tbuckley/cabot-search huggingface dataset:
Identifying genetic susceptibility for severe cardiac events in testicular cancer survivors.
Authors: Arkajyoti Bhattacharya, Ellen Laura Dorien Volders, Sjoukje Lubberts, Coby Meijer, Jan M. Kerst, Ronald De Wit, Sasja F. Mulder, Britt B.M. Suelmann, Flora Van Leeuwen, Rudolf Stephan Nicolaas Fehrmann, Michael Schaapveld, Jourik A. Gietema
Journal: Journal of Clinical Oncology (2025)

12048 Background: Testicular cancer (TC) survivors face an increased risk of cardiovascular diseases (CVD) as a late adverse effect of oncological treatment, especially after cisplatin-based chemotherapy. To explore genetic susceptibility, we performed a genome-wide association study using hierarchical clustering and assessed impact of polygenic risk scores (PRS). Methods: A subcohort of TC patients treated at expert centers in the Netherlands between 1976 and 2007 was established by hospital stratified random sampling, and enriched with all identified cases of severe CVD (coronary artery disease, myocardial infarction, heart failure) of the entire cohort (Lubberts et al J Clin Oncol 41:3512-3522, 2023). Genotyping was performed using the Global Screening Array. The study population consisted of 396 TC patients: 92 survivors with cardiac disease and 304 survivors without cardiac disease. Seven general population derived PRSs from the CARDIoGRAMplusC4D consortium were applied to assess cardiac risk, followed by hierarchical SNP aggregation based on linkage disequilibrium to identify cardiac risk-associated SNPs. These SNPs were used for co-functionality analysis and decision tree analyses to develop novel PRSs. Results: Five of the seven external PRSs were significantly associated with cardiac risk, explaining 8%-12% of the variance, with the CARDIoGRAM GWAS PRS showing the strongest association. Patient’s age at diagnosis explained the largest variance in cardiac risk (21%). Hierarchical SNP aggregation identified 67 cardiac risk-associated SNPs, individually explaining 3% - 12% of the variance. Co-functionality analysis revealed biological processes, including cardiovascular development, immune signaling, and DNA damage repair, as potential mediators of these SNPs' effects. Using decision tree analysis, a novel PRS was developed incorporating CVD risk-associated SNPs and clinical risk factors at start of treatment. This PRS+ achieved the highest concordance statistic of 0.783 (standard error 0.022) and explained maximum variance (50%) among all tested models. This PRS+ identified that patients diagnosed at age &gt; 41 years had higher cardiac risk, independent of genotype data. Whereas a subset of patients diagnosed at age ≤41 years could be identified as having increased cardiac risk based on the minor allele frequency of five SNPs (rs6830970, rs17666409, rs10782601, rs2446862, rs767707). Conclusions: This study introduces a novel PRS to identify TC patients with a higher risk of CVD, enabling the development of personalized cardiovascular risk management strategies at the start of their cancer treatment. It also advances understanding of the biological mechanisms underlying this increased risk. Clinical trial information: NCT02276430 .
Differences in supportive care service utilization among long term metastatic breast cancer survivors by rurality.
