tbuckley/cabot-search huggingface dataset:
Demographics of cancer screening in Providence’s homeless population.
Authors: Boris Martinez, Pamela Jennings, Matthew Strick, Kevin Simon, Kerri Wolfe, Sharmi Patel, Howard Safran
Journal: Journal of Clinical Oncology (2024)

1585 Background: Adults experiencing homelessness have a higher incidence and mortality from cancer. It is estimated that almost 60% of homeless people in the US are from racial and ethnic minorities. Therefore, cancer mortality among the homeless may be an important disparity. In recent years homelessness has increased in Providence RI due to high rents and end of covid subsidies. The objective of this project was to learn about the demographics of the homeless population in Providence, focusing on risk factors for cancer and barriers to screening, to acquire the necessary information to develop interventions to improve cancer screening in the unhoused population. Methods: We conducted a cross-sectional survey of homeless individuals in Providence, RI. Survey data was obtained at homeless shelters, on the street, at soup kitchens and at other community events supporting the homeless. The largest single source of participants was those attending the Matthewson Street Church Friendship Breakfast on Sunday mornings. Results: Data was obtained from 278 homeless individuals from September 2023 to December 2023. 70% were male, 30% female. Age ranges included 28 (10%) &lt; 40 years, 78 (28%) 40-49 years, 88 (32%) 50-59 years, 74 (27%) 60-69 years and 10 (4%) &gt; 70 years. Race/ethnicity included 56% White, 18% Black, 13% Hispanic/Latino, 2% Native American, 9% multiracial and 2% other. 51% were sleeping in a shelter, 29% were unsheltered (including outside, car or tent), 12% “couch surfing”, and 7% were recently housed. Most participants (92%) had health insurance, the majority being state Medicaid, and had PCP visits (59%), mostly to community health centers, within the last 12 months. 72% of individuals were current cigarette smokers and 45% currently used alcohol. Among women, only 32% were on schedule for mammogram and 61% were on schedule for cervical cancer screening. Colon cancer screening rate for individuals &gt; 45 years was 32%. Only 32% of males over 50 had prostate cancer screening. Barriers identified included needing to have other needs met such as food and housing, lack of transportation to healthcare facilities, and lack of awareness about the need to undergo screening. Conclusions: The most common age range of homelessness in Providence, ages 50-59, is when cancer screening should be ongoing. There is a higher incidence of homelessness among minorities. The homeless population have high risk factors for cancer but screening rates for breast, cervical, lung, prostate and colon cancer are well below national guidelines. This represents a health disparity. Given the proportion of participants with a PCP and health insurance, interventions to improve cancer screening in this population may be feasible. We plan to develop educational partnerships with community health centers during the next phase of this initiative to increase awareness and uptake of screening recommendations.
A gene with a thousand alleles: The hyper-variable effectors of plant-parasitic nematodes
Authors: Unnati Sonawala, Helen Beasley, Peter Thorpe, Kyriakos Varypatakis, Beatrice Senatori, John T. Jones, Lida Derevnina, Sebastian Eves-van den Akker
Journal: Cell Genomics (2024)

Pathogens are engaged in a fierce evolutionary arms race with their host. The genes at the forefront of the engagement between kingdoms are often part of diverse and highly mutable gene families. Even in this context, we discovered unprecedented variation in the hyper-variable (HYP) effectors of plant-parasitic nematodes. HYP effectors are single-gene loci that potentially harbor thousands of alleles. Alleles vary in the organization, as well as the number, of motifs within a central hyper-variable domain (HVD). We dramatically expand the HYP repertoire of two plant-parasitic nematodes and define distinct species-specific "rules" underlying the apparently flawless genetic rearrangements. Finally, by analyzing the HYPs in 68 individual nematodes, we unexpectedly found that despite the huge number of alleles, most individuals are germline homozygous. These data support a mechanism of programmed genetic variation, termed HVD editing, where alterations are locus specific, strictly governed by rules, and theoretically produce thousands of variants without errors.
