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1. Combining a WT1 Vaccine (Galinpepimut-S) With Checkpoint Inhibition (Nivolumab) in Patients With WT1–Expressing Diffuse Pleural Mesothelioma: A Phase 1 Study

Author

Prashasti Agrawal, MD, Michael Offin, MD, Victoria Lai, MD, Michelle S. Ginsberg, MD, Prasad S. Adusumilli, MD, FACS, Valerie W. Rusch, MD, Jennifer L. Sauter, MD, Teresa Ho, BS, Phillip Wong, PhD, and Marjorie G. Zauderer, MD

Subjects
Mesothelioma, Cancer vaccines, Immunotherapy, Phase 1, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Introduction: WT1 often presents on the surface of diffuse pleural mesotheliomas (DPMs) and is an ideal therapeutic target. Galinpepimut-S (GPS), a tetravalent, non–human leukocyte antigen–restricted, heteroclitic WT1–specific peptide vaccine was safe and effective in early phase clinical trials and upregulates T-cell suppressive programmed death-ligand 1 in the tumor microenvironment of other malignancies. A randomized phase 2 study of adjuvant GPS in patients with DPM trended toward improved median overall survival. Methods: To further enhance immunogenicity, we combined GPS with nivolumab, an anti-PD1 monoclonal antibody, in an open-label, single-center phase 1 study, examining tolerability and immunogenicity in patients with previously treated DPM. We enrolled patients with progressive or recurrent DPM treated with at least one course of pemetrexed-based chemotherapy. Patients received two doses of GPS followed by six doses of GPS with intravenous nivolumab every 2 weeks, and up to six additional cycles until disease progression or unacceptable toxicity. Results: Ten patients were treated; 70% experienced mostly mild treatment-related adverse events; two experienced a grade 3 or higher adverse event. Three of the 10 patients (30%) reported vaccine-specific T-cell responses. There were no partial responses; three patients had prolonged stable disease with up to 17% decrease in tumor volume. Median progression-free survival was 3.9 months and the median overall survival was 7.4 months. Conclusions: Coadministration of GPS and nivolumab reported a tolerable toxicity profile and induced immune responses in a subset of patients, but initial response and survival benefit were limited possibly owing to the small sample size.

Published
2025
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2. South-to-south collaboration to strengthen the health workforce: the case of paediatric cardiac surgery in Rwanda

Author

Zerihun Abebe, Abebe Bekele, Augustin Sendegeya, David J Bradley, Yayehyirad M Ejigu, Kara L Neil, Emmanuel Rusingiza, Gaston Nyirigira, Valerie W Rusch, Bertrand Byishimo, Roda Uwayesu, Menelas Nkeshimana, and Yvan Butera

Subjects
Medicine (General), R5-920, Infectious and parasitic diseases, RC109-216
Abstract

Paediatric cardiovascular diseases have been referred to as diseases of injustice as access to care is inequitable globally. For example, Africa only has 78 cardiac centres, with 22 located in Sub-Saharan Africa. Most of these centres rely on visiting surgical teams to provide clinical care. While visiting surgical teams provide essential care, building a sustainable and locally run cardiac workforce in Africa is critical to addressing these inequities in access to care. This paper considers the role of south-to-south partnerships in building sustainable surgical programmes using Rwanda’s paediatric cardiac surgery programme as an example.

Published
2024
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3. Genomic and transcriptomic analysis of a diffuse pleural mesothelioma patient-derived xenograft library

Author

Michael Offin, Jennifer L. Sauter, Sam E. Tischfield, Jacklynn V. Egger, Shweta Chavan, Nisargbhai S. Shah, Parvathy Manoj, Katia Ventura, Viola Allaj, Elisa de Stanchina, William Travis, Marc Ladanyi, Andreas Rimner, Valerie W. Rusch, Prasad S. Adusumilli, John T. Poirier, Marjorie G. Zauderer, Charles M. Rudin, and Triparna Sen

Subjects
Medicine, Genetics, QH426-470
Abstract

Abstract Background Diffuse pleural mesothelioma (DPM) is an aggressive malignancy that, despite recent treatment advances, has unacceptably poor outcomes. Therapeutic research in DPM is inhibited by a paucity of preclinical models that faithfully recapitulate the human disease. Methods We established 22 patient-derived xenografts (PDX) from 22 patients with DPM and performed multi-omic analyses to deconvolute the mutational landscapes, global expression profiles, and molecular subtypes of these PDX models and compared features to those of the matched primary patient tumors. Targeted next-generation sequencing (NGS; MSK-IMPACT), immunohistochemistry, and histologic subtyping were performed on all available samples. RNA sequencing was performed on all available PDX samples. Clinical outcomes and treatment history were annotated for all patients. Platinum-doublet progression-free survival (PFS) was determined from the start of chemotherapy until radiographic/clinical progression and grouped into < or ≥ 6 months. Results PDX models were established from both treatment naïve and previously treated samples and were noted to closely resemble the histology, genomic landscape, and proteomic profiles of the parent tumor. After establishing the validity of the models, transcriptomic analyses demonstrated overexpression in WNT/β-catenin, hedgehog, and TGF-β signaling and a consistent suppression of immune-related signaling in PDXs derived from patients with worse clinical outcomes. Conclusions These data demonstrate that DPM PDX models closely resemble the genotype and phenotype of parental tumors, and identify pathways altered in DPM for future exploration in preclinical studies.

Published
2022
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4. Correlative analysis from a phase I clinical trial of intrapleural administration of oncolytic vaccinia virus (Olvi-vec) in patients with malignant pleural mesothelioma

Author

Navin K. Chintala, Jennie K. Choe, Erin McGee, Rebecca Bellis, Jasmeen K. Saini, Srijita Banerjee, Andre L. Moreira, Marjorie G. Zauderer, Prasad S. Adusumilli, and Valerie W. Rusch

Subjects
pleural cancers, oncolytic viral therapy, tumor microenvironment, regional therapy, malignant pleural effusion (MPE), Immunologic diseases. Allergy, RC581-607
Abstract

BackgroundThe attenuated, genetically engineered vaccinia virus has been shown to be a promising oncolytic virus for the treatment of patients with solid tumors, through both direct cytotoxic and immune-activating effects. Whereas systemically administered oncolytic viruses can be neutralized by pre-existing antibodies, locoregionally administered viruses can infect tumor cells and generate immune responses. We conducted a phase I clinical trial to investigate the safety, feasibility and immune activating effects of intrapleural administration of oncolytic vaccinia virus (NCT01766739).MethodsEighteen patients with malignant pleural effusion due to either malignant pleural mesothelioma or metastatic disease (non-small cell lung cancer or breast cancer) underwent intrapleural administration of the oncolytic vaccinia virus using a dose-escalating method, following drainage of malignant pleural effusion. The primary objective of this trial was to determine a recommended dose of attenuated vaccinia virus. The secondary objectives were to assess feasibility, safety and tolerability; evaluate viral presence in the tumor and serum as well as viral shedding in pleural fluid, sputum, and urine; and evaluate anti-vaccinia virus immune response. Correlative analyses were performed on body fluids, peripheral blood, and tumor specimens obtained from pre- and post-treatment timepoints.ResultsTreatment with attenuated vaccinia virus at the dose of 1.00E+07 plaque-forming units (PFU) to 6.00E+09 PFU was feasible and safe, with no treatment-associated mortalities or dose-limiting toxicities. Vaccinia virus was detectable in tumor cells 2-5 days post-treatment, and treatment was associated with a decrease in tumor cell density and an increase in immune cell density as assessed by a pathologist blinded to the clinical observations. An increase in both effector (CD8+, NK, cytotoxic cells) and suppressor (Tregs) immune cell populations was observed following treatment. Dendritic cell and neutrophil populations were also increased, and immune effector and immune checkpoint proteins (granzyme B, perforin, PD-1, PD-L1, and PD-L2) and cytokines (IFN-γ, TNF-α, TGFβ1 and RANTES) were upregulated.ConclusionThe intrapleural administration of oncolytic vaccinia viral therapy is safe and feasible and generates regional immune response without overt systemic symptoms.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT01766739, identifier NCT01766739.

Published
2023
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5. A Phase 1 Safety Study of Avelumab Plus Stereotactic Body Radiation Therapy in Malignant Pleural Mesothelioma

Author

Andreas Rimner, MD, Prasad S. Adusumilli, MD, Michael D. Offin, MD, Stephen B. Solomon, MD, Etay Ziv, MD, Sara A. Hayes, MD, Michelle S. Ginsberg, MD, Jennifer L. Sauter, MD, Daphna Y. Gelblum, MD, Annemarie F. Shepherd, MD, David M. Guttmann, MD, Jordan E. Eichholz, MS, Zhigang Zhang, PhD, Erika Ritter, BS, Phillip Wong, PhD, Afsheen N. Iqbal, MD, Robert M. Daly, MD, Azadeh Namakydoust, MD, Henry Li, BS, Megan McCune, BS, Emily H. Gelb, BS, Neil K. Taunk, MD, Donata von Reibnitz, MD, Neelam Tyagi, PhD, Ellen D. Yorke, PhD, Valerie W. Rusch, MD, and Marjorie G. Zauderer, MD

Subjects
Malignant pleural mesothelioma, Stereotactic body radiation therapy, Avelumab, Safety, Phase I Study, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Introduction: Single-agent monoclonal antibody therapy against programmed death-ligand 1 (PD-L1) has modest effects in malignant pleural mesothelioma. Radiation therapy can enhance the antitumor effects of immunotherapy. Nevertheless, the safety of combining anti-PD-L1 therapy with stereotactic body radiation therapy (SBRT) is unknown. We present the results of a phase 1 trial to evaluate the safety of the anti-PD-L1 antibody avelumab plus SBRT in patients with malignant pleural mesothelioma. Methods: This was a single-arm, investigator-initiated trial in patients who progressed on prior chemotherapy. Avelumab was delivered every other week, and SBRT was delivered to one lesion in three to five fractions (minimum of 30 Gy) followed by continuation of avelumab up to 24 months or until disease progression. The primary end point of the study was safety on the basis of grade 3+ nonhematologic adverse events (AEs) within 3 months of SBRT. Results: Thirteen assessable patients received a median of seven cycles (range: 2–26 cycles) of avelumab. There were 27 grade 1, 17 grade 2, four grade 3, and no grade 4 or 5 avelumab-related AEs. The most common were infusion-related allergic reactions (n = 6), anorexia or weight loss (n = 6), fatigue (n = 6), thyroid disorders (n = 5), diarrhea (n = 3), and myalgia or arthralgias (n = 3). There were 10 grade 1, four grade 2, one grade 3, and no grade 4 or 5 SBRT-related AEs. The most common were diarrhea (n = 3), chest pain/myalgia (n = 2), fatigue (n = 2), cough (n = 2), dyspnea (n = 2), and nausea/vomiting (n = 2). Conclusions: Combination avelumab plus SBRT seems tolerable on the basis of the prespecified toxicity end points of the first stage of this Simon two-stage design phase 1 study.

