Pick Topic
Review Topic
List Experts
Examine Expert
Save Expert
  Site Guide ··   
Mesothelioma: HELP
Articles by Prasad S. Adusumilli
Based on 23 articles published since 2008
||||

Between 2008 and 2019, Prasad Adusumilli wrote the following 23 articles about Mesothelioma.
 
+ Citations + Abstracts
1 Editorial A regional approach for CAR T-cell therapy for mesothelioma: from mouse models to clinical trial. 2016

Mayor, Marissa / Zeltsman, Masha / McGee, Erin / Adusumilli, Prasad S. ·Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, NY, USA. ·Immunotherapy · Pubmed #27140404.

ABSTRACT: -- No abstract --

2 Editorial SMART or simply bold? 2016

Rusch, Valerie W / Rimner, Andreas / Adusumilli, Prasad S. ·Thoracic Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY. Electronic address: ruschv@mskcc.org. · Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY. · Thoracic Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY; Center for Cell Engineering, Memorial Sloan-Kettering Cancer Center, New York, NY. ·J Thorac Cardiovasc Surg · Pubmed #26586361.

ABSTRACT: -- No abstract --

3 Editorial Translational immunotherapeutics: chemoimmunotherapy for malignant pleural mesothelioma. 2014

Adusumilli, Prasad S. ·Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York; Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, New York. ·Cancer · Pubmed #24989696.

ABSTRACT: -- No abstract --

4 Review CAR T-cell therapy for lung cancer and malignant pleural mesothelioma. 2017

Zeltsman, Masha / Dozier, Jordan / McGee, Erin / Ngai, Daniel / Adusumilli, Prasad S. ·Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY. · Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY; Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, NY. Electronic address: adusumip@mskcc.org. ·Transl Res · Pubmed #28502785.

ABSTRACT: Immunotherapy is a promising field that harnesses the power of the immune system as a therapeutic agent for cancer treatment. Beneficial outcomes shown in patients with non-small cell lung cancer (NSCLC) and malignant pleural mesothelioma (MPM) with relatively higher tumor-infiltrating T cells, combined with impressive responses obtained in a cohort of patients with NSCLC following checkpoint blockade therapy, lays a strong foundation to promote effector immune responses in these patients. One such approach being investigated is administration of tumor antigen-targeted T cells with transduction of a chimeric antigen receptor (CAR). CARs are synthetic receptors that enhance T-cell antitumor effector function and have gained momentum to investigate in solid tumors based on recent successes of clinical trials treating patients with B-cell hematologic malignancies. This review summarizes target antigens for CAR T-cell therapy that are being investigated in preclinical studies and clinical trials for both NSCLC and MPM patients. We discuss the rationale for combination immunotherapies for NSCLC and MPM patients. Additionally, we have highlighted the challenges and strategies for overcoming the obstacles facing translation of CAR T-cell therapy to solid tumors.

5 Review Immune responses and immunotherapeutic interventions in malignant pleural mesothelioma. 2011

Bograd, Adam J / Suzuki, Kei / Vertes, Eva / Colovos, Christos / Morales, Eduardo A / Sadelain, Michel / Adusumilli, Prasad S. ·Division of Thoracic Surgery, Memorial Sloan-Kettering Cancer Center, NY 10065, USA. ·Cancer Immunol Immunother · Pubmed #21913025.

ABSTRACT: Malignant pleural mesothelioma (MPM) is an aggressive, primary pleural malignancy with poor prognosis, hypothesized to originate from a chronic inflammatory state within the pleura. Similar to what has been observed in other solid tumors (melanoma, ovarian and colorectal cancer), clinical and pre-clinical MPM investigations have correlated anti-tumor immune responses with improved survival. As such, a better understanding of the complex MPM tumor microenvironment is imperative in strategizing successful immunotherapies. Herein, we review the immune responses vital to the development and progression of MPM, as well as assess the role of immunomodulatory therapies, highlighting recent pre-clinical and clinical immunotherapy investigations.

6 Clinical Trial A Randomized Phase II Trial of Adjuvant Galinpepimut-S, WT-1 Analogue Peptide Vaccine, After Multimodality Therapy for Patients with Malignant Pleural Mesothelioma. 2017

Zauderer, Marjorie G / Tsao, Anne S / Dao, Tao / Panageas, Katherine / Lai, W Victoria / Rimner, Andreas / Rusch, Valerie W / Adusumilli, Prasad S / Ginsberg, Michelle S / Gomez, Daniel / Rice, David / Mehran, Reza / Scheinberg, David A / Krug, Lee M. ·Division of Solid Tumor Oncology, Department of Medicine, Thoracic Oncology Service Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, New York. zauderem@mskcc.org. · Division of Cancer Medicine, Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. · Molecular Pharmacology Program, Sloan Kettering Institute, New York, New York. · Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York. · Division of Solid Tumor Oncology, Department of Medicine, Thoracic Oncology Service Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, New York. · Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York. · Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York. · Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York. · Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. · Department of Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas. · Deparment of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. ·Clin Cancer Res · Pubmed #28972039.

ABSTRACT:

7 Clinical Trial Phase II Study of Hemithoracic Intensity-Modulated Pleural Radiation Therapy (IMPRINT) As Part of Lung-Sparing Multimodality Therapy in Patients With Malignant Pleural Mesothelioma. 2016

Rimner, Andreas / Zauderer, Marjorie G / Gomez, Daniel R / Adusumilli, Prasad S / Parhar, Preeti K / Wu, Abraham J / Woo, Kaitlin M / Shen, Ronglai / Ginsberg, Michelle S / Yorke, Ellen D / Rice, David C / Tsao, Anne S / Rosenzweig, Kenneth E / Rusch, Valerie W / Krug, Lee M. ·Andreas Rimner, Marjorie G. Zauderer, Prasad S. Adusumilli, Preeti K. Parhar, Abraham J. Wu, Kaitlin M. Woo, Ronglai Shen, Michelle S. Ginsberg, Ellen D. Yorke, Kenneth E. Rosenzweig, Valerie W. Rusch, and Lee M. Krug, Memorial Sloan Kettering Cancer Center, Weill Cornell Medical Center, New York, NY · and Daniel R. Gomez, David C. Rice, and Anne S. Tsao, MD Anderson Cancer Center, Houston, TX. ·J Clin Oncol · Pubmed #27325859.

