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2. Enhancing NSCLC recurrence prediction with PET/CT habitat imaging, ctDNA, and integrative radiogenomics-blood insights

Author

Sujit, Sheeba J., Aminu, Muhammad, Karpinets, Tatiana V., Chen, Pingjun, Saad, Maliazurina B., Salehjahromi, Morteza, Boom, John D., Qayati, Mohamed, George, James M., Allen, Haley, Antonoff, Mara B., Hong, Lingzhi, Hu, Xin, Heeke, Simon, Tran, Hai T., Le, Xiuning, Elamin, Yasir Y., Altan, Mehmet, Vokes, Natalie I., Sheshadri, Ajay, Lin, Julie, Zhang, Jianhua, Lu, Yang, Behrens, Carmen, Godoy, Myrna C. B., Wu, Carol C., Chang, Joe Y., Chung, Caroline, Jaffray, David A., Wistuba, Ignacio I., Lee, J. Jack, Vaporciyan, Ara A., Gibbons, Don L., Heymach, John, Zhang, Jianjun, Cascone, Tina, and Wu, Jia

Published
2024
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3. Comutations and KRASG12C Inhibitor Efficacy in Advanced NSCLC.

Author

Negrao, Marcelo, Araujo, Haniel, Lamberti, Giuseppe, Cooper, Alissa, Akhave, Neal, Zhou, Teng, Delasos, Lukas, Hicks, J, Aldea, Mihaela, Minuti, Gabriele, Hines, Jacobi, Aredo, Jacqueline, Dennis, Michael, Scott, Susan, Bironzo, Paolo, Scheffler, Matthias, Christopoulos, Petros, Stenzinger, Albrecht, Riess, Jonathan, Kim, So, Goldberg, Sarah, Li, Mingjia, Wang, Qi, Qing, Yun, Ni, Ying, Do, Minh, Lee, Richard, Ricciuti, Biagio, Alessi, Joao, Wang, Jing, Resuli, Blerina, Landi, Lorenza, Tseng, Shu-Chi, Nishino, Mizuki, Digumarthy, Subba, Rinsurongkawong, Waree, Rinsurongkawong, Vadeerat, Vaporciyan, Ara, Blumenschein, George, Zhang, Jianjun, Owen, Dwight, Mountzios, Giannis, Shu, Catherine, Bestvina, Christine, Garassino, Marina, Marrone, Kristen, Gray, Jhanelle, Patel, Sandip, Cummings, Amy, Wakelee, Heather, Wolf, Juergen, Scagliotti, Giorgio, Cappuzzo, Federico, Barlesi, Fabrice, Patil, Pradnya, Drusbosky, Leylah, Gibbons, Don, Meric-Bernstam, Funda, Lee, J, Heymach, John, Hong, David, Heist, Rebecca, Awad, Mark, Skoulidis, Ferdinandos, Blakely, Collin, and Chakrabarti, Turja

Subjects
Humans, Carcinoma, Non-Small-Cell Lung, Lung Neoplasms, Kelch-Like ECH-Associated Protein 1, Phosphatidylinositol 3-Kinases, Mutation, NF-E2-Related Factor 2, DNA Helicases, Nuclear Proteins, Transcription Factors
Abstract

UNLABELLED: Molecular modifiers of KRASG12C inhibitor (KRASG12Ci) efficacy in advanced KRASG12C-mutant NSCLC are poorly defined. In a large unbiased clinicogenomic analysis of 424 patients with non-small cell lung cancer (NSCLC), we identified and validated coalterations in KEAP1, SMARCA4, and CDKN2A as major independent determinants of inferior clinical outcomes with KRASG12Ci monotherapy. Collectively, comutations in these three tumor suppressor genes segregated patients into distinct prognostic subgroups and captured ∼50% of those with early disease progression (progression-free survival ≤3 months) with KRASG12Ci. Pathway-level integration of less prevalent coalterations in functionally related genes nominated PI3K/AKT/MTOR pathway and additional baseline RAS gene alterations, including amplifications, as candidate drivers of inferior outcomes with KRASG12Ci, and revealed a possible association between defective DNA damage response/repair and improved KRASG12Ci efficacy. Our findings propose a framework for patient stratification and clinical outcome prediction in KRASG12C-mutant NSCLC that can inform rational selection and appropriate tailoring of emerging combination therapies. SIGNIFICANCE: In this work, we identify co-occurring genomic alterations in KEAP1, SMARCA4, and CDKN2A as independent determinants of poor clinical outcomes with KRASG12Ci monotherapy in advanced NSCLC, and we propose a framework for patient stratification and treatment personalization based on the comutational status of individual tumors. See related commentary by Heng et al., p. 1513. This article is highlighted in the In This Issue feature, p. 1501.

Published
2023

4. Impact of select actionable genomic alterations on efficacy of neoadjuvant immunotherapy in resectable non-small cell lung cancer

Author

Charles Lu, Mehmet Altan, Apar Pataer, Tina Cascone, Annikka Weissferdt, Jianjun Zhang, Boris Sepesi, Ara A Vaporciyan, Marcelo V Negrao, Hai T Tran, Stephen G Swisher, John V Heymach, Don L Gibbons, Brett W Carter, Jack A Roth, Ferdinandos Skoulidis, Yasir Y Elamin, Xiuning Le, Wayne L Hofstetter, J Jack Lee, Bonnie S Glisson, Myrna C B Godoy, Garrett L Walsh, Jia Wu, Humam Kadara, George R Blumenschein, Heather Y Lin, Nicolas Zhou, William N William, Cheuk H Leung, Frank V Fossella, Anne S Tsao, Jonathan M Kurie, Lauren A Byers, Reza J Mehran, David C Rice, and Luisa M Solis Soto

