tbuckley/cabot-search huggingface dataset:
Older-onset hereditary breast and ovarian cancer (HBOC) syndrome patients and clinical value of germline multigene testing.
Authors: Rodoniki Iosifidou, Dimitrios Matthaios, Dimitrios George Petrakis, Eleftherios Kampletsas, Kevisa Potska, Christina Dogka, Anastasia Katseli, Georgios Tsaousis, Dimitra Stefanou, Dimitrios Mavroudis, Avraam Assi, Vasiliki Michalaki, Maria Paraskeva, Elli Tripodaki, Evangelia Moirogiorgou, Hasan Senol Coskun, Gokhan Karakaya, Evgenia Bleka, Angeliki Meintani, George Nasioulas
Journal: Journal of Clinical Oncology (2025)

e12548 Background: Germline genetic testing referral of HBOC syndrome and relevant cancer patients is being undertaken using criteria that maximize the probability of finding a disease-causing variant and its actionability. In young onset breast cancer (BC, ≤50 y), invasive epithelial non-mucinous ovarian cancer, metastatic or node positive prostate cancer and exocrine pancreatic cancer, germline genetic testing is universally accepted. Genetic testing in older onset BC patients (&gt;50 y) uses strict clinical criteria like triple negative phenotype or bilateral BC and the presence of family history (FH). This study investigated genetic differences between young- and older-onset HBOC patients to estimate whether the threshold of the likelihood of finding a disease-causing variant can be lowered. Methods: In this study we characterized the mutational landscape of a total of 7.694 suspected HBOC related syndrome individuals, that were referred- regardless of age and FH- for multigene genetic testing using NGS technology, during the period 2020-2024 in GENEKOR MEDICAL S.A. Among the examined individuals, 1,677 (21.8%) were carriers of a pathogenic/likely pathogenic variant and the reason of referral was breast cancer in 90.6%, ovarian cancer in 14.7%, pancreatic cancer in 3.50% and prostate cancer in 1.5% of the cases. Results: Among young BC patients the highest proportion of pathogenic variants were identified in BRCA1 (21%), CHEK2 (17.2%), BRCA2 (14.5%), ATM (5.5%) and PALB2 (3.8%), while FH does not change the landscape of genes mutated. In older BC patients the percentages were modified as following: BRCA2 (14.6%), CHEK2 (14.2%), BRCA1 (13.4%), PALB2 (3.8%) and ATM (5.6%). Even without FH, pathogenic variants, were still detected but in slightly lower percentages in the following genes CHEK2 (7.7%), BRCA1 (7.7%) and PALB2 (7.7%) in this cohort. Conclusions: The results of this study provide some evidence that the mutational landscape among young-onset BC patients is not different from those of older-onset BC patients, even when taking FH into account. Following strictly the age limit cut-off combined with FH as proposed by international guidelines would result in overlooking 1% of gene-testing positive BC patients and defective management of their families.
Impact of great circle distance on breast cancer survival in NCDB.
Authors: Yongzhe Wang, Christine Quinones, Elizabeth Gonzalez, Preeti Farmah, Hans Francis Schoellhammer, Lorena Gonzalez, Nikita Shah, Katharine Schultz-Costello, Jennifer Tseng, Veronica Christine Jones
Journal: Journal of Clinical Oncology (2025)

e13833 Background: Timeliness of breast cancer (BC) care, defined as initiation of treatment within 60 days of diagnosis, has a significant impact on survival. Barriers can cause delays and propagate disparities. Distance from the treatment facility may pose a significant delay to initiation of treatment and should be evaluated in relation to BC survival. We hypothesized that larger great circle distance (GCD), or distance from patient residence to treatment facility, leads to delayed timeliness of BC care and negatively impacts survival. Methods: We analyzed the National Cancer Database (NCDB) for primary BC cases diagnosed between 2004 and 2021. Demographic variables were captured. GCD was categorized as &lt;10 miles, 10.1–20 miles, and &gt; 20 miles. Chi-squared tests were used to assess the relationship between time to first treatment (surgery, chemotherapy, radiation) and GCD. Kaplan-Meier curves were utilized to evaluate overall survival, stratified by GCD and the first treatment received. Log-rank tests were used for comparison. Negative binomial regression models were used to evaluate associations between time-to-first treatment (in days) and GCD, with and without adjustments for social and clinical factors. Statistical significance was set at a p-value threshold of &lt; 0.05; all tests were two-tailed. Results: The final cohort consisted of 283,166 BC patients. Surgery was the most common first treatment (n = 237,761, 84%). Half of the patients had a GCD &lt; 10 miles of the treatment facility (n = 150,036; 53%), 66,506 (23%) lived between 10.1 and 20 miles, and 66,624 (24%) lived greater than 20 miles away. Increasing GCD was significantly associated with longer time to surgery (p &lt; 0.01). However, overall survival was significantly worst for patients with GCD&lt;10 miles and best for patients with GCD between 10.1 and 20 miles (p &lt; 0.001) when receiving surgery or chemotherapy as first treatment; no difference was observed when radiation was first treatment (p = 0.41). Compared to non-Hispanic White patients, non-Hispanic Black and Hispanic patients experienced 20% (95% CI: 1.19, 1.21) and 15% (95% CI: 1.12, 1.18) longer delays to surgery, respectively, translating to 1.2 days longer to surgery. These differences were also observed in adjusted models for time-to-first chemotherapy and time-to-first radiation. Conclusions: Race and ethnicity were associated with increased time to surgery. Although shorter GCD was associated with shorter time to first treatment, survival was significantly worse for patients with GCD &lt;10 miles. This may be attributable to factors related to neighborhood context surrounding the treatment facility.