ABSTRACT: PURPOSE: We conducted a two-center phase II study to determine the safety of hemithoracic intensity-modulated pleural radiation therapy (IMPRINT) after chemotherapy and pleurectomy-decortication (P/D) as part of a multimodality lung-sparing treatment. PATIENTS AND METHODS: Patients received up to four cycles of pemetrexed plus platinum. If feasible, P/D was performed. Hemithoracic IMPRINT was administered to a planned dose of 50.4 Gy in 28 fractions. The primary end point was the incidence of grade 3 or greater radiation pneumonitis (RP). RESULTS: A total of 45 patients were enrolled; 18 were not evaluable (because of disease progression before radiation therapy [RT], n = 9; refusal of surgery or RT, n = 5; extrapleural pneumonectomy at time of surgery, n = 2; or chemotherapy complications, n = 2). A total of 26 patients received pemetrexed plus cisplatin, 18 received pemetrexed plus carboplatin, and four received a combination. Thirteen patients (28.9%) had a partial response, 15 patients (33.3%) experienced disease progression, one patient died during chemotherapy, and all others had stable disease. Eight patients underwent P/D or an extended P/D, and 13 underwent a partial P/D. A total of 27 patients started IMPRINT (median dose, 46.8 Gy; range, 28.8 to 50.4 Gy) and were evaluable for the primary end point (median follow-up, 21.6 months). Six patients experienced grade 2 RP, and two patients experienced grade 3 RP; all recovered after corticosteroid initiation. No grade 4 or 5 radiation-related toxicities were observed. The median progression-free survival and overall survival (OS) were 12.4 and 23.7 months, respectively; the 2-year OS was 59% in patients with resectable tumors and was 25% in patients with unresectable tumors. CONCLUSIONS: Hemithoracic IMPRINT for malignant pleural mesothelioma (MPM) is safe and has an acceptable rate of RP. Its incorporation with chemotherapy and P/D forms a new lung-sparing treatment paradigm for patients with locally advanced MPM.

8 Clinical Trial Pleomorphic epithelioid diffuse malignant pleural mesothelioma: a clinicopathological review and conceptual proposal to reclassify as biphasic or sarcomatoid mesothelioma. 2011

Kadota, Kyuichi / Suzuki, Kei / Sima, Camelia S / Rusch, Valerie W / Adusumilli, Prasad S / Travis, William D. ·Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York City, New York 10065, USA. ·J Thorac Oncol · Pubmed #21358344.

ABSTRACT: INTRODUCTION: In patients with epithelioid diffuse malignant pleural mesothelioma (DMPM), clinical stage is the current primary prognostic factor. We sought to investigate whether histologic subtyping can prognostically stratify patients with epithelioid DMPM. METHODS: Hematoxylin and eosin-stained slides of 232 patients with epithelioid DMPM (14 stage I, 54 stage II, 130 stage III, and 34 stage IV) from a single institution were reviewed. We classified the tumors into five subtypes, according to the predominant histological pattern: trabecular, tubulopapillary, micropapillary, solid, and pleomorphic (≥10% of tumor). RESULTS: Median overall survival (OS) of all patients with epithelioid DMPM was 16.2 months. Patients with pleomorphic subtype (n = 34) had the worst median OS (8.1 months), followed by solid (n = 89, 13.7 months), micropapillary (n = 20, 15.8 months), tubulopapillary (n = 51, 17.9 months), and trabecular (n = 38, 24.9 months). The pleomorphic subtype was associated with lymphatic and vascular invasion (p < 0.001). The micropapillary subtype was associated with lymphatic invasion (p < 0.001). In univariate analyses, pleomorphic subtype was significantly associated with poor OS (p = 0.003). The pleomorphic subtype showed no significant difference on OS compared with biphasic and sarcomatoid DMPM. In a multivariate analysis, the pleomorphic subtype was an independent predictor of poor OS (p = 0.031). In patients who underwent R1 resection, pleomorphic subtype had the shortest median time to recurrence (13.7 months). CONCLUSION: Our finding that the pleomorphic subtype is a predictor of aggressive behavior in epithelioid DMPM with no survival difference from biphasic or sarcomatoid DMPM suggests that it may be best regarded as a sarcomatoid pattern rather than a subtype of epithelioid DMPM.

9 Article Nuclear grade and necrosis predict prognosis in malignant epithelioid pleural mesothelioma: a multi-institutional study. 2018

