The survival detriment of venous thromboembolism with epithelial ovarian cancer

Objective

The aim of this study is to evaluate the effect of venous thromboembolism (VTE) chronology with respect to surgery on survival with epithelial ovarian cancer (EOC).

Methods

An IRB approved, retrospective review was performed of patients treated for Stage I–IV EOC from 1996 to 2011. Cox proportional hazards model was used to assess associations between VTE and the primary outcomes of progression free survival (PFS) and overall survival (OS). SAS 9.3 was used for statistical analyses.

Results

586 patients met study criteria. Median age was 63 years (range, 17–94); median BMI was 27.1 kg/m² (range, 13.7–67.0). Most tumors were high grade serous (68.3%) and advanced stage (III/IV, 75.4%). 3.7% had a preoperative VTE; 13.2% had a postoperative VTE. Upon multivariate analysis adjusting for age, stage, histology, performance status, and residual disease, preoperative VTE was predictive of OS (HR 3.1, 95% CI: 1.6–6.1, p = 0.001) but not PFS (p = 0.55). Postoperative VTE was associated with shorter PFS (HR 1.45, 95% CI: 1.04–2.02, p = 0.03) and OS (HR 1.8, 95% CI: 1.3–2.6, p = 0.001). When VTE timing was modeled, preoperative VTE (HR 3.5, 95% CI: 1.8–6.9, p < 0.001) and postoperative VTE after primary therapy (HR 2.3, 95% CI: 1.4–3.6, p = 0.001) were predictive of OS.

Conclusion

Preoperative and postoperative VTE appear to have a detrimental effect on OS with EOC. When modeled as a binary variable, postoperative VTE attenuated PFS; however, when VTE timing was modeled, postoperative VTE was not associated with PFS. It is unclear whether VTE is an inherent poor prognostic marker or if improved VTE prophylaxis and treatment may enable similar survival to patients without these events.     

A comparison of primary intraperitoneal chemotherapy to consolidation intraperitoneal chemotherapy in optimally resected advanced ovarian cancer

Objective

To compare survival outcomes for patients with advanced epithelial ovarian cancer (EOC) who received primary intravenous/intraperitoneal (IV/IP) chemotherapy to those who received IV followed by consolidation (treatment given to patients in remission) IP chemotherapy.

Methods

Data were analyzed and compared for all patients with stage III–IV EOC who underwent optimal primary cytoreduction (residual disease ≤ 1 cm) followed by cisplatin-based consolidation IP chemotherapy (1/2001–12/2005) or primary IV/IP chemotherapy (1/2005–7/2011).

Results

We identified 224 patients; 62 (28%) received IV followed by consolidation IP chemotherapy and 162 (72%) received primary IV/IP chemotherapy. The primary IP group had significantly more patients with serous tumors. The consolidation IP group had a significantly greater median preoperative platelet count, CA-125, and amount of ascites. There were no differences in residual disease at the end of cytoreduction between both groups. The median progression-free survival (PFS) was greater for the primary IP group; however, this did not reach statistical significance (23.7 months vs 19.7 months; HR 0.78; 95% CI, 0.57–1.06; p = 0.11). The median overall survival (OS) was significantly greater for the primary IP group (78.8 months vs 57.5 months; HR 0.56; 95% CI, 0.38–0.83; p = 0.004). On multivariate analysis, after adjusting for confounders, the difference in PFS was not significant (HR 0.78; 95% CI, 0.56–1.11; p = 0.17), while the difference in OS remained significant (HR 0.59; 95% CI, 0.39–0.89; p = 0.01).

Conclusions

In our study, primary IV/IP chemotherapy was associated with improved OS compared to IV followed by consolidation IP chemotherapy in patients with optimally cytoreduced advanced EOC.     

Endometrial cancer in Asian and American Indian/Alaskan Native women: Tumor characteristics,treatment and outcome compared to non-Hispanic white women

Objective

The objective of this study is to compare survival of Asian (AS), American Indian/Alaskan Native (AI/AN) and non-Hispanic white (NHW) women with endometrial adenocarcinoma (EC).

Methods

Patients with EC were identified from the Surveillance, Epidemiology, and End Results program from 1988 to 2009. Kaplan–Meier survival methods and Cox proportional hazards regression were performed.

