Pleural Mesothelioma (PM) is an aggressive cancer that attacks thousands of people every year. One of the common treatments is surgery to remove the tumor. Unfortunately, around 11% of patients die from blood clots post-surgery. Current predictive factors such as C-reactive protein, D-Dimer, and abnormal platelet count lack specificity. To date, no blood-based protein biomarkers have been identified to reliably predict PM patients at risk of developing Venous Thromboembolism (VTE) post-surgery. In this study, we present a set of host-response plasma protein candidate biomarkers that could predict patients at risk of developing VTE. We employed a quantitative mass spectrometry-based proteomics approach integrated with a multilayered, structured, and systematic evaluation of candidate biomarkers in a cohort of 18 patients, comprising six mesothelioma cases, six mesothelioma controls, and six lung cancer controls. This is the first step towards personalized treatment plans for PM patients undergoing surgery. This study’s findings can potentially guide subsequent, larger-scale investigations, highlighting the value of small-scale exploratory research.

TPS8132 Background: Chemotherapy combined with PD-1 or PD-L1 blockade (chemo-immunotherapy, ChemoIO), administered in the neoadjuvant, adjuvant, or perioperative setting, has become standard of care for surgically resectable non-small cell lung cancer (NSCLC). However, ChemoIO may be associated with significant toxicity that may limit treatment delivery and compromise surgical fitness. Preclinical data demonstrate that non-ablative stereotactic body radiotherapy (SBRT) can synergize with immunotherapy by enhancing tumor antigen release, interferon signaling, T-cell priming, and systemic antitumor immunity. We previously completed a phase II trial comparing neoadjuvant non-ablative SBRT (24 Gy) plus immunotherapy (SBRT-IO) versus immunotherapy alone, demonstrating favorable tolerability and higher rates of major and complete pathological response (MPR, pCR) in the SBRT-IO arm. SBRT-IO may therefore represent a neoadjuvant alternative for selected patients, with the potential to reduce treatment-related toxicity. Methods: RICHIS (NCT06623656) is an open-label, multicenter, randomized phase II trial enrolling approximately 112 patients with histologically confirmed, surgically resectable clinical stage IB-III (N2) NSCLC. Eligible patients are ≥18 years old, have ECOG performance status 0-1, and lack EGFR mutations or ALK fusions. Participants are randomized 1:1 to receive neoadjuvant SBRT-IO (SBRT 8 Gy × 3 fractions plus up to three cycles of cemiplimab) or standard ChemoIO (platinum-based doublet chemotherapy plus up to three cycles of cemiplimab). Randomization is stratified by tumor PD-L1 expression ( < 1% vs. ≥1%) and clinical stage (IB/II vs. III). Following neoadjuvant therapy, all patients undergo surgical resection and receive adjuvant cemiplimab for up to 12 months; patients in the SBRT-IO arm may additionally receive adjuvant chemotherapy. The primary endpoint is pCR. Key secondary endpoints include grade 3-5 adverse events (neoadjuvant and postoperative), event-free survival, MPR, and postoperative length of stay. Correlative immune and molecular biomarker studies are planned. Trial enrollment began on 2/4/2025 and is currently enrolling across 2 sites, with planned enrollment at 5 US sites. 19 of 112 patients are currently accrued. Clinical trial information: 24-02027124 .

Background:Pleural mesothelioma (PM) represents an uncommon and exceptionally lethal malignancy. The sarcomatoid subtype constitutes the rarest histological variant, traditionally linked to the worst prognosis, while the advantages of operative intervention remain inadequately established. In this study, we present findings from a cohort of 34 sequential cases with sarcomatoid mesothelioma managed at a specialized high-volume center employing pleurectomy decortication (PD) within a comprehensive therapeutic strategy. We aim to identify patients in this cohort who may benefit from a multimodality approach. Methods:All patients diagnosed with sarcomatoid mesothelioma between 2007 and 2019 who received PD at our facility were enrolled, and relevant medical, histopathological, and operative data collected. Survival curves generated through Kaplan-Meier methodology alongside log-rank testing enabled comparison of longevity outcomes, while Cox proportional hazards modeling facilitated examination of predictive variables. Results:The cohort included 31 male subjects (91.2%), 24 procedures performed on the right side (70.6%), with a median patient age of 71.5 years (range, 51-85 years). Preoperative treatment was administered to 8 individuals (24.2%), while 23 participants (67.7%) underwent intraoperative heated chemotherapy (IOHC). Macroscopic complete resection (MCR) was accomplished in 22 cases (64.7%). Mortality at 30 and 90 days post-surgery stood at 2.9% and 14.7%, respectively. The median overall survival for the entire cohort reached 7.4 months, extending to 20.1 months among those with forced expiratory volume in 1 second (FEV1) at or above 80% predicted. In multivariate analysis, preoperative FEV1 ≥80% was associated with prolonged overall survival [P=0.01; hazard ratio (HR) =0.54]. Conclusions:As expected, the median survival for most patients with sarcomatoid histology who undergo surgery is under one year. However, a small subset of patients with FEV1 ≥80% do quite well using the multimodality approach.

