% vs. 43%), respectively (P < 0.0001). The survival disadvantage for elderly patients persisted following no adjuvant therapy, radiotherapy or chemotherapy alone, or CTRT (P < 0.0001). In stage III-IV disease, survival was superior following CTRT vs. radiotherapy when diagnosed <75 years (HR = 0.80, 95% CI = 0.69-0.93) but not in the elderly (HR = 0.99, P > 0.05). CONCLUSIONS: Age-associated risk of death increased at different rates in vulvar cancer and was larger in elderly vs. non-elderly patients. The impact of other prognostic factors was smaller in elderly vs. non-elderly women. The survival benefit of CTRT over radiotherapy in stage III-IV did not extend to the elderly.

Race-driven survival differential in women diagnosed with endometrial cancers in the USA.

OBJECTIVE: African American women are increasingly being diagnosed with advanced and type II histology endometrial cancers. Outcomes have been observed to be worse in African American women, but whether or not race itself is a factor is unclear. We sought to evaluate the rates of diagnosis and outcomes on a stage-by-stage basis with respect to race using a large national cancer registry database. METHODS: The National Cancer Data Base was searched for patients with surgically staged non-metastatic endometrial cancer between 2004 and 2015. Women were excluded if surgical stage/histology was unknown, there was no follow-up, or no information on subsequent treatment. Pairwise comparison was used to determine temporal trends and Cox hazards tests with Bonferroni correction were used to determine overall survival. RESULTS: A total of 286 920 women were diagnosed with endometrial cancer and met the criteria for analysis. Median follow-up was 51 months (IQR 25.7-85.3). In multivariable models, in women with stage I disease, African American women had a higher risk of death than Caucasian women (HR 1.262, 95% CI 1.191 to 1.338, p<0.001) and Asian/Pacific Islander women had a lower risk of death than Caucasian women (HR 0.742, 95% CI 0.689 to 0.801, p<0.001). This held for African American women with stage II type I and type II disease (HR 1.26, 95% CI 1.109 to 1.444, p<0.001 and HR 1.235, 95% CI 1.098 to 1.388, p<0.001) but not for Asian/Pacific Islander women. African American women with stage IIIA-B disease also had a higher risk of death for type I and type II disease versus Caucasian women (HR 1.221, 95% CI 1.045 to 1.422, p=0.010 and HR 1.295, 95% CI 1.155 to 1.452, p<0.001). Asian/Pacific Islander women had a lower risk of death than Caucasian women with type I disease (HR 0.783, 95% CI 0.638 to 0.960, p=0.019) and type II disease (HR 0.790, 95% CI 0.624 to 0.999, p=0.05). African American women with stage IIIC1-2 had a higher risk of death with type I disease (HR 1.343, 95% CI 1.207 to 1.494, p<0.001) and type II disease (HR 1.141, 95% CI 1.055 to 1.233, p=0.001) whereas there was no significant difference between Caucasian women and Asian/Pacific Islander women. CONCLUSION: Race appears to play an independent role in survival from endometrial cancer in the USA, with African American women having worse survival on a stage-for-stage basis compared with Caucasian women.

Workplace Harassment and Discrimination in Gynecology: Results of the AAGL Member Survey.

STUDY OBJECTIVE: To characterize workplace and sexual harassment and discrimination among physicians in gynecology. DESIGN: A beta-tested Internet survey was distributed by e-mail using the REDCap platform. All responses were anonymous. SETTING: The survey was distributed to the 7026 physician members of an international gynecologic society (AAGL), including faculty and trainees. PATIENTS: Not applicable. INTERVENTIONS: The survey was distributed on 3 occasions between July and September 2018. The survey contained questions on demographics, attitudes, experiences, and sequelae regarding harassment and discrimination in the workplace. Frequency distributions and nonparametric tests were performed to determine the percentages and types of harassment and discrimination among respondents. MEASUREMENTS AND MAIN RESULTS: A total of 907 physicians responded, including 603 US physicians and 304 non-US physicians; 59% identified as female and 40% as male, and 20% were trainees. Females were more likely than males to think the #MeToo movement was "justified and overdue" (p < .05), independent of age or trainee status. More females than males reported experiencing workplace discrimination (67% vs 39%; p < .001); gender-based discrimination was the most common basis for both. Females indicated decreased self-confidence and lower salary; males indicated fewer employment opportunities and lower patient volume. Harassment was reported by more females than males (53% vs 17%; p < .001), including sexual harassment (39% vs 11%, p <.05). Most experienced loss of self-confidence, felt the offender was in a position of power, and did not report the incident, often due to fear of reprisal. Multiple respondents experienced workplace-related sexual assault. CONCLUSION: Workplace harassment and discrimination are commonly experienced by female and male gynecologists and are usually related to a power differential. Improvements must be made in the workplace environment to achieve equity and a safe workplace free of harassment and discrimination.

