tbuckley/cabot-search huggingface dataset:
Evaluating the impact of COPD exacerbations on survival outcomes in non-small cell lung cancer patients receiving immunotherapy: A retrospective cohort analysis.
Authors: Jowan Al-Nusair, Omar Obeidat, Moh'd Masoudi, Thomas Wright, Zain Al-Momani, Adamsegd Isac Gebremedhen, Nizar Alnabahneh, Toni Pacioles, Muhammad O Jamil
Journal: Journal of Clinical Oncology (2025)

e20613 Background: Advances in immunotherapy have changed the treatment landscape for advanced non-small cell lung cancer (NSCLC). Recent studies suggest that patients with coexisting chronic obstructive pulmonary disease (COPD) may respond better to immunotherapy, possibly due to the unique immunological environment associated with COPD. However, frequent COPD exacerbations, which often necessitate the use of systemic corticosteroids, may affect the response to immunotherapy. We aimed to address a critical gap in knowledge by evaluating the survival outcomes of NSCLC patients with and without a history of COPD exacerbations undergoing immunotherapy. Methods: Data from 103 healthcare organizations in the TriNetX database were analyzed. Two matched cohorts of NSCLC patients treated with immunotherapy were identified: Cohort 1 included patients with a history of COPD exacerbations (n=1,335), and Cohort 2 included patients without COPD (n=1,335). The propensity score matching balanced age, sex, and co-morbidities. Kaplan-Meier survival analysis and Cox proportional hazards models assessed overall survival (OS), risk of death, and hazard ratios (HR). Statistical significance was set at p &lt; 0.05. Results: Baseline characteristics were well matched after propensity score adjustment, ensuring comparability between the groups. Patients with COPD exacerbations (Cohort 1) had significantly worse outcomes compared to those without COPD (Cohort 2). The risk of death was higher in Cohort 1 (64.2%) than in Cohort 2 (59.5%), with a risk difference of 4.7% (95% CI: 1.0-8.4%, p=0.012). Median OS was shorter in Cohort 1 (418 days) compared to 543 days in Cohort 2, reflecting a substantial difference in survival duration. Kaplan-Meier analysis showed a survival probability of 0.00% for Cohort 1 at the study endpoint, compared to 21.03% in Cohort 2 (log-rank p&lt;0.001). The hazard ratio for death in Cohort 1 was 1.22 (95% CI: 1.11-1.35, p&lt;0.001), indicating a 22% higher mortality risk. Conclusions: This study shows that NSCLC patients with COPD exacerbations experience significantly worse survival outcomes with immunotherapy compared to patients without COPD. These findings highlight the adverse impact of COPD exacerbations on immunotherapy efficacy and the need to explore treatment strategies that will improve patient outcomes. Impact of COPD exacerbations on mortality and survival outcomes in NSCLC patients. Cohort Risk of death Risk difference Median OS (days) HR NSCLC with history of COPD exacerbations (n=1,335) 64.2% 4.7% (95% CI: 1.0-8.4%, p=0.012) 418 1.22 (95% CI: 1.11-1.35, p&lt;0.001) NSCLC without COPD (n=1,335) 59.5% 543
Nutrition in head and neck cancer care: a roadmap and call for research
Authors: Xin Chen, Brooke Beilman, Heather D Gibbs, Jessica L Hamilton, Nathan Parker, Andrés M Bur, Jimmy J Caudell, Gregory N Gan, Jill M Hamilton-Reeves, Heather S L Jim, Kedar Kirtane, Chris Lominska, Sylvia L Crowder, Anna E Arthur
Journal: The Lancet Oncology (2025)
Contributions of cancer treatment and genetic predisposition to risk of subsequent neoplasms in long-term survivors of childhood cancer: a report from the St Jude Lifetime Cohort and the Childhood Cancer Survivor Study
Authors: Achal Neupane, Qi Liu, Siddhant Taneja, Jennifer French, Matthew J Ehrhardt, Tara M Brinkman, Rachel Webster, Jun J Yang, Cindy Im, Lucie M Turcotte, Joseph P Neglia, M Monica Gramatges, Rebecca M Howell, Smita Bhatia, Kirsten K Ness, Melissa M Hudson, Gregory T Armstrong, Leslie L Robison, Yutaka Yasui, Yadav Sapkota
Journal: The Lancet Oncology (2025)
Pembrolizumab vs chemotherapy in elderly patients with NSCLC: A comparative analysis of survival and adverse effects.