In this article, we summarize the progress made in lung cancer, mesothelioma, and thymic epithelial malignancy during the period 2005-2025. We enlisted multidisciplinary thoracic oncologic experts to tackle this task. The main focus of the article concerns how basic science with translational impact has improved the diagnosis, prognosis, and therapy of these cancers. During the past 20 years, we have come to the realization that "lung cancer" is a name that encompasses tumors with vast histologic, immune, and genomic differences that in turn influence prognosis and response to therapy. For example, programmed death-ligand 1 levels are being used as an immune signature which guides the use of immunotherapy. There is an 85% higher risk for developing lung cancer among first-degree relatives of patients with lung cancer. Accordingly, an increasing number of lung cancers are being identified in carriers of predisposing germline pathogenic inactivating mutations, suggesting that screening programs for early lung cancer detection may benefit family members. Underscoring the role of genetics, and the importance of germline testing, a different variant of mesothelioma has been identified developing in carriers of inactivating heterozygous germline mutations of BAP1 and of other tumor suppressor genes, including a new variant of mesothelioma caused by fusion genes. These variants of mesothelioma are characterized by specific histologic and molecular genetic alterations. These patients benefit from screening programs as they are at risk of multiple malignancies, their tumors are usually much less aggressive, and they are more responsive to therapy compared with sporadic, asbestos-induced mesotheliomas. Thus, the tailored therapeutic approach that is described here for lung cancer may extend to patients with mesothelioma, rather than the previous "one therapy fits all" approach. Progress in the rare thymic epithelial tumors has been less marked; however, recent insights into the biology of thymic tumors have resulted in the development of clinically relevant interventions.

BACKGROUND:Lung adenocarcinomas presenting as mixed ground-glass nodules (GGNs) are commonly treated by sublobar resection with favorable survival, but the optimal margin remains unclear. METHODS:We retrospectively reviewed patients with cT1 (≤3 cm) GGNs who underwent curative sublobar resection (January 2012-December 2020) and had invasive adenocarcinoma confirmed. Patients with uncertain/positive margins or positive lymph nodes were excluded. Margin distance was pathologically defined as the shortest distance from tumor edge to resection margin. Cox proportional hazards regression, Kaplan-Meier, and competing-risk analysis were used to assess the relationship between the margin-to-tumor diameter ratio (MTR) and margin-to-solid component ratio (MSR) and locoregional recurrence-free survival (LRFS). Optimal cutoffs for LRFS prediction were identified using recursive classification tree analysis. RESULTS:Among 208 patients (median follow-up, 64 months), median tumor, solid component, and margin sizes were 18.0, 6.25, and 12.0 mm, respectively. Recursive partitioning identified MTR as most predictive, with an optimal cutoff of ∼0.174. MTR and MSR were the top influential predictors and strongly correlated through a second-degree polynomial model. Patients with MTR ≥0.2 had significantly improved LRFS compared with those with MTR <0.2 (log-rank P = .0026) and reduced recurrence (subdistribution hazard ratio, 0.203; 95% CI, 0.067-0.619; P = .005). In multivariable Cox regression, MTR ≥0.2 remained an independent predictor of improved LRFS (hazard ratio, 0.15; 95% CI, 0.04-0.51; P = .003). CONCLUSIONS:For sublobar resection of invasive lung adenocarcinoma as mixed GGNs, a margin distance of >0.2 times the tumor diameter is clinically significant to optimize local control.

