JTO Clinical and Research Reports最新文献

{"title":"Distinct Progression and Efficacy of First-Line Osimertinib Treatment According to Mutation Subtypes in Metastatic NSCLC Harboring EGFR Mutations","authors":"Yuki Takeyasu MD ,&nbsp;Tatsuya Yoshida MD ,&nbsp;Ken Masuda MD ,&nbsp;Yuji Matsumoto MD ,&nbsp;Yuki Shinno MD ,&nbsp;Yusuke Okuma MD ,&nbsp;Yasushi Goto MD ,&nbsp;Hidehito Horinouchi MD ,&nbsp;Noboru Yamamoto MD ,&nbsp;Yuichiro Ohe MD","doi":"10.1016/j.jtocrr.2024.100636","DOIUrl":"10.1016/j.jtocrr.2024.100636","url":null,"abstract":"<div><h3>Introduction</h3><p>Osimertinib (OSI), a third-generation EGFR tyrosine kinase inhibitor, is the standard treatment for patients with naive EGFR-mutant NSCLC. Nevertheless, information on how the mutation subtype affects disease progression after the failure of OSI treatment is scarce.</p></div><div><h3>Methods</h3><p>We retrospectively reviewed patients with EGFR-mutant NSCLC who received OSI as a first-line treatment between April 2015 and December 2021.</p></div><div><h3>Results</h3><p>This study included 229 patients. The objective response rate was 71%, with intracranial and extracranial response rates of 71% and 90%, respectively. The median progression-free survival was 23.3 mo (95% confidence interval [CI]: 19.6–26.7), and the median overall survival was 33.7 mo (95% CI: 31.3–58.6). Multivariate analysis revealed that the EGFR exon 21 L858R point mutation (L858R) (hazard ratio [HR] = 1.56, 95% CI: 1.04–2.34, <em>p</em> = 0.0328) and liver metastasis (HR = 2.63, 95% CI: 1.53–4.49, <em>p</em> = 0.0004) were significant predictors of progression-free survival in OSI treatment. The concomitant disease progression involving the central nervous system metastasis was significantly more common in patients with L858R (<em>p</em> = 0.048), whereas concomitant disease progression involving primary lesions was significantly more common in patients with exon 19 deletion mutation (<em>p</em> = 0.01). In addition, the probability of disease progression over time was higher for L858R compared with that for exon 19 deletion mutation, in patients with central nervous system metastasis (log-rank test, <em>p</em> = 0.027).</p></div><div><h3>Conclusions</h3><p>The mutation subtype had an impact not only on the clinical outcome of the first-line OSI treatment but also on progression patterns after OSI treatment in patients with NSCLC harboring EGFR mutations.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 2","pages":"Article 100636"},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364324000067/pdfft?md5=15b5cae6f214b62146bf962b296ac182&pid=1-s2.0-S2666364324000067-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139632431","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":"Efficacy and Safety of Dose-Escalated Alectinib in Patients With Metastatic ALK-Positive NSCLC and Central Nervous System Relapse on Standard-Dose Alectinib","authors":"Justin M. Cheung MD ,&nbsp;Jiyoon Kang DO ,&nbsp;Beow Y. Yeap ScD ,&nbsp;Jennifer L. Peterson BS ,&nbsp;Andrew Do BS ,&nbsp;Justin F. Gainor MD ,&nbsp;Subba R. Digumarthy MD ,&nbsp;Jessica J. Lin MD","doi":"10.1016/j.jtocrr.2024.100645","DOIUrl":"https://doi.org/10.1016/j.jtocrr.2024.100645","url":null,"abstract":"<div><h3>Introduction</h3><p>Central nervous system (CNS) metastases remain a common challenge in patients with ALK-positive NSCLC. We previously reported reinduction of CNS responses using dose-intensified alectinib in two patients with CNS progression on standard-dose alectinib. Nevertheless, this strategy has not been assessed in larger cohorts.</p></div><div><h3>Methods</h3><p>Patients were eligible for this retrospective study if they had metastatic ALK-positive NSCLC with CNS relapse on alectinib 600 mg twice daily dosing and subsequently received escalated dosing (900 mg twice daily) of alectinib. CNS efficacy was assessed per the modified Response Evaluation Criteria in Solid Tumors version 1.1.