Does adjuvant chemotherapy dose modification have an impact on the outcome of patients diagnosed with advanced stage ovarian cancer? An NRG Oncology/Gynecologic Oncology Group study.

PURPOSE: To determine the relationship between chemotherapy dose modification (dose adjustment or treatment delay), overall survival (OS) and progression-free survival (PFS) for women with advanced-stage epithelial ovarian carcinoma (EOC) and primary peritoneal carcinoma (PPC) who receive carboplatin and paclitaxel. METHODS: Women with stages III and IV EOC and PPC treated on the Gynecologic Oncology Group phase III trial, protocol 182, who completed eight cycles of carboplatin with paclitaxel were evaluated in this study. The patients were grouped per dose modification and use of granulocyte colony stimulating factor (G-CSF). The primary end point was OS; Hazard ratios (HR) for PFS and OS were calculated for patients who completed eight cycles of chemotherapy. Patients without dose modification were the referent group. All statistical analyses were performed using the R programming language and environment. RESULTS: A total of 738 patients were included in this study; 229 (31%) required dose modification, 509 did not. The two groups were well-balanced for demographic and prognostic factors. The adjusted hazard ratios (HR) for disease progression and death among dose-modified patients were: 1.43 (95% CI, 1.19-1.72, P < 0.001) and 1.26 (95% CI, 1.04-1.54, P = 0.021), respectively. Use of G-CSF was more frequent in dose-modified patients with an odds ratio (OR) of 3.63 (95% CI: 2.51-5.26, P < 0.001) compared to dose-unmodified patients. CONCLUSION: Dose-modified patients were at a higher risk of disease progression and death. The need for chemotherapy dose modification may identify patients at greater risk for adverse outcomes in advanced stage EOC and PPC.

Predictive modeling for determination of microscopic residual disease at primary cytoreduction: An NRG Oncology/Gynecologic Oncology Group 182 Study.

OBJECTIVE: Microscopic residual disease following complete cytoreduction (R0) is associated with a significant survival benefit for patients with advanced epithelial ovarian cancer (EOC). Our objective was to develop a prediction model for R0 to support surgeons in their clinical care decisions. METHODS: Demographic, pathologic, surgical, and CA125 data were collected from GOG 182 records. Patients enrolled prior to September 1, 2003 were used for the training model while those enrolled after constituted the validation data set. Univariate analysis was performed to identify significant predictors of R0 and these variables were subsequently analyzed using multivariable regression. The regression model was reduced using backward selection and predictive accuracy was quantified using area under the receiver operating characteristic area under the curve (AUC) in both the training and the validation data sets. RESULTS: Of the 3882 patients enrolled in GOG 182, 1480 had complete clinical data available for the analysis. The training data set consisted of 1007 patients (234 with R0) while the validation set was comprised of 473 patients (122 with R0). The reduced multivariable regression model demonstrated several variables predictive of R0 at cytoreduction: Disease Score (DS) (p<0.001), stage (p=0.009), CA125 (p<0.001), ascites (p<0.001), and stage-age interaction (p=0.01). Applying the prediction model to the validation data resulted in an AUC of 0.73 (0.67 to 0.78, 95% CI). Inclusion of DS enhanced the model performance to an AUC of 0.83 (0.79 to 0.88, 95% CI). CONCLUSIONS: We developed and validated a prediction model for R0 that offers improved performance over previously reported models for prediction of residual disease. The performance of the prediction model suggests additional factors (i.e. imaging, molecular profiling, etc.) should be explored in the future for a more clinically actionable tool.

What is the role of retroperitoneal exploration in optimally debulked stage IIIC epithelial ovarian cancer? An NRG Oncology/Gynecologic Oncology Group ancillary data study.