Authors: Fayaz Khan, Godbless Ajenaghughrure, Muayad Alzamara, Brian Patrick Singeltary
Journal: Journal of Clinical Oncology (2025)

e20528 Background: Elderly patients with non-small cell lung cancer (NSCLC) require treatment strategies that balance efficacy and tolerability. Immunotherapy with pembrolizumab has emerged as a potential alternative to traditional platinum/taxane-based chemotherapy. This study compares mortality and adverse effects between these two regimens in patients aged 75 years and older. Methods: This retrospective analysis utilized the TriNetX database. Elderly patients with NSCLC were divided into two cohorts: the first cohort received pembrolizumab (1,556 patients), and the second received platinum/taxane-based chemotherapy (1,556 patients). Propensity score matching was used to balance baseline characteristics. Kaplan-Meier survival analysis was performed to assess mortality and adverse effects, with hazard ratios (HRs) calculated to evaluate relative risks. Results: Mortality was similar between the groups (HR: 1.069, 95% CI: 0.975–1.171, p=0.523). However, adverse effects were significantly higher in the chemotherapy group. Pembrolizumab reduced the risk of anemia (HR: 0.709, 95% CI: 0.636-0.790, p&lt;0.001), neutropenia (HR: 0.357, 95% CI: 0.287–0.443, p&lt;0.001), thrombocytopenia (HR: 0.698, 95% CI: 0.560–0.869, p=0.001), fever (HR: 0.774, 95% CI: 0.629–0.952, p=0.001), pneumonitis (HR: 0.470, 95% CI: 0.316–0.701, p=0.012), colitis (HR: 0.535, 95% CI: 0.391–0.732, p&lt;0.001). Conversely, chemotherapy had a lower risk of chronic kidney disease (HR: 1.347, 95% CI: 1.162–1.561, p&lt;0.001) and heart failure (HR: 1.328, 95% CI: 1.123–1.571, p=0.012). Myocarditis was rare, occurring only with pembrolizumab patients(0.6% vs. 0%, p=0.002). Conclusions: Pembrolizumab offers comparable survival to platinum/taxane-based chemotherapy while significantly reducing the risk of adverse effects such as neutropenia, thrombocytopenia pneumonitis, colitis, and anemia in elderly NSCLC patients. Although pembrolizumab is associated with a rare risk of myocarditis and higher chronic kidney disease incidence, its favorable safety profile makes it a preferred treatment option for this population. The large sample size strengthens the reliability of these findings for outcomes in elderly NSCLC patients. Outcome Hazard Ratio (95% CI) P-Value Favors Mortality 1.069 (0.975-1.171) 0.523 No significant difference Anemia 0.709 (0.636-0.790) &lt;0.001 Pembrolizumab Neutropenia 0.357 (0.287-0.443) &lt;0.001 Pembrolizumab Thrombocytopenia 0.698 (0.560-0.869) 0.001 Pembrolizumab Fever 0.774 (0.629-0.952) 0.001 Pembrolizumab Pneumonitis 0.470 (0.316-0.701) 0.012 Pembrolizumab Colitis 0.535 (0.391-0.732) &lt;0.001 Pembrolizumab CKD 1.347 (1.162-1.561) &lt;0.001 Chemotherapy Heart Failure 1.328 (1.123-1.571) 0.012 Chemotherapy
Patterns of mortality in lung cancer patients in the era of immunotherapy and targeted therapy: A single-center, retrospective, observational study.
