JTO Clinical and Research Reports最新文献

{"title":"Combined RET and MEK Inhibition as a Treatment for RET Fusion-Positive NSCLC With Acquired BRAF Fusion: A Case Report","authors":"Jacobi B. Hines MD ,&nbsp;Benjamin C. Bowar PharmD ,&nbsp;Margaret Colleton MMS ,&nbsp;Lydia Chelala MD ,&nbsp;Peng Wang MD ,&nbsp;Angad A. Chadha MD ,&nbsp;Jeremy Segal MD ,&nbsp;Christine M. Bestvina MD","doi":"10.1016/j.jtocrr.2024.100724","DOIUrl":"10.1016/j.jtocrr.2024.100724","url":null,"abstract":"<div><div><em>RET</em> fusions are present in 1% to 2% of NSCLCs. Although RET inhibitors like selpercatinib are effective, resistance inevitably develops. We present the case of a 28-year-old female with recurrent NSCLC and a <em>CCDC6::RET</em> fusion treated with selpercatinib. Testing at the time of progression revealed a new <em>SKAP2</em><em>:</em>:BRAF fusion. She was then treated with a combination of selpercatinib and trametinib, which led to a likely partial response, despite the combination demonstrating side effects. This case report details the first known instance of NSCLC with a <em>RET</em> fusion developing resistance by means of a <em>BRAF</em> fusion, treated with combined RET and MEK inhibition.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 11","pages":"Article 100724"},"PeriodicalIF":3.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142426752","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":"Unveiling the Molecular Features of SCLC With a Clinical RNA Expression Panel","authors":"Hilal Ozakinci MD ,&nbsp;Aileen Y. Alontaga PhD ,&nbsp;Pedro Cano MD ,&nbsp;John M. Koomen PhD ,&nbsp;Bradford A. Perez MD ,&nbsp;Amer A. Beg PhD ,&nbsp;Alberto A. Chiappori MD ,&nbsp;Eric B. Haura MD ,&nbsp;Theresa A. Boyle MD, PhD","doi":"10.1016/j.jtocrr.2024.100723","DOIUrl":"10.1016/j.jtocrr.2024.100723","url":null,"abstract":"<div><h3>Introduction</h3><div>The translation of gene expression profiles of SCLC to clinical testing remains relatively unexplored. In this study, gene expression variations in SCLC were evaluated to identify potential biomarkers.</div></div><div><h3>Methods</h3><div>RNA expression profiling was performed on 44 tumor samples from 35 patients diagnosed with SCLC using the clinically validated RNA Salah Targeted Expression Panel (RNA STEP). RNA sequencing (RNA-Seq) and immunohistochemistry were performed on two different SCLC cohorts, and correlation analyses were performed for the <em>ASCL1</em>, <em>NEUROD1</em>, <em>POU2F3</em>, and <em>YAP1</em> genes and their corresponding proteins. RNA STEP and RNA-Seq results were evaluated for gene expression profiles and heterogeneity between SCLC primary and metastatic sites. RNA STEP gene expression profiles of independent SCLC samples (n = 35) were compared with lung adenocarcinoma (n = 160) and squamous cell carcinoma results (n = 25).</div></div><div><h3>Results</h3><div>The RNA STEP results were highly correlated with RNA-Seq and immunohistochemistry results. The dominant transcription regulator by RNA STEP was <em>ASCL1</em> in 74.2% of the samples, <em>NEUROD1</em> in 20%, and <em>POU2F3</em> in 2.9%. The <em>ASCL1</em>, <em>NEUROD1</em>, and <em>POU2F3</em> gene expression profiles were heterogeneous between primary and metastatic sites. SCLCs displayed markedly high expression for targetable genes <em>DLL3</em>, <em>EZH2</em>, <em>TERT</em>, and <em>RET</em>. SCLCs were found to have relatively colder immune profiles than lung adenocarcinomas and squamous cell carcinomas, characterized by lower expression of <em>HLA</em> genes, immune cell, and immune checkpoint genes, except the <em>LAG3</em> gene.</div></div><div><h3>Conclusions</h3><div>Clinical-grade SCLC RNA expression profiling has value for SCLC subtyping, design of clinical trials, and identification of patients for trials and potential targeted therapy.