JTO Clinical and Research Reports最新文献

{"title":"ALKTERNATE: A Pilot Study Alternating Lorlatinib With Crizotinib in ALK-Positive NSCLC With Prior ALK Inhibitor Resistance","authors":"Malinda Itchins BMedSci, M.B.B.S., FRACP, PhD ,&nbsp;Shirley Liang BSc ,&nbsp;Chris Brown MBiostats, BSc ,&nbsp;Tristan Barnes BSc (Med), M.B.B.S., FRACP ,&nbsp;Gavin Marx BSc, M.B.B.S., FRACP ,&nbsp;Venessa Chin M.B.B.S., FRACP, PhD ,&nbsp;Steven Kao BHB, MBChB, PhD, FRACP ,&nbsp;Po Yee Yip MBChB, FRACP, PhD ,&nbsp;Antony J. Mersiades BMedSc, M.B.B.S., FRACP, MMed (Clin. Epi) ,&nbsp;Adnan Nagrial M.B.B.S., FRACP, PhD ,&nbsp;Victoria Bray M.B.B.S., FRACP, PhD ,&nbsp;Geoffrey Peters BPharm, M.B.B.S., FRACP ,&nbsp;Sagun Parakh BSc, MBChB, FRACP, PhD ,&nbsp;Kavita Garg PhD ,&nbsp;Bob T. Li MD, PhD, MPH ,&nbsp;Matthew McKay PhD ,&nbsp;Kenneth O'Byrne M.B.B.S., FRACP, FRCPA, MD ,&nbsp;Thomas John M.B.B.S., FRACP, PhD ,&nbsp;Anthony J. Gill MD, FRCPA ,&nbsp;Mark P. Molloy PhD ,&nbsp;Nick Pavlakis BSc, M.B.B.S., MMed (Clin. Epi), PhD, FRACP","doi":"10.1016/j.jtocrr.2024.100703","DOIUrl":"10.1016/j.jtocrr.2024.100703","url":null,"abstract":"<div><h3>Introduction</h3><p>ALK-positive lung cancers represent a molecularly diverse disease. With drug exposure, driving selection pressure, and resistance pathways, disease relapse will emerge. There is compelling rationale to investigate novel treatment strategies, informed by dynamic circulating tumor DNA (ctDNA) monitoring.</p></div><div><h3>Methods</h3><p>The single-arm, pilot study ALKTERNATE investigated fixed alternating cycles of lorlatinib intercalated with crizotinib in individuals resistant to second-generation ALK inhibitors. Dynamic ctDNA explored the correlation with disease response and disease recurrence and defined disease resistance. The primary outcome was time-to-treatment failure, a composite of tolerability, feasibility, and efficacy. Secondary outcomes included standard survival measures, toxicity, pharmacokinetic analysis, and patient-reported outcomes. Tertiary outcomes were proteogenomic analyses of tissue and plasma.</p></div><div><h3>Results</h3><p>A total of 15 individuals were enrolled; three encountered primary resistance to lorlatinib induction. There were 12 participants who received alternating therapy, and this approach revealed safety, feasibility, and effectiveness. Patient-reported outcomes were maintained or improved on therapy, and toxicity was consistent with previous reports. The pharmacokinetic measures were similar to the single-arm drug experience. Median time-to-treatment failure was 10 months; overall survival was 23 months. ctDNA profiles indicated inferior survival in those with preexistent TP53 mutations and those without clear or cleared ctDNA at trial induction. The study defined a vastly heterogeneous population with an abundance of ALK coexisting with non-ALK resistance variants.</p></div><div><h3>Conclusions</h3><p>ALKTERNATE revealed feasibility with a novel alternating ALK inhibitor strategy in ALK-positive NSCLC. Results support progressing inquiry into this approach and propose a flexible design with drug(s) selected and alternating time frames, informed by real-time plasma profiling. Moving this concept to treatment naive may also optimize impact.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 9","pages":"Article 100703"},"PeriodicalIF":3.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364324000730/pdfft?md5=c1c8bdf6e1c23cf14396ae61494671f9&pid=1-s2.0-S2666364324000730-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141716515","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":"Effect of FDG PET-CT for Staging and Radiotherapy Planning – A Comparison of Cohorts From Two Randomized Trials of Thoracic Radiotherapy in Limited-Stage SCLC","authors":"","doi":"10.1016/j.jtocrr.2024.100688","DOIUrl":"10.1016/j.jtocrr.2024.100688","url":null,"abstract":"<div><h3>Introduction</h3><p>¹⁸F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) is recommended for staging and defining target volume in limited-stage SCLC, though the impact on outcomes compared with CT staging and elective nodal irradiation (ENI) is not well documented. We analyzed patients receiving 45 Gy/30 fractions in two randomized trials of thoracic radiotherapy (TRT) in limited-stage SCLC (HAST and THORA trials) to evaluate whether PET-CT for staging and radiotherapy planning reduces radiotoxicity and improves survival.