</p></div><div><h3>Results</h3><p>Among 27 patients, median duration of dose-escalated alectinib was 7.7 months (95% confidence interval [CI]: 4.8–10.9), with median overall time-to-progression (TTP) of 7.1 months (95% CI: 4.4–9.6). Among 25 CNS response-assessable patients, CNS objective response rate was 12.0% (95% CI: 2.5–31.2) and CNS disease control rate was 92.0% (95% CI: 74.0–99.0), with median CNS duration of disease control of 5.3 months (95% CI: 3.4–8.3) and median CNS TTP of 7.1 months (95% CI: 4.4–9.6). Among four patients with measurable CNS disease at baseline, three experienced a best intracranial response of stable disease and one experienced intracranial partial response with CNS TTP ranging from 4.1 to 7.7 months. No patient required drug discontinuation due to treatment-related adverse event or experienced grade 3 or higher treatment-related adverse events.</p></div><div><h3>Conclusions</h3><p>Dose-intensified alectinib was found to have tolerability and activity in patients with ALK-positive NSCLC who experienced CNS relapse on standard-dose alectinib and represents one clinically viable strategy for this population.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 3","pages":"Article 100645"},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364324000158/pdfft?md5=5fbc81fc77a9b09f2ec2e3bf8f5dbe37&pid=1-s2.0-S2666364324000158-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139936164","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":"Detection of Tumor DNA in Bronchoscopic Fluids in Peripheral NSCLC: A Proof-of-Concept Study","authors":"Gwenaëlle Arhant MD ,&nbsp;Samy Lachkar MD ,&nbsp;Pierre-Alain Thiebaut MD, PhD ,&nbsp;Florent Marguet MD, PhD ,&nbsp;Aude Lamy PhD ,&nbsp;Luc Thiberville MD, PhD ,&nbsp;Mathieu Salaün MD, PhD ,&nbsp;Florian Guisier MD, PhD ,&nbsp;Jean-Christophe Sabourin MD, PhD ,&nbsp;Nicolas Piton MD, PhD","doi":"10.1016/j.jtocrr.2023.100596","DOIUrl":"10.1016/j.jtocrr.2023.100596","url":null,"abstract":"<div><h3>Introduction</h3><p>DNA genotyping from plasma is a useful tool for molecular characterization of NSCLC. Nevertheless, the false-negative rate justifies the development of methods with higher sensitivity, especially in difficult-to-reach peripheral lung tumors.</p></div><div><h3>Methods</h3><p>We aimed at comparing molecular analysis from the supernatant of guide sheath flush fluid collected during radial-EndoBronchial UltraSound (r-EBUS) bronchoscopy with plasma sampling and tumor biopsies in patients with peripheral NSCLC. The DNA was genotyped using high-throughput sequencing or the COBAS mutation test. There were 65 patients with peripheral lung tumors subjected to concomitant sampling of guide sheath flush supernatant, plasma tumor DNA, and tumor biopsy and cytology using r-EBUS. There were 33 patients (including 24 newly diagnosed with having NSCLC) with an identifiable tumor mutation in the primary lesion selected for the comparative analysis.</p></div><div><h3>Results</h3><p>Guide sheath flush-based genotyping yielded a mutation detection rate of 61.8% (17 of 24 mutated <em>EGFR</em>, one of two <em>ERBB2</em>, one of one <em>KRAS</em>, one of one <em>MAP2K</em>, one of four <em>MET</em>, and zero of one <em>STK11</em>), compared with 33% in plasma-based genotyping (<em>p</em> = 0.0151). Furthermore, in eight of 34 r-EBUS without tumor cells on microscopic examination, we were able to detect the mutation in four paired guide sheath flush supernatant, compared with only two in paired plasma.</p></div><div><h3>Conclusion</h3><p>The detection of tumor DNA in the supernatant of guide sheath flush fluid collected during r-EBUS bronchoscopy represents a sensitive and complementary method for genotyping NSCLC.