Stage III-IV Epithelial Ovarian Cancer Research Articles

Real-world study of lymphadenectomy in patients with advanced epithelial ovarian cancer.

The evidence on the role of retroperitoneal lymphadenectomy is limited to less common histology subtypes of epithelial advanced ovarian cancer. This retrospective cohort study utilized data from the Surveillance, Epidemiology, and End Results Program from January 1, 2010, to December 31, 2019. Patients with stage III-IV epithelial ovarian cancer were included and divided into two groups based on whether they received retroperitoneal lymphadenectomy. The primary outcomes are overall survival (OS) and cause-specific survival (CSS). Among the 10 184 included patients, 5472 patients underwent debulking surgery with retroperitoneal lymphadenectomy, while 4712 patients only underwent debulking surgery. No differences were found in the baseline information between the two groups after propensity score matching. Retroperitoneal lymphadenectomy during debulking surgery was associated with improved 5-year OS (43.41% vs. 37.49%, p < 0.001) and 5-year CSS (46.43% vs. 41.79%, p < 0.001). Subgroup analysis further validate the retroperitoneal lymphadenectomy increased the 5-year OS and CSS in patients with high-grade serous cancer. Although the results were not validated in the less common ovarian cancer (including endometrial cancer, mucinous cancer, low-grade serous cancer, and clear cell cancer), the tendency showed patients with the above four subtypes may benefit from the lymphadenectomy which is restricted for small sample size after propensity score matching. This study revealed that retroperitoneal lymphadenectomy could further improve the survival outcome during debulking surgery in patients with advanced epithelial ovarian cancer. The conclusion was affected by the histology subtypes of ovarian cancer and further studies are needed to validate the conclusion in less common ovarian cancer.

Comparison of survival outcomes between olaparib and niraparib maintenance therapy in BRCA-mutated, newly diagnosed advanced ovarian cancer

IntroductionThis multicenter retrospective cohort study aimed to compare survival outcomes and adverse events between maintenance therapy with two poly (ADP-ribose) polymerase (PARP) inhibitors, olaparib and niraparib, in patients with BRCA-mutated, newly diagnosed advanced epithelial ovarian cancer (EOC) who responded to platinum-based chemotherapy. MethodsWe enrolled stage III-IV EOC patients with germline and/or somatic BRCA1/2 mutations that had received maintenance therapy with olaparib or niraparib. A 3:1 propensity score matching was conducted using two variables: residual disease size and the presence of germline variants. The primary outcome was progression-free survival (PFS), and the secondary outcomes were time to first subsequent therapy (TFST), overall survival (OS), and treatment-emergent adverse events (TEAEs). ResultsIn the propensity score-matched analysis, 80 patients who received olaparib and 31 patients who received niraparib were matched (3:1). In the propensity score-matched cohort, median PFS with olaparib vs. niraparib was not reached vs 31.5 months (HR, 1.08; 95% CI, 0.47–2.52; p = 0.854). The median TFST was not reached vs 31.8 months (HR, 1.20; 95% CI, 0.51–2.81; p = 0.682), and neither olaparib nor niraparib reached the median OS (HR, 0.42; 95% CI, 0.01–17.61; p = 0.649). In terms of the incidence rates of any-grade hematologic or non-hematologic TEAEs, higher rates of thrombocytopenia (p = 0.021) and neutropenia (p = 0.011) were observed in the niraparib group. ConclusionAdvanced EOC patients with BRCA1/2 mutations exhibited no significant difference in OS between olaparib and niraparib, indicating the need to consider individualized strategies for selecting PARP inhibitors based on adverse event profiles.

Risk factors for the failure of first-line PARP inhibitor maintenance therapy in patients with advanced ovarian cancer: Gynecologic Oncology Research Investigators Collaboration Study (GORILLA-3004).