Results

Of the 105,083 women, 97,763 (93%) were NHW, 6699 (6.4%) were AS and 621 (0.6%) were AI/AN. AS and AI/AN were younger than NHW with mean age of 57.7 and 56.5 vs. 64.3 years (p < 0.001 and 0.059). Advanced stage and high-risk histology were more prominent in AS than NHW (15.6% vs. 13.3%, p = 0.04, 10.6% vs. 9.6%, p = 0.041). Lymphadenectomy was performed more frequently in AS than NHW (56.7% vs. 48.2%, p < 0.001). Asian immigrants were younger than Asian natives (mean age 57 vs. 60.5 years, p < 0.001).In multivariate analysis, AS had better overall (OS) (HR 0.86, 95% CI 0.81–0.91, p < 0.001) and cancer-specific survival (CSS) (HR 0.92, 95% CI 0.84–1.00, p = 0.05) than NHW. Further, Asian immigrants had better OS (HR 0.83, 95% CI 0.73–0.94, p = 0.002) and CSS (HR 0.66, 95% CI 0.54–0.80, p < 0.001) than Asian natives. In contrast, AI/AN had worse OS (HR 1.35, 95% CI 1.15–1.59, p < 0.001) but no difference in CSS (HR 1.06, 95% CI 0.80–1.40, p = 0.69) than NHW.

Conclusions

Asians were younger at presentation, more likely to have lymphadenectomy and had an improved outcome compared to NHW. Interestingly, Asian immigrants had more favorable outcome than Asians born in the US. Further studies are warranted to find possible explanations for such a difference.     

Prognostic factors and outcomes in endometrial stromal sarcoma with the 2009 FIGO staging system: A multicenter review of 114 cases

Objective

To assess prognostic factors associated with disease-related survival in endometrial stromal sarcoma (ESS) using the 2009 FIGO staging system.

Methods

From January 1990 to January 2012, 114 patients with ESS were identified at the Samsung and Asan Medical Center and data were retrospectively analyzed.

Results

Ten (8.7%) patients died of the disease and 33 (28.9%) patients relapsed. The 5- and 10-year overall survival (OS) rates for the entire cohort were 92.6% and 87.1%, respectively, and the 5- and 10-year recurrence-free survival (RFS) rates were 71.8% and 52.1%, respectively. The estimated median survival after recurrence for the 33 patients whose tumors relapsed was 133 months (95% CI, 7.7–258.4), and 5-year survival after recurrence was 68.9%. Stage I (P = 0.006), estrogen and/or progesterone receptor (ER/PR) positivity (P = 0.0027), and no nodal metastasis (P = 0.033) were associated with a good prognosis for OS in the univariate analysis. Ovarian preservation was revealed to be an independent predictor for poorer RFS (HR, 6.5; 95% CI, 1.23–34.19; P = 0.027). Positivity for ER/PR (HR, 0.05; 95% CI, 0.006–0.4; P = 0.006) and cytoreductive resection of recurrent lesions (HR, 0.14; 95% CI, 0.02–0.93; P = 0.042) were independent predictors of better survival after recurrence.

Conclusions

Stage, expression of ER/PR, and nodal metastasis are significantly associated with OS in ESS. Bilateral salpingo-oophorectomy (BSO) as the primary treatment and cytoreductive resection of recurrent lesions should be considered for improving survival of patients with ESS.     

The complex triad of obesity,diabetes and race in Type I and II endometrial cancers: Prevalence and prognostic significance

Background

We examined the distribution of obesity, diabetes, and race in Type I and Type II endometrial cancers (EC) and their associations with clinical outcomes.

Methods

A multi-institutional retrospective analysis of Type I and II EC cases from January 2005 to December 2010 was conducted. Type I (endometrioid), Type II (serous and clear cell), low grade (LG) (grade 1 and 2 endometrioid), and high grade (HG) (grade 3 endometrioid, serous, clear cell) cohorts were compared. Univariate and multivariate analyses were used to determine time-to-recurrence (TTR), recurrence-free survival (RFS), and overall survival (OS).

Results

Type I EC patients were more frequently obese than Type II (66% versus 51%, p < 0.0001) and had similar rates of diabetes (25% versus 23%, p = 0.69). African-Americans (AA) had higher median BMI than Caucasians in both Type I (p < 0.001) and II (p < 0.001) ECs, and were twice as likely to have diabetes (p < 0.001). In Type I EC, DM was associated with worse RFS and OS in unadjusted and adjusted models (RFS HR 1.38, 95%CI 1.01–1.89; OS HR 1.86, 95%CI 1.30–2.67), but not with TTR. BMI was associated with improved TTR in the adjusted analysis for Type I EC (HR 0.98, 95%CI 0.95–1.0), but not with RFS or OS. There was no association between DM or BMI and outcomes in Type II or HG EC. AA race was not associated with RFS or OS on adjusted analyses in any group.

