The effect of older age on treatment outcomes in women with advanced ovarian cancer receiving chemotherapy: An NRG-Oncology/Gynecologic Oncology Group (GOG-0182-ICON5) ancillary study.

OBJECTIVE: To assess the effect of age on overall survival (OS) in women with ovarian cancer receiving chemotherapy. Secondary objectives were to describe the effect of age on treatment compliance, toxicities, progression free survival (PFS), time from surgery to chemotherapy, and rates of optimal cytoreduction. METHODS: Women enrolled in GOG 0182-ICON5 with stage III or IV epithelial ovarian cancer (EOC) who underwent surgery and chemotherapy between 2001 and 2004 were included. Patients were divided into ages <70 and ≥ 70 years. Baseline characteristics, treatment compliance, toxicities, and clinical outcomes were compared. RESULTS: We included a total of 3686 patients, with 620 patients (16.8%) ≥ 70 years. OS was 37.2 months in older compared to 45.0 months in younger patients (HR 1.21, 95% CI, 1.09-1.34, p < 0.001). Older patients had an increased risk of cancer-specific-death (HR 1.16, 95% CI, 1.04-1.29) as well as non-cancer related deaths (HR 2.78, 95% CI, 2.00-3.87). Median PFS was 15.1 months in older compared to 16.0 months in younger patients (HR 1.10, 95% CI, 1.00-1.20, p = 0.056). In the carboplatin/paclitaxel arm, older patients were just as likely to complete therapy and more likely to develop grade ≥ 2 peripheral neuropathy (35.7 vs 19.7%, p < 0.001). Risk of other toxicities remained equal between groups. CONCLUSIONS: In women with advanced EOC receiving chemotherapy, age ≥ 70 was associated with shorter OS and cancer specific survival. Older patients receiving carboplatin and paclitaxel reported higher rates of grade ≥ 2 neuropathy but were not more likely to suffer from other chemotherapy related toxicities. Clintrials.gov: NCT00011986.

Participation of Patients With Limited English Proficiency in Gynecologic Oncology Clinical Trials.

BACKGROUND: Significant disparities exist in recruitment of minorities to clinical trials, with much of the prior literature focused on race/ethnicity only. Limited English proficiency (LEP) is a known barrier in healthcare that may also drive disparities in trial enrollment. We sought to determine participation rates in gynecologic oncology trials among patients with LEP and to explore barriers to their participation. METHODS: In a retrospective cohort study, electronic health record data from >2,700 patients treated over 2 years at one academic gynecologic oncology practice were abstracted and the primary exposure of having LEP was identified. The primary outcome was enrollment in a clinical trial. Demographic, financial, clinical, and healthcare access-related covariates were also abstracted and considered as potential confounders in a multivariable logistic regression model. Age, race, ethnicity, and insurance status were further examined for evidence of effect modification. In addition, a survey was administered to all gynecologic oncology research staff and gynecologic oncology providers (n=25) to assess barriers to research participation among patients with LEP. RESULTS: Clinical trial enrollment was 7.5% among fluent English speakers and 2.2% among patients with LEP (risk ratio, 0.29; 95% CI, 0.11-0.78; P=.007), and remained significantly lower in patients with LEP after adjusting for the identified confounders of Hispanic ethnicity and insurance payer (odds ratio, 0.34; 95% CI, 0.12-0.97; P=.043). There was a trend toward race and LEP interaction: Asian patients were equally likely to participate in research regardless of language fluency, whereas White and Black patients with LEP were less likely to participate than non-LEP patients in both groups (P=.07). Providers reported that the most significant barriers to enrollment of patients with LEP in research were unavailability of translated consent forms and increased time needed to enroll patients. CONCLUSIONS: Patients with LEP were 3.4 times less likely to participate in gynecologic oncology trials than fluent English speakers. De-aggregation of race, ethnicity, and language proficiency yielded important information about enrollment disparities. These findings offer avenues for future interventions to correct disparities.

Timing and duration of bevacizumab treatment and survival in patients with recurrent ovarian, fallopian tube, and peritoneal cancer: a multi-institution study.

