Carcinosarcoma of the ovary compared to papillary serous ovarian carcinoma: A SEER analysis

Objective

The aims of this study are to determine if outcomes of patients with ovarian carcinosarcoma (OCS) differ from women with high grade papillary serous ovarian carcinoma when compared by stage as well as to identify any associated clinico-pathologic factors.

Methods

The Surveillance, Epidemiology, and End Results (SEER) Program data for all 18 registries from 1998 to 2009 was reviewed to identify women with OCS and high grade papillary serous carcinoma of the ovary. Demographic and clinical data were compared, and the impact of tumor histology on survival was analyzed using the Kaplan–Meier method. Factors predictive of outcome were compared using the Cox proportional hazard model.

Results

The final study group consisted of 14,753 women. 1334 (9.04%) had OCS and 13,419 (90.96%) had high grade papillary serous carcinoma of the ovary. Overall, women with OCS had a worse five-year, disease specific survival rate, 28.2% vs. 38.4% (P < 0.001). This difference persisted for each FIGO disease stages I–IV, with five year survival consistently worse for women with OCS compared with papillary serous carcinoma. Over the entire study period, after adjusting for histology, age, period of diagnosis, SEER registry, marital status, stage, surgery, radiotherapy, lymph node dissection, and history of secondary malignancy after the diagnosis of ovarian cancer, carcinosarcoma histology was associated with decreased cancer-specific survival.

Conclusions

OCS is associated with a poor prognosis compared to high grade papillary serous carcinoma of the ovary. This difference was noted across all FIGO stages.     

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.     

Patterns of care,predictors, and outcomes of chemotherapy in elderly women with early-stage uterine carcinosarcoma: A population-based analysis

Objective

To examine the patterns of care, predictors, and impact of chemotherapy on survival in elderly women diagnosed with early-stage uterine carcinosarcoma.

Methods

The Surveillance, Epidemiology, and End Results (SEER)-Medicare database was used to identify women 65 years or older diagnosed with stage I–II uterine carcinosarcomas from 1991 through 2007. Multivariable logistic regression and Cox-proportional hazards models were used for statistical analysis.

Results

A total of 462 women met the eligibility criteria; 374 had stage I, and 88 had stage II uterine carcinosarcomas. There were no appreciable differences over time in the percentages of women administered chemotherapy for early stage uterine carcinosarcoma (14.7% in 1991–1995, 14.9% in 1996–2000, and 17.9% in 2001–2007, P = 0.67). On multivariable analysis, the factors positively associated with receipt of chemotherapy were younger age at diagnosis, higher disease stage, residence in the eastern part of the United States, and lack of administration of external beam radiation (P < 0.05). In the adjusted Cox-proportional hazards regression models, administration of three or more cycles of chemotherapy did not reduce the risk of death in stage I patients (HR: 1.45, 95% CI: 0.83–2.39) but was associated with non-significant decreased mortality in stage II patients (HR: 0.83, 95% CI: 0.32–1.95).

Conclusions

Approximately 15–18% of elderly patients diagnosed with early-stage uterine carcinosarcoma were treated with chemotherapy. This trend remained stable over time, and chemotherapy was not associated with any significant survival benefit in this patient population.     

Estrogen receptor expression and increased risk of lymphovascular space invasion in high-grade serous ovarian carcinoma

Objective

Recent studies have demonstrated that lymphovascular space invasion (LVSI) is associated with increased risk of hematogenous and lymphatic metastasis and poor clinical outcome of women with epithelial ovarian cancer. Given the suspected role of estrogen in promoting ovarian cancer metastasis, we examined potential links between estrogen receptor and LVSI in high-grade serous ovarian carcinoma.

Methods

Tumoral expression of ER, PR, p53, MDR1, EGFR, HER2, DNA ploidy, and S-phase fraction was examined for 121 cases of stage I–IV high-grade serous ovarian carcinoma samples obtained at primary cytoreductive surgery. Biomarker expression was correlated to LVSI and survival outcomes.