Conclusions

Obesity and diabetes are highly prevalent in Type I and II ECs, especially in AA. DM was associated with worse RFS and OS in Type I EC. Neither DM nor BMI was associated with outcomes in Type II or HG EC.     

Type II endometrial cancer in Hispanic women: Tumor characteristics,treatment and survival compared to non-Hispanic white women

Objectives

To compare survival of Hispanic white (HW) and non-Hispanic white (NHW) women with type II endometrial adenocarcinoma (EC).

Methods

Patients with serous, clear cell or grade 3 endometrioid EC were identified from the Surveillance, Epidemiology, and End Results (SEER) program 1988–2009 and were divided into HW and NHW. HW were subdivided into natives and immigrants.

Results

Of the 14,434 women, 13,012 (90.2%) were NHW and 1422 (9.8%) were HW. HW were younger than NHW (mean 63 vs. 68 years, p < 0.001). A higher proportion of HW presented with late stage disease than NHW (43.8% vs. 36.6%, p = 0.04). Performing lymphadenectomy was not different but HW were more likely to have positive lymph nodes than NHW (27.6% vs. 23.1%, p = 0.02). Further, HW were less likely to receive radiation than NHW (39.5% vs. 42.3%, p = 0.04). No difference in clinicopathologic characteristics was found between immigrant and native HW. In multivariate models adjusting for age, stage, histology, surgical treatment, extent of lymphadenectomy, and radiation therapy, no difference in overall survival (OS) (HR 1.06, 95% CI 0.97–1.16, p = 0.19) and cancer-specific survival (CSS) (HR 1.02, 95% CI 0.91–1.14, p = 0.75) was found between HW and NHW. Interestingly, immigrant HW had better OS (HR 0.74, 95% CI 0.62–0.89, p < 0.001) and CSS (HR 0.72, 95% CI 0.58–0.90, P = 0.003) than native HW.

Conclusions

Although they were more likely to present with advanced stage and positive nodal disease, no difference in outcome was noted between Hispanic and non-Hispanic whites with EC. Interestingly, immigrant HW had more favorable outcome compared to native HW.     

Overall survival after pelvic exenteration for gynecologic malignancy

Background

Five-Year survival after pelvic exenteration for gynecologic malignancies has been reported as high as 60%. The objective of this study was to determine overall survival (OS) after pelvic exenteration and evaluate factors impacting outcome.

Methods

A retrospective review of all women who underwent pelvic exenteration at our institution between February 1993 and December 2010 was performed. OS was defined as time from exenteration to date of death or last contact. Survival analysis was performed using the Kaplan Meyer method. Multivariate analysis was performed to determine the impact of clinical and pathologic factors on survival outcomes.

Results

One hundred sixty patients with gynecologic malignancy underwent pelvic exenteration. Five-year recurrence free survival (RFS) was 33% (95%CI 0.25–0.40). Factors which negatively impacted RFS included shorter treatment-free interval (p = .050), vulvar primary (p = .032), positive margins (p < .001), lymphovascular space invasion (LVSI, p < .001), positive lymph nodes (p < .001) and perineural invasion (p = 0.030). In multivariate analysis, positive margins (p = .040), positive nodes (p < .001) and lymphovascular space invasion (LVSI, p = .003) retained a significant impact on RFS.Five-year OS was 40% (95% CI 0.32–0.48). Factors which negatively impacted OS included vulvar primary (p = .04), positive margins (p < .001), LVSI (p < .001), positive lymph nodes (p < .001) and perineural invasion (p = .008). In multivariate analysis, positive nodes (p = .001) and LVSI (p = .001) retained a significant impact on OS.

Conclusion

Five-year OS after pelvic exenteration was 40%. Survival outcomes have not significantly improved despite improvements in technique and patient selection. Multiple non-modifiable factors at the time of exenteration are associated with poor survival.     

Ovary and uterus-sparing procedures for low-grade endometrial stromal sarcoma: A retrospective study of 153 cases

Objective

To discuss the optimal treatment options for low grade endometrial stromal sarcoma (LG-ESS).

