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Background: The precise mechanism by which the immune system is adversely affected in cancer patients remains poorly understood, but the accumulation of immunosuppressive/protumorigenic myeloid-derived suppressor cells (MDSCs) is thought to be a prominent mechanism contributing to immunologic tolerance of malignant cells in epithelial ovarian cancer (EOC). To this end, we hypothesized genetic variation in MDSC pathway genes would be associated with survival after EOC diagnoses.Methods: We measured the hazard of death due to EOC within 10 years of diagnosis, overall and by invasive subtype, attributable to SNPs in 24 genes relevant in the MDSC pathway in 10,751 women diagnosed with invasive EOC. Versatile Gene-based Association Study and the admixture likelihood method were used to test gene and pathway associations with survival.Results: We did not identify individual SNPs that were significantly associated with survival after correction for multiple testing (P < 3.5 × 10-5), nor did we identify significant associations between the MDSC pathway overall, or the 24 individual genes and EOC survival.Conclusions: In this well-powered analysis, we observed no evidence that inherited variations in MDSC-associated SNPs, individual genes, or the collective genetic pathway contributed to EOC survival outcomes.Impact: Common inherited variation in genes relevant to MDSCs was not associated with survival in women diagnosed with invasive EOC. Cancer Epidemiol Biomarkers Prev; 26(3); 420-4. ©2016 AACR.

Background The association of body composition with epithelial ovarian carcinoma (EOC) mortality is poorly understood. To date, evidence suggests that high adiposity is associated with decreased mortality (an obesity paradox), but the impact of muscle on this association has not been investigated. Herein, we define associations of muscle and adiposity joint-exposure body composition phenotypes with EOC mortality. Methods Body composition from 500 women in the Body Composition and Epithelial Ovarian Cancer Survival Study was dichotomized as normal or low skeletal muscle index (SMI), a proxy for sarcopenia, and high or low adiposity. Four phenotypes were classified as fit (normal SMI and low adiposity; reference; 16.2%), overweight or obese (normal SMI and high adiposity; 51.2%), sarcopenia and overweight or obese (low SMI and high adiposity; 15.6%), and sarcopenia or cachexia (low SMI and low adiposity; 17%). We used multivariable Cox models to estimate associations of each phenotype with mortality for EOC overall and high-grade serous ovarian carcinoma (HGSOC). Results Overweight or obesity was associated with up to 51% and 104% increased mortality in EOC and HGSOC [Hazard Ratio (HR)] = 1.51, 95% CI = 1.05 to 2.19 and HR = 2.04, 95% CI = 1.29 to 3.21). Sarcopenia and overweight or obesity was associated with up to 66% and 67% increased mortality in EOC and HGSOC (HR = 1.66, 95% CI = 1.13 to 2.45 and HR = 1.67, 95% CI = 1.05 to 2.68). Sarcopenia or cachexia was associated with up to 73% and 109% increased mortality in EOC and HGSOC (HR = 1.73, 95% CI = 1.14 to 2.63 and HR = 2.09, 95% CI = 1.25 to 3.50). Conclusions Overweight or obesity, sarcopenia and overweight or obesity, and sarcopenia or cachexia phenotypes were each associated with increased mortality in EOC and HGSOC. Exercise and dietary interventions could be leveraged as ancillary treatment strategies for improving outcomes in the most fatal gynecological malignancy with no previously established modifiable prognostic factors. [ABSTRACT FROM AUTHOR]

BackgroundRegulatory T (Treg) cells, a subset of CD4+ T lymphocytes, are mediators of immunosuppression in cancer, and, thus, variants in genes encoding Treg cell immune molecules could be associated with ovarian cancer.MethodsIn a population of 15,596 epithelial ovarian cancer (EOC) cases and 23,236 controls, we measured genetic associations of 1,351 SNPs in Treg cell pathway genes with odds of ovarian cancer and tested pathway and gene-level associations, overall and by histotype, for the 25 genes, using the admixture likelihood (AML) method. The most significant single SNP associations were tested for correlation with expression levels in 44 ovarian cancer patients.ResultsThe most significant global associations for all genes in the pathway were seen in endometrioid ( p = 0.082) and clear cell ( p = 0.083), with the most significant gene level association seen with TGFBR2 ( p = 0.001) and clear cell EOC. Gene associations with histotypes at p < 0.05 included: IL12 ( p = 0.005 and p = 0.008, serous and high-grade serous, respectively), IL8RA ( p = 0.035, endometrioid and mucinous), LGALS1 ( p = 0.03, mucinous), STAT5B ( p = 0.022, clear cell), TGFBR1 ( p = 0.021 endometrioid) and TGFBR2 ( p = 0.017 and p = 0.025, endometrioid and mucinous, respectively).ConclusionsCommon inherited gene variation in Treg cell pathways shows some evidence of germline genetic contribution to odds of EOC that varies by histologic subtype and may be associated with mRNA expression of immune-complex receptor in EOC patients.