Bevacizumab has demonstrated significant benefit in recurrent ovarian, fallopian tube and peritoneal cancer (OC), but its optimal position within the sequence of systemic therapies remains controversial. Since rebound progression after bevacizumab has been observed in other cancers, and because bevacizumab is incorporated in several regimens used in the recurrent setting, the duration of treatment may impact survival. We sought to identify whether earlier bevacizumab exposure is associated with prolonged bevacizumab therapy and survival by conducting a multi-institution retrospective study of recurrent OC patients treated with bevacizumab from 2004-2014. Multivariate logistic regression identified factors associated with receiving more than six bevacizumab cycles. Overall survival by duration and ordinal sequence of bevacizumab therapy were evaluated using logrank testing and Cox regression. In total, 318 patients were identified. 89.1% had stage III or IV disease; 36% had primary platinum resistance; 40.5% received two or fewer prior chemotherapy regimens. Multivariate logistic regression demonstrated that primary platinum sensitivity (Odds Ratio (OR) 2.34, p = 0.001) or initiating bevacizumab at the first or second recurrence (OR 2.73, p < 0.001) were independently associated with receiving more than six cycles of bevacizumab. Receiving more cycles of bevacizumab was associated with improved overall survival whether measured from time of diagnosis (logrank p < 0.001), bevacizumab initiation (logrank p < 0.001), or bevacizumab discontinuation (logrank p = 0.017). Waiting one additional recurrence to initiate bevacizumab resulted in a 27% increased hazard of death (Hazard Ratio (HR) 1.27, p < 0.001) by multivariate analysis. In conclusion, patients with primary platinum sensitive disease who received fewer prior lines of chemotherapy were able to receive more cycles of bevacizumab, which was associated with improved overall survival. Survival worsened when bevacizumab was initiated later in the ordinal sequence of therapies.

OVARIO phase II trial of combination niraparib plus bevacizumab maintenance therapy in advanced ovarian cancer following first-line platinum-based chemotherapy with bevacizumab.

OBJECTIVE: To assess safety and efficacy of niraparib + bevacizumab as a first-line maintenance therapy for patients with newly diagnosed advanced ovarian cancer. METHODS: This multicenter, phase II, single-arm, open-label study enrolled adult patients with stage IIIB to IV ovarian, fallopian tube, or primary peritoneal cancer (NCT03326193). Patients were required to have an attempt at debulking surgery and have a complete response, partial response, or no evidence of disease following first-line, platinum-based chemotherapy with ≥3 cycles of bevacizumab. The primary endpoint was the progression-free survival (PFS) rate at 18 months. Secondary endpoints included PFS, overall survival, and safety. RESULTS: Among the 105 evaluable patients, the PFS rate at 18 months was 62% (95% CI 52-71%) in the overall population and 76% (95% CI 61-87) in the homologous recombination deficient (HRd), 47% (95% CI 31-64%) in the HR proficient (HRp), and 56% (95% CI 31-79%) in the HR not determined (HRnd) subgroups (December 24, 2020, cutoff). After a median follow-up time of 28.7 months (IQR, 23.9-32.5 months), median PFS was 19.6 months (95% CI 16.5-25.1) in the overall population (N = 105) and 28.3 months (95% CI 19.9-NE), 14.2 months (95% CI 8.6-16.8), and 12.1 months (95% CI 8.0-NE) in the HRd, HRp, and HRnd subgroups, respectively (June 16, 2021, cutoff). The most common any-grade treatment-related adverse events (related to niraparib and/or bevacizumab) were thrombocytopenia (74/105), fatigue (60/105), and anemia (55/105; December 24, 2020, cutoff). CONCLUSION: Niraparib + bevacizumab first-line maintenance therapy displayed promising PFS results. Safety was consistent with the known safety profiles of niraparib and bevacizumab as monotherapy.

NCCN Guidelines® Insights: Ovarian Cancer, Version 3.2022.

Epithelial ovarian cancer is the leading cause of death from gynecologic cancer in the United States, with less than half of patients living >5 years following diagnosis. The NCCN Guidelines for Ovarian Cancer provide recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with ovarian, fallopian tube, and primary peritoneal cancers. These NCCN Guidelines Insights summarize the panel discussion behind recent important updates to the guidelines, including revised guidance on alternative chemotherapy regimens for patients with advanced age and/or comorbidities, a new algorithm for recurrent low-grade serous carcinoma based on developing research and novel therapeutic agents, and updated language regarding tumor molecular analysis applications in ovarian cancer.

Cognitive skill training improves memory, function, and use of cognitive strategies in cancer survivors.

