Journal of Thoracic Oncology

INTRODUCTION: For patients with KRASG12C-mutated NSCLC who are treated with sotorasib, there is a lack of biomarkers to guide treatment decisions. We therefore investigated the clinical utility of pre-treatment and on-treatment circulating tumor DNA (ctDNA), as well as treatment-emergent alterations upon disease progression. METHODS: Patients with KRASG12C-mutated NSCLC treated with sotorasib were prospectively enrolled in our biomarker study (NCT05221372). Plasma samples were collected prior to sotorasib treatment, at first response evaluation and at disease progression...

Due to major advances in the field of radiation oncology, patients with lung cancer (LC) can now receive technically individualised radiotherapy treatments. However, in the era of precision oncology, radiotherapy-based treatment selection needs to be improved as many patients do not benefit or are not offered optimum therapies. Cost-effective robust biomarkers can address this knowledge gap and lead to individuals being offered more bespoke treatments leading to improved outcome. This narrative review discusses some of the current achievements and challenges in the realisation of personalised radiotherapy delivery in patients with LC...

INTRODUCTION: The aim of this study was to validate the discriminatory ability and clinical utility of the N descriptor of the newly proposed 9th edition of the TNM staging system for lung cancer in a large independent cohort. METHODS: We retrospectively analyzed patients who underwent curative surgery for non-small cell lung cancer (NSCLC) between January 2004 and December 2019. The N descriptor of patients included in this study was retrospectively reclassified based on the 9th edition of the TNM classification...

OBJECTIVE: Aim of this study is to describe characteristics and survival outcome of patients who underwent surgical treatment for distant thymoma relapse according to the International Thymic Malignancy Interest Group definition(ITMIG). METHODS: Data of patients affected by thymoma recurrence from 4 different Institution were collected and retrospectively reviewed.Patients with loco-regional metastases, who underwent non-surgical therapies and with incomplete data on follow-up were excluded...

BACKGROUND: Thymomas are rare intrathoracic malignancies that can relapse after surgery. Whether or not Post-Operative Radiotherapy (PORT) should be delivered after surgery remains a major issue. RADIORYTHMIC is an ongoing, multicenter, randomized phase 3 trial addressing this question in patients with completely R0 resected Masaoka-Koga stage IIb/III thymoma. Experts in the field met to develop recommendations for PORT. METHODS: A scientific committee from the RYTHMIC network identified key issues regarding the modalities of PORT in completely resected thymoma...

BACKGROUND: Recent insights regarding mechanisms mediating stemness, heterogeneity, and metastatic potential of lung cancers have yet to be fully translated to effective regimens for the treatment of these malignancies. This study sought to identify novel targets for lung cancer therapy. METHODS: Transcriptomes and DNA methylomes of 14 SCLC and 10 NSCLC lines were compared to normal human small airway epithelial cells (SAEC) and induced pluripotent stem cell (iPSC) clones derived from SAEC...

The goal of surgical resection is to completely remove a cancer; it is useful to have a system to describe how well this was accomplished. This is captured by the residual tumor (R) classification, which is separate from the TNM classification that describes the anatomic extent of a cancer independent of treatment. The traditional R-classification designates as R0 a complete resection, as R1 a macroscopically complete resection but with microscopic tumor at the surgical margin, and as R2 a resection that leaves gross tumor behind...

INTRODUCTION: EGFR-mutated NSCLC is characterized by an immunosuppressive microenvironment that confers limited clinical effectiveness to anti-PD1/PD-L1 antibodies. Despite the discouraging outcomes of immunotherapy, novel immune checkpoints are constantly emerging, among which the specific vulnerability for therapeutic intervention in the context of EGFR-mutated NSCLC remains unresolved. METHODS: Datasets of patient- and cell line-levels were utilized for screening and mutual validation of association between EGFR mutation and a panel of immune checkpoint-related genes...

BACKGROUND: The primary tumor (T) component in the 8th edition of pleural mesothelioma (PM) staging system is based on pleural involvement and extent of invasion. Quantitative assessment of pleural tumor has been shown to be prognostic. We explored quantitative and qualitative metrics to develop recommendations for T descriptors in the upcoming 9th edition of the PM staging system. METHODS: The International Association for the Study of Lung Cancer (IASLC) prospectively collected data on PM patients...

Spread through air spaces (STAS) consists of lung cancer tumor cells that are identified beyond the edge of the main tumor in the surrounding alveolar parenchyma. It has been reported by meta-analyses to be an independent prognostic factor in the major histologic types of lung cancer, but its role in lung cancer staging is not established. To assess the clinical importance of STAS in lung cancer staging, we evaluated 4061 surgically resected pathologic Stage I R0 nonsmall cell carcinomas (NSCLC) collected from around the world in the IASLC database...