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 2","pages":"Article 100596"},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266636432300139X/pdfft?md5=8db19b80b91d02baea2f91a5c01fb365&pid=1-s2.0-S266636432300139X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135963645","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":"Long-Term Efficacy of Immune Checkpoint Inhibitor for Squamous Cell Carcinoma Lesion Transformed From EGFR-Mutated Adenocarcinoma After Osimertinib Treatment: A Case Report","authors":"Shota Takahashi MD ,&nbsp;Yuki Sato MD ,&nbsp;Yoshiharu Sato PhD ,&nbsp;Ryosuke Hirabayashi MD ,&nbsp;Shigeo Hara MD, PhD ,&nbsp;Yutaka Takahashi MD, PhD ,&nbsp;Keisuke Tomii MD, PhD","doi":"10.1016/j.jtocrr.2024.100639","DOIUrl":"10.1016/j.jtocrr.2024.100639","url":null,"abstract":"<div><p>Histologic transformation is one of the mechanisms of resistance to EGFR tyrosine kinase inhibitor in patients with NSCLC with <em>EGFR</em> mutation. The transformation from adenocarcinoma to squamous cell carcinoma (SCC) has been recently recognized as a mechanism of resistance to osimertinib. The prognosis after transformation to SCC is considered to be poor, and the therapeutic strategy for these patients is unclear. Herein, we report a case of long-term response to pembrolizumab monotherapy for an SCC-transformed lesion in a patient with <em>EGFR</em>-mutated adenocarcinoma after osimertinib treatment. A 68-year-old man underwent right upper lobectomy and was diagnosed with lung adenocarcinoma, pathologic stage IIA, with <em>EGFR L858R</em>. Five years after the surgery, he was diagnosed with recurrence and administered osimertinib. Ten months after, biopsy for an enlarged subpleural lesion revealed SCC with <em>EGFR L858R</em>, leading to a diagnosis of histologic transformation. Notably, the programmed death-ligand 1 expression level of the transformed lesion was higher than that of the adenocarcinoma (90% versus &lt;1%). The size of the SCC lesion had reduced with pembrolizumab monotherapy, and the reduction was maintained for over 47 months since transformation. Nevertheless, the original adenocarcinoma lesion progressed after pembrolizumab therapy and was controlled by other cytotoxic drugs and readministration of osimertinib. Immune checkpoint inhibitor therapy is generally ineffective against <em>EGFR</em>-mutated adenocarcinoma. Nevertheless, it may be promising for achieving a good prognosis when <em>EGFR</em>-mutated adenocarcinoma transforms to SCC after developing EGFR tyrosine kinase inhibitor resistance—particularly if the transformed lesion has high programmed death-ligand 1 expression.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 2","pages":"Article 100639"},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364324000092/pdfft?md5=53489d0154501c53961f3bc7bc602380&pid=1-s2.0-S2666364324000092-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139539486","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":"Genomic Landscape of NSCLC in the Republic of Ireland","authors":"Rachel J. Keogh MB BCH BAO ,&nbsp;Martin P. Barr PhD ,&nbsp;Anna Keogh MB BCH BAO ,&nbsp;David McMahon MB BCH BAO ,&nbsp;Cathal O’Brien PhD ,&nbsp;Stephen P. Finn MD ,&nbsp;Jarushka Naidoo MBBCH, MHS","doi":"10.1016/j.jtocrr.2023.100627","DOIUrl":"https://doi.org/10.1016/j.jtocrr.2023.100627","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;p&gt;The identification of genomic “targets” through next-generation sequencing (NGS) of patient’s NSCLC tumors has resulted in a rapid expansion of targeted treatment options for selected patients. This retrospective study aims to identify the proportion of patients with advanced NSCLC in the Republic of Ireland whose tumors harbor actionable genomic alterations through broad NGS panel testing.