Ziming Li, Zhengbo Song, Yanqiu Zhao, Pingli Wang, Liyan Jiang, Yi Gong, Jianying Zhou, Hong Jian, Xiaorong Dong, Wu Zhuang, Shundong Cang, Nong Yang, Jian Fang, Jianhua Shi, Junguo Lu, Rui Ma, Ping Wu, Yingqian Zhang, Mengmeng Song, Chun-Wei Xu, Zhe Shi, Ling Zhang, Yaolin Wang, Xicheng Wang, Yiping Zhang, Shun Lu
INTRODUCTION: D-1553 (garsorasib) is a potent and selective oral KRASG12C inhibitor. We report results from a phase I dose-escalation/dose-expansion study of D-1553 in patients with KRAS G12C-mutated NSCLC in multiple sites of China. METHODS: Patients with KRAS G12C-mutated NSCLC were administrated D-1553 600 mg orally once daily, 800 mg once daily, 1200 mg once daily, 400 mg twice a day, or 600 mg twice a day in dose escalation. In dose expansion, all patients received 600 mg twice a day...
March 20, 2023: Journal of Thoracic Oncology
Dongchen Sun, Jiaqing Liu, Huaqiang Zhou, Mengting Shi, Jiya Sun, Shen Zhao, Gang Chen, Yaxiong Zhang, Ting Zhou, Yuxiang Ma, Yuanyuan Zhao, Wenfeng Fang, Hongyun Zhao, Yan Huang, Yunpeng Yang, Li Zhang
BACKGROUND: According to mechanisms of adaptive immune resistance, tumor immune microenvironment (TIME) is classified into four types: PD-L1- /TIL- (type I); PD-L1+ /TIL+ (type II); PD-L1- /TIL+ (type III); and PD-L1+ /TIL- (type IV). However, the relationship of TIME classification model and immunotherapy efficacy has not been validated by any large-scale randomized controlled clinical trial among patients with advanced non-small cell lung cancer (NSCLC). METHODS: Based on RNA-sequencing and immunohistochemistry data from ORIENT-11 study, we optimized TIME classification model and evaluated its predictive value for efficacy of immunotherapy plus chemotherapy...
March 20, 2023: Journal of Thoracic Oncology
Olawale Akinbobola, Meredith A Ray, Carrie Fehnel, Andrea Saulsberry, Kourtney Dortch, Matthew Smeltzer, Nicholas R Faris, Raymond U Osarogiagbon
BACKGROUND: Lung cancer surgery with a lymph node kit improves patient-level outcomes, but institution-level impact is unproven. METHODS: Using an institutional stepped-wedge implementation study design, we compared lung cancer resection quality between institutions in pre- and post-implementation phases of kit deployment and, within implementing institutions, resections without versus with the kit. Benchmarks included rates of non-examination of lymph nodes (pNX), non-examination of mediastinal lymph nodes and attainment of American College of Surgeons Operative Standard 5...
March 15, 2023: Journal of Thoracic Oncology
Jun Zhao, Liang Zhao, Wei Guo, Shuhang Wang, Xiuli Tao, Lin Li, Yousheng Mao, Fengwei Tan, Yushun Gao, Ning Wu, Jianming Ying, Qi Xue, Ning Li, Shugeng Gao, Jie He
BACKGROUND: Camrelizumab (an anti-PD-1 antibody) combined with apatinib (an antiangiogenic agent) have conferred benefits for advanced non-small-cell lung cancer (NSCLC). We aimed to assess the activity and safety of neoadjuvant camrelizumab plus apatinib in resectable NSCLC patients. METHODS: In this phase 2 trial, patients with histologically confirmed resectable stage IIA-IIIB NSCLC (stage IIIB, T3N2 only) received intravenous camrelizumab (200 mg) every 2 weeks for three cycles and oral apatinib (250 mg) once daily for 5 days followed by 2 days off for 6 weeks...
March 2, 2023: Journal of Thoracic Oncology
Kai He, David Berz, Shirish M Gadgeel, Wade T Iams, Debora S Bruno, Collin M Blakely, Alexander I Spira, Manish R Patel, David M Waterhouse, Donald A Richards, Anthony Pham, Robert Jotte, David S Hong, Edward B Garon, Anne Traynor, Peter Olson, Lisa Latven, Xiaohong Yan, Ronald Shazer, Ticiana A Leal
INTRODUCTION: Sitravatinib, a receptor tyrosine kinase inhibitor targeting TAM receptors and VEGFR2, can shift the tumor microenvironment towards an immunostimulatory state. Combining sitravatinib with checkpoint inhibitors (CPI) may augment antitumor activity. METHODS: The phase 2 MRTX-500 study evaluated sitravatinib (120 mg daily) with nivolumab (every 2/4 weeks) in patients with advanced non-squamous non-small cell lung cancer (NSCLC) who progressed on/after prior CPI (CPI-experienced) or chemotherapy (CPI-naïve)...
