Primary Treatment Of Ovarian Cancer Research Articles

Abstract 5906: A new combinatorial therapy that synergistically targets the NuRD complex and proteostasis to eradicate quiescent ovarian cancer cells

Abstract Despite advances in immune and targeted therapies, chemotherapy remains the primary treatment for ovarian cancer (OvCa) patients. Unfortunately, most OvCa patients develop chemotherapy-resistant disease that is inevitably fatal. Quiescence is an important yet poorly understood mechanism underlying chemotherapy resistance. Therefore, we aimed to characterize quiescent ovarian cancer (qOvCa) cells to identify novel therapeutic targets to improve OvCa patient outcomes. Primary patient-derived qOvCa cells and proliferating cells were isolated using a single-cell microfluidics culture device and collected for single-cell RNA-seq. scRNA-seq of qOvCa cells identified (i) downregulation of MBD3 and CHD4, which are components of the Nucleosome Remodeling and Deacetylase (NuRD) complex, and (ii) upregulation of proteasome-associated genes. Knockdown of either MBD3 or CHD4 by shRNA, or NuRD complex pharmacologic inhibition with the HDAC inhibitors such as Vorinostat resulted in significant cell growth arrest without cell death. Standard and Fucci reporter-based cell cycle analysis further confirmed that inhibition of the NuRD complex with Vorinostat induced 94.47% cells in the G0 phase (p<0.0001), suggesting a dense quiescent state. Through cell cycle phase maps produced by iterative immunofluorescence of 30 core cell cycle regulators and manifold learning, we found Vorinostat-treated OvCa cells demonstrated a completely different cell cycle structure from control cells, with most of the cells in an extreme G0 phase. Bulk RNA-seq of Vorinostat-treated cells in three OvCa cell lines validated the downregulation of pathways relating to cell cycle, cell division, and DNA replication (LFC<-1, p<0.05), which is consistent with stem cells. Upregulation of several pathways involved in proteostasis were also noted. We therefore performed a targeted drug screen for combinatorial therapy approaches to eradicate qOvCa. We found that Vorinostat combined with the proteasome inhibitor Carfilzomib demonstrated the most profound synergistic cell death (Loewe index synergy score 23-73). Increased proteasome activity was also found in both primary and Vorinostat-induced qOvCa, suggesting the essential role of the proteasome in qOvCa. Tumor xenograft studies confirmed that Vorinostat alone can delay tumor growth (p<0.05) and combinatorial therapy of Vorinostat and Carfilzomib is more efficacious (p=0.0049). Taken together, NuRD complex inhibition induces quiescence. Combination therapy with Vorinostat to induce quiescence combined with proteasome inhibitors resulted in the profound death of therapy-resistant quiescent cells. Our work suggests this is a novel therapeutic approach to eradicate chemoresistant qOvCa cells and increase cure rates. Citation Format: Qi Jiang, Michelle Ertel, Santiago Panesso- Gómez, Sara Sannino, April Sagan, Alexander J. Cole, Stacy C. McGonigal, Betsy Ann Varghese, Wayne Stallaert, Jeffrey L. Brodsky, Hatice U. Osmanbeyoglu, Ronald J. Buckanovich. A new combinatorial therapy that synergistically targets the NuRD complex and proteostasis to eradicate quiescent ovarian cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5906.

Mental health and diet quality after primary treatment for ovarian cancer.