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;Institutional review board approval was obtained before study initiation. Patients with NSCLC whose tumors underwent genomic testing through the largest available NGS panel at a nationally funded Cancer Molecular Diagnostics laboratory (St. James’s Hospital) between June 2017 and June 2022 were identified. Patient demographics and tumor-related data were collected by retrospective review from all cancer centers in Ireland, referring to the Cancer Molecular Diagnostics laboratory. A total of 203 (9%) tumor samples were excluded due to insufficient neoplastic cell content. Genomic data were collected through retrospective search of Ion Reporter software. The spectrum and proportion of patients with oncogenic driver mutations were evaluated using descriptive statistics (SPSS version 29.0).&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;In total, 2052 patients were identified. Patients were referred from 23 different hospital sites and all four geographic regions (Leinster = 1091, 53%; Munster = 763, 37.2%; Connacht = 191, 9.3%; Ulster = 7, 0.3%). Median age was 69 (range: 26–94) years; 53% were male. The most common tumor histologic subtype was adenocarcinoma (77%, n = 1577). An actionable genomic alteration was identified in 1099 cases (53%), the most common of which was &lt;em&gt;KRAS&lt;/em&gt; (n = 657, 32%). Less frequently, NSCLC tumors harbored the following: &lt;em&gt;MET&lt;/em&gt; exon 14 skipping (n = 53, 2.6%), &lt;em&gt;MET&lt;/em&gt; amplification (n = 26, 1.3%), &lt;em&gt;EGFR&lt;/em&gt; (n = 181, 8.8%), &lt;em&gt;HER2&lt;/em&gt; (n = 35, 1.7%), and &lt;em&gt;BRAF&lt;/em&gt; (n = 72, 3.5%) mutations. Fusions were detected in 76 patients (3.7%) including &lt;em&gt;ALK&lt;/em&gt; (n = 44, 58%), &lt;em&gt;RET&lt;/em&gt; (n = 11, 14.5%), &lt;em&gt;ROS1&lt;/em&gt; (n = 16, 21%), and &lt;em&gt;FGFR3&lt;/em&gt; (n = 5, 6.6%), whereas no &lt;em&gt;NTRK&lt;/em&gt; fusion was identified. Co-alterations were detected in 114 patients (5.6%), the most common of which was &lt;em&gt;KRAS&lt;/em&gt;/&lt;em&gt;PIK3CA&lt;/em&gt; (n = 19, 17%), &lt;em&gt;EGFR/PIK3CA&lt;/em&gt; (n = 10, 8.5%), and &lt;em&gt;KRAS/IDH1&lt;/em&gt; (n = 9, 8%). Other co-alterations of interest identified included &lt;em&gt;KRAS G12A/ROS1&lt;/em&gt; fusion (n = 1) and &lt;em&gt;KRAS G12C/BRAF G469A&lt;/em&gt; (n = 2).&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;p&gt;This is the first retrospective study to comprehensively characterize the genomic landscape of NSCLC in Ireland, using the broadest available NGS panel. Actionable alterations were identified in 53.4% of the patients, and &lt;em&gt;KRAS&lt;/em&gt; was the most common oncogenic driver alteration. Our study revealed a lower prevalence of patients whose tumor harbors &lt;em&gt;ALK&lt;/em&gt;, &lt;em&gt;ROS1&lt;/em&gt;, and &lt;em&gt;RET","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 2","pages":"Article 100627"},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364323001704/pdfft?md5=e879d8ce419187bfe27ae56a2b830587&pid=1-s2.0-S2666364323001704-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139675279","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: Comprehensive Clinicogenomic Profiling of Small Cell Transformation From EGFR-Mutant NSCLC Informs Potential Therapeutic Targets","authors":"Bingnan Zhang MD, MBA ,&nbsp;Whitney Lewis PharmD ,&nbsp;C. Allison Stewart PhD ,&nbsp;Benjamin B. Morris PhD ,&nbsp;Luisa M. Solis MD ,&nbsp;Alejandra Serrano MD ,&nbsp;Yuanxin Xi PhD ,&nbsp;Qi Wang PhD ,&nbsp;Elyse R. Lopez MD ,&nbsp;Kyle Concannon MD ,&nbsp;Simon Heeke PhD ,&nbsp;Ximing Tang MD, PhD ,&nbsp;Gabriela Raso MD ,&nbsp;Robert J. Cardnell PhD ,&nbsp;Natalie Vokes MD ,&nbsp;George Blumenschein MD ,&nbsp;Yasir Elamin MD ,&nbsp;Frank Fosella MD ,&nbsp;Anne Tsao MD ,&nbsp;Ferdinandos Skoulidis MD, PhD ,&nbsp;Xiuning Le