Intestinal CXCR6+ ILC3s migrate to the kidney and exacerbate renal fibrosis via IL-23 receptor signaling enhanced by PD-1 expression
Authors: Zhou Liang, Ziwen Tang, Changjian Zhu, Feng Li, Shuaijiabin Chen, Xu Han, Ruilin Zheng, Xinrong Hu, Ruoni Lin, Qiaoqiao Pei, Changjun Yin, Ji Wang, Ce Tang, Nan Cao, Jincun Zhao, Rong Wang, Xiaoyan Li, Ning Luo, Qiong Wen, Jianwen Yu, Jianbo Li, Xi Xia, Xunhua Zheng, Xin Wang, Naya Huang, Zhong Zhong, Chengqiang Mo, Peisong Chen, Yating Wang, Jinjin Fan, Yun Guo, Haojie Zhong, Jiaqi Liu, Zhenwei Peng, Haiping Mao, Guo-Ping Shi, Joseph V. Bonventre, Wei Chen, Yi Zhou
Journal: Immunity (2024)
FDA Approval Summary: Fruquintinib for the Treatment of Refractory Metastatic Colorectal Cancer
Authors: Michael J. Fusco, Sandra J. Casak, Sirisha L. Mushti, Joyce Cheng, Brian J. Christmas, Matthew D. Thompson, Wentao Fu, Hezhen Wang, Miyoung Yoon, Yuching Yang, Jason N. Moore, Youwei Bi, Yang Nan, Craig E. Long, Doris Auth, Nam A. Rahman, Shenghui Tang, Richard Pazdur, Lola A. Fashoyin-Aje, Paul G. Kluetz, Steven J. Lemery
Journal: Clinical Cancer Research (2024)

Abstract On November 8, 2023, the FDA approved fruquintinib, an inhibitor of vascular endothelial growth factor receptor (VEGFR)-1, -2, and -3, for the treatment of patients with metastatic colorectal cancer (mCRC) who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF therapy, and if RAS wild-type and medically appropriate, an anti-EGFR therapy. Approval was based on Study FRESCO-2, a globally conducted, double-blind, placebo-controlled randomized trial. The primary endpoint was overall survival (OS). The key secondary endpoint was progression-free survival. A total of 691 patients were randomly assigned (461 and 230 into the fruquintinib and placebo arms, respectively). Fruquintinib provided a statistically significant improvement in OS with a hazard ratio (HR) of 0.66 [95% confidence interval (CI), 0.55, 0.80; P &amp;lt; 0.001]. The median OS was 7.4 months (95% CI, 6.7, 8.2) in the fruquintinib arm and 4.8 months (95% CI, 4.0, 5.8) for the placebo arm. Adverse events observed were generally consistent with the known safety profile associated with the inhibition of VEGFR. The results of FRESCO-2 were supported by the FRESCO study, a double-blind, single-country, placebo-controlled, randomized trial in patients with refractory mCRC who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy. In FRESCO, the OS HR was 0.65 (95% CI, 0.51, 0.83; P &amp;lt; 0.001). FDA concluded that the totality of the evidence from FRESCO-2 and FRESCO supported an indication for patients with mCRC with prior treatment with fluoropyrimidine, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type and medically appropriate, an anti-EGFR therapy.
Start low, go slow: A systematic review and meta-analysis of upfront tailored treatment dosing in older adults with advanced cancer.
Authors: Gabriel Aleixo, William J. Ferrell, Julianne Ani, Tej A. Patel, Ravi Bharat Parikh, Ramy Sedhom
Journal: Journal of Clinical Oncology (2024)

1625 Background: Older adults aged ≥65 with advanced cancer are underrepresented in treatment trials. This gap limits informed decision-making regarding the dose and tolerability of proposed therapies. Standard chemotherapy is associated with &gt;50% serious adverse event rate among older adults, with frequent dose reduction and early treatment discontinuation. A "start low, go slow" (SLGS) approach begins systemic therapy at lower-than-standard doses and increases the dose if well-tolerated. This alternative dosing strategy has shown value in minimizing adverse events and functional decline without compromising the overall effectiveness of treatments. We conducted the first systematic review and meta-analysis of SLGS effectiveness among older adults across advanced cancers. Methods: This review, was registered with PROSPERO and adhered to PRISMA criteria, covering PubMed, Journal of Geriatric Oncology and EMBASE from January 2000 until December 15, 2024. Eligible study designs were randomized controlled trials, retrospective trials, and non-randomized clinical trials with patients with advanced cancers who underwent systemic therapy. We reported all studies that studied the SLGS approach. Our studied outcomes were overall survival (OS), progression-free survival (PFS), treatment discontinuation, and toxicity. Data