Published
2023
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6. Brief Report: Contralateral Lobectomy for Second Primary NSCLC: Perioperative and Long-Term Outcomes

Author

Jennie K. Choe, MD, Amy Zhu, BS, Alexander J. Byun, MD, Junting Zheng, MS, Kay See Tan, PhD, Joe Dycoco, BS, Manjit S. Bains, MD, Matthew J. Bott, MD, Robert J. Downey, MD, James Huang, MD, James M. Isbell, MD, Daniela Molena, MD, Valerie W. Rusch, MD, Bernard J. Park, MD, Gaetano Rocco, MD, Smita Sihag, MD, David R. Jones, MD, and Prasad S. Adusumilli, MD, FACS

Subjects
Bilateral lobectomy, Sequential lobectomy, Outcomes, Complications, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Introduction: Anatomical resection—often by lobectomy—is the standard of care for patients with early stage NSCLC. With increased diagnosis, survival, and prevalence of persons with early stage NSCLC, the incidence of second primary NSCLC, and consequently, the need for contralateral lobectomy for a metachronous cancer, is increasing. Perioperative outcomes after contralateral lobectomy are unknown. Methods: Among patients who underwent contralateral lobectomy for second primary NSCLC during 1995 to 2020, we evaluated 90-day mortality and major morbidity (Clavien-Dindo grades 3–5) rates and their association with clinicopathologic variables, including the year of contralateral lobectomy and duration between lobectomies. Results: A total of 98 patients underwent contralateral lobectomy for second primary NSCLC; 51 during an early time period (1995–2009) and 47 from a late time period (2010–2020). There were five mortalities and 23 patients with major morbidities after contralateral lobectomy; both rates decreased in 2010 to 2020 compared with 1995 to 2009 (mortality 10%–0%, major morbidity 35%–11%). Major morbidity was associated with an interval of less than 1 year between lobectomies, a diffusing capacity of the lung for carbon monoxide

Published
2022
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7. Waiting to Operate

Author

Thomas Boerner, Caitlin Harrington, Kay See Tan, Prasad S. Adusumilli, Manjit S. Bains, Matthew J. Bott, Robert J. Downey, James Huang, David H. Ilson, James M. Isbell, Yelena Y. Janjigian, Bernard J. Park, Gaetano Rocco, Valerie W. Rusch, Smita Sihag, Abraham J. Wu, David R. Jones, and Daniela Molena

Subjects
Surgery
Published
2023
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8. Multimodality Therapy in Patients With Primary Pericardial Mesothelioma

Author

Michael Offin, Dilanka L. De Silva, Jennifer L. Sauter, Jacklynn V. Egger, Ellen Yorke, Prasad S. Adusumilli, Andreas Rimner, Valerie W. Rusch, and Marjorie G. Zauderer

Subjects
Adult, Mesothelioma, Pulmonary and Respiratory Medicine, Lung Neoplasms, Pleural Neoplasms, Mesothelioma, Malignant, Thymus Neoplasms, Middle Aged, Combined Modality Therapy, Young Adult, Oncology, Humans, Female, Aged
Abstract

Primary pericardial mesothelioma (PPM) has no accepted standard-of-care treatment options with management and outcomes often extrapolated from diffuse pleural mesothelioma. Disease-specific research is needed to better define PPM. We report our institutional experience with PPM highlighting the potential role for multimodality therapy.Patients with PPM diagnosed by a multidisciplinary team of medical oncologists, thoracic surgeons, thoracic pathologists, and radiologists between January 2011 and January 2022 were followed to February 2022. Clinicopathologic features and treatment outcomes were annotated. Overall survival (OS) was defined from the date of pathologic diagnosis.The median age at diagnosis of the 12 patients identified with having PPM was 51 (range: 21-71) years old. Most patients were of female sex (n = 8; 67%), 75% of the samples were epithelioid (n = 9), and 25% were nonepithelioid (two sarcomatoid and one biphasic). Most cases (92%, 11 of 12) had expression of at least two mesothelial markers on immunohistochemistry. The median OS of the cohort was 25.9 months. Five patients had an OS greater than 12 months; four of whom received pericardial radiation. Three of the patients who received radiation did so as part of a trimodality approach (surgical resection, adjuvant chemotherapy, and radiation); the OS for patients who received trimodality therapy was 70.3 months versus 8.2 months for those who did not.PPM represents a distinct disease with no universally accepted treatment options. Our findings suggest that trimodality therapy may improve outcomes in selected patients with PPM.

Published
2022
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9. Five decades of progress in surgical oncology: Tumors of the lung and esophagus

Author

Valerie W, Rusch

Subjects
Lung Neoplasms, Surgical Oncology, Esophageal Neoplasms, Oncology, Humans, Surgery, General Medicine, Lung
Abstract

During the past 50 years, there has been a remarkable transformation in the management of lung and esophageal cancers. Improved methods of diagnosis, better staging and patient selection for surgery, the advent of minimally invasive approaches to resection, decreasing operative mortality, greater insights into tumor biology, and the development of effective multimodality therapies and precision medicine have contributed to this transformation. Progress has been most notable in lung cancer.

Published
2022
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10. Patterns and influence of nodal metastases after neoadjuvant chemoradiation and R0 resection in esophageal adenocarcinoma

Author

Caitlin A, Harrington, Rebecca A, Carr, Meier, Hsu, Kay See, Tan, Smita, Sihag, Prasad S, Adusumilli, Manjit S, Bains, Matthew J, Bott, James M, Isbell, Bernard J, Park, Gaetano, Rocco, Valerie W, Rusch, David R, Jones, and Daniela, Molena

Subjects
Esophagectomy, Pulmonary and Respiratory Medicine, Esophageal Neoplasms, Humans, Surgery, Lymph Nodes, Adenocarcinoma, Prognosis, Cardiology and Cardiovascular Medicine, Neoadjuvant Therapy, Neoplasm Staging, Retrospective Studies
Abstract

Little is known about the pattern of nodal metastases in patients with esophageal adenocarcinoma who have received neoadjuvant chemoradiation and undergone surgery. We sought to assess this pattern and evaluate its association with prognosis.All patients with esophageal adenocarcinoma who underwent neoadjuvant chemoradiation and R0 esophagectomy between 2010 and 2018 at our institution were included (n = 537). The primary objective was to evaluate the association of sites of lymph node metastases with disease-free survival. The number of nodal stations and individual sites of nodal metastases were evaluated first in univariable then in separate multivariable Cox regression models adjusted for clinical factors.Of 537 patients, 193 (36%) had pathologic nodal metastases at the time of surgery; 153 (28%) had single-station disease, 32 (6.0%) had 2-station disease, and 8 (1.5%) had 3-station disease. The majority of patients with multiple positive nodal stations had positive nodes in the paraesophageal (93%) and/or left gastric stations (60%). Multivariable models controlling for clinical factors showed that an increasing number of positive nodal stations (hazard ratio, 1.59; 95% CI, 1.35-1.84; P .01)-in particular, the subcarinal (hazard ratio, 2.78; 95% CI, 1.54-5.03; P .01) and paraesophageal stations (hazard ratio, 2.0; 95% CI, 1.58-2.54; P .01)-was associated with increased risk of recurrence.One-third of patients who have undergone R0 resection for esophageal adenocarcinoma following induction chemoradiation therapy have metastatic lymph nodes. An increasing number of nodal stations, particularly paraesophageal and subcarinal metastases, were associated with increased risk of recurrence.

Published
2022
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11. Systemic and Oligo-Acquired Resistance to PD-(L)1 Blockade in Lung Cancer

Author

Adam J. Schoenfeld, Hira A. Rizvi, Danish Memon, Narek Shaverdian, Matthew J. Bott, Jennifer L. Sauter, C. Jillian Tsai, Jayon Lihm, David Hoyos, Andrew J. Plodkowski, Rocio Perez-Johnston, Peter Sawan, Jacklynn V. Egger, Benjamin D. Greenbaum, Andreas Rimner, Gregory J. Riely, Charles M. Rudin, Valerie W. Rusch, Daniel R. Gomez, and Matthew D. Hellmann

Subjects
Cancer Research, Lung Neoplasms, Oncology, Carcinoma, Non-Small-Cell Lung, Biomarkers, Tumor, Humans, Immunotherapy, B7-H1 Antigen, Tumor Burden
Abstract

Purpose: Clinical patterns and the associated optimal management of acquired resistance to PD-(L)1 blockade are poorly understood. Experimental Design: All cases of metastatic lung cancer treated with PD-(L)1 blockade at Memorial Sloan Kettering were reviewed. In acquired resistance (complete/partial response per RECIST, followed by progression), clinical patterns were distinguished as oligo (OligoAR ≤ 3 lesions of disease progression) or systemic (sAR). We analyzed the relationships between patient characteristics, burden/location of disease, outcomes, and efficacy of therapeutic interventions. Results: Of 1,536 patients, 312 (20%) had an initial response and 143 developed AR (9% overall, 46% of responders). OligoAR was the most common pattern (80/143, 56%). Baseline tumor mutational burden, depth of response, and duration of response were significantly increased in oligoAR compared with sAR (P < 0.001, P = 0.03, P = 0.04, respectively), whereas baseline PD-L1 and tumor burden were similar. Post-progression, oligoAR was associated with improved overall survival (median 28 months vs. 10 months, P < 0.001) compared with sAR. Within oligoAR, post-progression survival was greater among patients treated with locally-directed therapy (e.g., radiation, surgery; HR, 0.41; P = 0.039). Fifty-eight percent of patients with oligoAR treated with locally-directed therapy alone are progression-free at last follow-up (median 16 months), including 13 patients who are progression-free more than 2 years after local therapy. Conclusions: OligoAR is a common and distinct pattern of acquired resistance to PD-(L)1 blockade compared with sAR. OligoAR is associated with improved post-progression survival and some cases can be effectively managed with local therapies with durable benefit.

