Introduction: Immune checkpoint inhibitors (ICIs) are increasingly being used to treat lung cancer perioperatively. Although ICI use has led to long-term improvements in patient outcomes, its high costs have increased medical expenses. We evaluated the cost-effectiveness of perioperative ICI therapy for NSCLC in Japan, the USA, and Brazil. Methods: Hazard ratios of disease-free survival and overall survival for neoadjuvant or adjuvant chemotherapy and neoadjuvant, adjuvant, or neoadjuvant plus adjuvant therapy with ICI were estimated from landmark phase III trials using a network meta-analysis. A partitioned survival model was used to estimate quality-adjusted life-years and life-years. Drug and hospitalization costs were included using standard regimens as of April 2023, discounted at 2% annually. Results: The incremental cost-effectiveness ratio (ICER) per quality-adjusted life-years for neoadjuvant chemotherapy compared with no perioperative treatment was ¥714,940 ($4468) in Japan. That for neoadjuvant therapy by ICI compared with neoadjuvant chemotherapy was ¥5,285,770 ($33,036). The ICERs for other regimens were not calculated because of their dominance. In the USA and Brazil, the ICERs for neoadjuvant chemotherapy were $32,726 and $29,320, respectively, whereas those for neoadjuvant therapy with ICI were $228,467 and $92,573, respectively. Conclusions: The ICER threshold in Japan is generally ¥5 million and ¥7.5 million for essential drugs such as anticancer agents. The ICER of neoadjuvant chemotherapy was lower than the former threshold, whereas that of neoadjuvant nivolumab was lower than only the latter threshold. Therefore, neoadjuvant chemotherapy is cost-effective in Japan, the USA, and Brazil, whereas neoadjuvant nivolumab is only cost-effective in Japan.

Background:Obesity's impact on cancer treatment outcomes is poorly understood, especially in the context of immuno-oncology. This study explores how obesity and medical comorbidities are associated with overall survival in cancer patients receiving immune checkpoint inhibitors (ICIs). Additionally, considering the influence of sex on body composition in obesity, this study examines the relationship between sex, obesity, medical comorbidities, and survival. Methods:This cohort study involved 688 patients with metastatic cancer received ICIs as first- or second-line therapy. Obesity was assessed using body mass index (BMI). Cox proportional hazard models and Kaplan-Meier survival analysis were used to examine associations between predictors and overall survival. Results:Patients with higher BMI had longer overall survival, and hazard ratio (HR) for death was 0.83 (95% CI 0.73-0.95) for every 10 units increased in BMI. Additionally, patients belonged to the highest BMI group (≥ 40) had the lowest risk of death when comparing to patients with BMI 18.5 to < 30 with HR 0.58 (95% CI 0.37-0.90). In subgroup analysis, a significant association between high BMI and decreased HR for death was predominantly observed in the male cohort. In multivariate analysis, the prognostic value of BMI remained significant after adjusting for performance status, line of therapy, age-adjusted medical comorbidities, and cancer type. Conclusions:Obesity was associated with decreased mortality risk for cancer patients who had received ICIs. There could be a sex-dependent association between survival benefit and obesity.