BACKGROUND: The purpose of this study was to determine the effect of retroperitoneal (RP) exploration on progression-free survival (PFS) and overall survival (OS) in epithelial ovarian cancer (EOC) patients with stage IIIC disease who underwent optimal debulking surgery. METHODS: Data were collected from records of the Gynecologic Oncology Group 182 (GOG-182) study of stage IIIC EOC patients cytoreduced to no gross residual disease (R0) or minimal gross residual (<1 cm) disease (MGRD) at primary surgery. Patients with stage IIIC disease by intraperitoneal (IP) tumor were included and divided into 3 groups: 1) > 2 cm IP tumor without lymph node involvement (IP/RP-), 2) > 2 cm IP tumor with lymph node involvement (IP/RP+), and 3) > 2 cm IP tumor with no RP exploration (IP/RP?). The effects of disease distribution and RP exploration on PFS and OS were assessed using Kaplan-Meier and proportional hazards methods. RESULTS: There were 1871 stage IIIC patients in GOG-182 who underwent optimal primary debulking surgery. Of these, 689 (36.8%) underwent RP exploration with removal of lymph nodes from at least 1 para-aortic site, and 1182 (63.2%) did not. There were 269 patients in the IP/RP- group, 420 patients in the IP/RP + group, and 1182 patients in the IP/RP? group. Improved PFS (18.5 vs 16.0 months; P < .0001) and OS (53.3 vs 42.8 months; P < .0001) were associated with RP exploration versus no exploration. Patients with MGRD had improved PFS (16.8 vs 15.1 months, P = 0.0108) and OS (44.9 vs 40.5 months, P = 0.0076) versus no exploration. CONCLUSIONS: RP exploration at the time of primary surgery in patients with optimally debulked stage IIIC EOC is associated with a survival benefit. Cancer 2017;123:985-93. © 2016 American Cancer Society.

Genome-wide association study evaluating single-nucleotide polymorphisms and outcomes in patients with advanced stage serous ovarian or primary peritoneal cancer: An NRG Oncology/Gynecologic Oncology Group study.

OBJECTIVE: This study evaluated single nucleotide polymorphisms (SNPs) associated with progression free (PFS) and overall survival (OS) in patients with advanced stage serous EOC. METHODS: Patients enrolled in GOG-172 and 182 who provided specimens for translational research and consent were included. Germline DNA was evaluated with the Illumina's HumanOMNI1-Quad beadchips and scanned using Illumina's iScan optical imaging system. SNPs with allele frequency>0.05 and genotyping rate>0.98 were included. Analysis of SNPs for PFS and OS was done using Cox regression. Statistical significance was determined using Bonferroni corrected p-values with genomic control adjustment. RESULTS: The initial GWAS analysis included 1,124,677 markers in 396 patients. To obtain the final data set, quality control checks were performed and limited to serous tumors and self-identified Caucasian race. In total 636,555 SNPs and 289 patients passed all the filters. The pre-specified statistical level of significance was 7.855e-08. No SNPs met this criteria for PFS or OS, however, two SNPs were close to significance (rs10899426 p-2.144e-08) (rs6256 p-9.774e-07) for PFS and 2 different SNPs were identified (rs295315 p-7.536e-07; rs17693104 p-7.734e-07) which were close to significance for OS. CONCLUSIONS: Using the pre-specified level of significance of 1×10-08, we did not identify any SNPs of statistical significance for OS or PFS, however several were close. The SNP's identified in this GWAS study will require validation and these preliminary findings may lead to identification of novel pathways and biomarkers.

A cost-effectiveness analysis of a chemoresponse assay for treatment of patients with recurrent epithelial ovarian cancer.

OBJECTIVE: Clinical validation of a chemoresponse assay was recently published, demonstrating a significant increase in overall survival in recurrent ovarian cancer patients treated with therapies to which their tumor was sensitive in the assay. The current study investigates the cost effectiveness of using the assay at the time of ovarian cancer recurrence from the payer's perspective. METHODS: Using a Markov state transition model, patient characteristics and survival data from the recent clinical study, the cumulative costs over the study horizon (71 months) for both the baseline (no assay) and intervention (assay consistent, hypothetical) cohorts were evaluated. RESULTS: The assay consistent cohort had an incremental cost effectiveness ratio (ICER) of $6206 per life year saved (LYS), as compared to the baseline cohort. Cost-effectiveness was further demonstrated in platinum-sensitive and platinum-resistant populations treated with assay-sensitive therapies, with ICERs of $2773 per LYS and $2736 per LYS, respectively. CONCLUSIONS: The use of a chemoresponse assay to inform treatment decisions in recurrent ovarian cancer patients has the potential to be cost-effective in both platinum-sensitive and platinum-resistant patients.