Published
2022
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12. Evolving Landscape of Initial Treatments for Patients with Malignant Pleural Mesotheliomas: Clinical Trials to Clinical Practice

Author

Michael Offin, Valerie W Rusch, Andreas Rimner, Prasad S Adusumilli, and Marjorie G Zauderer

Subjects
Clinical Trials as Topic, Cancer Research, Oncology, Mesothelioma, Malignant, Humans
Abstract

Malignant pleural mesothelioma (MPM) is the most common form of mesothelioma and the type most often studied in prospective clinical trials.This review reports the trials that have shaped first-line treatment for patients with advanced/unresectable MPM and the real-world integration of first-line immune checkpoint inhibitors into clinical practice.

Published
2022
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13. The International Association for the Study of Lung Cancer Staging Project: Methods and Guiding Principles for the Development of the Ninth Edition TNM Classification

Author

Frank C, Detterbeck, Katherine K, Nishimura, Vanessa J, Cilento, Meredith, Giuliani, Mirella, Marino, Raymond U, Osarogiagbon, Ramon, Rami-Porta, Valerie W, Rusch, and Hisao, Asamura

Subjects
Pulmonary and Respiratory Medicine, Lung Neoplasms, Databases, Factual, Oncology, Humans, Pleura, Prognosis, Lung, Neoplasm Staging
Abstract

Stage classification provides a consistent and concise nomenclature about the anatomic extent of the cancer. This is a fundamental cornerstone in the management of patients; it enables reporting results and facilitates comparing one treatment to another and judging how closely clinical trial results apply to an individual patient. A nomenclature must be relatively static; however, periodical refinement is needed to adjust to a changing landscape of clinical relevance. Changes must be well justified and thoughtfully developed to maintain the ability to communicate clearly and facilitate comparisons across time.For thoracic malignancies (lung, pleura, thymus, and esophagus), the International Association for the Study of Lung Cancer (IASLC) has leveraged its worldwide multidisciplinary reach, permitting a sophisticated approach to this process. Refinement of stage classification for the ninth edition of TNM is underway; this article describes the approach adopted by the IASLC Staging and Prognostic Factors Committee.Key guiding principles include the ability to maintain communication over time, a classification that discriminates homogeneous cohorts of tumors consistently across the world in multiple settings, treatment approaches, and patient characteristics, including clinical relevance and practical applicability. The IASLC has again assembled a large international database to permit multifaceted analysis. Providing confidence that the classification performs consistently in multiple settings, treatments, and patients requires consistent discrimination in multiple subset analyses. Although observed outcomes of patients in the 2011 to 2019 database are essential, considerations about how the classification will be used are also important to ensure clinical relevance and applicability.The strategy developed by the Staging and Prognostic Factors Committee is carefully designed to provide useful refinements to the stage classification of thoracic malignancies for the ninth edition of TNM classification of cancers.

Published
2022
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14. Amiodarone with or withoutN-Acetylcysteine for the Prevention of Atrial Fibrillation after Thoracic Surgery: A Double-blind, Randomized Trial

Author

David Amar, Hao Zhang, Mina K. Chung, Kay See Tan, Dawn Desiderio, Bernard J. Park, Alessia Pedoto, Nancy Roistacher, James M. Isbell, Daniela Molena, Ginger L. Milne, Bryan F. Meyers, Gregory W. Fischer, Valerie W. Rusch, and David R. Jones

Subjects
Anesthesiology and Pain Medicine
Abstract

BackgroundPostoperative atrial fibrillation may identify patients at risk of subsequent atrial fibrillation, with its greater risk of stroke. This study hypothesized that N-acetylcysteine mitigates inflammation and oxidative stress to reduce the incidence of postoperative atrial fibrillation.MethodsIn this double-blind, placebo-controlled trial, patients at high risk of postoperative atrial fibrillation scheduled to undergo major thoracic surgery were randomized to N-acetylcysteine plus amiodarone or placebo plus amiodarone. On arrival to the postanesthesia care unit, N-acetylcysteine or placebo intravenous bolus (50 mg/kg) and then continuous infusion (100 mg/kg over the course of 48 h) was administered plus intravenous amiodarone (bolus of 150 mg and then continuous infusion of 2 g over the course of 48 h). The primary outcome was sustained atrial fibrillation longer than 30 s by telemetry (first 72 h) or symptoms requiring intervention and confirmed by electrocardiography within 7 days of surgery. Systemic markers of inflammation (interleukin-6, interleukin-8, tumor necrosis factor α, C-reactive protein) and oxidative stress (F2-isoprostane prostaglandin F2α; isofuran) were assessed immediately after surgery and on postoperative day 2. Patients were telephoned monthly to assess the occurrence of atrial fibrillation in the first year.ResultsAmong 154 patients included, postoperative atrial fibrillation occurred in 15 of 78 who received N-acetylcysteine (19%) and 13 of 76 who received placebo (17%; odds ratio, 1.24; 95.1% CI, 0.53 to 2.88; P = 0.615). The trial was stopped at the interim analysis because of futility. Of the 28 patients with postoperative atrial fibrillation, 3 (11%) were discharged in atrial fibrillation. Regardless of treatment at 1 yr, 7 of 28 patients with postoperative atrial fibrillation (25%) had recurrent episodes of atrial fibrillation. Inflammatory and oxidative stress markers were similar between groups.ConclusionsDual therapy comprising N-acetylcysteine plus amiodarone did not reduce the incidence of postoperative atrial fibrillation or markers of inflammation and oxidative stress early after major thoracic surgery, compared with amiodarone alone. Recurrent atrial fibrillation episodes are common among patients with postoperative atrial fibrillation within 1 yr of major thoracic surgery.Editor’s PerspectiveWhat We Already Know about This TopicWhat This Article Tells Us That Is New

Published
2022
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15. The contribution of microvascular free flaps and pedicled flaps to successful chest wall surgery

Author

Stijn Vanstraelen, Barkat Ali, Manjit S. Bains, Farooq Shahzad, Robert J. Allen, Evan Matros, Joe Dycoco, Prasad S. Adusumilli, Matthew J. Bott, Robert J. Downey, James Huang, James M. Isbell, Daniela Molena, Bernard J. Park, Valerie W. Rusch, Smita Sihag, Peter G. Cordeiro, Michelle R. Coriddi, Joseph H. Dayan, Joseph Disa, Colleen M. McCarthy, Jonas A. Nelson, Carrie Stern, Babak Mehrara, David R. Jones, and Gaetano Rocco

Subjects
Pulmonary and Respiratory Medicine, Surgery, Cardiology and Cardiovascular Medicine
Published
2023
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17. Data from Integrative Molecular Characterization of Malignant Pleural Mesothelioma