Authors: Nikhila Sampath Kumar, Bhavesh Mohan Lal, Supriya Peshin, Konstantinos Arnaoutakis
Journal: Journal of Clinical Oncology (2025)

e20627 Background: Over the past decade, immunotherapies and targeted therapies have revolutionized the treatment of lung cancer patients. While the outcomes have greatly improved, lung cancer still remains the leading cause of cancer deaths worldwide. Previous studies have shown cardiovascular and pulmonary problems to be the leading causes of death in these patients. However, the common causes of death in the era of immunotherapy and targeted therapy remain unclear. Methods: In this single-center retrospective observational study, we explored the patterns of mortality in patients with lung cancer in the current era. We chart reviewed all patients diagnosed with lung cancer between July 2020 and June 2023, stratified them according to the tumor histology and presence of metastasis, and collected details about their mortality. We performed survival analysis using Kaplan-Meier curves. Results: A total of 646 patients were diagnosed with primary lung cancer, with 329 (50.9%) patients having adenocarcinoma (ADC), 151 (23.4%) patients having squamous cell cancer (SCC), and 154 (23.8%) patients having small cell lung cancer (SCLC). 12 patients had mixed histology. 73.9%, 71.55%, and 80.5%, respectively, of the patients with ADC, SCC, and SCLC had metastatic lung cancer at diagnosis. The average age was 69 years, with 58.4% being males. At the last follow-up, 271 (42.7%) of the 634 patients had died. The median overall survival (OS) for all patients was 29.5 months, with 36.4 months, 45.9 months, and 12.4 months, respectively, in patients with ADC, SCC, and SCLC (p &lt; 0.001). The median OS for patients with metastatic ADC, SCC, and SCLC were 19.8 months, 23.6 months, and 10.5 months, respectively (p &lt; 0.001). When compared to patients with SCLC (4.5%), patients with ADC (20.1%) and SCC (34.4%) had a much higher chance of having concomitant second primary malignancy (p &lt; 0.001). Most patients had more than one factor contributing to their death. Disease progression/metastasis contributed to 70.1%, 66.7%, and 77.9% of the deaths in patients with ADC, SCC, and SCLC, respectively. The cause of death was unknown in 20.7% of the patients, most of whom died at home. Among patients without progressive disease, infection (38.9%) was the leading cause of death. Cardiovascular causes (30%) were the second most common in the ADC group, whereas respiratory failure (35%) was more common in the SCC group. Other causes included neurological (5.2%), gastrointestinal (3.9%), and other miscellaneous causes (7.8%). Conclusions: While progressive disease still remains the most common cause of death in patients with lung cancer, infections, respiratory failure, and cardiovascular causes contribute to ~65% of deaths in patients without progressive disease. Understanding common factors contributing to mortality and addressing them is vital to improving outcomes in these patients.
Molecular subtyping and insights into sarcoma biology and prognosis.
Authors: Aleksei Shevkoplias, Angelina Khachatryan, Vladimir Kushnarev, Konstantin Chernyshov, Nikita Kotlov, Oleg Baranov, Nathan Hale Fowler
Journal: Journal of Clinical Oncology (2025)

11536 Background: Sarcomas represent a diverse group of mesenchymal malignancies, with over 200 subtypes recognized by the WHO. This heterogeneity, combined with rarity, complicates diagnosis. Here, comprehensive molecular profiling and unsupervised clustering were applied to define sarcoma subtypes associated with differentiation, genomic events, and prognosis. Methods: Whole exome and transcriptome sequencing was performed on 1,046 sarcoma samples via the BostonGene Tumor Portrait test. Hierarchical expression-based clustering was integrated with somatic mutations, fusions, copy number alterations, genome segmentation, and signatures, validated on 23 external datasets (n = 1,678). Results: Nine molecular clusters (C1-C9) reflecting distinct biological patterns were identified (Table). Stable, lineage-restricted clusters included leiomyosarcoma (C2) marked by smooth muscle differentiation pathways and TP53 , ATRX , and RB1 mutations; vascular