JTO Clinical and Research Reports最新文献

{"title":"State of Lung Cancer in Egypt: Moving Towards Improved Guidelines for Prevention, Screening, Treatment, and Clinical Care Programs","authors":"Nagla Abdel Karim MD ,&nbsp;Ahmed Magdy Rabea MD ,&nbsp;Philip C. Mack PhD ,&nbsp;Janakiraman Subramanian MD ,&nbsp;Ehab Khalil MD ,&nbsp;Mai Sherif MD ,&nbsp;Radwa Marawan MD ,&nbsp;Tagrid Gaafar MD ,&nbsp;Lobna Shash MD ,&nbsp;Kei Suzuki MD ,&nbsp;Manmeet Ahluwalia MD ,&nbsp;Hisham Wahba MD ,&nbsp;Salma Aboelela MSc ,&nbsp;Asrar Al Ahmadi MD ,&nbsp;Hamed Al Husaini MD ,&nbsp;Nada Mohsen MD ,&nbsp;Rana Khaled MD ,&nbsp;Neemat Kassem MD ,&nbsp;Hussein Khaled MD ,&nbsp;Noha El Said MD ,&nbsp;Triparna Sen PhD","doi":"10.1016/j.jtocrr.2024.100776","DOIUrl":"10.1016/j.jtocrr.2024.100776","url":null,"abstract":"<div><div>Lung cancer remains a leading cause of cancer-related mortality globally and presents significant challenges in Egypt. In 2023, the first annual meeting of the Thoracic Oncology Multidisciplinary Faculty, organized by the Egyptian Cancer Research Network and the Egyptian Society of Respiratory Neoplasms, was held in Cairo, Egypt. The meeting aimed to address gaps in lung cancer management across Egypt and the broader Middle East and North Africa region. The discussions focused on the challenges posed by NSCLC and SCLC and emphasized the need for enhanced prevention, early detection, and treatment strategies. Key areas of concern include limited access to advanced diagnostics, such as comprehensive genomic profiling, and the underutilization of targeted therapies and immunotherapies, mainly owing to financial barriers. The meeting highlighted the importance of strengthening lung cancer screening programs, improving smoking cessation efforts, and addressing environmental risk factors like air pollution. Furthermore, the event underscored the need for greater research and collaboration, particularly in areas like precision oncology. The conference concluded with strategic recommendations to improve lung cancer prevention, screening, and treatment, aligning Egypt’s lung cancer care with global advancements and ensuring equitable access to cutting-edge therapies.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 1","pages":"Article 100776"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11712008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142950777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Brief Report: Clinical Characteristics and Outcomes of Patients With Thoracic SMARCA4-Deficient Undifferentiated Tumors","authors":"Alissa J. Cooper MD ,&nbsp;Andrea Arfe PhD ,&nbsp;Biagio Ricciuti MD ,&nbsp;Andréanne Gagné MD, PhD ,&nbsp;Lynette M. Sholl MD ,&nbsp;Alessandro Di Federico MD ,&nbsp;Mark M. Awad MD, PhD ,&nbsp;Mihaela Aldea MD, PhD ,&nbsp;Maria Rosa Ghigna MD ,&nbsp;Miruna Grecea MD ,&nbsp;Phoebe Clark MS ,&nbsp;Jamie E. Chaft MD ,&nbsp;Mark G. Kris MD ,&nbsp;Gregory J. Riely MD ,&nbsp;Charles M. Rudin MD, PhD ,&nbsp;Ibiayi Dagogo-Jack MD ,&nbsp;Mari Mino-Kenudson MD ,&nbsp;Lingzhi Hong MD, PhD ,&nbsp;Neda Kalhor MD ,&nbsp;Natalie Vokes MD ,&nbsp;Adam J. Schoenfeld MD","doi":"10.1016/j.jtocrr.2024.100759","DOIUrl":"10.1016/j.jtocrr.2024.100759","url":null,"abstract":"<div><h3>Introduction</h3><div>Thoracic SMARCA4-deficient undifferentiated tumors (SMARCA4-UTs) are a recently defined group of aggressive cancers in which the effectiveness of standard treatments for lung cancer is unknown.</div></div><div><h3>Methods</h3><div>We collected clinical, pathologic, and demographic variables from five institutions for patients whose tumors met criteria for SMARCA4-UTs (undifferentiated phenotype and loss of SMARCA4 (BRG1) by immunohistochemistry).