To identify the risk factors for failure of first-line poly (ADP-ribose) polymerase inhibitor (PARPi) maintenance therapy in patients with advanced ovarian cancer. Patients with stage III-IV epithelial ovarian cancer who received first-line PARPi maintenance therapy were retrospectively reviewed. Clinicopathologic factors were compared between two groups-recur/progression of disease (PD) and non-recur/PD. In total, 191 patients were included. Median follow-up was 9.9 months, and recurrence rate was 20.9%. BRCA mutations were found in 63.4% patients. Postoperative residual tumor (60.5% vs. 37.8%), non-high grade serous carcinoma (HGSC) (15.0% vs. 6.0%), neoadjuvant chemotherapy (NAC) (55.0% vs. 35.8%), and pre-PARPi serum CA-125 levels ≥23.5 U/mL (35.9% vs. 15.2%) were more frequently observed in the recur/PD group. Multivariate Cox-regression analysis revealed pre-PARPi serum CA-125 levels ≥23.5 U/mL (HR, 2.17; 95%CI, 1.03-4.57; p = 0.042), non-HGSC (3.28; 1.20-8.97; p = 0.021), NAC (2.11; 1.04-4.26; p = 0.037), and no BRCA mutation (2.23; 1.12-4.44; p = 0.023) as independent risk factors associated with poor progression-free survival (PFS). A subgroup analysis according to BRCA mutation status showed that pre-PARPi serum CA-125 levels ≥26.4 U/mL were the only independent risk factor for poor PFS in women with BRCA mutations (2.75; 1.03-7.39; p = 0.044). Non-HGSC (5.05; 1.80-14.18; p = 0.002) and NAC (3.36; 1.25-9.04; p = 0.016) were independent risk factors in women without BRCA mutations. High pre-PARPi serum CA-125 levels, non-HGSC histology, NAC, and no BRCA mutation might be risk factors for early failure of first-line PARPi maintenance therapy. In women with BRCA mutations, high pre-PARPi serum CA-125 levels, which represent a large tumor burden before PARPi, were the only independent risk factor for poor PFS.

Peroperative extent of peritoneal metastases affects the surgical outcome and survival in advanced ovarian cancer

ObjectiveDetermining whether cytoreductive surgery (CRS) is feasible in patients with advanced ovarian cancer and whether extensive surgery is justified is challenging. Accurate patient selection for CRS based on pre- and peroperative parameters will be valuable. The aim of this study is to assess the association between the extent of peritoneal metastases as determined during surgery and completeness of interval CRS and survival. MethodsThis single-center observational cohort study included consecutive patients with newly diagnosed stage III-IV epithelial ovarian cancer who received neoadjuvant chemotherapy and underwent interval CRS. The 7 Region Count (7RC) was recorded during surgical exploration to systematically quantify the extent of peritoneal metastases. Logistic regression analysis was performed to predict surgical outcomes, and Cox regression analysis was done for survival outcomes. ResultsA total of 316 patients were included for analyses. The median 7RC was 4 (interquartile range: 2–6). Complete CRS was performed in 58%, optimal CRS in 30%, and incomplete CRS in 12% of patients. A higher 7RC was independently associated with lower odds of complete or optimal CRS in multivariable analysis (odds ratio [OR] = 0.45, 95% confidence interval [CI]: 0.33–0.63, p < 0.001). Similarly, a higher 7RC was independently associated with worse progression-free survival (hazard ratio [HR] = 1.17, 95% CI 1.08–1.26, p < 0.001) and overall survival (HR = 1.14, 95% CI 1.04–1.25, p = 0.007). ConclusionThe extent of peritoneal metastases, as expressed by the 7RC during surgery, is an independent predictor for completeness of CRS and has independent prognostic value for progression-free survival and overall survival in addition to completeness of CRS.

Facility level variation in the adoption of neo-adjuvant chemotherapy is associated with higher surgical morbidity for patients with advanced stage epithelial ovarian carcinoma (558)

Facility level variation in the adoption of neo-adjuvant chemotherapy is associated with higher surgical morbidity for patients with advanced stage epithelial ovarian carcinoma (558)

Cost-utility analysis of management strategies after frontline treatment of women with epithelial ovarian cancer (339)