Abstract Resistance to radiation, chemotherapy, and immunotherapy remains a major challenge in non-small cell lung cancer (NSCLC), and emerging evidence suggests tumor-resident microbes may influence therapeutic response. To address this, we combined patient-level modeling with mechanistic studies in preclinical models. We first analyzed RNA-sequencing data from 2,156 NSCLC tumors collected under the Total Cancer Care Protocol (NCT03977402) within the ORIEN network using a contamination-aware pipeline to quantify intratumoral Candida albicans (CA) and assess its impact on treatment outcomes. We developed MEC-TX (Mechanistic Clustering Treatment), a digital-twin framework that compares patients receiving similar treatment regimens differing only by CA burden. CA was detected in ∼55% of tumors; high CA burden was associated with significantly shorter overall survival (hazard ratio 1.6, p < 0.01), and similar trends were observed in radiation- and chemotherapy-treated cohorts defined by MEC-TX. After adjusting for clinical covariates (age, sex, stage, BMI), CA remained an independent predictor of poor survival, underscoring MEC-TX’s ability to isolate biologically meaningful signals. Transcriptomic profiling revealed CA-high tumors had elevated hypoxia-related gene expression (p = 0.0045), suggesting a link between fungal infiltration and tumor microenvironment. To test this, we implanted Lewis lung carcinoma cells into syngeneic C57BL/6 mice and gavaged them with CA, Blautia obeum (commensal control), or saline (vehicle control). CA-gavaged tumors were significantly larger (p = 0.0108) and exhibited lower pH (p = 0.024) and reduced intratumoral pO2 (p = 0.051) compared to controls, as measured by EPR oximetry, after adjusting for tumor size, supporting CA’s role in creating a hypoxic, therapy-resistant niche. In vitro, CA-conditioned media conferred radioresistance across multiple cell lines (p = 0.001), implicating secreted molecules as drivers of this phenotype. Collectively, these findings reveal a novel mechanism by which intratumoral fungi promote hypoxia and treatment resistance, providing a strong rationale for microbiome-informed strategies to overcome hypoxia-driven resistance and improve precision oncology. Citation Format: Dipankor Chatterjee, Dennis J. Grencewicz, Alexander Loncar, Ruohan Wu, Alex Samouilov, Sylvain Ferrandon, McKenzie Kreamer, Yogita Mehra, Aspen Carson, Rebecca Hoyd, Shiva Jahanbakhshi, Fouad Choueiry, Matthew Anderson, Martin Benej, Dustin Bosch, Jiangjiang (Chris) Zhu, Jinghai Wu, Thèrése Bocklage, Martin McCarter, Ahmad Tarhini, Bodour Salhia, Christopher A. Moskaluk, Gregory Riedlinger, Song Yao, Ashiq Masood, Sheetal Hardikar, Mmadili N. Ilozumba, Cornelia M. Ulrich, Abdul Rafeh Naqash, Carlos H.F. Chan, Craig D. Shriver, Dinesh Pal Mudaranthakam, Aaditya Pallerla, Michelle Churchman, Robert J. Rounbehler, Laura Chambers, Matthew F. Kalady, Nicholas C. Denko, David P. Carbone, Dan Spakowicz. Intratumoral Candida albicans associates with hypoxia and poor outcomes in non small cell lung cancer (NSCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 63.

Metastasis remains the leading cause of cancer-related mortality, yet predicting future metastasis is a major clinical challenge due to the lack of validated biomarkers and effective assessment methods. Here, we present EmitGCL, a deep-learning framework that accurately predicts future metastasis and its corresponding biomarkers. Based on a comprehensive benchmarking comparison, EmitGCL outperforms other computational tools across six cancer types from seven cohorts of patients with superior sensitivity and specificity. It captures occult metastatic cells in a patient with a lymph node-negative breast cancer, who was declared to have no evidence of disease by conventional imaging methods but was later confirmed to have metastatic disease. Notably, EmitGCL identifies HSP90AA1 and HSP90AB1 as predictable biomarkers for future breast cancer metastasis, which we validate by in-vitro pharmacological inhibition of HSP90 that reduced breast cancer cell migration and further support across five independent cohorts of patients (n = 420). Furthermore, we demonstrate YY1 transcription factor as a key driver of breast cancer metastasis, which we corroborate with in-silico, CRISPR-based migration assays, and in vivo mouse lung colonization experiments, suggesting that YY1 is a potential therapeutic target for further investigation.

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of non-small cell lung cancer (NSCLC). However, their low response rates and poor 5-year survivals indicate a need for improvement. One key factor in this resistance may be molecules that mediate immunosuppression within the tumor microenvironment (TME), such as adenosine. Combining therapies that mitigate the effects of adenosine with ICIs could potentially overcome these limitations. We utilized the Lewis lung carcinoma (LLC) and CMT167 murine lung carcinoma models to investigate the combined use of the A2B receptor antagonist PBF1129 and anti-PD-1 ICI. The mechanisms underlying the efficacy of this combination therapy were explored using single-cell RNA sequencing (scRNA-seq). In both models, combination therapy improved tumor control. Our scRNA-seq analysis characterized alterations in malignant cells, macrophages, cancer-associated fibroblasts (CAFs), T cells, and endothelial cells in the tumor after treatment. Malignant cells treated with combination therapy exhibited reduced inflammatory, epithelial-to-mesenchymal transition (EMT) and angiogenic signatures. Malignant cells and M2-like macrophages showed high expression of TGFβ pathway genes, which were significantly reduced in the combination therapy group. We also observed decreased interactions between M2-like macrophages and CAFs as well as T cells, and dramatically increased Gzmb expression in M1-like macrophages with combination therapy. Combination therapy modulated TGFβ-mediated cellular crosstalk and extracellular matrix (ECM) remodeling. Our findings suggest that inhibition of adenosine activity by blocking the A2B receptor reduces TGFβ signaling and enhances the efficacy of ICI therapy in NSCLC.