Methods

Medical records of consecutive patients with LG-ESS in our institute were collected. The pertinent data, including clinicopathological characteristics, treatment and prognostic information were evaluated.

Results

A total of 153 cases of LG-ESS were included. The 5-year relapse free survival (RFS), overall survival (OS) and survival after relapse (SAR) rates were 66.1%, 95.8% and 82.9%, respectively. Ovary-sparing procedures, positive resection-margins, and myomectomy were the independent adverse factors for relapse (P < 0.0001, = 0.0041, and = 0.0075, respectively). Post-menopause, cervical involvement, and positive lymphovascular space involvement were significantly associated with survival (P < 0.0001, = 0.0020, and = 0.0163, respectively). Distance recurrence and macroscopically residual tumors negatively affected SAR (P = 0.0137 and = 0.0004, respectively). No benefit was found for lymphadenectomy in terms of both RFS and OS (P = 0.1187 and = 0.5138, respectively). Initial ovary-sparing procedures and myomectomy had no impact on OS (P = 0.0810 and = 0.8845, respectively). Adjuvant treatment had a slightly beneficial effect both on OS and SAR.

Conclusion

Hysterectomy with bilateral salpingo-oophorectomy and complete resection of the macroscopic lesion should be treated as the initial and salvage mainstay treatments for LG-ESS patients. Ovary-sparing procedures could be considered for young women without cervical involvement; however, long-term follow-up should be mandatory. Myomectomy should only be conserved for young patients with a strong desire for future fertility, with fully informed consent; hysterectomy was recommended after the completion of pregnancy and delivery. However, the roles of lymphadenectomy and adjuvant treatment deserve further investigation.     

The importance of chemotherapy and radiation in uterine papillary serous carcinoma

Purpose

To identify prognostic and predictive factors of overall survival (OS), relapse-free survival (RFS) and toxicity for patients with uterine papillary serous carcinoma (UPSC).

Materials and methods

Patient, tumor, treatment and relapse characteristics of 135 women with Stages I-IVA UPSC treated between 1980 and 2006 at Dana-Farber/Brigham and Women's Cancer Center (DF/BWCC) were analyzed using Cox regression models to determine prognostic and predictive factors for OS, RFS and toxicity.

Results

Mean follow-up was 5.5 years (range, 0.01-25.2). Median 5-year OS was 52%, and RFS was 42% for all patients. On Cox regression analysis, increasing age, stage, and myometrial invasion were prognostic factors associated with shorter OS and RFS. A paclitaxel-platinum chemotherapy regimen was significantly associated with longer OS (hazard ratio [HR] = 0.34, 95% confidence interval [CI] 0.15-0.74, p = 0.007) and RFS (HR = 0.45, 95% CI 0.22-0.92, p = 0.03). RFS was improved for patients treated with RT (HR = 0.44, 95% CI 0.25-0.77, p = 0.004). The 5-year grade 3+ toxicity rate was 3.5% for those who received RT and was 2.9% for those who did not (p = NS).

Conclusion

Uterine papillary serous cancer can be an aggressive tumor type with a poor prognosis. RFS was improved by radiation and chemotherapy with few grade 3 or higher complications. Using radiation and paclitaxel-platinum chemotherapy should be attempted whenever feasible for patients with UPSC who do not have distant metastases at diagnosis.     

Metformin is associated with improved survival in endometrial cancer

Objective

Preclinical evidence suggests that metformin exhibits anti-tumorigenic effects in endometrial cancer. We sought to investigate the association of metformin on endometrial cancer outcomes.

Methods

A multi-institutional IRB-approved retrospective cohort analysis was conducted comparing endometrial cancer patients with diabetes mellitus who used metformin (based on medication review at the time of diagnosis) to those who did not use metformin from 2005 to 2010. Metformin use on treatment related outcomes (TTR: time to recurrence; RFS: recurrence free survival; OS: overall survival) were evaluated using univariate and multivariate modeling.

Results

24% (363/1495) endometrial cancer patients were diabetic, of whom 54% used metformin. Metformin users were younger and heavier than non-users, though nearly all were postmenopausal and obese. 75% of both groups had endometrioid histology. Stage, grade, and adjuvant therapy distributions were similar. Metformin users had improved RFS and OS. Non-metformin users had 1.8 times worse RFS (95% CI: 1.1–2.9, p = 0.02) and 2.3 times worse OS (95% CI: 1.3–4.2, p = 0.005) after adjusting for age, stage, grade, histology and adjuvant treatment. Metformin use was not associated with TTR.

