Predictors of reduced relative dose intensity and its relationship to mortality in women receiving multi-agent chemotherapy for epithelial ovarian cancer.

OBJECTIVE: There is limited information concerning the role of relative dose intensity (RDI) on clinical outcomes in solid tumors. The objectives of our study were to evaluate the prognostic significance of RDI and predictors of reduced RDI in women with newly diagnosed advanced stage epithelial ovarian carcinoma (EOC) treated with platinum-based chemotherapy. METHODS: A multi-center retrospective study of women with FIGO stage III-IV epithelial ovarian cancer treated postoperatively with multi-agent intravenous chemotherapy between 1995 and 2009 was conducted. Data were obtained to include the first four chemotherapy cycles administered. Outcomes included: (1) planned and delivered relative dose intensity (RDI), (2) progression-free (PFS) and overall (OS) survival. Survival estimates were based on Kaplan and Meier method, and multivariate analyses were based on logistic regression and Cox proportional hazards regression. RESULTS: Evaluable subjects included 325 women. With median follow-up of 34 months (range, 0.4-170), progression or recurrence was recorded in 241 (73.9%) and death in 179 (54.9%). In multivariate analysis, predictors of reduced planned RDI were: treatment off research protocols (odds ratio [OR]=4.3; P<0.001) and BSA >2m(2) (OR=6.14; P<0.001); predictors of reduced delivered RDI were: BMI over 30 kg/m(2) (OR=2.35; P=0.008) and use of carboplatin (OR=2.71; P=0.008). In multivariate analysis, the following factors were independently associated with OS: delivered RDI <85% (hazard ratio [HR]=1.71; P=0.003) and elevated CA-125 at cycle 1 (HR=2.29; P=0.017). CONCLUSION: In this retrospective analysis, reduced chemotherapy RDI for ovarian cancer was associated with lower OS, but not PFS, despite adjustment for established prognostic factors.

Obesity as a risk for the recurrence of anterior vaginal wall prolapse after anterior colporrhaphy.

OBJECTIVE: To determine whether obese body mass index is associated with the recurrence of anterior vaginal wall prolapse after anterior colporrhaphy. STUDY DESIGN: We conducted a retrospective cohort study of the risk of recurrent anterior prolapse 6 months after anterior colporrhaphy in normal weight/overweight versus obese women from January 2004 to December 2010. Women who underwent a concurrent apical prolapse procedure were excluded. Data were abstracted regarding sociodemographics, physical examination, operative reports, and postoperative follow-up visits. RESULTS: Of 282 subjects 192 (68%) were normal/overweight and 90 (32%) were obese. Median time of follow-up was 1.8 months (interquartile range [IQR] 1.4-6.2) in the normal/overweight group and 2.0 months (IQR 1.4-5.9) in the obese group. The overall risk of recurrent prolapse was 15.2%. In bivariate analysis there was a trend towards higher recurrence in the obese versus the normal/overweight cohort (21.1% vs. 12.5%, p = 0.06). In the logistic regression model, which adjusted for age, race, diabetes, constipation, cigarette use, concurrent sling, and prior hysterectomy, obesity became significantly associated with recurrent anterior prolapse (odds ratio 2.5, 95% confidence interval 1.2-5.3). CONCLUSION: The risk of recurrence after anterior colporrhaphy is relatively high in the short-term. Obesity is associated with increased odds of anatomic recurrence of anterior vaginal wall prolapse.

Predictors of severe and febrile neutropenia during primary chemotherapy for ovarian cancer.

OBJECTIVE: To identify factors that increase the risk of neutropenic events in women with advanced ovarian carcinoma receiving initial chemotherapy. METHODS: Multi-center retrospective study of women with FIGO stage III-IV epithelial ovarian cancer treated postoperatively with multi-agent intravenous chemotherapy from 1995 to 2008. Outcomes were severe (SN; absolute neutrophil count [ANC]<500/mm(3)) and febrile neutropenia (FN; ANC<1000/mm(3) and temperature>38.1°C). Cumulative risk of neutropenic events was estimated by Kaplan Meier method. Multivariate analysis was by Cox proportional hazard regression. RESULTS: Three hundred twenty-six patients met inclusion criteria. There were 251 SN events among 140 (43%) patients and 24 FN events among 22 (7%) patients. Univariate predictors of SN were body surface area<2.0m(2) (p=0.03), body mass index (BMI)<30 kg/m(2) (p<0.01), Caucasian race (p<0.01), treatment on research protocols (p<0.01), non-carboplatin-containing regimens (p<0.01), and planned relative dose intensity (RDI)>85% of standard (p=0.02). Women over age 60 were more likely to develop FN (p=0.05). Multivariate predictors of SN were treatment on research protocols (hazard ratio [HR] 1.93; p<0.01), Caucasian race (HR 2.13; p=0.01), and planned RDI>85% (HR 1.69; p=0.05); predictors of FN were age>60 (HR 2.84; p=0.05) and non-carboplatin containing regimens (HR 4.06; p<0.01). CONCLUSION: While SN is fairly common, FN occurs infrequently in women with EOC undergoing taxane and platin-based chemotherapy and primary prophylactic growth factor support is not indicated. However, women older than 60 years of age receiving non-carboplatin containing regimens are at higher risk for FN and warrant closer surveillance.