Rosen, Lauren E / Karrison, Theodore / Ananthanarayanan, Vijayalakshmi / Gallan, Alexander J / Adusumilli, Prasad S / Alchami, Fouad S / Attanoos, Richard / Brcic, Luka / Butnor, Kelly J / Galateau-Sallé, Françoise / Hiroshima, Kenzo / Kadota, Kyuichi / Klampatsa, Astero / Stang, Nolween Le / Lindenmann, Joerg / Litzky, Leslie A / Marchevsky, Alberto / Medeiros, Filomena / Montero, M Angeles / Moore, David A / Nabeshima, Kazuki / Pavlisko, Elizabeth N / Roggli, Victor L / Sauter, Jennifer L / Sharma, Anupama / Sheaff, Michael / Travis, William D / Vigneswaran, Wickii T / Vrugt, Bart / Walts, Ann E / Tjota, Melissa Y / Krausz, Thomas / Husain, Aliya N. ·Department of Pathology, The University of Chicago Medicine, Chicago, IL, USA. · Department of Public Health Sciences, The University of Chicago, Chicago, IL, USA. · Department of Pathology, Loyola University Medical Center, Chicago, IL, USA. · Department of Thoracic Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Department of Cellular Pathology, University Hospital of Wales, Cardiff, UK. · Department of Cellular Pathology, University Hospital of Wales and Cardiff University, Cardiff, UK. · Medical University of Graz, Institute of Pathology, Graz, Austria. · Department of Pathology, University of Vermont Medical Center, Burlington, VT, USA. · Centre Léon Bérard, BioPathologie, Lyon, France. · Department of Pathology, Tokyo Women's Medical University Yachiyo Medical Center, Yachiyo, Japan. · Department of Diagnostic Pathology, Kagawa University, Takamatsu, Japan. · Division of Pulmonary, Allergy and Critical Care, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. · Division of Thoracic and Hyperbaric Surgery, Department of Surgery,Medical University of Graz, Graz, Austria. · ,Department of Pathology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. · Department of Pathology & Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA. · Basildon & Thurrock University Hospital, Department of Pathology, Basildon, UK. · Department of Histopathology, Royal Brompton and Harefield Hospitals Imperial College of London, London, UK. · Department of Cancer Studies, University of Leicester, Leicester, UK. · Fukuoka University, Department of Pathology, Fukuoka, Japan. · Department of Pathology, Duke University Medical Center, Durham, NC, USA. · Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. · Department of Pathology, University of Pittsburgh Medical Center and VA Pittsburgh Healthcare System, Pittsburgh, PA, USA. · Department of Pathology, Barts Health NHS Trust, London, UK. · Department of Thoracic and Cardiovascular Surgery, Loyola University Medical Center, Chicago, IL, USA. · University Hospital Zurich, Institute for Pathology and Molecular Pathology, Zurich, Switzerland. ·Mod Pathol · Pubmed #29327706.

ABSTRACT: A recently described nuclear grading system predicted survival in patients with epithelioid malignant pleural mesothelioma. The current study was undertaken to validate the grading system and to identify additional prognostic factors. We analyzed cases of epithelioid malignant pleural mesothelioma from 17 institutions across the globe from 1998 to 2014. Nuclear grade was computed combining nuclear atypia and mitotic count into a grade of I-III using the published system. Nuclear grade was assessed by one pathologist for three institutions, the remaining were scored independently. The presence or absence of necrosis and predominant growth pattern were also evaluated. Two additional scoring systems were evaluated, one combining nuclear grade and necrosis and the other mitotic count and necrosis. Median overall survival was the primary endpoint. A total of 776 cases were identified including 301 (39%) nuclear grade I tumors, 354 (45%) grade II tumors and 121 (16%) grade III tumors. The overall survival was 16 months, and correlated independently with age (P=0.006), sex (0.015), necrosis (0.030), mitotic count (0.001), nuclear atypia (0.009), nuclear grade (<0.0001), and mitosis and necrosis score (<0.0001). The addition of necrosis to nuclear grade further stratified overall survival, allowing classification of epithelioid malignant pleural mesothelioma into four distinct prognostic groups: nuclear grade I tumors without necrosis (29 months), nuclear grade I tumors with necrosis and grade II tumors without necrosis (16 months), nuclear grade II tumors with necrosis (10 months) and nuclear grade III tumors (8 months). The mitosis-necrosis score stratified patients by survival, but not as well as the combination of necrosis and nuclear grade. This study confirms that nuclear grade predicts survival in epithelioid malignant pleural mesothelioma, identifies necrosis as factor that further stratifies overall survival, and validates the grading system across multiple institutions and among both biopsy and resection specimens. An alternative scoring system, the mitosis-necrosis score is also proposed.

10 Article Heart Dosimetry is Correlated With Risk of Radiation Pneumonitis After Lung-Sparing Hemithoracic Pleural Intensity Modulated Radiation Therapy for Malignant Pleural Mesothelioma. 2017

Yorke, Ellen D / Jackson, Andrew / Kuo, Li Cheng / Ojo, Anthonia / Panchoo, Kelly / Adusumilli, Prasad / Zauderer, Marjorie G / Rusch, Valerie W / Shepherd, Annemarie / Rimner, Andreas. ·Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York. Electronic address: yorkee@mskcc.org. · Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York. · Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York. · Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York. · Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York. ·Int J Radiat Oncol Biol Phys · Pubmed #28816162.

ABSTRACT: PURPOSE: To determine clinically helpful dose-volume and clinical metrics correlating with symptomatic radiation pneumonitis (RP) in malignant pleural mesothelioma (MPM) patients with 2 lungs treated with hemithoracic intensity modulated pleural radiation therapy (IMPRINT). METHODS AND MATERIALS: Treatment plans and resulting normal organ dose-volume histograms of 103 consecutive MPM patients treated with IMPRINT (February 2005 to January 2015) to the highest dose ≤50.4 Gy satisfying departmental normal tissue constraints were uniformly recalculated. Patient records provided maximum RP grade (Common Terminology Criteria for Toxicity and Adverse Event version 4.0) and clinical and demographic information. Correlations analyzed with the Cox model were grade ≥2 RP (RP2+) and grade ≥3 RP (RP3+) with clinical variables, with volumes of planning target volume (PTV) and PTV-lung overlap and with mean dose, percent volume receiving dose D (V RESULTS: Twenty-seven patients had RP2+ (14 with RP3+). The median prescription dose was 46.8 Gy (39.6-50.4 Gy, 1.8 Gy/fraction). The median age was 67.6 years (range, 42-83 years). There were 79 men, 40 never-smokers, and 44 with left-sided MPM. There were no significant (P≤.05) correlations with clinical variables, prescription dose, total lung dose-volume metrics, and PTV-lung overlap volume. Dose-volume correlations for heart were RP2+ with V CONCLUSIONS: Heart dose correlated strongly with symptomatic RP in this large cohort of MPM patients with 2 lungs treated with IMPRINT. Planning constraints to reduce future heart doses are suggested.