Author

Erik Zmuda, Hongxin Zhang, Hailei Zhang, Jiashan Zhang, Jean C. Zenklusen, Marjorie G. Zauderer, Liming Yang, Shogo Yamamoto, Ye Wu, Tina Wong, Ignacio Wistuba, Lisa Wise, Matthew D. Wilkerson, Daniel J. Weisenberger, John N. Weinstein, Joellen Weaver, Jing Wang, Zhining Wang, Yunhu Wan, Douglas Voet, Luciano S. Viana, Umadevi Veluvolu, Nico van Zandwijk, David J. Van Den Berg, Federico Valdivieso, Tohru Tsujimura, Kane Tse, Anne Tsao, Eric Thompson, Nina Thiessen, Barry S Taylor, Kenji Tatsuno, Roy Tarnuzzer, Donghui Tan, Angela Tam, Qiang Sun, Josh Stuart, Chip Stewart, Paul Spellman, Matthew G. Soloway, Heidi J. Sofia, Tara Skelly, Payal Sipahimalani, Janae V. Simons, Henrique C. S. Silveira, Ilya Shmulevich, Yuichi Shiraishi, Yan Shi, Robert Sheridan, Troy Shelton, Candace Shelton, David T Severson, Tanguy Seiwert, Steven E. Schumacher, Nikolaus Schultz, Jacqueline E. Schein, Cristovam Scapulatempo-Neto, Ayuko Sato, Chris Sander, Gordon Saksena, Sara Sadeghi, Valerie Rusch, Jeffrey Roach, Robert C. Rintoul, William G Richards, David Rice, Sheila M. Reynolds, Rui M. Reis, Glen Reid, Gloria Ravegnini, Doris M. Rassl, Nilsa C. Ramirez, Todd Pihl, Charles M. Perou, Robert Penny, Nathan A. Pennell, Arjun Pennathur, Joseph Paulauskis, Harvey I. Pass, Joel S. Parker, Hatice Osmanbeyoglu, Angelica Ochoa, Yulia Newton, Rashi Naresh, Takashi Nakano, Karen Mungall, Andrew J. Mungall, Lisle E. Mose, Scott Morris, Cesar Moran, Richard A. Moore, Gordon B. Mills, Piotr A. Mieczkowski, Matthew Meyerson, Shaowu Meng, Jonathan Melamed, Sam Meier, Michael Mayo, Marco A. Marra, David Mallory, Dennis T. Maglinte, Yussanne Ma, James Luketich, Yiling Lu, Adhemar Longatto-Filho, Laxmi Lolla, Eric Minwei Liu, Wenbin Liu, Jia Liu, Pei Lin, Tara M. Lichtenberg, Kristen M. Leraas, Darlene Lee, Michael S. Lawrence, Peter W. Laird, Phillip H. Lai, David J. Kwiatkowski, Kozo Kuribayashi, Ritika Kundra, Thomas Krausz, Nobuyuki Kondo, Jaegil Kim, Katayoon Kasaian, Rupa S. Kanchi, Corbin D. Jones, Steven J.M. Jones, Stuart R. Jefferys, Carolyn M. Hutter, Aliya Husain, Alan P. Hoyle, Robert A. Holt, Katherine A. Hoadley, Zachary Heins, David I. Heiman, D. Neil Hayes, David Haussler, Seiki Hasegawa, Guangwu Guo, Benjamin Gross, Chandra Goparaju, Gad Getz, Mark Gerken, Nils Gehlenborg, Julie M. Gastier-Foster, Johanna Gardner, Jianjiong Gao, Françoise Galateau Sallé, Stacey B. Gabriel, Shiro Fukuda, Martin L. Ferguson, Michael Feldman, Rajiv Dhir, Noreen Dhalla, John A. Demchok, Timothy DeFreitas, Assunta De Rienzo, Ludmila Danilova, Erin Curley, Daniel Crain, Leslie Cope, Carrie Cibulskis, Sudha Chudamani, Eric Chuah, Juok Cho, Lucian Chirieac, Dorothy Cheung, Andrew D. Cherniack, Andre L. Carvalho, Rebecca Carlsen, Flávio M. Cárcano, Lauren Averett Byers, Denise Brooks, Moiz S. Bootwalla, Tom Bodenheimer, Craig Bielski, Rameen Beroukhim, Carmen Behrens, Michael Becich, Stephen B. Baylin, Saianand Balu, Miruna Balasundaram, J. Todd Auman, Joshua Armenia, Pavana Anur, Adrian Ally, Marc Ladanyi, Peter Campbell, Bruce W. Robinson, Hiroyuki Aburatani, Ronglai Shen, A. Gordon Robertson, Jonathan A. Fletcher, Michael S. Noble, Lauren A. Byers, Rehan Akbani, Jean Claude Zenklusen, Ina Felau, Jay Bowen, Kristen Leraas, Tara Lichtenberg, Jenette Creaney, Anne S. Tsao, Raphael Bueno, Hedy Kindler, Harvey Pass, Valerie W. Rusch, Henrique C. Silveira, Aliya N. Husain, Junya Fujimoto, Françoise Galateau-Sallé, Lucian R. Chirieac, Sanja Dacic, William D. Travis, Achim A. Jungbluth, Patrice Desmeules, David T. Severson, Havish Kantheti, Lisa Iype, Vesteinn Thorsson, David L. Gibbs, Lixia Diao, Carl M. Gay, Manaswi Gupta, Kiley Graim, Jumpei Takeshita, Yoshitaka Sekido, Hatice U. Osmanbeyoglu, Rupa Kanchi, Reanne Bowlby, Ewan A. Gibb, Esther Drill, Patrick Tarpey, David Heiman, Juliann Shih, Francisco Sanchez-Vega, and Julija Hmeljak

Abstract

Malignant pleural mesothelioma (MPM) is a highly lethal cancer of the lining of the chest cavity. To expand our understanding of MPM, we conducted a comprehensive integrated genomic study, including the most detailed analysis of BAP1 alterations to date. We identified histology-independent molecular prognostic subsets, and defined a novel genomic subtype with TP53 and SETDB1 mutations and extensive loss of heterozygosity. We also report strong expression of the immune-checkpoint gene VISTA in epithelioid MPM, strikingly higher than in other solid cancers, with implications for the immune response to MPM and for its immunotherapy. Our findings highlight new avenues for further investigation of MPM biology and novel therapeutic options.Significance:Through a comprehensive integrated genomic study of 74 MPMs, we provide a deeper understanding of histology-independent determinants of aggressive behavior, define a novel genomic subtype with TP53 and SETDB1 mutations and extensive loss of heterozygosity, and discovered strong expression of the immune-checkpoint gene VISTA in epithelioid MPM.See related commentary by Aggarwal and Albelda, p. 1508.This article is highlighted in the In This Issue feature, p. 1494

Published
2023
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18. Table S3 from Integrative Molecular Characterization of Malignant Pleural Mesothelioma

Author

Erik Zmuda, Hongxin Zhang, Hailei Zhang, Jiashan Zhang, Jean C. Zenklusen, Marjorie G. Zauderer, Liming Yang, Shogo Yamamoto, Ye Wu, Tina Wong, Ignacio Wistuba, Lisa Wise, Matthew D. Wilkerson, Daniel J. Weisenberger, John N. Weinstein, Joellen Weaver, Jing Wang, Zhining Wang, Yunhu Wan, Douglas Voet, Luciano S. Viana, Umadevi Veluvolu, Nico van Zandwijk, David J. Van Den Berg, Federico Valdivieso, Tohru Tsujimura, Kane Tse, Anne Tsao, Eric Thompson, Nina Thiessen, Barry S Taylor, Kenji Tatsuno, Roy Tarnuzzer, Donghui Tan, Angela Tam, Qiang Sun, Josh Stuart, Chip Stewart, Paul Spellman, Matthew G. Soloway, Heidi J. Sofia, Tara Skelly, Payal Sipahimalani, Janae V. Simons, Henrique C. S. Silveira, Ilya Shmulevich, Yuichi Shiraishi, Yan Shi, Robert Sheridan, Troy Shelton, Candace Shelton, David T Severson, Tanguy Seiwert, Steven E. Schumacher, Nikolaus Schultz, Jacqueline E. Schein, Cristovam Scapulatempo-Neto, Ayuko Sato, Chris Sander, Gordon Saksena, Sara Sadeghi, Valerie Rusch, Jeffrey Roach, Robert C. Rintoul, William G Richards, David Rice, Sheila M. Reynolds, Rui M. Reis, Glen Reid, Gloria Ravegnini, Doris M. Rassl, Nilsa C. Ramirez, Todd Pihl, Charles M. Perou, Robert Penny, Nathan A. Pennell, Arjun Pennathur, Joseph Paulauskis, Harvey I. Pass, Joel S. Parker, Hatice Osmanbeyoglu, Angelica Ochoa, Yulia Newton, Rashi Naresh, Takashi Nakano, Karen Mungall, Andrew J. Mungall, Lisle E. Mose, Scott Morris, Cesar Moran, Richard A. Moore, Gordon B. Mills, Piotr A. Mieczkowski, Matthew Meyerson, Shaowu Meng, Jonathan Melamed, Sam Meier, Michael Mayo, Marco A. Marra, David Mallory, Dennis T. Maglinte, Yussanne Ma, James Luketich, Yiling Lu, Adhemar Longatto-Filho, Laxmi Lolla, Eric Minwei Liu, Wenbin Liu, Jia Liu, Pei Lin, Tara M. Lichtenberg, Kristen M. Leraas, Darlene Lee, Michael S. Lawrence, Peter W. Laird, Phillip H. Lai, David J. Kwiatkowski, Kozo Kuribayashi, Ritika Kundra, Thomas Krausz, Nobuyuki Kondo, Jaegil Kim, Katayoon Kasaian, Rupa S. Kanchi, Corbin D. Jones, Steven J.M. Jones, Stuart R. Jefferys, Carolyn M. Hutter, Aliya Husain, Alan P. Hoyle, Robert A. Holt, Katherine A. Hoadley, Zachary Heins, David I. Heiman, D. Neil Hayes, David Haussler, Seiki Hasegawa, Guangwu Guo, Benjamin Gross, Chandra Goparaju, Gad Getz, Mark Gerken, Nils Gehlenborg, Julie M. Gastier-Foster, Johanna Gardner, Jianjiong Gao, Françoise Galateau Sallé, Stacey B. Gabriel, Shiro Fukuda, Martin L. Ferguson, Michael Feldman, Rajiv Dhir, Noreen Dhalla, John A. Demchok, Timothy DeFreitas, Assunta De Rienzo, Ludmila Danilova, Erin Curley, Daniel Crain, Leslie Cope, Carrie Cibulskis, Sudha Chudamani, Eric Chuah, Juok Cho, Lucian Chirieac, Dorothy Cheung, Andrew D. Cherniack, Andre L. Carvalho, Rebecca Carlsen, Flávio M. Cárcano, Lauren Averett Byers, Denise Brooks, Moiz S. Bootwalla, Tom Bodenheimer, Craig Bielski, Rameen Beroukhim, Carmen Behrens, Michael Becich, Stephen B. Baylin, Saianand Balu, Miruna Balasundaram, J. Todd Auman, Joshua Armenia, Pavana Anur, Adrian Ally, Marc Ladanyi, Peter Campbell, Bruce W. Robinson, Hiroyuki Aburatani, Ronglai Shen, A. Gordon Robertson, Jonathan A. Fletcher, Michael S. Noble, Lauren A. Byers, Rehan Akbani, Jean Claude Zenklusen, Ina Felau, Jay Bowen, Kristen Leraas, Tara Lichtenberg, Jenette Creaney, Anne S. Tsao, Raphael Bueno, Hedy Kindler, Harvey Pass, Valerie W. Rusch, Henrique C. Silveira, Aliya N. Husain, Junya Fujimoto, Françoise Galateau-Sallé, Lucian R. Chirieac, Sanja Dacic, William D. Travis, Achim A. Jungbluth, Patrice Desmeules, David T. Severson, Havish Kantheti, Lisa Iype, Vesteinn Thorsson, David L. Gibbs, Lixia Diao, Carl M. Gay, Manaswi Gupta, Kiley Graim, Jumpei Takeshita, Yoshitaka Sekido, Hatice U. Osmanbeyoglu, Rupa Kanchi, Reanne Bowlby, Ewan A. Gibb, Esther Drill, Patrick Tarpey, David Heiman, Juliann Shih, Francisco Sanchez-Vega, and Julija Hmeljak

Abstract

Table S3 contains the karyotypes of 16 genome-wide LOH MPM cases from the BWH cohort.