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Background Neoadjuvant immune checkpoint inhibitors (ICIs) have improved survival outcomes compared with chemotherapy in resectable non-small cell lung cancer (NSCLC). However, the impact of actionable genomic alterations (AGAs) on the efficacy of neoadjuvant ICIs remains unclear. We report the influence of AGAs on treatment failure (TF) in patients with resectable NSCLC treated with neoadjuvant ICIs.Methods Tumor molecular profiles were obtained from patients with stage I–IIIA resectable NSCLC (American Joint Committee on Cancer seventh edition) treated with either neoadjuvant nivolumab (N, n=23) or nivolumab+ipilimumab (NI, n=21) followed by surgery in a previously reported phase-2 randomized study (NCT03158129). TF was defined as any progression of primary lung cancer after neoadjuvant ICI therapy in patients without surgery, radiographic and/or biopsy-proven primary lung cancer recurrence after surgery, or death from possibly treatment-related complications or from primary lung cancer since randomization. Tumors with AGAs (n=12) were compared with tumors without AGAs and non-profiled squamous cell carcinomas (non-AGAs+NP SCC, n=20).Results With a median follow-up of 60.2 months, the overall TF rate was 34.1% (15/44). Tumor molecular profiling was retrospectively obtained in 47.7% (21/44) of patients and select AGAs were identified in 12 patients: 5 epidermal growth factor receptor (EGFR), 2 KRAS, 1 ERBB2, and 1 BRAF mutations, 2 anaplastic lymphoma kinase (ALK) and 1 RET fusions. The median time to TF in patients with AGAs was 24.7 months (95% CI: 12.6 to 40.4), compared with not reached (95% CI: not evaluable (NE)–NE) in the non-AGAs+NP SCC group. The TF risk was higher in AGAs (HR: 5.51, 95% CI: 1.68 to 18.1), and lower in former/current smokers (HR: 0.24, 95% CI: 0.08 to 0.75). The odds of major pathological response were 4.71 (95% CI: 0.49 to 45.2) times higher in the non-AGAs+NP SCC group, and the median percentage of residual viable tumor was 72.5% in AGAs compared with 33.0% in non-AGS+NP SCC tumors.Conclusions Patients with NSCLC harboring select AGAs, including EGFR and ALK alterations, have a higher risk for TF, shorter median time to TF, and diminished pathological regression after neoadjuvant ICIs. The suboptimal efficacy of neoadjuvant chemotherapy-sparing, ICI-based regimens in this patient subset underscores the importance of tumor molecular testing prior to initiation of neoadjuvant ICI therapy in patients with resectable NSCLC.

Published
2024
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6. Perioperative and oncologic outcomes of pulmonary resection for synchronous oligometastatic non–small cell lung cancer: Evidence for surgery in advanced disease

Author

Deboever, Nathaniel, Mitchell, Kyle G., Farooqi, Ahsan, Ludmir, Ethan B., Hofstetter, Wayne L., Mehran, Reza J., Rajaram, Ravi, Rice, David C., Sepesi, Boris, Swisher, Stephen G., Vaporciyan, Ara A., Walsh, Garrett L., Heymach, John V., Gomez, Daniel R., Gandhi, Saumil J., and Antonoff, Mara B.

Published
2024
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9. Surgical outcomes after chemotherapy plus nivolumab and chemotherapy plus nivolumab and ipilimumab in patients with non–small cell lung cancer

Author

Feldman, Hope, Sepesi, Boris, Leung, Cheuk H., Lin, Heather, Weissferdt, Annikka, Pataer, Apar, William, William N., Jr., Walsh, Garrett L., Rice, David C., Roth, Jack A., Mehran, Reza J., Hofstetter, Wayne L., Antonoff, Mara B., Rajaram, Ravi, Gibbons, Don L., Lee, J. Jack, Heymach, John V., Vaporciyan, Ara A., Swisher, Stephen G., and Cascone, Tina

Published
2024
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10. Synthetic PET from CT improves diagnosis and prognosis for lung cancer: Proof of concept

Author

Salehjahromi, Morteza, Karpinets, Tatiana V., Sujit, Sheeba J., Qayati, Mohamed, Chen, Pingjun, Aminu, Muhammad, Saad, Maliazurina B., Bandyopadhyay, Rukhmini, Hong, Lingzhi, Sheshadri, Ajay, Lin, Julie, Antonoff, Mara B., Sepesi, Boris, Ostrin, Edwin J., Toumazis, Iakovos, Huang, Peng, Cheng, Chao, Cascone, Tina, Vokes, Natalie I., Behrens, Carmen, Siewerdsen, Jeffrey H., Hazle, John D., Chang, Joe Y., Zhang, Jianhua, Lu, Yang, Godoy, Myrna C.B., Chung, Caroline, Jaffray, David, Wistuba, Ignacio, Lee, J. Jack, Vaporciyan, Ara A., Gibbons, Don L., Gladish, Gregory, Heymach, John V., Wu, Carol C., Zhang, Jianjun, and Wu, Jia

Published
2024
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15. Case report: Molecular profiling facilitates the diagnosis of a challenging case of lung cancer with choriocarcinoma features

Author

Hui Li, Xin Hu, Matthew S. Ning, Gregory N. Fuller, John M. Stewart, Jared C. Gilliam, Jia Wu, Xiuning Le, Ara A. Vaporciyan, J. Jack Lee, Don L. Gibbons, John V. Heymach, Andrew Futreal, and Jianjun Zhang