</p></div><div><h3>Methods</h3><p>Patients in HAST were staged with CT of the thorax and upper abdomen and brain magnetic resonance imaging of the brain. Patients in THORA were staged with PET-CT in addition. All patients were to receive four courses of platinum/etoposide chemotherapy and concurrent TRT starting three to four weeks after the first chemotherapy course. In HAST, target volumes included pathological lesions on CT plus ENI of lymph node stations 4–7 (bilateral). In THORA, target volumes were limited to PET-CT-positive lesions (selective nodal irradiation [SNI]).</p></div><div><h3>Results</h3><p>A total of 149 patients were included (PET-CT/SNI: n = 76, CT/ENI: n=73); the median age was 64 years, 56% were women, 85% had PS 0 to 1, and 81% had stage III disease. The PET-CT/SNI group experienced less grade 3-4 esophagitis (18% versus 33%, <em>p</em> = 0.043), less grade &gt;=1 pneumonitis (5% versus 16%, <em>p</em> = 0.028), and less dysphagia after TRT (mean scores on European Organisation for Research and Treatment of Cancer 13-item lung cancer module: 45 versus 72). There was no difference in median overall survival (24 versus 25 mo, <em>p</em> = 0.59) or progression-free survival (11 versus 11 mo, <em>p</em> = 0.23).</p></div><div><h3>Conclusions</h3><p>Using PET-CT for staging and target volume definition of TRT reduces acute radiotoxicity but does not improve overall or progression-free survival in limited-stage SCLC.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 9","pages":"Article 100688"},"PeriodicalIF":3.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364324000584/pdfft?md5=bf75f29edc6b92975d18460f22eafb5e&pid=1-s2.0-S2666364324000584-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141047048","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 Brief Report of Lung Cancer Screening Utilization Before, During, and in the Later Stages of the COVID-19 Pandemic in the United States","authors":"Hermine Poghosyan PhD, MPH, FAAN ,&nbsp;Sayantani Sarkar PhD ,&nbsp;Ilana Richman MD, MHS ,&nbsp;Robert H. Pietrzak PhD, MPH ,&nbsp;Lisa Carter-Bawa PhD, MPH, APRN, ANP-C, FAAN ,&nbsp;Mary E. Cooley PhD, RN, FAAN","doi":"10.1016/j.jtocrr.2024.100705","DOIUrl":"10.1016/j.jtocrr.2024.100705","url":null,"abstract":"<div><h3>Introduction</h3><p>Although COVID-19 has affected health care and screening utilization, its impact on lung cancer screening (LCS) uptake remains unclear. Our study investigated LCS utilization and associated predictors among adults eligible for LCS before (2019), during (2020–2021), and at a later stage (2022) of COVID-19.</p></div><div><h3>Methods</h3><p>We used cross-sectional, nationally representative, population-based data from the Behavioral Risk Factor Surveillance System over 4 consecutive years: 2019 (n = 4484; weighted n = 1,559,37), 2020 (n = 1239; weighted n = 200,301), 2021 (n = 1673; weighted n = 668,359), and 2022 (n = 20,804; weighted n = 9,458,907). The outcome was self-reported LCS uptake (0 = did not have LCS in the past 12 mo and 1 = underwent LCS in the past 12 mo). We conducted weighted statistics and multivariable logistic regression.</p></div><div><h3>Results</h3><p>Overall, of 11,886,704 million individuals eligible for LCS, 2,129,900 received LCS in 4 years (2019–2022). National rates of LCS among individuals eligible for screening were 16.3% (95% confidence interval [CI]:14.4–18.5), 19.4% (95% CI:15.3–24.3), 18.3% (95% CI:15.6–21.3), and 18.1% (95% CI:17.1–19.2) in 2019, 2020, 2021, and 2022, respectively. Respondents reporting lung disease and cancer (other than lung cancer) history were more likely to receive LCS across all 4 years. During the pandemic (2020), Hispanic (versus White), and rural (versus urban) residents had lower odds of LCS utilization. In 2022, men had increased odds of reporting LCS use relative to women. No sex differences in LCS use were observed in previous years.</p></div><div><h3>Conclusions</h3><p>Our findings indicate consistently low LCS utilization (&lt;20%) over 4 years. Nationwide efforts to boost LCS awareness and utilization are essential for mitigating the lung cancer burden in the United States.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 9","pages":"Article 100705"},"PeriodicalIF":3.