To investigate anxiety and depression after primary treatment for ovarian cancer in relation to diet quality and intake. In a cohort of women with ovarian cancer in Australia, levels of anxiety and depression (normal, subclinical, and clinical) were assessed using the Hospital Anxiety and Depression Scale at 9 months post-diagnosis. Dietary intake was assessed using a validated food frequency questionnaire at 12 months post-diagnosis and scored using the Healthy Eating Index 2015. Multinomial logistic regression and bivariate analyses were used to investigate relationships between levels of anxiety and depression and subsequent diet quality and intake of food groups. Of 595 women, anxiety and depression were identified among 128 (21%) and 80 (13%) women, respectively. Compared to women without anxiety or depression, women with subclinical anxiety (odds ratio = 0.49, 95% confidence interval: 0.25-0.98) and those with clinical depression (odds ratio = 0.25, 95% confidence interval: 0.07-0.93) were less likely to score in the highest quartile for diet quality. Separate adjustment for age, education, employment, disease stage, body mass index, and smoking status did not attenuate these associations. In bivariate analyses, women with subclinical anxiety were more likely to report higher intakes of sweet foods. Those with clinical depression were more likely to report lower intakes of orange vegetables and wholegrains, higher intakes of sweetened beverages, and not consume alcohol or soya foods. Anxiety or depression after primary treatment for ovarian cancer may be associated with poorer diet quality. Efforts to improve diet quality post-treatment should consider support for mental health.

Correlation between progression-free survival and overall survival in patients with ovarian cancer after cytoreductive surgery: a systematic literature review

ObjectivesThis analysis aimed to better define the relationship between progression-free survival and overall survival in adult patients with ovarian cancer (including fallopian tube or primary peritoneal cancer) following primary cytoreductive...

Justification of the choice of hormone therapy for ovarian cancer

BACKGROUND. Hormonal dependence of ovarian cancer remains a debatable issue in modern oncogynecology. Its decision will allow not only to clarify the pathogenesis of the development of ovarian cancer, its prognosis, but also to substantiate the indications for hormone therapy as a component of complex treatment.
 OBJECTIVE. To study the experience of domestic and foreign specialists regarding the pathogenetic rationale for prescribing hormone therapy to patients with ovarian cancer and its effectiveness.
 MATERIALS AND METHODS. Generalization and analysis of scientific publications on the research topic.
 RESULTS. The article summarizes data on the pathogenetic rationale for the appointment of hormone therapy, as well as the effectiveness of antiestrogens and aromatase inhibitors in the treatment of primary ovarian cancer and recurrences of the disease.
 CONCLUSIONS. To date, indications for the appointment and criteria for the use of hormone therapy in the complex treatment of ovarian cancer are not developed. The question of the reliability of the factors of the disease prognosis, taking into account the hormonal receptor status of ovarian cancer, remains open.

Association of Protein Intake with Recurrence and Survival Following Primary Treatment of Ovarian Cancer

BackgroundMalnutrition is common during treatment of ovarian cancer, and 1 in 3 patients report multiple symptoms affecting food intake after primary treatment. Little is known about diet posttreatment in relation to ovarian cancer survival; however, general recommendations for cancer survivors are to maintain a higher level of protein intake to support recovery and minimize nutritional deficits. ObjectivesTo investigate whether intake of protein and protein food sources following primary treatment of ovarian cancer is associated with recurrence and survival. MethodsIntake levels of protein and protein food groups were calculated from dietary data collected ∼12 mo postdiagnosis using a validated FFQ in an Australian cohort of women with invasive epithelial ovarian cancer. Disease recurrence and survival status were abstracted from medical records (median 4.9 y follow-up). Cox proportional hazards regression was used to calculate adjusted HRs and 95% CIs for protein intake and progression-free and overall survival. ResultsAmong 591 women who were progression-free at 12 mo follow-up, 329 (56%) subsequently experienced cancer recurrence and 231 (39%) died. A higher level of protein intake was associated with better progression-free survival (>1–1.5 compared with ≤1 g/kg body weight, HRadjusted: 0.69, 95% CI: 0.48, 1.00; >1.5 compared with ≤1 g/kg, HRadjusted: 0.61, 95% CI: 0.41, 0.90; >20% compared with ≤20% total EI from protein, HRadjusted: 0.77, 95% CI: 0.61, 0.96). There was no evidence for better progression-free survival with any particular protein food sources. There was a suggestion of better overall survival among those with higher total intakes of animal-based protein foods, particularly dairy products (HR: 0.71; 95% CI: 0.51, 0.99 for highest compared with lowest tertiles of total dairy intake). ConclusionsAfter primary treatment of ovarian cancer, a higher level of protein intake may benefit progression-free survival. Ovarian cancer survivors should avoid dietary practices that limit intake of protein-rich foods.

