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.     

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.     

Black race independently predicts worse survival in uterine carcinosarcoma

Objective

GOG 150 suggested that Black women had worse survival compared to White women with uterine carcinosarcoma. Our objective was to compare treatment and survival outcomes between Black and White women at a National Comprehensive Cancer Network (NCCN) cancer center serving a diverse racial population.

Methods

An IRB approved retrospective cohort study of uterine carcinosarcoma patients diagnosed between 2000 and 2012 was performed. Survival was compared by race and stratified by stage. Median progression free and overall survival (PFS and OS) were calculated using Kaplan–Meier estimates and compared with the log-rank test. Multivariate survival analysis was performed with Cox proportional hazards model.

Results

158 women were included: 93 (59%) were Black and 65 (41%) were White. 95 (60%) had early stage disease and 63 (40%) had advanced stage disease. Black women had a shorter PFS (7.9 vs. 14.2 months, p < 0.001) and OS (13.4 vs. 30.8 months, p < 0.001). There was no difference in survival between Black and White women with advanced stage disease (OS 8.5 vs. 11.8, p = 0.18). However, PFS and OS were worse in Black women compared to White women with early stage disease (PFS 13.6 vs. 77.4, p = 0.001), (OS 25.4 vs. 94.7, p = 0.003). On multivariate analysis accounting for age, stage, BMI, and adjuvant treatment, Black race remained independently associated with risk of death (HR 2.0; 95% CI 1.25–3.23).

Conclusions

Black women with uterine carcinosarcoma have worse survival compared to White women despite similar patient and treatment characteristics. This difference is largely due to differences in survival in early stage disease.     

Radiotherapy with concurrent cisplatin-based doublet or weekly cisplatin for cervical cancer: A systematic review and meta-analysis

Background

Treatment with weekly cisplatin (CDDP) plus radiotherapy (RT) is the standard regimen for stage IB to stage IVA cervical carcinoma (CC). We performed a systematic review and meta-analysis of published studies to evaluate whether CDDP-based doublet therapy improves survival compared to weekly CDDP plus RT in patients with CC.

Materials and methods

We conducted a systematic search for randomized and nonrandomized studies in PubMed, EMBASE, Web of Science, Scopus, and the Cochrane Register of Controlled Trials. We then carried out a meta-analysis by using the fixed- or random-effects models. The primary endpoints were overall survival (OS) and progression-free survival (PFS), reported as odds ratios (ORs) and 95% confidence intervals (CIs).

Results

Four randomized trials and 4 retrospective studies that included a total of 1500 patients matched our selection criteria. Meta-analysis showed that for locally advanced CC, concurrent RT and with CDDP-based doublet chemotherapy significantly improved the OS (OR, 0.65; 95% CI, 0.51–0.81; p = 0.0002), PFS (OR, 0.71; 95% CI, 0.55–0.91; p = 0.006), and rate of locoregional relapse (OR, 0.64; 95% CI, 0.47–0.89; p = 0.008), compared to RT with concurrent weekly CDDP alone.

Conclusions

In patients with CC, platinum-based doublet chemotherapy plus concurrent RT was associated with improvements in the OS and PFS of 35% and 30% patients, respectively, compared to RT plus weekly CDDP. Therefore, platinum-based combination therapy plus RT should be the preferred treatment over weekly CDDP plus RT for stage IB–IVA CC.     

Diabetes mellitus and ovarian cancer: More complex than just increasing risk

Objective

Diabetes mellitus (DM) is a risk factor for endometrial cancer and is associated with poorer outcomes in breast and colon cancers. This association is less clear in epithelial ovarian cancer (EOC). We sought to examine the effect of DM on progression-free (PFS) and overall survival (OS) in women with EOC.

Methods

A retrospective cohort study of EOC patients diagnosed between 2004 and 2009 at a single institution was performed. Demographic, pathologic and DM diagnosis data were abstracted. Pearson chi-square test and t test were used to compare variables. The Kaplan–Meier method and the log rank test were used to compare PFS and OS between non-diabetic (ND) and DM patients.

Results

62 (17%) of 367 patients had a diagnosis of DM. No differences in age, histology, debulking status, or administration of intraperitoneal chemotherapy between ND and DM patients were present, although there were more stage I and IV patients in the ND group (p = 0.04). BMI was significantly different between the two groups (ND vs. DM, 27.5 vs. 30.7 kg/m², p < 0.001). While there were no differences in survival based on BMI, diabetic patients had a poorer PFS (10.3 vs. 16.3 months, p = 0.024) and OS (26.1 vs. 42.2 months, p = 0.005) compared to ND patients. Metformin use among diabetic patients did not appear to affect PFS or OS.

