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PurposeThe aim of this study was to compare the overexpression of specific biomarkers in primary advanced and recurrent epithelial ovarian cancers.MethodsBiomarker expression by epithelial ovarian cancer specimens from primary and metastatic sites was examined by immunohistochemistry and flow cytometry. Biomarker expression by subpopulations of tissues consisting of matched pairs of synchronous and metachronous lesions was also studied.ResultsA total of 3173 epithelial ovarian cancer specimens were retrieved from women with FIGO Stage III/IV disease. These included lesions from 1036 primary and 2137 metastatic sites. The percentages of biomarker expression for primary and metastatic lesions, respectively, were MDR1, 12 and 10%; p53, 55 and 60%; HER2, 12 and 11%; EGF-R, 26 and 33%; increased microvessel counts (CD31), 21 and 36%. Approximately 73% of both primary and metastatic specimens were aneuploid, and approximately 57% of both sets had an S-phase fraction >7%. Only EGF-R and CD31 expression were found to be significantly different between the primary and metastatic tumors (P < 0.05). Of the paired synchronous cases (n = 48) evaluated, 88% of aneuploid primary lesions were associated with aneuploid metastases. Similarly, the distributions for MDR1, HER2, and p53 expression did not vary significantly between primary and metastatic sites. Pairings of metachronous cases (n = 66) revealed that nearly 80% of primary aneuploid tumors (n = 39) retained their aneuploid status at the time of relapse. Furthermore, there were no significant changes in MDR1, p53, or HER2 expression at relapse.ConclusionsWith the exception of EGF-R and CD31, clonal divergence of the biomarkers evaluated in this study probably does not play a significant role in imparting clinical heterogeneity during the advanced and recurrent stages of epithelial ovarian cancer. These particular genes likely undergo alterations early in the tumorigenesis process before metastases have become established.

Chronic pain is a frequent complication of cancer and its treatments and is often underreported, underdiagnosed, and undertreated. Pain in cancer survivors is caused by residual tissue damage from the cancer and/or the cancer therapy. This pain can be divided into 3 pathophysiologic categories: somatic, visceral, and neuropathic. The most common treatment-induced chronic pain syndromes are neuropathies secondary to surgery, radiation therapy, and chemotherapy. Comfort and function are optimized in cancer survivors by a multidisciplinary approach using an individually tailored combination of opioids, coanalgesics, physical therapy, interventional procedures, psychosocial interventions, and complementary and alternative modalities. Management of chronic pain must be integrated into comprehensive cancer care so that cancer patients can fully enjoy their survival. [ABSTRACT FROM AUTHOR]

Acute lower gastrointestinal GVHD (aLGI-GVHD) is a serious complication of allogeneic hematopoietic stem cell transplantation. Although the intestinal microbiota is associated with the incidence of aLGI-GVHD, how the intestinal microbiota impacts treatment responses in aLGI-GVHD has not been thoroughly studied. In a cohort of patients with aLGI-GVHD (n = 37), we found that non-response to standard therapy with corticosteroids was associated with prior treatment with carbapenem antibiotics and a disrupted fecal microbiome characterized by reduced abundances of Bacteroides ovatus. In a murine GVHD model aggravated by carbapenem antibiotics, introducing B. ovatus reduced GVHD severity and improved survival. These beneficial effects of Bacteroides ovatus were linked to its ability to metabolize dietary polysaccharides into monosaccharides, which suppressed the mucus-degrading capabilities of colonic mucus degraders such as Bacteroides thetaiotaomicron and Akkermansia muciniphila, thus reducing GVHD-related mortality. Collectively, these findings reveal the importance of microbiota in aLGI-GVHD and therapeutic potential of B. ovatus., Competing Interests: Declaration of interests R.R.J. has served as a consultant or advisory board member for Postbiotics Plus, Merck, Microbiome DX, Karius, MaaT Pharma, LISCure, Seres, Kaleido, and Prolacta and has received patent license fee or stock options from Seres, Kaleido, and Postbiotics Plus. E.J.S. has served as a consultant or advisory board member for Adaptimmune, Axio, Navan, Fibroblasts, and FibroBiologics, NY Blood Center, and Celaid Therapeutics and has received patent license fee from Takeda and Affimed. J.U.P. reports research funding, intellectual property fees, and travel reimbursement from Seres Therapeutics, and consulting fees from DaVolterra, CSL Behring, Crestone Inc, and from MaaT Pharma. J.U.P. serves on an advisory board of and holds equity in Postbiotics Plus Research. J.U.P. has filed intellectual property applications related to the microbiome (reference numbers #62/843,849, #62/977,908, and #15/756,845). Memorial Sloan Kettering Cancer Center (MSK) has financial interests relative to Seres Therapeutics. E.H., M.A.J., J.L.K., and R.R.J. are inventors on a patent application by The University of Texas MD Anderson Cancer Center supported by results of the current study entitled, “Methods and Compositions for Treating Cancer therapy-induced Neutropenic Fever and/or GVHD.”, (Copyright © 2024 Elsevier Inc. All rights reserved.)