11 Article Improved Outcomes with Modern Lung-Sparing Trimodality Therapy in Patients with Malignant Pleural Mesothelioma. 2017

Shaikh, Fauzia / Zauderer, Marjorie G / von Reibnitz, Donata / Wu, Abraham J / Yorke, Ellen D / Foster, Amanda / Shi, Weiji / Zhang, Zhigang / Adusumilli, Prasad S / Rosenzweig, Kenneth E / Krug, Lee M / Rusch, Valerie W / Rimner, Andreas. ·Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York. · Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Medicine, Weill Cornell Medical College, New York, New York. · Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York. · Department of Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York. · Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York. · Department of Radiation Oncology, Mount Sinai Medical Center, New York, New York. · Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York. Electronic address: rimnera@mskcc.org. ·J Thorac Oncol · Pubmed #28341225.

ABSTRACT: INTRODUCTION: Higher target conformity and better sparing of organs at risk with modern radiotherapy (RT) may result in higher tumor control and less toxicity. In this study, we compare our institutional multimodality therapy experience of adjuvant chemotherapy and hemithoracic intensity-modulated pleural RT (IMPRINT) with previously used adjuvant conventional RT (CONV) in patients with malignant pleural mesothelioma (MPM) treated with lung-sparing pleurectomy/decortication (P/D). METHODS: We analyzed 209 patients who underwent P/D and adjuvant RT (131 who received CONV and 78 who received IMPRINT) for MPM between 1974 and 2015. The primary end point was overall survival (OS). The Kaplan-Meier method and Cox proportional hazards model were used to calculate OS; competing risks analysis was performed for local failure-free survival and progression-free survival. Univariate analysis and multivariate analysis were performed with relevant clinical and treatment factors. RESULTS: The median age was 64 years, and 80% of the patients were male. Patients receiving IMPRINT had significantly higher rates of the epithelial histological type, advanced pathological stage, and chemotherapy treatment. OS was significantly higher after IMPRINT (median 20.2 versus 12.3 months, p = 0.001). Higher Karnofsky performance score, epithelioid histological type, macroscopically complete resection, and use of chemotherapy/IMPRINT were found to be significant factors for longer OS in multivariate analysis. No significant predictive factors were identified for local failure or progression. Grade 2 or higher esophagitis developed in fewer patients after IMPRINT than after CONV (23% versus 47%). CONCLUSIONS: Trimodality therapy including adjuvant hemithoracic IMPRINT, chemotherapy, and P/D is associated with promising OS rates and decreased toxicity in patients with MPM. Dose constraints should be applied vigilantly to minimize serious adverse events.

12 Article Human CAR T cells with cell-intrinsic PD-1 checkpoint blockade resist tumor-mediated inhibition. 2016

Cherkassky, Leonid / Morello, Aurore / Villena-Vargas, Jonathan / Feng, Yang / Dimitrov, Dimiter S / Jones, David R / Sadelain, Michel / Adusumilli, Prasad S. · ·J Clin Invest · Pubmed #27454297.

ABSTRACT: Following immune attack, solid tumors upregulate coinhibitory ligands that bind to inhibitory receptors on T cells. This adaptive resistance compromises the efficacy of chimeric antigen receptor (CAR) T cell therapies, which redirect T cells to solid tumors. Here, we investigated whether programmed death-1-mediated (PD-1-mediated) T cell exhaustion affects mesothelin-targeted CAR T cells and explored cell-intrinsic strategies to overcome inhibition of CAR T cells. Using an orthotopic mouse model of pleural mesothelioma, we determined that relatively high doses of both CD28- and 4-1BB-based second-generation CAR T cells achieved tumor eradication. CAR-mediated CD28 and 4-1BB costimulation resulted in similar levels of T cell persistence in animals treated with low T cell doses; however, PD-1 upregulation within the tumor microenvironment inhibited T cell function. At lower doses, 4-1BB CAR T cells retained their cytotoxic and cytokine secretion functions longer than CD28 CAR T cells. The prolonged function of 4-1BB CAR T cells correlated with improved survival. PD-1/PD-1 ligand [PD-L1] pathway interference, through PD-1 antibody checkpoint blockade, cell-intrinsic PD-1 shRNA blockade, or a PD-1 dominant negative receptor, restored the effector function of CD28 CAR T cells. These findings provide mechanistic insights into human CAR T cell exhaustion in solid tumors and suggest that PD-1/PD-L1 blockade may be an effective strategy for improving the potency of CAR T cell therapies.

13 Article Loss of BAP1 function leads to EZH2-dependent transformation. 2015

LaFave, Lindsay M / Béguelin, Wendy / Koche, Richard / Teater, Matt / Spitzer, Barbara / Chramiec, Alan / Papalexi, Efthymia / Keller, Matthew D / Hricik, Todd / Konstantinoff, Katerina / Micol, Jean-Baptiste / Durham, Benjamin / Knutson, Sarah K / Campbell, John E / Blum, Gil / Shi, Xinxu / Doud, Emma H / Krivtsov, Andrei V / Chung, Young Rock / Khodos, Inna / de Stanchina, Elisa / Ouerfelli, Ouathek / Adusumilli, Prasad S / Thomas, Paul M / Kelleher, Neil L / Luo, Minkui / Keilhack, Heike / Abdel-Wahab, Omar / Melnick, Ari / Armstrong, Scott A / Levine, Ross L. ·Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA. · Gerstner Sloan Kettering School of Biomedical Sciences, New York, New York, USA. · Department of Hematology/Oncology, Weill Cornell Medical College, New York, New York, USA. · The Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, New York, USA. · Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA. · Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York, USA. · Epizyme, Inc., Cambridge, Massachusetts, USA. · Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, New York. · Tri-Institutional Program in Chemical Biology, Memorial Sloan Kettering Cancer Center, New York, New York, USA. · Chemical Synthesis Core, Memorial Sloan Kettering Cancer Center, New York, New York, USA. · Proteomics Center of Excellence, Northwestern University, Evanston, Illinois, USA. · Anti-Tumor Assessment Core, Memorial Sloan Kettering Cancer Center, New York, New York, USA. · Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA. · Leukemia Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA. ·Nat Med · Pubmed #26437366.