Conclusions

EOC patients with DM have poorer survival than patients without diabetes; this association is independent of obesity. Metformin use did not affect outcomes. The pathophysiology of this observation requires more inquiry.     

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.     

Venous thromboembolism during primary treatment of ovarian clear cell carcinoma is associated with decreased survival

Objectives

To determine the impact of venous thromboembolism (VTE) during primary treatment of ovarian clear cell carcinoma (OCCC) on survival.

Methods

After Institutional Review Board approval, 74 cases of OCCC were retrieved from our pathology files. Clinical and pathological data were obtained by medical record and pathology review. Standard statistical analyses were performed.

Results

Among 74 patients with OCCC, VTE was diagnosed in 11 (15%) during primary treatment and 7 (9%) at time of cancer recurrence. 56 (76%) patients never developed VTE. Patients with VTE during OCCC primary treatment had shorter progression-free survival (PFS) and overall survival (OS) than OCCC patients without VTE (median PFS 11 vs. 76 months, p = 0.01, median OS 19 vs. 90 months, p = 0.001). Patients with VTE during OCCC primary treatment had a 3.9-fold increase in risk of recurrence (p = 0.007) and a 6.3-fold increase in risk of death (p < 0.001). After controlling for cancer stage, VTE during OCCC primary treatment remained an independent prognostic factor for death (HR = 3.6, p = 0.005). No patient died of VTE.

Conclusions

VTE during OCCC primary treatment is associated with a significantly higher risk of cancer recurrence and death. This increased risk is not attributable to VTE-related mortality and raises the possibility that a paracrine circuit involving thrombosis might contribute to a more aggressive tumor biology.     

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.     

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.     

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.     

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.     

Surgical outcomes and national comprehensive cancer network compliance in advanced ovarian cancer surgery in a low volume military treatment facility

Objective

To evaluate the optimal cytoreduction (OPT) rate, National Comprehensive Cancer Network (NCCN) treatment guideline compliance rate and patient outcomes for advanced stage epithelial ovarian cancer (EOC) patients at our low volume institution.

Methods

Following IRB approval, records of patients with Stage III-IV EOC, primary peritoneal, or fallopian tube carcinoma completing both primary surgery and adjuvant chemotherapy were reviewed. Patient demographics, clinicopathologic variables, cytoreduction status (optimal or suboptimal), NCCN treatment guideline compliance, and survival were reviewed. Standard statistical tests including the t-test, Chi-square or Fisher's exact test and Kaplan–Meier Survival curves were utilized.

Results

Overall, 48 patients met all inclusion criteria. 35(73%) and 13 (27%) achieved optimal and suboptimal cytoreduction, respectively. Median overall survival (OS) for all patients was 37.1 months (95% CI 23.2 – 51.1 months) and NCCN treatment guideline compliance was 85.4%. Compared to sub-optimally cytoreduced patients the optimally cytoreduced patients were significantly older (62.2 vs. 53.5 yrs; p = 0.015); no other significant clinicopathologic differences were observed between the two groups. 19 of 48 (39.6%) patients enrolled in an upfront cooperative group trial. Median OS was 43.4 months for optimally compared to 15.6 months in sub-optimally cytoreduced patients (p = 0.012).

Conclusions

NCCN treatment guideline compliance, OPT, and median OS rates in our low volume institution are similar to those reported nationally, and argue against using volume alone as a rationale for centralization of care.     

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.     

Should stage IIIC ovarian cancer be further stratified by intraperitoneal vs. retroperitoneal only disease?: a Gynecologic Oncology Group study

Objective

To examine whether clinical outcomes varied with intraperitoneal (IP) and/or retroperitoneal (RP) involvement in stage IIIC epithelial ovarian cancer (EOC) patients with microscopic residual disease after cytoreduction.

Methods

Retrospective review was performed for EOC patients enrolled in Gynecologic Oncology Group (GOG)-182 who underwent primary cytoreduction to microscopic residual disease. Patients were divided into 3 groups: stage IIIC by lymphadenopathy with < 2 cm IP spread (RP); > 2 cm IP spread and negative nodes (IP/RP−); and > 2 cm IP dissemination and positive lymphadenopathy (IP/RP+). Product-limit and multivariate proportional hazards modeling were used.