Abstract Background: Lung cancer in young adults is biologically distinct, with 84% harboring targetable mutations largely unassociated with active and passive tobacco exposure. Environmental risk factors remain poorly characterized in this predominantly female, non–tobacco smoking population. Methods: We analyzed 187 patients in the Epidemiology of Young Lung Cancer study using biological pathway groupings: EGFR Pathway (EGFR + ERBB2), Fusion-Positive (ALK + ROS1 + RET + NTRK), and Other/Mixed Mutations (KRAS, BRAF, MET exon 14 skipping, TP53, and additional alterations). Dietary quality was assessed using the Healthy Eating Index (HEI)-2015 and compared with US reference values from National Health and Nutrition Examination Survey. Statistical comparisons used one-sample t tests. Results: Active and passive tobacco use diverged from traditional mutation associations. In the Other/Mixed Mutations group, 68.8% never used tobacco despite these mutations being linked to tobacco exposure. Conversely, the EGFR Pathway group included 32.9% with a history of tobacco use. Oral contraceptive use among females was consistently elevated (81.7%–90.2%). Dietary analysis revealed that EGFR Pathway and Fusion-Positive patients demonstrated higher HEI-2015 scores versus the US reference (64.9 ± 10.7 and 65.5 ± 9.8 vs. 58) and consumed more total vegetables (4.2 vs. 3.5), fruits (3.3 vs. 2.5), and whole grains (3.9 vs. 2.6). Conclusions: Young patients with lung cancer demonstrated mutation-specific environmental exposure patterns distinct from older populations. EGFR Pathway and Fusion-Positive patients had the highest diet quality scores, driven primarily by higher intake of vegetables, fruits, and whole grains—food categories with established protective associations and documented pesticide residues. Impact: These findings highlight nontobacco environmental exposures in young patients with lung cancer and support further investigation of dietary patterns and hormonal factors in mutation-specific disease pathways.

Abstract Small-cell lung cancer is an aggressive subtype of lung cancer with poor prognosis and comprises approximately 15% of all lung cancers. The frontline therapy for SCLC is platinum-etoposide chemotherapy. However, patients almost relapse shortly after the start of therapy, and second line therapies typically provide only a few months of benefit. Clearly, better therapeutics are necessary for the treatment of SCLC. Cancer cells often have dysregulated metabolic pathways. These changes are often necessary to enable the continued proliferation of cancer cells. Dihydroorotate dehydrogenase (DHODH), which catalyzes the conversion of dihydroorotate to orotate in the pyrimidine de novo synthesis pathway, has a particular role in the survival of multiple cancers including SCLC. Recent studies have shown that SCLC cells are thought to respond to therapy but recur due to a chemotherapy-resistant “stem cell” or “persister” population of tumor cells induced by therapy. Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is a receptor tyrosine kinase that is re-expressed in multiple cancers, including SCLC, where its expression is associated with shorter survival and rapid relapse. Therefore, targeting ROR1 may reduce stem-like tumor cells and improve therapeutic response in SCLC. We evaluated the effect of HOSU-53, a DHODH inhibitor, on SCLC tumor growth in vitro. We measured IC50s of 18 SCLC cell lines and most SCLC cells showed promising sensitivity to HOSU-53 treatment. However, some SCLC cells demonstrated resistance to DHODH inhibition. Therefore, we evaluated the synergy between HOSU-53 and KAN0441571C, a ROR1 inhibitor in vitro. SCLC cells were treated with the compounds as single agents as well as the combination. Synergy was observed between KAN0441571C and HOSU-53 in SCLC cells. To evaluate the effect of DHODH inhibition on SCLC tumor growth in vivo, we treated xenograft models with HOSU-53 alone or in combination with etoposide plus cisplatin. We observed a significant decrease in tumor volume when HOSU-53 was used alone and in combination, without significant animal weight loss. Additionally, to evaluate the effect of HOSU-53 and ROR1 inhibition on tumor burden in vivo, a treatment-resistant xenograft SCLC model was treated with HOSU-53 and KAN0441571C as single agents and the combination. We observed a significant reduction in tumor volume in the combination arm compared with the single-agent treatment arms, without significant loss of body weight. Together, these data demonstrated the promising efficacy of HOSU-53 as single agent as well as in combination with KAN0441571C in treatment-resistant SCLC models. These findings support the initiation of a phase l clinical trial to evaluate the preliminary efficacy and tolerability of HOSU-53 and support the strategy of targeting DHODH and ROR1 as a potential therapeutic approach for the treatment of SCLC. Citation Format: Bahareh Nourmohammadi, Ola A. Elgamal, Sandip Vibhute, Christopher C. Coss, Thomas E. Goodwin, Erin Hertlein, Joseph M. Amann, Ju Hwan Cho, Chad E. Bennett, John C. Byrd, David P. Carbone. Dihydroorotate dehydrogenase (DHODH) inhibition as a promising therapeutic strategy with synergistic targeting of ROR1 in small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7905.