February 24, 2023: Journal of Thoracic Oncology
Yang Zhang, Chaoqiang Deng, Qiang Zheng, Bin Qian, Junjie Ma, Chunyang Zhang, Yan Jin, Xuxia Shen, Yibing Zang, Yufeng Guo, Fangqiu Fu, Hang Li, Shanbo Zheng, Haoxuan Wu, Qingyuan Huang, Shengping Wang, Quan Liu, Ting Ye, Yihua Sun, Yawei Zhang, Jiaqing Xiang, Hong Hu, Yuan Li, Haiquan Chen
INTRODUCTION: We aimed to prospectively evaluate our previously proposed selective mediastinal lymph node (LN) dissection strategy for peripheral clinical T1N0 invasive non-small cell lung cancer (NSCLC). METHODS: This is a multicenter, prospective clinical trial in China. We set six criteria for predicting negative LN stations and finally guiding selective LN dissection. Consolidation tumor ratio ≤ 0.5, segment location, lepidic predominant adenocarcinoma (LPA), negative hilar nodes (stations 10/11/12) and negative visceral pleural invasion (VPI) were used separately or in combination as predictors of negative LN status in the whole, superior or inferior mediastinal zone...
February 23, 2023: Journal of Thoracic Oncology
Maria Carmela Piccirillo, Quincy Chu, Penelope Bradbury, Wei Tu, Courtney H Coschi, Federica Grosso, Marie Florescu, Manlio Mencoboni, John R Goffin, Maria Pagano, Fortunato Ciardiello, Fabiana Letizia Cecere, Mark Vincent, Roberto Ferrara, David E Dawe, Desiree Hao, Christopher W Lee, Alessandro Morabito, Cesare Gridelli, Luigi Cavanna, Mussawar Iqbal, Normand Blais, Natasha B Leighl, Paul Wheatley-Price, Ming-Sound Tsao, Francesca Ugo, Hazem El-Osta, Piera Gargiulo, Pierre-Olivier Gaudreau, Dongsheng Tu, Joana Sederias, Pamela Brown-Walker, Francesco Perrone, Lesley Seymour, Scott A Laurie
Immune checkpoint inhibitors have activity in mesothelioma. IND.227 was a phase II trial (120 patients planned) comparing progression free survival (PFS) of standard platinum pemetrexed (CP) versus CP/pembrolizumab (CP/pembro) versus pembrolizumab (pembro) . Accrual to pembro arm was discontinued based on interim analysis (IA - 16 week disease control rate (DCR)). CP/pembro was tolerable, with PFS similar between arms and median survival (OS) and overall response rate (RR) higher than CP alone (19.8 months [95% CI 8...
February 23, 2023: Journal of Thoracic Oncology
Jarushka Naidoo, Scott Antonia, Yi-Long Wu, Byoung Chul Cho, Piruntha Thiyagarajah, Helen Mann, Michael Newton, Corinne Faivre-Finn
INTRODUCTION: Consolidation durvalumab (the 'PACIFIC regimen') is standard of care for patients with unresectable stage III NSCLC who have not progressed following chemoradiotherapy (CRT), based on data from the phase 3 placebo-controlled PACIFIC study (NCT02125461). However, the benefit of immunotherapy in patients with stage III EGFR-mutant (EGFRm) NSCLC is not well characterized. Here, we report a post-hoc exploratory efficacy and safety analysis from a subgroup of patients with EGFRm NSCLC from PACIFIC...
February 23, 2023: Journal of Thoracic Oncology
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February 11, 2023: Journal of Thoracic Oncology
Joao V Alessi, Arielle Elkrief, Biagio Ricciuti, Xinan Wang, Alessio Cortellini, Victor R Vaz, Giuseppe Lamberti, Rosa L Frias, Deepti Venkatraman, Claudia A M Fulgenzi, Federica Pecci, Gonzalo Recondo, Alessandro Di Federico, Adriana Barrichello, Hyesun Park, Mizuki Nishino, Grace M Hambelton, Jacklynn V Egger, Marc Ladanyi, Subba Digumarthy, Bruce E Johnson, David C Christiani, Xihong Lin, Justin F Gainor, Jessica J Lin, David J Pinato, Adam J Schoenfeld, Mark M Awad
INTRODUCTION: Although programmed cell death protein 1 and programmed death-ligand 1 (PD-L1) blockade in combination with platinum-doublet chemotherapy has become a mainstay of first-line treatment for advanced NSCLC, factors associated with efficacy of chemoimmunotherapy (CIT) are not well characterized. METHODS: In this multicenter retrospective analysis, clinicopathologic and genomic data were collected from patients with advanced NSCLC (lacking sensitizing genomic alterations in EGFR and ALK) and evaluated with clinical outcomes to first-line CIT...