ABSTRACT: The tumor suppressors BAP1 and ASXL1 interact to form a polycomb deubiquitinase complex that removes monoubiquitin from histone H2A lysine 119 (H2AK119Ub). However, BAP1 and ASXL1 are mutated in distinct cancer types, consistent with independent roles in regulating epigenetic state and malignant transformation. Here we demonstrate that Bap1 loss in mice results in increased trimethylated histone H3 lysine 27 (H3K27me3), elevated enhancer of zeste 2 polycomb repressive complex 2 subunit (Ezh2) expression, and enhanced repression of polycomb repressive complex 2 (PRC2) targets. These findings contrast with the reduction in H3K27me3 levels seen with Asxl1 loss. Conditional deletion of Bap1 and Ezh2 in vivo abrogates the myeloid progenitor expansion induced by Bap1 loss alone. Loss of BAP1 results in a marked decrease in H4K20 monomethylation (H4K20me1). Consistent with a role for H4K20me1 in the transcriptional regulation of EZH2, expression of SETD8-the H4K20me1 methyltransferase-reduces EZH2 expression and abrogates the proliferation of BAP1-mutant cells. Furthermore, mesothelioma cells that lack BAP1 are sensitive to EZH2 pharmacologic inhibition, suggesting a novel therapeutic approach for BAP1-mutant malignancies.

14 Article Tumoral CD10 expression correlates with aggressive histology and prognosis in patients with malignant pleural mesothelioma. 2015

Kadota, Kyuichi / Villena-Vargas, Jonathan / Nitadori, Jun-Ichi / Sima, Camelia S / Jones, David R / Travis, William D / Adusumilli, Prasad S. ·Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA. ·Ann Surg Oncol · Pubmed #25608772.

ABSTRACT: BACKGROUND: Currently, tumor-node-metastasis stage and histologic type are the established prognostic factors for malignant pleural mesothelioma, whereas no prognostic markers have been established for clinical practice. We investigated the prognostic value of CD10, a metalloproteinase that can promote cancer aggressiveness through enzymatic degradation and intracellular signaling crosstalk, in malignant pleural mesothelioma. METHODS: CD10 immunostaining was performed for 176 cases of malignant pleural mesothelioma (epithelioid, 148; biphasic, 14; sarcomatoid, 14), and its expression was dichotomized as negative (no staining) or positive (any staining). Epithelioid tumors were classified as pleomorphic subtype when cytologic pleomorphism was ≥10 % of the tumor. Overall survival (OS) was analyzed by log-rank tests and Cox proportional hazard models. RESULTS: Tumoral CD10 expression was identified in 42 % of epithelioid non-pleomorphic tumors, 57 % of epithelioid pleomorphic tumors, 79 % of biphasic tumors, and 93 % of sarcomatoid tumors (p < 0.001). Positive CD10 expression was correlated with higher mitotic count (p = 0.002). Overall survival for patients with positive CD10 expression was significantly shorter than that for patients with negative CD10 expression in all patients (p = 0.001) and in patients with epithelioid tumor (p = 0.04). On multivariate analysis, CD10 expression was an independent prognostic factor for all patients (hazard ratio 1.48; p = 0.019). CONCLUSIONS: Tumoral CD10 expression correlated with aggressive histologic types and higher mitotic activity and is an independent prognostic factor for patients with malignant pleural mesothelioma.

15 Article Regional delivery of mesothelin-targeted CAR T cell therapy generates potent and long-lasting CD4-dependent tumor immunity. 2014

Adusumilli, Prasad S / Cherkassky, Leonid / Villena-Vargas, Jonathan / Colovos, Christos / Servais, Elliot / Plotkin, Jason / Jones, David R / Sadelain, Michel. ·Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. adusumip@mskcc.org sadelaim@mskcc.org. · Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. · Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. · Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. · Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Immunology Program, Sloan Kettering Institute, New York, NY 10065, USA. adusumip@mskcc.org sadelaim@mskcc.org. ·Sci Transl Med · Pubmed #25378643.

ABSTRACT: Translating the recent success of chimeric antigen receptor (CAR) T cell therapy for hematological malignancies to solid tumors will necessitate overcoming several obstacles, including inefficient T cell tumor infiltration and insufficient functional persistence. Taking advantage of an orthotopic model that faithfully mimics human pleural malignancy, we evaluated two routes of administration of mesothelin-targeted T cells using the M28z CAR. We found that intrapleurally administered CAR T cells vastly outperformed systemically infused T cells, requiring 30-fold fewer M28z T cells to induce long-term complete remissions. After intrapleural T cell administration, prompt in vivo antigen-induced T cell activation allowed robust CAR T cell expansion and effector differentiation, resulting in enhanced antitumor efficacy and functional T cell persistence for 200 days. Regional T cell administration also promoted efficient elimination of extrathoracic tumor sites. This therapeutic efficacy was dependent on early CD4(+) T cell activation associated with a higher intratumoral CD4/CD8 cell ratios and CD28-dependent CD4(+) T cell-mediated cytotoxicity. In contrast, intravenously delivered CAR T cells, even when accumulated at equivalent numbers in the pleural tumor, did not achieve comparable activation, tumor eradication, or persistence. The ability of intrapleurally administered T cells to circulate and persist supports the concept of delivering optimal CAR T cell therapy through "regional distribution centers." On the basis of these results, we are opening a phase 1 clinical trial to evaluate the safety of intrapleural administration of mesothelin-targeted CAR T cells in patients with primary or secondary pleural malignancies.