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 11","pages":"Article 100723"},"PeriodicalIF":3.0,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142358682","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: Impact of Maintenance Pemetrexed Cessation on Clinical Outcomes of Patients With Metastatic Nonsquamous NSCLC","authors":"Shreya Bhatia BS ,&nbsp;Matthew Lu MD ,&nbsp;Spencer Lessans MD ,&nbsp;Michael Libre BA ,&nbsp;Heidi Chen PhD ,&nbsp;Wade T. Iams MD","doi":"10.1016/j.jtocrr.2024.100717","DOIUrl":"10.1016/j.jtocrr.2024.100717","url":null,"abstract":"<div><h3>Introduction</h3><div>Combination chemoimmunotherapy including pemetrexed and a PD(L)1 inhibitor is a common first-line systemic therapy approach for patients with metastatic nonsquamous NSCLC. Patients often discontinue maintenance pemetrexed due to adverse effects, and little is known about the impact of maintenance pemetrexed cessation on real-world progression-free survival (rwPFS) and overall survival (OS).</div></div><div><h3>Methods</h3><div>A total of 121 patients with stage IV or recurrent, metastatic nonsquamous NSCLC treated at Vanderbilt University Medical Center (VUMC) were included in this retrospective analysis. Patients diagnosed between July 2017 and September 2023 were included if they received maintenance pemetrexed and pembrolizumab. Patients were divided into two groups: those who stopped pemetrexed due to toxicity and those who did not. rwPFS and OS were measured from time of stage IV or metastatic diagnosis to the date of radiographic progression or death, respectively.</div></div><div><h3>Results</h3><div>Among patients with stage IV or recurrent, metastatic NSCLC (n = 121), who remained on maintenance pemetrexed and pembrolizumab (n = 68), the median rwPFS was 11.7 months (95% confidence interval [CI]: 7.47–not applicable [NA]) compared with 24.3 months (95% CI, 19.37–NA) among patients who stopped maintenance pemetrexed (n = 53) (<em>p</em> = 0.1). The median OS in the same patient groups was 25.8 months (95% CI: 13.8–NA) compared with 36.4 months (95% CI: 26.9–NA) (<em>p</em> = 0.15), respectively.</div></div><div><h3>Conclusions</h3><div>In this study of patients with metastatic nonsquamous NSCLC who received maintenance pemetrexed and pembrolizumab, patients who stopped pemetrexed due to toxicity experienced similar outcomes to those who continued with pemetrexed. The optimal duration of maintenance chemotherapy should be further evaluated in the immunotherapy era.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 11","pages":"Article 100717"},"PeriodicalIF":3.0,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142426751","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":"Assessing the Uptake of the Lung Cancer Core Outcome Set: A Cross-Sectional Analysis","authors":"Andrew V. Tran BS ,&nbsp;Brody Dennis BS ,&nbsp;Matthew Rashid BS ,&nbsp;Kyle Fitzgerald BS ,&nbsp;Garrett Jones BS ,&nbsp;Kimberly Magana MEd ,&nbsp;Jay Modi BS ,&nbsp;Trevor Magee BS ,&nbsp;Shaelyn Ward BS ,&nbsp;Griffin Hughes BA, BS ,&nbsp;Alicia Ito Ford PhD ,&nbsp;Matt Vassar PhD","doi":"10.1016/j.jtocrr.2024.100713","DOIUrl":"10.1016/j.jtocrr.2024.100713","url":null,"abstract":"<div><h3>Introduction</h3><div>A core outcome set (COS) helps standardize outcome measurements across clinical trials. Although lung cancer is the leading cause of cancer-related deaths, research exploring COS implementation across lung cancer trials remains limited. We aim to analyze the uptake of the lung cancer COS and identify potential gaps in COS adherence.</div></div><div><h3>Methods</h3><div>On June 26, 2023, we conducted a cross-sectional analysis of clinical trials that evaluated lung cancer interventions. Our sample consisted of studies registered on ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform between September 2011 and June 2023. In a masked and duplicate fashion, investigators extracted data regarding trial characteristics and COS adoption. An interrupted time series analysis was conducted to evaluate the adherence of lung cancer COS before and after its publication.</div></div><div><h3>Results</h3><div>Of the 626 observed trials, we found no overall significant difference in lung cancer COS uptake pre- and post-publication (0.01%, 95% confidence interval: −0.16% to 0.19%, <em>p</em>=0.85). The most frequently measured outcomes were “overall survival” (91.69%%) and “treatment-related mortalities” (54.69%). Health-related quality of life questionnaires were typically used to evaluate outcomes in the “Degree of health” domain (49.20%). Outcomes related to “time from diagnosis to treatment” (0%), “place of death” (0.16%), and “duration of time spent in the hospital at the end of life” (1.60%) were rarely measured.