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364324000754/pdfft?md5=e7d83c19636d902394cdbac4aa9b92ae&pid=1-s2.0-S2666364324000754-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141712889","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":"Three-Year Overall Survival Outcomes and Correlative Analyses in Patients With NSCLC and High (50%–89%) Versus Very High (≥90%) Programmed Death-Ligand 1 Expression Treated With First-Line Pembrolizumab or Cemiplimab","authors":"","doi":"10.1016/j.jtocrr.2024.100675","DOIUrl":"10.1016/j.jtocrr.2024.100675","url":null,"abstract":"<div><h3>Introduction</h3><div>Responses to first-line programmed cell death protein 1 inhibition vary among patients with metastatic NSCLC and a programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) greater than or equal to 50%. We previously reported improved clinical outcomes to first-line programmed cell death protein 1 inhibition in patients with metastatic NSCLC with a PD-L1 TPS of greater than or equal to 90% versus 50% to 89% in a pilot study. Here, we report the three-year survival with first-line pembrolizumab and cemiplimab in two large independent cohorts of patients with PD-L1 TPS greater than or equal to 90% versus 50% to 89% and characterize genomic and immunophenotypic differences between these PD-L1 expression groups, which were largely unknown.</div></div><div><h3>Methods</h3><div>We analyzed three-year outcomes of the following two independent cohorts: (1) a multicenter cohort of patients from four academic centers in the United States treated with pembrolizumab and (2) EMPOWER-Lung 1, randomized, phase III trial comparing first-line cemiplimab with chemotherapy. Tumor genomic profiling and multiplexed immunofluorescence were performed to evaluate genomic and immunophenotypic correlates of very high PD-L1 expression.</div></div><div><h3>Results</h3><div>At three years of follow-up, progression-free survival (hazard ratio [HR], 0.69; <em>p</em> &lt; 0.001) and overall survival (HR, 0.70; <em>p</em> &lt; 0.01) to first-line commercial pembrolizumab were significantly improved in patients with a PD-L1 TPS greater than or equal to 90% versus 50% to 89%. In the EMPOWER-Lung 1, patients assigned to the cemiplimab arm with a PD-L1 TPS greater than or equal to 90% also had significant improvements in progression-free survival (HR, 0.53; <em>p</em> &lt; 0.0001) and overall survival (HR, 0.63; <em>p</em> = 0.007) compared with those with a PD-L1 of 50% to 89%. Tumor genomic profiling of 553 NSCLC samples revealed that mutations in <em>STK11</em> and <em>SMARCA4</em> were significantly more frequent in tumors with a PD-L1 TPS of 50% to 89% compared with those with a PD-L1 TPS greater than or equal to 90% (Q &lt; 0.15), whereas <em>BRCA2</em> was enriched in NSCLC samples with a PD-L1 TPS greater than or equal to 90% (Q &lt; 0.15). Multiplexed immunofluorescence on 93 NSCLC samples identified higher intratumoral CD8⁺PD1⁺ T cells (<em>p</em> = 0.02) in tumors with PD-L1 TPS greater than or equal to 90% versus 50% to 89%.</div></div><div><h3>Conclusion</h3><div>Pembrolizumab and cemiplimab were found to have long-term survival benefit and favorable genomic and immunophenotypic profile in patients with advanced NSCLC with PD-L1 TPS greater than or equal to 90% compared with TPS 50% to 89%.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 9","pages":"Article 100675"},"PeriodicalIF":3.0,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140786686","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":"Eftilagimod Alpha (a Soluble LAG-3 Protein) Combined With Pembrolizumab in Second-Line Metastatic NSCLC Refractory to Anti–Programmed Cell Death Protein 1/Programmed Death-Ligand 1-Based Therapy: Final Results from a Phase 2 Study","authors":"Matthew G. Krebs MD ,&nbsp;Martin Forster MD, PhD ,&nbsp;Margarita Majem MD, PhD ,&nbsp;Julio Peguero MD ,&nbsp;Wade Iams MD ,&nbsp;Tim Clay MD ,&nbsp;Patricia Roxburgh MD, PhD ,&nbsp;Bernard Doger MD, PhD ,&nbsp;Pawan Bajaj MD ,&nbsp;Andres Barba MD ,&nbsp;Suvini Perera MS ,&nbsp;Christian Mueller MS ,&nbsp;Frédéric Triebel MD, PhD","doi":"10.1016/j.jtocrr.2024.100725","DOIUrl":"10.1016/j.jtocrr.2024.100725","url":null,"abstract":"<div><h3>Introduction</h3><div>Eftilagimod alpha (efti), a soluble lymphocyte activation gene-3 protein, triggers antigen-presenting cell and T-cell (CD4⁺ and CD8⁺) activation and helps overcome resistance to programmed cell death protein 1 or programmed cell death-ligand 1 (PD-(L)1) inhibitors. We assessed efti plus pembrolizumab in second-line anti–PD-(L)1-refractory metastatic patients with NSCLC.