extraction included author, patient, cancer type, treatment, and survival outcomes. A meta-analysis using fixed effects and risk ratios (RR) was performed when sufficient data was available; significant outcomes had α&lt;0.05. Results: Our search identified 13 studies testing SLGS strategies in oncology, including 3,508 patients, with a median age 63-78 years. The -represented cancers included colorectal (6 studies, 3059 patients total), lung (2 studies, 113 pts), chronic myeloid leukemia (2 studies, 127 pts), non-Hodgkin lymphoma (1 study, 45 pts), and prostate (2 studies, 164 pts) cancers. Ten (77%) studies assessed OS and PFS. Five studies (39%) compared SLGS against standard doses, finding no significant differences in PFS and OS across all trials. Dose escalation rates for SLGS ranged from 5% to 60%. The ability to complete planned cycles was higher with SLGS compared to standard dose (1 study, 43% vs 26%, p=0.04). Treatment discontinuation was not different for SLGL vs. standard dose (5 studies, meta-analysis RR 1.07, 95% CI 0.90-1.27, p=0.42). Toxicity ranged from 5% to 89% across studies; SLGS had lower grade ≥3 adverse events compared to standard dose (4 studies, meta-analysis RR 0.88, 95% CI 0.80-0.94, p &lt; 0.001). Conclusions: This is the first systematic review and meta-analysis analyzing the SLGS approach to systemic therapy dosing in older adults with advanced cancer. Compared to standard-dose systemic therapy, older adults pursuing a SLGS strategy had greater completion of planned cycles, reduced toxicity, and similar survival.
Identifying factors underlying increased emergency care needs of Black patients with pancreas cancer.
Authors: Kristen M John, Tanya C. Louis, Deepak Saluja, Daniel King
Journal: Journal of Clinical Oncology (2024)

e13749 Background: In a retrospective study, we observed that African American/Black patients are 2.8x more likely to have recurrent ED visits than non-Black patients. These findings motivated this prospective study using a standardized questionnaire to better understand the factors leading to ED visits among Black patients. Methods: A study of Black patients with pancreas cancer who had at least 1 ED visit in a 5 month period in 2022-2023 was conducted. Computational identification of health system encounters by patients with pancreas cancer was performed using ICD10 C25* as a cohort identifier. The cohort was filtered by encounter type for ED and self-reported race for Black. Weekly, an African American oncology nurse practitioner called these patients to administer a questionnaire regarding social determinants of health and discuss reasons underlying the ED visit. Three attempts were made to contact each patient. Demographic and clinical features were obtained from the electronic health record. Results: During this 5-month period, 31 patients meeting criteria were identified; among these 31 who had at least 1 ED visit, 45% had ≥2 ED visits and 13% had ≥5 ED visits. The cohort was 68% female with mean age of 70.3 and median household income of $92,608. 74% had non-metastatic disease and 35% were on chemotherapy at the time of visit. 52% of patients had Medicare, 35% had commercial insurance, 10% had Medicaid, and 3% were uninsured. We reached 55% patients, of whom 71% agreed to participate. Notably, 83% endorsed high school as their highest level of education, 25% were immigrants to the United States, and 17% experienced financial barriers to care (Table). 33% had been seen at our institution’s pancreas cancer multidisciplinary clinic. Two recurrent themes noted during discussions with these patients were that that those with multiple ED visits were nearing end-of-life and/or had caretakers or family members in the medical field. Conclusions: We identified female gender, education level, immigrant status, and financial barriers to care as themes associated with ED visit burden in Black patients with pancreas cancer. Having caretakers in the medical field, who may have witnessed the consequences of healthcare disparities, may also contribute to higher rates of ED use. We hope to use these data to inform interventions to address these disparities. [Table: see text]
Impact of extent of disease at presentation on oncologic outcomes according to pathologic response to neoadjuvant systemic therapy among participants of the I-SPY2 clinical trial.