<b>Objectives:</b> Performed a cost-utility analysis comparing maintenance therapies for advanced epithelial ovarian cancer to surveillance based on genetic mutation. <b>Methods:</b> We developed Markov models of post-frontline treatment disease course until death for women diagnosed with stage III-IV epithelial ovarian cancer to compare niraparib, olaparib, bevacizumab, and olaparib+bevacizumab with active surveillance. Four subgroups were analyzed: <i>(1)</i> all-comers, <i>(2) BRCA, (3) non-BRCA</i> homologous recombination deficiency (HRD), and <i>(4)</i> homologous recombination proficient (HR proficient). Transition probabilities for progression-free survival and adverse events were derived from randomized controlled trials, for all-cause mortality from US life tables, and for disease-specific mortality after recurrence from SEER. Utilities for maintenance treatment, grade 3-4 adverse events, disease-free off treatment, recurrence, and death were derived from ovarian cancer-specific time trade-off studies. Costs of treatment, adverse events, recurrence, and death were obtained from Centers for Medicare & Medicaid Services (CMS) fee schedules and published studies. Analysis was conducted from CMS's perspective. We considered a 3-month cycle length, a lifetime time horizon and applied a 3% annual discount rate. The primary outcome of interest was the incremental cost-effectiveness ratio (ICER), defined as the ratio of incremental cost to incremental quality-adjusted life-year (QALY). Uncertainty was evaluated using deterministic and probabilistic sensitivity analyses and represented by cost-effectiveness at willingness-to-pay (WTP) thresholds up to $200K/QALY. <b>Results:</b> For all-comers, surveillance and olaparib+bevacizumab were undominated (more effective and less costly), and the ICER of olaparib+bevacizumab in reference to surveillance was $182,823/ QALY. The probability of cost-effectiveness of olaparib+bevacizumab at a WTP threshold of $100K/QALY was 20%. For <i>BRCA</i> patients, surveillance and olaparib were nominated, and the ICER of olaparib was $49,896/QALY. The probability of olaparib being cost-effective at a WTP threshold of $100K/QALY was 71%. For non-<i>BRCA</i> HRD patients, surveillance and olaparib+bevacizumab were both undominated, and the ICER of olaparib+bevacizumab was $98,685/QALY. At a WTP threshold of $100,000/QALY, olaparib+bevacizumab had a higher probability of being cost-effective (48%) than niraparib (6%) or bevacizumab alone (4%). For HR proficient patients, surveillance was undominated and had the highest probability of being cost-effective at all WTP thresholds. <b>Conclusions:</b> Compared to active surveillance, olaparib+bevacizumab was the most cost-effective maintenance strategy for all-comers and non-<i>BRCA</i> HRD patients. At the same time, olaparib was most costeffective for women with <i>BRCA</i> mutations. The likelihood of any maintenance therapy being cost-effective for women with HR proficient disease was low.

Biological Role of Tumor/Stromal CXCR4-CXCL12-CXCR7 in MITO16A/MaNGO-OV2 Advanced Ovarian Cancer Patients.

Simple SummaryDespite rapid progress in the research on epithelial ovarian cancer (EOC), it is usually diagnosed during the advanced stage with only 30% of patients surviving longer than 5 years. This is the first study in which the whole CXCR4-CXCL12-CXCR7 axis was systematically evaluated in tumor and stromal cells, through rigorous statistical methods in a prospective clinical trial. CXCL12 expression in cancer cells is associated with worse progression-free survival in stage III EOC patients, and deserves further attention as a potential prognostic and therapeutic target.This study investigated the prognostic role of the CXCR4-CXCL12-CXCR7 axis in advanced epithelial ovarian cancer (EOC) patients receiving first-line treatment within the MITO16A/MaNGO-OV2 phase-IV trial. CXCR4-CXCL12-CXCR7 expression was evaluated in the epithelial and stromal component of 308 EOC IHC-stained tumor samples. The statistical analysis focused on biomarkers’ expression, their association with other variables and prognostic value. Zero-inflated tests, shrinkage, bootstrap procedures, and multivariable models were applied. The majority of EOC (75.0%) expressed CXCR4 and CXCR7, 56.5% expressed the entire CXCR4-CXCL12-CXCR7 axis, while only 4.6% were negative for CXCL12 and its cognate receptors, in regard to the epithelial component. Stromal CXCL12 and CXCR7, expressed in 11.2% and 65.5%, respectively, were associated with the FIGO stage. High CXCL12 in epithelial cancer cells was associated with shorter progression-free and overall survival. However, after adjusting for overfitting due to best cut-off multiplicity testing, the significance was lost. This is a wide-ranging, prospective study in which CXCR4-CXCL12-CXCR7 were systematically evaluated in epithelial and stromal components, in selected stage III-IV EOC. Although CXCL12 was not prognostic, epithelial expression identified high-risk FIGO stage III patients for PFS. These data suggest that it might be worth studying the CXCL12 axis as a therapeutic target to improve treatment efficacy in EOC patients.

Modified Intraperitoneal Chemotherapy Without Bevacizumab as a First-Line Therapy for Newly Diagnosed Advanced Epithelial Ovarian Cancer-Two Centers Experiences.

ObjectivesTo evaluate whether the modified intraperitoneal plus intravenous chemotherapy regimen as a first-line therapy for advanced epithelial ovarian cancer (EOC) in China can be well-tolerated or confer any potential benefit on survival.MethodsWe evaluated the outcomes of women with newly diagnosed advanced-stage III-IV EOC treated with optimal cytoreductive surgery (<1 cm) and subsequent intraperitoneal plus intravenous chemotherapy or intravenous chemotherapy from January 2005 to December 2017 at two Gynecologic Oncology Centers in China. Kaplan-Meier survival analysis and Cox regression multivariate analysis models were performed to determine the toxicities and survival outcomes.ResultsA total of 463 patients with stage III-IV EOC were enrolled. According to the propensity scores (1:2), 85 patients who received intraperitoneal plus intravenous chemotherapy (group A) were matched to 170 patients who received intravenous chemotherapy (group B). The median follow-up time was 41 months (range 6–155 months). However, there was no statistically significant difference in the median progression-free survival (PFS) (20 vs. 22 months, P = 0.351) or 3-year overall survival (OS) rate (80 vs. 78%, P = 0.749) between the two groups. R0 primary cytoreductive surgery was the only factor related to PFS (P = 0.028) and OS (P = 0.005) by Cox regression analysis. The incidence of grade 3/4 adverse events did not significantly differ between the two groups.ConclusionThe efficacy of intraperitoneal chemotherapy mainly comes from the intraperitoneal drug dose intensity and cumulative dose. High-efficiency and low-toxicity intraperitoneal chemotherapy regimens still need to be found and validated.