Results

LVSI was observed in 101 (83.5%) of all cases. Immunohistochemistry of tested biomarkers showed ER (86.7%) to be the most commonly expressed followed by p53 (71.4%), HER2 (68.3%), EGFR (52.1%), MDR-1 (14.3%), and PR (8.9%). ER expression was positively correlated to PR expression (r = 0.31, p = 0.001). LVSI was only correlated with ER (odds ratio 6.27, 95%CI 1.93–20.4, p = 0.002) but not with other biomarkers. In multivariate analysis, ER remained significantly associated with LVSI (p = 0.039). LVSI remained a significant prognostic factor for decreased progression-free survival (HR 3.01, 95%CI 1.54–5.88, p = 0.001) and overall survival (HR 2.69, 95%CI 1.18–6.23, p = 0.021) while ER-expression did not remain as a significant variable in multivariate analysis.

Conclusion

Our data demonstrated that estrogen receptor was positively correlated with LVSI that was an independent prognostic indicator of poor survival outcomes of high-grade serous ovarian carcinoma. This study emphasizes the importance of estrogen pathway in promoting lymphatic or vascular spread of high-grade serous ovarian carcinoma.     

Outcomes of ovarian preservation in a cohort of premenopausal women with early-stage endometrial cancer: A Korean Gynecologic Oncology Group study

Objective

The aim of this study was to evaluate the impact of ovarian preservation on the recurrence and survival rates of premenopausal women with early-stage endometrial cancer.

Methods

Using medical records of premenopausal women who received primary surgical treatment for stage I–II endometrial cancer, the demographics and survival rates were compared retrospectively for patients who had ovarian preservation and those who underwent bilateral salpingo-oophorectomy. Cox proportional hazards models with inverse probability of treatment weighting (IPTW) based on propensity score were performed to adjust for selection bias between the two groups.

Results

A total of 495 women were identified, including 176 patients who had ovarian preservation. The ovarian preservation group was younger (P < 0.001) and had an earlier year of diagnosis (P = 0.014), a lower prevalence of lymphadenectomy (P < 0.001), and a marginally significant association with lower tumor grade (P = 0.052). The Kaplan–Meier curve and the log rank test showed no difference in either recurrence-free survival (P = 0.742) or overall survival (P = 0.462) between the two groups. In a multivariate Cox model adjusted by IPTW and covariates, ovarian preservation had no effect on either recurrence (hazard ratio [HR], 0.73; 95% CI, 0.29–1.81) or overall survival (HR, 1.33; 95% CI, 0.43–4.09).

Conclusions

Ovarian preservation does not appear to be associated with an adverse impact on the outcomes of premenopausal women with early-stage endometrial cancer. The present study has useful implications for physicians counseling young women who want to preserve their ovaries.     

Body mass index,physical activity,and mortality in women diagnosed with ovarian cancer: Results from the Women's Health Initiative

Background

Ovarian cancer is often diagnosed at late stages and consequently the 5-year survival rate is only 44%. However, there is limited knowledge of the association of modifiable lifestyle factors, such as physical activity and obesity on mortality among women diagnosed with ovarian cancer. The purpose of our study was to prospectively investigate the association of (1) measured body mass index (BMI), and (2) self-reported physical activity with ovarian cancer-specific and all-cause mortality in postmenopausal women enrolled in the Women's Health Initiative (WHI).

Methods

Participants were 600 women diagnosed with primary ovarian cancer subsequent to enrollment in WHI. Exposure data, including measured height and weight and reported physical activity from recreation and walking, used in this analysis were ascertained at the baseline visit for the WHI. Cox proportional hazard regression was used to examine the associations between BMI, physical activity and mortality endpoints.

Results

Vigorous-intensity physical activity was associated with a 26% lower risk of ovarian cancer specific-mortality (HR = 0.74; 95% CI: 0.56–0.98) and a 24% lower risk of all-cause mortality (HR = 0.76; 95% CI: 0.58–0.98) compared to no vigorous-intensity physical activity. BMI was not associated with mortality.

Conclusions

Participating in vigorous-intensity physical activity, assessed prior to ovarian cancer diagnosis, appears to be associated with a lower risk of ovarian cancer mortality.     

A binary histologic grading system for ovarian serous carcinoma is an independent prognostic factor: a population-based study of 4317 women diagnosed in Denmark 1978-2006

Objective

To evaluate the prognostic significance of histologic grade on survival of ovarian serous cancer in Denmark during nearly 30 years.