Improving the collection of patient-reported outcomes: Key factors influencing completion and drop-off rates.
Authors: Fernanda C.G. Polubriaginof, Allison Lipitz-Snyderman, Susan Chimonas, Peter D. Stetson, Gilad Kuperman
Journal: Journal of Clinical Oncology (2025)

e23204 Background: Incorporating patient-reported outcomes (PROs) into healthcare processes can improve patient engagement and inform clinical decision-making. However, achieving high adoption rates and minimizing drop-off can be challenging. Understanding the factors that contribute to completion and drop-off is essential to optimizing PRO survey design and implementation. Methods: We conducted a retrospective study of questionnaires sent to patients in 2024 at a major cancer center. The questionnaires were used across standard of care, research, and quality improvement projects. A governance process to oversee the development of questionnaires and related content was utilized to ensure satisfactory experience for patients. We analyzed metrics including the number of questionnaires developed, the number of questionnaires sent and completed, and patient burden as measured by completion time, drop-off rates defined as a questionnaire started but not completed, and median time to completion. We also identified the highest and lowest completion rates and drop-off rates across specific questionnaires. Results: A total of 1,181,058 responses were collected across all questionnaires. The median completion time was 2 minutes. Our analysis revealed significant variability in the completion rates, drop-off rates, and time to completion across survey categories. The standard of care questionnaires demonstrated the highest completion rate (72%) and the lowest drop-off rate (2%). In comparison, research questionnaires had a completion rate of 59% with a drop-off rate of 4%, and quality improvement questionnaires had a completion rate of 49% and a drop-off rate of 3%. Table 1 shows the 3 questionnaires with the highest drop-off rates. Conclusions: Our findings suggest that drop-off rates are significantly influenced by survey design and content complexity. The higher completion and lower drop-off rates observed in standard of care surveys underscore the importance of a governance structure to review questionnaire length, language, and integration with clinical workflows. While shorter completion times are important, they do not necessarily reduce drop-off if the survey is perceived as burdensome. For example, the Patient Values Assessment and other emotionally charged surveys can be more difficult for patients to complete, resulting in lower completion rates and higher drop-off. Our results suggest that refining survey design, tailoring content to patient needs, and optimizing integration into clinical workflows can improve patient participation in PRO surveys. Questionnaire Total Completed Completion Rate Drop-Off Rate Median Time to Complete (IQR) Family History Questionnaire 22,408 65% 21% 8.1 minutes (0, 32.8) COVID-19 Research Follow-Up Questionnaire 350 36% 19% 14.1 minutes (9.6, 379) Patient Values Assessment 879 59% 14% 9.25 minutes (3.8, 55.3)
A phase III randomized controlled trial comparing palliative stereotactic body radiotherapy vs. palliative standard radiotherapy in patients with advanced head and neck cancer (NCT06641791).