The prognostic effect of residual tumor for advanced epithelial ovarian cancer treated with neoadjuvant chemotherapy or primary debulking surgery.

PurposeThe role of neoadjuvant chemotherapy (NACT) and primary debulking surgery (PDS) in advanced epithelial ovarian cancer (EOC) remains controversial. This study aimed to investigate the prognosis between NACT and PDS in advanced EOC. We also investigated the prognostic effect of the residual tumor (RT) after NACT and PDS.MethodsPatients with stage III‐IV EOC diagnosed between 2010 and 2017 were included from the Surveillance, Epidemiology, and End Results (SEER) database. Chi‐square test, multivariate logistic regression analysis, Kaplan–Meier curves, and Cox proportional hazards model were used for statistical analyses.ResultsA total of 5522 women patients were identified, 2017 (36.5%) and 3505 (63.5%) patients received NACT and PDS, respectively. There were 2971 (53.8%), 1637 (29.6%), and 914 (16.6%) patients who had no residual tumor, RT ≤1 cm, and RT >1 cm, respectively. There were 25.5% of patients receiving NACT in 2010 and 48.4% in 2017 (p < 0.001). Women treated with NACT were not related to a higher chance of complete resection than the PDS group (p = 0.098). Patients receiving PDS had significantly better cancer‐specific survival (CSS) than those receiving NACT (p < 0.001). The 5‐year CSS was 35.3% and 51.1% in those receiving NACT and PDS, respectively. In patients receiving NACT, those who had no residual tumor had significantly better CSS compared to those who had RT ≤1 cm (p < 0.001), while comparable CSS was found between those who had RT ≤1 cm and RT >1 cm (p = 0.442). In those receiving PDS, the CSS was decreased with a RT increase (p < 0.001).ConclusionsOur study suggests that PDS may be the optimal procedure for the majority of advanced EOC patients. Complete resection of all residual diseases should be the goal with the increased utilization of NACT.

Long-Term Survival Among Histological Subtypes in Advanced Epithelial Ovarian Cancer: Population-Based Study Using the Surveillance, Epidemiology, and End Results Database.

BackgroundActual long-term survival rates for advanced epithelial ovarian cancer (EOC) are rarely reported.ObjectiveThis study aimed to assess the role of histological subtypes in predicting the prognosis among long-term survivors (≥5 years) of advanced EOC.MethodsWe performed a retrospective analysis of data among patients with stage III-IV EOC diagnosed from 2000 to 2014 using the Surveillance, Epidemiology, and End Results cancer data of the United States. We used the chi-square test, Kaplan–Meier analysis, and multivariate Cox proportional hazards model for the analyses.ResultsWe included 8050 patients in this study, including 6929 (86.1%), 743 (9.2%), 237 (2.9%), and 141 (1.8%) patients with serous, endometrioid, clear cell, and mucinous tumors, respectively. With a median follow-up of 91 months, the most common cause of death was primary ovarian cancer (80.3%), followed by other cancers (8.1%), other causes of death (7.3%), cardiac-related death (3.2%), and nonmalignant pulmonary disease (3.2%). Patients with the serous subtype were more likely to die from primary ovarian cancer, and patients with the mucinous subtype were more likely to die from other cancers and cardiac-related disease. Multivariate Cox analysis showed that patients with endometrioid (hazard ratio [HR] 0.534, P<.001), mucinous (HR 0.454, P<.001), and clear cell (HR 0.563, P<.001) subtypes showed better ovarian cancer-specific survival than those with the serous subtype. Similar results were found regarding overall survival. However, ovarian cancer–specific survival and overall survival were comparable among those with endometrioid, clear cell, and mucinous tumors.ConclusionsOvarian cancer remains the primary cause of death in long-term ovarian cancer survivors. Moreover, the probability of death was significantly different among those with different histological subtypes. It is important for clinicians to individualize the surveillance program for long-term ovarian cancer survivors.