MODERN APPROACHES TO THE SYSTEMIC TREATMENT OF RECURRENT OVARIAN CANCER

Introduction: Introduction: Recurrent ovarian cancer is one of the most challenging issues in medical oncology. Being the fifth in the cancer mortality list among women, ovarian cancer is the reason of more deaths than any other cancer of the female reproductive system. A meta-analysis was conducted to investigate the optimal treatment options for recurrent platinum-sensitive and platinum-resistant ovarian cancer. Methods: Data for writing this article was collected from the publications in English, Russian and Italian from 2002 to 2023. PubMed and Web of Science were searched for the relevant articles. Survival rates, particularly overall survival (OS), progression-free survival (PFS), and adverse events (AEs) of the chemotherapy regimens were discussed. We analyzed the literature data comparing the effectiveness and safety of chemotherapy, antiangiogenic therapy, the use of poly-ADP ribose polymerase (PARP) inhibitors, and checkpoint inhibitors in the treatment of recurrent ovarian cancer. Results: An overview of the literature devoted to modern approaches to the systemic treatment of recurrent ovarian cancer is given in the article. General principles of classification and treatment of recurrent ovarian cancer are analyzed. The existing regimens of chemotherapy in combination with targeted therapy are given separately for various types of ovarian cancer relapses. Chemotherapy with doublet platinum compounds (carboplatin or cisplatin) continues to be the standard of care in platinum-sensitive relapsed ovarian cancer with or without targeted therapy. Treatment with poly-ADP ribose polymerase inhibitors, vascular endothelial growth factor inhibitors, immunotherapy with checkpoint inhibitors, and antibody-drug conjugate for patients with folate receptor alpha-positive, can be considered in platinumresistant epithelial ovarian cancer. Conclusion: In summary, we can conclude that despite the success of the primary treatment of ovarian cancer, the majority of patients with a widespread tumor process develop a relapse of the disease over the next two years, which is the cause of death of these patients. The development of effective treatment regimens for recurrent ovarian/fallopian tube/primary peritoneal cancer remains particularly acute and important in gynecological oncology and requires further study.

Impact of robotic surgery on patient flow and resource use intensity in ovarian cancer.

There is an emerging focus on the role of robotic surgery in ovarian cancer. To date, the operational and cost implications of the procedure remain unknown. The objective of the current study was to evaluate the impact of integrating minimally invasive robotic surgery on patient flow, resource utilization, and hospital costs associated with the treatment of ovarian cancer during the in-hospital and post-discharge processes. 261 patients operated for the primary treatment of ovarian cancer between January 2006 and November 2014 at a university-affiliated tertiary hospital were included in this study. Outcomes were compared by surgical approach (robotic vs. open surgery) as well as pre- and post-implementation of the robotics platform for use in ovarian cancer. The in-hospital patient flow and number of emergency room visits within 3months of surgery were evaluated using multi-state Markov models and generalized linear regression models, respectively. Robotic surgery cases were associated with lower rates of postoperative complications, resulted in a more expedited postoperative patient flow (e.g., shorter time in the recovery room, ICU, and inpatient ward), and were between $10,376 and $7,421 less expensive than the average laparotomy, depending on whether or not depreciation and amortization of the robotic platform were included. After discharge, patients who underwent robotic surgery were less likely to return to the ER (IRR 0.42, p = 0.02, and IRR 0.47, p = 0.055, in the univariate and multivariable models, respectively). With appropriate use of the technology, the addition of robotics to the medical armamentarium for the management of ovarian cancer, when clinically feasible, can bring about operational efficiencies and entails cost savings.