MD, PhD","doi":"10.1016/j.jtocrr.2023.100623","DOIUrl":"https://doi.org/10.1016/j.jtocrr.2023.100623","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;p&gt;NSCLC transformation to SCLC has been best characterized with &lt;em&gt;EGFR&lt;/em&gt;-mutant NSCLC, with emerging case reports seen in &lt;em&gt;ALK&lt;/em&gt;, &lt;em&gt;RET&lt;/em&gt;, and &lt;em&gt;KRAS&lt;/em&gt;-altered NSCLC. Previous reports revealed transformed SCLC from &lt;em&gt;EGFR&lt;/em&gt;-mutant NSCLC portends very poor prognosis and lack effective treatment. Genomic analyses revealed &lt;em&gt;TP53&lt;/em&gt; and &lt;em&gt;RB1&lt;/em&gt; 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.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;p&gt;In this study, we conducted a single-center retrospective analysis of clinical and genomic characteristics of patients with &lt;em&gt;EGFR&lt;/em&gt;-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 &lt;em&gt;EGFR&lt;/em&gt; 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.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;p&gt;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 &lt;em&gt;EGFR&lt;/em&gt; 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 &lt;em&gt;PIK3CA&lt;/em&gt; 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 &lt;em&gt;TP53, RB1, PIK3CA&lt;/em&gt; alterations. ScRNA-seq revealed potential therapeutic targets including DLL3, CD276 (B7-H3) and PTK7 were widely expressed in transformed SCLC.&lt;/p&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;p&gt;SCLC transformation is a potential treatment resistance mechanism in driver-mutant NSCLC. In our cohort of 34 &lt;em&gt;EGFR&lt;/em&gt;-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. Furt","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 2","pages":"Article 100623"},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364323001662/pdfft?md5=aba5d65bda03a790b7d04e58ff623ea7&pid=1-s2.0-S2666364323001662-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139709819","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":"A Prospective Observational Study of Physical Activity Levels and Physical Fitness of People at High Risk for Lung Cancer","authors":"Asha Bonney MBBS ,&nbsp;Catherine L. Granger PhD ,&nbsp;Daniel Steinfort PhD ,&nbsp;Henry M. Marshall PhD ,&nbsp;Emily Stone PhD ,&nbsp;Annette McWilliams PhD ,&nbsp;Fraser Brims PhD ,&nbsp;Paul Fogarty MBBS ,&nbsp;Linda Lin MBBS ,&nbsp;Jiashi Li MD ,&nbsp;Siyuan Pang MD ,&nbsp;Stephen Lam PhD ,&nbsp;Kwun M. Fong PhD ,&nbsp;Renee Manser PhD","doi":"10.1016/j.jtocrr.2024.100633","DOIUrl":"https://doi.org/10.1016/j.jtocrr.2024.100633","url":null,"abstract":"<div><h3>Introduction</h3><p>Physical activity (PA) is a potentially modifiable risk factor for lung cancer, with previous research revealing that people who engage in more PA have lower risk of developing lung cancer. PA levels of lung cancer screening participants have not previously been explored.</p></div><div><h3>Methods</h3><p>Participants at a single Australian International Lung Screen Trial site were eligible for assessment of self-reported PA levels (International Physical Activity Questionnaire and Physical Activity Scale for the Elderly) and physical assessments (6-min walk distance, hand grip muscle strength, daily step count, and body composition) at a single time point during lung cancer screening. Statistics were predominantly descriptive, with parametric data presented as mean and SD and nonparametric data presented as median and interquartile range (IQR).</p></div><div><h3>Results</h3><p>A total of 178 participants were enrolled in this study, with a median age of 61 years. Of the participants, 61% were men and 51% were people who currently smoke. The median total International Physical Activity Questionnaire score was 1756 MET/min/wk (IQR 689, 4049). Mean total Physical Activity Scale for the Elderly score was 160 (SD 72), higher than described in healthy sedentary adults. The median daily step count was 7237 steps (IQR 5353, 10,038) and mean 6-minute walk distance was 545 m (SD 92). Median grip strengths were within predicted normal range, with an elevated median percentage body fat and low skeletal muscle mass found on body composition.