Published
2023
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19. Data from Genetic Predictors of Response to Systemic Therapy in Esophagogastric Cancer

Author

Nikolaus Schultz, David B. Solit, Barry S. Taylor, Laura Tang, Michael F. Berger, David H. Ilson, Neal Rosen, Marc Ladanyi, Maurizio Scaltriti, David M. Hyman, Ahmet Zehir, Sumit Middha, Marinela Capanu, Mark E. Robson, Jinru Shia, Daniela Molena, David R. Jones, Valerie W. Rusch, Zsofia K. Stadler, Manjit Bains, Daniel G. Coit, Hans Gerdes, Mark Schattner, Vivian E. Strong, Liying Zhang, David P. Kelsen, Benjamin E. Gross, Zachary J. Heins, Jianjiong Gao, Efsevia Vakiani, Nancy Bouvier, Ritika Kundra, Yaelle Tuvy, Jamie C. Riches, Geoffrey Y. Ku, Jaclyn F. Hechtman, Walid K. Chatila, Philip Jonsson, Francisco Sanchez-Vega, and Yelena Y. Janjigian

Abstract

The incidence of esophagogastric cancer is rapidly rising, but only a minority of patients derive durable benefit from current therapies. Chemotherapy as well as anti-HER2 and PD-1 antibodies are standard treatments. To identify predictive biomarkers of drug sensitivity and mechanisms of resistance, we implemented prospective tumor sequencing of patients with metastatic esophagogastric cancer. There was no association between homologous recombination deficiency defects and response to platinum-based chemotherapy. Patients with microsatellite instability–high tumors were intrinsically resistant to chemotherapy but more likely to achieve durable responses to immunotherapy. The single Epstein–Barr virus–positive patient achieved a durable, complete response to immunotherapy. The level of ERBB2 amplification as determined by sequencing was predictive of trastuzumab benefit. Selection for a tumor subclone lacking ERBB2 amplification, deletion of ERBB2 exon 16, and comutations in the receptor tyrosine kinase, RAS, and PI3K pathways were associated with intrinsic and/or acquired trastuzumab resistance. Prospective genomic profiling can identify patients most likely to derive durable benefit to immunotherapy and trastuzumab and guide strategies to overcome drug resistance.Significance: Clinical application of multiplex sequencing can identify biomarkers of treatment response to contemporary systemic therapies in metastatic esophagogastric cancer. This large prospective analysis sheds light on the biological complexity and the dynamic nature of therapeutic resistance in metastatic esophagogastric cancers. Cancer Discov; 8(1); 49–58. ©2017 AACR.See related commentary by Sundar and Tan, p. 14.See related article by Pectasides et al., p. 37.This article is highlighted in the In This Issue feature, p. 1

Published
2023
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20. Figure S2 from Genetic Predictors of Response to Systemic Therapy in Esophagogastric Cancer

Author

Nikolaus Schultz, David B. Solit, Barry S. Taylor, Laura Tang, Michael F. Berger, David H. Ilson, Neal Rosen, Marc Ladanyi, Maurizio Scaltriti, David M. Hyman, Ahmet Zehir, Sumit Middha, Marinela Capanu, Mark E. Robson, Jinru Shia, Daniela Molena, David R. Jones, Valerie W. Rusch, Zsofia K. Stadler, Manjit Bains, Daniel G. Coit, Hans Gerdes, Mark Schattner, Vivian E. Strong, Liying Zhang, David P. Kelsen, Benjamin E. Gross, Zachary J. Heins, Jianjiong Gao, Efsevia Vakiani, Nancy Bouvier, Ritika Kundra, Yaelle Tuvy, Jamie C. Riches, Geoffrey Y. Ku, Jaclyn F. Hechtman, Walid K. Chatila, Philip Jonsson, Francisco Sanchez-Vega, and Yelena Y. Janjigian

Abstract

Concordance between copy-number inferred from next generation sequencing and protein overexpression by IHC or gene amplification by FISH.

Published
2023
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21. Supplementary Figure 4 from Prospective Comprehensive Molecular Characterization of Lung Adenocarcinomas for Efficient Patient Matching to Approved and Emerging Therapies

Author

Gregory J. Riely, Marc Ladanyi, David B. Solit, Michael F. Berger, David M. Hyman, Charles M. Rudin, Nikolaus Schultz, Barry S. Taylor, José Baselga, Jamie E. Chaft, Mark G. Kris, Valerie W. Rusch, Ryma Benayed, Dalicia N. Reales, Matthew D. Hellmann, Alexander Drilon, Paul K. Paik, Helena A. Yu, Bob T. Li, Michelle S. Ginsberg, Natasha Rekhtman, Ahmet Zehir, Aphrothiti J. Hanrahan, Hannah C. Johnsen, Sizhi Paul Gao, Gowtham Jayakumaran, Philip Jonsson, Ritika Kundra, Andy Ni, Matthew T. Chang, JianJiong Gao, Debyani Chakravarty, David Barron, Maria E. Arcila, Hyunjae R. Kim, and Emmet J. Jordan

Abstract

Breakdown of RET and ROS1 fusion positive patients

Published
2023
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22. Supplementary Figure 1 from Prospective Comprehensive Molecular Characterization of Lung Adenocarcinomas for Efficient Patient Matching to Approved and Emerging Therapies

Author

Gregory J. Riely, Marc Ladanyi, David B. Solit, Michael F. Berger, David M. Hyman, Charles M. Rudin, Nikolaus Schultz, Barry S. Taylor, José Baselga, Jamie E. Chaft, Mark G. Kris, Valerie W. Rusch, Ryma Benayed, Dalicia N. Reales, Matthew D. Hellmann, Alexander Drilon, Paul K. Paik, Helena A. Yu, Bob T. Li, Michelle S. Ginsberg, Natasha Rekhtman, Ahmet Zehir, Aphrothiti J. Hanrahan, Hannah C. Johnsen, Sizhi Paul Gao, Gowtham Jayakumaran, Philip Jonsson, Ritika Kundra, Andy Ni, Matthew T. Chang, JianJiong Gao, Debyani Chakravarty, David Barron, Maria E. Arcila, Hyunjae R. Kim, and Emmet J. Jordan

Abstract

Co-occurring Level 1-3 alterations by MSK-IMPACT in 52 patients

Published
2023
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23. Supplementary Figure 6 from Prospective Comprehensive Molecular Characterization of Lung Adenocarcinomas for Efficient Patient Matching to Approved and Emerging Therapies

Author

Gregory J. Riely, Marc Ladanyi, David B. Solit, Michael F. Berger, David M. Hyman, Charles M. Rudin, Nikolaus Schultz, Barry S. Taylor, José Baselga, Jamie E. Chaft, Mark G. Kris, Valerie W. Rusch, Ryma Benayed, Dalicia N. Reales, Matthew D. Hellmann, Alexander Drilon, Paul K. Paik, Helena A. Yu, Bob T. Li, Michelle S. Ginsberg, Natasha Rekhtman, Ahmet Zehir, Aphrothiti J. Hanrahan, Hannah C. Johnsen, Sizhi Paul Gao, Gowtham Jayakumaran, Philip Jonsson, Ritika Kundra, Andy Ni, Matthew T. Chang, JianJiong Gao, Debyani Chakravarty, David Barron, Maria E. Arcila, Hyunjae R. Kim, and Emmet J. Jordan

Abstract

Types of Clinical trials patients enrolled to according to level 1-4 and UMD assigned samples

Published
2023
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24. Supplementary tables S1-4 from Prospective Comprehensive Molecular Characterization of Lung Adenocarcinomas for Efficient Patient Matching to Approved and Emerging Therapies

Author

Gregory J. Riely, Marc Ladanyi, David B. Solit, Michael F. Berger, David M. Hyman, Charles M. Rudin, Nikolaus Schultz, Barry S. Taylor, José Baselga, Jamie E. Chaft, Mark G. Kris, Valerie W. Rusch, Ryma Benayed, Dalicia N. Reales, Matthew D. Hellmann, Alexander Drilon, Paul K. Paik, Helena A. Yu, Bob T. Li, Michelle S. Ginsberg, Natasha Rekhtman, Ahmet Zehir, Aphrothiti J. Hanrahan, Hannah C. Johnsen, Sizhi Paul Gao, Gowtham Jayakumaran, Philip Jonsson, Ritika Kundra, Andy Ni, Matthew T. Chang, JianJiong Gao, Debyani Chakravarty, David Barron, Maria E. Arcila, Hyunjae R. Kim, and Emmet J. Jordan

Abstract

Supplementary Table S1: List of actionable genes and potential matched therapy Supplementary Table S2: List of co-occurring Level 1-4 mutations Supplementary Table S3: EGFR mutations identified and associated therapy Supplementary Table S4: List of 410 genes in MSK-IMPACT assay

Published
2023
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25. Supplementary Figure Legends from Genetic Predictors of Response to Systemic Therapy in Esophagogastric Cancer

Author

Nikolaus Schultz, David B. Solit, Barry S. Taylor, Laura Tang, Michael F. Berger, David H. Ilson, Neal Rosen, Marc Ladanyi, Maurizio Scaltriti, David M. Hyman, Ahmet Zehir, Sumit Middha, Marinela Capanu, Mark E. Robson, Jinru Shia, Daniela Molena, David R. Jones, Valerie W. Rusch, Zsofia K. Stadler, Manjit Bains, Daniel G. Coit, Hans Gerdes, Mark Schattner, Vivian E. Strong, Liying Zhang, David P. Kelsen, Benjamin E. Gross, Zachary J. Heins, Jianjiong Gao, Efsevia Vakiani, Nancy Bouvier, Ritika Kundra, Yaelle Tuvy, Jamie C. Riches, Geoffrey Y. Ku, Jaclyn F. Hechtman, Walid K. Chatila, Philip Jonsson, Francisco Sanchez-Vega, and Yelena Y. Janjigian

Abstract

Text legends for Supplementary Figures S1-S4.