</div></div><div><h3>Results</h3><div>We identified 92 patients with SMARCA4-UTs; 58 (63%) had stage IV disease at diagnosis and 16 (17%) developed recurrent or metastatic disease after initial diagnosis. Median overall survival from metastatic diagnosis was 7.3 (95% confidence interval [CI]: 4.6–12.8) months. Of patients with metastatic disease, 58 (78%) received first-line systemic treatment. Most often, patients received chemo and immunotherapy combination (41%), chemotherapy alone (33%), or immunotherapy alone (16%). Median progression-free survival from start of systemic therapy was 1.9 (95% CI: 1.4–14.5) months for chemo and immunotherapy, 1.6 (95% CI: 1.1–5.8) months for chemotherapy, and 3.3 (95% CI: 1.2–undefined) months for immunotherapy alone. Five patients had durable responses (≥2 y); all received immunotherapy as part of first-line regimens. Nine (16%) of 55 tumor samples tested had programmed death-ligand 1 expression more than or equal to 50%, with 24 (44%) negative samples. Tumor mutational burden was available in 48 cases (52%), and median was 10.5 (range: 2–48) mutations per megabase.</div></div><div><h3>Conclusions</h3><div>This multi-institution retrospective cohort analysis revealed a population of patients with short progression-free survival to standard therapies and poor overall survival. A few patients had remarkable response to regimens including immunotherapy. Prospective clinical studies are urgently needed to identify better therapeutic approaches to treat this aggressive malignancy, and this analysis may serve as a benchmark for future clinical trial design.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 1","pages":"Article 100759"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11719837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic Impact of Adjuvant Immunotherapy in Patients With Resectable NSCLC After Neoadjuvant Chemoimmunotherapy: A Brief Report","authors":"Yichen Dong MD ,&nbsp;Long Xu MD ,&nbsp;Jialiang Wen MD ,&nbsp;Haojie Si MD ,&nbsp;Juemin Yu MD ,&nbsp;Tao Chen MD ,&nbsp;Huikang Xie MD ,&nbsp;Xinjian Li MD ,&nbsp;Minglei Yang MD ,&nbsp;Junqiang Fan MD ,&nbsp;Junqi Wu MD ,&nbsp;Yunlang She MD ,&nbsp;Deping Zhao MD ,&nbsp;Chang Chen MD, PhD","doi":"10.1016/j.jtocrr.2024.100763","DOIUrl":"10.1016/j.jtocrr.2024.100763","url":null,"abstract":"<div><h3>Objective</h3><div>The potential survival benefits of adjuvant immunotherapy for resectable NSCLC after neoadjuvant chemoimmunotherapy, and the optimal number of adjuvant immunotherapy cycles, remain uncertain. This study aims to evaluate the prognostic impact of adjuvant immunotherapy and determine the optimal number of cycles.</div></div><div><h3>Methods</h3><div>A total of 438 patients who received neoadjuvant chemoimmunotherapy between August 2019 and June 2022 across four hospitals were enrolled in this study, with a median follow-up time of 31.3 months. Recurrence-free survival (RFS) and overall survival (OS) were estimated using Kaplan-Meier methods and tested by log-rank test. Unstratified Cox proportional hazards models were fitted to the subgroups.</div></div><div><h3>Results</h3><div>In this multi-center cohort, 29.7% of patients (n = 130) achieved a pathologic complete response. Patients who received adjuvant immunotherapy experienced significant survival benefits compared with those who did not (RFS: hazard ratio [HR] = 0.63, 95% confidence interval: 0.41–0.98, <em>p</em> = 0.037; OS: hazard ratio = 0.27, 95% confidence interval: 0.13–0.57, <em>p</em> &lt; 0.001). Subgroup analyses found that patients with a squamous histologic type, positive PD-L1 expression, and those with a major pathologic response particularly benefited from adjuvant immunotherapy. In addition, we found that six cycles of adjuvant immunotherapy served as a threshold for better prognostic differentiation, suggesting that six or more cycles may be more beneficial.</div></div><div><h3>Conclusions</h3><div>Our study found that the addition of adjuvant immunotherapy to neoadjuvant chemoimmunotherapy is significantly associated with improved RFS and OS in patients with resectable NSCLC. We also identified that six cycles of adjuvant immunotherapy may be the optimal regimen for these patients.