Authors: Ashley Pariser Davenport, Chloe Hery, Kayla Willams, Juan Peng, Michelle Joy Naughton
Journal: Journal of Clinical Oncology (2025)

12093 Background: Patients living with metastatic breast cancer (MBC) have unique psychosocial and medical needs, which often go unrecognized. Many patients living in rural areas travel farther for care. We examined differences in supportive care service referrals and utilization by sociodemographic, psychosocial, and clinical predictors among long term MBC survivors living in rural versus urban areas. Methods: 233 patients from the Ohio State University Stefanie Spielman Comprehensive Breast Center, who had been diagnosed with MBC for ≥1 year, were asked to complete a one-time, online survey to assess their demographic characteristics, quality of life, self-rated health, symptoms, and supportive care needs. Chi-square and fisher exact tests were used for categorical variables and two sample t-tests were used for continuous variables to determine sociodemographic (age, race, education, income, rural/urban residency), psychosocial/quality of life (PROMIS physical component score, PROMIS mental component score, MOS social support), and clinical factors (time since diagnosis, current treatment, metastasis site, fatigue, pain, and sleep) associated with utilization of supportive care services. Results: 66 patients residing in rural areas (RURAL) and 167 patients residing in urban areas (URBAN) were recruited. There was a higher rate of supportive care service utilization among URBAN (n=82, 49.1%) versus RURAL (n=22, 33.3%) patients. For URBAN, service utilization was associated with lower (worse) PROMIS physical scores, PROMIS mental scores, MOS social support total scores, and greater fatigue and pain scores. However, no significant associations were seen for RURAL. Higher education and income levels were associated with increased service utilization for RURAL, but not URBAN participants. The Table details referral and utilization rates for the top 5 supportive care services. Conclusions: Patients living in rural areas had lower supportive care utilization compared to patients living in urban areas. However, urban patients reported worse PROMIS and social support scores. While a no cost service (dietitian) had similar utilization rates between URBAN and RURAL, another (James Care for Life programs) did not. Services amenable to same day coordination had no statistical differences in utilization rates between URBAN and RURAL. More research is needed to evaluate the impact of distance, financial, and time barriers on equitable access to supportive care services. Top 5 supportive care referrals and utilization. Rural Urban Referred Utilized Referred Utilized Counseling 8 (12.1%) 4 (50%) 34 (20.4%) 20 (58.8%) Dietitian 11 (16.7%) 8 (72.7%) 35 (21%) 27 (77.1%) James Care for Life Programs 8 (12.1%) 3 (37.5%) 27 (16.2%) 15 (75%) Living Well with Advanced Breast Cancer Clinic 14 (21.2%) 2 (14.3%) 20 (12%) 15 (75%) Physical Therapy 7 (10.6%) 6 (85.7%) 36 (21.6%) 29 (75%)
Out of touch: Understanding the frequency and trajectory of chemotherapy-induced neuropathy peripheral (CIPN) in breast cancer survivors.
Authors: Savannah Liddell, Ioannis Kournoutas, Robert A. Vierkant, Nicole Larson, Janet E. Olson, Fergus Couch, Elizabeth Jane Cathcart-Rake, Charles L. Loprinzi, Kathryn Jean Ruddy
Journal: Journal of Clinical Oncology (2025)

12038 Background: CIPN, primarily associated with sensory neuropathy rather than motor or autonomic dysfunction, is a potentially long-term complication of cancer treatment including taxanes and platinums (T/Ps), and can negatively impact quality of life for breast cancer (BC) survivors. This project aims to quantify the severity of neuropathic symptoms at one and three years after diagnosis in BC survivors, comparing recipients of T/P to non-recipients. Methods: In the Mayo Clinic Breast Registry (MCBDR), a longitudinal cohort, surveys and medical record data from patients with stage 1-3 BC were used to understand the burden of neuropathic symptoms at 1- and 3-years post-diagnosis (denoted as Y1 and Y3). Y1 and Y3 raw scores from The Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20 (CIPN20) composite (CIPN20-C) and sensory subscale (CIPN-S) were converted to a 0-100 point scale, with lower scores corresponding to worse symptoms. Patients with BC recurrence prior to Y3 or incomplete surveys were excluded. We used two sample t-tests and multivariable linear regression modeling to compare recipients of T/P to non-recipients of T/P (with threshold for statistical significance p &lt;0.05). Results: 786 patients were included, 112 of whom (14.2%) received T/P. T/P recipients were younger (p&lt;0.001), more likely to have Stage II/III disease (p&lt;0.001), and less likely to have received endocrine therapy (p&lt;0.001). Univariate analyses revealed worse CIPN20-C score at Y1 (p=0.02) and worse CIPN20-S scores (p=0.004) at Y1 and Y3 in T/P recipients compared to non-recipients (Table). However, differences between the groups were no longer statistically significant after adjustment for age, stage and endocrine therapy. Conclusions: In this cohort, neuropathic symptom severity at Y1 and Y3 after a breast cancer diagnosis did not differ between recipients of taxane and/or platinum agents and nonrecipients after adjustment for age, stage, and endocrine therapy. These data may reassure patients and clinicians who are concerned about CIPN and considering use of these chemotherapies in this setting. Patient demographics and CIPN20 results. Clinical characteristic T/P recipients Non-recipients of T/P Age at diagnosis, mean (SD) 55.3 (11.6)* 59.8 (11.9) White race, N (%) 108 (96.4%) 660 (97.9%) Clinical stage II/III, N (%) 76 (68.5%)* 250 (37.5%) Endocrine therapy, N (%) 73 (65.2%)* 636 (94.4%) Diabetes mellitus, N (%) 9 (8.9%) 52 (8.6%) Y1 CIPN20-C score, mean (SD) 89.6 (10.9)* 92.0 (9.7) Y3 CIPN-C score, mean (SD) 89.4 (11.4) 91.1 (9.7) Y1 CIPN20- S score, mean (SD) 87.3 (15.1)* 91.3 (13.0) Y3 CIPN20-S score, mean (SD) 88.2 (14.1)* 91.1 (11.7) *Statistically significant (p &lt;0.05) on univariate analysis.