</div></div><div><h3>Conclusions</h3><div>Despite the advantages of COS implementation, adherence across lung cancer clinical trials remains alarmingly low—which could compromise data reliability and patient care. Our findings showcase these inconsistencies and emphasize the need for proactive approaches to improve uptake.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 12","pages":"Article 100713"},"PeriodicalIF":3.0,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142534272","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":"Final Analysis Data and Exploratory Biomarker Analysis of a Randomized Phase 2 Study of Osimertinib Plus Bevacizumab Versus Osimertinib Monotherapy for Untreated Patients With Nonsquamous NSCLC Harboring EGFR Mutations: The WJOG9717L Study","authors":"Hirotsugu Kenmotsu MD, PhD ,&nbsp;Kazuko Sakai PhD ,&nbsp;Keita Mori PhD ,&nbsp;Terufumi Kato MD ,&nbsp;Shunichi Sugawara MD, PhD ,&nbsp;Keisuke Kirita MD, PhD ,&nbsp;Yasuto Yoneshima MD, PhD ,&nbsp;Koichi Azuma MD, PhD ,&nbsp;Kazumi Nishino MD, PhD ,&nbsp;Shunsuke Teraoka MD ,&nbsp;Ryo Koyama MD, PhD ,&nbsp;Ken Masuda MD, PhD ,&nbsp;Hidetoshi Hayashi MD, PhD ,&nbsp;Ryo Toyozawa MD, PhD ,&nbsp;Satoru Miura MD, PhD ,&nbsp;Yuki Sato MD, PhD ,&nbsp;Kazuhiko Nakagawa MD, PhD ,&nbsp;Nobuyuki Yamamoto MD, PhD ,&nbsp;Kazuto Nishio MD, PhD ,&nbsp;Toshiaki Takahashi MD, PhD","doi":"10.1016/j.jtocrr.2024.100716","DOIUrl":"10.1016/j.jtocrr.2024.100716","url":null,"abstract":"<div><h3>Introduction</h3><div>EGFR tyrosine kinase inhibitors have been the standard treatment for patients with NSCLC who have sensitive <em>EGFR</em> mutations. This study revealed final analysis survival data, biomarkers, and resistance mechanisms of osimertinib plus bevacizumab or osimertinib monotherapy in previously untreated patients with advanced <em>EGFR</em>-positive nonsquamous NSCLC.</div></div><div><h3>Methods</h3><div>We previously reported the primary results of a randomized, open-label, phase 2 study comparing osimertinib plus bevacizumab with osimertinib monotherapy for this population. In this exploratory analysis using tissue and plasma samples, we evaluated gene profiles at baseline and disease progression or the last dose using targeted deep sequencing.</div></div><div><h3>Results</h3><div>The median progression-free survival (PFS) by the blinded independent central reviewer was 22.1 months for the osimertinib plus bevacizumab arm and 20.2 months for the osimertinib arm (hazard ratio [HR] = 0.864, 95% confidence interval [CI]: 0.549–1.359). The 3-year overall survival was not different between the two arms (osimertinib plus bevacizumab: 57.1%; osimertinib monotherapy: 65.0%; HR 1.271, 95% CI: 0.727–2.223). A total of 94 patients had assessable plasma samples at baseline, and 40 had assessable pretreatment tissue samples. <em>EGFR</em> mutations (76.6%) and <em>TP53</em> mutations (44.7%) were detected in plasma samples at baseline. In patients with plasma <em>TP53</em> mutations (n = 42), the median PFS by blinded independent central reviewer was 19.8 months for the osimertinib plus bevacizumab arm and 20.2 months for the osimertinib arm (HR = 1.107, 95% CI: 0.534–2.297).</div></div><div><h3>Conclusions</h3><div>There was also no significant difference in the PFS between the two arms, even in patients with <em>TP53</em> mutations.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 11","pages":"Article 100716"},"PeriodicalIF":3.0,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142328172","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":"Outcomes of Resected Lung Cancer Diagnosed Through Screening and Incidental Pulmonary Nodule Programs in a Mississippi Delta Cohort","authors":"","doi":"10.1016/j.jtocrr.2024.100684","DOIUrl":"10.1016/j.jtocrr.2024.100684","url":null,"abstract":"<div><h3>Introduction</h3><p>Early lung cancer detection programs improve surgical resection rates and survival but may skew toward more indolent cancers.