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 1","pages":"Article 100763"},"PeriodicalIF":3.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11699361/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142932208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pembrolizumab and Pemetrexed for Older Patients With Nonsquamous NSCLC and Programmed Cell Death-Ligand 1 Tumor Proportion Scores of Less Than 50%","authors":"Yoshihito Kogure MD, PhD ,&nbsp;Hiroya Hashimoto PhD ,&nbsp;Haruko Daga MD, PhD ,&nbsp;Yasushi Fukuda MD ,&nbsp;Akihiro Bessho MD, PhD ,&nbsp;Tadaaki Yamada MD, PhD ,&nbsp;Yukihiro Toi MD ,&nbsp;Tomoki Kimura MD, PhD ,&nbsp;Hiroshige Yoshioka MD, PhD ,&nbsp;Koichi Azuma MD, PhD ,&nbsp;Naoki Furuya MD, PhD ,&nbsp;Yasutaka Fukui MD, PhD ,&nbsp;Akiko M. Saito MD, PhD ,&nbsp;Nobuyuki Yamamoto MD, PhD ,&nbsp;Hideo Saka MD ,&nbsp;Masashi Kondo MD, PhD","doi":"10.1016/j.jtocrr.2024.100784","DOIUrl":"10.1016/j.jtocrr.2024.100784","url":null,"abstract":"<div><h3>Introduction</h3><div>Pembrolizumab with pemetrexed and cisplatin/carboplatin is an approved first-line treatment for metastatic nonsquamous NSCLC. Nevertheless, its efficacy and safety in patients aged 75 years and above remain unclear. We assessed the efficacy and safety of pembrolizumab with pemetrexed in patients with programmed cell death-ligand 1 expression tumor proportion scores of less than 50%.</div></div><div><h3>Methods</h3><div>This multicenter, open-label, phase 2 trial involved 42 institutions across Japan. Eligible participants had metastatic or recurrent nonsquamous NSCLC without sensitizing <em>EGFR</em> or <em>ALK</em> alterations, were aged 75 years or above, had a programmed cell death-ligand 1 tumor proportion score of less than 50%, had not undergone systemic chemotherapy, and had an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients received pemetrexed (500 mg/m²) and pembrolizumab (200 mg) on day 1 of each 21-day cycle. The primary endpoint was the objective response rate. The secondary endpoints included progression-free survival, overall survival, and safety.</div></div><div><h3>Results</h3><div>Forty-nine patients were enrolled in this study between July 2020 and May 2022. The objective response rate was 36.7% (95% confidence interval [CI]: 23.4%–51.7%). The disease control rate was 65.3% (95% CI: 50.4–78.3%). The median progression-free survival was 7.6 months (95% CI: 4.8–16.2), and the median overall survival was 19.4 months (95% CI: 11.8 mo–unreached). The most common grade 3 or 4 adverse events were neutropenia (31.3%), leukopenia (20.8%), and anemia (12.5%). No treatment-related deaths occurred during this period.</div></div><div><h3>Conclusions</h3><div>Pembrolizumab with pemetrexed is a promising first-line treatment option for older patients with metastatic nonsquamous NSCLC. This trial was registered at <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> (NCT04396457) and the Japan Registry of Clinical Trials (jRCTs041200012).</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 3","pages":"Article 100784"},"PeriodicalIF":3.0,"publicationDate":"2024-12-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143348351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Humanized Mouse Models for Immuno-Oncology Research: A Review and Implications in Lung Cancer Research","authors":"Cheol-Kyu Park MD, PhD ,&nbsp;Maryam Khalil BSc ,&nbsp;Nhu-An Pham PhD ,&nbsp;Stephanie Wong BSc ,&nbsp;Dalam Ly PhD ,&nbsp;Adrian Sacher MD, FRCPC ,&nbsp;Ming-Sound Tsao MD, FRCPC","doi":"10.1016/j.jtocrr.2024.100781","DOIUrl":"10.1016/j.jtocrr.2024.100781","url":null,"abstract":"<div><div>Cancer immunotherapy has brought significant clinical benefits to patients with cancer, including those with lung cancer. Patient-derived tumor xenograft mouse models have become