HLA-mismatched unrelated donors and haploidentical related donors are suitable stem cell sources for hematopoietic cell transplantation (HCT) when patients lack HLA-matched donors. Clinical outcome after mismatched HCT is influenced by HLA factors including the similarity of peptide-binding motifs (PBMs) between the patient and unrelated donor, and of the HLA-B leader in unrelated and haploidentical donors. Whether these factors can aid in the selection between mismatched unrelated and haploidentical donors is not known. To address this question, we investigated outcomes between the two donor types defined by matching for the PBM and leader peptide. We compared PBM-matched (n = 614) and mismatched (n = 958) MMUDs with calcineurin-inhibitor-based prophylaxis to four haploidentical groups that received post-transplant cyclophosphamide (PTCy)-based prophylaxis. The haploidentical groups were B-leader matched/DRB1-mismatched (n = 722), B-leader matched/DRB1-matched (n = 154), B-leader mismatched/DRB1-mismatched (n = 493), and B-leader mismatched/DRB1-matched (n = 63). Multivariate analysis showed that the B-leader matched/DRB1-mismatched haploidentical group had the best overall survival (OS) compared to the PBM-matched MMUD, while other haploidentical groups had comparable OS. The PBM-mismatched MMUD showed the poorest outcomes, similar to the B-leader mismatched/DRB1-matched haploidentical group. Among non-HLA factors, donor age was the most significant predictor of OS. These results suggest that a B-leader matched/DRB1 mismatched haploidentical donor might be the preferred choice among donors of similar age. If such a donor is not available, the youngest donor from either PBM-matched unrelated or other haploidentical groups could be a beneficial choice. These findings need validation with both donor groups receiving PTCy-based graft-versus-host disease prophylaxis., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

HLA-matched sibling donors (MSDs) are preferred for hematopoietic cell transplantation (HCT). However, the use of alternative donors, especially haploidentical, is increasing, as is our understanding of the impact of HLA factors such as B-leader and DRB1-matching on its outcomes. Yet, data comparing these donor types, particularly considering these HLA factors, is lacking. Herein, we compared haploidentical-HCT (n=1052) to MSD-HCT (n=400), both with posttransplant cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis. The haploidentical group included older patients (median 49 vs. 46 years) with younger donors (39 vs. 45 years) compared to MSD recipients. Other characteristics were similar. In multivariate analysis, haploidentical group had similar overall survival (OS) [hazard ratio (HR), [95% confidence interval] 0.94, [0.78-1.14], p=.54], non-relapse mortality (HR 0.98 [0.72-1.32], p=.87) and relapse (HR 0.87, [0.70-1.08], p=.20) as the MSD group. Younger donors age was a significant predictor of improved OS. Next, we directly compared the outcomes of 'younger' haploidentical (donor age <35 years, n=347) versus an 'older' MSD (donor age >=50 years, n=143) in 'older' recipients (patient age >=50 years). Patients with 'younger' haploidentical B-leader matched donors had significantly superior OS (HR 0.65, [0.48-0.90], p=.009) compared to 'older' MSD group. Additionally, patients with 'younger' DRB1-mismatched haploidentical donors (HR 0.63 [0.46-0.87], p=.004) had significantly lower risk of relapse than 'older' MSDs. Our study suggests that haploidentical-HCT may offer comparable outcomes to MSD-PTCy HCT. Moreover, among 'older' patients, a 'younger' haploidentical B-leader matched donor might be preferable to an 'older' MSD. These findings need validation in larger datasets., (Copyright © 2024 American Society of Hematology.)