</p></div><div><h3>Methods</h3><p>Hypothesizing that differences in stage-stratified survival indicate differences in biological aggressiveness and possible length-time and overdiagnosis bias, we assessed a cohort who had curative-intent resection, categorized by diagnostic pathways: screening, incidental pulmonary nodule program, and non–program based. Survival was analyzed using Kaplan-Meier plots, log-rank tests, and Cox regression, comparing aggregate and stage-stratified survival across cohorts with Tukey’s method for multiple testing.</p></div><div><h3>Results</h3><p>Of 1588 patients, 111 patients (7%), 357 patients (22.5%), and 1120 patients (70.5%) were diagnosed through screening, pulmonary nodule, and non–program-based pathways; 0% versus 9% versus 6% were older than 80 years (<em>p</em> = 0.0048); 17%, 23%, and 24% had a Charlson Comorbidity score greater than or equal to 2 (<em>p</em> = 0.0143); 7%, 6%, and 9% had lepidic adenocarcinoma; 26%, 31%, and 34% had poorly or undifferentiated tumors (<em>p</em> = 0.1544); and 93%, 87%, and 77% had clinical stage I (<em>p</em> &lt; 0.0001).</p><p>Aggregate 5-year survival was 87%, 72%, and 65% (<em>p</em> = 0.0009), including 95%, 74%, and 74% for pathologic stage I. Adjusted pairwise comparisons showed similar survival in screening and nodule program cohorts (<em>p</em> = 0.9905). Nevertheless, differences were significant between screening and non–program-based cohorts (<em>p</em> = 0.0007, adjusted hazard ratio 0.33 [95% confidence interval: 0.18–0.6]) and between nodule and nonprogram cohorts (adjusted hazard ratio 0.77 [95% confidence interval: 0.61–0.99]). Stage I comparisons yielded <em>p</em> = 0.2256, 0.1131, and 0.911. In respective pathways, 0%, 2%, and 2% of patients with stage I disease who were older than 80 years had a Charlson score greater than or equal to 2 (<em>p</em> = 0.3849).</p></div><div><h3>Conclusions</h3><p>Neither length-time nor overdiagnosis bias was evident in NSCLC diagnosed through screening or incidental pulmonary nodule programs.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 8","pages":"Article 100684"},"PeriodicalIF":3.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364324000547/pdfft?md5=fe71fffad0f93d3e07e846b753b44c5b&pid=1-s2.0-S2666364324000547-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141032750","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":"What Is the Accuracy of Clinical Staging for Stage III-Single-station N2 NSCLC? A Multi-Centre UK Study","authors":"Christopher Craig MBChB ,&nbsp;Janet Johnston M.B.B.S. ,&nbsp;Patrick Goodley MB BChir ,&nbsp;Paul Bishop BA, MB BCh, FRCPath ,&nbsp;Haider Al-Najjar MBChB, FRCP ,&nbsp;Louise Brown MD, MRCP ,&nbsp;Joanna Gallagher MBChB ,&nbsp;Ramachandran Sundar M.B.B.S. ,&nbsp;Sara Upperton MBChB ,&nbsp;Matthew Callister BM BCh ,&nbsp;David Meek BM, MRCP SCE ,&nbsp;Laura Succony BM ,&nbsp;Wadood Parvez M.B.B.S. ,&nbsp;Muhammad Tufail M.B.B.S., FRCP ,&nbsp;Geeshath Jayasekera MBChB, MRCP, PhD ,&nbsp;John Maclay MBChB ,&nbsp;Alana Livesey MB BChir ,&nbsp;Ian Woolhouse M.B.B.S. ,&nbsp;Natalie Smith BSc, MBChB ,&nbsp;Anna Bibby MBChB, PhD ,&nbsp;Matthew Evison MD, MRCP, MBChB","doi":"10.1016/j.jtocrr.2024.100694","DOIUrl":"10.1016/j.jtocrr.2024.100694","url":null,"abstract":"<div><h3>Introduction</h3><p>Single-station N2 (ssN2) versus multi-station N2 has been used as a selection criterion for treatment recommendations between surgical versus non-surgical multimodality treatment in stage III-N2 NSCLC. We hypothesized that clinical staging would be susceptible to upstaging on pathologic staging and, therefore, challenge this practice.</p></div><div><h3>Methods</h3><p>A retrospective study of prospectively collected routine clinical data for patients with stage III-N2 NSCLC that had completed computed tomography (CT), positron emission tomography (PET), and staging endobronchial ultrasound (EBUS) and had been confirmed clinical stage III-ssN2 at multidisciplinary team discussion and went on to complete surgical resection as the first treatment to provide pathologic staging. The study was completed in two cohorts (A) across a single cancer alliance in England (Greater Manchester) January 1, 2015 to December 31, 2018 and (B) across five United Kingdom centers to validate the findings in part A January 1, 2016 to December 31, 2020.