Simple Summary: Individuals living with multiple myeloma are likely to have bone destruction as a consequence of their disease, leading healthcare providers to be reluctant to recommend physical activity. The aim of this prospective trial was to assess the feasibility of six-month strength training and walking interventions in patients with multiple myeloma. Various assessments of physical function and pain were performed at multiple timepoints throughout the trial. Participants saw improvements in mobility, leg strength, aerobic capacity, and endurance, with more pronounced and sustained improvements in the strength training arm, particularly in leg strength. This small trial showed the feasibility and benefits of both strength training and walking interventions in patients living with multiple myeloma. A larger trial extending these findings is underway at our institution. Because of the high prevalence of bone destruction in patients with multiple myeloma (MM), physical exercise is oftentimes discouraged by healthcare providers. The goal of this prospective trial was to investigate the feasibility of two six-month exercise interventions in patients with MM (N = 42): a remotely prompted home-based walking intervention or a supervised strength training intervention. Physical function and pain were assessed with the Activity Measure for Post-Acute Care (AM-PAC) Basic Mobility Short Form raw score, a six-minute walk test (6 MWT), a 30-second sit-to-stand test (30 SST), a timed up-and-go (TUG) test, a visual analog scale (VAS) for pain, handheld dynamometer tests, heart rate at rest, blood oxygen saturation at rest, and body mass index. No intervention-related serious adverse events were observed. Adverse events mostly affected the musculoskeletal system. In the resistance training group (n = 24), patients showed significant improvements in AM-PAC, TUG, 6 MWT, and 30 SST, with all effects but the 6 MWT sustained six months after the intervention. The walking group (n = 18) saw improvements in the AM-PAC, TUG, 6 MWT, and 30 SST, with a sustained change in the AM-PAC and TUG. This trial shows the feasibility of both exercise interventions with a sustained beneficial effect on the physical functioning of a six-month strength training intervention and, to a lesser extent, a six-month unsupervised walking intervention. A larger study building on these findings is currently underway. [ABSTRACT FROM AUTHOR]

Introduction: Plasma cell disorders (PCD) are a group of conditions characterized by disproportionate proliferation of a single clone of B lymphocytes. Multiple myeloma (MM) is a malignant type of plasma cell disorders. Improvements in MM survival have led patients and physicians to pursue strategies to improve quality of life for those living longer with this disease. Bone disease and instability associated with MM have made physicians reluctant to recommend physical activity (PA) to this patient population. The goal of this study was to examine the relationship between PA and physical and psychosocial patient-reported outcomes in patients withMMand precursor conditions. Methods: We used a cross-sectional study design. Questionnaires on PA, demographics, fatigue, distress, and other aspects of quality of life were posted on the HealthTree® Cure Hub website, a patient portal through which individuals withMMand related disorders obtain support, track laboratories and other information about their diseases, and participate in research. Results: A total of 794 individuals, including 664 with MM, are included in the current analysis. We observed potential inverse associations between PA and poor quality of life, including problems with sleep, fatigue, neuropathy, distress, and several psychosocial states. On average, patients reported that their PA levels have declined since diagnosis and that theywould like to be evenmore active in the future than theywere before their diagnosis. Conclusions: In our cross-sectional study, regular PA was associated with multiple quality-of-life indicators and other patient-reported outcomes, including better sleep and less fatigue, neuropathy, and distress. The findings of this study can help guide the design of prospective studies of the role of PA in MM survivorship. [ABSTRACT FROM AUTHOR]