sarcoma (C7) with vascular signaling and angiogenic amplifications; synovial sarcoma (C6) defined by WNT activation and SS18-SSX fusions; and Ewing sarcoma (C9) characterized by neuronal development signatures and EWSR1-FLI1 fusions. Clusters progressing toward undifferentiated pleomorphic sarcoma (UPS)-like phenotypes included liposarcoma (C3) progressing from adipocyte differentiation with MDM2/CDK4 amplifications; chondrosarcoma/chordoma (C5) transitioning from cartilage development pathways with TGFβ activation; and bone and UPS-like (C1) characterized by angiogenesis signatures, genomic instability, TP53 mutations, and the poorest survival (logrank p &lt; 0.05). Molecular clusters predicted survival regardless of the specific diagnosis. For example, liposarcoma and leiomyosarcoma patients in cluster C1 had a worse prognosis than those in C2 with the same diagnosis. Conclusions: The proposed molecular subtypes simplify sarcoma classification, providing unique prognostic insights missing in the current diagnostic framework. These findings suggest molecular subtypes could offer valuable knowledge for sarcoma research and patient treatment. Сharacterization of molecular sarcoma subtypes. Cluster Predominant diagnoses Undifferentiation progression Biology Alterations (chi-sq p &lt; 0.01) C1 Bone and UPS-like Progressing Undifferentiated or nearly undifferentiated TP53 mutation (35%) C2 Leiomyosarcoma Stable Smooth muscle differentiation TP53 (53%), ATRX (18%), RB1 (15%) mutations C3 Liposarcoma Progressing Adipocyte differentiation MDM2/CDK4 amplifications (45%) C4 Progressing Biologically diverse C5 Chondrosarcoma, chordoma Progressing Cartilage development C6 Synovial sarcoma Stable WNT activation SS18 - SSX fusions (68%) C7 Vascular sarcoma Stable Vascular signalling, angiogenesis C8 Progressing Biologically diverse C9 Ewing sarcoma Stable Neuronal development signatures EWSR1-FLI1 fusions (92%)
Advancing precision oncology in soft tissue sarcomas: The role of iTRAC in metastatic risk stratification and treatment personalization.
Authors: Fred Chibon, Ataaillah Benhaddou, Gaëlle Pérot, Philippe Rochaix, Thibaud Valentin, Gwenael Ferron
Journal: Journal of Clinical Oncology (2025)

11534 Background: Soft Tissue Sarcomas (STS), known for their extensive Genomic instability (GIN), often result in poor clinical outcomes. Grading systems, such as FNCLCC, have limited prognostic accuracy in stratifying metastatic risk for STS patients. We introduce transcription-associated GIN indice (iTRAC) to improve prognostic precision and guide treatment decisions. Methods: This study analyzed 226 STS tumor samples using RNA sequencing (RNAseq) to assess breakpoint distribution from fusion transcripts as a surrogate for GIN. We calculated iTRAC to quantify transcription-associated GIN. Kaplan-Meier survival analysis were used to evaluate prognostic relevance in patients receiving or not chemotherapy. Multivariate analysis was performed to evaluate the iTRAC compared to FNCLCC and CINSARC for metastatic risk stratification. Results: STS patients with medium iTRAC level had the poorest metastasis-free survival (MFS) compared to low and high iTRAC levels. Importantly, patients with low iTRAC have a poorer outcome when treated with chemotherapy than those untreated, but at the contrary patients with medium iTRAC and treated by chemotherapy have a better outcome, raising the question of the potential predictive value of iTRAC for adjuvant chemotherapy in STS patients. FNCLCC and CINSARC groups did not show significant difference in MFS between treated and not treated patients. Conclusions: iTRAC is a novel biomarker for stratifying metastatic risk and guiding personalized treatment in STS. It outperforms molecular and histological prognosis systems like CINSARC and FNCLCC grade by revealing distinct MFS between patients receiving or not chemotherapy. This could enable better identification of patients who may benefit from chemotherapy and alternative options for those with poor responses. Prospective clinical trials are needed for validation and integration for patients care.
Trends and disparities in lung cancer and respiratory failure mortality in the US: A 24-year retrospective study.