Evaluation of in vitro chemoresponse profiles in women with Type I and Type II epithelial ovarian cancers: An observational study ancillary analysis.

OBJECTIVE: Type I epithelial ovarian cancers (EOCs) are reported to be relatively chemoresistant. This study sought to compare pretreatment chemoresponse assays in Type I vs. Type II EOCs. STUDY DESIGN: 383 women with stage III-IV EOC enrolled in an observational study, with known chemoresponse assay results for 7 common therapeutic agents, were included. Type I EOCs were defined as grade 1 serous/endometrioid cancers and all clear cell/mucinous cancers. Type II EOCs were classified as grade 2-3 serous/endometrioid cancers and undifferentiated cancers. Chemotherapy assay responses were classified as sensitive (S), intermediately sensitive (I), or resistant (R). All patients were treated with platinum/taxane therapy following cytoreductive surgery. RESULTS: Thirty (7.8%) tumors were classified as Type I EOC, and 353 (92.2%) as Type II EOC. Type I patients were younger at the time of diagnosis (median age: 57 vs. 62 years, p=0.018) and had longer survival compared to Type II patients (mPFS: 25.8 vs. 16.4 months, HR=1.71, p=0.042). Eighty-six percent of Type I EOC specimens demonstrated a sensitive chemoresponse assay result to at least 1 agent; 35.7% were pan-S to all 7 agents. After adjusting for stage, debulking status, and type of EOC, multi-drug resistance was twice as likely in women with Type I EOC compared to Type II EOC (pan-R, 14.3% vs. 6.8% (p=0.268); pan-S, 35.7% vs. 51.2% (p=0.183)), but did not attain statistical significance. CONCLUSION(S): The majority of women with Type I EOC displayed assay sensitivity to at least one agent. Given the small sample size these findings need to be evaluated further.

Impact of adjuvant chemotherapy with radiation for node-positive vulvar cancer: A National Cancer Data Base (NCDB) analysis.

BACKGROUND: For node-positive vulvar cancer, adjuvant radiotherapy has an established benefit, whereas the impact of chemotherapy is unknown. A National Cancer Data Base (NCDB) analysis was conducted to determine patterns of care and evaluate the survival impact of adjuvant chemotherapy. METHODS: The NCDB was queried for vulvar cancer patients diagnosed from 1998-2011 who underwent extirpative surgery with confirmed inguinal nodal involvement treated with adjuvant radiotherapy. Patients with inadequate follow-up or non-squamous histologies were excluded. Chi-square test, logistic regression analysis, log-rank test and multivariable Cox proportional regression modeling with adjustment using propensity score with inverse probability of treatment weights (IPTW) were conducted to establish factors associated with utilization and survival. RESULTS: A total of 1797 patients were identified: 26.3% received adjuvant chemotherapy and 76.6% had 1-3 involved lymph nodes. Adoption of adjuvant chemotherapy significantly increased over time, from 10.8% in 1998 to 41.0% in 2006 (p<0.001). Lower utilization was seen in older patients, Northeast or Southern facilities, and patients with more extensive nodal dissection, whereas greater number of involved nodes, stage IVA disease and positive surgical margins led to a higher probability of receiving chemotherapy. Unadjusted median survival without and with adjuvant chemotherapy was 29.7months and 44.0months (p=0.001). On IPTW-adjusted Cox proportional regression modeling, delivery of adjuvant chemotherapy resulted in a 38% reduction in the risk of death (HR 0.62, 95% CI 0.48-0.79, p<0.001). CONCLUSION: In a large population-based analysis, adjuvant chemotherapy resulted in a significant reduction in mortality risk for node-positive vulvar cancer patients who received adjuvant radiotherapy.

Cost-utility comparison of neoadjuvant chemotherapy versus primary debulking surgery for treatment of advanced-stage ovarian cancer in patients 65 years old or older.