BACKGROUND: Cancer survivors commonly report symptoms of impaired cognition. This project examined effectiveness of a behavioral skills training intervention to improve cognition and reduce cognitive dysfunction symptoms in cancer survivors. METHODS: Participants were randomly assigned to group-based workshops focused on learning new cognitive skills (skills treatment-TX) or an active control of education workshops (education control-EC) or a passive control of wait list (WL). Participants were evaluated pre- and post intervention with subjective mood and symptom questionnaires and objective neurocognitive tests. RESULTS: One hundred twenty-eight participants (mean age 59 years), average 4.6 years (+ / - 5.5 years) post cancer treatment with various cancer types (breast, bladder, prostate, colon, uterine), were enrolled. Analysis of all participants who attended workshop(s) revealed improvement in the TX workshop completers on all objective cognitive measures (attention, concentration, declarative, and working memory) save one test of selective attention, and improvement on a single measure (verbal memory) and decline (selective attention) in the EC group. TX workshop completers also improved on all symptom and mood measures, in contrast to EC group which improved on a single subscale of a symptom measure, but increased on an anxiety measure. TX group alone improved on a quantified measure of each participants' unique, "top three," self-described cognitive symptoms. CONCLUSION: Improvement from behavioral skills training was evident from objective cognitive tests, subjective symptom measures, and quantified, individual patient-specific symptoms. Behavioral skill training is an effective treatment for cognitive dysfunction in cancer survivors, and should be considered as a treatment option by health care providers.

Post hoc analyses of GOG 9923: Does BRCA status affect toxicities?: An NRG oncology study.

OBJECTIVE: To evaluate how women with epithelial ovarian cancer (EOC), dichotomized by BRCA status, tolerate intravenous (IV) or intraperitoneal (IP) chemotherapy given with veliparib and bevacizumab (bev) on a GOG phase I study (GOG 9923, NCT00989651). METHODS: This is an unplanned, post hoc analysis of an IRB approved, multi-institutional, prospective study (GOG 9923). Clinical characteristics and toxicity data based on BRCA status were evaluated and descriptive statistics were used to summarize baseline patient characteristics and toxicities. The Kaplan Meier method was used to generate survival estimates. RESULTS: Four hundred twenty-four patients were evaluable. Patients were treated with IV carboplatin, paclitaxel, and bev every 21 days (regimen 1), weekly IV paclitaxel with carboplatin and bev (regimen 2) or IV paclitaxel and bev with IP cisplatin (regimen 3). Bev was continued as maintenance in all arms. Within each of these regimens, veliparib was given either twice daily for the entirety of each cycle (continuous) or on days -2 to 5 (intermittent). Ten percent of patients treated on regimen 1, 12% on regimen 2, and 19.8% on regimen 3 had BRCA-associated tumors. Patients with BRCA-associated tumors, when compared to wild type, experienced similar rates of anemia, febrile neutropenia (, abdominal pain, colonic perforation, nausea, vomiting, and peripheral sensory neuropathy. Median progression free survival (PFS) was not significantly different between BRCA-associated and wild type cancers (HR 0.96, CI 0.65-1.42), though this study's primary aim was not to evaluate outcomes. CONCLUSIONS: Germline BRCA mutations positively affect chemosensitivity in EOC, but whether differences in toxicities among BRCA-associated and BRCA wild type tumors existed was previously not reported. In this population with newly diagnosed ovarian cancer no differences in reported toxicity between the two groups was observed.

Ovarian Cancer, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology.

Epithelial ovarian cancer is the leading cause of death from gynecologic cancer in the United States and is the country's fifth most common cause of cancer mortality in women. A major challenge in treating ovarian cancer is that most patients have advanced disease at initial diagnosis. These NCCN Guidelines discuss cancers originating in the ovary, fallopian tube, or peritoneum, as these are all managed in a similar manner. Most of the recommendations are based on data from patients with the most common subtypes─high-grade serous and grade 2/3 endometrioid. The NCCN Guidelines also include recommendations specifically for patients with less common ovarian cancers, which in the guidelines include the following: carcinosarcoma, clear cell carcinoma, mucinous carcinoma, low-grade serous, grade 1 endometrioid, borderline epithelial, malignant sex cord-stromal, and malignant germ cell tumors. This manuscript focuses on certain aspects of primary treatment, including primary surgery, adjuvant therapy, and maintenance therapy options (including PARP inhibitors) after completion of first-line chemotherapy.

Postoperative narcotic use in patients with ovarian cancer on an Enhanced Recovery After Surgery (ERAS) pathway.