16 Article Failure patterns after hemithoracic pleural intensity modulated radiation therapy for malignant pleural mesothelioma. 2014

Rimner, Andreas / Spratt, Daniel E / Zauderer, Marjorie G / Rosenzweig, Kenneth E / Wu, Abraham J / Foster, Amanda / Yorke, Ellen D / Adusumilli, Prasad / Rusch, Valerie W / Krug, Lee M. ·Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York. Electronic address: rimnera@mskcc.org. · Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York. · Department of Medicine, Thoracic Oncology Service, Memorial Sloan-Kettering Cancer Center; Weill Cornell Medical College, New York, New York. · Department of Radiation Oncology, Mount Sinai Medical Center, New York, New York. · Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York. · Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York. ·Int J Radiat Oncol Biol Phys · Pubmed #25073664.

ABSTRACT: PURPOSE: We previously reported our technique for delivering intensity modulated radiation therapy (IMRT) to the entire pleura while attempting to spare the lung in patients with malignant pleural mesothelioma (MPM). Herein, we report a detailed pattern-of-failure analysis in patients with MPM who were unresectable or underwent pleurectomy/decortication (P/D), uniformly treated with hemithoracic pleural IMRT. METHODS AND MATERIALS: Sixty-seven patients with MPM were treated with definitive or adjuvant hemithoracic pleural IMRT between November 2004 and May 2013. Pretreatment imaging, treatment plans, and posttreatment imaging were retrospectively reviewed to determine failure location(s). Failures were categorized as in-field (within the 90% isodose line), marginal (<90% and ≥50% isodose lines), out-of-field (outside the 50% isodose line), or distant. RESULTS: The median follow-up was 24 months from diagnosis and the median time to in-field local failure from the end of RT was 10 months. Forty-three in-field local failures (64%) were found with a 1- and 2-year actuarial failure rate of 56% and 74%, respectively. For patients who underwent P/D versus those who received a partial pleurectomy or were deemed unresectable, the median time to in-field local failure was 14 months versus 6 months, respectively, with 1- and 2-year actuarial in-field local failure rates of 43% and 60% versus 66% and 83%, respectively (P=.03). There were 13 marginal failures (19%). Five of the marginal failures (38%) were located within the costomediastinal recess. Marginal failures decreased with increasing institutional experience (P=.04). Twenty-five patients (37%) had out-of-field failures. Distant failures occurred in 32 patients (48%). CONCLUSIONS: After hemithoracic pleural IMRT, local failure remains the dominant form of failure pattern. Patients treated with adjuvant hemithoracic pleural IMRT after P/D experience a significantly longer time to local and distant failure than patients treated with definitive pleural IMRT. Increasing experience and improvement in target delineation minimize the incidence of avoidable marginal failures.

17 Article High SUVmax on FDG-PET indicates pleomorphic subtype in epithelioid malignant pleural mesothelioma: supportive evidence to reclassify pleomorphic as nonepithelioid histology. 2012

Kadota, Kyuichi / Kachala, Stefan S / Nitadori, Jun-Ichi / Suzuki, Kei / Dunphy, Mark P S / Sima, Camelia S / Travis, William D / Rusch, Valerie W / Adusumilli, Prasad S. ·Division of Thoracic Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. ·J Thorac Oncol · Pubmed #22617244.

ABSTRACT: BACKGROUND: We have recently proposed to reclassify the pleomorphic subtype of epithelioid malignant pleural mesothelioma (MPM) as nonepithelioid (biphasic/sarcomatoid) histology because of its similarly poor prognosis. We sought to investigate whether preoperative maximum standardized uptake value (SUVmax) on F-fluorodeoxyglucose (FDG) positron emission tomography (PET) correlates with histologic subtype in MPM. METHODS: Clinical data were collected for 78 patients with MPM who underwent preoperative FDG-PET. We retrospectively classified the epithelioid tumors into five subtypes: trabecular, tubulopapillary, micropapillary, solid, and pleomorphic. Tumors were categorized by SUVmax into two groups: low (<10.0) and high (≥10.0). RESULTS: The median overall survival of epithelioid tumors with high SUVmax (n = 12) was significantly shorter (7.1 months) than that of epithelioid tumors with low SUVmax (n = 54, 18.9 months, p < 0.001) and comparable to nonepithelioid tumors (n = 12, 7.2 months). Epithelioid tumors with pleomorphic subtype (n = 9) had marginally higher SUVmax (mean ± SD: 10.6 ± 5.9) than epithelioid nonpleomorphic subtype (n = 57, 6.5 ± 3.2, p = 0.050), and were comparable to that of nonepithelioid tumors (n = 12, 9.1 ± 4.8). Among the epithelioid tumors with high SUVmax (n = 12), 50% (n = 6) showed pleomorphic subtype. In contrast, among epithelioid tumors with low SUVmax (n = 54), 6% (n = 3) showed epithelioid pleomorphic subtypes (p = 0.001). A positive correlation between mitotic count and SUVmax was observed (r = 0.30, p = 0.010). CONCLUSIONS: Pleomorphic subtype of epithelioid MPM showed higher SUVmax than the epithelioid nonpleomorphic subtype and was similar to nonepithelioid histology. Preoperative SUVmax on FDG-PET in epithelioid MPM can indicate patients with pleomorphic subtype with poor prognosis, supporting their reclassification as nonepithelioid.