the preferred animal model for translational cancer research and preclinical studies. Given the unmet need for improved predictive models in immuno-oncology, humanized mouse models which are co-engrafted with both human tumors and immune system components have been used to investigate novel immunotherapeutics. These models have similarly been used to predict immune-related adverse events and to develop predictive biomarkers. This review summarizes key concepts related to humanized mouse models. We highlight the various approaches to generate them, factors that are critical to successfully establishing such models, their respective limitations, and considerations in model selection for preclinical lung cancer immuno-oncology research and therapeutic studies.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 3","pages":"Article 100781"},"PeriodicalIF":3.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143174198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Solid Predominant Histology and High Podoplanin Expression in Cancer-Associated Fibroblast Predict Primary Resistance to Osimertinib in EGFR-Mutated Lung Adenocarcinoma","authors":"Yuji Uehara MD ,&nbsp;Hiroki Izumi MD, PhD ,&nbsp;Tetsuro Taki MD, PhD ,&nbsp;Tetsuya Sakai MD, PhD ,&nbsp;Hibiki Udagawa MD, PhD ,&nbsp;Eri Sugiyama MD, PhD ,&nbsp;Shigeki Umemura MD, PhD ,&nbsp;Yoshitaka Zenke MD, PhD ,&nbsp;Shingo Matsumoto MD, PhD ,&nbsp;Kiyotaka Yoh MD, PhD ,&nbsp;Shoko Kubota MD, PhD ,&nbsp;Keiju Aokage MD, PhD ,&nbsp;Naoya Sakamoto MD, PhD ,&nbsp;Shingo Sakashita MD, PhD ,&nbsp;Motohiro Kojima MD, PhD ,&nbsp;Michiko Nagamine MD, PhD ,&nbsp;Yukio Hosomi MD, PhD ,&nbsp;Masahiro Tsuboi MD, PhD ,&nbsp;Koichi Goto MD, PhD ,&nbsp;Genichiro Ishii MD, PhD","doi":"10.1016/j.jtocrr.2024.100779","DOIUrl":"10.1016/j.jtocrr.2024.100779","url":null,"abstract":"<div><h3>Introduction</h3><div>Resistance to EGFR tyrosine kinase inhibitors is influenced by tumor-intrinsic and -extrinsic factors. We investigated the impact of tumor cell histology and tumor microenvironment on the efficacy of osimertinib.</div></div><div><h3>Methods</h3><div>We evaluated surgically resected adenocarcinoma from patients treated with first-line osimertinib at the National Cancer Center Hospital East (2016–2023), evaluating clinicopathologic characteristics, tumor cell histology, podoplanin expression in cancer-associated fibroblasts (CAFs) identified by immunohistochemistry, and outcomes. We also investigated HGF mRNA expression levels, using The Cancer Genome Atlas Program and Singapore Oncology Data Portal cohorts.</div></div><div><h3>Results</h3><div>The study included 93 patients. Solid (n = 19) versus non-solid predominant (n = 74) histology was not associated with worse disease-free survival after surgery (<em>p</em> = 0.12), but was significantly associated with worse progression-free survival (PFS) and overall survival following osimertinib treatment (<em>p</em> = 0.026, <em>p</em> = 0.004). Similarly, high-podoplanin (n = 31) versus low-podoplanin (n = 62) expression in CAFs was not associated with worse disease-free survival after surgery (<em>p</em> = 0.65), but was significantly associated with worse PFS and showed a trend towards worse overall survival following osimertinib treatment (<em>p</em> &lt; 0.001, <em>p</em> = 0.11). In the multivariable analysis, solid predominant histology and high-podoplanin expression in CAFs were independently associated with worse PFS. In the cohorts of The Cancer Genome Atlas Program and Singapore Oncology Data Portal, <em>EGFR</em>-mutated lung adenocarcinoma with solid predominant histology or high-podoplanin expression exhibited significantly higher HGF expression.</div></div><div><h3>Conclusions</h3><div>Solid predominant histology and high-podoplanin expression in CAFs predicted osimertinib resistance, potentially guiding the selection of patients for more intensive treatments beyond osimertinib monotherapy.