Quality control index for standardized diagnosis and treatment of primary ovarian cancer in China (2022 edition)

Quality control index for standardized diagnosis and treatment of primary ovarian cancer in China (2022 edition)

Dietary Practices After Primary Treatment for Ovarian Cancer: A Qualitative Analysis From the OPAL Study

BackgroundLittle is known about the dietary practices of women who have completed primary treatment for ovarian cancer, many of whom will go on to have cancer recurrence and further treatment. Knowledge of dietary practices is needed to optimize care. ObjectiveOur aim was to identify dietary practices after primary treatment for ovarian cancer and evaluate how these practices differ by disease recurrence and treatment status. DesignWomen with invasive epithelial ovarian cancer were provided with the following open-ended question after completing a food frequency questionnaire: “Is there anything we haven’t asked you about your diet in the last 1 to 2 months that you feel is important?” Participants/settingParticipants were from the OPAL (Ovarian Cancer Prognosis and Lifestyle) Study in Australia. Main outcomesThe main outcomes were dietary practices after primary treatment for ovarian cancer and factors affecting these practices. AnalysisParticipants’ responses were analyzed using content analysis. Individual content codes were categorized and reported by recurrence and treatment status at questionnaire completion. ResultsTwo hundred eighty-six women provided responses on 363 questionnaires. Those undergoing further treatment for recurrence commonly reported dietary regimens with clinical indications (eg, low fiber to avoid bowel obstructions, high energy/protein to minimize nutritional deficits). Those not undergoing further treatment frequently reported “popular” diets (eg, organic, plant-based, and alkaline). For women with cancer recurrence, dietary practices were affected by poor appetite and late effects of treatment. For women without recurrence, other comorbidities, geographical location, family, and friends appeared to influence dietary practices. In both groups, nutrition information sources and personal beliefs informed dietary practices. Participant responses that referenced media or online sources often included misinformation. ConclusionsAfter primary treatment for ovarian cancer, women report dietary practices that may not be captured in standard food frequency questionnaires. Dietary practices and factors affecting these practices likely differ by treatment and recurrence status. Improved access to evidence-based dietary information and support is needed.

The roles and limitations of bevacizumab in the treatment of ovarian cancer.

Bevacizumab, an anti-VEGF antibody, targets mainly tumor blood vessels and exerts a cytostatic antitumor effect. In primary ovarian cancer, bevacizumab is used for 15months, but its effect on progression-free survival disappears after 2years and does not prolong overall survival. And in the treatment of primary ovarian cancer, there is no evidence that bevacizumab increases the intratumor concentration of chemotherapy and enhances response rates. On the other hand, bevacizumab is not affected by resistance mechanisms to chemotherapeutic agents or poly(ADP-ribose) polymerase (PARP) inhibitors. In the era of using PARP inhibitors for primary ovarian cancer, bevacizumab will become a molecularly targeted drug that will play a central role in chemo-refractory and recurrent ovarian cancer.

Primary treatment of advanced ovarian cancer: how does the 'real world' practice?

Aims: This study evaluated primary treatment modalities in advanced ovarian cancer according to sociodemographic characteristics and characterized chemotherapy regimens used. Methods: This was a retrospective study of newly diagnosed advanced ovarian, tubal or peritoneal cancer patients at two hospitals from 2011 to 2016. Results: Of 175 women, 41% received neoadjuvant chemotherapy and 59% received primarycytoreductive surgery. Within the neoadjuvant chemotherapy group, 23% did not have a surgical consultation prior to initiating treatment. Women receiving neoadjuvant chemotherapy lived closer to an academic center and more frequently received carboplatin/paclitaxel every 3weeks. Cytoreductive surgery patients more frequently received intraperitoneal chemotherapy. Conclusion: The authors identified disparities in age, insurance, distance from treatment center and chemotherapy choice in the primary treatment for ovarian cancer.

Movement of Poly-ADP Ribose (PARP) Inhibition into Frontline Treatment of Ovarian Cancer.