OBJECTIVE: Treatment for advanced-stage epithelial ovarian cancer (AEOC) includes primary debulking surgery (PDS) or neoadjuvant chemotherapy (NACT). A randomized controlled trial comparing these treatments resulted in comparable overall survival (OS). Studies report more complications and lower chemotherapy completion rates in patients 65 years old or older receiving PDS. We sought to evaluate the cost implications of NACT relative to PDS in AEOC patients 65 years old or older. STUDY DESIGN: A 5 year Markov model was created. Arm 1 modeled PDS followed by 6 cycles of carboplatin and paclitaxel (CT). Arm 2 modeled 3 cycles of CT, followed by interval debulking surgery and then 3 additional cycles of CT. Parameters included OS, surgical complications, probability of treatment initiation, treatment cost, and quality of life (QOL). OS was assumed to be equal based on the findings of the international randomized control trial. Differences in surgical complexity were accounted for in base surgical cost plus add-on procedure costs weighted by occurrence rates. Hospital cost was a weighted average of diagnosis-related group costs weighted by composite estimates of complication rates. Sensitivity analyses were performed. RESULTS: Assuming equal survival, NACT produces a cost savings of $5616. If PDS improved median OS by 1.5 months or longer, PDS would be cost effective (CE) at a $100,000/quality-adjusted life-year threshold. If PDS improved OS by 3.2 months or longer, it would be CE at a $50,000 threshold. The model was robust to variation in costs and complication rates. Moderate decreases in the QOL with NACT would result in PDS being CE. CONCLUSION: A model based on the RCT comparing NACT and PDS showed NACT is a cost-saving treatment compared with PDS for AEOC in patients 65 years old or older. Small increases in OS with PDS or moderate declines in QOL with NACT would result in PDS being CE at the $100,000/quality-adjusted life-year threshold. Our results support further evaluation of the effects of PDS on OS, QOL and complications in AEOC patients 65 years old or older.

Adoption and impact of concurrent chemoradiation therapy for vaginal cancer: a National Cancer Data Base (NCDB) study.

BACKGROUND: Vaginal cancer is an uncommon entity for which concurrent chemoradiation (CCRT) may be used based on small retrospective series and extrapolation from cervical cancer. We explored the adoption rate of CCRT and determined its impact on survival. METHODS: Patients entered into the National Cancer Data Base (NCDB) diagnosed with vaginal cancer from 1998 to 2011 who received definitive radiation therapy were included. Univariate/multivariable exploratory analyses of factors associated with CCRT were performed. Log-rank test and Cox proportional hazards modeling identified the contribution of CCRT on survival. RESULTS: Of the 13,689 patients identified, 8222 (60.1%) received radiation therapy. Of these, 3932 (47.8%) received CCRT and its use increased from 20.8% to 59.1% (1998-2011). Of the 23 patient, disease, facility, and treatment factors, 13 were significantly associated with patient outcomes and were entered into a binary logistic regression model. This evaluation revealed that younger age, larger tumor size, later year of diagnosis, higher facility volume, squamous histology, and higher stage (in order of increasing association) are independently associated with CCRT use. Median overall survival is longer with CCRT compared to radiation alone (56.2 vs. 41.2 months, p<0.0005). On multivariable analysis, younger age, higher facility volume, squamous histology, lower comorbidity score, CCRT, brachytherapy utilization and lower stage (in order of increasing association) are independently prognostic of improved survival. CONCLUSIONS: Use of CCRT for patients with vaginal cancer has increased and is associated with a significant improvement in survival in this large, national cohort. CCRT should be integrated into treatment guidelines for vaginal cancer.

Impact of facility volume on therapy and survival for locally advanced cervical cancer.

OBJECTIVE: Chemosensitizing radiation with brachytherapy is standard of care for treatment of locally advanced cervical cancer, an increasingly rare disease. Treatment facility volume has been correlated with outcome in many diseases. Treatment outcome and likelihood of receiving standard therapy in locally advanced cervical cancer based on facility volume were examined using a large national cancer database. METHODS: The National Cancer Data Base was queried for patients with stage IIB - IIIB cervical cancer from 1/1998 through 12/2010. Facility volumes were tallied. Overall survival was estimated using Kaplan-Meier method. Univariate and multivariable analyses were performed to determine variables affecting survival, receiving standard therapy, and total duration of radiotherapy. RESULTS: We identified a total of 27,660 patients who were treated at 1361 facilities. Thirty of the facilities (2.2%) treated the highest quartile volume of patients (>9.4 patients annually) while 1072 facilities (78.8%) treated <2.4 patients annually. The median age of patients was 53, the majority were Caucasian, treated in a metropolitan area, and of squamous cell histology. Median survival of patients treated at lowest- and highest-volume centers were 42.3 months (95% CI 39.8-44.8) and 53.8 months (50.1-57.5), respectively (p < 0.001). The proportions of patients receiving brachytherapy and chemotherapy were 54.8% and 79.9%, respectively. On multivariable analysis, higher facility volume independently predicted improved survival (p = 0.022), increased likelihood of receiving brachytherapy (p < 0.0005) and chemotherapy (p = 0.013), and shorter time to radiotherapy completion (p < 0.0005). CONCLUSIONS: Patients with locally advanced cervical cancer treated at high volume centers are more likely to receive standard therapy, complete therapy sooner, and experience better survival.