Subjects
lung cancer with choriocarcinoma features, whole transcriptome sequencing, whole exome sequencing, immune checkpoint inhibitors, nivolumab, ipilimumab, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Accurate diagnoses are crucial in determining the most effective treatment across different cancers. In challenging cases, morphology-based traditional pathology methods have important limitations, while molecular profiling can provide valuable information to guide clinical decisions. We present a 35-year female with lung cancer with choriocarcinoma features. Her disease involved the right lower lung, brain, and thoracic lymph nodes. The pathology from brain metastasis was reported as “metastatic choriocarcinoma” (a germ cell tumor) by local pathologists. She initiated carboplatin and etoposide, a regimen for choriocarcinoma. Subsequently, her case was assessed by pathologists from an academic cancer center, who gave the diagnosis of “adenocarcinoma with aberrant expression of β-hCG” and finally pathologists at our hospital, who gave the diagnosis of “poorly differentiated carcinoma with choriocarcinoma features”. Genomic profiling detected a KRAS G13R mutation and transcriptomics profiling was suggestive of lung origin. The patient was treated with carboplatin/paclitaxel/ipilimumab/nivolumab followed by consolidation radiation therapy. She had no evidence of progression to date, 16 months after the initial presentation. The molecular profiling could facilitate diagnosing of challenging cancer cases. In addition, chemoimmunotherapy and local consolidation radiation therapy may provide promising therapeutic options for patients with lung cancer exhibiting choriocarcinoma features.

Published
2024
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16. Brief Report: Comprehensive Clinicogenomic Profiling of Small Cell Transformation From EGFR-Mutant NSCLC Informs Potential Therapeutic Targets

Author

Bingnan Zhang, MD, MBA, Whitney Lewis, PharmD, C. Allison Stewart, PhD, Benjamin B. Morris, PhD, Luisa M. Solis, MD, Alejandra Serrano, MD, Yuanxin Xi, PhD, Qi Wang, PhD, Elyse R. Lopez, MD, Kyle Concannon, MD, Simon Heeke, PhD, Ximing Tang, MD, PhD, Gabriela Raso, MD, Robert J. Cardnell, PhD, Natalie Vokes, MD, George Blumenschein, MD, Yasir Elamin, MD, Frank Fosella, MD, Anne Tsao, MD, Ferdinandos Skoulidis, MD, PhD, Celyne Bueno Hume, MD, Koji Sasak, MD, PhD, Jeff Lewis, BS, Waree Rinsurongkawong, PhD, Vadeerat Rinsurongkawong, PhD, Jack Lee, PhD, Hai Tran, PhD, Jianjun Zhang, MD, PhD, Don Gibbons, MD, PhD, Ara Vaporciyan, MD, Jing Wang, PhD, Keunchil Park, MD, PhD, John V. Heymach, MD, PhD, Lauren A. Byers, MD, Carl M. Gay, MD, PhD, and Xiuning Le, MD, PhD

Subjects
Histologic transformation, SCLC, NSCLC, Resistance mechanism, Osimertinib, Cell surface target, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Introduction: NSCLC transformation to SCLC has been best characterized with EGFR-mutant NSCLC, with emerging case reports seen in ALK, RET, and KRAS-altered NSCLC. Previous reports revealed transformed SCLC from EGFR-mutant NSCLC portends very poor prognosis and lack effective treatment. Genomic analyses revealed TP53 and RB1 loss of function increase the risk of SCLC transformation. Little has been reported on the detailed clinicogenomic characteristics and potential therapeutic targets for this patient population. Methods: In this study, we conducted a single-center retrospective analysis of clinical and genomic characteristics of patients with EGFR-mutant NSCLC transformed to SCLC. Demographic data, treatment course, and clinical molecular testing reports were extracted from electronic medical records. Kaplan-Meier analyses were used to estimate survival outcomes. Next generation sequencing-based assays was used to identify EGFR and co-occurring genetic alterations in tissue or plasma before and after SCLC transformation. Single-cell RNA sequencing (scRNA-seq) was performed on a patient-derived-xenograft model generated from a patient with EGFR-NSCLC transformed SCLC tumor. Results: A total of 34 patients were identified in our study. Median age at initial diagnosis was 58, and median time to SCLC transformation was 24.2 months. 68% were female and 82% were never smokers. 79% of patients were diagnosed as stage IV disease, and over half had brain metastases at baseline. Median overall survival of the entire cohort was 38.3 months from initial diagnoses and 12.4 months from time of SCLC transformation. Most patients harbored EGFR exon19 deletions as opposed to exon21 L858R alteration. Continuing EGFR tyrosine kinase inhibitor post-transformation did not improve overall survival compared with those patients where tyrosine kinase inhibitor was stopped in our cohort. In the 20 paired pretransformed and post-transformed patient samples, statistically significant enrichment was seen with PIK3CA alterations (p = 0.04) post-transformation. Profiling of longitudinal liquid biopsy samples suggest emergence of SCLC genetic alterations before biopsy-proven SCLC, as shown by increasing variant allele frequency of TP53, RB1, PIK3CA alterations. ScRNA-seq revealed potential therapeutic targets including DLL3, CD276 (B7-H3) and PTK7 were widely expressed in transformed SCLC. Conclusions: SCLC transformation is a potential treatment resistance mechanism in driver-mutant NSCLC. In our cohort of 34 EGFR-mutant NSCLC, poor prognosis was observed after SCLC transformation. Clinicogenomic analyses of paired and longitudinal samples identified genomic alterations emerging post-transformation and scRNA-seq reveal potential therapeutic targets in this population. Further studies are needed to rigorously validate biomarkers and therapeutic targets for this patient population.