The use of poly (ADP-ribose) polymerase (PARP) inhibitors in the front-line management of advanced ovarian cancer has recently emerged as an exciting strategy with the potential to improve outcomes for patients with advanced ovarian cancer. In this article, we review the results of four recently published Phase III randomised controlled trials evaluating the use of PARP inhibitors in the primary treatment of ovarian cancer (SOLO1, PRIMA, PAOLA-1, and VELIA). Collectively, the studies suggest that PARP maintenance in the upfront setting is most beneficial among patients with BRCA-associated ovarian cancers (hazard ratios range from 0.31 to 0.44), followed by patients with tumours that harbour homologous recombination deficiencies (hazard ratios range from 0.33 to 0.57). All three studies that included an all-comer population were able to demonstrate benefit of PARP inhibitors, regardless of biomarker status. The FDA has approved olaparib for front-line maintenance therapy among patients with BRCA-associated ovarian cancers, and niraparib for all patients, regardless of biomarker status. In determining which patients should be offered front-line maintenance PARP inhibitors, and which agent to use, there are multiple factors to consider, including FDA indication, dosing preference, toxicity, risks versus benefits for each patient population, and cost. There are ongoing studies further exploring the front-line use of PARP inhibitors, including the potential downstream effects of PARP-inhibitor resistance in the recurrent setting, combining PARP-inhibitors with other anti-angiogenic drugs, immunotherapeutic agents, and inhibitors of pathways implicated in PARP inhibitor resistance.

When will I feel normal again? Trajectories and predictors of persistent symptoms and poor wellbeing after primary chemotherapy for ovarian cancer

ObjectivesAfter treatment for ovarian cancer, women want to know when they will feel ‘normal’ again. Our objective was to document the proportions of women with high levels of physical and emotional symptoms at the end of treatment, determine if/when they return to normal and identify groups at risk of persistent symptoms/delayed recovery. MethodsWomen in the OPAL (Ovarian cancer Prognosis And Lifestyle) study who received ≥3 cycles of first-line chemotherapy and completed patient-reported outcome (PRO) questionnaires on or < 6 weeks after completing chemotherapy (baseline) were included in this analysis (n = 527). PRO measures included anxiety, depression, insomnia, fatigue and wellbeing (quality-of-life) at baseline, 3, 6, 9 and 18 months post-baseline. Group-based trajectory models identified clusters of individuals who followed similar patterns. Logistic and Cox regression identified factors associated with persistent symptoms and delayed recovery, respectively. ResultsAt baseline, 57% of women reported moderate-to-severe fatigue, 22% anxiety, 20% depression, 14% clinical insomnia and 45% had quality-of-life scores significantly lower than the general population. Between 50 and 75% of individual PRO scores normalised within six months, with the exception of emotional wellbeing (42%), but approximately two-in-five women still had at least one persistently poor PRO at 18 months. Women with more severe symptoms at baseline, who were younger, or had a history of anxiety/depression were more likely to have persistent symptoms or delayed recovery. ConclusionsTwo-in-five women might never fully return to ‘normal’ after completing primary treatment for ovarian cancer. Those with risk factors should be triaged for early supportive interventions.

PARP inhibitors in ovarian cancer: evidence for maintenance and treatment strategies.

Ovarian cancer is the most lethal gynecologic malignancy. The long-established primary treatment for ovarian cancer consisted of surgical cytoreduction followed by platinum-based chemotherapy. Unfortunately, this therapeutic approach is related to a high frequency of early relapses. Further chemotherapy is necessary for recurrent disease, but very few patients can be cured. Poly (ADP-ribose) polymerase (PARP) is a family of proteins involved in various DNA repair activities. PARP inhibition leads to synthetic lethality in BRCA mutated or homologous recombination deficient tumors. The development of PARP inhibitors has changed the way ovarian cancer patients are treated. Olaparib, niraparib and rucaparib are orally active and have demonstrated efficacy for both maintenance and treatment settings. These three drugs have gained regulatory approval for different clinical circumstances. They have an acceptable toxicity profile and are generally well tolerated. Common class toxicities include hematologic effects, gastrointestinal effects and fatigue. Moreover, new treatment strategies that combine PARP inhibitors with other drugs, such as angiogenic agents, are being explored. The purpose of this review is to describe the evidence that define the current clinical role of PARP inhibitors in ovarian cancer. The implementation of rationally designed new clinical trials will be crucial to facilitate the best selection of patients and to continue improving clinical outcomes.