Abstract Purpose: To identify variables associated with early detriment on first-line dual immunotherapy from the phase III CheckMate 227 and CheckMate 9LA studies. Patients and Methods: Adults with stage IV/recurrent non–small cell lung cancer (NSCLC) lacking EGFR/ALK alterations were randomized to nivolumab plus ipilimumab, nivolumab (PD-L1 ≥1%) or nivolumab plus chemotherapy (PD-L1 <1%), or chemotherapy in CheckMate 227 or to nivolumab plus ipilimumab with chemotherapy or chemotherapy in CheckMate 9LA. Multivariable analyses were used to identify factors associated with rapid progression (progression or death within 3 months of randomization) from nivolumab plus ipilimumab in CheckMate 227, and univariate analyses were used to assess rapid progression from nivolumab plus ipilimumab with/without the addition of chemotherapy from CheckMate 227 and CheckMate 9LA. Results: Rapid progression rates were 40% with nivolumab plus ipilimumab versus 26% with chemotherapy. High neutrophil-to-leukocyte ratio, baseline tumor mutational burden (TMB) <14 mutations per megabase, tumor PD-L1 <1%, low albumin level, and higher-than-median baseline monocytic myeloid-derived suppressor cell (M-MDSC) level were associated with rapid progression in patients treated with nivolumab plus ipilimumab. Early detriment was not observed with nivolumab plus ipilimumab with chemotherapy across subgroups from CheckMate 9LA. Long-term survival favored nivolumab plus ipilimumab–containing treatment across subgroups. Conclusions: Neutrophil-to-leukocyte ratio, TMB, tumor PD-L1 expression, albumin level, and baseline M-MDSC level were associated with rapid progression in patients with metastatic NSCLC treated with first-line nivolumab plus ipilimumab. Relative to chemotherapy, early detriment was observed with nivolumab plus ipilimumab across biomarker subgroups but not with nivolumab plus ipilimumab with chemotherapy. Long-term benefit was maintained with both regimens.