Preoperative extent of peritoneal metastases affects overall survival in ovarian cancer despite complete interval cytoreductive surgery

Objectives: We investigated whether the extent of peritoneal metastases, as expressed by the 7 Region Count (7RC), and other surgical findings are predictive of the completeness of interval cytoreductive surgery (CRS) and overall survival in patients with advanced ovarian cancer. Methods: This single center retrospective cohort study included consecutive patients with FIGO stage III-IV epithelial ovarian, fallopian tube, or primary peritoneal cancer who had received neoadjuvant chemotherapy and were planned for interval CRS between January 2013 to April 2019. The gynecological oncologists routinely recorded the 7RC during surgical exploration to systematically quantify the extent of peritoneal metastases. Baseline, treatment and follow-up data were extracted from the local electronic patient database. Logistic regression analysis was performed to predict surgical outcome and cox regression analysis for survival. Results: 317 patients were included for analysis. At exploratory laparotomy with intent to perform interval CRS, the median 7RC was 4 (interquartile range: 2-6). Complete CRS was achieved in 58% of patients and optimal CRS was achieved in 30% of patients. The 7RC showed an AUC 0.81 (95% CI: 0.74-0.88) for predicting at least optimal CRS. After multivariate logistic regression, non-bowel abdominal organ involvement, preoperative CA-125 levels, and involvement of the small bowel or mesentery were shown predictive of complete or optimal CRS additionally to the 7RC. From this model an AUC was achieved of 0.902 (95% CI: 0.85-0.95), which was significantly higher than the 7RC alone (p<0.001). The most effective model of overall survival included the 7RC with a hazard radio of 1.14 (95% confidence interval: 1.05-1.24) as well as surgical outcome with a hazard radio of 1.78 (95% confidence interval: 1.40- 2.27). Other important factors that were included were FIGO stage, age, involvement of the colon, involvement of the small bowel or mesentery and ASA physical status. The median follow-up was 21 months (interquartile range: 12-34 months). Conclusions: The extent of peritoneal metastases, as expressed by the 7RC, is not only a strong predictor for complete or optimal interval CRS but also has an independent prognostic value regardless of the completeness of cytoreduction. Currently, the 7RC is being evaluated on preoperative imaging to incorporate in preoperative decision making. We investigated whether the extent of peritoneal metastases, as expressed by the 7 Region Count (7RC), and other surgical findings are predictive of the completeness of interval cytoreductive surgery (CRS) and overall survival in patients with advanced ovarian cancer. This single center retrospective cohort study included consecutive patients with FIGO stage III-IV epithelial ovarian, fallopian tube, or primary peritoneal cancer who had received neoadjuvant chemotherapy and were planned for interval CRS between January 2013 to April 2019. The gynecological oncologists routinely recorded the 7RC during surgical exploration to systematically quantify the extent of peritoneal metastases. Baseline, treatment and follow-up data were extracted from the local electronic patient database. Logistic regression analysis was performed to predict surgical outcome and cox regression analysis for survival. 317 patients were included for analysis. At exploratory laparotomy with intent to perform interval CRS, the median 7RC was 4 (interquartile range: 2-6). Complete CRS was achieved in 58% of patients and optimal CRS was achieved in 30% of patients. The 7RC showed an AUC 0.81 (95% CI: 0.74-0.88) for predicting at least optimal CRS. After multivariate logistic regression, non-bowel abdominal organ involvement, preoperative CA-125 levels, and involvement of the small bowel or mesentery were shown predictive of complete or optimal CRS additionally to the 7RC. From this model an AUC was achieved of 0.902 (95% CI: 0.85-0.95), which was significantly higher than the 7RC alone (p<0.001). The most effective model of overall survival included the 7RC with a hazard radio of 1.14 (95% confidence interval: 1.05-1.24) as well as surgical outcome with a hazard radio of 1.78 (95% confidence interval: 1.40- 2.27). Other important factors that were included were FIGO stage, age, involvement of the colon, involvement of the small bowel or mesentery and ASA physical status. The median follow-up was 21 months (interquartile range: 12-34 months). The extent of peritoneal metastases, as expressed by the 7RC, is not only a strong predictor for complete or optimal interval CRS but also has an independent prognostic value regardless of the completeness of cytoreduction. Currently, the 7RC is being evaluated on preoperative imaging to incorporate in preoperative decision making.

Interval debulking surgery is not worth the wait: a National Cancer Database study comparing primary cytoreductive surgery versus neoadjuvant chemotherapy

ObjectiveIn previous studies, neoadjuvant chemotherapy followed by interval debulking surgery was not inferior to primary cytoreductive surgery as initial treatment for advanced epithelial ovarian cancer. Our study aimed to compare...