Since 2005 there has been steady decline in chronic graft-versus-host disease (cGVHD) at Fred Hutchinson Cancer Center (FHCC). To better understand this phenomenon, we studied the risk of cGVHD requiring systemic immunosuppression (cGVHD-IS) as a function of hematopoietic cell transplantation (HCT)-date in 3066 survivors from 2005 through 2019. Cox regression models were fit to assess associations of HCT-date (as a continuous linear variable) with cause-specific hazards of cGVHD, using unadjusted and adjusted models. Median follow-up for study subjects was 7.0 years (range, 1.0-17.2). Two-year probabilities of cGVHD-IS declined among all survivors from 45-52% (2005-2007) to approximately 40% (2008-2012) and then further to ~26% by 2017. A decline was also observed when the analysis was restricted to 502 pediatric survivors, with cGVHD-IS probabilities being <10% since 2013. Among 305 adult and pediatric survivors who were transplanted for nonmalignant diseases, cGVHD rates showed greater fluctuation but remained <20% after 2016. Each 5-year increase in HCT-date was associated with a 27% decrease in the cause-specific hazard of cGVHD (unadjusted hazard ratio [HR] 0.73; 95% confidence interval [CI] 0.68-0.78, p<.0001); the HR was 0.81 (95% CI 0.75-0.87, p<.0001) even after adjusting for various factors (age, donor/stem-cell source, race, sex, conditioning intensity, GVHD prophylaxis, among others) that could lead to cGVHD reduction. The decline in cGVHD was not fully explained by demographic shifts and greater use of HCT approaches generally associated with lower cGVHD rates. This observation underscores that single-cohort cGVHD-prevention studies should use contemporaneous and not historical controls for comparisons., (Copyright © 2024 American Society of Hematology.)

Background & Aims: Epidemiologic evidence for dietary influence on colorectal cancer (CRC) risk through the gut microbiome remains limited., Methods: Leveraging 307 men and 212 women with stool metagenomes and dietary data, we characterized and validated a sex-specific dietary pattern associated with the CRC-related gut microbial signature (CRC Microbial Dietary Score [CMDS]). We evaluated the associations of CMDS with CRC risk according to Fusobacterium nucleatum, pks + Escherichia coli, and enterotoxigenic Bacteroides fragilis status in tumor tissue using Cox proportional hazards regression in the Health Professionals Follow-Up Study (1986-2018), Nurses' Health Study (1984-2020), and Nurses' Health Study II (1991-2019)., Results: The CMDS was characterized by high industrially processed food and low unprocessed fiber-rich food intakes. In 259,200 participants, we documented 3854 incident CRC cases over 6,467,378 person-years of follow-up. CMDS was associated with a higher risk of CRC (P trend < .001), with a multivariable hazard ratio (HR Q5 vs Q1 ) of 1.25 (95% CI, 1.13-1.39). The association remained after adjusting for previously established dietary patterns, for example, the Western and prudent diets. Notably, the association was stronger for tumoral F nucleatum-positive (HR Q5 vs Q1 , 2.51; 95% CI, 1.68-3.75; P trend < .001; P heterogeneity  = .03, positivity vs negativity), pks + E coli-positive (HR Q5 vs Q1 , 1.68; 95% CI, 0.84-3.38; P trend  = .005; P heterogeneity  = .01, positivity vs negativity), and enterotoxigenic Bacteroides fragilis-positive CRC (HR Q5 vs Q1 , 2.06; 95% CI, 1.10-3.88; P trend  = .016; P heterogeneity  = .06, positivity vs negativity), compared with their negative counterparts., Conclusions: CMDS was associated with increased CRC risk, especially for tumors with detectable F nucleatum, pks + E coli, and enterotoxigenic Bacteroides fragilis in tissue. Our findings support a potential role of the gut microbiome underlying the dietary effects on CRC., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

In 10/10 HLA-matched unrelated donor (MUD) hematopoietic cell transplantation (HCT) with calcineurin-inhibitor (CNI)-based prophylaxis, T-cell epitope DP-matched and permissive mismatched donors are associated with similar overall survival (OS) while donors with non-permissive mismatches should be avoided. Younger unrelated donors are also favored over older donors. We explored outcomes associated with different combinations of DP-matching and donor age (dichotomized at 35 years) to further guide donor selection. Using a Center for International Blood and Marrow Transplant Research dataset, we categorized 10,783 patients into six groups: DP-matched/younger donor (n=1591), DP-matched/older donor (n=526), permissive-mismatched/younger donor (n=3845), permissive-mismatched/older donor (n=1184), non-permissive mismatched/younger donor (n=2659), non-permissive mismatched/older donor (n=978). We noted that younger donor age, rather than DP-matching, was associated with better OS. Younger donors with permissive mismatches were associated with improved OS compared to older matched donors. Furthermore, younger donors with non-permissive mismatches were associated with improved OS compared to older donors with permissive mismatches. Our study adds further information about the association of DP-matching and donor age with HCT outcomes. Donor age should be prioritized over DP-matching in patients undergoing 10/10 HLA-MUD with CNI prophylaxis. Among those with younger donors, permissive-mismatched or DP-matched donors are preferred over non-permissive mismatched donors., (Copyright © 2024 American Society of Hematology.)