Authors: Roberto Antonio Leon-Ferre, Katrina Dimitroff, Christina Yau, Karthik Giridhar, Rita A. Mukhtar, Gillian L. Hirst, Nola Hylton, W. Fraser Fraser Symmans, Matthew P. Goetz, Laura Esserman, Judy Caroline Boughey
Journal: Journal of Clinical Oncology (2024)

594 Background: Recent analyses in HER2+ and triple negative (TN) breast cancer (BC) treated with neoadjuvant systemic therapy (NAST) suggest that extent of disease at presentation (tumor [T] size and nodal [N] involvement) influences outcomes independently of response to NAST, even in the context of pathologic complete response (pCR). Given this, we evaluated the association of clinical T and N status prior to NAST with long-term outcomes in I-SPY2. Methods: We identified patients (pts) with TN and HER2+ BC who received NAST on the I-SPY2 trial with available clinical T size and N status prior to NAST, pathologic response after NAST, and follow up for recurrence and survival. We conducted univariable and multivariable (MV) Cox proportional models for Event Free (EFS), Distant Recurrence Free (DRFS), and Overall Survival (OS) in TN and HER2+ BC according to response after NAST, adjusting for residual cancer burden (RCB) category. Results: Of 1,170 pts with TN or HER2+ BC, 1,013 were eligible (TN: 623 and HER2+: 390), after 157 pts were excluded due to missing critical variables. Median follow up was 4.4 years (range 0.3-10.2). Median age was 48 for TN and 49 for HER2+ BC. Following NAST, pCR was achieved in 277 (45%) pts with TN and 197 (51%) pts with HER2+ BC. Among pts with pCR, separate MV analyses for TN and HER2+ BC showed no independent association between clinical T and N category with EFS, DRFS or OS (p values all &gt; 0.05). However, among pts with residual disease, clinical T category (but not clinical N status) prior to NAST retained independent prognostic information in both TN and HER2+ BC in a MV model adjusting for age, RCB class, and hormone receptor status (for HER2+ BC). Compared to cT1-2, cT3-4 stage at diagnosis was associated with worse EFS, DRFS, and OS in TNBC, and with worse EFS, DRFS (but not OS) in HER2+ BC (Table). Additionally, hormone receptor status was independently associated with outcomes in HER2+ BC with residual disease (data not shown). The 5y EFS for cT1-2 vs cT3-4 according to RCB class in TNBC were: RCB0: 94% vs 95%, RCB1: 90% vs 65%, RCB2: 74% vs 44% and RCB3: 45% vs 20%. The 5y EFS for cT1-2 vs cT3-4 according to RCB class in HER2+ were: RCB0: 95% vs 88%, RCB1: 89% vs 84%, RCB2: 85% vs 64% and RCB3: 56% vs 50%. Conclusions: Tumor size (but not N involvement) prior to NAST was independently associated with outcomes in TN and HER2+ BC with residual disease, independently of RCB class. TN and HER2+ BC achieving pCR exhibited favorable outcomes regardless of extent of disease prior to NAST. These data are consistent with prior findings of the Neobioscore contributing only in the context of residual disease. Clinical trial information: NCT01042379 . [Table: see text]
Therapeutic response and outcomes with less common breast cancer subtypes in the I-SPY trial 2011-2022.
Authors: Alexandra Thomas, Denise M. Wolf, Ronald Balassanian, Yunn-Yi Chen, Julia Ye, Poonam Vohra, Evin H Gulbahce, Alexander D. Borowsky, Lamorna Brown Swigart, Gillian L. Hirst, Sara Venters, Rita Nanda, Rebecca Arielle Shatsky, Ralph D'Agostino, Rita A. Mukhtar, Sarah Hatcher, Christina Yau, Angela DeMichele, Laura van 't Veer, Laura Esserman
Journal: Journal of Clinical Oncology (2024)

582 Background: Uncommon histologies are over-represented among high-risk breast cancer (BC) and denote an area with limited trial data and of significant unmet medical need. To better understand trial outcomes in this group and identify signals of tumor responsiveness, we report pathologic complete response (pCR) and early event-free survival (EFS) by disease subtype in the I-SPY2 trial. Additionally, the I-SPY2 trial currently utilizes a combination of tumor molecular signature and receptor status to determine response predictive subtype (RPS) first developed from 987 I-SPY2 patients (1). We report disease response rates for those who received what is now known to be optimal RPS guided therapy. Methods: The I-SPY2 platform trial tests novel agents given neo-adjuvantly with a chemotherapy backbone in high-risk BC (HER2 positive, triple negative and high molecular risk estrogen receptor positive BC). Histologic images of research biopsies, local biopsy and surgical pathology reports were reviewed centrally by I-SPY pathologists. Receptor subtype distribution and pCR rates were summarized. EFS was estimated using the Kaplan Meier method. Association between pCR and EFS was evaluated using the Cox proportional hazard model with significance assessed by the log rank test. Results: 144/2118 (7%) of I-SPY2 participants were identified with metaplastic (60), lobular (55), mucinous (9), micropapillary (8), neuroendocrine (4) and other (8) BCs. Tumor receptor status, pCR rate and EFS by tumor type are shown in the Table. For the full cohort, pCR was associated with better EFS (hazard ratio (95% CI): 0.12 (0.02 - 0.88), p = 0.01). Within metaplastic (metapBC) 11/32 (34%) and 5/28 (18%) patients had a pCR with or without checkpoint blockade, respectively. By RPS group, 9 of 18 (50%) (13 metapBC, 3 other, 2 lobular) in the HER2-Immune+ group who received RPS optimized therapy had a pCR. In this group 6/13 (46%) with metapBC had a pCR. In the HER2+ driven RPS groups, pCR rate in the HER+HER2orBasal was 88% (7/8) and 0% (0/3) in the HER2+Luminal. Conclusions: High pCR rates observed in metapBC and other among subsets of often difficult to treat BC subtypes support novel approaches and provide a roadmap for future study of uncommon BCs. Outcomes were improved when therapy matched RPS vulnerabilities. Participants presenting with uncommon BC subtypes will be prospectively identified in the I-SPY2.2 trial to further develop effective approaches for this group. 1. Wolf et al, Cancer Cell 2022. Clinical trial information: NCT01042379 . [Table: see text]
Association of circulating T lymphocytes and their functional states with pathologic complete response (pCR) in breast cancer (BC). A prospective Italian study.