Histological Tumor Type is Associated with One-Year Cause-Specific Survival in Women with Stage III-IV Epithelial Ovarian Cancer: A Surveillance, Epidemiology, and End Results (SEER) Database Population Study, 2004-2014.

BackgroundThe prognosis of epithelial ovarian cancer (EOC) remains poor. Cause-specific survival (CSS) is an overall survival measure of cancer survival that excludes other causes of death. This retrospective population study used the Surveillance, Epidemiology, and End Results (SEER) database to evaluate prognostic factors associated with one-year CSS in women with stage III–IV EOC between 2004–2014.Material/MethodsData from the SEER program included a cohort of patients with stage III–IV EOC between 2004–2014. Binomial logistic regression analysis, Kaplan-Meier survival curves, and multivariate Cox proportional hazards models were used for analysis of patient outcome, including the one-year CSS.ResultsThere were 14,798 patients with stage III–IV EOC identified from SEER between 2004–2014, including 13,134 (88.8%), 892 (6.0%), 448 (3.0%), and 324 (2.2%) patients with serous, endometrioid, clear cell, and mucinous ovarian cancer, respectively. The overall one-year CSS was 91.2%. One-year CSS was 92.5%, 92.2%, 74.0%, and 62.5% in patients with serous, endometrioid, clear cell, and mucinous ovarian cancer, respectively (P<0.001). Histological tumor type was an independent prognostic factor of one-year CSS. Patients with mucinous EOC (HR, 8.807; 95% CI, 6.563–9.965; P<0.001) and clear cell EOC (HR, 4.581; 95% CI, 3.774–5.560; P<0.001) had a significantly lower one-year CSS compared with patients with endometrioid and serous EOC who had comparable one-year CSS (HR, 1.247; 95% CI, 0.978–1.590; P=0.075).ConclusionsA retrospective population study of the SEER database between 2004–2014 identified that histological tumor type was associated with one-year CSS in women with stage III–IV EOC.

Interval debulking surgery is not worth the wait: A National Cancer Database study comparing primary cytoreductive surgery versus neoadjuvant chemotherapy

Objective In previous studies, neoadjuvant chemotherapy followed by interval debulking surgery was not inferior to primary cytoreductive surgery as initial treatment for advanced epithelial ovarian cancer. Our study aimed to compare surgical and survival outcomes between the two treatments in a large national database. Methods Data were extracted from the National Cancer Database from January 2004 to December 2015. Patients with FIGO (International Federation of Gynecologists and Obstetricians) stage III-IV epithelial ovarian cancer and known sequence of treatment were included: primary cytoreductive (surgery=26 717 and neoadjuvant chemotherapy=9885). Tubal and primary peritoneal cancer diagnostic codes were not included. Residual disease after treatment was defined based on recorded data: R0 defined as microscopic or no residual disease; R1 defined as macroscopic residual disease. Multivariate Cox proportional HR was used for survival analysis. Multivariate logistic regression analysis was utilized to compare mortality between groups. Outcomes were adjusted for significant covariates. Validation was performed using propensity score matching of significant covariates. Results A total of 36 602 patients were included in the analysis. Patients who underwent primary cytoreductive surgery had better survival than those treated with neoadjuvant chemotherapy followed by interval surgery, after adjusting for age, co-morbidities, stage, and residual disease (p Conclusions Most patients with advanced epithelial ovarian cancer may benefit from primary cytoreductive surgery. Patients treated with neoadjuvant chemotherapy should be those with co-morbidities unfit for surgery.

JAVELIN ovarian PARP 100 study design: Phase III trial of avelumab + chemotherapy followed by avelumab + talazoparib maintenance in previously untreated epithelial ovarian cancer.