Rationale and Objectives Accurate clinical staging in pleural mesothelioma (PM) is limited by the subjectivity of conventional imaging assessment, which introduces inter- and intraobserver variability. Tumor volume, pleural thickness and diaphragmatic thickness measurements individually prognostic — offer objective, quantifiable surrogates for locoregional tumor burden. We evaluated these Magnetic Resonance Imaging (MRI)-derived metrics to develop a reproducible quantitative clinical T-classification strategy for PM that offers objective, reproducible surrogates for tumor burden with reduced interobserver variability compared to qualitative MRI staging. Materials and Methods Patients referred for surgical evaluation of PM between 2009 and 2014 who underwent MRI using an IRB-approved protocol were included. For survival analyses, only patients with complete data and uniform treatment were analyzed. Quantitative measures included MR-derived tumor volume (VolMR), summed unidimensional pleural thickness (Psum) and Fissural and diaphragmatic thickness (Ptotal= Psum+Fmax+Dtotal) Optimal categorical thresholds were derived by survival-based optimization using the log-rank statistic, implemented via Classification and Regression Trees (CART) with 20-fold cross-validation. Predictive accuracy was assessed using univariable Cox models and C-statistics, and survival curves were generated using Kaplan-Meier estimates. Continuous variable Cox models were also constructed for VolMR and Ptotal. Analyses were stratified by surgical modality to assess robustness. Results Of 695 patients evaluated, 377 had eligible MR imaging. Median age was 68 years; 77% were male and 60% had epithelioid tumors. Clinical Tumor Node Metastasis staging was concordant with pathology in 52.5%, understaged in 33%, and overstaged in 14% of patients. Among evaluated metrics, diaphragmatic thickness (C-statistic = 0.5996) and total pleural thickness (0.5868) demonstrated the highest predictive accuracy. Survival curves showed strong stratification using Ptotal and VolMR. Head-to-head comparison with AJCC 8th edition qualitative T staging (C-statistic 0.6022) showed that Ptotal-based categories (C=0.6217) and VolMR-based categories (C=0.6364) provided superior survival stratification. Conclusion Quantitative MR-derived Ptotal and VolMR improve upon qualitative T category in PM by offering objective, reproducible surrogates for tumor burden with strong prognostic stratification when appropriate cut points are applied. These metrics could support future Tumor Node Metastasis refinements and individualized treatment planning.

TPS9616 Background: Tumor infiltrating lymphocyte (TIL) therapy is an autologous cellular therapy isolated from a patient's tumor. Clinical data demonstrated that TIL therapy in heavily pretreated melanoma patients yielded an objective response rate (ORR) in 30% of patients with 5-year overall survival (OS) of approximately 20%. TILs were approved by the FDA in February 2024 for the treatment of metastatic or unresectable melanoma that have progressed on anti-PD-1 therapy and BRAF+MEK inhibitors (in patients with BRAFV600 mutation). Non-melanoma skin cancers, including cutaneous squamous cell cancer (CSCC) and Merkel cell cancer (MCC), share biologic features with melanoma, including an “inflamed” tumor microenvironment and high responsiveness to anti-PD-1 therapy. However, approximately, a third of patients will experience disease progression after anti-PD-1 therapy or will discontinue treatment due to toxicity and subsequently experience disease progression. Given the overlap between melanoma and CSCC/MCC, we hypothesize that TIL therapy may induce immune response against non-melanoma skin cancers. Because some of these tumors are superficial and are often ulcerated and can contain polymicrobial contamination, this trial will also assess the feasibility of TIL production in this unique patient population, alongside its safety and efficacy. Methods: Ten patients with CSCC (Cohort A) and 4 patients with MCC (Cohort B) adults will be eligible for TIL if they have disease progression after anti-PD-1 therapy. Eligible patients should have adequate organ function and be able to receive dose-reduced non-myeloablative lymphodepletion (NMA-LD) and interlukin-2 (IL-2). Following tumor harvest and TIL manufacturing, patients will receive NMA-LD including cyclophosphamide (30 mg/kg on days –5 and –4), and fludarabine (25 mg/m2 on days –5 to –1). Subsequently, patients will receive TIL on day 0 followed by IL-2 (600,000 IU/kg) for up to 6 doses. The primary objective is to evaluate feasibility and safety of TIL production and administration in cohorts A and B (defined by successful tumor harvest that leads to a TIL product that contains ≥ 1 x 10^9 cells, administration of NMA-LD, infusion of TIL therapy and complete at least 1 dose administered of IL-2). Secondary objectives include ORR, progression-free survival, duration of response, OS and correlative studies. Within Cohort A, efforts will be made to achieve an approximately equal distribution of ulcerated and non-ulcerated lesions. To maintain this balance, ulceration status will be monitored throughout the enrollment process, and eligibility criteria may be modified as necessary to ensure proportional representation of each subtype. Clinical trial information: NCT07288073 .