</div></div><div><h3>Methods</h3><div>After confirmed progression on anti-PD-(L)1-based first-line therapy, patients received efti (30 mg subcutaneously every 2 weeks for eight 3-week cycles and then every 3 weeks for up to 54 weeks) plus pembrolizumab (200 mg intravenously every 3 weeks for up to 105 weeks). The primary endpoint was the objective response rate by modified Response Evaluation Criteria in Solid Tumors version 1.1 for immune-based therapies. Secondary endpoints included disease control rate, progression-free survival, overall survival (OS), and tolerability. Exploratory endpoints included tumor growth kinetics and predefined subgroup analyses. Programmed cell death-ligand 1 tumor proportion score was assessed centrally.</div></div><div><h3>Results</h3><div>Thirty-six patients were enrolled from April 2019 to August 2021 using Simon’s two-stage design. Most patients (81.8%) had low or negative (&lt;50%) PD-(L)1 tumor proportion score. First-line therapy was anti–PD-(L)1-based for all patients, combined with chemotherapy for 66.7%. The confirmed objective response and disease control rates were 8.3% and 33.3%. The median progression-free survival was 2.1 months and the median OS was 9.9 months. Patients exhibiting high PD-(L)1 expression or acquired resistance to PD-(L)1 inhibitors revealed superior response and survival outcomes, and OS was closely correlated with disease control. No treatment-emergent adverse event led to permanent discontinuation of study treatment.</div></div><div><h3>Conclusions</h3><div>Efti plus pembrolizumab was well-tolerated and revealed signs of antitumor activity in patients with NSCLC resistant to PD-(L)1 inhibitors, warranting further investigation. Trial registration number: NCT03625323.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 11","pages":"Article 100725"},"PeriodicalIF":3.0,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142358683","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":"Rearranged During Transfection Rearrangement Detection by Fluorescence In Situ Hybridization Compared With Other Techniques in NSCLC","authors":"Anne Mc Leer PhD ,&nbsp;Julie Mondet PharmD, PhD ,&nbsp;Nelly Magnat MSc ,&nbsp;Mailys Mersch MSc ,&nbsp;Diane Giovannini MD ,&nbsp;Camille Emprou MD ,&nbsp;Anne-Claire Toffart MD, PhD ,&nbsp;Nathalie Sturm MD, PhD ,&nbsp;Sylvie Lantuéjoul MD, PhD ,&nbsp;David Benito PhD","doi":"10.1016/j.jtocrr.2024.100714","DOIUrl":"10.1016/j.jtocrr.2024.100714","url":null,"abstract":"<div><h3>Introduction</h3><div><em>RET</em> rearrangements occur in 1% to 2% NSCLCs. Since no clinically validated RET antibody is currently available, fluorescence in situ hybridization (FISH) is often used as a screening tool to identify patients likely to benefit from RET-targeted therapy. In this study, we performed a comprehensive review of publications in which <em>RET</em>-rearrangement testing was performed by FISH and compared the methods and results with our data.</div></div><div><h3>Methods</h3><div>The findings of an electronic search for publications using <em>RET</em>-FISH in lung cancer were compared with the results obtained at the Grenoble University Hospital where 784 <em>EGFR</em><em>-</em>, <em>KRAS</em><em>-</em>, <em>ALK</em>-, and <em>ROS1</em>-negative NSCLCs were tested by <em>RET</em> break-apart FISH and confirmed by RNA-sequencing (RNA-seq).</div></div><div><h3>Results</h3><div>Out of the 85 publications using <em>RET</em>-FISH analysis, 52 pertained to patients with lung cancer. The most often used positivity threshold was 15%. Six publications compared <em>RET</em>-FISH with at least one other molecular technique on at least eight samples, and the concordance was variable, from 5.9% to 66.7% for FISH-positive cases. Regarding our data, out of the 784 analyzed samples, 32 (4%) were positive by <em>RET</em>-FISH. The concordance between <em>RET</em>-FISH and RNA-seq in <em>RET</em>-FISH positive samples was 69%.</div></div><div><h3>Conclusions</h3><div>Overall, both existing literature and our data suggest that <em>RET</em>-FISH testing can be used for rapid screening of <em>RET</em> rearrangements in NSCLC. Nevertheless, using an orthogonal technique such as RNA-seq to confirm <em>RET</em>-FISH-positive cases is essential for ensuring that only patients likely to benefit from <em>RET</em>-target therapy receive the treatment.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 12","pages":"Article 100714"},"PeriodicalIF":3.0,"publicationDate":"2024-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142534274","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":"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}