18 Article Mesothelin overexpression promotes mesothelioma cell invasion and MMP-9 secretion in an orthotopic mouse model and in epithelioid pleural mesothelioma patients. 2012

Servais, Elliot L / Colovos, Christos / Rodriguez, Luis / Bograd, Adam J / Nitadori, Jun-ichi / Sima, Camelia / Rusch, Valerie W / Sadelain, Michel / Adusumilli, Prasad S. ·Division of Thoracic Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. ·Clin Cancer Res · Pubmed #22371455.

ABSTRACT: PURPOSE: Mesothelin (MSLN) is a tumor-associated antigen, being investigated as a biomarker and therapeutic target in malignant pleural mesothelioma (MPM). The biologic function of MSLN overexpression in MPM is unknown. We hypothesized that MSLN may promote tumor invasion in MPM, a tumor characterized primarily by regional aggressiveness and rare distant metastases. EXPERIMENTAL DESIGN: Human and murine MPM cells with MSLN forced expression and short hairpin RNA knockdown were examined for proliferation, invasion, and matrix metalloproteinase (MMP) secretion. The influence of MSLN overexpression on MPM cell invasion was assessed in an orthotopic mouse model and in patient samples. RESULTS: MSLN expression promotes MPM cell invasion and MMP secretion in both human and murine MPM cells. In an orthotopic MPM mouse model characterized by our laboratory, MPM cells with MSLN overexpression preferentially localized to the tumor invading edge, colocalized with MMP-9 expression, and promoted decreased survival without an increase in tumor burden progression. In a tissue microarray from epithelioid MPM patients (n = 139, 729 cores), MSLN overexpression correlated with higher MMP-9 expression at individual core level. Among stage III MPM patients (n = 72), high MSLN expression was observed in 26% of T2 tumors and 51% of T3 tumors. CONCLUSIONS: Our data provide evidence elucidating a biologic role for MSLN as a factor promoting tumor invasion and MMP-9 expression in MSLN expressing MPM. As regional invasion is the characteristic feature in MSLN expressing solid cancers (MPM, pancreas, and ovarian), our observations add rationale to studies investigating MSLN as a therapeutic target.

19 Article A nuclear grading system is a strong predictor of survival in epitheloid diffuse malignant pleural mesothelioma. 2012

Kadota, Kyuichi / Suzuki, Kei / Colovos, Christos / Sima, Camelia S / Rusch, Valerie W / Travis, William D / Adusumilli, Prasad S. ·Division of Thoracic Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. ·Mod Pathol · Pubmed #21983936.

ABSTRACT: Epithelioid mesothelioma is the most prevalent subtype of diffuse malignant pleural mesothelioma in which only staging is prognostic for survival. In this study of epithelioid diffuse malignant pleural mesothelioma, we investigate the prognostic utility of nuclear features. The slides of 232 epithelioid diffuse malignant pleural mesothelioma patients (14 stage I, 54 stage II, 130 stage III, and 34 stage IV) from a single institution were reviewed for the following seven nuclear features: nuclear atypia, nuclear/cytoplasmic ratio, chromatin pattern, intranuclear inclusions, prominence of nucleoli, mitotic count, and atypical mitoses. MIB-1 immunohistochemistry was performed using tissue microarray, and MIB-1 labeling index was recorded as the percentage of positive tumor cells. Median overall survival of all patients was 16 months and correlated with nuclear atypia (P<0.001), chromatin pattern (P=0.031), prominence of nucleoli (P<0.001), mitotic count (P<0.001), and atypical mitoses (P<0.001) by univariate analysis. Multivariate analysis revealed nuclear atypia (P=0.012) and mitotic count (P<0.001) as independent prognostic factors, and these two factors were utilized to create a three-tier nuclear grade score. The resulting nuclear grade stratified patients into three distinct prognostic groups: grade I (n=107, median overall survival=28 months), grade II (n=91, 14 months), and grade III (n=34, 5 months). Not only was nuclear grade an independent predictor of overall survival (P<0.001), but it was also a stronger discriminator of survival than all currently available factors. Furthermore, nuclear grade was associated with time to recurrence (P=0.004) in patients who underwent complete surgical resection (n=159). MIB-1 labeling index correlated with mitotic count (P<0.001) and nuclear atypia (P=0.037) and stratified overall survival (P<0.001) and time to recurrence (P=0.048), confirming the prognostic value of the nuclear grade. Nuclear grading in epithelioid mesothelioma provides a simple, practical, and cost-effective prognostic tool that better stratifies clinical outcome and time to recurrence than currently available clinicopathologic factors.

20 Article An in vivo platform for tumor biomarker assessment. 2011

Servais, Elliot L / Suzuki, Kei / Colovos, Christos / Rodriguez, Luis / Sima, Camelia / Fleisher, Martin / Rusch, Valerie W / Sadelain, Michel / Adusumilli, Prasad S. ·Division of Thoracic Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America. ·PLoS One · Pubmed #22046338.

ABSTRACT: Tumor biomarkers provide a quantitative tool for following tumor progression and response to therapy. However, investigations of clinically useful tumor biomarkers are time-consuming, costly, and limited by patient and tumor heterogeneity. In addition, assessment of biomarkers as indicators of therapy response is confounded by the concomitant use of multiple therapeutic interventions. Herein we report our use of a clinically relevant orthotopic animal model of malignant pleural mesothelioma for investigating tumor biomarkers. Utilizing multi-modality imaging with correlative histopathology, we demonstrate the utility and accuracy of the mouse model in investigating tumor biomarkers--serum soluble mesothelin-related peptide (SMRP) and osteopontin (OPN). This model revealed percentage change in SMRP level to be an accurate biomarker of tumor progression and therapeutic response--a finding consistent with recent clinical studies. This in vivo platform demonstrates the advantages of a validated mouse model for the timely and cost-effective acceleration of human biomarker translational research.