Is it possible to improve primary therapy of advanced ovarian cancer?

In 2011, a standard approach to the treatment of primary ovarian cancer (OC) included a cytoreductive surgery, which could be performed after 2–3 cycles of neoadjuvant chemotherapy, and chemotherapy consisting of platinum and taxanes. Such approach was provided for all patients, regardless of tumour histology and any molecular biological and genetic factors. The most complete picture of management and therapy of patients can be made using the treatment of a specific patient as an example. After application to the N.N. Blokhin National Medical Research Center of Oncology in 2011, the patient with OC received standard primary therapy and subsequent treatment of the recurrent disease, which was accompanied by various types of adverse events resulting in the poor quality of life for the patient. The data that some patients with OC have a BRCA1/2 mutation that is significant for prognosis and treatment came to hand later and, unfortunately, the awareness of a significant germinal BRCA1 mutation was of no use to the woman any longer. The life expectancy of this patient was 47 months. This is the average life expectancy for patients with stage IIIC OC. Major changes have been brought in the primary therapy of OC. If a diagnosis of low-grade IIIC ovarian adenocarcinoma was established in this patient today, needless to say that the BRCA1 mutation would be identified during the first-line chemotherapy, and in case of full or partial treatment effect, we would prescribe olaparib as maintenance therapy to the patient. Considering the fact that the median progression-free survival has not yet been achieved in the patients of SOLO-1 study, who received olaparib therapy, and is only approaching 54 months, it can be assumed that even the first relapse could not have developed in this patient.

Highly selective and sensitive FRET based ratiometric two-photon fluorescent probe for endogenous β-galactosidase detection in living cells and tissues

In vivo measurement of abnormal β-galactosidase (β-gal) in living cells and tissues is urgently required for early diagnosis and treatment of primary ovarian cancer. Herein, a FRET-based ratiometric two-photon fluorescent probe FTR-βgal with a large emission shift, rapid response and low cytotoxicity was developed for sensitively detecting β-gal activity in vivo. FTR-βgal was designed with a naphthalene derivative as the energy donor and a rhodol derivative as the energy acceptor, which provided an efficient FRET strategy. Remarkably, FTR-βgal was successfully applied in TP imaging of β-gal with the ratio signal rapidly transform from 0.15 to 5.9 (∼40-fold) between 540 nm and 450 nm. Furthermore, FTR-βgal was used to visualize β-gal levels in tumor upon tissue penetration of 30–150 μm achieved. Therefore, FTR-βgal was applicable for clinical detection in living cells and tissues as a promising strategy for diagnosis of various associated cancers.

Hyperthermic Intraperitoneal Chemotherapy (HIPEC) as Primary Treatment of Ovarian Cancer: A Review of the Current Literature

HIPEC has been proposed as an addition in the treatment of ovarian cancer. The purpose of this review was to evaluate the evidence and use of HIPEC after cytoreductive surgery as up-front therapy for inpatients with primary ovarian cancer. We performed a search on PubMed and Web of Science. Additional studies were identified by cross-referencing past reviews and published studies. Primary endpoints were overall survival and progression-free survival. Secondary endpoints were morbidity, mortality and completeness of cytoreduction score. We found 15 cohort studies eligible for review with data available for 2285 patients in total of which 924 had primary ovarian cancer and received CRS + HIPEC as up-front or interval debulking therapy. Seven studies reported a median OS higher than 50 months in 445 patients. Additionally, four studies reported a 5-year survival rate > 30% in 111 patients. The lowest survival rates were 35.4–43 months. CC-0 score of more than 90% was reported in four studies. PFS ranged from 11.8 to 30 months. Major morbidity directly related to HIPEC included leukopenia, thrombocytopenia and renal failure. Forty deaths were reported overall. CRS and HIPEC seems promising as treatment for primary ovarian cancer, however the vast number of patients reported treated with CRS + HIPEC are reported in retrospective studies without standard protocols therefor further randomized clinical trials are needed.

