Our large study, which is representative of the United States population and incorporates the most current knowledge of ovarian cancer pathogenesis, highlights the need to recognize ovarian cancer as a set of distinct diseases and not a single entity. Only then will we be able to effectively target the unique features of each histotype to reduce ovarian cancer mortality.
PURPOSE Idecabtagene vicleucel (ide-cel) is an autologous B-cell maturation antigen–directed chimeric antigen receptor T-cell therapy approved for relapsed/refractory multiple myeloma (RRMM) on the basis of the phase II pivotal KarMMa trial, which demonstrated best overall and ≥ complete response rates of 73% and 33%, respectively. We report clinical outcomes with standard-of-care (SOC) ide-cel under the commercial Food and Drug Administration label. METHODS Data were retrospectively collected from patients with RRMM who underwent leukapheresis as of February 28, 2022, at 11 US institutions with intent to receive SOC ide-cel. Toxicities were graded per American Society for Transplantation and Cellular Therapy guidelines and managed according to each institution's policies. Responses were graded on the basis of the International Myeloma Working Group response criteria. RESULTS One hundred fifty-nine of 196 leukapheresed patients received ide-cel by data cutoff. One hundred twenty (75%) infused patients would have been ineligible for participation in the KarMMa clinical trial because of comorbidities at the time of leukapheresis. Any grade and grade ≥ 3 cytokine release syndrome and neurotoxicity occurred in 82/3% and 18/6%, respectively. Best overall and ≥ complete response rates were 84% and 42%, respectively. At a median follow-up of 6.1 months from chimeric antigen receptor T infusion, the median progression-free survival was 8.5 months (95% CI, 6.5 to not reached) and the median overall survival was 12.5 months (95% CI, 11.3 to not reached). Patients with previous exposure to B-cell maturation antigen–targeted therapy, high-risk cytogenetics, Eastern Cooperative Oncology Group performance status ≥ 2 at lymphodepletion, and younger age had inferior progression-free survival on multivariable analysis. CONCLUSION The safety and efficacy of ide-cel in patients with RRMM in the SOC setting were comparable with those in the phase II pivotal KarMMa trial despite most patients (75%) not meeting trial eligibility criteria.
Background:The Deepwater Horizon Oil Spill (DHOS) is the largest oil spill in U.S. history, negatively impacting Gulf Coast residents and the surrounding ecosystem. To date, no studies have been published concerning physical health outcomes associated with the DHOS in the general community.Objectives:We characterized individual DHOS exposure using survey data and examined the association between DHOS exposure and physical health.Methods:Baseline data from 2,126 adult women residing in southern Louisiana and enrolled in the Women and Their Children’s Health study were analyzed. Exploratory factor analysis was used to characterize DHOS exposure. Odds ratios and 95% confidence intervals for the associations between DHOS exposure and physical health symptoms were estimated using multivariate logistic regression.Results:A two-factor solution was identified as the best fit for DHOS exposure: physical–environmental exposure and economic exposure. High physical–environmental exposure was significantly associated with all of the physical health symptoms, with the strongest associations for burning in nose, throat, or lungs (OR = 4.73; 95% CI: 3.10, 7.22), sore throat (OR = 4.66; 95% CI: 2.89, 7.51), dizziness (OR = 4.21; 95% CI: 2.69, 6.58), and wheezing (OR = 4.20; 95% CI: 2.86, 6.17). Women who had high-economic exposure were significantly more likely to report wheezing (OR = 1.92; 95% CI: 1.32, 2.79); headaches (OR = 1.81; 95% CI: 1.41, 2.58); watery, burning, itchy eyes (OR = 1.61; 95% CI: 1.20, 2.16); and stuffy, itchy, runny nose (OR = 1.56; 95% CI: 1.16, 2.08).Conclusions:Among southern Louisiana women, both physical–environmental and economic exposure to the DHOS were associated with an increase in self-reported physical health outcomes. Additional longitudinal studies of this unique cohort are needed to elucidate the impact of the DHOS on short- and long-term human health.Citation:Peres LC, Trapido E, Rung AL, Harrington DJ, Oral E, Fang Z, Fontham E, Peters ES. 2016. The Deepwater Horizon Oil Spill and physical health among adult women in southern Louisiana: the Women and Their Children’s Health (WaTCH) study. Environ Health Perspect 124:1208–1213; http://dx.doi.org/10.1289/ehp.1510348
Chronic inflammation has been implicated in the development of epithelial ovarian cancer (EOC); yet, the contribution of inflammatory foods and nutrients to EOC risk has been understudied. We investigated the association between the dietary inflammatory index (DII), a novel literature-derived tool to assess the inflammatory potential of one’s diet, and EOC risk in African American (AA) women in the African American Cancer Epidemiology Study (AACES), the largest population-based case-control study of EOC in AA women to date. The energy-adjusted DII (E-DII) was computed per 1,000 kilocalories from dietary intake data collected through a food frequency questionnaire, which measured usual dietary intake in the year prior to diagnosis for cases or interview for controls. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariable logistic regression for the association between the E-DII and EOC risk. 493 cases and 662 controls were included in the analyses. We observed a 10% increase in EOC risk per a one-unit change in the E-DII (OR=1.10, 95% CI=1.03–1.17). Similarly, women consuming the most pro-inflammatory diet had a statistically significant increased EOC risk in comparison to the most anti-inflammatory diet (ORQuartile4/Quartile1=1.72; 95% CI=1.18–2.51). We also observed effect modification by age (p<0.05), where a strong, significant association between the E-DII and EOC risk was observed among women older than 60 years, but no association was observed in women aged 60 years or younger. Our findings suggest that a more pro-inflammatory diet was associated with an increased EOC risk, especially among women older than 60 years.