OBJECTIVES: To determine the impact of an ERAS pathway on post-discharge narcotic use for patients with ovarian cancer undergoing open surgery. METHODS: This was a retrospective cohort study of women who underwent open ovarian cancer surgeries in 2014 prior to ERAS ("pre-ERAS") and in 2016/2018 after ERAS was instituted ("ERAS"). Patients taking chronic narcotics were excluded. A statewide prescription monitoring program was used to identify narcotic prescriptions filled in the three months after surgery. Quantity of narcotic medication is referenced in morphine milligram equivalents (MME). RESULTS: 42 pre-ERAS and 94 ERAS patients were included. The groups were similar in age, BMI, diabetes, tobacco use, mean number of prior abdominal/pelvic surgeries, and advanced stage disease. ERAS patients had a shorter hospital stay (6.7 days pre-ERAS vs 4.2 days ERAS, p = 0.003), used less narcotic in the 24 h prior to discharge (74.0 MME pre-ERAS vs 25.8 MME ERAS, p = 0.002), and filled prescriptions at time of discharge for less narcotic (519.9 MME pre-ERAS vs 339.7 MME ERAS, p = 0.011). After hospital discharge, ERAS patients filled fewer additional prescriptions (52.4% pre-ERAS, vs 29.4% ERAS, p = 0.012). In total, ERAS patients filled prescriptions for 55% fewer narcotics in the three months after surgery than the pre-ERAS group (1101.4 MME pre-ERAS vs 492.1 MME ERAS, p < 0.001). CONCLUSIONS: Institution of an ERAS protocol appears to decrease the narcotic needs of patients in the three months after ovarian cancer surgery.

A phase I study of intravenous or intraperitoneal platinum based chemotherapy in combination with veliparib and bevacizumab in newly diagnosed ovarian, primary peritoneal and fallopian tube cancer.

BACKGROUND: Improvements in disease free survival for epithelial ovarian, peritoneal or fallopian tube cancer (EOC) will only come with improved primary therapy. Incorporation of poly-ADP-ribose inhibitors (PARPi) in the frontline setting may represent one strategy. This study sought to determine the maximum tolerated and feasible doses of the PARPi veliparib in combination with chemotherapy for EOC. METHODS: A phase I, 3 + 3 dose escalation evaluated dose-limiting toxicities (DLTs) in cycles 1-2. Once <2/6 patients experienced a DLT, that dose level expanded to evaluate feasibility over 4 cycles. This study opened 10/2009 and closed 8/2016. Eligible patients had untreated, stage II-IV EOC. Veliparib was added either continuous (day 1-21) or intermittent (day - 2 to 5) during 6 cycles of chemotherapy. Three chemotherapy backbones were evaluated (2 intravenous (q3week and weekly) and 1 intraperitoneal (IP)) all inclusive of bevacizumab with and as maintenance to 22 cycles. FINDINGS: Dose evaluations for 424 treated patients were available. Regimen 1 (q3 week), continuous (Reg1c) the maximum tolerated dose (MTD) was 250 mg veliparib BID and feasible dose was 150 mg BID. For regimen 1, intermittent (Reg1i) the MTD and feasible dose were 400 and 250 mg BID. For Reg2c (weekly paclitaxel) the MTD and feasible dose were 150 mg BID. For Reg2i the MTD and feasible dose were 250 and 150 mg BID. For Reg3c (IP) the MTD and feasible dose were 150 mg BID and for Reg3i (IP), the MTD and feasible dose were 400 mg and 300 mg BID. INTERPRETATION: The feasible dose for Reg1c, 2c, 2i and 3c was 150 mg po BID. For Reg1i and 3i the dose was pushed to 250 and 300 mg po BID respectively. There is no apparent difference in efficacy between continuous and intermittent dosing indicating that the higher doses achieved in intermittent dosing may not be needed. (NCT00989651). FUNDING: National Cancer Institute.

Intraperitoneal ports placed at the time of bowel resection for treatment of ovarian cancer: Complications and surgical outcomes.