Authors: Ian Poon, Irene Karam, Houda Bahig, Brock J. Debenham, Adam Mutsaers, Murali M. Rajaraman, Chiaojung Jillian Tsai, Lee Chin, Madette Galapin, Scott Victor Bratman, Jolie Ringash, Ambika Parmar, Koren S. Smith, Sarah Radcliffe, Wei Tu, Wendy R. Parulekar
Journal: Journal of Clinical Oncology (2025)

TPS6118 Background: The optimal radiotherapy (RT) treatment regimen for patients with advanced head and neck cancer (AHNC) unsuitable to receive curative intent RT is undefined. Stereotactic body radiotherapy (SBRT) is a promising technique but rigorous multicentre evaluation is required prior to adoption. Methods: This is a Phase III randomized controlled trial comparing palliative SBRT to palliative standard RT (SRT) in participants with advanced mucosal, squamous cell head and neck cancer unable to tolerate curative intent RT. Key eligibility criteria: Unsuitable for curative intent therapy, no evidence of metastatic disease, stages TX or T0-T4/N0-N3, geriatric 8 score [1] ≤14. Treatment arms: (Experimental) SBRT 4500 cGy/ 5fr (twice a week to primary and nodal GTV (BED 10 85) OR 4000 cGy /5 fr twice a week if organs at risk (BED 10 -72) versus (standard) 2400 cGy/ 3fr (day 0/7/21 (BED 10 43) or 2500 cGy/ 5fr over 1 week (BED 10 38). Primary objective: To compare OS between arms. Secondary objectives evaluate progression-free survival (PFS), locoregional failure-free survival, distant metastases-free survival, response rates, acute and long-term toxicity (CTCAE v5.0), treatment compliance, patient-reported outcomes (PRO-CTCAE, FACT-HN), resource utilization, and health utilities. Statistical design : The trial aims to enroll 196 patients with a 2:1 randomization ratio (SBRT:SRT). The study is powered at 80% with a two-sided alpha of 0.05 to detect a difference in 1-year OS of 40.3% vs. 22% (HR = 0.6), assuming a 15% drop-out/lost to follow-up rate. Conduct to Date : This trial was activated on October 31, 2024. Supported by CCS grant #707213; CIHR #175014. [1] Takahashi M, Takahashi M, Komine K, Yamada H, Kasahara Y, Chikamatsu S, et al. (2017) The G8 screening tool enhances prognostic value to ECOG performance status in elderly cancer patients: A retrospective, single institutional study. PLoS ONE 12(6): e0179694. https://doi.org/10.1371/journal.pone.0179694. Clinical trial information: NCT06641791 .
BCI biomarker performance in premenopausal women with breast cancer.
Authors: Ananya Chandrika Nanduri, Jennie Tan, Andrea Nicholson, Krystal Hunter, Prathamesh Patil, Ahmed Kamel Abou Hussein
Journal: Journal of Clinical Oncology (2025)

e12506 Background: Breast Cancer Index (BCI) is a gene expression biomarker that evaluates cell proliferation and estrogen signaling to guide extended endocrine therapy treatment in hormone receptor-positive breast cancer. BCI assay predicts the benefit of extended endocrine therapy and provides a prognostic score to assess both overall recurrence risk (0-10 years) and late distant recurrence risk (5-10 years). While the assay is validated in trials like MA-17, TEAM, IDEAL, aTTom and NSABP-B42, these studies focused on postmenopausal patients. The role of BCI in premenopausal women, with their unique hormonal and therapeutic profiles, remains underexplored. This retrospective, single-center study seeks to validate BCI in a premenopausal cohort. Methods: Premenopausal status was defined by self-reported last menstrual period or age &lt;50 years. A total of 99 premenopausal patients with hormone receptor-positive breast cancer were included. Clinical and pathological data were collected, and BCI scores were evaluated for their prognostic and predictive value regarding recurrence risk and extended endocrine therapy benefit. One-way ANOVA assessed the relationship between disease grade, stage, and BCI scores, and an independent t-test identified the significance of grade 3 disease with higher mean BCI scores. Results: Grade 3 disease was associated with a significantly higher mean BCI score compared to lower-grade disease (11.03 vs. 5.18; p&lt;0.001, independent t-test). One-way ANOVA showed strong correlations between both grade and stage of disease and BCI scores, with stage 3 patients having the highest mean score (12.03) compared to stage 1 (4.88) and stage 2 (7.74) patients (p&lt;0.001) (Table 1). ER/PR/HER2 status also significantly influenced BCI scores (p&lt;0.001), with ER+/PR+/HER2+ tumors showing the highest scores (15.20), followed by ER+/HER2+ (10.20) and ER+/PR+/HER2- (4.68). Conclusions: This study underscores the role of the Breast Cancer Index (BCI) in stratifying recurrence risk and guiding treatment in premenopausal women with hormone receptor-positive breast cancer. The ability of BCI assay to differentiate risk by grade, stage, and receptor status may refine treatment approaches and inform future guidelines. Larger studies with extended follow-up are needed to validate these findings and expand the clinical applications of BCI, particularly in diverse premenopausal populations and across ER/PR/HER2 receptor variations. Association of tumor grade and stage with mean BCI scores in premenopausal breast cancer patients. Grade Number of Patients Mean BCI Standard Deviation P-value 1 26 4.15 2.45 &lt;0.001 2 54 5.68 3.48 3 18 11.03 4.53 Stage 1 58 4.88 2.64 &lt;0.001 2 37 7.74 5.08 3 4 12.03 3.59 A one-way ANOVA analysis demonstrated a significant correlation (p &lt; 0.001); higher tumor grade and advanced stage are associated with elevated BCI scores.