Conclusion

Metformin use was associated with improved RFS and OS but not TTR, most likely due to improving all-cause mortality. Its role in modifying cancer recurrence remains unclear. Prospective studies that capture metformin exposure prior to, during and post endometrial cancer treatment may help define the role of metformin upon cancer specific and overall health outcomes.     

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.     

Menopausal status: A possible predictive factor for recurrence in women with cancer of the uterine cervix without pelvic lymph node metastasis

Objectives

To evaluate risk factors for recurrence of carcinoma of the uterine cervix among women who had undergone radical hysterectomy without pelvic lymph node metastasis, while taking into consideration not only the classical histopathological factors but also sociodemographic, clinical and treatment-related factors.

Study design

This was an exploratory analysis on 233 women with carcinoma of the uterine cervix (stages IB and IIA) who were treated by means of radical hysterectomy and pelvic lymphadenectomy, with free surgical margins and without lymph node metastases on conventional histopathological examination. Women with histologically normal lymph nodes but with micrometastases in the immunohistochemical analysis (AE1/AE3) were excluded. Disease-free survival for sociodemographic, clinical and histopathological variables was calculated using the Kaplan–Meier method. The Cox proportional hazards model was used to identify the independent risk factors for recurrence.

Results

Twenty-seven recurrences were recorded (11.6%), of which 18 were pelvic, four were distant, four were pelvic + distant and one was of unknown location. The five-year disease-free survival rate among the study population was 88.4%. The independent risk factors for recurrence in the multivariate analysis were: postmenopausal status (HR 14.1; 95% CI: 3.7–53.6; P < 0.001), absence of or slight inflammatory reaction (HR 7.9; 95% CI: 1.7–36.5; P = 0.008) and invasion of the deepest third of the cervix (HR 6.1; 95% CI: 1.3–29.1; P = 0.021). Postoperative radiotherapy was identified as a protective factor against recurrence (HR 0.02; 95% CI: 0.001–0.25; P = 0.003).

Conclusion

Postmenopausal status is a possible independent risk factor for recurrence even when adjusted for classical prognostic factors (such as tumour size, depth of tumour invasion, capillary embolisation) and treatment-related factors (period of treatment and postoperative radiotherapy status).     

Survival impact of capsule rupture in stage I clear cell carcinoma of the ovary in comparison with other histological types

Objective

We analyzed a large number of stage I clear cell carcinoma of the ovary (CCC) patients to estimate the survival impact of the capsule status in stage I CCC patients, particularly in comparison with non-CCC patients.

Methods

Clinicopathologic data on 564 patients with stage I epithelial ovarian cancer (EOC) collected under the central pathological review system were subjected to uni- and multivariable analyses to evaluate the disease-free survival (DFS) and overall survival (OS).

Results

There was no significant difference in both the OS and DFS of CCC patients between IA and IC(ir) (intraoperative capsule rupture) {IA vs. IC(ir); OS: P = 0.1402, DFS: P = 0.2701}. In contrast, CCC patients at IC(non-ir) {IC excluding for IC(ir), such as preoperative capsule rupture, positive ascites/washing, and surface involvement} showed a poorer OS and DFS than those at IC(ir), or those at the corresponding stage in non-CCC. In multivariable analysis, the capsule status was an independent prognostic factor of a poor OS and DFS {OS: HR, 2.832; 95% CI 1.156-6.938; P = 0.023; DFS: HR, 4.327; 95% CI, 1.937-9.667; P = 0.0004)} {In contrast, non-CCC: N.S. (OS/DFS)}. Furthermore, in CCC patients, intraperitoneal recurrences were more frequently observed in IC(non-ir) CCC than IA or IC(ir) CCC (P = 0.0083) {In contrast, non-CCC: N.S.}.

Conclusion

This study suggests that CCC patients other than those with intraoperative capsule rupture show a considerable risk for mortality despite adjuvant chemotherapy.     

Measurements of adiposity as clinical biomarkers for first-line bevacizumab-based chemotherapy in epithelial ovarian cancer

Objective

There is a lack of reliable indicators to predict who will benefit most from anti-angiogenic therapy, such as bevacizumab. Recognizing obesity is associated with increased levels of VEGF, the main target of bevacizumab, we sought to assess if adiposity, measured in terms of BMI, subcutaneous fat area (SFA), and visceral fat area (VFA) was prognostic.