National Cancer Data Base analysis of radiation therapy consolidation modality for cervical cancer: the impact of new technological advancements.

PURPOSE: To utilize the National Cancer Data Base to evaluate trends in brachytherapy and alternative radiation therapy utilization in the treatment of cervical cancer, to identify associations with outcomes between the various radiation therapy modalities. METHODS AND MATERIALS: Patients with International Federation of Gynecology and Obstetrics stage IIB-IVA cervical cancer in the National Cancer Data Base who received treatment from January 2004 to December 2011 were analyzed. Overall survival was estimated by the Kaplan-Meier method. Univariate and multivariable analyses were performed to identify factors associated with type of boost radiation modality used and its impact on survival. RESULTS: A total of 7654 patients had information regarding boost modality. A predominant proportion of patients were Caucasian (76.2%), had stage IIIB (48.9%) disease with squamous (82.0%) histology, were treated at academic/research centers (47.7%) in the South (34.8%), and lived 0 to 5 miles (27.9%) from the treating facility. A majority received brachytherapy (90.3%). From 2004 to 2011, brachytherapy use decreased from 96.7% to 86.1%, whereas intensity modulated radiation therapy (IMRT) and stereotactic body radiation therapy (SBRT) use increased from 3.3% to 13.9% in the same period (P<.01). Factors associated with decreased brachytherapy utilization included older age, stage IVA disease, smaller tumor size, later year of diagnosis, lower-volume treatment centers, and facility type. After controlling for significant factors from survival analyses, IMRT or SBRT boost resulted in inferior overall survival (hazard ratio, 1.86; 95% confidence interval, 1.35-2.55; P<.01) as compared with brachytherapy. In fact, the survival detriment associated with IMRT or SBRT boost was stronger than that associated with excluding chemotherapy (hazard ratio, 1.61' 95% confidence interval, 1.27-2.04' P<.01). CONCLUSIONS: Consolidation brachytherapy is a critical treatment component for locally advanced cervical cancer; however, there has been declining utilization of brachytherapy. Increased use of IMRT and SBRT boost coupled with increased mortality risk should raise concerns about utilizing these approaches over brachytherapy.

Retreatment with bevacizumab in patients with gynecologic malignancy is associated with clinical response and does not increase morbidity.

PURPOSE: Bevacizumab (Bev) is associated with improved progression-free survival in advanced epithelial ovarian cancer. The use of Bev in patients with gynecologic malignancy is increasing; however, little is known about cumulative toxicity and response in patients retreated with Bev. Our goal was to determine cumulative side effects and response in patients retreated with Bev. PATIENTS AND METHODS: Women with recurrent gynecologic malignancy treated with Bev between January 2007 and March 2012 at a single institution were identified, including a subset who received Bev in a subsequent regimen. The primary outcome was Bev-associated toxicity, and the secondary outcome was response. RESULTS: Of 83 patients that received Bev for recurrent disease, 23 were retreated with Bev and four received Bev maintenance. Three patients (13%) developed grade 3 or 4 hypertension; all had a history of chronic hypertension. One (4.3%) patient developed grade 3 proteinuria, and one (4.3%) developed an enterovaginal fistula. Four patients discontinued Bev secondary to toxicity. Toxicity was not related to the cumulative number of cycles. Twenty-six percent of patients responded to Bev retreatment. On univariate analysis, there was a significant (P=0.003) overall survival advantage when the Bev-free interval was >9 months (95% confidence interval [CI] 4.9-43.7) compared to ≤9 months (95% CI 2.1-11.5), 24.3 months, and 6.8 months. CONCLUSION: Retreatment of patients with recurrent gynecologic malignancy with Bev did not increase morbidity and was associated with treatment response. Physicians treating women with recurrent disease may consider a Bev-containing regimen even if prior regimen(s) included Bev. Future studies should prospectively evaluate the efficacy of this treatment strategy.