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 3","pages":"Article 100779"},"PeriodicalIF":3.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143348095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Access to Diagnostics and Treatment for People With Metastatic EGFR-Positive NSCLC: Lessons From Project PRIORITY","authors":"Jill Feldman MA ,&nbsp;Ivy Elkins MBA ,&nbsp;Zofia Piotrowska MD ,&nbsp;Bellinda L. King-Kallimanis PhD ,&nbsp;Tendai Chihuri MD ,&nbsp;Carly Johnson BS ,&nbsp;Alecia Clary PhD ,&nbsp;Teri Kennedy MA ,&nbsp;Upal Basu Roy PhD, MPH","doi":"10.1016/j.jtocrr.2024.100782","DOIUrl":"10.1016/j.jtocrr.2024.100782","url":null,"abstract":"<div><h3>Introduction</h3><div>The treatment landscape for people diagnosed with EGFR-mutated (EGFR-m) NSCLC has rapidly evolved, yet there remains limited self-reported information about the lived experience. In this paper, we describe the clinical characteristics and treatment experiences of people living with EGFR-m lung cancer from Project PRIORITY, a patient-driven study.</div></div><div><h3>Methods</h3><div>An online survey was distributed among the EGFR Resisters community between April 2019 and January 2020. The survey captured participants’ demographics and lung cancer risk factors, diagnostic and treatment pathways, and prevalence of side effects. Descriptive statistics were used and included subgroups based on residency and cancer stage.</div></div><div><h3>Results</h3><div>Of the 425 participants, most were female (67%), under 60 years old (53%), and resided in the United States (74%). The most frequently reported symptom at diagnosis was cough (54%), though 18% reported no symptoms. In addition, 89% reported receiving at least one tyrosine kinase inhibitor (TKI); osimertinib was the most prescribed first-line TKI for stage IV participants diagnosed after 2017. Participants residing in the United States were more likely to have access to advanced diagnostic (next-generating sequencing) and newer treatments such as osimertinib. Just under half of the sample (47%) had experienced progressive disease and were no longer on first-line treatment.</div></div><div><h3>Conclusion</h3><div>The TKI era has been practice changing; however, little is understood from the perspective of people living with EGFR-m NSCLC. This paper is the first to explore this and found it is possible to have people self-report complex health information about their lung cancer. In addition, although most participants were diagnosed after osimertinib became guideline-recommended treatment, disparities in treatment were identified.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 3","pages":"Article 100782"},"PeriodicalIF":3.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143348096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"J-TAIL-2: A Prospective, Observational Study of Atezolizumab Combined With Carboplatin and Etoposide in Patients With Extensive-Stage SCLC in Japan","authors":"Eisaku Miyauchi MD, PhD ,&nbsp;Makoto Nishio MD, PhD ,&nbsp;Kadoaki Ohashi MD, PhD ,&nbsp;Atsushi Osoegawa MD, PhD ,&nbsp;Eiki Kikuchi MD, PhD ,&nbsp;Hideharu Kimura MD, PhD ,&nbsp;Yasushi Goto MD, PhD ,&nbsp;Junichi Shimizu MD, PhD ,&nbsp;Hiroshige Yoshioka MD, PhD ,&nbsp;Ichiro Yoshino MD, PhD ,&nbsp;Toshihiro Misumi PhD ,&nbsp;Nobuyuki Katakami MD, PhD ,&nbsp;Masahide Oki MD, PhD ,&nbsp;Takashi Kijima MD, PhD ,&nbsp;Kenichi Chikamori MD, PhD ,&nbsp;Kazumi Nishino MD, PhD ,&nbsp;Yuki Kobayashi MS ,&nbsp;Asako Miwa BA ,&nbsp;Misa Tanaka MS ,&nbsp;Akihiko Gemma PhD","doi":"10.1016/j.jtocrr.2024.100783","DOIUrl":"10.1016/j.jtocrr.2024.100783","url":null,"abstract":"<div><h3>Introduction</h3><div>On the basis of the IMpower133 trial, atezolizumab plus carboplatin and etoposide (CE) is approved as first-line treatment for extensive-stage (ES)-SCLC. The J-TAIL-2 study evaluated atezolizumab plus CE in routine clinical practice settings.