OBJECTIVES: To determine if intraperitoneal (IP) ports placed concurrently with bowel resection during surgical treatment of ovarian cancer is associated with more complications than those ports placed without concurrent bowel resection. METHODS: The medical records of all patients who had an IP port placed at our institution between 2005 and 2016 were reviewed. Two groups were analyzed: IP ports placed with bowel resection (IP-BR) and those without (IP). RESULTS: Of 306 patient charts reviewed, 31% had a surgery with IP port placement and concurrent bowel resection (IP-BR). Demographics were similar except for mean BMI (25.6 IP-BR vs 27.4 IP, p = 0.007). More IP-BR patients had stage IIIC disease (83.3% IP-BR vs 56.9% IP, p ≤0.01). Patients were cytoreduced to R0 in 48.7% IP-BR vs 56.4% IP (p = 0.253). For adjuvant treatment, IV chemotherapy was administered before IP chemotherapy in 90.4% IP-BR (median 2 cycles), and 50.3% IP, (median 2 cycles, p < 0.01). Ultimately 80.2% IP-BR (median 4 cycles) and 77.8% IP (median 5 cycles) received IP chemotherapy (p = 0.65). Rates of total IP port complications were similar (19.2% IP-BR vs 23.2% IP, p = 0.397), including IP port infections (0% IP-BR vs 0.7% IP, p = 0.5). Eleven percent of IP-BR patients had a bowel complication (e.g. obstruction or perforation) while IP port was in situ vs 2.7% IP (p = 0.01). Only 2.7% IP-BR and 6% IP discontinued IP chemotherapy due to IP port complication (p = 0.3). CONCLUSIONS: Patients who have IP ports placed concurrently with a bowel resection do not appear to have more complications, nor lower rates of IP chemotherapy administration.

Revisiting Minimally Invasive Surgery in the Management of Early-Stage Cervical Cancer.

Minimally invasive surgery (MIS) was previously considered an acceptable alternative to open radical hysterectomy in the management of early-stage cervical cancer (ESCC), but adequately powered, high-quality prospective trials evaluating survival outcomes were lacking. Recently, a large randomized phase III trial, the Laparoscopic Approach to Cervical Cancer (LACC) trial, showed that MIS for ESCC is associated with a higher risk of recurrence and death compared with open surgery. We review the LACC trial findings in depth, as well as a recent National Cancer Database analysis using propensity score weighting that supports the LACC trial findings. Additional studies are needed to better understand the mechanisms explaining the worse survival associated with MIS for ESCC. This review discusses considerations for integrating the findings of the LACC trial into clinical practice. Based on the high-quality evidence now available, open radical hysterectomy should be offered as standard of care for stage IA2-IB1 cervical cancer and patients should be guided appropriately to make informed shared decision-making if they still desire MIS.

NCCN Guidelines Insights: Ovarian Cancer, Version 1.2019.

Epithelial ovarian cancer is the leading cause of death from gynecologic cancer in the United States, with less than half of patients living >5 years from diagnosis. A major challenge in treating ovarian cancer is that most patients have advanced disease at initial diagnosis. The best outcomes are observed in patients whose primary treatment includes complete resection of all visible disease plus combination platinum-based chemotherapy. Research efforts are focused on primary neoadjuvant treatments that may improve resectability, as well as systemic therapies providing improved long-term survival. These NCCN Guidelines Insights focus on recent updates to neoadjuvant chemotherapy recommendations, including the addition of hyperthermic intraperitoneal chemotherapy, and the role of PARP inhibitors and bevacizumab as maintenance therapy options in select patients who have completed primary chemotherapy.

Phase I combination study of the PARP inhibitor veliparib plus carboplatin and gemcitabine in patients with advanced ovarian cancer and other solid malignancies.

OBJECTIVE: Determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of veliparib combined with carboplatin and gemcitabine in patients with advanced ovarian cancer and other nonhematologic malignancies. METHODS: In this phase I study, patients with metastatic or unresectable solid tumors and ≤2 prior chemotherapy regimens received veliparib combined with carboplatin area under the curve (AUC) 4 on day 1 and gemcitabine 800mg/m2 on days 1 and 8 of a 21-day cycle for maximum 10cycles, followed by optional veliparib maintenance therapy. Veliparib dosing commenced twice-daily (BID) continuously on day 1 of cycle 2; granulocyte colony-stimulating factor was permitted. Dose escalation used a Bayesian continual reassessment method. Safety, tolerability, and efficacy were evaluated. RESULTS: Seventy-five patients were enrolled (ovarian cancer, n=54; breast cancer, n=12). Thirty-six patients with ovarian cancer (67%) had known germline BRCA mutations. Most common treatment-related adverse events (TRAEs; ≥60%) were thrombocytopenia, neutropenia, nausea, and anemia. Most common grade 3/4 TRAEs (≥40%) were neutropenia and thrombocytopenia. Dose-limiting toxicities were thrombocytopenia and neutropenia. The MTD/RP2D was established at veliparib 250mg with carboplatin AUC 4 plus gemcitabine 800mg/m2. Responses were observed in 69% of patients with BRCA-deficient ovarian cancer (45% partial, 24% complete responses). Five patients remained on veliparib (80-310mg BID) for >34cycles. CONCLUSIONS: Veliparib plus carboplatin/gemcitabine is tolerated, with a safety profile similar to carboplatin and gemcitabine alone. Combination therapy demonstrated promising preliminary antitumor activity in platinum-sensitive ovarian cancer patients with germline BRCA mutations. Trial registration ID: NCT01063816.