February 10, 2023: Journal of Thoracic Oncology
Junjie Huang, Sze Chai Chan, Wing Sze Pang, Shui Hang Chow, Veeleah Lok, Lin Zhang, Xu Lin, Don Eliseo Lucero-Prisno, Wanghong Xu, Zhi-Jie Zheng, Edmar Elcarte, Mellissa Withers, Martin C S Wong
INTRODUCTION: Mesothelioma is an uncommon type of cancer which has received little attention. This study aims to evaluate the global disease burden; trends of mesothelioma by age, sex, and geographic locations; and its risk factors on the population level. METHODS: The Global Cancer Observatory, Cancer Incidence in Five Continents Plus, and Global Burden of Disease were accessed for mesothelioma incidence and its risk factors worldwide. The associations between mesothelioma incidence and asbestos were evaluated for each country by multivariable linear regression analysis by sex and age...
February 10, 2023: Journal of Thoracic Oncology
Natthaya Triphuridet, Shannon S Zhang, Misako Nagasaka, Yanfei Gao, Joseph J Zhao, Nicholas L Syn, Takaomi Hanaoka, Sai-Hong Ignatius Ou, Elaine Shum
INTRODUCTION: Lung cancer in never-smokers is the major cancer cause of death globally. We compared the efficacy of low-dose computed tomography (LDCT) lung cancer screening among never-smokers versus ever-smokers using systematic review and meta-analysis. METHODS: LDCT lung cancer screening studies simultaneously included both ever-smoker and never-smoker participants published by April 30, 2021 were searched via Pubmed/Scopus. Primary outcome measure was relative risk (RR) of lung cancer diagnosed among never-smokers versus ever-smokers...
February 10, 2023: Journal of Thoracic Oncology
Mitchell Chen, Haonan Lu, Susan J Copley, Yidong Han, Andrew Logan, Patrizia Viola, Alessio Cortellini, David J Pinato, Danielle Power, Eric O Aboagye
INTRODUCTION: Patient selection for checkpoint inhibitor immunotherapy is currently guided by programmed death-ligand 1 (PD-L1) expression obtained from immunohistochemical staining of tumor tissue samples. This approach is susceptible to limitations resulting from the dynamic and heterogeneous nature of cancer cells and the invasiveness of the tissue sampling procedure. To address these challenges, we developed a novel computed tomography (CT) radiomic-based signature for predicting disease response in patients with NSCLC undergoing programmed cell death protein 1 (PD-1) or PD-L1 checkpoint inhibitor immunotherapy...
February 10, 2023: Journal of Thoracic Oncology
Hisao Asamura, Katherine K Nishimura, Dorothy J Giroux, Kari Chansky, Antje Hoering, Valerie Rusch, Ramon Rami-Porta
Over the past 20 years, the International Association for the Study of Lung Cancer (IASLC) has been working on a global project to revise the tumor, node and metastasis (TNM) classification of lung cancer. The first and second phases of the staging projects proposed recommendations for revision of the TNM classification, which were adopted by the Union for International Cancer Control and the American Joint Committee on Cancer as their 7th and 8th editions of the TNM classifications of lung cancer. For the third phase of the IASLC staging project, a new database of lung cancer cases diagnosed between January 2011 and December 2019 has been established...
February 9, 2023: Journal of Thoracic Oncology
Sai-Hong Ignatius Ou, Jin-Liern Hong, Petros Christopoulos, Huamao M Lin, Sylvie Vincent, Eric N Churchill, Junpei Soeda, Daniel Kazdal, Albrecht Stenzinger, Michael Thomas
INTRODUCTION: Epidermal growth factor receptor (EGFR) exon 20 insertion (ex20ins) mutations represent 5%-10% of EGFR mutations in non-small cell lung cancer (NSCLC). Identifying patients with EGFR ex20ins is challenging due to the limited coverage of polymerase chain reaction (PCR) assays and the relatively recent use of next-generation sequencing (NGS). This study analyzes the spectrum of EGFR ex20ins variants in a large patient population from a global clinical trial and several real-world cohorts and the ability of PCR kits to identify these alterations...