BACKGROUND:Pleural mesothelioma (PM) is a rare and complex thoracic malignancy for which treatment regimens continue to evolve. The role of surgery in the management of PM is controversial. We reviewed contemporary literature to provide consensus recommendations from an expert multidisciplinary panel on the multimodal treatment of PM with an emphasis on surgical intervention to update management pathways. METHODS:An international, multidisciplinary panel developed Population, Intervention, Comparator, Outcomes (PICO)-based questions and conducted a comprehensive literature review to identify relevant literature. Consensus statements were developed using a modified Delphi process with at least 75% agreement over three voting rounds. RESULTS:The panel developed 13 PICO questions, and detailed summary statements were provided for each PICO subtopic based on systematic literature review and multidisciplinary expert panel discussion. There was strong consensus that accurate diagnosis depends on adequate pleural biopsy specimens and that clinical evaluation should include, at a minimum, computed tomographic and positron emission tomographic imaging. Therapeutic decisions should be discussed by a multidisciplinary tumor board, including thoracic surgeons with expertise in PM treatment. If surgical resection is deemed appropriate, it should be part of a multimodal treatment plan. Pleurectomy/decortication or extended pleurectomy/decortication is strongly favored over extrapleural pneumonectomy as the approach to resection. CONCLUSIONS:This Society of Thoracic Surgeons Expert Consensus Document includes contemporary treatment recommendations for PM based on systematic literature review and multidisciplinary expert panel discussion and provides a management framework for practicing thoracic surgeons.

Current lung cancer screening fails to identify many individuals at risk beyond heavy smokers, highlighting the need for additional predictive biomarkers. This study profiles circulating exosomal small non-coding RNAs (sncRNAs) in a prospective cohort of 202 smokers, including 68 incident lung cancer cases with up to 16 years of follow-up. A structured 5 × 5 nested cross-validation framework incorporating feature selection, classifier comparison, and outer-loop evaluation identifies a panel of 31 sncRNA risk biomarkers. The optimized random forest model achieves an area under the curve (AUC) of 0.97 in outer-fold testing (sensitivity = 0.93; specificity = 1.00). The derived risk score remains independently associated with incident lung cancer after adjustment for demographic and smoking variables (odds ratio [OR] = 13.19, 95% confidence interval [CI] 6.83-25.45) and is associated with shorter time-to-diagnosis in competing risks analysis (subdistribution hazard ratio [sHR] = 4.78, 95% CI 3.57-6.41). Associations are observed up to 10 years prior to diagnosis. Target gene analysis implicates pathways relevant to lung tumorigenesis, including PI3K-Akt, p53, and MAPK signaling. These findings suggest that plasma exosomal sncRNAs may contribute to early lung cancer risk assessment and warrant further evaluation in independent pre-diagnostic cohorts.

BACKGROUND:With widespread adoption of segmentectomy for early-stage non-small cell lung cancer (NSCLC), the need to convert segmentectomy to lobectomy for nodal disease comes into question. We aimed to determine whether extent of resection impacts overall survival or locoregional recurrence-free survival (LRFS) in patients with occult N1 NSCLC. METHODS:We identified patients who underwent segmentectomy or lobectomy for NSCLC and were upstaged from cN0 to pN1 in our prospective institutional database from January 2006 to January 2023. Patients receiving neoadjuvant treatment or parenchymal resection beyond the segment(s) or lobe of interest were excluded. Propensity score weighting was used to control for potential confounders. Overall survival and LRFS were evaluated using Kaplan-Meier curves and compared with log-rank tests. Cox proportional hazards regression was used to calculate hazard ratios. RESULTS:Of 185 patients with occult N1 disease, 30 (16.2%) underwent segmentectomy and 155 (83.8%) lobectomy. Patients undergoing lobectomy had larger pathologic tumor sizes than those undergoing segmentectomy (3.4 cm [interquartile range, 2.30-4.45 cm] vs 1.95 cm [interquartile range, 1.43-2.83 cm], P < .005). There was no difference in rates of adjuvant therapy between segmentectomy and lobectomy (67% vs 70%, P = .7). Median follow-up was 60 months. There were no differences in 5-year survival or LRFS between segmentectomy and lobectomy before or after propensity weighting (weighted overall survival: 79.69% vs 66.22%, log-rank P = .401). In multivariable analysis of survival and recurrence, procedure type was not a predictor of outcome. CONCLUSIONS:Segmentectomy is associated with similar overall survival and LRFS to lobectomy for patients with occult N1 NSCLC.