Combining a symptom index, CA125 and HE4 (triple screen) to detect ovarian cancer in women with a pelvic mass.

OBJECTIVES: To assess a simple algorithm of CA125, HE4 and Symptom Index to predict ovarian cancer in women with a pelvic mass. METHODS: This was a prospective study of women referred to a gynecologic oncology clinic for surgical evaluation of a pelvic mass. Preoperatively, women completed a SI and had serum markers drawn. Results were correlated with pathology. A triple screen was considered positive if at least 2 of the 3 markers were abnormal (positive SI, CA125≥35U/mL, HE4≥140pmol/L). RESULTS: 218 patients enrolled in the study. 66 patients (30%) had ovarian or fallopian tube cancer (97% epithelial), 124 (57%) had benign masses, 17 (8%) had borderline tumors, and 11 (5%) had metastatic disease. The SI, CA125 and HE4 were positive in 87.9%, 74.2% and 60.6% of ovarian cancer patients, respectively. Of the 112 women with a positive SI 58 (52%) had ovarian cancer and 75 (67%) had non-benign masses. Excluding borderline and metastatic cancers the sensitivity of the triple screen was 79%; specificity 91%, PPV 83% and NPV 89%. CA125 alone had a sensitivity, specificity, PPV and NPV of 79%, 76%, 63% and 87% respectively. Requiring only one of the three tests to be abnormal resulted in a sensitivity of 97% but specificity dropped to 50%. CONCLUSIONS: An algorithm using SI, CA125 and HE4 has good performance statistics for predicting cancer in women with pelvic masses. The triple screen has higher specificity and PPV than CA125 alone but similar sensitivity and NPV for predicting ovarian cancer.

Ovarian cancer outcomes: Predictors of early death.

OBJECTIVE: To describe the outcomes and mortality in advanced ovarian cancer patients in a population-based cohort in the 90 days after diagnosis. METHODS: Using the linked Surveillance, Epidemiology and End Results (SEER)-Medicare database, we identified a cohort of women with stage III/IV epithelial ovarian cancer diagnosed between 1995 and 2007. A χ(2) test was used to assess demographic and clinical factors. Kaplan-Meier curves and Cox proportional hazards models were used to assess factors associated with variation in survival. RESULTS: Of the 9491 patients with stage III/IV ovarian cancer identified from the SEER/Medicare system, 4131 (43.6%) patients died in the first year after diagnosis. Of these, 2472 (26.0%) patients died in the first 90 days after diagnosis. Over the study period, the number of patients who died in the first 90 days after diagnosis slightly increased (p=0.053). Older age (>75 years of age), increased comorbidity, stage IV disease, lack of a visit with a gynecologic oncologist, and surgery were associated with an increase in 90-day mortality. Chemotherapy was associated with a reduction in 90-day mortality. CONCLUSIONS: Approximately 25% of patients with advanced ovarian cancer in our study period died within 90 days of diagnosis, and more than 40% died within the first year of diagnosis. In addition, a substantial proportion of patients did not receive any treatment. Further research into the characteristics of these patients should be performed to elucidate clinical areas for intervention to either prevent these poor outcomes or allocate appropriate resources to patients with extremely poor prognoses.

Neoplastic cellularity is associated with clinical and molecular features of high-grade serous ovarian carcinoma.