Methods

Reviewed 46 patients with advanced EOC who received primary treatment with bevacizumab-based chemotherapy (N = 21) or chemotherapy alone (N = 25) for whom complete records, CT prior to the first cycle of chemo, and serum were available. CT was used to measure SFA and VFA by radiologists blinded to outcomes. ELISA was used to measure serum levels of VEGF and angiopoietin-2 in the bevacizumab group.

Results

BMI, SFA, and VFA were dichotomized using the median and categorized as “high” or “low”. In the bevacizumab group median PFS was shorter for patients with high BMI (9.8 vs. 24.7 months, p = 0.03), while in the chemotherapy group median PFS was similar between high and low BMI (17.6 vs. 11.9 months, p = 0.19). In the bevacizumab group patients with a high BMI had higher median levels of VEGF and angiopoietin-2, 371.9 vs. 191.4 pg/ml (p = 0.05) and 45.9 vs. 16.6 pg/ml (p = 0.09) respectively. On multivariate analysis neither BMI, SFA, nor VFA were associated with PFS (p = 0.13, p = 0.86, p = 0.16 respectively) or OS (p = 0.14, p = 0.93, p = 0.28 respectively) in the chemotherapy group. However, in the bevacizumab group BMI was significantly associated with PFS (p = 0.02); accounting for confounders adjusted HR for high vs. low BMI was 5.16 (95% CI 1.31–20.24). Additionally in the bevacizumab group SFA was significantly associated with OS (p = 0.03); accounting for confounders adjusted HR for high vs. low SFA was 3.58 (95% CI 1.12–11.43).

Conclusion

Results provide the first evidence in EOC that patients with high levels of adiposity may not derive benefit from bevacizumab and that measurements of adiposity are likely to be a useful biomarker.     

Histopathology predicts clinical outcome in advanced epithelial ovarian cancer patients treated with neoadjuvant chemotherapy and debulking surgery

Objective

To analyze the factors prognostic of survival in patients with advanced epithelial ovarian cancer (EOC) treated with neoadjuvant chemotherapy (NAC) followed by interval debulking surgery.

Methods

Outcomes were retrospectively in patients with advanced EOC or peritoneal cancer who received neoadjuvant paclitaxel and carboplatin chemotherapy every 3 weeks for three to four cycles, followed by interval debulking surgery and three additional cycles of the same regimens from January 2001 to November 2010. Therapeutic response was assessed histopathologically as grade 0 to 3, based on the degree of disappearance of cancer cells, displacement by necrotic and fibrotic tissue, and tumor-induced inflammation. Factors prognostic of progression-free survival (PFS) and overall survival (OS) were calculated.

Results

The 124 enrolled patients had a median age of 62 years (range, 35–79 years). Viable cancer cells were observed in specimens resected from 72 patients (58%) at interval debulking surgery after NAC. Multivariate analysis using the Cox proportional hazard model showed that advanced (stage IV) disease (hazard ratio [HR] = 1.94, p = 0.003), residual cancer at the end of surgery ≥ 1 cm (HR = 3.78, p < 0.001), and histological grade 0–1 (HR = 1.65, p = 0.03) were independent predictors of decreased OS. Grade 0–1 was also an independent predictor of increased risk of relapse within 6 months (odds ratio = 8.42, p = 0.003).

Conclusions

Residual disease of ≥ 1 cm, advanced stage, and the presence of more viable disease in resected specimens are prognostic factors for survival in advanced EOC patients receiving NAC followed by interval debulking surgery.     

Impact of obesity on surgical and oncologic outcomes in ovarian cancer

Objectives

The aim of this study is to determine the impact of obesity on surgical and oncologic outcomes after primary debulking surgery (PDS) in advanced epithelial ovarian cancer (EOC).

Methods

Women with stage IIIC/IV EOC who underwent PDS with curative intent between 1/2/2003 and 12/30/2011 were included. Patient characteristics, intraoperative and postoperative outcomes, recurrence and status were abstracted. Complications were graded according to the 4-point Accordion classification. For analyses, patients were divided into three groups according to body mass index (BMI): group 1—BMI < 25.0 kg/m²; group 2—BMI 25.0–39.9 kg/m²; and group 3—BMI ≥ 40.0 kg/m².