Methods

Using the nationwide Danish Pathology Data Bank, we evaluated 4317 women with ovarian serous carcinoma in 1978-2006. All pathology reports were scrutinized and tumors classified as either low-grade serous carcinomas (LGSC) or high-grade serous carcinomas (HGSC). Tumors in which the original pathology reports were described as well-differentiated were classified as LGSC, and those that were described as moderately or poorly differentiated were classified as HGSC. We obtained histologic slides from the pathology departments for women with a diagnosis of well-differentiated serous carcinoma during 1997-2006, which were then reviewed by expert gynecologic pathologists. Data were analyzed using Kaplan-Meier methods and Cox proportional hazards regression analysis with follow-up through June 2009.

Results

Women with HGSC had a significantly increased risk of dying (HR = 1.9; 95% CI: 1.6-2.3) compared with women with LGSC while adjusting for age and stage. Expert review of 171 women originally classified as well-differentiated in 1997-2006 were interpreted as LGSC in 30% of cases, whereas 12% were interpreted as HGSC and 50% as serous borderline ovarian tumors (SBT). Compared with women with confirmed LGSC, women with SBT at review had a significantly lower risk of dying (HR = 0.5; 95% CI: 0.22-0.99), and women with HGSC at review had a non-significantly increased risk of dying (HR = 1.6; 95% CI: 0.7-3.4).

Conclusions

A binary grading system is a significant predictor of survival for ovarian serous carcinoma.     

Applicability of the concept of “platinum sensitivity” to recurrent endometrial cancer: The SGSG-012/GOTIC-004/Intergroup study

Objective

The concept of “platinum sensitivity” has been widely applied in the management of recurrent ovarian cancer. This study aimed to evaluate the applicability of this concept to recurrent endometrial cancer.

Patients and methods

In this multicenter retrospective cohort study, the clinical data of patients with recurrent endometrial cancer, who had a history of receiving first-line platinum-based chemotherapy and who received second-line platinum-based chemotherapy at the time of recurrence between January 2005 and December 2009 were reviewed.

Results

A total of 262 patients from 30 centers with initial FIGO stage classifications of I (29), II (23), III (122), and IV (88) were enrolled. In total, 153 endometrioid adenocarcinomas, 34 serous adenocarcinomas, 17 clear cell adenocarcinomas, 36 carcinosarcomas, and 22 “other” tumors were documented. The response rates for patients with platinum-free intervals of < 6 months, 6–11 months, 12–23 months, and ≥ 24 months were 25%, 38%, 61%, and 65%, respectively. The median progression-free survival after second-line platinum-based chemotherapy for patients with platinum-free intervals of < 12 months and ≥ 12 months was 4.4 (95% confidence interval (CI) = 3.7–5.8) months and 10.3 (95% CI = 8.2–12.6) months, respectively (log-rank P < 0.0001), and the median overall survival was 13.8 (95% CI = 10.6–18.1) months and 40.9 (95% CI = 25.3–54.2) months, respectively (log-rank P < 0.0001).

Conclusion

Platinum-free interval is a predictor of response and survival after second-line platinum-based chemotherapy in patients with recurrent endometrial cancer. The concept of “platinum sensitivity” could be applicable to recurrent endometrial cancer.     

The time interval from surgery to start of chemotherapy significantly impacts prognosis in patients with advanced serous ovarian carcinoma — Analysis of patient data in the prospective OVCAD study

Objective

Cytoreductive surgery and platinum-based systemic therapy constitute the standard treatment of patients with advanced ovarian cancer. The aim of the present study was to evaluate whether the time interval from surgery to start of chemotherapy has an impact on clinical outcome.

Methods

Data of 191 patients with advanced serous (FIGO III–IV) ovarian cancer from the prospective multicenter study OVCAD (OVarian CAncer Diagnosis) were analyzed. All patients underwent primary surgery followed by platinum-based chemotherapy.