INTRODUCTION: Uncommon EGFR mutations represent a rare subgroup of non-small cell lung cancer. Data on the efficacy of different generations of tyrosine kinase inhibitors (TKIs) in these rare mutations is scattered and limited to mostly retrospective small cohorts, as these patients were usually excluded from clinical trials. METHODS: This was a systematic review on the efficacy of TKIs in patients harboring uncommon EGFR mutations, defined as mutations other than ex20ins or T790M...

INTRODUCTION: Controversy remains as to whether pathologic complete response (pCR) and major pathologic response (MPR) represent surrogate endpoints for event free survival (EFS) and overall survival (OS) in neoadjuvant trials for resectable non-small cell lung cancer (NSCLC). METHODS: A search of PubMed and archives of international conference abstracts was performed from June 2017 through October 31, 2023. Studies incorporating a neoadjuvant arm with immune checkpoint blockade alone or in combination with chemotherapy were included...

INTRODUCTION: Extensive-stage SCLC (ES-SCLC) prognosis remains poor. The phase 3 RATIONALE-312 study aimed to evaluate the efficacy and safety of tislelizumab plus chemotherapy as first-line treatment for ES-SCLC. METHODS: RATIONALE-312 is a randomized, double-blind, placebo-controlled trial, conducted in the People's Republic of China. Eligible patients with previously untreated ES-SCLC were randomized 1:1 to receive four cycles of tislelizumab 200 mg or placebo, with etoposide plus carboplatin or cisplatin intravenously every 3 weeks, followed by tislelizumab 200 mg or placebo as maintenance...

INTRODUCTION: The TNM classification of lung cancer is periodically revised. The International Association for the Study of Lung Cancer collected and analyzed a new database to inform the forthcoming ninth edition of the TNM classification. The results are herewith presented. METHODS: After exclusions, 76,518 patients from a total of 124,581 registered patients were available for analyses: 58,193 with clinical stage, 39,192 with pathologic stage, and 62,611 with best stage NSCLC...

INTRODUCTION: The International Agency for Research on Cancer has classified passive smoking (PS) or secondhand smoke exposure as a Group 1 carcinogen linked to lung cancer; however, in contrast to active smoking, the mutagenic properties of PS remain unclear. METHODS: A consecutive cohort of 564 lung adenocarcinoma samples from female never-smokers, who provided detailed information about their exposure to PS during adolescence and in their thirties through a questionnaire, was prepared...

Adjuvant osimertinib represents a recent paradigm shift in the management of resected EGFR-mutated lung cancer. The optimal subsequent treatment of patients who relapse after completion of 3 years of adjuvant osimertinib is unknown. Here, we report two cases of complete response to osimertinib rechallenge after relapse from previous adjuvant osimertinib use, and a serial molecular panel exhibiting a lack of acquired resistance mechanisms. Future prospective studies are warranted to confirm the optimal treatment of patients who relapse after previous adjuvant osimertinib...

INTRODUCTION: This study analyzed all metastatic categories of the current tumor, node, and metastasis (TNM) classification of non-small cell lung cancer to propose modifications of the M component in the next edition (9th ) of the classification. METHODS: A database of 124,581 patients diagnosed between 2011 and 2019 was established; of these, 14,937 with NSCLC in stage IVA-IVB were available for this analysis. Overall survival was calculated using the Kaplan-Meier method, and prognosis assessed using multivariable-adjusted Cox proportional hazards regression...

INTRODUCTION: Household Particulate matter (PM) air pollution is significantly associated with lung cancer. Nevertheless, the global burden of lung cancer attributable to household PM2.5 is still uncertain. METHODS: In this study, data from the Global Burden and Disease Study (GBD) 2019 are used to thoroughly assess the burden of lung cancer associated with household PM2.5. RESULTS: The number of deaths and disability-adjusted life years (DALYs) attributable to household PM2...

The International Association for the Study of Lung Cancer (IASLC) collaborated with the International Mesothelioma Interest Group to propose the first tumor, node, and metastasis (TNM) stage classification system for diffuse pleural mesothelioma in 1995, accepted by the Union for International Cancer Control and the American Joint Committee on Cancer for the 6th and 7th edition stage classification manuals. The IASLC Staging and Prognostic Factors Committee Mesothelioma Domain developed and analyzed an international registry of patients with pleural mesothelioma and updated TNM descriptors for the 8th edition of the stage classification system...

INTRODUCTION: Treatment options for second-generation (2nd -gen) ALK tyrosine kinase inhibitor (TKI)-resistant patients are limited. We evaluated the safety, pharmacokinetics, and efficacy of ficonalkib (SY-3505), a third-generation (3rd -gen) ALK TKI, in patients with advanced ALK-positive non-small cell lung cancer. METHODS: This first-in-human, phase 1/2 study (Chinese Clinical Trial Registry identifier: ChiCTR1900025619; ClinicalTrials.gov identifier: NCT05257512) had two parts...