Results

Of the 620 patients included in the study, 36.6%, 56.9%, and 6.5% were in weight groups 1, 2, and 3, respectively.Weight group 3 was an independent predictor of severe complications after adjusting for confounders (adjusted odds ratio (95% CI): 2.93 (1.38, 6.20) for group 3 vs. group 2). Weight group was not associated with differences in residual disease (p = 0.80). The 90-day mortality rates were 11.9%, 6.7%, and 15.7%, respectively, in weight group 1, 2, and 3 (p = 0.049 unadjusted, p = 0.01 adjusted). There was no difference in OS (p = 0.52) or PFS (p = 0.23) between weight groups.

Conclusions

BMI ≥ 40.0 kg/m² is an independent predictor of severe 30-day postoperative morbidity and 90-day mortality after PDS for EOC—information useful in preoperative counseling. BMI does not appear to impact long-term oncologic outcomes including residual disease at PDS, although we had limited power at the extremes of BMI. BMI may be an important factor to consider in risk-adjustment models and reimbursement strategies.     

A prognostic nomogram to predict overall survival in women with recurrent ovarian cancer treated with bevacizumab and chemotherapy

Objective

To develop a nomogram to predict overall survival (OS) in women with recurrent ovarian cancer treated with bevacizumab and chemotherapy.

Methods

A multicenter retrospective study was conducted. Potential prognostic variables included age; stage; grade; histology; performance status; residual disease; presence of ascites and/or pleural effusions; number of chemotherapy regimens, treatment-free interval (TFI) prior to bevacizumab administration, and platinum sensitivity. Multivariate analysis was performed using Cox proportional hazards regression. The predictive model was developed into a nomogram to predict five-year OS.

Results

312 women with recurrent ovarian cancer treated with bevacizumab and chemotherapy were identified; median age was 59 (range: 19–85); 86% women had advanced stage (III–IV) disease. The majority had serous histology (74%), high grade cancers (93.5%), and optimal cytoreductions (69.5%). Fifty-one percent of women received greater than two prior chemotherapeutic regimens. TFI (AHR = 0.98, 95% CI 0.97–1.00, p = 0.022) was the only statistically significant predictor in a multivariate progression-free survival (PFS) analysis. In a multivariate OS analysis, prior number of chemotherapy regimens, TFI, platinum sensitivity, and presence of ascites were significant. A nomogram to predict five-year OS was constructed and internally validated (bootstrap-corrected concordance index = 0.737).

Conclusion

Our multivariate model identified prior number of chemotherapy regimens, TFI, platinum sensitivity, and the presence of ascites as prognostic variables for OS in women with recurrent ovarian cancer treated with bevacizumab combined with chemotherapy. Our nomogram to predict five-year OS may be used to identify women who may benefit from bevacizumab and chemotherapy, but further validation is needed.     

Phase II study of bevacizumab and pemetrexed for recurrent or persistent epithelial ovarian,fallopian tube or primary peritoneal cancer

Objective

We aimed to evaluate the efficacy and safety of combination bevacizumab/pemetrexed for the treatment of recurrent epithelial ovarian cancer (EOC).

Methods

Platinum-sensitive or -resistant patients with recurrent or persistent EOC were eligible if they had received up to 2 prior chemotherapy regimens, including a platinum/taxane regimen without prior bevacizumab. Pemetrexed 500 mg/m² IV and bevacizumab 15 mg/kg IV were administered every 3 weeks. The primary endpoint was 6-month progression-free survival (PFS); other endpoints included toxicities, PFS and overall survival (OS).

Results

Thirty-four patients received a median of 7 treatment cycles (range, 2–26). Median follow-up was 25.7 months (range, 3.0–47.2). Six month progression-free survival (PFS) was 56% (95% CI: 38–71). The following response rates were documented (%; 95% CI): 0 complete response, 14 partial responses (41%; 25–59), 18 stable disease (53%; 35–70) and 2 progressive disease (6%; 1–20). Median PFS was 7.9 months (95% CI, 4.6–10.9), with a median OS of 25.7 months (95% CI, 15.4–29.8). Twenty-two patients (64.7%) had a platinum-free interval (PFI) of > 6 months prior to enrollment. Grade 3–4 hematologic toxicities included neutropenia (50%), leukopenia (26%), thrombocytopenia (12%) and anemia (9%). Non-hematologic grade 3–4 toxicities included metabolic (29%), constitutional (18%), pain (18%) and gastrointestinal (15%). Two patients developed hematologic malignancies within one year of treatment.