Published
2024
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17. Efficacy and clinicogenomic correlates of response to immune checkpoint inhibitors alone or with chemotherapy in non-small cell lung cancer

Author

Hong, Lingzhi, Aminu, Muhammad, Li, Shenduo, Lu, Xuetao, Petranovic, Milena, Saad, Maliazurina B., Chen, Pingjun, Qin, Kang, Varghese, Susan, Rinsurongkawong, Waree, Rinsurongkawong, Vadeerat, Spelman, Amy, Elamin, Yasir Y., Negrao, Marcelo V., Skoulidis, Ferdinandos, Gay, Carl M., Cascone, Tina, Gandhi, Saumil J., Lin, Steven H., Lee, Percy P., Carter, Brett W., Wu, Carol C., Antonoff, Mara B., Sepesi, Boris, Lewis, Jeff, Gibbons, Don L., Vaporciyan, Ara A., Le, Xiuning, Jack Lee, J., Roy-Chowdhuri, Sinchita, Routbort, Mark J., Gainor, Justin F., Heymach, John V., Lou, Yanyan, Wu, Jia, Zhang, Jianjun, and Vokes, Natalie I.

Published
2023
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18. Initial patient characteristics of Thoracic Surgical Oncology Group 102: A multicenter prospective registry of active surveillance in patients with multiple ground-glass opacities

Author

Huang, James, Tan, Kay See, Altorki, Nasser, Antonoff, Mara, Blackmon, Shanda, Bueno, Raphael, Burt, Bryan, Demmy, Todd, Evans, Nathaniel, Donahoe, Laura, Harpole, David, Jarrar, Doraid, Kozower, Benjamin, Lanuti, Michael, Liberman, Moishe, Lin, Jules, Liou, Douglas, Liptay, Michael, Luketich, James, Pennathur, Arjun, Petersen, Gerard, Ripley, Robert, Rochefort, Matthew, Seder, Christopher W., Shrager, Joseph, Su, Stacey, Tong, Betty, Shargall, Yaron, Vaporciyan, Ara, Waddell, Thomas, Weksler, Benny, Wigle, Dennis, Yendamuri, Sai, and Jones, David R.

Published
2024
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22. Effect of colchicine on perioperative atrial fibrillation and myocardial injury after non-cardiac surgery in patients undergoing major thoracic surgery (COP-AF): an international randomised trial

