JTO Clinical and Research Reports最新文献

{"title":"Real-World Treatment and Outcomes in ALK-Rearranged NSCLC: Results From a Large U.S.-Based Database","authors":"","doi":"10.1016/j.jtocrr.2024.100662","DOIUrl":"10.1016/j.jtocrr.2024.100662","url":null,"abstract":"<div><h3>Introduction</h3><p><em>ALK–</em>rearranged advanced NSCLC (aNSCLC) represents 4% of all NSCLCs, and multiple ALK-targeted therapies (ALK-inhibitors) are now available for use. Little is known about changes in treatment patterns, or how prognostic factors and sequence of therapy may impact overall survival in the real-world setting. We aim to describe initial and subsequent treatments used, survival outcomes, prognostic factors, and the impact of treatment on overall survival in the largest (N = 739) real-world cohort of patients with ALK+ aNSCLC reported in the literature.</p></div><div><h3>Methods</h3><p>Retrospective observational cohort study with data drawn from a U.S.-based electronic health record–derived, deidentified database. Eligible patients were diagnosed with ALK+ aNSCLC between 2011-2020 and were treated in multiple different cancer clinics and across multiple geographic regions throughout the United States.</p></div><div><h3>Results</h3><p>From a cohort of 63,667 patients with aNSCLC, 739 patients with ALK+ NSCLC were eligible for analysis, median age was 63 years, 54% patients were female, and 85% were managed in community setting. More than 168 different treatment sequences were observed, and treatment utilization changed over time. Cohort median overall survival was 37 months (95% confidence interval: 33–45). Positive prognostic factors were as follows: never-smoking history, younger age, treatment in an academic setting, and initial early stage at diagnosis. Initial treatment with a second-generation ALK-inhibitor was associated with improved survival compared with chemotherapy.</p></div><div><h3>Conclusions</h3><p>For people with ALK+ aNSCLC, this study has identified several important clinical prognostic factors and is practice affirming; first-line treatment with a second-generation ALK-inhibitor improves survival compared with chemotherapy.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 8","pages":"Article 100662"},"PeriodicalIF":3.0,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364324000328/pdfft?md5=f57f80cfebffaae1dc6256f5d66f5534&pid=1-s2.0-S2666364324000328-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140282011","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: Understanding Program-Level Impact of COVID-19 in Lung Cancer Screening Programs in the United States","authors":"Valeda Yong MD, MSEd ,&nbsp;Lynde Lutzow MD, MPH ,&nbsp;Andrew Ciupek PhD ,&nbsp;Angela Criswell MA ,&nbsp;Jennifer C. King PhD ,&nbsp;Grace X. Ma PhD ,&nbsp;Cherie P. Erkmen MD","doi":"10.1016/j.jtocrr.2024.100709","DOIUrl":"10.1016/j.jtocrr.2024.100709","url":null,"abstract":"<div><h3>Introduction</h3><p>Lung cancer screening (LCS) reduces lung cancer mortality, yet uptake pre– and post–coronavirus disease 2019 (COVID-19) remains low. The impact of COVID-19 on LCS programs across the United States is unknown. Ours is the first multi-institutional study to identify barriers to LCS experienced during the pandemic. Our work will hopefully inform the development of targeted resources to facilitate increased uptake of LCS.</p></div><div><h3>Methods</h3><p>A nationwide survey of Centers of Excellence (SCOE) in LCS was conducted by GO2 for Lung Cancer Foundation. In 2021, survey items included questions regarding program structure, screening rates, and systemic barriers to LCS delivery experienced amid COVID-19.</p></div><div><h3>Results</h3><p>A total of 99 programs representing 1112 screening sites responded. A median of 868 patients were screened during the year of 2020. Patient recruitment, patient education, and in-person service access were negatively affected by COVID-19, whereas the use of telemedicine was positively affected. Coordination of care and timely reporting of results were largely unaffected by the pandemic.</p></div><div><h3>Conclusions</h3><p>Our findings provide a real-world snapshot of how COVID-19 affected LCS from a program perspective. These findings highlight ongoing challenges with educating and engaging those at high risk for lung cancer in LCS. Program resources should be directed toward increasing adherence to LCS among eligible patients.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 10","pages":"Article 100709"},"PeriodicalIF":3.0,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364324000791/pdfft?md5=67fe24a9b0ff142f49b80fe608f91f3c&pid=1-s2.0-S2666364324000791-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142241860","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":"Antibiotic Use and Survival in Patients With Late-Stage NSCLC Treated With Chemoimmunotherapy","authors":"Emanuela Taioli MD, PhD ,&nbsp;Raja M. Flores MD ,&nbsp;Arwa Abdelhamid MPH ,&nbsp;Matthew Untalan MPH ,&nbsp;Tara Ivic-Pavlicic MPH ,&nbsp;Stephanie Tuminello PhD, MPH","doi":"10.1016/j.jtocrr.2024.100710","DOIUrl":"10.1016/j.jtocrr.2024.100710","url":null,"abstract":"<div><h3>Introduction</h3><div>Immunotherapy has improved survival in patients with advanced NSCLC. Efficacy may decrease when patients are treated with antibiotics, possibly due to gut microbiome disruption, but few studies have investigated this using real-world, patient-level populations in the United States.