Oxaliplatin salvage for recurrent ovarian cancer: a single institution's experience in patient populations with platinum resistant disease or a history of platinum hypersensitivity.

OBJECTIVE: Hypersensitivity reactions can preclude platinum re-challenge for patients receiving second-line and higher carboplatin/cisplatin salvage therapy. The objective is to report our patient experience with oxaliplatin in recurrent or progressive epithelial ovarian (EOC), primary peritoneal (PPC) or fallopian tube cancer (FTC), including those with prior hypersensitivity reaction. METHODS: A single institution, retrospective review from 1995 to 2012 of patients receiving oxaliplatin for treatment of recurrent or progressive EOC, PPC, or FTC was performed. Data collected included patient demographics, diagnosis date, prior chemotherapy regimens, platinum-free interval(s), prior hypersensitivity reactions, oxaliplatin toxicity, length of therapy, disease response, and last follow-up. Those who received ≥1 cycles were included. A response to therapy was determined after ≥2 cycles. RESULTS: Forty-four patients were identified. All had prior carboplatin and 38.6% had prior cisplatin therapy. Twenty-three had a prior platinum hypersensitivity reaction. Patients received a median of 2 prior platinum containing regimens and 5 chemotherapy lines prior to oxaliplatin exposure. One patient experienced grade 3 pain. No grade 4 toxicities occurred. No treatment delays for pancytopenia noted. Nausea and dysesthesias were controlled medically and weren't dose-limiting. No nephropathy or neuropathy progressed on oxaliplatin or were dose-limiting. Disease response was observed in 43.2%. Of the responders, 36.8% had a prior platinum hypersensitivity reaction. Median number of 5 cycles of an oxaliplatin containing regimen was given. Median follow-up was 15.5 months. CONCLUSIONS: In our experience, oxaliplatin is well tolerated and should be considered for platinum challenge after hypersensitivity even in patients with platinum resistant disease with a reasonable chance of response.

The prognostic significance of pre- and post-treatment CA-125 in grade 1 serous ovarian carcinoma: a gynecologic Oncology Group study.

OBJECTIVES: The study objective was to determine the prognostic significance of serum CA-125 levels in patients with grade 1 serous ovarian carcinoma (SOC) enrolled in a Phase III study. METHODS: An ancillary analysis of a phase III study of women with advanced epithelial ovarian cancer treated with carboplatin/paclitaxel versus triplet or sequential doublet regimens. Grade 1 SOC was used as a surrogate for low-grade serous carcinoma. RESULTS: Among 3686 enrolled patients, 184 (5%) had grade 1 disease and CA-125 levels available. For those with grade 1 SOC, the median patient age was 56.5; 87.3% had Stage III disease. Median follow-up was 102 months and there was no difference in pre-chemotherapy CA-125 by treatment arm (P=0.91). Median pretreatment CA-125 for those with grade 1 SOC was lower (119.1) than for patients with grade 2-3 SOC (246.7; P<0.001). In those with grade 1, pretreatment CA-125 was not prognostic of outcome. However, patients with CA-125 levels that normalized after cycle 1, 2 or 3 were 60-64% less likely to experience disease progression as compared to those who never normalized or normalized after 4 cycles (P ≤ 0.024). Normalization of CA-125 levels before the second cycle was negatively associated with death, with a HR of 0.45 (P=0.025). CONCLUSIONS: Pretreatment CA-125 level was significantly lower in women with grade 1 SOC compared to those with high-grade SOC. While pretreatment CA-125 was not associated with survival, serial CA-125 measurements during chemotherapy treatment were prognostic, with normalization before the second chemotherapy cycle associated with a decreased risk of death.