Objective: Segmentectomy is becoming the standard of care for small, peripheral non-small cell lung cancer. To improve perioperative management in this population, this study aims to identify factors influencing hospital length of stay after segmentectomy. Methods: Patients who underwent segmentectomy for any indication between January 2018 and May 2023 were identified using a prospectively maintained institutional database. Multivariable logistic regression models were used to estimate associations between clinical features and prolonged (>= 3 days) hospital stay. A nomogram was designed to understand better and possibly calculate the individual risk of prolonged hospital stays. Results: In total, 533 cases were included; 337 (63%) were female. Median age was 66 years (interquartile range [IQR], 63-75). The median size of resected lesions was 1.6 cm (IQR, 1.3-2.1 cm). Median hospital stay was 3 days (IQR, 2-4 days). Major adverse events occurred in 31 (5.8%) cases. The 30-day readmission rate was 5.8% (n = 31). There was no 30-day mortality; 90-day mortality was<1%. Patients older than 75 years (odds ratio [OR], 2.01, 95% confidence interval [CI], 1.15-3.57, P = .02), those with forced expiratory volume in 1 second < 88 % predicted (OR, 1.99; 95% CI, 1.38-2.89, P < .001), or positive smoking history (OR, 1.72; 95% CI, 1.15-2.60, P = .01) were more likely to have prolonged hospital stays after segmentectomy. A nomogram accounting for age, sex, forced expiratory volume in 1 second, body mass index, smoking history, and comorbidities was created to predict the probability of prolonged hospital stay with an area under the receiver operating characteristic curve of 0.66. Conclusions: Older patients, those with reduced pulmonary function, and current and past smokers have elevated risk for prolonged hospital stays after segmentectomy. Validation of our nomogram could improve perioperative risk stratification in patients who undergo segmentectomy.

Liquid biopsy is a promising non-invasive technology that is capable of diagnosing cancer. However, current ctDNA-based approaches detect only a minority of early-stage disease. We set out to improve the sensitivity of liquid biopsy by harnessing tumor recognition by T cells through the sequencing of the circulating T-cell receptor repertoire. We studied a cohort of 463 patients with lung cancer (86% stage I) and 587 subjects without cancer using gDNA extracted from blood buffy coats. We performed TCR β chain sequencing to yield a median of 113,571 TCR clonotypes per sample and built a TCR sequence similarity graph to cluster clonotypes into TCR repertoire functional units (RFUs). The TCR frequencies of RFUs were tested for association with cancer status and RFUs with a statistically significant association were combined into a cancer score using a support vector machine model. The model was evaluated by 10-fold cross-validation and compared with a ctDNA panel of 237 mutation hotspots in 154 lung cancer driver genes and 17 cancer related protein biomarkers in 85 subjects. We identified 327 cancer-associated TCR RFUs with a false discovery rate (FDR) ≤ 0.1, including 157 enriched in cancer samples and 170 enriched in controls. Levels of 247/327 (76%) RFUs were correlated with the presence of an HLA allele at FDR ≤ 0.1 and tumor-infiltrating lymphocyte TCRs from multiple RFUs bound HLA presented tumor antigen peptides, suggesting antigen recognition as a driver of the cancer-RFU associations found. The RFU cancer score detected nearly 50% of stage I lung cancers at a specificity of 80% and boosted the sensitivity by up to 20 percentage points when added to ctDNA and circulating proteins in a multi-analyte cancer screening test. Overall, we show that circulating TCR repertoire functional unit analysis can complement established analytes to improve liquid biopsy sensitivity for early-stage cancer.

Introduction The phase 3 randomized controlled trial of extended pleurectomy decortication and chemotherapy versus chemotherapy alone for pleural mesothelioma (PM) (MARS2) reported “extended pleurectomy decortication was associated with worse survival to 2 years, and more serious adverse events for individuals with resectable PM, compared with chemotherapy alone.” These results have led to considerable discourse regarding the future role of surgery for PM, and there has not been unanimity in the mesothelioma surgical community regarding the trial interpretation. This “perspective” evaluates MARS2 using internationally renowned PM experts who either agreed with the trial interpretation or who found issues with its conduct which may have influenced the results. Methods A facilitator (HP) worked with team leaders (GW, IO) to assemble individuals offering opinions regarding the trial and its conclusions. Arguments agreeing or not agreeing with the trial interpretation were written only after publication of the full trial. Once both arguments were received by the facilitator, the individual team manuscripts were combined and sent to each team allowing editing for changes in perceived factual errors. Findings Insightful arguments include (but were not limited to) the difficulties yet advantages of randomization, quality assurance, selection of histologic subtypes, the timing of randomization, use of preoperative staging, statistical methods, and reasons for surgical mortality. Conclusions The decision to operate for PM in the future will continue to be defined by consensus guidelines and health payer willingness, and the interpretation of MARS2 may play an important role in modulating the role of surgery in the future.