</p></div><div><h3>Conclusion</h3><p>Almost a quarter of International Lung Screen Trial participants assessed reported low levels of PA and have a potentially modifiable risk factor to improve health outcomes. Larger studies are needed to characterize the burden of inactivity among high-risk lung cancer screening populations.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 2","pages":"Article 100633"},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364324000031/pdfft?md5=bb55777c15706d0e08b94f39b7f793d0&pid=1-s2.0-S2666364324000031-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139718766","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":"Severe Drug-Induced Interstitial Lung Disease After Administration of Osimertinib as Adjuvant Treatment for Resected EGFR-Mutated NSCLC: A Case Report","authors":"Sho Mitsuya MD ,&nbsp;Masahiro Arai MD ,&nbsp;Kiyoe Kanaoka MD ,&nbsp;Tomoya Funamoto MD ,&nbsp;Hiroyuki Tsuji MD ,&nbsp;Kenjiro Tsuruoka MD, PhD ,&nbsp;Ninso Matsunaga MD ,&nbsp;Takahiko Nakamura MD ,&nbsp;Yosuke Tamura MD, PhD ,&nbsp;Masafumi Imanishi MD, PhD ,&nbsp;Soichiro Ikeda MD, PhD ,&nbsp;Akihisa Imagawa MD, PhD ,&nbsp;Yasuhito Fujisaka MD, PhD","doi":"10.1016/j.jtocrr.2024.100631","DOIUrl":"10.1016/j.jtocrr.2024.100631","url":null,"abstract":"<div><p>Osimertinib administration has been approved as an adjuvant treatment after complete surgical resection in patients with EGFR-mutated NSCLC. This article presents the first report of life-threatening postoperative osimertinib-induced interstitial lung disease. An 83-year-old male patient underwent right upper lobectomy (pathologic stage IIA) and osimertinib (80 mg/d) was initiated on postoperative day 75. On day 44 of osimertinib administration, chest computed tomography revealed diffuse ground-glass opacities; accordingly, osimertinib-induced interstitial lung disease was diagnosed. Steroid pulse therapy was initiated using a high-flow nasal cannula to treat dyspnea and hypoxemia, rapidly improving the respiratory status and imaging findings; moreover, the patient’s clinical course was excellent. This case report suggests that the postoperative occurrence of severe osimertinib-induced interstitial lung disease is a crucial factor that must be considered in patient decision-making regarding perioperative treatment.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 2","pages":"Article 100631"},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364324000018/pdfft?md5=df332c61af156cd7360621cd0b49595e&pid=1-s2.0-S2666364324000018-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139395878","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":"Lorlatinib After Alectinib-Induced Pneumonitis: A Case Report","authors":"James A. Fletcher M.B.B.S. ,&nbsp;William J. Mullally MBBCh BAO ,&nbsp;Rahul Ladwa MPhil ,&nbsp;Kenneth J. O’Byrne MD","doi":"10.1016/j.jtocrr.2023.100591","DOIUrl":"10.1016/j.jtocrr.2023.100591","url":null,"abstract":"<div><p><em>ALK</em> gene rearrangements are detected in approximately 3% to 5% of NSCLC. <em>ALK</em> tyrosine kinase inhibitors, such as third-generation lorlatinib, have exhibited remarkable efficacy in <em>ALK</em>-rearranged NSCLC; however, they have been associated with a low incidence of treatment-limiting and potentially fatal drug-induced interstitial lung disease (ILD). There is concern that this may represent a class effect, a theory that is supported by a number of case reports. Because of clinical trial exclusion criteria, there are limited prospective data to guide decision-making after <em>ALK</em> tyrosine kinase inhibitors–induced ILD. A systematic review of the literature was conducted and only identified four reported cases of lorlatinib safety in this context. Here, we report the successful sequencing of lorlatinib in a patient who discontinued alectinib secondary to grade 3 drug-induced ILD.