TPS9 Background: Preclinical studies suggest that chemotherapy (CTX) and PARP inhibitors may increase tumor antigenicity, providing a rationale for combined treatment with checkpoint inhibitors in patients (pts) with ovarian cancer (OC). Talazoparib is a potent, orally bioavailable PARP inhibitor with a dual mechanism (PARP trapping and enzyme inhibition) that has shown clinical activity in BRCA-mutated OC and is a US-approved treatment for BRCA-mutated HER2– breast cancer. Avelumab is an anti–PD-L1 checkpoint inhibitor approved for the treatment of metastatic Merkel cell carcinoma and advanced platinum-treated urothelial carcinoma. In phase 1b studies, avelumab showed antitumor activity and acceptable safety in pts with platinum-resistant OC. The JAVELIN Ovarian PARP 100 trial is evaluating the efficacy of avelumab + CTX followed by avelumab + talazoparib maintenance compared with CTX + bevacizumab followed by bevacizumab maintenance in pts with previously untreated epithelial OC. Methods: JAVELIN Ovarian PARP 100 is a phase 3, randomized, open-label, multicenter trial. Eligible pts have previously untreated Stage III-IV epithelial ovarian, fallopian tube, or primary peritoneal cancer; are candidates for platinum-based CTX + bevacizumab; and have completed primary debulking surgery or are candidates for neoadjuvant CTX with planned interval debulking surgery. Approximately 720 pts will be randomized in a 2.5:1:2.5 ratio to receive: CTX (paclitaxel 175 mg/m2 + carboplatin AUC 5/6 IV Q3W for 6 cycles) + avelumab (800 mg IV Q3W) followed by avelumab (800 mg Q2W) + talazoparib (0.75 mg QD orally) maintenance for up to 24 months (Arm A); CTX followed by talazoparib (0.75 mg QD) maintenance for up to 24 months (Arm B); or CTX + bevacizumab (15 mg/kg IV Q3W) followed by bevacizumab (15 mg/kg Q3W) maintenance for up to 21 doses or 22 per local approval (Arm C). Pts are stratified by germline BRCA1/2 mutation and resection status. The primary endpoint is progression-free survival (PFS) by blinded independent central review per RECIST v1.1. Other endpoints include overall survival, PFS2, health-related quality of life, and PK. Clinical trial information: NCT03642132.

Neoadjuvant chemotherapy in elderly women with ovarian cancer: Rates of use and effectiveness

BackgroundNeoadjuvant chemotherapy (NACT) may reduce perioperative morbidity in women undergoing primary treatment for ovarian cancer. We evaluated patterns of use and outcomes in a population-based cohort of elderly women with ovarian cancer (OC). MethodsA cohort of patients ≥66 years old diagnosed between 2000 and 2013 with stage III-IV epithelial OC who received surgery and platinum/taxane chemotherapy for primary treatment was identified from the SEER-Medicare database. Propensity-score matching methods were used to examine differences in outcomes. Kaplan–Meier analysis was performed to compare overall survival (OS) in the matched cohort. ResultsFrom 2000 to 2013, 22.5% of older women received NACT. The use of NACT increased over time from 16% in 2000 to 35.4% in 2013 (p < .0001). Among women who received PCS, the rate of ostomy creation was higher compared with NACT (23.3% vs. 10.8%, p < .0001). Infectious and other surgical complications were higher among those who had PCS, regardless of stage. Median OS of women III ovarian cancer who underwent PCS was longer compared with NACT (38.8 vs. 28 months, p ≤ .0001). There were no survival differences between NACT and PCS in women with stage IV disease (29.4 vs. 29.8 months, p = .61) or for women aged >80. ConclusionCareful consideration should be given to older patients prior to undergoing PCS. Survival outcomes were similar for patients with stage IV disease, although NACT was associated with decreased perioperative morbidity compared with PCS. Among women with stage III disease, PCS was associated with improved overall survival, but higher rates of perioperative morbidity and acute care.

Inflammatory Indexes as Prognostic and Predictive Factors in Ovarian Cancer Treated with Chemotherapy Alone or Together with Bevacizumab. A Multicenter, Retrospective Analysis by the MITO Group (MITO 24).

The variability in progression-free survival (PFS) and overall survival (OS) among patients with epithelial ovarian cancer (EOC) makes it difficult to reliably predict outcomes. A predictive biomarker of bevacizumab efficacy as first-line therapy in EOC is still lacking. The MITO group conducted a multicenter, retrospective study (MITO 24) to investigate the role of inflammatory indexes as prognostic factors and predictors of treatment efficacy in FIGO stage III-IV EOC patients treated with first-line chemotherapy alone or in combination with bevacizumab. Of the 375 patients recruited, 301 received chemotherapy alone and 74 received chemotherapy with bevacizumab. The pre-treatment neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune inflammation index (SII) were evaluated to identify a potential correlation with PFS and OS in both the overall population and the two treatment arms. In the overall population, the PFS and OS were significantly longer in patients with low inflammatory indexes (p < 0.0001). In multivariate analyses, the NLR was significantly associated with OS (p = 0.016), and the PLR was significantly associated with PFS (p = 0.024). Inflammatory indexes were significantly correlated with patient prognosis in the chemotherapy-alone group (p < 0.0001). Patients in the chemotherapy with bevacizumab group with a high NLR had a higher PFS and OS (p = 0.026 and p = 0.029, respectively) than those in the chemotherapy-alone group. Conversely, PFS and OS were significantly poorer in patients with a high SII (p = 0.024 and p = 0.017, respectively). Our results suggest that bevacizumab improves clinical outcome in patients with a high NLR but may be detrimental in those with a high SII.

Pre-operative core muscle index in combination with hypoalbuminemia is associated with poor prognosis in advanced ovarian cancer.