February 2, 2023: Journal of Thoracic Oncology
Alan McWilliam, Azadeh Abravan, Kathryn Banfill, Corinne Faivre-Finn, Marcel van Herk
INTRODUCTION: The RTOG 0617 trial presented worse survival for patients with lung cancer treated in the high-dose (74Gy) arm. In multivariable models, radiation level and whole heart volumetric dose parameters were associated with survival. In this work, we consider heart sub-regions to explain the observed survival difference between radiation levels. METHODS: Voxel-based analysis identified anatomical regions where dose was associated with survival. Bootstrapping clinical and dosimetric variables into an elastic-net model selected variables associated with survival...
February 2, 2023: Journal of Thoracic Oncology
Xue Hou, Chengzhi Zhou, Guowu Wu, Wen Lin, Zhanhong Xie, Haibo Zhang, Jiqun Yi, Zheng Peng, Lifeng Yin, Chi Ma, Likun Chen
INTRODUCTION: Systemic treatment options for non-small-cell lung cancer (NSCLC) with brain metastases (BMs) are scarce. We evaluated the activity and safety of camrelizumab plus chemotherapy as first-line therapy in advanced non-squamous NSCLC patients with BMs. METHODS: This was a multicentre, single-arm, phase 2 trial (NCT04211090) conducted at seven hospitals in China. Eligible patients were treatment-naïve metastatic non-squamous NSCLC and BMs that were asymptomatic or symptoms controlled with dehydration therapy, and no previous systemic treatment or local therapy for the target brain lesion...
February 2, 2023: Journal of Thoracic Oncology
Kristin Toftaker Killingberg, Bjørn Henning Grønberg, Marit Slaaen, Øyvind Kirkevold, Tarje Onsøien Halvorsen
INTRODUCTION: Half of patients with limited stage small cell lung cancer (LS SCLC) are >70 years, but account for <20% of participants in most trials. Comorbidities, reduced organ- and physical function might lead to more treatment toxicity and population-based studies indicate that fewer older than younger LS SCLC patients receive standard chemoradiotherapy, although there is limited evidence for such a policy. METHODS: We compared baseline characteristics, comorbidity, survival, treatment completion, toxicity, health related quality of life (HRQoL) and treatment outcomes between patients >70 and <70 years in an open label randomized phase II trial comparing twice-daily thoracic radiotherapy (TRT) of 45 Gy in 30 fractions with 60 Gy in 40 fractions in LS SCLC...
January 27, 2023: Journal of Thoracic Oncology
Yan Li, Alexander J Byun, Jennie K Choe, Shaohua Lu, David Restle, Takashi Eguchi, Kay See Tan, Jasmeen Saini, James Huang, Gaetano Rocco, David R Jones, William D Travis, Prasad S Adusumilli
INTRODUCTION: High-grade histologic patterns are associated with poor prognosis in patients with primary nonmucinous lung adenocarcinoma (ADC). We investigated whether the presence of micropapillary and/or solid patterns (MIP/SOL) in lymph node (LN) metastases has prognostic value. METHODS: Patients who underwent lobectomy for pathologic stage II-III lung ADC with N1 or N2 LN metastases (n=360; 2000-2012) were analyzed. We assessed overall survival (OS), lung cancer-specific cumulative incidence of death (LC-CID), and cumulative incidence of recurrence (CIR) between patients with and without MIP/SOL patterns in LN metastases...
January 18, 2023: Journal of Thoracic Oncology
Yonina R Murciano-Goroff, Christina J Falcon, Sabrina T Lin, Christina Chacko, Grace Grimaldi, Dazhi Liu, Clare Wilhelm, Alexia Iasonos, Alexander Drilon
BACKGROUND: Central nervous system (CNS) metastases develop in nearly half of patients and cause morbidity and mortality in RET fusion-positive non-small cell lung cancers (NSCLCs). The selective RET inhibitor selpercatinib treats existing intracranial disease, but no studies have investigated whether early initiation of selpercatinib is associated with decreased development of CNS metastases. PATIENTS AND METHODS: Sixty-one patients with RET fusion-positive advanced NSCLC with and without CNS metastases treated with selpercatinib on the LIBRETTO-001 trial (NCT03157128) or the LIBRETTO-201 expanded access program (EAP, NCT03906331) were identified...
January 16, 2023: Journal of Thoracic Oncology
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