OBJECTIVE: Most molecular analyses of high-grade serous ovarian, peritoneal and fallopian tube carcinomas (HGSC) require ≥70% tumor (neoplastic) cell nuclei. We characterized the distribution of the percentage of neoplastic nuclei (PNN) in a large cohort of HGSC and correlated PNN with clinical outcomes to determine the fraction of cases outside this range and whether this cut-off introduces selection bias. METHODS: Subjects were prospectively enrolled and normal and neoplastic tissues were snap-frozen. All subjects had grade 2 to 3 HGSC. Subjects that received neoadjuvant chemotherapy were excluded. PNN was determined by estimating the fraction of neoplastic nuclei relative to non-neoplastic nuclei on a representative hematoxylin and eosin stained frozen section from the primary neoplasm. Germline BRCA mutation status was determined with Sanger or BROCA sequencing. RESULTS: PNN was <70% in 101 (33%) of 306 cases. PNN was significantly higher among subjects without optimal cytoreduction (P=0.018). 55 subjects had germline BRCA1/BRCA2 mutations. HGSC associated with BRCA2 but not BRCA1 mutations had significantly lower PNN compared to HGSC in non-carriers (54% vs. 70%, P=0.018). Overall survival was not significantly different between subjects with <70% or ≥70% PNN (median survival 51.8 vs. 46.6months, P=0.858). CONCLUSIONS: One-third of HGSC has PNN <70%. Higher PNN is associated with suboptimal cytoreduction, while lower PNN is associated with inherited BRCA2 mutations. Our findings suggest a nonrandom distribution of PNN that may reflect cancer biology. Further studies exploring the stromal microenvironment are needed. Molecular analyses of HGSC selected for high PNN exclude a significant fraction of patients.

Route of hysterectomy and surgical outcomes from a statewide gynecologic oncology population: is there a role for vaginal hysterectomy?

BACKGROUND: Recent policy changes by insurance companies have been instituted to encourage vaginal hysterectomy (VH) as the preferred route for removal of the uterus. It is not known if advantages of VH for benign indications apply to women with gynecologic cancer. OBJECTIVE: The goal of this study was to assess trends in surgical approach to hysterectomy among gynecologic cancer patients and to evaluate outcomes by approach. We hypothesized that, among gynecologic oncology patients, postoperative complications and hospital stay would differ by surgical approach, and that advantages of VH for benign indications may not apply to gynecologic cancer patients. STUDY DESIGN: We performed a population-based retrospective cohort study of cervical, endometrial, or ovarian/fallopian tube cancer patients treated surgically in Washington State from 2004 through 2013 using the Comprehensive Hospital Abstract Reporting System. Surgery was categorized as abdominal hysterectomy (AH), laparoscopic hysterectomy (LH), or VH. We determined rate of surgical approach by year and the association with length of stay, 30-day readmission rate, and perioperative complications. RESULTS: We identified 10,117 patients who underwent surgery for gynecologic cancer, with 346 (3.4%) VH, 2698 (26.7%) LH, and 7073 (69.9%) AH. Patients undergoing AH had more comorbidities than patients with VH or LH (Charlson Comorbidity Index ≥2: 11.3%, 7.9%, and 8.1%, respectively; P < .001). From 2004 through 2013 AH and VH declined (94.4-47.9% and 4.4-0.8%, respectively; P < .001) while LH increased from 1.2-51.4% in 2013 (P < .001). Mean length of stay was 4.6 days for women undergoing AH and was 1.9 days shorter for VH (95% confidence interval, 1.6-2.3 days) and 2.6 days shorter for LH (95% confidence interval, 2.4-2.7 days) (P < .001). Risk of 30-day readmission for patients undergoing LH was 40% less likely compared to AH but not different for VH vs AH. CONCLUSION: AH and LH remain the preferred routes for hysterectomy in gynecologic oncology. Over the past decade, there has been a significant shift to LH with lower 30-day readmission and complication rates. There may be a limited role for VH in select patients. Current efforts to standardize the surgical approach to hysterectomy should not apply to patients with known or suspected gynecologic cancer.

Ovarian Cancer, Version 1.2016, NCCN Clinical Practice Guidelines in Oncology.

This selection from the NCCN Guidelines for Ovarian Cancer focuses on the less common ovarian histopathologies (LCOHs), because new algorithms were added for LCOHs and current algorithms were revised for the 2016 update. The new LCOHs algorithms include clear cell carcinomas, mucinous carcinomas, and grade 1 (low-grade) serous carcinomas/endometrioid epithelial carcinomas. The LCOHs also include carcinosarcomas (malignant mixed Müllerian tumors of the ovary), borderline epithelial tumors (also known as low malignant potential tumors), malignant sex cord-stromal tumors, and malignant germ cell tumors.