Our findings suggest that histotype assignment is fairly consistent regardless of classification approach, but that progressive improvements in classification accuracy for some less common histotypes are achieved with pathologic review using the 2014 WHO criteria and with IHC integration. We additionally recommend a classification scheme to fit historic data into the 2014 WHO categories to answer histotype-specific research questions.
Idecabtagene vicleucel (ide-cel) was FDA approved in March 2021 for the treatment of relapsed/refractory multiple myeloma (RRMM) after 4 lines of therapy. On the KarMMa trial, grade ≥3 cytopenias and infections were common. We sought to characterize cytopenias and infections within 100 days after ide-cel in the standard of care (SOC) setting. This multi-center retrospective study included 52 patients who received SOC ide-cel; 47 reached day 90 follow-up. Data was censored at day 100. Grade ≥3 cytopenia was present among 65% of patients at day 30 and 40% of patients at day 90. Granulocyte colony stimulating factor (G-CSF) was administered to 88%, packed red blood cell (pRBC) transfusions to 63%, platelet transfusions to 42%, thrombopoietin (TPO) agonists to 21%, intravenous immunoglobulin (IVIG) to 13%, and CD34+ stem cell boosts to 8%. At day 100, 19% and 13% of patients had ongoing use of TPO agonists and G-CSF, respectively. Infections occurred in 54% of patients and were grade ≥3 in 23%. Earlier infections in the first 30 days were typically bacterial (68%) and severe (50%). Later infections between days 31 - 100 were 50% bacterial and 42% viral; only 13% were grade ≥3. On univariate analysis, high pre-CAR-T marrow myeloma burden (>/= 50%), circulating plasma cells at pre-lymphodepletion (LD), and grade ≥3 anemia at pre-LD were associated with grade ≥3 cytopenia at both days 30 and 90. Longer time from last bridging treatment to LD was the only significant risk factor for infection.
Purpose of review Only recently has it become clear that epithelial ovarian cancer (EOC) is comprised of such distinct histotypes--with different cells of origin, morphology, molecular features, epidemiologic factors, clinical features, and survival patterns—that they can be thought of as different diseases sharing an anatomical location. Herein, we review opportunities and challenges in studying EOC heterogeneity, Recent findings The 2014 World Health Organization diagnostic guidelines incorporate accumulated evidence that high- and low-grade serous tumors have different underlying pathogenesis, and that, on the basis of shared molecular features, most high grade tumors, including some previously classified as endometrioid, are now considered to be high-grade serous. At the same time, several studies have reported that high-grade serous EOC, which is the most common histotype, is itself made up of reproducible subtypes discernable by gene expression patterns. Summary These major advances in understanding set the stage for a new era of research on EOC risk and clinical outcomes with the potential to reduce morbidity and mortality. We highlight the need for multidisciplinary studies with pathology review using the current guidelines, further molecular characterization of the histotypes and subtypes, inclusion of women of diverse racial/ethnic and socioeconomic backgrounds, and updated epidemiologic and clinical data relevant to current generations of women at risk of EOC.
Background Epidemiologic studies indicate increased ovarian cancer risk among women who use genital powder, but this has not been thoroughly investigated in African American (AA) women, a group with a high prevalence of use. We evaluate the relationship between use of genital powder and non-genital powder in invasive epithelial ovarian cancer (EOC). Methods Subjects are 584 cases and 745 controls enrolled in the African American Epidemiology Cancer Study, an ongoing, population-based case-control study of EOC in AA women in 11 geographic locations in the U.S. AA controls were frequency matched to cases on residence and age. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between genital and non-genital powder exposure and EOC risk, controlling for potential confounders. Results Powder use was common (62.8 % of cases and 52.9% of controls). Genital powder was associated with an increased risk of EOC (OR = 1.44, 95% CI: 1.11, 1.86) and a dose-response relationship was found for duration of use and number of lifetime applications (p <0.05). Non-genital use was also associated with EOC risk, particularly among non-serous EOC cases (OR = 2.28; 95% CI: 1.39, 3.74). An association between powder use and upper respiratory conditions suggests an enhanced inflammatory response may explain the association between body powder and EOC. Conclusion In a study of AA women, body powder use was significantly associated with EOC risk. Impact The results support that body powder is a modifiable risk factor for EOC among AA women.
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