Results

The 25%, 50%, and 75% quartiles of intervals from surgery to start of chemotherapy were 22, 28, and 38 days, respectively (range, 4–158 days). Preoperative performance status (P < 0.001), extent of surgery (P < 0.001), and perioperative complications (P < 0.001) correlated with intervals from surgery to initiation of chemotherapy. Timing of cytotoxic treatment [≤ 28 days versus > 28 days; hazard ratio (HR) 1.73 (95% confidence interval 1.08–2.78), P = 0.022], residual disease [HR 2.95 (95% confidence interval 1.87–4.67), P < 0.001], and FIGO stage [HR 2.26 (95% confidence interval 1.41–3.64), P = 0.001] were significant prognostic factors for overall survival in multivariate analysis. While the interval from surgery to start of chemotherapy did not possess prognostic significance in patients without postoperative residual disease (n = 121), it significantly correlated with overall survival in patients with postoperative residual disease [n = 70, HR 2.24 (95% confidence interval 1.08–4.66), P = 0.031].

Conclusion

Our findings suggest that delayed initiation of chemotherapy might compromise overall survival in patients with advanced serous ovarian cancer, especially when suboptimally debulked.     

Malignant ovarian germ cell tumors: Presentation,survival and second cancer in a population based Norwegian cohort (1953–2009)

Purpose

To quantify and compare survival in women with malignant ovarian germ cell tumors (MOGCTs) in Norway before and after the introduction of cisplatin-based chemotherapy (around 1980), and to explore the association between different types of treatment and the development of a second cancer.

Patients and methods

We identified 351 patients diagnosed with MOGCTs from 1953 to 2009 in the Cancer Registry of Norway. Ovarian cancer-specific survival was calculated separately for patients diagnosed before and after 1980. Patients were divided into subgroups by histological subtype (pure dysgerminoma, malignant teratoma, other MOGCTs) and extent of disease (localized and metastatic). We estimated the cumulative incidence of a second cancer in 10-year MOGCT survivors. Kaplan–Meier estimates were used, and p < 0.05 was considered significant.

Results

20-Year ovarian cancer-specific survival increased from 59% (95% CI 51% to 66%) before 1980 to 88% (95% CI 83%–93%) thereafter. Significant improvement was observed in all subgroups. No second cancer was diagnosed in any of 31 10-year MOGCT survivors treated with surgery only; second cancer was diagnosed in 23 of 139 patients who underwent cytotoxic treatment (98 radiotherapy ± chemotherapy, 41 chemotherapy only; p = 0.08). Patients aged > 50 years had a significantly poorer ovarian cancer-specific survival than younger patients (HR = 5.98, 95% CI 3.39–10.57) after adjustment for histological subtype and stage at presentation. Our results favor the treatment of patients with metastatic MOGCTs at large cancer centers.

Conclusion

Today women with MOGCTs have an excellent prognosis if treated according to modern therapeutic principles.     

Pre-diagnostic serum levels of inflammation markers and risk of ovarian cancer in the Prostate,Lung, Colorectal and Ovarian Cancer (PLCO) Screening Trial

Objective

Pro-inflammatory mechanisms may explain the increased ovarian cancer risk linked to more lifetime ovulations, endometriosis, and exposure to talc and asbestos, as well as decreased risk with non-steroidal anti-inflammatory drugs. Limited data are available to estimate ovarian cancer risk associated with levels of circulating inflammatory markers.

Methods

We conducted a nested case–control study within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Pre-diagnostic serum levels of 46 inflammation-related biomarkers (11 with a priori hypotheses; 35 agnostic) were measured in 149 incident ovarian cancer cases and 149 matched controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression and adjusted for identified covariates.

Results

Increased ovarian cancer risk was associated with elevated levels of C-reactive protein (CRP) [tertile (T)3 vs. T1: OR (95% CI) 2.04 (1.06–3.93), p-trend = 0.03], interleukin (IL)-1α [detectable vs. undetectable: 2.23 (1.14–4.34)] and tumor necrosis factor alpha (TNF-α) [T3 vs. T1: 2.21 (1.06–4.63), p-trend = 0.04]. Elevated IL-8 was non-significantly associated with risk [T3 vs. T1: 1.86 (0.96–3.61), p-trend = 0.05]. In analyses restricted to serous ovarian cancer (n = 83), the associations with CRP and IL-8 remained or strengthened [CRP T3 vs. T1: 3.96 (1.14–11.14), p-trend = 0.008; IL-8 T3 vs. T1: 3.05 (1.09–8.51), p-trend = 0.03]. Elevated levels of CRP and TNF-α remained positively associated with ovarian cancer risk in analysis restricted to specimens collected at least 5 years before diagnosis (n = 56).