Author

Conen, David, Devereaux, PJ, Vincent, Jessica, Wang, Michael Ke, Wells, Jennifer R., Healey, Jeff S., Landoni, Giovanni, McIntyre, William F., Popova, Ekaterine, Sessler, Daniel I., Srinathan, Sadeesh K., Amir, Mohammed, Bangdiwala, Shrikant I., Bossard, Matthias, Chan, Matthew TV, Eikelboom, John W., Fleischmann, Edith, Jolly, Sanjit, Montes, Felix Ramón, Reimer, Cara, Schmartz, Denis, Wang, Chew Yin, Ofori, Sandra N., Blum, Steffen, Alvarez-Garcia, Jesus, Lo Bianco, Giuliana, Traquair, Hugh, Guerrero-Pinedo, Fernando Andres, Oleynick, Christopher, Meyre, Pascal B., Méndez-Zurita, Francisco, Chiarella-Redfern, Helene, Marcucci, Maura, Donati, Francesco, Gonzalez-Osuna, Aranzazu, Minervini, Fabrizio, Moreno Weidmann, Zoraida, Guerra-Ramos, Jose M., Dion, Gabriel, Ramos-Pachón, Anna, Borges, Flavia K., de Sa Boasquevisque, Danielle, Mosconi, Maria Giulia, Amarenco, Pierre, Mitchell, L. Brent, Wyse, George, Cheng, Davy, McAlister, Finlay A., Wells, George A., Baskaran, Geethan, Burns, Andrew T., Gennaccaro, Julia, Howe, Rosemary, Mastrangelo, Louise, Pettit, Shirley, Popovic, Michelle, Shahbaz, Subana, Tosh, Makayla, Zucchetto, Simona J., Heenan, Laura, Lee, Shun Fu, Li, Zhuoru, Xu, Lizhen, Kabon, Barbara, Hoetzenecker, Konrad, Schweiger, Thomas, Reiterer, Christian, Zotti, Oliver, Bsuchner, Paul, Hochreiter, Beatrix, Taschner, Alexander, Adamowitsch, Nikolas, Horvath, Katharina, Hantáková, Nicole, Bidgoli, Javad, Huybrechts, Isabelle, Cappeliez, Serge, Neary, John D., Shargall, Yaron, Tandon, Vikas, Finley, Christian, Agzarian, John, Hanna, Waël, Abdulrahman, Muammar, Lawrence, Kelly, Gregus, Krysten, Quraishi, Faraaz, Wikkerink, Spencer, Wallace, Christine, Prine, Merissa, Gregus, Emily, Hare, Jacqueline, Lombardo, Kristen, Fezia, Behashta, Columbus, Teresa, Rushton, Jacob, DuMerton, Deborah, Reid, Ken, Parlow, Joel, Chung, Wiley, Karizhenskaia, Maria, Malik, Aftab, Tanzola, Rob, Giles, Andrew, McLean, Sean R., McGuire, Anna, Lohser, Jens, Lim, Shirley, Grey, Rebecca, Yee, John, Grant, Kyle, Lee, Alex L., Choi, James J., Dewar, Leith R., Durkin, Christopher, Schisler, Travis, Hecht, Patrick, Hughes, Bevan, Kidane, Biniam, Liu, Richard, Tan, Lawrence, Gowing, Stephen, Buduhan, Gordon, Enns, Stephanie, Poole, Emma, Graham, Kristin, Dubik, Niina, Chin, Alex, Maziak, Donna E., Seely, Andrew JE, Gilbert, Sebastien, Villeneuve, P. James, Sundaresan, Sudhir, Gingrich, Molly, Fazekas, Anna, Bucciero, Kirby, Malthaner, Richard A., Lewis, Deb, Fortin, Dalilah, Qiabi, Mehdi, Nayak, Rahul, Plourde, Madelaine Marie, Haider, Tehmina, Murphy, Rowan, Sellers, Daniel, Donahoe, Laura, Lefebvre, Marco, Lanthier, Luc, Ko, Michael Augustine, Parente, David, Cheung, Victoria, Schieman, Colin, Bessissow, Amal, Wong, Randolph HL, Joynt, Gavin M., Lam, Carmen KM, Lau, Rainbow WH, Wan, Innes YP, Underwood, Malcolm J., Wu, William KK, Wong, Wai Tat, Choi, Gordon YS, Lee, Eva, Hui, Ka Yan, Fung, Beaker, Chan, Chee Sam, Ng, Fung Kei, Thung, Kin Hoi, Gutiérrez-Soriano, Laura, Castañeda, Laura Carmenza, Téllez, Luis Jaime, Ortiz-Ramirez, Lina Marcela, Baiardo-Redaelli, Martina, Belletti, Alessandro, Dieci, Elisa, Monaco, Fabrizio, Muriana, Piergiorgio, Nakhnoukh, Cristina, Novellis, Pierluigi, Turi, Stefano, Viscardi, Stefano, Veronesi, Giulia, Voltolini, Luca, Bongiolatti, Stefano, Salvicchi, Alberto, Gatteschi, Lavinia, Indino, Rossella, Tombelli, Simone, Ravasin, Alice, Salimbene, Ottavia, Rosboch, Giulio Luca, Balzani, Eleonora, Ceraolo, Edoardo, Neitzert, Luca, Brazzi, Luca, Londero, Francesco, Grossi, William, Massullo, Domenico, Fiorelli, Silvia, Margaritora, Stefano, Hashim, Shahrul Amry, Krishnasamy, Sivakumar, See, Woan Shiang, Nawaz, Mohammed Asghar, Bilal, Haris, Trujillo Reyes, Juan Carlos, Martínez-Téllez, Elisabeth, Belda Sanchis, Josep, Planas Canovas, Georgina, Libreros Niño, Alejandra, Parera Ruiz, Ana, Cladellas Gutierrez, Esther, Guarino, Mauro, Urrutia Cuchi, Gerard, Argilaga Nogues, Marta, Rovira Juan, Anna, Medina-Aedo, Melixa, Turró Castillejo, Mª Asunción, Gil Sanchez, Josep Mª, Araúz-Sarmiento, Ibell, Herranz Perez, Gracia, Chavarria Murillo, Stephania, Garcia-Osuna, Alvaro, Rodriguez-Arias, Ainhoa, Berga Garrote, Nuria, Martín Grande, Ascension, Parise Roux, Diego, Gajate Martín, Luis, De Pablo Pajares, Angélica, Candela Toha, Angel Manuel, Moreno Mata, Nicolás, Muñoz Molina, Gema, Caballero Silva, Usue, Cabañero, Alberto, Fra Fernandez, Sara, Cavestany García-Matres, Cristina, Simón, Luisa, Montenegro, Cristina, Pozo, Sergio, Gonzàlez-Tallada, Anna, González Suarez, Susana, Ribas Ball, Montserrat, De Nadal Clanchet, Miriam, Pérez Vélez, Javier, Cruz, Patrícia, Sánchez-Pedrosa, Guillermo, Duque, Patricia, González, Guillermo, Huerta, Luis, Rodríguez, Laura, Garutti, Ignacio, Ruiz-Villa, Laura, Martí-Ejarque, Maria del Mar, Gili-Bueno, Mireia, Maddio Vieyra, Ricardo Matias, Fibla, Juan J., Durán, Núria, de Temple Pla, Marina, Rodríguez-Fuster, Alberto, Bermejo-Martínez, Silvia, Carramiñana, Albert, Opitz, Isabelle, Etienne, Harry, Cata, Juan P., Guerra-Londono, Juan Jose, Rajaram, Ravi, Corrales, German, Vaporciyan, Ara, Mehran, Reza, Sepesi, Boris, Walsh, Garrett, Rice, David, Cukierman, Daniel S., Swisher, Stephen, Marchant, Bryan E., Harris, Lynne C., Cusson, Bruce D., Miller, Scott A., Ayad, Sabry, Araujo, Jorge, Marquez-Roa, Leonardo, Hofstra, Richard L., Wudel, Jr., Leonard J., Minear, Steven C., Teixeira, Camila, Pimentel, Mario, Popoff, Andrew M., Marsack, Kelly, Meehan, Sarah, Chen, Tzonghuei H., Essandoh, Michael, Poppers, Jeremy S., Ke Wang, Michael, Chan, Matthew T V, Cata, Juan P, McLean, Sean R, Srinathan, Sadeesh K, Reyes, Juan Carlos Trujillo, Grande, Ascension Martín, Tallada, Anna Gonzalez, Sessler, Daniel I, Maziak, Donna E, McIntyre, William F, Wong, Randolph H L, McGuire, Anna L, Roux, Diego Parise, Wells, Jennifer R, Ofori, Sandra N, Eikelboom, John W, Jolly, Sanjit S, Healey, Jeff S, and Devereaux, P J

Published
2023
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23. Neoadjuvant chemotherapy plus nivolumab with or without ipilimumab in operable non-small cell lung cancer: the phase 2 platform NEOSTAR trial