Transfusion-related cost and time burden offsets in patients with myelofibrosis treated with pacritinib compared to best available therapy based on PERSIST-2 trial.
Authors: Abiola Oladapo, Karisse Roman-Torres, Aaron Thomas Gerds, Stephen Oh
Journal: Journal of Clinical Oncology (2025)

11061 Background: Anemia in patients (pts) with myelofibrosis (MF) is associated with a significant disease burden, especially in pts who require red blood cell (RBC) transfusions, as it negatively impacts quality of life and disease prognosis. In the PERSIST-2 trial, treatment with pacritinib (PAC), a JAK1 sparing inhibitor of JAK2/IRAK1/ACVR1, was associated with anemia benefit. A significant proportion of non-transfusion independent (non-TI) pts at baseline on PAC compared to best available treatment (BAT) achieved transfusion independence (TI) (37% vs 7%) in any 12 weeks over a 24-week interval and significantly more had a ≥50% reduction in transfusion burden (49% vs 9%) (Oh ST, et al. 2023) with lower RBC transfusion rates (Mean [2.45 vs 3.54/30-day]) (Data on file). This study aimed at estimating the projected differences in transfusion-related cost and time burden with PAC vs BAT. Methods: An economic evaluation based on transfusion-related data in pts treated with PAC or BAT (including ruxolitinib [RUX] and erythroid support [ES]) from the PERSIST-2 trial (NCT02055781). Transfusion status (TI and non-TI) at baseline and over any 12-week interval within the 24-week study period was defined based on the Gale criteria (i.e. presence or absence of RBC transfusions). RBC transfusion rates over 30-day periods, including all reported transfusions within the initial 24-week study period, were annualized and used as proxy for transfusion-related visits. Annual transfusion-related cost estimates by transfusion status were based on a previous MF burden of illness study which utilized IBM MarketScan data (Gerds AT, et al. 2022) and was adjusted to 2024 US dollars using the medical component of the Consumer Price Index. Transfusion-related time burden estimates were based on previously reported RBC transfusion visits in transfusion dependent pts with β-thalassemia (Knoth RL, et al. 2022). Results: Annual transfusion-related cost with PAC was projected to be 19.5% lower, with a cost saving of ~$61K compared to BAT (~$252K vs ~$313K). Annual transfusion-related time burden with PAC vs BAT was lower by 25.3% with a time saving of ~172 hrs (~508 vs ~680 hrs). Among pts who were non-TI at baseline, projected annual cost and time savings for PAC vs BAT were ~$73K and ~204 hrs, respectively. Results remained robust regardless of type of BAT (i.e. RUX or ES therapies). Conclusions: The reduction in transfusion rates associated with PAC treatment relative to BAT is projected to result in decreased transfusion-related medical cost and time burden for pts with MF and anemia.
Efficacy of immune checkpoint inhibitors in smokers vs non-smokers: A large real-world retrospective cohort analysis.