Problem: Previous studies identified circulating CD14+HLA‐DRlo/− monocytic cells as an immune suppressive subset in solid malignancies, such as prostate, renal cell carcinoma, and pancreatic cancer. Such monocytic cells have been implicated not only in tumour progression but also as a potential barrier for immunotherapy. This study examined the relationship between the frequency of circulating monocytic cells and epithelial ovarian cancer (EOC) progression pre‐ and post‐frontline chemotherapy, defined by disease stage, which is a leading prognostic factor for this malignancy. Method of study: Incident cases of 236 women with EOC were recruited and comprehensive flow cytometry was utilized to assess the frequency of peripheral blood CD33+CD11b+HLA‐DR−/lowCD14+CD15− monocytic cells, henceforth termed CD14+HLA‐DRlo/− monocytic cells, prior to and after completion of frontline chemotherapy. Multivariable odds ratios (OR) were used to estimate the association between CD14+HLA‐DRlo/− monocytic cell percentages and disease stage. Wilcoxon signed‐rank tests evaluated changes in these monocytic cell levels pre‐ and post‐chemotherapy in a patient subset (n = 70). Results: Patients with elevated frequencies of circulating CD14+HLA‐DRlo/− monocytic cells at diagnosis were at 3.33‐fold greater odds of having advanced stage (III/IV) EOC (CI: 1.04‐10.64), with a significant trend in increasing CD14+HLA‐DRlo/−monocytic cell levels (P =.04). There was a 2.02% median decrease of these monocytic cells post‐chemotherapy among a subset of patients with advanced stage disease (P <.0001). Conclusion: These findings support the potential clinical relevance of CD14+HLA‐DRlo/−monocytic cells in EOC for prognosis and may indicate a non‐invasive biomarker to measure disease progression. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between regular cruciferous vegetable intake and stomach cancer. Methods: A hospital-based, case-control study was conducted at Roswell Park Comprehensive Cancer Center in Buffalo, NY, which included 292 stomach cancer patients and 1168 cancer-free controls recruited between 1992 and 1998 as part of the Patient Epidemiology Data System (PEDS). Dietary and other epidemiologic and confounding variables were collected by questionnaire. Multivariable logistic regression analyses were utilized to estimate odds ratios (OR) and 95% confidence intervals (CI) for associations between usual pre-diagnostic cruciferous vegetable intake and stomach cancer, with adjustment for other stomach cancer risk factors and dietary characteristics. Results: We observed strong inverse associations between stomach cancer and highest versus lowest intakes of total cruciferous vegetables (OR = 0.59, 95% CI: 0.42–0.83), raw cruciferous vegetables (OR = 0.53, 95% CI: 0.38–0.73), raw broccoli (OR = 0.61, 95% CI: 0.43–0.86), raw cauliflower (OR = 0.51, 95% CI: 0.35–0.73), and Brussels sprouts (OR = 0.66, 95% CI = 0.48–0.91). Conclusions: These data suggest that consuming raw cruciferous vegetables may be associated with a lower odds of stomach cancer, even after considering other dietary characteristics. [ABSTRACT FROM AUTHOR]

Background: Little is known about modifiable behaviours that may be associated with epithelial ovarian cancer (EOC) survival. We conducted a pooled analysis of 12 studies from the Ovarian Cancer Association Consortium to investigate the association between pre-diagnostic physical inactivity and mortality.Methods: Participants included 6806 women with a primary diagnosis of invasive EOC. In accordance with the Physical Activity Guidelines for Americans, women reporting no regular, weekly recreational physical activity were classified as inactive. We utilised Cox proportional hazard models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) representing the associations of inactivity with mortality censored at 5 years.Results: In multivariate analysis, inactive women had significantly higher mortality risks, with (HR=1.34, 95% CI: 1.18-1.52) and without (HR=1.22, 95% CI: 1.12-1.33) further adjustment for residual disease, respectively.Conclusion: In this large pooled analysis, lack of recreational physical activity was associated with increased mortality among women with invasive EOC. [ABSTRACT FROM AUTHOR]