Impact of neighborhood disadvantage and residential isolation on cognitive outcomes in cancer survivors.
Authors: Noha Sharafeldin, Ariann Nassel, Andie Grimm, Donna Murdaugh, Elizabeth Baker, Gabriela R. Oates
Journal: Journal of Clinical Oncology (2025)

12056 Background: The Social Vulnerability Index (SVI), a composite measure of socioeconomic deprivation, household composition, minority status, and housing type and transportation, is a reliable marker of neighborhood disadvantage. Residential Segregation measures the degree to which a minority group is distributed differently than the majority group across census tracts. The isolation index is a measure of segragation that captures the extent to which minority members are exposed only to one another. These measures have been associated with poor survival in patients with cancer, yet studies on adverse outcomes in surviors are limited. Cognitive impairment is an adverse outcome highly prevalent in up to 40% and persists up to 5y in hematologic cancer survivors treated with blood or marrow transplantation (BMT). We postulate that neighbohood disadvantage and residential isolation may have a negative effect on cognitive outcomes in BMT survivors. Methods: We included 71 patients treated with allogeneic BMT, enrolled in the the Cognitive Training and Genetics Attitudes (cTAG) study. Objective cognitive function was measured using a comprehensive in-person battery of standardized neuropsychological tests. Standardized T-scores were categorized as deficit scores (range 0 to 5), and averaged across all tests to estimate a global deficit score(GDS), which was used as a measure of cognitive impairment. Residential addresses, geocoded and joined to corresponding Census block group and tract, were used to match patients with their corresponding SVI and residential segregation scores. Multivariable logistic regression models adjusted for age, sex, race, and clustering at the tract level were used to estimate associations with GDS. Results: Median age at study participation was 58y (IQR: 46, 63), 57.8% were male, and 16.9% were non-Hispanic Black. Primary diagnosis was 66.2% acute leukemia and 22.5 myelodysplastic/myeloproliferative neoplasms. Average time since BMT was 1.5y (SD = 1.2). Prevalence of global cognitive impairment was 19.7% (95%CI: 11.2-30.9). A high overall SVI score was associated with GDS (aOR = 4.7, 95%CI: 1.1, 20.2, p = 0.035). Vulnerability related to socioeconomic status (aOR = 4.9, 95%CI: 1.2, 20.2, p = 0.03) and housing type and transportation (aOR = 4.0, 95%CI: 1.1, 15.2, p = 0.04) were significantly associated with GDS. Higher residential isolation index ( &gt; 0.6) was significantly associated with increase in GDS (aOR = 5.4, 95%CI: 1.3, 22.5, p = 0.02) adjusting for age, sex, race, and clustering at the tract level. Conclusions: Cancer survivors residing in areas with higher indicators of social vulnerability and isolation are at increased risk of cognitive decline post-BMT. These findings highlight the overall need for dedicating appropriate resources and care planning especially for individuals surrounded by others from their same group within their residential areas.
PROPAN: Bayesian dose-finding of propranolol combined with metronomic fixed-dose cyclophosphamide based on bivariate efficacy-tolerability outcomes in patients with locally advanced or metastatic angiosarcoma (LAMA): A phase I-II sequential trial by the French Sarcoma Group.