Authors: Saliha Maryam, Abdul Qadeer, Muneeb Khawar, Sardar Muhammad Imran Khan, Muhammad Waqas, Anisha Manzoor, Muhammad Abdullah Humayun, Atta Ur Rehman, Hamza Saleem, Mobeen Zaka Haider, Aamir Laghari, Robert W Kirchoff
Journal: Journal of Clinical Oncology (2025)

e20629 Background: Lung cancer (LC) and respiratory failure (RF) are major contributors to mortality in adults globally. Understanding long-term mortality trends across demographic, racial, geographic, and socio-economic groups is crucial to addressing disparities and improving outcomes. This study examines national mortality patterns for LC and RF in the United States from 1999 to 2023, providing critical insights into changes over time and identifying key disparities in age-adjusted mortality rates (AAMRs). Methods: A descriptive analysis of mortality data from the CDC WONDER database (1999-2023) identified deaths due to LC (ICD-10 code C34) and RF (ICD-10 code J96) in adults aged 25+. AAMRs per 100,000 population were calculated and stratified by gender, race/ethnicity, region, state, and urban-rural classification. Temporal trends were analyzed with Joinpoint regression to compute APCs and 95% CIs. Statistical significance was set at p&lt;0.05. The study followed STROBE guidelines. Results: From 1999 to 2023, a total of 456,325 adult deaths (age 25-85+) were attributed to Lung cancer and Renal failure. Age-adjusted mortality rates (AAMRs) for lung cancer (LC) and respiratory failure (RF) decreased from 1999 to 2010 (APC = -1.2, 95% CI: -1.6 to -0.9), followed by an increase from 2010 to 2023 (APC = 1.4, 95% CI: 1.1 to 1.7). Gender trends revealed a steady decline for men, while women's Age-Adjusted Mortality Rates (AAMr) initially decreased, then increased from 2011-2023 (APC: 2.0, 95% CI: 1.7 to 2.5). Non-Hispanic White populations experienced a rapid increase in age-adjusted mortality rates from 2014 to 2017 (APC: 2.7; 95% CI: 0.9 to 3.3), while other racial/ethnic groups exhibited varied trends with declines, increases, and stabilizations. Geographically, AAMRs were highest in the Northeast (8.6; 95% CI: 8.5 to 8.7) and lowest in the Midwest (7.1; 95% CI: 7.0 to 7.1). Metropolitan areas saw declining trends until 2006, stabilizing briefly, and increasing thereafter. Non-metropolitan areas experienced notable increases post-2009 (APC = 2.3, 95% CI: 1.8 to 3.1). State-level disparities revealed Mississippi with the highest AAMR (14.0; 95% CI: 13.7 to 14.4) and Wisconsin with the lowest (3.7; 95% CI: 3.5 to 3.8). These findings highlight significant demographic, racial, and geographic variations in LC and RF mortality trends. Conclusions: LC and RF-related mortality rates initially declined from 1999 to 2010 but increased significantly from 2010 onward, with notable demographic, racial, and geographic disparities. These findings highlight the urgent need for targeted interventions and resource allocation to address these rising trends and reduce inequities across vulnerable populations.
Subgroup analysis of the phase 2 part of the RINGSIDE phase 2/3 trial of varegacestat for treatment of desmoid tumors.
Authors: Rashmi Chugh, Mrinal M. Gounder, Arun S. Singh, Brian Andrew Van Tine, Vladimir Andelkovic, Janet Yoon, Edwin Choy, Jeremy Howard Lewin, Javier Martin Broto, Ravin Ratan, Nam Bui, Winette T.A. Van Der Graaf, Lara E. Davis, Atrayee Basu Mallick, Hyo Song Kim, Robin Lewis Jones, Eric Song, Katie Newhall, Jonathan Yovell, Bernd Kasper
Journal: Journal of Clinical Oncology (2025)

11516 Background: Gamma secretase inhibitors (GSIs) have shown antitumor activity against desmoid tumors (DT). The RINGSIDE Phase 2 study (NCT04871282) demonstrated early and continued response to three dose regimens of varegacestat (AL102) in patients with DTs. We evaluated treatment response in key subgroups. Methods: RINGSIDE Phase 2 is an open-label, dose-finding study in adults with progressing DT (≥10% unidimensional growth ≤18 months or DT-related pain requiring non-opioid medication). Participants were randomized to three dose regimens: 1.2 mg once daily (n=14), 2 mg intermittent (n=14) or 4 mg intermittent (n=14) (intermittent = 2 days on, 5 days off). In