</p></div><div><h3>Results</h3><p>A total of 115 patients met the inclusion criteria across cohort A (56 patients) and cohort B (59 patients) across 15 United Kingdom hospitals. The proportion of cases in which clinical stage III-ssN2 was upstaged to pathologic stage III-multi-station N2 was 34% (19 of 56) in cohort A, 32% in cohort B (19 of 59), and 33% across the combined study cohort (38 of 115). Most patients had a single radiologically abnormal lymph node on CT and PET (88%, 105 of 115). In the majority, the reasons for missed N2 disease on staging EBUS were due to inaccessible (stations 5, 6, 8, 9) N2 nodes at EBUS (34%, 13 of 38) and accessible lymph nodes not sampled during staging EBUS as not meeting sampling threshold (40%, 15 of 38) rather than false-negative sampling during EBUS (26%, 10 of 38).</p></div><div><h3>Conclusions</h3><p>During multidisciplinary team discussions, clinicians must be aware that one-third of patients with stage III-ssN2 on the basis of CT, PET, and staging EBUS do not truly have ssN2 and this questions the use of this criterion to define treatment recommendations.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 8","pages":"Article 100694"},"PeriodicalIF":3.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S266636432400064X/pdfft?md5=e1d99c1775c09c768cbd9f7b6d17a11b&pid=1-s2.0-S266636432400064X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141954595","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":"Characteristics of Long-Term Survivors With EGFR-Mutant Metastatic NSCLC","authors":"","doi":"10.1016/j.jtocrr.2024.100669","DOIUrl":"10.1016/j.jtocrr.2024.100669","url":null,"abstract":"<div><h3>Introduction</h3><p>Characteristics of long-term survivors in EGFR-mutant (EGFRm) NSCLC are not fully understood. This retrospective analysis evaluated a multi-institution cohort of patients with EGFRm NSCLC treated in the pre-osimertinib era and sought to describe characteristics of long-term survivors.</p></div><div><h3>Methods</h3><p>Clinical characteristics and outcomes were abstracted from the electronic medical records of patients with EGFRm metastatic NSCLC who started first-line therapy before 2015. Demographics and comutations were compared between greater than or equal to 5-year survivors and less than 5-year survivors. Multivariable Cox proportional hazard and logistic regression models were used to evaluate factors associated with survival and the odds of death within 5 years, respectively.</p></div><div><h3>Results</h3><p>Overall, 133 patients were greater than or equal to 5-year survivors; 127 were less than 5-year survivors. Burden of pathogenic comutations including TP53 and PIK3CA was similar between greater than or equal to 5-year survivors and less than 5-year survivors. Receipt of first-line chemotherapy rather than EGFR tyrosine kinase inhibitor was similar between the groups (22% of &lt;5-y versus 31% of ≥5-y). Baseline brain metastasis and history of smoking were associated with higher odds of death within 5 years (odds ratio = 2.16, <em>p</em> = 0.029 and odds ratio = 1.90, <em>p</em> = 0.046, respectively). Among patients without baseline brain metastases, cumulative incidence of brain metastases at 5 years was 42.3%. Both baseline and post-baseline brain metastasis were associated with worse overall survival compared with no brain metastasis (hazard ratio = 3.26, <em>p</em> &lt; 0.001 and hazard ratio = 4.99, <em>p</em> &lt; 0.001, respectively).</p></div><div><h3>Conclusions</h3><p>Within patients treated for EGFRm metastatic NSCLC before 2015, absence of brain metastasis and nonsmoking status were predictive of 5-year survival. Our findings help to define a subset of patients with EGFRm NSCLC with excellent survival outcomes who may not require intensification of initial therapy.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 8","pages":"Article 100669"},"PeriodicalIF":3.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364324000390/pdfft?md5=7beef34d332e2623a0877e47948d1c1b&pid=1-s2.0-S2666364324000390-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140400551","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 I Trial of Atezolizumab and Varlilumab in Combination With Radiation in Patients With Metastatic NSCLC","authors":"Jyoti Malhotra MD, MPH ,&nbsp;Yong Lin PhD ,&nbsp;Malini Patel MD ,&nbsp;Michael J. Yellin MD ,&nbsp;Emmanuel Zachariah PhD ,&nbsp;Curtis Krier PhD ,&nbsp;Ankit Saxena PhD ,&nbsp;Salma K. Jabbour MD","doi":"10.1016/j.jtocrr.2024.100687","DOIUrl":"10.1016/j.jtocrr.2024.100687","url":null,"abstract":"<div><h3>Introduction</h3><p>Anti-programmed cell death 1 (PD-1) immunotherapy is the standard of care for metastatic NSCLC but many tumors develop resistance. We hypothesized that combining a T-cell agonist such as varlilumab (anti-CD27 antibody) with checkpoint inhibition may be synergistic and this synergy may be potentiated further by using targeted radiation (RT).