Conclusions

Combination bevacizumab/pemetrexed is an active option for both platinum-sensitive and -resistant recurrent EOC. Further investigation of cost and novel toxicities associated with this regimen may be warranted.     

Weekly carboplatin with paclitaxel compared to standard three-weekly treatment in advanced epithelial ovarian carcinoma — a retrospective study

Objective

To retrospectively compare primary treatment with weekly carboplatin/paclitaxel (PC-W) to the standard 3-weekly carboplatin/paclitaxel (PC-3W) in women with advanced epithelial ovarian cancer, tubal carcinoma and primary peritoneal carcinoma.

Methods

Medical records were assessed for age, stage of disease, tumor histology and grade, BRCA mutation status, and platinum sensitivity. Patients were treated with either paclitaxel (175 mg/m²) and carboplatin (AUC 6) every three weeks (PC-3W; 133 patients), or with weekly paclitaxel (80 mg/m²) and weekly carboplatin (AUC 2) on days 1, 8, and 15 every 28 days (PC-W; 267 patients).

Results

Patient baseline characteristics were similar in both groups. Median overall survival (OS) was similar for PC-W and PC-3W (64.5 months vs. 61.5 months), but PC-W had longer median progression-free survival [PFS: 27.4 months (95% CI, 22.7–31.4) vs. 19.5 months (95% CI, 15.6–22.2) for PC-3W, p = 0.0024] and a longer median platinum-free interval [PFI: 22.1 months (95% CI, 16.0–24.5) vs. 14.2 months (95% CI, 10.7–17.2) for PC-3W, p = 0.0075]. PC-W showed a significantly higher response rate (86.4% vs. 77.9% for PC-3W, p = 0.0435). Multivariate analysis including for age at diagnosis, stage of disease, optimal debulking, histology, BRCA status, pretreatment CA-125 and PFI revealed that the PC-W women had lower risk of death (HR = 0.587, 95% CI, 0.402–0.857, p = 0.0058), lower risk of disease progression (HR = 0.494, 95% CI, 0.359–0.680, p < 0.0001), higher 2- and 3-year survival rates, and decreased grade II hair loss, neuropathy and thrombocytopenia compared with the PC-3W women.

Conclusion

The PC-W protocol improved PFS and had a similar OS as PC-3W.     

Impact of Age-Adjusted Charlson Comorbidity score on outcomes for patients with early-stage endometrial cancer

Objectives

To determine the impact of Age-Adjusted Charlson Comorbidity (AAC) index score on survival outcomes for patients with early stage endometrial cancer.

Methods

After IRB-approval, AAC score at time of hysterectomy was retrospectively tabulated by physician chart review for 671 patients with 2009 FIGO stage I–II endometrioid adenocarcinoma. Patients were grouped based on their AAC scores as follows: 0–1 (n = 204), 2–3 (n = 293) and > 3 (n = 174). Kaplan–Meier and log-rank test methods and univariate and multivariate modeling with Cox regression analysis was used to determine significant predictors of each survival endpoint.

Results

After a median follow-up of 85 months, 225 deaths were recorded (34 from EC and 191 from other causes) with a 7-year Overall (OS) and Disease-specific survival (DSS) of 77.6% and 94.0%, respectively. Based on AAC grouping, the 7-year OS, DSS, and Recurrence-free survival (RFS) were: 92.9%, 96.8%, and 94.9% for AAC 0–1; 81.7%, 95.3%, and 89.8% for AAC 2–3: and 56%, 88.2%, and 84.9% for AAC > 3 (p < 0.0001, p = 0.005 and p = 0.013, respectively). On multivariate analyses, higher AAC score, tumor grade, lower uterine segment involvement, and lymphovascular space invasion were significantly independent predictors for shorter OS, while for DSS and RFS, higher tumor grade and lymphovascular space invasion were significant predictors of worse outcome, but higher AAC score was not.

Conclusions

Comorbidity score is as important as pathological features for predicting overall survival outcomes in patients with early-stage endometrioid endometrial carcinoma. Higher AAC scores accurately predicted for worse OS. Comorbidity score should be considered in prospective clinical trials of endometrial carcinoma.