</div></div><div><h3>Methods</h3><div>J-TAIL-2 was a prospective, multicenter observational study in Japan. Patients with ES-SCLC received atezolizumab plus CE in clinical practice. The primary end point was 12-month OS rate. Secondary end points included overall survival (OS), progression-free survival (PFS), and safety in select subgroups, including the IMpower133-unlike (i.e., Eastern Cooperative Oncology Group performance status 2 or more, interstitial lung disease, autoimmune disease) versus IMpower133-like groups.</div></div><div><h3>Results</h3><div>Overall, 403 patients were included; the median age was 71 years, 16.6% (n = 67) had an Eastern Cooperative Oncology Group performance status 2 or more, 26.8% (n = 108) had brain metastasis, 6.9% (n = 28) had interstitial lung disease, 4.0% (n = 16) had autoimmune disease, and 72.7% (n = 293) were IMpower133-unlike. In the efficacy population (n = 399), the 12-month OS rate was 63.7%, median OS was 16.5 months, and median PFS was 5.1 months. In IMpower133-unlike versus IMpower133-like subgroups, the 12-month OS rate was 58.5% versus 77.5%, median OS was 15.5 versus 19.1 months (hazard ratio, 1.32; 95% confidence interval: 0.98–1.77), and median PFS was 4.8 versus 5.4 months (hazard ratio, 1.14; 95% confidence interval: 0.90–1.45). No new safety signals were observed (safety population, n = 400); safety outcomes in the IMpower133-unlike and IMpower133-like subgroups were similar.</div></div><div><h3>Conclusions</h3><div>In J-TAIL-2, atezolizumab plus CE had efficacy in patients with ES-SCLC in clinical practice that was consistent with that in IMpower133. Taken together with the acceptable safety profile, these data support the use of atezolizumab plus CE in patients with ES-SCLC in Japan, including those who would have been ineligible for IMpower133.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 3","pages":"Article 100783"},"PeriodicalIF":3.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143173721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Utility of Combined Tissue and Plasma Next-Generation Sequencing in Patients With Advanced, Treatment-Naïve NSCLC","authors":"Helena Bote-de Cabo MD ,&nbsp;Marco Siringo MD ,&nbsp;Esther Conde MD, PhD ,&nbsp;Susana Hernández PhD ,&nbsp;Fernando López-Ríos MD, PhD ,&nbsp;Alicia Castelo-Loureiro MD ,&nbsp;Esther García-Lorenzo MD ,&nbsp;Javier Baena MD-PhD ,&nbsp;Mercedes Herrera MD ,&nbsp;Ana Belén Enguita MD ,&nbsp;Yolanda Ruano PhD ,&nbsp;Jon Zugazagoitia MD, PhD ,&nbsp;Luis Paz-Ares MD, PhD","doi":"10.1016/j.jtocrr.2024.100778","DOIUrl":"10.1016/j.jtocrr.2024.100778","url":null,"abstract":"<div><h3>Introduction</h3><div>Tissue and plasma-based next-generation sequencing (NGS) have complementary roles in patients with advanced NSCLC. Nevertheless, whether there is any added clinical value in combining both methods in the treatment of naïve patients remains unclear.</div></div><div><h3>Methods</h3><div>We retrospectively collected clinical and genomic data from 275 patients with treatment-naïve advanced NSCLC who had undergone plasma-based NGS at diagnosis in our institution. We analyzed patient data in two separate cohorts, each assessed with a different plasma-based NGS method: cohort 1 (n = 127, Guardant360), and cohort 2 (n = 148, FoundationACT/FoundationOne Liquid CDx). Ninety-five patients (75%) in cohort 1 and 108 patients (73%) in cohort 2 underwent concurrent amplicon-based tissue NGS testing locally.