</p></div><div><h3>Methods</h3><p>We conducted an open-label, single-center, phase I trial (NCT04081688) to determine the safety and clinical benefit of the atezolizumab and varlilumab in combination with palliative RT in patients with advanced or metastatic NSCLC with progression on prior programmed cell death ligand 1therapy. On day 1 of each 21-day cycle, patients received varlilumab followed by atezolizumab on day 2. RT to a lung lesion was administered between cycle 1 and cycle 2.</p></div><div><h3>Results</h3><p>A total of 15 patients were enrolled (one patient did not start treatment). The median age was 64 years; 10 patients were female. Eight patients (57%) had at least one treatment-related adverse event (AE) and 7 (50%) had at least one grade III or worse treatment-related AE. There was only one grade III immune-related AE requiring steroids (1 diarrhea and colitis); there were no treatment-related deaths. Of the 12 patients evaluable for efficacy, three patients had stable disease (2 with stable disease &gt; 4 mo) and the clinical benefit rate was 25%. The median progression-free survival was two months and the median overall survival was 6.4 months.</p></div><div><h3>Conclusions</h3><p>Varlilumab in combination with atezolizumab and RT was safe and well tolerated; no additional signal was identified for toxicity. Clinical activity for the combination was modest with 25% of patients with stable disease as the best response.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 8","pages":"Article 100687"},"PeriodicalIF":3.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364324000572/pdfft?md5=6104558ad0c5aa0670e2088012026883&pid=1-s2.0-S2666364324000572-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141954642","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":"The Overlooked Cornerstone in Precise Medicine: Personalized Postoperative Surveillance Plan for NSCLC","authors":"Chenyu Jiang MD ,&nbsp;Yang Zhang MD ,&nbsp;Penghao Deng MD ,&nbsp;Han Lin MD ,&nbsp;Fangqiu Fu MD ,&nbsp;Chaoqiang Deng MD ,&nbsp;Haiquan Chen MD, PhD","doi":"10.1016/j.jtocrr.2024.100701","DOIUrl":"10.1016/j.jtocrr.2024.100701","url":null,"abstract":"<div><p>Non-small cell lung cancer recurrence after curative-intent surgery remains a challenge despite advancements in treatment. We review postoperative surveillance strategies and their impact on overall survival, highlighting recommendations from clinical guidelines and controversies. Studies suggest no clear benefit from more intensive imaging, whereas computed tomography scans reveal promise in detecting recurrence. For early-stage disease, including ground-glass opacities and adenocarcinoma in situ or minimally invasive adenocarcinoma, less frequent surveillance may suffice owing to favorable prognosis. Liquid biopsy, especially circulating tumor deoxyribonucleic acid, holds potential for detecting minimal residual disease. Clinicopathologic factors and genomic profiles can also provide information about site-specific metastases. Machine learning may enable personalized surveillance plans on the basis of multi-omics data. Although precision medicine transforms non-small cell lung cancer treatment, optimizing surveillance strategies remains essential. Tailored surveillance strategies and emerging technologies may enhance early detection and improve patients’ survival, necessitating further research for evidence-based protocols.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 8","pages":"Article 100701"},"PeriodicalIF":3.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364324000717/pdfft?md5=ea3804e17d8c2f249d9023aef03a4942&pid=1-s2.0-S2666364324000717-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141961913","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}