INTRODUCTION:Intraoperative hypoxemia is a frequent complication during one-lung ventilation (OLV) and may contribute to postoperative morbidity. Although hypoxemic events are often transient, their cumulative physiological impact remains poorly understood. This study evaluated the association between cumulative hypoxemia during OLV and postoperative pulmonary complications in patients undergoing lung surgery. METHODS:We conducted a retrospective cohort study of adult patients (≥18 years) who underwent thoracic surgery with OLV between January 2017 and February 2022. Cumulative hypoxemic burden was calculated as the area under the curve (AUC) below a peripheral oxygen saturation (SpO2) of 90% using trapezoidal integration. The primary outcome was a composite of severe pulmonary complications, including reintubation, prolonged mechanical ventilation, acute respiratory distress syndrome, extended non-invasive ventilatory support, and pneumonia. Multivariable logistic regression analysis was used to assess associations with outcomes, adjusting for potential confounders based on univariate analysis and biological plausibility. RESULTS:A total of 2748 patients were included in this cohort, of which 60% underwent lung wedge resections, 25% lobectomies, and 14% segmentectomies. The incidence of severe pulmonary complications was 2.5%. In multivariable analysis adjusting for confounders, AUC of SpO2 < 90% was independently associated with the composite outcome with an estimated odds ratio (OR) of 1.21 (95% confidence interval [CI] 1.02-1.44) per 1% x hour increase in AUC. There was no significant association between AUC of hypoxemia and secondary outcomes such as acute kidney injury (OR 1.14, 95%CI 0.96-1.36, P = 0.130), atrial fibrillation (OR 0.94, 95%CI 0.71-1.25, P = 0.680), delirium (OR 1.10, 95%CI 0.82-1.48, P = 0.523), and five-year all-cause mortality (hazard ratio 0.95, 95%CI 0.77-1.17, P = 0.620). CONCLUSIONS:Cumulative hypoxemia during OLV is independently associated with increased risk of severe postoperative pulmonary complications. Prolonged hypoxemia (≥30 min) may be clinically significant and portend pulmonary complications. Further studies are warranted to explore features mediating this association.

Background/Objectives: Unlike other thoracic malignancies, seeding malignant cells along surgical tracts is a known complication of invasive diagnostic or therapeutic procedures for pleural mesothelioma (PM). We report the tract dissemination rate and risk factors in 308 consecutive patients treated over 9 years in a single institution who underwent pleurectomy decortication (PD). Methods: Clinical and outcome data were reviewed. Fisher's exact test, Kaplan-Meier estimators, and log-rank tests were used to identify significant risk factors for surgical tract dissemination and to compare overall survival. Results: There were 233 males (75.6%), 187 right-sided operations (61%), 190 (61.7%) epithelioid histology cases, and the median age was 69 (29-84). During the study, malignant cell dissemination in resected surgical tracts was diagnosed in 69 (22.4%) patients. The dissemination rates in epithelioid, biphasic, and sarcomatoid tumors were 24.7%, 20.4%, and 0%, respectively. Disseminated malignant surgical tract was associated with advanced nodal status (p = 0.001), advanced staging by the American Joint Committee on Cancer (AJCC 8th edition, p = 0.03), female sex (0.02), side of surgery (p = 0.03), and the number of video-assisted thoracoscopic surgery (VATS) ports (p = 0.003). In epithelioid mesothelioma, the median survival from diagnosis was 19.7 months in patients with tract seeding versus 36.3 months in patients without seeding (hazard ratio, 1.9; p = 0.001). Conclusions: Procedure tract dissemination occurs in almost every fourth patient with pleural mesothelioma and is associated with shorter overall survival in the epithelioid subtype.

Fig. S1. BMS-986408 DGK family selectivity and activity and in T cell functional assays.

Fig. S5. Phosphoproteomics analysis of DGKα/ζ dual- and mono- inhibition.