Authors: Nanda Siva, Shanawar Ali Waris, Adnan Saifuddin, Nolan Holley, Yashan Thakkar, Salah Ud Din Safi
Journal: Journal of Clinical Oncology (2025)

11065 Background: Immune checkpoint inhibitors (ICIs) play a critical role in strengthening the immune response against tumors. Prior literature has shown higher objective response rates of ICIs in lung cancer patients who are smokers vs. non-smokers, thought to be due to increased expression of PD-1/PD-L1 in smokers. This study aims to assess the clinical impact of smoking on the efficacy of ICIs across multiple cancer types. Methods: This multicenter retrospective study utilized the TriNetX Network, a database containing over 130 million deidentified patient records to identify patients diagnosed with lung, breast, melanoma, colorectal, head and neck, bladder, hepatocellular, and renal cell carcinomas, who underwent subsequent treatment with ICIs (PD-1, PD-L1, and CTLA-4 inhibitors). Kaplan-Meier survival analysis was performed to assess three-year survivability. Propensity-score matching (PSM) was performed based on demographics, lab work, and pertinent comorbidities between smokers and non-smokers in each cancer type. The analysis included patients who had documented smoking status (ICD 10: Z72.0) prior to ICI therapy. Results: A total of 95,178 cancer patients receiving ICI met the inclusion criteria, of whom 15.5% were tobacco users. After PSM, 12,203 patients were in the smoking group and 12,203 were in the non-smoker group. For lung cancer patients, there was statistically significant superior survivability in the smoker group compared to the nonsmoker group, (HR: 0.894, 95% CI [0.854, 0.935]). A similar trend was identified in the colon, hepatocellular, and breast cancer groups, however, this was not statistically significant. There was no significant difference in mortality seen in the smoker versus non-smoker groups in melanoma, bladder, head and neck, and renal cell cancers. Conclusions: Our findings reaffirm previous studies demonstrating superior efficacy of ICIs in smokers with lung cancer. Additionally, this study highlights other cancer types, such as colon, hepatocellular, and breast cancers, that may exhibit improved outcomes in smokers, while also identifying cancers such as melanoma, bladder, head and neck, and renal cell carcinomas where smoking status appears to have no apparent effect on survivability. To our knowledge, this is the largest retrospective cohort study examining the impact of smoking status on ICI therapy outcomes across multiple cancer types. Survivability in smokers compared to non-smokers treated with ICIs. Cancer type (ICD 10) N (smoker) N (non-smoker) 3-year HR 95% CI Colon (C18) 292 292 0.808 (0.622,1.048) Liver (C22.0) 559 559 0.884 (0.748,1.045) Lung (C34) 8130 8130 0.894 (0.854,0.935) Breast (C50) 540 540 0.934 (0.756,1.154) Bladder (C67) 713 713 1.001 (0.856,1.169) Renal cell (C64) 706 706 1.016 (0.859,1.202) Head &amp; neck (C76.0) 583 583 1.042 (0.888,1.224) Melanoma (C43) 680 680 1.087 (0.889,1.328)
Distinct cellular interactions in the TNBC tumor microenvironment in association with PD-L1 expression and pathologic complete response based on spatial analysis.
Authors: Sung Gwe Ahn, Kyung Soo Kim, Jee Hung Kim, Soong June Bae, Soeun Park, Joon Jeong, Yoon Jin Cha
Journal: Journal of Clinical Oncology (2025)

e12544 Background: Immune-activated tumor microenvironments (TMEs), characterized by PD-L1 positivity or an abundance of tumor-infiltrating lymphocytes, are associated with pathologic complete response (pCR) in patients with triple-negative breast cancer (TNBC) treated with neoadjuvant systemic therapies (NAST). We performed a spatial analysis of the TME using a highly multiplexed imaging technique in treatment-naïve TNBC tumor samples treated with NAST. Methods: We collected 28 biopsied tumor samples before NAST. Of these, 6 patients underwent preoperative immunochemotherapy with pembrolizumab. Spatial analysis of the TME was performed using CO-Detection by indexing (CODEX). Physical cell-to-cell interactions were analyzed by assessing the rate of direct contact and the closest distance between different cell types. PD-L1 expression was evaluated using the Ventana SP142 PD-L1 assay. Results: The rate of PD-L1 positivity and pCR were 42.8% and 53.6%, respectively. CD8+ T cells were classified into two groups by immune checkpoint (IC) markers (PD1, LAG3, CXCL13): CD8+IC high and CD8+IC low . Direct contact between CD8+IC high and CD4+FoxP3 low T cells was enriched in tumors with PD-L1-negative or non-pCR. In PD-L1-positive tumors, podoplanin exhibited direct interactions with various immune cell types, including CD8+IC low , CD4, CD8, and myeloid cells. When analyzing cell-to-cell distances, the distances between B cells and various cells including tumor epithelial cells were significantly shorter in cases with pCR compared to those without pCR. Conclusions: Direct interaction between CD8+IC high and CD4+FoxP3 low cells may be associated with PD-L1-negative TNBC. Podoplain potentially plays a role in the PD-L1-expressing TME in TNBC. Active physical interaction between B cells and neighbor cells was observed in tumors with pCR. Our findings, based on spatial analysis of TME, may enhance our understanding of immune-cold TNBC and its lack of response to immunochemotherapy.