Conclusion

These results suggest that CRP, IL-1α, IL-8, and TNF-α are associated with increased risk of subsequently developing ovarian cancer.     

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 prognostic significance of preoperative leukocytosis in epithelial ovarian carcinoma: A retrospective cohort study

Objective

Preoperative leukocytosis is known to be a negative prognostic factor for several gynecologic malignancies, but its relationship with epithelial ovarian carcinoma (EOC) is unknown. We sought to evaluate the prognostic implications of preoperative leukocytosis for women with EOC.

Methods

We retrospectively reviewed the medical records of patients who underwent primary debulking surgery and adjuvant platinum-based chemotherapy for EOC between January 1993 and October 2011. Associations between leukocytosis and recurrence-free survival (RFS) and overall survival (OS) were determined by univariate analyses. Multivariate Cox proportional hazards regression was used to identify independent prognostic factors for RFS and OS.

Results

Of 155 women, 23 (14.8%) had leukocytosis and 132 (85.2%) did not have leukocytosis. RFS and OS were significantly shorter for women with leukocytosis than for women without leukocytosis (P = 0.009 and P < 0.0001, respectively). The mortality rate was also higher among women with leukocytosis (P < 0.0001). Multivariate analysis revealed that preoperative leukocytosis (hazard ratio [HR]: 2.15; 95% confidence interval [CI]: 1.55–4.41; P = 0.009), advanced stage (HR: 3.12; 95% CI: 1.44–6.75; P = 0.004), and optimal cytoreduction (HR: 0.38; 95% CI: 0.14-0.70; P = 0.031) were independent prognostic factors for RFS. Additionally, preoperative leukocytosis was independently associated with decreased OS (HR: 7.66; 95% CI: 2.78–21.16; P < 0.0001).

Conclusions

Among women with EOC, preoperative leukocytosis might be an independent prognostic factor for RFS and OS. A larger-scaled, prospective study is needed to verify these results.     

Adjuvant radiation in early stage,unfavorable histology endometrial carcinoma is associated with improved local control and survival

Objective

Unfavorable histology endometrial carcinomas confer worse prognosis. We determined the association of adjuvant radiation on local recurrence and survival for unfavorable, early stage endometrial cancer.

Methods

We retrospectively identified 125 patients who had a hysterectomy for early stage (FIGO IA), unfavorable histology (clear cell, papillary serous or grade 3 endometrioid), endometrial carcinoma treated between 1992 and 2011. Patients were restaged according to current FIGO 2009 guidelines. Primary endpoint was local control and secondary endpoints were distant recurrence and overall survival.

Results

The median age of the cohort was 67 years old with a mean follow up 152 months. Adjuvant radiation was delivered in 60 patients (48%). There were a total of 24 recurrences; 5 had local–regional recurrences, 4 local and distant recurrence, 12 distant only recurrences, and 3 had unspecified recurrences. The 5-year local–regional control was 97.8% in patients who received radiation and 80.1% in patients who did not receive radiation (p = 0.018). The 5-year overall survival rate was 68.1% if patients did not receive radiation and 84.9% if they did receive radiation (p = 0.0062). On univariate analysis, only radiation (HR 0.12, 95% CI: 0.03 to 0.49, p-value = 0.018) was associated with a significant increase in local relapse free survival.

Conclusions

Adjuvant radiation therapy was significantly associated with an improvement in local–regional control and overall survival in patients with unfavorable histology, early stage endometrial cancer.     

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.     

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.     

Is it possible to define an optimal time for chemotherapy after surgery for ovarian cancer?

Objective

The aims of this study are to investigate the actual time from primary surgery for epithelial ovarian cancer (OC) to initiation of chemotherapy (TI) amongst Danish women in 2005–2006, and to compare the survival for groups with early initiation (≤ median TI) and late initiation of adjuvant chemotherapy (> median TI).