Abstract 4235: Race differences in treatment and survival of ovarian cancer

Abstract Black women have lower incidence rates of ovarian cancer than white women in the U.S., but their cancers are more often fatal. Factors associated with lower survival among blacks include advanced stage at diagnosis and fewer women receiving a surgery-chemotherapy sequence consistent with national guidelines for treatment of primary ovarian cancer. We examined treatment and survival among 365 white and 95 black ovarian cancer patients captured by the Hollings Cancer Center Cancer Registry in Charleston, S.C. from 2000 to 2015 with the aim of identifying factors to explain observed racial disparities. Outcomes of interest were receipt of a cytoreductive surgery-chemotherapy sequence, with or without neoadjuvant therapy, and overall survival (OS) calculated as months from diagnosis to death. We used unconditional logistic regression to estimate odds ratios (ORs) of black vs. white race associated with receipt of surgery-chemotherapy, controlling for clinical stage, histology, insurance status, smoking status, and severity of comorbidities (none, mild, moderate, moderate-severe, severe), assessed using the age-adjusted Charlson index. For survival comparisons, we plotted Kaplan-Meier curves by race and estimated the death hazard ratio (HR) using Cox proportional hazards regression. We assessed statistical interaction between race and comorbidities using −2 log likelihood tests. Age, stage and histology distributions were similar between blacks and whites; however, white women were more likely than blacks to be current or former smokers (44% vs. 32%) and to have private health insurance (38% vs. 26%), while blacks were more likely to have moderate-severe or severe comorbidities (37% vs. 30%), although differences were not statistically significant. There were significant racial differences in receipt of surgery-chemotherapy (blacks 44% vs. whites 69%, p&amp;lt;0.0001). Women who did not receive a surgery-chemotherapy sequence were 3 times more likely to be black (adjusted OR 3.13, 95% confidence interval (CI) 1.90−5.16), but the disparity was observed only in women with comorbidity as opposed to none (interaction p=0.01). Median OS was 29.3 months among black women and 49.2 months among whites (log rank p&amp;lt;0.001). The survival disadvantage among blacks persisted after controlling for treatment, comorbidities, stage, smoking, and insurance (HR 1.87, 95% CI 1.41−2.48), and no statistical interaction between race and comorbidities was evident (p=0.17). In this study, black women, particularly those with comorbidities, were significantly less likely than whites to receive a surgery-chemotherapy sequence for treatment of ovarian cancer. Black race was associated with an 87% higher fatality rate independent of treatment, stage, comorbidities, and insurance status. More research is needed to understand race-specific reasons for nonadherence to guideline based care and racial disparities in survival after ovarian cancer diagnosis. Citation Format: Janet S. Hildebrand, Kristin Wallace, Linda E. Kelemen. Race differences in treatment and survival of ovarian cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4235.

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.

Metastatic gynecologic malignancies: advances in treatment and management.

Gynecologic cancers comprise of mostly uterine, ovarian, and cervical malignancies and are responsible for 95,000 new cases annually in the United States. Uterine cancer is the most common and the number of new cases and mortality has been increasing. Cervical cancer has decreased due to screening, early detection, and treatment of pre-invasive cancers. However, ovarian cancer remains the most lethal because of advanced stage at diagnosis and drug resistance. The metastatic spread pattern differs amongst these cancers, with uterine and cervical cancer found mostly in the primary organ and ovarian cancer disseminating throughout the peritoneum and upper abdomen at presentation. The primary treatment of ovarian cancer typically involves surgery followed by systemic therapy for more advanced disease. Previously, systemic chemotherapy with platinums, taxanes, doxorubicin, topotecan, and gemcitabine has been the standard in either upfront or recurrent setting. With molecular and genetic breakthroughs, we now have over eight new indications and five novel biologic therapies including antiangiogenics, poly ADP ribose polymerase inhibitors, and immunotherapies approved over the last 3years. In this review, we will examine the biology of gynecologic cancer metastasis and focus on new treatment options for these cancers with a focus on ovarian cancer.