BACKGROUND:Crizotinib is an established first-generation anaplastic lymphoma kinase (ALK) inhibitor approved for the treatment of advanced ALK-positive non-small-cell lung cancer (NSCLC). E4512 aimed to evaluate the effect of adjuvant crizotinib on disease-free survival (DFS) in patients with resected, early-stage ALK-positive NSCLC. METHODS:In this randomised, controlled, phase 3 trial conducted in 1618 sites across the USA, Guam, and Puerto Rico, patients were randomly assigned 1:1 by computer-generated sequence to receive crizotinib 250 mg orally twice daily or observation (changed from initial double-blind placebo) for up 2 years. Eligible patients had resected NSCLC tumours that were 4 cm or larger in diameter or lymph node-positive, negative surgical margins, no neoadjuvant therapy, ALK positivity by local or central testing, and an Eastern Cooperative Oncology Group performance status of 0-1. Adjuvant chemotherapy was allowed but not required. Stratification factors were stage, previous radiation therapy, and sex. The primary endpoint was disease-free survival (DFS) in the centrally tested ALK-positive intention-to-treat population and presented as hazard ratio with 90% and 95% CI. The trial was registered at ClinicalTrials.gov (NCT02201992) and is completed. Safety was assessed in all patients whose tumours tested ALK-positive and who received the study drug. FINDINGS:Between Aug 18, 2014, and May 10, 2024, 166 patients (of 168 planned) were enrolled (85 to crizotinib and 81 to observation). Accrual was stopped when the US Food and Drug Administration approved adjuvant alectinib for resected ALK-positive NSCLC. Overall, 153 (92%) patients had centrally confirmed ALK-positive tumours. Among these 153 individuals, 99 (65%) were female, 54 (35%) were male, and 121 (79%) were White. After a median follow-up of 65·7 months (IQR 37·5-85·6), median DFS was 74·6 (95% CI 71·2 to not assessable) months in the crizotinib group and 106·2 (67·8 to NA) months in the observation group (HR 1·08 [90% CI 0·67-1·73; 95% CI 0·61-1·90; p=0·80). In the crizotinib group, 46 (58%) patients had grade 3 or higher adverse events of any attribution (most commonly diarrhoea, in eight [10%] patients; oedema, in four [5%] patients; and hypertension, in four [5%] patients), including one death that was not deemed treatment-related. 21 (27%) patients had serious adverse events, most commonly dyspnoea (three [4%] patients), abdominal pain (two [3%] patients), thromboembolic event (two [3%] patients), diarrhoea (two [3%] patients), dehydration (two [3%] patients), and hypertension (two [3%] patients). INTERPRETATION:Adjuvant crizotinib does not prolong DFS in patients with surgically resected ALK-positive NSCLC. These findings suggest that crizotinib should not be recommended as an adjuvant therapy for patients with resected ALK-positive NSCLC. FUNDING:National Cancer Institute of the US National Institutes of Health.

Inhalable particulate matter (PM) has emerged as a critical yet underappreciated carcinogenic factor in lung cancer, especially affecting non-smokers and populations residing in heavily polluted regions. Epidemiological research has confirmed the link between PM exposure and lung cancer risk, but the underlying biological pathways and clinical relevance are still not well understood. Here, we provide a comprehensive synthesis of current advances in PM-associated lung carcinogenesis, from population-level risk patterns to molecular pathogenesis and translational strategies. We outline the epidemiological burden and unique clinical features of PM-related lung cancer. We then propose a "Hallmarks of PM-associated lung cancer" framework, summarizing 12 features of how lung cancer evolves under PM exposure. This involves a complex interplay of cell-intrinsic oncogenic traits induced by PM (genetic alterations, epigenetic reprogramming, metabolic remodeling, stemness) and microenvironment reshaped by PM (inflammatory responses, immune suppression, angiogenesis, and pre-metastatic niche formation). Moreover, we critically examine the technical challenges in mechanistic studies and propose future solutions. Finally, we highlight urgent opportunities for integrating PM exposure into lung cancer screening, risk stratification, and prevention policies. This review offers a comprehensive framework for strategies to downsize the impact of air pollution on global lung health.

Lung cancer is the leading cause of cancer mortality worldwide, including young adults. While it is well known that cigarette smoking is the dominant risk factor for lung cancer, the inhalation of heated aerosolized vaping oil has now replaced cigarette smoking as the major source of nicotine among young people. We, therefore, studied the potential role of both vaping and cigarette smoking in the development of early onset lung cancer. Using a case-control study design, we compared the smoking and vaping habits of 256 young adults (< 50 years of age) diagnosed with pathologically confirmed lung cancer to that of 2,921 control subjects without cancer that were group matched by age (within 5 years), sex, race and location to the cases. The odds ratio for those who both vaped and smoked (OR = 13.8, 95% CI: 7.7-24,9) was 2.8 times higher than for smoking alone (OR = 5.0, 95% CI: 3.7-6.9). Pulmonary adenocarcinomas accounted for 72% of the early onset lung tumors among the cases, and risk estimates for this specific cell type were 3.7 times higher for those who smoked and vaped (OR = 14.8, 95% CI = 8.0-27.4) compared to those who only smoked (OR = 4.0, 95% CI = 2.9-5.6). Our findings suggest that compared to smoking alone, vaping and smoking together accelerate lung cancer risk among young people, particularly in the development of pulmonary adenocarcinoma.