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 2","pages":"Article 100591"},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364323001340/pdfft?md5=bd98224b5ca00552f89132e9ae085664&pid=1-s2.0-S2666364323001340-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135922167","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":"A Phase 1/2 Study to Evaluate the Safety and Activity of Nivolumab in Combination With Vorolanib, a Vascular Endothelial Growth Factor Tyrosine Kinase Inhibitor, in Patients With Refractory Thoracic Tumors","authors":"Kathryn E. Beckermann MD, PhD ,&nbsp;Christine M. Bestvina MD ,&nbsp;Badi El Osta MD ,&nbsp;Rachel E. Sanborn MD ,&nbsp;Hossein Borghaei MD ,&nbsp;Philip Edward Lammers MD, MSCI ,&nbsp;Giovanni Selvaggi MD ,&nbsp;Jennifer G. Whisenant PhD ,&nbsp;Ellen Heimann-Nichols MBA ,&nbsp;Lynne Berry PhD ,&nbsp;Chih-Yuan Hsu PhD ,&nbsp;Yu Shyr PhD ,&nbsp;Leora Horn MD, MSc, MHPE ,&nbsp;Heather Wakelee MD, FASCO","doi":"10.1016/j.jtocrr.2023.100619","DOIUrl":"10.1016/j.jtocrr.2023.100619","url":null,"abstract":"<div><h3>Introduction</h3><p>Targeting the tumor microenvironment may enhance response to immunotherapy (immune checkpoint inhibitors) and improve outcomes for patients. This study tested the safety and efficacy of vorolanib, a novel tyrosine kinase inhibitor of vascular endothelial growth factor, platelet-derived growth factor, and c-KIT, in combination with programmed cell death protein 1 blockade using nivolumab for refractory thoracic malignancies.</p></div><div><h3>Methods</h3><p>This single-arm multicenter study enrolled patients with extensive-stage SCLC, thymic carcinoma, and NSCLC, either naive or had progressed on previous chemotherapy or immune checkpoint inhibitors (either primary or acquired resistance). The primary objective of phase 1 was to determine the maximum tolerated dose, and the primary end point for each dose-expansion cohort was the objective response rate.</p></div><div><h3>Results</h3><p>A total of 88 patients were enrolled in phase 1 (n = 11) and dose expansion (n = 77) cohorts. Transaminitis was dose-limiting and expansion proceeded with oral vorolanib 200 mg daily combined with intravenous nivolumab 240 mg every 2 weeks. The objective response rate per cohort were as follows: NSCLC naive 33% (five of 15, 95% confidence interval [CI]: 13%–60%), NSCLC primary refractory 5.9% (one of 17, 95% CI: 0%–17.6%), NSCLC acquired resistance 11.1% (two of 18, 95% CI: 0%–27.8%); SCLC 0% (zero of 18), and thymic carcinoma 11% (one of nine, 95% CI: 0%–33%). Disease control rate ranged from 11.1% in SCLC (two of 18, 0%–27.8%) to 66.7 % in thymic carcinoma (six of nine, 95% CI: 33.3%–100%). The most common adverse events were fatigue (32%), aspartate transaminase (27%) and alanine transaminase elevation (25%), and diarrhea (19%). Transaminitis was more common in patients with thymic carcinoma than other tumors.</p></div><div><h3>Conclusions</h3><p>Vorolanib plus nivolumab had a manageable safety profile and may have clinical benefits in various thoracic malignancies. The disease control rate in thymic malignancies warrants further assessment.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 2","pages":"Article 100619"},"PeriodicalIF":0.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364323001625/pdfft?md5=dccb3d4c2096d1c8b2f2221d50859b62&pid=1-s2.0-S2666364323001625-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139016968","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}