Methods

All Danish women who underwent surgery for OC in the period 1 January 2005 to 31 December 2006 and recorded in the Danish Gynaecological Cancer Database (DGCD) were included. The five-year survival was estimated overall and by TI exposure. The Cox proportional hazard regression analysis was used to compute the adjusted hazard ratio (HR).

Results

The median TI was 32 days (25–75% quartile: 24 days; 41 days). The strongest prognostic factors for death were residual tumour and the International Federation of Obstetrics and Gynecology (FIGO) stage.The unadjusted HR for death in patients with TI > 32 days compared with TI ≤ 32 days was 0.85 (95% CI: 0.70; 1.04), p-value 0.12. When adjusted for residual tumour and FIGO-stage the HR was 1.13 (95% CI: 0.92; 1.39), p-value 0.26. The overall five-year survival was 42.8%, (95% CI: 38.9%; 46.5%).

Conclusions

This nationwide population-based cohort study revealed a non-significant increased risk of death for patients with TI > 32 days compared with the reference TI ≤ 32 days. The strongest prognostic factors were residual tumour after surgery and FIGO-stage. The overall five-year survival was 42.8% (95% CI: 38.9%; 46.5%).     

The effect of bisphosphonates on the risk of endometrial and ovarian malignancies

Objective

The use of bisphosphonates has been associated with reduced risk and improved survival of breast and colorectal malignancies. This study was aimed at studying the effects of bisphosphonates on gynecological cancers.

Methods

The Cancer in the Ovary and Uterus Study (CITOUS) is a case–control study of newly diagnosed cases of gynecological malignancies and age/clinic/ethnic-group matched population controls. The use of bisphosphonates prior to, and following, diagnosis was assessed in 424 cases of ovarian and endometrial cancers and 341 controls, all postmenopausal at recruitment, enrolled in Clalit Health Services (CHS), using pharmacy records.

Results

The use of bisphosphonates for more than 1 year prior to diagnosis was associated with a significantly reduced risk of ovarian cancer (OR = 0.49, 95% CI: 0.26–0.93) and endometrial cancer (OR = 0.39, 95% CI: 0.24–0.63). The association with endometrial cancer (OR = 0.48, 0.27–0.84) remained statistically significant after adjustment for a variety of putative effect modifiers (RR = 0.48, 0.26–0.89). The association with ovarian cancer remained significant when adjusted to statin use (0.46, 0.23–0.90) but not for other modifiers (0.58, 0.29–1.18). A strong negative association was found in an adjusted model for the use of either bisphosphonates or statins for more than 1 year (0.40, 0.23–0.68).

Conclusion

The use of bisphosphonates, with or without statins, for more than 1 year before diagnosis was associated with reduced risk of endometrial and ovarian cancers.     

Prognostic and predictive value of the Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) score in surgery for recurrent ovarian cancer

Objectives

The Arbeitsgemeinschaft Gynaekologische Onkologie (AGO) score was developed as selection criteria and validated as predictor of a high probability for complete resection in recurrent ovarian cancer. It is not defined whether the predictive value is independent from underlying tumor biology or is solely based on a selection of good prognostic risks.

Methods

We performed an exploratory analysis of all consecutive patients with cytoreductive surgery in recurrent ovarian cancer in a tertiary referral center 1999–2013, before and after introduction of the AGO score.

Results

217 consecutive patients were included of whom 112 patients were AGO score positive and 105 patients were score negative. Corresponding complete resection rates were 89.3% and 66.7%, respectively, and confirm the score's predictive value. However, a positive AGO score was also associated with better outcome after adjustment for surgical outcome. Patients with complete resection and a positive AGO score showed a median overall survival of 63.9 months (95% CI 48.1–79.6) compared to 48.4 months (95% CI 30.3–66.5) after complete resection and negative score (log-rank p = 0.10). However, in multivariate analysis the only independent prognostic factor was complete resection (HR 2.450; 95% CI: 1.542–3.891).

Conclusions

The AGO score could identify suitable candidates for secondary cytoreductive surgery but failed to prove an independent prognostic value thus suggesting an effect of successful surgery on its own. However, the latter has to be proven prospectively. In addition, further studies should evaluate the predictive and prognostic impact of a negative score.