the open-label extension (OLE) period, all active participants began receiving 1.2 mg once daily. We performed descriptive analyses of objective response rate (ORR) in the following subgroups with at least 5 participants: age (≤40 years vs. &gt;40 years), tumor size (&lt;70 mm vs. ≥70 mm), prior lines of therapy (0, 1, or 2+), tumor location (intra-abdominal vs. extra-abdominal) and mutational biomarkers ( APC vs CTNNB1 ). Subgroups were analyzed by pooling across dose regimens. Results: RINGSIDE Phase 2 enrolled 42 participants, of whom 29 (69%) entered the OLE. As of April 10, 2024, median time on treatment was 23.1 months (range 0.7 – 26.6) and 23 participants (55%) were still on treatment. Median age was 38.5 years (range 19 – 72), 74% were women, and 69% received prior DT therapy. ORR ranged from 43% to 78% across age, tumor size, prior therapy, tumor location and mutation subgroups (Table). Response rates were comparable across all subgroups examined. Conclusions: Comparable, objective tumor responses to oral varegacestat therapy were shown in all subgroups examined. These findings support continued evaluation of all desmoid tumor patients independent of subgroups in the ongoing, double-blind, randomized, placebo-controlled Phase 3 study of varegacestat (RINGSIDE NCT04871282). Clinical trial information: NCT04871282 . Varegacestat response in subgroups. Subgroups ORRResponder (%) Age ≤40 years (n=22) vs. &gt;40 years (n=14) 13 (59) vs. 10 (71) Tumor size &lt;70 mm (n=18) vs. ≥70 mm (n=14) 13 (72) vs. 9 (64) Prior lines of therapy: 0 (n=11), 1 (n=16), or 2+ (n=9) 6 (55), 10 (63), 7 (78) Intra-abdominal (n=9) vs. extra-abdominal (n=27) 4 (44) vs. 19 (70) APC (n=7) vs CTNNB1 (n=19) mutation 3 (43) vs. 13 (68)
Beyond maximum grade: using patient-generated data to inform tolerability of treatments for haematological malignancies
Authors: Vishal Bhatnagar, Amylou C Dueck, Fabio Efficace, Paul Kluetz, Lori Minasian, Galina Velikova, Caitlin Drew, Gita Thanarajasingam
Journal: The Lancet Haematology (2025)
Efficacy and safety of nivolumab and docetaxel combination therapy versus nivolumab monotherapy for the treatment of advanced non-small cell lung cancer: A systematic review and meta-analysis.
Authors: Malik WZ Khan, Muhammad Ahmad, Sundus Huma, Mustafa Ali Samejo, Sarah Yousaf, Areen Arif, Farah Naz Afridi, Aizaz Ali, Amna Gul, Shammas Bajwa
Journal: Journal of Clinical Oncology (2025)

e20619 Background: Nivolumab has demonstrated efficacy over chemotherapy for the management of advanced non-small cell lung cancer (NSLC). Recent evidence suggests that combining nivolumab with docetaxel may enhance outcomes compared to nivolumab monotherapy. Therefore, we conducted this meta-analysis to evaluate the efficacy and safety of nivolumab and docetaxel combination therapy versus nivolumab monotherapy in the treatment of advanced NSLC. Methods: PubMed, Cochrane and Embase databases were searched to identify relevant studies. The primary endpoints included overall survival (OS) and progression free survival (PFS). Grade 3-5 adverse events, objective response rate (ORR) and disease control rate (DCR) comprised the secondary endpoints. Results: A total of three studies including 227 patients were included in the analysis. Combination therapy was associated with a significantly increased OS (Pooled RR: 1.66, 95% CI: 1.23 to 2.25, P=0.001, I2=0%), PFS (Pooled RR: 2.36, 95% CI: 1.54 to 3.61, P&lt;0.0001, I 2 =0%) and DCR (MD: 39.88, 95% CI: 29.22 to 50.53, P&lt;0.00001, I 2 =0%). The incidence of grade 3-5 adverse events was higher in the combination arm (Pooled RR: 5.38, 95% CI: 1.60 to 18.11, P=0.007, I 2 =0%), however treatment discontinuations (Pooled RR: 1.84, 95% CI: 0.62 to 5.40, P=0.27, I 2 =0%) due to adverse events did not significantly differ between the two groups. Conclusions: Nivolumab and Docetaxel combination therapy demonstrates greater efficacy compared to monotherapy for the management of advanced NSLC. However, careful patient selection and monitoring is imperative to minimize adverse events. Further, well designed trials and real-world studies are needed to confirm these findings and guide patient management.