</div></div><div><h3>Results</h3><div>Forty-three patients in cohort 1 (34%) and 49 patients in cohort 2 (33%) harbored European Society for Medical Oncology Scale for Clinical Actionability of Molecular Targets (ESCAT) I or II targetable driver alterations. The addition of orthogonal biopsy (tissue to liquid, or liquid to tissue) offered no relevant clinical value in cases with ESCAT I or II targetable drivers already detected by one method. In contrast, adding orthogonal biopsy incremented the detection of ESCAT I or II targetable drivers not only in cases with uninformative testing (undetectable circulating tumor DNA, unavailable/inadequate tissue) but also in about 5% of the patients with seemingly informative but driver undetected molecular results. The prevalence of ESCAT I or II targetable drivers in plasma was significantly higher in patients with adenocarcinoma, 20 pack-year or less smoking history, and abdominal metastases.</div></div><div><h3>Conclusions</h3><div>Our study suggests that the addition of sequential orthogonal biopsy should be considered whenever an ESCAT I or II targetable driver has not been detected by the initial method, including cases with seemingly informative molecular analysis.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 3","pages":"Article 100778"},"PeriodicalIF":3.0,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143348094","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Individualized Cell-Free DNA Monitoring With Chromosomal Junctions for Mesothelioma","authors":"Kaushal Parikh MD ,&nbsp;Faye R. Harris MS ,&nbsp;Giannoula Karagouga MS ,&nbsp;Amy Schrandt CRA ,&nbsp;Jay Mandrekar PhD ,&nbsp;Sarah Johnson MS ,&nbsp;Alexa McCune BS ,&nbsp;Dorsay Sadeghian MD ,&nbsp;Debarshi Roy PhD ,&nbsp;Katarzyna Polonis PhD ,&nbsp;Athanasios Gaitatzes MS ,&nbsp;Aaron O. Bungum BS ,&nbsp;Eric S. Edell MD ,&nbsp;Mitesh J. Borad MD ,&nbsp;Tobias Peikert MD ,&nbsp;Farhad Kosari PhD ,&nbsp;John Cheville MD ,&nbsp;George Vasmatzis PhD ,&nbsp;Aaron S. Mansfield MD","doi":"10.1016/j.jtocrr.2024.100692","DOIUrl":"10.1016/j.jtocrr.2024.100692","url":null,"abstract":"<div><h3>Introduction</h3><div>The spatially complex nature of mesothelioma and interventions like pleurodesis, surgery, and radiation often complicate imaging-based assessment. Further, cell-free DNA (cfDNA) based monitoring strategies are inadequate for mesothelioma, given the presence of a few recurring nonsynonymous somatic variants. However, patient-specific chromosomal rearrangements are commonly found in mesothelioma. Our study objective was to develop an individualized cfDNA assay to enable blood-based monitoring using circulating tumor DNA (ctDNA) in mesothelioma. We hypothesized that the unique chromosomal rearrangement junctions found in mesothelioma could be employed for individualized ctDNA detection and disease monitoring.</div></div><div><h3>Methods</h3><div>DNA was extracted from tumor specimens for whole genome sequencing. Chromosomal junctions, prioritized by highest allele frequency and low homology to the rest of the genome, were selected for detection. Primers and Taqman probes were designed to span the junctions, forming personalized junction panels. Patient plasma obtained before therapy and at response assessment was tested for the presence of personalized junctions via quantitative polymerase chain reaction.</div></div><div><h3>Results</h3><div>Our study included nine patients, four with peritoneal and five with pleural mesothelioma. 763 chromosomal junctions were identified in the tumors of all cases. We selected three to five junctions per sample for quantitative polymerase chain reaction. We detected 25/30 (83%) of selected junctions in the plasma of seven out of nine patients (78%). Cell-free junction detection at follow-up was concordant with disease status: cfDNA junctions were detected in three patients with persistent disease, and not detected in a patient with no evidence of disease after surgery.</div></div><div><h3>Conclusions</h3><div>With further validation, individualized ctDNA junction assays could supplement imaging for disease monitoring in mesothelioma.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 12","pages":"Article 100692"},"PeriodicalIF":3.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141131670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}