Purpose: We observed that the tumor microenvironment (TME) in metastatic epithelial ovarian cancer (EOC) and in other solid tumors can reprogram normal neutrophils to acquire a complement-dependent suppressor phenotype characterized by inhibition of stimulated T cell activation. This study aims to evaluate whether serum markers of neutrophil activation and complement at diagnosis of EOC would be associated with clinical outcomes., Experimental Design: We conducted a two-center prospective study of patients with newly diagnosed EOC (N = 188). Blood and ascites fluid were collected at diagnosis for biomarker analysis. Patients were evaluated for progression-free survival (PFS) and overall survival (OS)., Results: The median OS was 47 months (95 % CI: 34-58) and the median PFS was 12 months (95 % CI: 11-15). Pre-treatment serum levels of genomic DNA (gDNA), markers of neutrophil degranulation (myeloperoxidase [MPO]) and neutrophil extracellular traps (NETs) (citrullinated histone H3 [CitH3]), and complement activation (C3b/c) were each associated with worse OS in univariate analysis. In multivariate analyses controlling for age, stage, and optimal debulking, serum gDNA, MPO, and CitH3 remained associated with worse OS, while C3b/c levels were not. In an exploratory analysis, the largest magnitude of difference in 2-year OS occurred in patients with low C3b/c and low CitH3 compared to all other patients (87 % vs 46 % survival, respectively). In ascites fluid, increased factor H, a negative regulator of complement activation, was associated with improved OS in univariate analysis., Conclusions: These results point to serum gDNA, NETs, and complement activation as potential prognostic biomarkers in patients with newly diagnosed EOC., Competing Interests: Declaration of competing interest B. Segal has a Sponsored Research Agreement and serves as a member of the Scientific Advisory Board of NextCure. K. Odunsi is a Co-Founder of Tactiva Therapeutics. I. Jongerius is an employee at Genmab (Denmark). Genmab was not involved financially in this project. All other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Despite patient interest in knowing whether diet is linked to multiple myeloma (MM), there is limited research on dietary patterns and MM risk. Two studies have assessed this risk, albeit with a small number of MM cases. The EPIC-Oxford cohort and Oxford Vegetarian study (65 MM cases) showed that fish eaters, vegetarians and vegans had significantly reduced MM risk compared to meat eaters. The Nurses' Health Study and Health Professionals Follow-up Study (478 MM cases) showed a significantly increased MM risk in men with Empirical Dietary Inflammatory Pattern., Methods: The NIH-AARP Diet and Health study is a prospective cohort of 567,169 persons who completed a food frequency questionnaire in 1995-1996 and were followed until December 2011. Healthy Eating Index-2015 (HEI-2015), Healthy Diet Score (HDS), alternate Mediterranean Diet (aMED) and healthful Plant-based Diet Index (hPDI) scores were calculated using a priori defined methods and grouped into quartiles, with higher scores reflecting healthier eating patterns. We prospectively evaluated the association between pre-diagnosis dietary patterns and MM incidence in this cohort. Hazard ratios (HR) and 95% confidence intervals (95%CI) were estimated using multivariate Cox proportional hazards models adjusted for age at study entry, sex, race, body mass index, education, and total energy intake (by residual method). Sensitivity analysis was conducted to assess reverse causality by excluding MM cases diagnosed within one year of follow-up., Results: Among 392,589 participants (after exclusions), a total of 1,366 MM cases (59% males; 92% non-Hispanic whites) were identified during the follow-up period. Analysis revealed a significant association between hPDI scores and reduced MM risk (highest vs lowest quartile, HR 0.85; 95%CI 0.73-1.0; p=0.043) (Table). In sensitivity analysis (1,302 MM cases), the association was no longer significant (HR 0.87; 95%CI 0.74-1.03; p 0.09) but trended in the same direction. This may be due to small sample size, given MM is a rare disease. HEI-2015, HDS and aMED scores were not associated with MM risk., Conclusions: A healthful plant-based diet was associated with reduced MM risk in the NIH-AARP cohort. These results will help oncologists and patients make informed choices about their diet. To our knowledge, this is the largest epidemiologic study to date assessing pre-diagnosis dietary patterns and MM risk., Competing Interests: Competing Interests U.A. Shah reports research funding support from Celgene/BMS, Janssen, Plantable, Sabinsa pharmaceuticals, VeggieDoctor and M and M labs to the institution, non-financial research support; personal fees from ACCC, MashUp MD, Janssen Biotech, Sanofi, BMS, MJH LifeSciences, Intellisphere, Phillips Gilmore Oncology Communications, i3 Health and RedMedEd outside the submitted work. A.M. Lesokhin reports grants from Bristol Myers Squibb and Genentech; grants, personal fees, and non-financial support from Pfizer; and grants and personal fees from Janssen outside the submitted work. A.M. Lesokhin has a patent for US20150037346A1 licensed and with royalties paid from Serametrix, Inc. S. Z. Usmani reports grants/personal fees from Amgen, Celgene, Sanofi, Seattle Genetics, Janssen, Takeda, SkylineDx, Netherlands; Merck, and GSK; grant funding from Bristol Myers Squibb and Pharmacyclics; and personal fees from AbbVie, MundiPharma, Gilead, Genentech, and Oncopeptides. No disclosures were reported by the other authors.