Authors: Rahma Ben Ayed, Benedetta Conte, Veronica Martini, Renzo Boldorini, Simone Gobbato, Beatrice Ruffilli, Francesca Vezzoli, Rami Alsati, Letizia Negrini, Nicole Sala, Letizia Matera, Carmen Branni, Ivan Dodaro, Anna Gambaro, Valentina Rossi, Francesca D'Avanzo, Alessandra Gennari
Journal: Journal of Clinical Oncology (2024)

559 Background: In BC, pCR is associated with substantial survival benefit. Hence, escalated neoadjuvant treatments (NATs) are being increasingly employed to improve pCR rates, warranting biomarkers for better patients’ selection. T-cell exhaustion and senescence are dysfunctional states that coexist in patients with cancer, impairing antitumor immunity and sustaining a suppressive immune microenvironment. Here, we assessed the impact of such states on pCR across different BC subtypes and NATs. Methods: This is a prospective study on patients undergoing NAT for BC at the Maggiore Hospital of Novara, Italy. Blood was collected at baseline and after NAT. Circulating T lymphocytes were characterized with exhausted (CD28, PD1, LAG3) and senescent (CD57, KLRG-1) biomarkers utilizing flow cytometry. Neutrophiles/lymphocytes ratio (NLR) and lymphocytes/monocytes ratio (LMR) were also retrieved. Subpopulations with frequency &lt;1% were normalized for total CD3+ cells. Results: From October 2020 to January 2024, 134 patients were enrolled and 115 completed NAT (85.8%). Fifty-one (38,1%) had adequate samples for analysis, 16 (31,4%) with hormone receptor positive HER2 negative BC (HR+HER2-), 15 (29,4%) with HER2+, and 20 (39,2%) with triple negative BC (TN). At baseline, patients with TNBC had the lowest NLR (p=0.018) and lowest senescent CD4+CD28- (p=0.042). Associations with pCR are shown in the Table. Overall, LMR associated with increased pCR (OR 1.34 [95% CIs 1.00-1.89]), and NLR with decreased pCR (OR 0.67 [0.39-1.04]). Both associations were driven by HR+ status (interaction p = 0.061 and 0.060). Senescent CD4+ predicted lower pCR in both HR-HER2+ (OR 0.10 [0.01-0.36]) and TNBC (OR 0.10 [0.01-0.5]). In TNBC, exhausted CD8+ predicted higher pCR (OR 1.78 [1.08-3.79]). When assessed separately in patients who received NAT with or without pembrolizumab, exhausted CD8+ remained predictor of pCR in chemotherapy + pembrolizumab (OR 1.84 [1.03-5.00]), but not with chemotherapy alone (p=0.203). The dynamics of paired pre-NAT and post-NAT TNBC samples revealed significant differences. Senescent CD4+ increased after chemotherapy, but not with chemotherapy + pembrolizumab (p=0.007). Pembrolizumab was associated with depletion of PD1-positive CD8+, while chemotherapy alone was not (p=0.020). Conclusions: The characterization of circulating T lymphocytes could help identify patients who benefit more in terms of pCR from specific NATs, including chemoimmunotherapy. [Table: see text]