Authors: Sebastien Salas, Christine Chevreau, Elisabeth Jouve, Nicolas Penel, Axel Le Cesne, Emmanuelle Bompas, Francois Bertucci, Jean Emmanuel Kurtz, Nicolas Isambert, Loic Chaigneau, Joelle Micallef, Eva Foinet, Nicolas Andre, Sarah Zohar, Jean-Yves Blay
Journal: Journal of Clinical Oncology (2025)

e23542 Background: Angiosarcoma is a rare, aggressive vascular malignancy with limited treatment options. Preclinical data suggest beta-adrenergic blockers like propranolol may have anti-tumor effects. Only one window-of-opportunity trial (Embaby et al., 2024) has prospectively evaluated the activity of propranolol in angiosarcoma. Propranolol's efficacy is believed to fluctuate dose-dependently. We used an innovative phase I-II dose-finding method integrating toxicity, efficacy, and a time-to-event parameter (Rivière et al., 2018), tailored to small samples and optimizing recruitment. The PROPAN trial aimed to determine the optimal dose of propranolol combined with metronomic cyclophosphamide in patients with LAMA, using a sequential dose-finding design based on a bivariate continual reassessment method. Methods: Patients were enrolled in cohorts of 2, with sequential dose adaptations made for the next cohort among three dose levels (80, 120, or 160 mg/d) based on toxicity (grade ≥3 at 1 month per NCI-CTCAE v4.0) and efficacy (non-progression rate at 3 months per RECIST 1.1). The safe most successful dose (sMSD) was determined using a Bayesian model (dfmta package), balancing an non progression efficacy of 15, 30 and 50 % for respectively 80, 120 and 160 mg/j and ≤25% toxicity). This approach determined the next adapted dose based only on toxicity assessed early compared to efficacy, reducing waiting time between cohorts. The trial ended early if all doses failed efficacy or exceeded toxicity targets, with a maximum of 24 patients. Results: Fifteen patients were enrolled, with 12 used for dose optimization. 2 patients were treated in the second line, and the others in the third lines Efficacy data were unavailable for 3 in the final model. One grade 3 toxicity (dyspnea at 120 mg/d) was reported, and 4 patients met the non-progression endpoint at 3 months (3 at 80 mg/d, 1 at 120 mg/d). The final model identifies 80 mg/day as the optimal dose minimizing toxicity, with no efficacy gain at higher doses. Median progression-free survival was 3 months (0.7-6). Conclusions: This trial confirms a favorable safety profile but limited efficacy. This innovative method demonstrates feasibility for rare diseases. However, dose adjustment based on early toxicity assessment optimizes patient recruitment but risks over-reliance on toxicity data for dose optimization. Clinical trial information: NCT02732678 .
Sorafenib plus hepatic arterial infusion chemotherapy versus sorafenib plus transarterial chemoembolization in advanced hepatocellular carcinoma: An update on SHATA-001 study.
Authors: Zefeng Du, Zhicheng Lai, Anna Kan, MinKe He, Ming Shi
Journal: Journal of Clinical Oncology (2025)

4100 Background: Although sorafenib plus transcatheter arterial chemoembolization (SoraTACE) has been widely applied for advanced hepatocellular carcinoma (HCC) in most Asian countries, sorafenib plus hepatic arteria infusion chemotherapy (SoraHAIC) may be a better alternative. Herein, we compared the efficacy and safety between the two groups in advanced HCC. Additionally, we validated a predictive model from our previous phase III trial (NCT02973685, cohort1). Methods: This phase III trial (NCT02856126) recruited participants with advanced HCC. Eligible participants were randomly assigned (2:1) to receive Sorafenib (400mg orally twice daily) plus HAIC per 3 weeks or TACE until disease progression or unacceptable toxicity. The Primary endpoint was overall survival (OS). Whole-exome sequencing (WES), RNA sequencing, and DNA methylation analysis of tumor biopsy samples were performed for predictive biomarker exploration (cohort 1) and validation (SHATA-001). Results: From August 2016 to October 2020, a total of 207 participants were allocated to receive SoraHAIC (n = 141) or SoraTACE (n = 66). The trial met the prespecified endpoints. SoraHAIC significantly prolonged OS compared to SoraTACE (median OS, 15.7 versus 11.2 months; p &lt; 0.001). In the SoraTACE group, 56.7% of participants experienced grade 3 or 4 treatment-related adverse events, which were significantly higher than the SoraHAIC group (39.3%; p &lt; 0.023). Severe adverse events were also more frequent in SoraTACE (15.7% vs 26.7%, p = 0.07). WES analysis found no ideal indicator in the mutational landscape for treatment outcome. We identified 1226 and 506 differentially methylated probes (DMPs) among the non-responsive specimens in the HAIC and TACE groups. Then we performed RNA-seq analysis. By comparing the transcriptome between the responsive and non-responsive groups, 685 and 600 differentially expressed genes (DEGs) were generated in the two treatment groups, respectively. In the HAIC group, pathways including leukocyte-mediated immunity and immune response-activating signaling pathway were enriched in the responders, while metabolic-related pathways including steroid metabolic process and alcohol biosynthetic process were enriched in the non-responders in the TACE group. Integrative analysis of DEGs and DMPs indicated phosphofructokinase (PFKM) could potentially stratify patients to HAIC or TACE as higher expression of PFKM was associated with favorable outcomes accepting TACE. Such performance could also be validated in this study as participants with elevated PFKM tended to benefit from SoraTACE. Conclusions: This trial demonstrated SoraHAIC significantly improved OS over SoraTACE in participants with advanced HCC. Participants with high PFKM expression benefited more from TACE. Clinical trial information: NCT02856126 .