Published
2023
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26. Supplementary Tables from A Phase I Trial of Regional Mesothelin-Targeted CAR T-cell Therapy in Patients with Malignant Pleural Disease, in Combination with the Anti–PD-1 Agent Pembrolizumab

Author

Michel Sadelain, David R. Jones, Renier J. Brentjens, Charles M. Rudin, Mithat Gönen, William D. Travis, Xiuyan Wang, Brigitte Senechal, Devanjan Sikder, Shanu Modi, Jennifer L. Sauter, Claudia Diamonte, Alain Vincent, Erin McGee, Daniel Ngai, Jose A. Araujo Filho, Bobby Daly, Kay See Tan, Rocio Perez-Johnston, John Pineda, Elizabeth Halton, Navin K. Chintala, Waseem Cheema, Amy Zhu, Roisin E. O'Cearbhaill, Valerie W. Rusch, Stephen B. Solomon, Isabelle Rivière, Marjorie G. Zauderer, and Prasad S. Adusumilli

Abstract

Supplemental Tables

Published
2023
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27. Supplementary Figure 5 from Prospective Comprehensive Molecular Characterization of Lung Adenocarcinomas for Efficient Patient Matching to Approved and Emerging Therapies

Author

Gregory J. Riely, Marc Ladanyi, David B. Solit, Michael F. Berger, David M. Hyman, Charles M. Rudin, Nikolaus Schultz, Barry S. Taylor, José Baselga, Jamie E. Chaft, Mark G. Kris, Valerie W. Rusch, Ryma Benayed, Dalicia N. Reales, Matthew D. Hellmann, Alexander Drilon, Paul K. Paik, Helena A. Yu, Bob T. Li, Michelle S. Ginsberg, Natasha Rekhtman, Ahmet Zehir, Aphrothiti J. Hanrahan, Hannah C. Johnsen, Sizhi Paul Gao, Gowtham Jayakumaran, Philip Jonsson, Ritika Kundra, Andy Ni, Matthew T. Chang, JianJiong Gao, Debyani Chakravarty, David Barron, Maria E. Arcila, Hyunjae R. Kim, and Emmet J. Jordan

Abstract

Breakdown of MAP2K1, RAF1, ARAF, FGFR3-TACC3 fusion and CDKN2A loss patients

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2023
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28. Supplementary Figure 2 from Prospective Comprehensive Molecular Characterization of Lung Adenocarcinomas for Efficient Patient Matching to Approved and Emerging Therapies

Author

Gregory J. Riely, Marc Ladanyi, David B. Solit, Michael F. Berger, David M. Hyman, Charles M. Rudin, Nikolaus Schultz, Barry S. Taylor, José Baselga, Jamie E. Chaft, Mark G. Kris, Valerie W. Rusch, Ryma Benayed, Dalicia N. Reales, Matthew D. Hellmann, Alexander Drilon, Paul K. Paik, Helena A. Yu, Bob T. Li, Michelle S. Ginsberg, Natasha Rekhtman, Ahmet Zehir, Aphrothiti J. Hanrahan, Hannah C. Johnsen, Sizhi Paul Gao, Gowtham Jayakumaran, Philip Jonsson, Ritika Kundra, Andy Ni, Matthew T. Chang, JianJiong Gao, Debyani Chakravarty, David Barron, Maria E. Arcila, Hyunjae R. Kim, and Emmet J. Jordan

Abstract

Patient 1 Concurrent EGFR and KRAS mutations in a patient identified by MSK-IMPACT

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2023
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29. Supplementary Figure 7 from Prospective Comprehensive Molecular Characterization of Lung Adenocarcinomas for Efficient Patient Matching to Approved and Emerging Therapies

Author

Gregory J. Riely, Marc Ladanyi, David B. Solit, Michael F. Berger, David M. Hyman, Charles M. Rudin, Nikolaus Schultz, Barry S. Taylor, José Baselga, Jamie E. Chaft, Mark G. Kris, Valerie W. Rusch, Ryma Benayed, Dalicia N. Reales, Matthew D. Hellmann, Alexander Drilon, Paul K. Paik, Helena A. Yu, Bob T. Li, Michelle S. Ginsberg, Natasha Rekhtman, Ahmet Zehir, Aphrothiti J. Hanrahan, Hannah C. Johnsen, Sizhi Paul Gao, Gowtham Jayakumaran, Philip Jonsson, Ritika Kundra, Andy Ni, Matthew T. Chang, JianJiong Gao, Debyani Chakravarty, David Barron, Maria E. Arcila, Hyunjae R. Kim, and Emmet J. Jordan

Abstract

Median number of mutations in samples sequenced by MSK-IMPACT in patients with a Level 1-4 alteration or assigned to the unknown mitogenic driver cohort.

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2023
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30. Data from A Phase I Trial of Regional Mesothelin-Targeted CAR T-cell Therapy in Patients with Malignant Pleural Disease, in Combination with the Anti–PD-1 Agent Pembrolizumab

Author

Michel Sadelain, David R. Jones, Renier J. Brentjens, Charles M. Rudin, Mithat Gönen, William D. Travis, Xiuyan Wang, Brigitte Senechal, Devanjan Sikder, Shanu Modi, Jennifer L. Sauter, Claudia Diamonte, Alain Vincent, Erin McGee, Daniel Ngai, Jose A. Araujo Filho, Bobby Daly, Kay See Tan, Rocio Perez-Johnston, John Pineda, Elizabeth Halton, Navin K. Chintala, Waseem Cheema, Amy Zhu, Roisin E. O'Cearbhaill, Valerie W. Rusch, Stephen B. Solomon, Isabelle Rivière, Marjorie G. Zauderer, and Prasad S. Adusumilli

Abstract

Malignant pleural diseases, comprising metastatic lung and breast cancers and malignant pleural mesothelioma (MPM), are aggressive solid tumors with poor therapeutic response. We developed and conducted a first-in-human, phase I study of regionally delivered, autologous, mesothelin-targeted chimeric antigen receptor (CAR) T-cell therapy. Intrapleural administration of 0.3M to 60M CAR T cells/kg in 27 patients (25 with MPM) was safe and well tolerated. CAR T cells were detected in peripheral blood for >100 days in 39% of patients. Following our demonstration that PD-1 blockade enhances CAR T-cell function in mice, 18 patients with MPM also received pembrolizumab safely. Among those patients, median overall survival from CAR T-cell infusion was 23.9 months (1-year overall survival, 83%). Stable disease was sustained for ≥6 months in 8 patients; 2 exhibited complete metabolic response on PET scan. Combination immunotherapy with CAR T cells and PD-1 blockade agents should be further evaluated in patients with solid tumors.Significance:Regional delivery of mesothelin-targeted CAR T-cell therapy followed by pembrolizumab administration is feasible, safe, and demonstrates evidence of antitumor efficacy in patients with malignant pleural diseases. Our data support the investigation of combination immunotherapy with CAR T cells and PD-1 blockade agents in solid tumors.See related commentary by Aldea et al., p. 2674.This article is highlighted in the In This Issue feature, p. 2659

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2023
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31. Tables S1-S5 from Genetic Predictors of Response to Systemic Therapy in Esophagogastric Cancer

Author

Nikolaus Schultz, David B. Solit, Barry S. Taylor, Laura Tang, Michael F. Berger, David H. Ilson, Neal Rosen, Marc Ladanyi, Maurizio Scaltriti, David M. Hyman, Ahmet Zehir, Sumit Middha, Marinela Capanu, Mark E. Robson, Jinru Shia, Daniela Molena, David R. Jones, Valerie W. Rusch, Zsofia K. Stadler, Manjit Bains, Daniel G. Coit, Hans Gerdes, Mark Schattner, Vivian E. Strong, Liying Zhang, David P. Kelsen, Benjamin E. Gross, Zachary J. Heins, Jianjiong Gao, Efsevia Vakiani, Nancy Bouvier, Ritika Kundra, Yaelle Tuvy, Jamie C. Riches, Geoffrey Y. Ku, Jaclyn F. Hechtman, Walid K. Chatila, Philip Jonsson, Francisco Sanchez-Vega, and Yelena Y. Janjigian

Abstract

Supplementary Table 1: Comprehensive clinical data and sample IDs. Supplementary Table 2: Summary of baseline patient and sample characteristics. Supplementary Table 3: List of somatic mutations identified in all samples. Supplementary Table 4: Detailed data for assesment of ERBB2 amplification. Supplementary Table 5: Genes included on MSK-IMPACT platform

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2023
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32. Supplementary Figure 3 from Prospective Comprehensive Molecular Characterization of Lung Adenocarcinomas for Efficient Patient Matching to Approved and Emerging Therapies

Author

Gregory J. Riely, Marc Ladanyi, David B. Solit, Michael F. Berger, David M. Hyman, Charles M. Rudin, Nikolaus Schultz, Barry S. Taylor, José Baselga, Jamie E. Chaft, Mark G. Kris, Valerie W. Rusch, Ryma Benayed, Dalicia N. Reales, Matthew D. Hellmann, Alexander Drilon, Paul K. Paik, Helena A. Yu, Bob T. Li, Michelle S. Ginsberg, Natasha Rekhtman, Ahmet Zehir, Aphrothiti J. Hanrahan, Hannah C. Johnsen, Sizhi Paul Gao, Gowtham Jayakumaran, Philip Jonsson, Ritika Kundra, Andy Ni, Matthew T. Chang, JianJiong Gao, Debyani Chakravarty, David Barron, Maria E. Arcila, Hyunjae R. Kim, and Emmet J. Jordan

Abstract

Patient 2 Concurrent EGFR and KRAS mutations in a patient identified by MSK-IMPACT

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2023
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33. Supplementary Data from Integrative Molecular Characterization of Malignant Pleural Mesothelioma