Author

Cascone, Tina, Leung, Cheuk H., Weissferdt, Annikka, Pataer, Apar, Carter, Brett W., Godoy, Myrna C. B., Feldman, Hope, William, Jr, William N., Xi, Yuanxin, Basu, Sreyashi, Sun, Jing Jing, Yadav, Shalini S., Rojas Alvarez, Frank R., Lee, Younghee, Mishra, Aditya K., Chen, Lili, Pradhan, Monika, Guo, Haiping, Sinjab, Ansam, Zhou, Nicolas, Negrao, Marcelo V., Le, Xiuning, Gay, Carl M., Tsao, Anne S., Byers, Lauren Averett, Altan, Mehmet, Glisson, Bonnie S., Fossella, Frank V., Elamin, Yasir Y., Blumenschein, Jr, George, Zhang, Jianjun, Skoulidis, Ferdinandos, Wu, Jia, Mehran, Reza J., Rice, David C., Walsh, Garrett L., Hofstetter, Wayne L., Rajaram, Ravi, Antonoff, Mara B., Fujimoto, Junya, Solis, Luisa M., Parra, Edwin R., Haymaker, Cara, Wistuba, Ignacio I., Swisher, Stephen G., Vaporciyan, Ara A., Lin, Heather Y., Wang, Jing, Gibbons, Don L., Jack Lee, J., Ajami, Nadim J., Wargo, Jennifer A., Allison, James P., Sharma, Padmanee, Kadara, Humam, Heymach, John V., and Sepesi, Boris

Published
2023
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24. Stereotactic ablative radiotherapy with or without immunotherapy for early-stage or isolated lung parenchymal recurrent node-negative non-small-cell lung cancer: an open-label, randomised, phase 2 trial

Author

Chang, Joe Y, Lin, Steven H, Dong, Wenli, Liao, Zhongxing, Gandhi, Saumil J, Gay, Carl M, Zhang, Jianjun, Chun, Stephen G, Elamin, Yasir Y, Fossella, Frank V, Blumenschein, George, Cascone, Tina, Le, Xiuning, Pozadzides, Jenny V, Tsao, Anne, Verma, Vivek, Welsh, James W, Chen, Aileen B, Altan, Mehmet, Mehran, Reza J, Vaporciyan, Ara A, Swisher, Stephen G, Balter, Peter A, Fujimoto, Junya, Wistuba, Ignacio I, Feng, Lei, Lee, J Jack, and Heymach, John V

Published
2023
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26. Predicting benefit from immune checkpoint inhibitors in patients with non-small-cell lung cancer by CT-based ensemble deep learning: a retrospective study

Author

Saad, Maliazurina B, Hong, Lingzhi, Aminu, Muhammad, Vokes, Natalie I, Chen, Pingjun, Salehjahromi, Morteza, Qin, Kang, Sujit, Sheeba J, Lu, Xuetao, Young, Elliana, Al-Tashi, Qasem, Qureshi, Rizwan, Wu, Carol C, Carter, Brett W, Lin, Steven H, Lee, Percy P, Gandhi, Saumil, Chang, Joe Y, Li, Ruijiang, Gensheimer, Michael F, Wakelee, Heather A, Neal, Joel W, Lee, Hyun-Sung, Cheng, Chao, Velcheti, Vamsidhar, Lou, Yanyan, Petranovic, Milena, Rinsurongkawong, Waree, Le, Xiuning, Rinsurongkawong, Vadeerat, Spelman, Amy, Elamin, Yasir Y, Negrao, Marcelo V, Skoulidis, Ferdinandos, Gay, Carl M, Cascone, Tina, Antonoff, Mara B, Sepesi, Boris, Lewis, Jeff, Wistuba, Ignacio I, Hazle, John D, Chung, Caroline, Jaffray, David, Gibbons, Don L, Vaporciyan, Ara, Lee, J Jack, Heymach, John V, Zhang, Jianjun, and Wu, Jia

Published
2023
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31. Intraoperative challenges after induction therapy for non–small cell lung cancer: Effect of nodal disease on technical complexityCentral MessagePerspective

Author

Hope A. Feldman, MD, Nicolas Zhou, DO, Nathanial Deboever, MD, Wayne Hofstetter, MD, Reza Mehran, MD, Ravi Rajaram, MD, David Rice, MD, Jack A. Roth, MD, Boris Sepesi, MD, Stephen Swisher, MD, Ara Vaporciyan, MD, Garrett Walsh, MD, Myrna Godoy, MD, PhD, Chad Strange, MD, and Mara B. Antonoff, MD

Subjects
non–small cell lung cancer, neoadjuvant therapy, surgery, pulmonary artery, nodal disease, Diseases of the circulatory (Cardiovascular) system, RC666-701, Surgery, RD1-811
Abstract

Objectives: Neoadjuvant therapy has been theorized to increase complexity of non–small cell lung cancer resections; however, specific factors that contribute to intraoperative challenges after induction therapy have not been well described. We aimed to characterize the effect of nodal involvement and nodal treatment response on surgical complexity after neoadjuvant therapy. Methods: We identified patients treated with neoadjuvant therapy followed by anatomic lung resection for cN + non–small cell lung cancer between 2010 and 2020. Patients were categorized according to clinical N1 versus N2 disease. To evaluate the effect of nodal response to therapy, thoracic radiologists measured clinically suspected and pathologically involved lymph nodes before and after induction therapy. Operative reports were reviewed to identify technical challenges specifically related to nodal disease. Categorical outcomes were compared using Fisher exact test. Results: One hundred twenty-four patients met inclusion criteria, among whom 107 (86.3%) were treated with neoadjuvant chemotherapy, whereas chemoradiation (n = 8) and targeted therapy (n = 9) were less common. In cases with N1 disease, 8/38 (21.0%) required proximal pulmonary arterial control, whereas this was necessary in only 2/88 (2.3%) of N2 cases (P = .001). Likewise, sleeve resection and arterioplasty were needed more frequently during resection of N1 disease (7/38, 18.4%) versus N2 disease (0/88, P