Abstract Immune checkpoint inhibitors (ICIs) are seminal advances in cancer therapeutics, yet response rates are variable. The gut microbiome is increasingly recognized as a modifiable determinant of ICI efficacy. The BEWELL trial delivered a black raspberry (BRB) nectar dietary intervention that significantly enriched the colonic microbiome with members of the Lachnospiraceae family. When BRB-modulated microbiomes were transferred into mice, these microbiomes enhanced ICI antitumor activity, implicating specific taxa in shaping therapeutic responsiveness.To investigate the mechanism by which Lachnospiraceae altered ICI effectiveness, we individually supplemented the microbiomes of mice with closely related strains enriched by BRB: Blautia obeum, Blautia massiliensis, and Agathobacter rectalis. In a heterotopic mouse model (1×106 MC38 cells injected subcutaneously into C57BL/6 mice, treated every 3 days with anti-PD1 or IgG), B. obeum and B. massiliensis improved ICI effectiveness, whereas A. rectalis did not. We compared the genomes of these organisms and identified 177 KEGG orthologs uniquely shared by B. obeum and B. massiliensis but absent in A. rectalis. KO pathway assignments and enrichment analyses were conducted using KEGGREST mapping and clusterProfiler overrepresentation testing, with all genome-encoded KOs as the background.We identified four relevant pathways associated with immunity and ICI response:(1) Key genes for the Wood-Ljungdahl pathway, a major route for producing acetate, shown to be a T-cell energy source (acetyl-CoA decarbonylase/synthase (K00194, K00197, K00198) and putative phosphotransacetylase (K01490));(2) Genes for synthesizing vitamins essential for T-cell proliferation—folate (B9) (dihydropteroate synthase (K00796), GTP cyclohydrolase I (K022391), methylenetetrahydrofolate reductase (K00297)) and cobalamin (B12) (cob(I)alamin adenosyltransferase (K019221), corrinoid adenosyltransferase (K0174), cobalamin reductase (K0175));(3) L-rhamnose synthesis genes whose cell-wall decorations act as microbe-associated molecular patterns, priming innate immunity (dTDP-4-dehydrorhamnose reductase (K00067) and dTDP-glucose 4,6-dehydratase (K00935)); and(4) Genes converting bile acids to secondary, iso-bile acids that interact with host receptors (FXR, TGR5) to regulate Th17/Treg balance (3-alpha-hydroxycholanate dehydrogenase (K0164)) Collectively, these processes align with host-relevant metabolic and signaling environments that may impact anti-tumor immunity. Our study suggests that novel food products can be developed for human testing to enhance anticancer immunotherapeutics. Furthermore, BRB-responsive Lachnospiraceae possess enriched metabolic and immunomodulatory gene programs that may underlie their association with improved tumor response to ICI treatment. Citation Format: Shiva Jahanbakhshi, Amna Bibi, Rebecca Hoyd, Caroline Dravillas, Nyelia Williams, Shiqi Zhang, Aaditya Pallerla, Shankar Suman, Joseph Amann, Mounika Goruganthu, Tamio Okimoto, Yangyang Liu, Marisa A. Bittoni, Ni Shi, Alvin Anand, Bailey Conrad, Lane Nevers, Kristen Heitman, Maxine Webb, Elizabeth M. Grainger, Madison Grogan, Christian Quiles, Tong Chen, Carolyn J. Presley, Lang Li, Patrick Bradley, Yael Vodovotz, David P. Carbone, Steven K. Clinton, Jiangjiang Zhu, Daniel Spakowicz, . Comparative genomics of gut commensal Lachnospiraceae and their associations with cancer treatment response with immune checkpoint inhibitors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 2861.

The amount of data collected in oncology clinical trials has grown exponentially over recent years, posing significant burdens on trial participants, investigators, and trial sites. The frequency, magnitude, and strict standardization of trial-related assessments and data collection do not reflect routine clinical care and can limit participation of some patients and trial sites in clinical research. Though the use of simplified trial designs to align trial conduct more closely with routine care has been promoted across stakeholders, including the US Food and Drug Administration, there remains a dearth of guidance as to how to put this concept into practice in specific use cases. Focusing specifically on trials intended to support a supplemental application for a new indication of an approved therapy, a multistakeholder working group convened by LUNGevity Foundation developed recommendations for streamlining lung cancer clinical trial assessments. The present report details important considerations raised by the working group for establishing the frequency, conduct, and location of common lung cancer trial protocol assessments.