Background: Patients with multiple myeloma (MM) may be on therapy for years, which can lead to financial toxicity (FinTox) or time toxicity (TimeTox). The prevalence, predictors, and quality of life (QOL) impacts of FinTox and TimeTox during different phases of MM treatment have not been characterized., Patients and Methods: We conducted a single-center cross-sectional survey of patients with MM who had undergone transplantation. FinTox+ was defined as a COST-FACIT score <23, TimeTox+ as MM-related interactions (including phone calls) ≥1x weekly or ≥1x monthly in-person among far-residing patients, QOL using PROMIS Global Health, and functional status using patient-reported Karnofsky performance status (KPS)., Results: Of 252 patients, 22% and 40% met FinTox+ and TimeTox+ criteria respectively. Respective FinTox+ and TimeTox+ proportions were 22%/37% for patients on maintenance, 22%/82% with active therapy, and 20%/14% with observation. FinTox+ predictors included annual income (P < .01) and out-of-pocket costs (P < .01). TimeTox+ predictors included disease status (P < .001), caregiver status (P = .01), far-residing status (P < .001), and out-of-pocket costs (P = .03). FinTox+ was associated with a clinically meaningful decrease in mental QOL, while TimeTox+ patients were more likely to have KPS ≤ 80., Conclusions: In our large study, monetary status but not disease status predicted FinTox. Over a third of patients on maintenance reported TimeTox. FinTox+ was associated with decreased mental health, while TimeTox+ was associated with worse performance status. These two toxicities may negatively impact patient wellbeing, and studies of strategies to mitigate their impact are in development., Competing Interests: Disclosure COI: R.B.: Consulting: BMS, Caribou Biosciences, Genentech, Janssen, Karyopharm, Pfizer, Sanofi, SparkCures; Research: Novartis, Pack Health. AJC: Consulting: BMS, Adaptive; Research: Adaptive Biotechnologies, Harpoon, Nektar, BMS, Janssen, Sanofi, AbbVie. PAC: Research: Incyte, Janssen, AbbVie, and Sanofi. CJL: Consulting: Incyte, Sanofi, Frenesius; Honoraria: Sanofi, Kite, BMS, Kadmon; Research: Incyte. RSM: Research: Incyte, Kadmon, CSL Behring. NMK: Consulting: Astra Zeneca, Janssen, Pfizer, BMS, Beyond Springs, G1 Therapeutics, Sandoz, Seattle Genetics, Fresenius. SJL: Consulting: Equillium, Kadmon, Mallinckrodt, Novartis, Incyte.; Research funding: Amgen, AstraZeneca, Incyte, Kadmon, Pfizer, Sanofi, Syndax., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Frontline healthcare workers are at higher risk for COVID-19 infection and due to lack of availability of adequate personal protective equipment (PPE), lack of knowledge and good practices results in more deaths each year due to occupational accidents and diseases., Objective: The aim of the study was to assess the awareness of personal safety, the association between the level of awareness with selected socio-demographic variables and to identify the correlation between knowledge and practice of personal safety., Materials and Methods: A descriptive cross-sectional study design was conducted among 106 Frontline Healthcare workers who have worked in the COVID ward. The study was conducted between 7 August 2022 and June 2023. A convenient sampling technique was used for sample selection. A validated self-administered questionnaire was used to assess the awareness of personal safety. Descriptive statistics (mean, SD frequency and percentage) and inferential statistics (χ 2 and Spearman's correlation rank) were used for the data analysis., Results: Among the respondents, there were 38 doctors and 68 nurses. The majority of the respondents had a moderate level of knowledge (79.2%) and practice (52.8%) with a mean score of 13.52±2.10 and 14.51± 2.35, respectively. Doctors have slightly higher levels of knowledge (14.01±1.62) and practice (14.57±2.07) as compared to Nurses (13.19±2.27, 14.48±2.5), respectively. Knowledge was found to be associated with the education level and age of the respondents, and practice has a significant association with training/demonstration with a P value of less than 0.05. Knowledge and practice were found to have a partial positive correlation (r value of 0.27)., Conclusion: This study concluded that those having higher levels of education had good levels of knowledge and those who have attended formal or informal training or demonstrations regarding personal safety had good practices regarding personal safety., Competing Interests: The author declared no relevant financial conflict or any other conflict of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)