Author

Erik Zmuda, Hongxin Zhang, Hailei Zhang, Jiashan Zhang, Jean C. Zenklusen, Marjorie G. Zauderer, Liming Yang, Shogo Yamamoto, Ye Wu, Tina Wong, Ignacio Wistuba, Lisa Wise, Matthew D. Wilkerson, Daniel J. Weisenberger, John N. Weinstein, Joellen Weaver, Jing Wang, Zhining Wang, Yunhu Wan, Douglas Voet, Luciano S. Viana, Umadevi Veluvolu, Nico van Zandwijk, David J. Van Den Berg, Federico Valdivieso, Tohru Tsujimura, Kane Tse, Anne Tsao, Eric Thompson, Nina Thiessen, Barry S Taylor, Kenji Tatsuno, Roy Tarnuzzer, Donghui Tan, Angela Tam, Qiang Sun, Josh Stuart, Chip Stewart, Paul Spellman, Matthew G. Soloway, Heidi J. Sofia, Tara Skelly, Payal Sipahimalani, Janae V. Simons, Henrique C. S. Silveira, Ilya Shmulevich, Yuichi Shiraishi, Yan Shi, Robert Sheridan, Troy Shelton, Candace Shelton, David T Severson, Tanguy Seiwert, Steven E. Schumacher, Nikolaus Schultz, Jacqueline E. Schein, Cristovam Scapulatempo-Neto, Ayuko Sato, Chris Sander, Gordon Saksena, Sara Sadeghi, Valerie Rusch, Jeffrey Roach, Robert C. Rintoul, William G Richards, David Rice, Sheila M. Reynolds, Rui M. Reis, Glen Reid, Gloria Ravegnini, Doris M. Rassl, Nilsa C. Ramirez, Todd Pihl, Charles M. Perou, Robert Penny, Nathan A. Pennell, Arjun Pennathur, Joseph Paulauskis, Harvey I. Pass, Joel S. Parker, Hatice Osmanbeyoglu, Angelica Ochoa, Yulia Newton, Rashi Naresh, Takashi Nakano, Karen Mungall, Andrew J. Mungall, Lisle E. Mose, Scott Morris, Cesar Moran, Richard A. Moore, Gordon B. Mills, Piotr A. Mieczkowski, Matthew Meyerson, Shaowu Meng, Jonathan Melamed, Sam Meier, Michael Mayo, Marco A. Marra, David Mallory, Dennis T. Maglinte, Yussanne Ma, James Luketich, Yiling Lu, Adhemar Longatto-Filho, Laxmi Lolla, Eric Minwei Liu, Wenbin Liu, Jia Liu, Pei Lin, Tara M. Lichtenberg, Kristen M. Leraas, Darlene Lee, Michael S. Lawrence, Peter W. Laird, Phillip H. Lai, David J. Kwiatkowski, Kozo Kuribayashi, Ritika Kundra, Thomas Krausz, Nobuyuki Kondo, Jaegil Kim, Katayoon Kasaian, Rupa S. Kanchi, Corbin D. Jones, Steven J.M. Jones, Stuart R. Jefferys, Carolyn M. Hutter, Aliya Husain, Alan P. Hoyle, Robert A. Holt, Katherine A. Hoadley, Zachary Heins, David I. Heiman, D. Neil Hayes, David Haussler, Seiki Hasegawa, Guangwu Guo, Benjamin Gross, Chandra Goparaju, Gad Getz, Mark Gerken, Nils Gehlenborg, Julie M. Gastier-Foster, Johanna Gardner, Jianjiong Gao, Françoise Galateau Sallé, Stacey B. Gabriel, Shiro Fukuda, Martin L. Ferguson, Michael Feldman, Rajiv Dhir, Noreen Dhalla, John A. Demchok, Timothy DeFreitas, Assunta De Rienzo, Ludmila Danilova, Erin Curley, Daniel Crain, Leslie Cope, Carrie Cibulskis, Sudha Chudamani, Eric Chuah, Juok Cho, Lucian Chirieac, Dorothy Cheung, Andrew D. Cherniack, Andre L. Carvalho, Rebecca Carlsen, Flávio M. Cárcano, Lauren Averett Byers, Denise Brooks, Moiz S. Bootwalla, Tom Bodenheimer, Craig Bielski, Rameen Beroukhim, Carmen Behrens, Michael Becich, Stephen B. Baylin, Saianand Balu, Miruna Balasundaram, J. Todd Auman, Joshua Armenia, Pavana Anur, Adrian Ally, Marc Ladanyi, Peter Campbell, Bruce W. Robinson, Hiroyuki Aburatani, Ronglai Shen, A. Gordon Robertson, Jonathan A. Fletcher, Michael S. Noble, Lauren A. Byers, Rehan Akbani, Jean Claude Zenklusen, Ina Felau, Jay Bowen, Kristen Leraas, Tara Lichtenberg, Jenette Creaney, Anne S. Tsao, Raphael Bueno, Hedy Kindler, Harvey Pass, Valerie W. Rusch, Henrique C. Silveira, Aliya N. Husain, Junya Fujimoto, Françoise Galateau-Sallé, Lucian R. Chirieac, Sanja Dacic, William D. Travis, Achim A. Jungbluth, Patrice Desmeules, David T. Severson, Havish Kantheti, Lisa Iype, Vesteinn Thorsson, David L. Gibbs, Lixia Diao, Carl M. Gay, Manaswi Gupta, Kiley Graim, Jumpei Takeshita, Yoshitaka Sekido, Hatice U. Osmanbeyoglu, Rupa Kanchi, Reanne Bowlby, Ewan A. Gibb, Esther Drill, Patrick Tarpey, David Heiman, Juliann Shih, Francisco Sanchez-Vega, and Julija Hmeljak

Abstract

Supplementary materials and methods, as well as supplementary figures S1-S7.

Published
2023
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34. Supplementary Figures from A Phase I Trial of Regional Mesothelin-Targeted CAR T-cell Therapy in Patients with Malignant Pleural Disease, in Combination with the Anti–PD-1 Agent Pembrolizumab

Author

Michel Sadelain, David R. Jones, Renier J. Brentjens, Charles M. Rudin, Mithat Gönen, William D. Travis, Xiuyan Wang, Brigitte Senechal, Devanjan Sikder, Shanu Modi, Jennifer L. Sauter, Claudia Diamonte, Alain Vincent, Erin McGee, Daniel Ngai, Jose A. Araujo Filho, Bobby Daly, Kay See Tan, Rocio Perez-Johnston, John Pineda, Elizabeth Halton, Navin K. Chintala, Waseem Cheema, Amy Zhu, Roisin E. O'Cearbhaill, Valerie W. Rusch, Stephen B. Solomon, Isabelle Rivière, Marjorie G. Zauderer, and Prasad S. Adusumilli

Abstract

Supplemental Figures

Published
2023
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35. Supplementary Material from A Phase I Trial of Regional Mesothelin-Targeted CAR T-cell Therapy in Patients with Malignant Pleural Disease, in Combination with the Anti–PD-1 Agent Pembrolizumab

Author

Michel Sadelain, David R. Jones, Renier J. Brentjens, Charles M. Rudin, Mithat Gönen, William D. Travis, Xiuyan Wang, Brigitte Senechal, Devanjan Sikder, Shanu Modi, Jennifer L. Sauter, Claudia Diamonte, Alain Vincent, Erin McGee, Daniel Ngai, Jose A. Araujo Filho, Bobby Daly, Kay See Tan, Rocio Perez-Johnston, John Pineda, Elizabeth Halton, Navin K. Chintala, Waseem Cheema, Amy Zhu, Roisin E. O'Cearbhaill, Valerie W. Rusch, Stephen B. Solomon, Isabelle Rivière, Marjorie G. Zauderer, and Prasad S. Adusumilli

Abstract

Supplemental Material

Published
2023
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36. Data from Prognostic Immune Markers in Non–Small Cell Lung Cancer

Author

Prasad S. Adusumilli, William D. Travis, Valerie W. Rusch, David G. Beer, Qianxing Mo, Ronglai Shen, Kyuichi Kadota, Stefan S. Kachala, and Kei Suzuki

Abstract

Tumor-associated immune responses have polarized effects in regulating tumor growth. Although a clear association has been shown between the tumor immune response and clinical outcome in colorectal and ovarian cancers, the role of immune markers for stratifying prognosis in non–small cell lung cancer (NSCLC) is less defined. Herein, we review the prognostic significance of published immune markers in the tumor microenvironment and peripheral blood of NSCLC patients. To identify prognostic immune genes, we reviewed all published gene-profiling studies in NSCLC and delineated the significance of immune genes by doing subanalysis on the microarray database of the NIH Director's Challenge study. This first comprehensive review of prognostic immune markers provides a foundation for further investigating immune responses in NSCLC. Clin Cancer Res; 17(16); 5247–56. ©2011 AACR.

Published
2023
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37. Data from Mesothelin Overexpression Promotes Mesothelioma Cell Invasion and MMP-9 Secretion in an Orthotopic Mouse Model and in Epithelioid Pleural Mesothelioma Patients

Author

Prasad S. Adusumilli, Michel Sadelain, Valerie W. Rusch, Camelia Sima, Jun-ichi Nitadori, Adam J. Bograd, Luis Rodriguez, Christos Colovos, and Elliot L. Servais

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. Clin Cancer Res; 18(9); 2478–89. ©2012 AACR.