Results

Analyses included 417 stage IIIC women who underwent primary cytoreduction with lymphadenectomy to microscopic residual. There were 203, 123, and 91 in the RP, IP/RP−, and IP/RP+ groups, respectively. IP/RP+ and IP/RP− were associated with worse progression-free survival (PFS) (Hazard Ratio (HR) 1.68, 95% confidence interval (CI) 1.23-2.30; HR 1.38, 95% CI 1.04-1.84) vs. RP only. IP/RP+ was associated with worse overall survival (OS) (HR 1.79, 95% CI 1.24-2.57) while IP/RP− trended towards worse OS (HR 1.21, 95% CI 0.85-1.73) vs. RP only. Median PFS for IP/RP+ and IP/RP− groups was 21 and 29 months, respectively, vs. 48 months in the RP group (p = 0.0007) and median OS of 63 and 79 months vs. “not reached,” respectively (p = 0.0038).

Conclusions

Among EOC patients surgically cytoreduced to microscopic residual disease, those upstaged to IIIC by retroperitoneal involvement demonstrated significant improvement in PFS and OS compared to patients with intraperitoneal tumor, suggesting that these women may represent a unique subset of FIGO stage IIIC patients.     

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).     

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.     

Interferon-gamma in ascites could be a predictive biomarker of outcome in ovarian carcinoma

Objective

The ovarian cancer-associated ascites is an ideal material for evaluating the interaction between the host immune system and cancer cells in the tumor micro-environment. The aim of this study was to investigate whether the selected target cytokine expression levels in ascites could serve as an immune biomarker for predicting outcomes in ovarian cancer.

Methods

Eighty-eight specimens of ovarian cancer-associated ascites were evaluated to select the target cytokine by a cytokine profiling kit. The 144 total samples were subsequently analyzed for this target cytokine. The correlation between the target cytokine and clinical characteristics was analyzed.

Results

Interferon-gamma (IFN-γ) was identified as the target cytokine. Higher levels of IFN-γ in the ascites of the tumor micro-environment were associated with advanced disease (p = 0.012), higher tumor histological grading (p = 0.004), and sub-optimal surgical status (p = 0.040). By multivariate analysis, the adjusted hazard ratios (HRs) were 2.74 (95% confidence interval (CI) 1.85–4.05, p < 0.001) for disease-free survival (DFS) and 1.72 (95% CI 1.01–2.93, p = 0.048) for overall survival (OS) for a 10-fold increase in IFN-γ concentration in the ascites. An inverse dose–response relationship between IFN-γ level and survival was also noted (P_trend < 0.001 for DFS and P_trend < 0.042 for OS).

Conclusions

Patients with ovarian cancer and higher IFN-γ expression levels in cancer-associated ascites will have shorter DFS and OS. IFN-γ levels in the ascites may be a prognostic marker and a potential reference for immunotherapy targeting IFN-γ.     

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.     

Progranulin is a potential prognostic biomarker in advanced epithelial ovarian cancers

Objective

There are few validated relapse prediction biomarkers for epithelial ovarian cancer (EOC). We have shown progranulin (PGRN) and secretory leukocyte protease inhibitor (SLPI) are up regulated, overexpressed survival factors in EOC. We hypothesized they would predict presence of occult EOC.

Method

PGRN, SLPI, and the known biomarker HE4 were measured in EOC patient plasma samples, prospectively collected every 3 months from initial remission until relapse. Clinical data and CA125 results were incorporated into statistical analyses. Exploratory Kaplan-Meier estimates, dividing markers at median values, evaluated association with progression-free survival (PFS) and overall survival (OS). Area-under-the-curve (AUC) statistics were computed from receiver operating characteristic (ROC) curves to evaluate discrimination ability. A Cox proportional hazards model assessed the association between PFS, OS, and biomarkers, adjusting for clinical prognostic factors.

Results

Samples from 23 advanced stage EOC patients were evaluated. PGRN at 3 months was the only biomarker independently associated with PFS (P < 0.0001) and OS (P < 0.003). When used to predict progression by 18 months, sensitivity and specificity were 93% and 100%, respectively, with AUC = 0.944. The Cox model hazard ratio for PFS, divided at 59 ng/ml by ROC analysis and adjusted for clinical factors, was 23.5 (95% CI: 2.49-220). Combinations with SLPI, HE4, and/or CA125 did not improve the model.

Conclusions

We report pilot data indicating a potential independent association of PGRN on EOC patient PFS and OS. A validation study will be required to confirm this finding and to inform whether PGRN warrants evaluation as a potential screening biomarker.