Published
2022
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32. Radiographic response to neoadjuvant therapy in pleural mesothelioma should serve as a guide for patient selection for cytoreductive operations

Author

Nathaniel Deboever, Nicolas Zhou, Daniel J. McGrail, Katarzyna Tomczak, Jacqueline L. Oliva, Hope A. Feldman, Edwin Parra, Jianjun Zhang, Percy P. Lee, Mara B. Antonoff, Wayne L. Hofstetter, Reza J. Mehran, Ravi Rajaram, David C. Rice, Jack A. Roth, Stephen S. Swisher, Ara A. Vaporciyan, Mehmet Altan, Annikka Weissferdt, Anne S. Tsao, Cara L. Haymaker, and Boris Sepesi

Subjects
malignant pleural mesothelioma, neoadjuvant therapy, radiographic response, cytoreductive resection, patient-centered care, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

BackgroundMalignant pleural mesothelioma (MPM) is associated with poor prognosis despite advances in multimodal therapeutic strategies. While patients with resectable disease may benefit from added survival with oncologic resection, patient selection for mesothelioma operations often relies on both objective and subjective evaluation metrics. We sought to evaluate factors associated with improved overall survival (OS) in patients with mesothelioma who underwent macroscopic complete resection (MCR).MethodsPatients with MPM who received neoadjuvant therapy and underwent MCR were identified in a prospectively maintained departmental database. Clinicopathologic, blood-based, and radiographic variables were collected and included in a Cox regression analysis (CRA). Response to neoadjuvant therapy was characterized by a change in tumor thickness from pretherapy to preoperative scans using the modified RECIST criteria.ResultsIn this study, 99 patients met the inclusion criteria. The median age of the included patients was 64.7 years, who were predominantly men, had smoking and asbestos exposure, and who received neoadjuvant therapy. The median change in tumor thickness following neoadjuvant therapy was –16.5% (interquartile range of -49.7% to +14.2%). CRA demonstrated reduced OS associated with non-epithelioid histology [hazard ratio (HR): 3.06, 95% confidence interval (CI): 1.62–5.78, p < 0.001] and a response to neoadjuvant therapy inferior to the median (HR: 2.70, CI: 1.55–4.72, p < 0.001). Patients who responded poorly (below median) to neoadjuvant therapy had lower median survival (15.8 months compared to 38.2 months, p < 0.001).ConclusionPoor response to neoadjuvant therapy in patients with MPM is associated with poor outcomes even following maximum surgical cytoreduction and should warrant a patient-centered discussion regarding goals of care and may therefore help guide further therapeutic decisions.

Published
2023
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33. Brief Report: Clinical Response, Toxicity, and Resistance Mechanisms to Osimertinib Plus MET Inhibitors in Patients With EGFR-Mutant MET-Amplified NSCLC

Author

Kaiwen Wang, PharmD, Robyn Du, BS, Sinchita Roy-Chowdhuri, MD, Ziping T. Li, MD, Lingzhi Hong, MD, Natalie Vokes, MD, Yasir Y. Elamin, MD, Celyne Bueno Hume, MD, Ferdinandos Skoulidis, MD, PhD, Carl M. Gay, MD, PhD, George Blumenschein, MD, Frank V. Fossella, MD, Anne Tsao, MD, Jianjun Zhang, MD, PhD, Niki Karachaliou, MD, Aurora O’Brate, PhD, Claudia-Nanette Gann, MD, Jeff Lewis, MS, Waree Rinsurongkawong, PhD, J. Jack Lee, PhD, MS, DDS, Don Lynn Gibbons, MD, PhD, Ara A. Vaporciyan, MD, John V. Heymach, MD, PhD, Mehmet Altan, MD, and Xiuning Le, MD, PhD

Subjects
Resistance mechanisms, MET, EGFR, NSCLC, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Introduction: MET amplification is a known resistance mechanism to EGFR tyrosine kinase inhibitor (TKI) treatment in EGFR-mutant NSCLC. Dual EGFR-MET inhibition has been reported with success in overcoming such resistance and inducing clinical benefit. Resistance mechanisms to dual EGFR-MET inhibition require further investigation and characterization. Methods: Patients with NSCLC with both MET amplification and EGFR mutation who have received crizotinib, capmatinib, savolitinib, or tepotinib plus osimertinib (OSI) after progression on OSI at MD Anderson Cancer Center were included in this study. Molecular profiling was completed by means of fluorescence in situ hybridization (FISH) and next-generation sequencing (NGS). Radiological response was assessed on the basis of Response Evaluation Criteria in Solid Tumors version 1.1. Results: From March 2016 to March 2022, 23 treatments with dual MET inhibitor and osi were identified with a total of 20 patients included. Three patients received capmatinib plus OSI after progression on crizotinib plus OSI. Median age was 64 (38–89) years old and 75% were female. MET amplification was detected by FISH in 14 patients in the tissue, NGS in 10 patients, and circulating tumor DNA in three patients. Median MET gene copy number was 13.6 (6.4–20). Overall response rate was 34.8% (eight of 23). In assessable patients, tumor shrinkage was observed in 82.4% (14 of 17). Median time on treatment was 27 months. Two of three patients responded to capmatinib plus OSI after progression on crizotinib plus OSI. Dual EGFR-MET inhibition was overall well tolerated. Two patients on crizotinib plus OSI and one pt on capmatinib plus OSI discontinued therapy due to pneumonitis. One pt discontinued crizotinib plus OSI due to gastrointestinal toxicity. Six patients were still on double TKI treatment. At disease progression to dual EGFR-MET inhibition, FISH and NGS on tumor and plasma were completed in six patients. Notable resistance mechanisms observed include acquired MET D1246H (n = 1), acquired EGFR C797S (n = 2), FGFR2 fusion (n = 1, concurrent with C797S), and EGFR G796S (n = 1, concurrent with C797S). Four patients lost MET amplification. Conclusions: Dual EGFR and MET inhibition yielded high clinical response rate after progression on OSI. Resistance mechanisms to EGFR-MET double TKI inhibition include MET secondary mutation, EGFR secondary mutation, or loss of MET amplification.