A phase 1b study of SHR-2017, a RANKL/NGF targeted antibody, in patients (pts) with breast cancer bone metastasis.
Authors: Xu Liang, Yaxin Liu, Hanfang Jiang, Guohong Song, Yun Zhang, Qian Zhao, Yuanyuan Huang, Tengrui Yin, Gang Cheng, Lingling Xu, Huiping Li
Journal: Journal of Clinical Oncology (2025)

12059 Background: Bone metastasis is a common site of metastasis in malignant tumors. For patients (pts) with bone metastasis, pain is the predominant symptom, significantly impairing the quality of life. SHR-2017, a first-in-class fully human monoclonal antibody targeting RANKL/NGF, is designed to prevent skeletal-related events and alleviate pain in pts with bone metastasis. Here, we present the preliminary pharmacokinetics, pharmacodynamics, efficacy and safety results from a multicenter, open-label, single-arm phase 1b study in pts with bone metastasis from breast cancer. Methods: Breast cancer pts with at least one bone metastasis and an average Numeric Rating Scale (NRS) score of ≥ 4 at the index bone metastasis cancer pain site at baseline were eligible. Pts could be undergoing stable anti-tumor treatment or have no plan to change their anti-tumor treatment within 2 weeks after drug administration in this study. Pts received subcutaneous injection of SHR-2017 at 180 mg every 4 weeks for 6 cycles. To assess pain, pts maintained a diary (daily through week 8 and then weekly to week 48) to record the average and worst pain over the previous 24 h (on a numeric rating scale from 0 = no pain to 10 = worst possible pain) at the index bone metastasis cancer pain site. Results: As of Dec 31, 2024, 22 pts were enrolled and treated (prior bone targeted agents [BTA] use, 36%; mean NRS of average pain, 4.17 [SD: 0.76]). Following a single dose, the median time to peak concentration of SHR-2017 was 7 days, with a mean half-life (t 1/2 ) of 11.4 days and a mean clearance (CL/F) of 0.88 L/day. Among 12 pts without prior BTA use, a reduction in urine N-telopeptide of type I collagen adjusted for urine creatinine (uNTX/Cr), a biomarker for bone resorption, was evident by cycle 1 and sustained over time; the median reduction from baseline was -83.0% (range -96.9% to -60.6%) at week 5 (C2D1). By week 13 (C4D1), among 8 pts without prior BTA use, the median reduction in uNTX/Cr was -78.7% (range -93.1% to -64.6%). Daily NRS score showed a continuous decrease during cycle 1 in all pts, the mean reductions from baseline in average and worst pain were -1.95 (SD: 1.21) and -1.90 (SD: 1.46) at week 2, respectively. By week 4, the reductions were -2.46 (SD: 1.03) and -2.45 (SD: 1.45), respectively. Treatment-related AEs (TRAEs) occurred in 7 (32%) pts (grade 1, n = 6; grade 2, n = 1), with the most common being increased parathyroid hormone (PTH), the one grade 2 TRAE being rash. There were no TRAEs leading to dose discontinuation. Conclusions: Preliminary data indicated promising anti-bone resorption and analgesic effects, with a favorable safety profile for SHR-2017 in pts with bone metastasis from breast cancer. The trial is ongoing to further evaluate SHR-2017 following multiple dosing. Clinical trial information: NCT06380881 .