Published
2023
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38. Table S3 from Comprehensive Next-Generation Sequencing Unambiguously Distinguishes Separate Primary Lung Carcinomas From Intrapulmonary Metastases: Comparison with Standard Histopathologic Approach

Author

Natasha Rekhtman, Marc Ladanyi, William D. Travis, Maria E. Arcila, David R. Jones, Valerie W. Rusch, Gregory J. Riely, Francis M. Bodd, Patrice Desmeules, Sounak Gupta, Chad M. Vanderbilt, Darren J. Buonocore, Jennifer L. Sauter, Andrew Golden, Venkatraman Seshan, Kay See Tan, Matthew Bott, Deepu Alex, and Jason C. Chang

Abstract

Supplemental Table 3

Published
2023
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39. Supplementary Data from Analysis of Tumor Genomic Pathway Alterations Using Broad-Panel Next-Generation Sequencing in Surgically Resected Lung Adenocarcinoma

Author

David R. Jones, Nikolaus Schultz, Michael F. Berger, David B. Solit, Marc Ladanyi, Fan Yang, Natasha Rekhtman, Walid K. Chatila, Valerie W. Rusch, Daniela Molena, Smita Sihag, James M. Isbell, James Huang, Matthew Bott, Prasad S. Adusumilli, Shi Yan, Gregory D. Jones, Whitney S. Brandt, Kay See Tan, Raul Caso, Francisco Sanchez-Vega, and Jian Zhou

Abstract

Online supplement

Published
2023
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40. Supplemental Tables from Comprehensive Molecular and Clinicopathologic Analysis of 200 Pulmonary Invasive Mucinous Adenocarcinomas Identifies Distinct Characteristics of Molecular Subtypes

Author

Natasha Rekhtman, Alexander Drilon, Marc Ladanyi, William D. Travis, Maria E. Arcila, Alison M. Schram, Bob T. Li, Laetitia Borsu, Khedoudja Nafa, Ryma Benayed, Joshua K. Sabari, Sarah Teed, Valerie W. Rusch, Prasad S. Adusumilli, Kyuichi Kadota, Patrice Desmeules, Joseph Montecalvo, Sharon Amir, Helen H. Won, Vasilisa A. Rudneva, Fanli Meng, Brian R. Houck-Loomis, David Brown, Christina Falcon, Michael Offin, and Jason C. Chang

Abstract

Supplemental Tables 1-11

Published
2023
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41. Supplementary Figures from KRASG12C Mutation Is Associated with Increased Risk of Recurrence in Surgically Resected Lung Adenocarcinoma

Author

James M. Isbell, Bob T. Li, David R. Jones, Charles M. Rudin, David C. Lyden, Haiying Zhang, Piro Lito, Neal Rosen, Gregory J. Riely, Kathryn C. Arbour, Alexander Drilon, Rona Yaeger, Sandra Misale, Smita Sihag, Valerie W. Rusch, Gaetano Rocco, Daniela Molena, Prasad S. Adusumilli, Matthew J. Bott, Yonina R. Murciano-Goroff, James G. Connolly, Yuan Liu, Francisco Sanchez-Vega, Brooke Mastrogiacomo, Kay See Tan, Raul Caso, and Gregory D. Jones

Abstract

Supplementary Figures

Published
2023
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42. Supplemental Methods 2 from Comprehensive Molecular and Clinicopathologic Analysis of 200 Pulmonary Invasive Mucinous Adenocarcinomas Identifies Distinct Characteristics of Molecular Subtypes

Author

Natasha Rekhtman, Alexander Drilon, Marc Ladanyi, William D. Travis, Maria E. Arcila, Alison M. Schram, Bob T. Li, Laetitia Borsu, Khedoudja Nafa, Ryma Benayed, Joshua K. Sabari, Sarah Teed, Valerie W. Rusch, Prasad S. Adusumilli, Kyuichi Kadota, Patrice Desmeules, Joseph Montecalvo, Sharon Amir, Helen H. Won, Vasilisa A. Rudneva, Fanli Meng, Brian R. Houck-Loomis, David Brown, Christina Falcon, Michael Offin, and Jason C. Chang

Abstract

Supplemental Methods 2

Published
2023
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44. Data from Tissue and Serum Mesothelin Are Potential Markers of Neoplastic Progression in Barrett's Associated Esophageal Adenocarcinoma

Author

Prasad S. Adusumilli, Valerie W. Rusch, Martin Fleisher, Hans Gerdes, Camelia S. Sima, Laura H. Tang, Elliot L. Servais, and Nabil P. Rizk

Abstract

Background: Mesothelin is overexpressed in several malignancies and is purportedly a specific marker of malignant transformation. In this pilot study, we investigated whether tissue and serum mesothelin are potential markers of neoplastic progression in Barrett's esophagus (BE) and in esophageal adenocarcinoma (EAC).Methods: Mesothelin expression was retrospectively evaluated in normal, BE, and EAC tissue from surgically resected esophageal specimens (n = 125). In addition, soluble mesothelin-related peptide (SMRP) levels were measured in serum.Results: Normal esophageal mucosa did not express mesothelin. BE tissue with high-grade dysplasia specifically expressed mesothelin, whereas BE tissue with low-grade or without dysplasia did not. Fifty-seven (46%) EAC tumors were positive for mesothelin. EAC tumors with BE expressed mesothelin more often than those without BE (58% vs. 35%, P = 0.01). SMRP levels were elevated in 70% of EAC patients (mean = 0.89 nmol/L; range: 0.03–3.77 nmol/L), but not in patients with acid reflux and/or BE.Conclusions: Mesothelin is commonly expressed in BE-associated EAC. On the basis of this pilot study, a prospective study is under way to evaluate tissue and serum mesothelin which are potential markers of neoplastic progression in BE and in EAC (NCT01393483).Impact: Current surveillance methods in Barrett's esophagus are invasive and neither cost-effective nor sensitive. This pilot study suggests that serum mesothelin is a marker of neoplastic transformation in BE and may provide a noninvasive method to improve identification of malignant transformation. Cancer Epidemiol Biomarkers Prev; 21(3); 482–6. ©2012 AACR.

Published
2023
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46. Data from Analysis of Tumor Genomic Pathway Alterations Using Broad-Panel Next-Generation Sequencing in Surgically Resected Lung Adenocarcinoma

Author

David R. Jones, Nikolaus Schultz, Michael F. Berger, David B. Solit, Marc Ladanyi, Fan Yang, Natasha Rekhtman, Walid K. Chatila, Valerie W. Rusch, Daniela Molena, Smita Sihag, James M. Isbell, James Huang, Matthew Bott, Prasad S. Adusumilli, Shi Yan, Gregory D. Jones, Whitney S. Brandt, Kay See Tan, Raul Caso, Francisco Sanchez-Vega, and Jian Zhou

Abstract

Purpose:The majority of broad-panel tumor genomic profiling has used a gene-centric approach, although much of that data is unused in clinical decision making. We hypothesized that a pathway-centric approach using next-generation sequencing (NGS), combined with conventional clinicopathologic features, may better predict disease-free survival (DFS) in early stage lung adenocarcinoma.Experimental Design:Utilizing our prospectively maintained database, we analyzed 492 patients with primary, untreated, completely surgically resected lung adenocarcinoma. Ten canonical pathways were analyzed using broad-panel NGS. The correlations of DFS and number (and type) of pathway (NPA) were analyzed using the Kaplan–Meier method and log-rank test. Associations between altered pathways and clinicopathologic variables, as well as identification of actionable therapeutic strategies were explored.Results:Median NPA for the cohort was two (range, 0–5). Smoking status, solid morphologic appearance on preoperative CT, maximal standardized uptake value, pathologic tumor size, aggressive histologic subtype, lymphovascular invasion, visceral pleural invasion, and positive lymph nodes were significantly associated with NPA (P < 0.05). Of 543 actionable genetic alterations identified, 455 (84%) were within the RTK/RAS pathway. A total of 86 tumors had actionable therapeutic genomic alterations in >1 pathway. On multivariable analysis, higher NPA was significantly associated with worse DFS (HR, 1.31; P = 0.014).Conclusions:NPA and specific pathway alterations are associated with clinicopathologic features in patients with surgically resected lung adenocarcinoma. Cell cycle, Hippo, TGFβ, and p53 pathway alterations are associated with poor DFS. Finally, NPA is an independent risk factor for poor DFS in our cohort.See related commentary by Blakely, p. 7269

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2023
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47. Supplementary Table 1 from A Randomized Phase II Trial of Adjuvant Galinpepimut-S, WT-1 Analogue Peptide Vaccine, After Multimodality Therapy for Patients with Malignant Pleural Mesothelioma

Author

Lee M. Krug, David A. Scheinberg, Reza Mehran, David Rice, Daniel Gomez, Michelle S. Ginsberg, Prasad S. Adusumilli, Valerie W. Rusch, Andreas Rimner, W. Victoria Lai, Katherine Panageas, Tao Dao, Anne S. Tsao, and Marjorie G. Zauderer

Abstract

Includes peptide sequences for WT1 vaccine

Published
2023
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49. Supplementary Data from Comprehensive Genomic Analysis Reveals Clinically Relevant Molecular Distinctions between Thymic Carcinomas and Thymomas

Author

William Pao, Mark G. Kris, Valerie W. Rusch, William D. Travis, Cristina R. Antonescu, Agnes Viale, Marc Ladanyi, Alex E. Lash, Christopher Lau, James Huang, Gregory J. Riely, Adriana Heguy, Maureen F. Zakowski, Tianhua Guo, Ronglai Shen, and Nicolas Girard

Abstract

Supplementary Data from Comprehensive Genomic Analysis Reveals Clinically Relevant Molecular Distinctions between Thymic Carcinomas and Thymomas

Published
2023
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50. Supplemental Figure 1 from Comprehensive Molecular and Clinicopathologic Analysis of 200 Pulmonary Invasive Mucinous Adenocarcinomas Identifies Distinct Characteristics of Molecular Subtypes

Author

Natasha Rekhtman, Alexander Drilon, Marc Ladanyi, William D. Travis, Maria E. Arcila, Alison M. Schram, Bob T. Li, Laetitia Borsu, Khedoudja Nafa, Ryma Benayed, Joshua K. Sabari, Sarah Teed, Valerie W. Rusch, Prasad S. Adusumilli, Kyuichi Kadota, Patrice Desmeules, Joseph Montecalvo, Sharon Amir, Helen H. Won, Vasilisa A. Rudneva, Fanli Meng, Brian R. Houck-Loomis, David Brown, Christina Falcon, Michael Offin, and Jason C. Chang

Abstract

Supplemental Figure 1. Consort diagram summarizing the molecular workflow of cases.

Published
2023
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