Published
2023
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34. Salvage Esophagectomy Definition Influences Comparative Outcomes in Esophageal Squamous Cell Cancers

Author

Zhou, Nicolas, Hofstetter, Wayne L., Mitchell, Kyle G., Bayley, Erin M., Ajani, Jaffer A., Antonoff, Mara B., Betancourt, Sonia L., Blum-Murphy, Mariela, Feldman, Hope A., Lin, Steven H., Maru, Dipen M., Mehran, Reza J., Rajaram, Ravi, Rice, David C., Roth, Jack A., Sepesi, Boris, Swisher, Stephen G., Vaporciyan, Ara A., Walsh, Garrett L., and Weston, Brian R.

Published
2022
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36. Surgical outcomes after neoadjuvant nivolumab or nivolumab with ipilimumab in patients with non–small cell lung cancer

Author

Sepesi, Boris, Zhou, Nicolas, William, William N., Jr., Lin, Heather Y., Leung, Cheuk H., Weissferdt, Annikka, Mitchell, Kyle G., Pataer, Apar, Walsh, Garrett L., Rice, David C., Roth, Jack A., Mehran, Reza J., Hofstetter, Wayne L., Antonoff, Mara B., Rajaram, Ravi, Negrao, Marcelo V., Tsao, Anne S., Gibbons, Don L., Lee, J. Jack, Heymach, John V., Vaporciyan, Ara A., Swisher, Stephen G., and Cascone, Tina

Published
2022
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37. Immunogenomic profiling of lung adenocarcinoma reveals poorly differentiated tumors are associated with an immunogenic tumor microenvironment

Author

Akhave, Neal, Zhang, Jiexin, Bayley, Erin, Frank, Meredith, Chiou, Shin-Heng, Behrens, Carmen, Chen, Runzhe, Hu, Xin, Parra, Edwin Roger, Lee, Won-Chul, Swisher, Stephen, Solis, Luisa, Weissferdt, Annikka, Moran, Cesar, Kalhor, Neda, Zhang, Jianhua, Scheet, Paul, Vaporciyan, Ara A., Sepesi, Boris, Gibbons, Don L., Heymach, John V., Lee, Jack J., Wistuba, Ignacio I., Andrew Futreal, P., Zhang, Jianjun, Fujimoto, Junya, and Reuben, Alexandre

Published
2022
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39. Resident Readiness for Senior Level Decision Making: Identifying the Domains for Formative Assessment and Feedback

Author

AbdelFattah, Kareem R., Alam, Hasan B., Brown, Carlos V.R., Choi, Jennifer N., Cochran, Amalia, Delman, Keith A., Demetriades, Demetrios, Dort, Jonathan M., Frey, E. Shields, Gauvin, Jeffrey, Hildreth, Amy N., Jarman, Benjamin T., Johnson, Jason M., Jung, Enjae, Katz, Steven G., Kooby, David A., Korndorffer, James R., Jr., LaFemina, Jennifer, Lau, James N., Lazar, Eric L., Lipsett, Pamela A., Maier, Ronald V., Maker, Ajay V., Maker, Vijay K., Mellinger, John D., Meyerson, Shari Lynn, Morrissey, Shawna Lynn, Napolitano, Lena M., Narayan, Mayur, Reilly, Linda M., Sanfey, Hilary, Salcedo, Edgardo S., Schropp, Kurt P., Stuke, Lance E., Tracy, Thomas F., Jr., Vaporciyan, Ara A., Verrier, Edward D., Vetto, John T., Yang, Stephen C., Park, Keon Min, Gesbeck, Melissa M., Alseidi, Adnan A., Park, Yoon Soo, Sullivan, Maura E., Blair, Patrice Gabler, Liscum, Kathy, and Sachdeva, Ajit K.

Published
2022
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49. Epstein Barr virus–positive B-cell lymphoma is highly vulnerable to MDM2 inhibitors in vivo

Author

Zhang, Xiaoshan, Zhang, Ran, Ren, Chenghui, Xu, Yi, Wu, Shuhong, Meng, Carrie, Pataer, Apar, Song, Xingzhi, Zhang, Jianhua, Yao, Yixin, He, Hua, Chen, Huiqin, Ma, Wencai, Wang, Jing, Meric-Bernstam, Funda, Champlin, Richard E., Heymach, John V., Rooney, Cliona M., Swisher, Stephen G., Vaporciyan, Ara A., Roth, Jack A., You, M. James, Wang, Michael, and Fang, Bingliang

Published
2022
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50. Surgical approach does not influence changes in circulating immune cell populations following lung cancer resection

Author

Deboever, Nathaniel, McGrail, Daniel J., Lee, Younghee, Tran, Hai T., Mitchell, Kyle G., Antonoff, Mara B., Hofstetter, Wayne L., Mehran, Reza J., Rice, David C., Roth, Jack A., Swisher, Stephen G., Vaporciyan, Ara A., Walsh, Garrett L., Bernatchez, Chantale, Vailati Negrao, Marcelo, Zhang, Jianjun, Wistuba, Ignacio I., Heymach, John V., Cascone, Tina, Gibbons, Don L., Haymaker, Cara L., and Sepesi, Boris

Published
2022
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