Age and frailty have been correlated with poor clinical outcomes in cancer. Core muscle index (CMI) and nutritional status are integral in assessing frailty. We explored the effect of pre-operative serum albumin and body composition on clinical outcomes in patients with epithelial ovarian cancer (EOC). We identified stage III-IV EOC patients undergoing primary cytoreductive surgery from 2007 to 2015. Data were abstracted from medical records. Body composition measurements were obtained from pre-operative imaging. Psoas muscle cross-sectional area was normalized to height2 to determine CMI. Sarcopenia was defined as CMI below the population mean. The influence of sarcopenia on short-term morbidity was evaluated. Relationships among body composition measurements and albumin were assessed with Spearman correlations. Patient characteristics and body composition measurements between patients with and without sarcopenia were compared with parametric and non-parametric statistical methods. Kaplan-Meier survival curves were compared using log-rank. 102 women met inclusion criteria. Sarcopenia correlated with albumin (P = 0.0002). Sarcopenia was not associated with short-term morbidity or time to recurrence. Sarcopenia was associated with nearly a fourfold increased risk of death when hypoalbuminemia was present (P = 0.02). Pre-operative sarcopenia in combination with hypoalbuminemia was associated with significantly worse survival.

Neoadjuvant chemotherapy versus primary debulking surgery in advanced epithelial ovarian cancer: A meta-analysis of peri-operative outcome.

ObjectiveTo assess whether neoadjuvant chemotherapy (NACT) is superior to primary debulking surgery (PDS) with regard to optimal cytoreduction, peri-operative morbidity, mortality, and quality of life (QOL) in advanced epithelial ovarian cancer (EOC).MethodsWe searched the PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, Registers of Clinical Trials for randomized controlled trials (RCTs) comparing NACT to PDS in women with Federation of International Gynaecologists and Obstetricians stage Ⅲ-Ⅳ EOC. RevMan 5.3 software was utilized for statistical analysis.ResultsFour RCTs involving 1,607 women with advanced EOC were included. Compared with PDS, NACT provided a higher rate of complete cytoreduction (risk ratio [RR], 1.95; 95% confidence interval [CI], 1.33 to 2.87), optimal cytoreduction (RR: 1.61 [95%CI: 1.05 to 2.47]), but there was no significant difference in residual disease 0–1 cm (p = 0.49). NACT was associated with lower peri-operative morbidity with respect to infection (RR: 0.30 [95% CI: 0.16 to 0.56]), gastrointestinal fistula (RR: 0.24 [95% CI: 0.06 to 0.95]), any grade 3 or 4 adverse event (RR: 0.29 [95% CI: 0.11 to 0.78]), and less post-surgical death within 28 days (RR: 0.14 [95% CI: 0.04 to 0.49]). NACT provided better QOL in terms of fatigue (weight mean difference [WMD], -3.28; [95% CI: -3.99 to -2.57]), role functioning (WMD: 5.29 [95% CI: 4.44 to 6.14]), emotional functioning (WMD: 6.19 [95% CI: 5.57 to 6.82]), and cognitive functioning (WMD: 1.02 [95% CI: 0.43 to 1.61]) at 6-month follow-up compared with PDS.ConclusionsNACT is associated with superior optimal cytoreduction, lower peri-operative morbidity as well as post-surgical mortality, and better QOL compared to initial surgery in patients with advanced EOC. Future research should focus on improving the efficacy of NACT.

Extra-peritoneal hysteroannessiectomy with eventual concomitant en bloc rectal resection and cytoreductive surgery in epithelial ovarian cancer (and other peritoneal surface malignancies): technical details

Surgery allows the correct evaluation of the peritoneal dissemination of the epithelial ovarian cancer (EOC) and the removal of as much tumor as possible to maximize adjuvant chemotherapy. Neoadjuvant chemotherapy (NACT) and interval debulking surgery have been proposed as a reasonable alternative to primary complete cytoreductive surgery (CRS) in patients not fit for an initial extensive debulking surgery. Intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) has been offered as a promising therapeutic procedure to increase survival by treating the microscopic component of the neoplastic disease. Matherial and Method. 419 eligible patients with stage III-IV EOC were subjected to CRS, previous NACT in 343 patients, 20 of which with CRS combined with extraperitoneal hysterectomy (EH) + HIPEC. Purposes of our four years retrospective observational study are the revision of the surgical approaches to the EOC, a detailed report of the pelvic peritonectomy in association to hysteroannessiectomy (+/- consensual rectal resection) and the prospective review of the results. Conclusions. This study shows that EH + HIPEC is feasible. The detailed description of the technique here depicted could help to standardize this type of peritonectomy.