21 Article Pre-clinical mouse models of primary and metastatic pleural cancers of the lung and breast and the use of bioluminescent imaging to monitor pleural tumor burden. 2011

Servais, Elliot L / Colovos, Christos / Kachala, Stefan S / Adusumilli, Prasad S. ·Memorial Sloan-Kettering Cancer Center, New York, NY, USA. ·Curr Protoc Pharmacol · Pubmed #21898334.

ABSTRACT: Malignant pleural disease (MPD) results in an estimated 150,000 cases of malignant pleural effusions (MPE) annually. The most common malignancies associated with MPD are primary malignant pleural mesothelioma (MPM) and metastatic lung cancer, breast cancer, and lymphoma. MPM is a rare, regionally aggressive malignancy whose incidence is increasing secondarily to the latency of disease progression. MPD is characteristic of advanced-stage pleural disease and portends a grave clinical prognosis with a median survival between 3 and 12 months. Preclinical investigations conducted in flank and intraperitoneal tumor models do not fully recapitulate the pleural tumor microenvironment, and the results are not directly translatable to the clinical setting. The protocol described herein provides a mouse model of MPM and MPD from nonhematogenous tumors, resulting in reproducible tumor location, tumor progression, animal survival, and histopathology. Pleural tumor growth in this model resembles the regionally aggressive clinical course and tumor microenvironment of human pleural cancers and provides an optimal animal model to investigate MPD biology and therapies.

22 Article Chronic inflammation in tumor stroma is an independent predictor of prolonged survival in epithelioid malignant pleural mesothelioma patients. 2011

Suzuki, Kei / Kadota, Kyuichi / Sima, Camelia S / Sadelain, Michel / Rusch, Valerie W / Travis, William D / Adusumilli, Prasad S. ·Division of Thoracic Surgery, Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. ·Cancer Immunol Immunother · Pubmed #21769693.

ABSTRACT: This study aims to determine whether a semi-quantitative assessment of inflammatory response in tumor and stroma on routine hematoxylin and eosin-stained (H&E) slides can predict survival in patients with epithelioid malignant pleural mesothelioma (MPM). H&E sections of 175 epithelioid MPM specimens from a single institution (1989-2009) were reviewed. Patients who received neoadjuvant chemotherapy were excluded from analysis. Each tumor was histologically assessed for acute and chronic inflammatory response both within the tumor and the stromal component. Inflammatory response was graded: low (none to mild infiltrate) or high (moderate to severe infiltrate). Log-rank test and Cox proportional hazards regression were used to investigate the association between the degree of inflammation (acute/tumor, acute/stroma, chronic/tumor, and chronic/stroma) and overall survival (OS). Patients with high chronic inflammatory response in stroma (n = 59) had improved survival compared to low (n = 116) (median OS = 19.4 vs. 15.0 months, P = 0.01). This prognostic stratification remained significant in stage III patients (median OS = 16.0 vs. 9.3 months, P = 0.03). In multivariate analysis, chronic inflammation in stroma was an independent predictor of survival (HR = 0.659, 95% CI 0.464-0.937, P = 0.02). While high degree of chronic inflammatory cell infiltration in the stromal component was associated with improved overall survival, degree of other inflammatory responses did not show significant correlation with OS. Our study for the first time investigates inflammatory response in tumor and stroma and not only suggests the prognostic value of inflammatory response in epithelioid MPM but also provides rationale for investigation of immunotherapy to benefit epithelioid MPM patients.

23 Article Frequency of use and predictors of cancer-directed surgery in the management of malignant pleural mesothelioma in a community-based (Surveillance, Epidemiology, and End Results [SEER]) population. 2010

Flores, Raja M / Riedel, Elyn / Donington, Jessica Scott / Alago, William / Ihekweazu, Ugonna / Krug, Lee / Rosenzweig, Kenneth / Adusumilli, Prasad S / Carbone, Michele / Pass, Harvey I. ·Division of Thoracic Surgery, Mount Sinai Medical Center, New York, New York 10029, USA. Raja.flores@mountsinai.org ·J Thorac Oncol · Pubmed #20871264.

ABSTRACT: INTRODUCTION: Surgical intervention rates for mesothelioma patients treated at specialized tertiary hospitals are well more than 42%. Mesothelioma surgical strategies in the community are less well defined. This study evaluates the frequency of use and predictors of cancer-directed surgical intervention in a nontertiary-based population and the predictors for surgical intervention. METHODS: The Surveillance, Epidemiology, and End Results database was searched from 1990 to 2004. Variables analyzed included age, sex, race, year of diagnosis, region, vital status, stage, surgery, and reasons for no surgery. The association of patient variables on receipt of cancer-directed surgery was evaluated using χ(2) tests and logistic regression. The incidence of mesothelioma was also evaluated over this period of time. RESULTS: Pathologically proven malignant pleural mesothelioma was identified in 1166 women and 4771 men. The rate of cancer-directed surgery was 22% (n = 1317). Significant predictors of receiving cancer-directed surgery included race, age, and stage (all p < 0.0001). A landmark analysis on the effect of cancer-directed surgery on survival after adjusting for patient and disease characteristics demonstrated a hazard ratio of 0.68 (p < 0.0001). The incidence rate of malignant pleural mesothelioma has remained constant. CONCLUSIONS: The rate of surgical intervention in the community is lower compared with tertiary referral centers. Age, stage, and race predict the likelihood of receiving cancer-directed surgery. A lower rate of cancer-directed surgery and worse overall outcome were observed in black patients. As part of quality assurance, referral of patients to centers with multidisciplinary programs that include thoracic surgical expertise should be considered.