</div></div><div><h3>Methods</h3><div>We have analyzed antibiotic use in patients with stage IV first, primary NSCLC diagnosed in 2015 and treated with chemotherapy or chemoimmunotherapy, drawn from the Surveillance, Epidemiology, and End Results-Medicare data set. Patients had to have continuous part A, part B, and part D Medicare coverage. Survival was determined through Kaplan-Meier and Cox proportional hazards models. All data analyses were performed using SAS.</div></div><div><h3>Results</h3><div>The study included 788 patients, 440 (56%) of whom received antibiotics within 2 months before or after starting systemic treatment. The median follow-up time was 11.64 months. There was a statistically significant difference in survival for patients who received antibiotics (<em>p</em> = 0.007) and who had more than 1 round of antibiotics versus zero or 1 round (<em>p</em> &lt; 0.0001). After adjustment, receipt of antibiotics (hazard ratio [HR]_adj: 1.17, 95% confidence interval [CI]: 0.99–1.37) and receipt of multiple rounds of antibiotics (HR_adj: 1.35, 95% CI: 1.14–1.60) were statistically significantly associated with worse survival. Among just those receiving chemoimmunotherapy (n = 203; 26%), there was still an increased risk of death for those receiving multiple antibiotic rounds (HR_adj: 1.52, 95% CI: 1.09–2.13).</div></div><div><h3>Conclusions</h3><div>Antibiotic use concurrent with chemoimmunotherapy seems to be associated with worse survival. This is more pronounced when more cycles of antibiotics are given.</div></div><div><h3>IRB approval number</h3><div>STUDY-19-00500.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 12","pages":"Article 100710"},"PeriodicalIF":3.0,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142577760","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":"Tarlatamab for Large Cell Neuroendocrine Carcinoma in a Young Adult: A Case Report","authors":"Shetal A. Patel MD, PhD ,&nbsp;Young Whang MD, PhD ,&nbsp;Chaely Medley NP ,&nbsp;Kevin Chen PharmD ,&nbsp;Jasmine Jordan BS ,&nbsp;Dante Bortone PhD ,&nbsp;Benjamin Vincent MD, PhD ,&nbsp;Jared Weiss MD","doi":"10.1016/j.jtocrr.2024.100712","DOIUrl":"10.1016/j.jtocrr.2024.100712","url":null,"abstract":"<div><p>A 20-year-old man with metastatic large cell neuroendocrine carcinoma of the lung was treated with the delta-like ligand 3–targeting bispecific T cell engager, tarlatamab. Treatment was complicated by transient cytokine release syndrome but resulted in a partial response. Bispecific T cell engagers may offer a novel treatment approach for large cell neuroendocrine carcinoma of the lung.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 10","pages":"Article 100712"},"PeriodicalIF":3.0,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364324000821/pdfft?md5=e7a77021a0e8cd2cd380bfac2c94fab0&pid=1-s2.0-S2666364324000821-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142161829","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":"Immune Cell Dynamics in EGFR-Mutated NSCLC Treated With Afatinib and Pembrolizumab: Results From a Phase IB Study","authors":"Jonathan W. Riess MD ,&nbsp;Matthew S. Lara BS ,&nbsp;Miguel Lopez de Rodas MD ,&nbsp;Guillaume Luxardi PhD ,&nbsp;Samantha Herbert MSPH ,&nbsp;Michiko Shimoda PhD ,&nbsp;Karen Kelly MD ,&nbsp;Alexander Meerlev PhD ,&nbsp;Elizabeth Moore MD ,&nbsp;Laurel Beckett PhD ,&nbsp;Arta Monjazeb MD, PhD ,&nbsp;Kurt Schalper MD, PhD ,&nbsp;Emanual Maverakis MD ,&nbsp;David R. Gandara MD","doi":"10.1016/j.jtocrr.2024.100706","DOIUrl":"10.1016/j.jtocrr.2024.100706","url":null,"abstract":"<div><h3>Introduction</h3><p>EGFR-mutated NSCLC is minimally responsive to programmed cell death protein 1 or programmed death-ligand 1 blockade. We evaluated the safety, tolerability, and immunomodulatory effects of the EGFR tyrosine kinase inhibitor (TKI) afatinib in combination with the programmed cell death protein 1 antibody pembrolizumab in patients with EGFR-mutant NSCLC.</p></div><div><h3>Methods</h3><p>Patients with advanced EGFR-mutant NSCLC with progression (PD) on previous EGFR TKI(s), aged above or equal to 18 years, Eastern Cooperative Oncology Group performance status less than or equal to 1, acceptable organ function, no significant autoimmune disease, measurable disease, and controlled brain metastases were eligible. Primary end point was determination of the maximum tolerated dose and recommended phase 2 dose. Serial specimens were collected to assess for alterations in cytokines and immune cell subsets by quantitative immunofluorescence in tissue and Luminex and flow cytometry in the blood.</p></div><div><h3>Results</h3><p>A total of 11 patients were enrolled, six in dose finding and five in dose expansion. No dose-limiting toxicities were observed. The maximum tolerated dose was determined to be afatinib 40 mg orally daily and pembrolizumab 200 mg intravenously every 21 days. Four (36%) patients had immune-related adverse events (irAEs). Ten patients were assessable for response: two partial response, seven stable disease, and one PD. Peripheral natural killer and natural killer T-cells (<em>p</em> = 0.027, <em>p</em> = 0.01) increased and exhausted CD8+ T-cells decreased on treatment (<em>p</em> = 0.0035). Peripheral CD4/CD8 T-cells (area under the curve = 0.96, <em>p</em> = 0.042) and central memory T-cells (CD4/CD8) (area under the curve = 1.0, <em>p</em> = 0.0006) increased in patients who had disease control more than 6 months or partial response to afatinib/pembrolizumab as did CD3+ T-cells in a patient with progression-free survival more than 6 months after afatinib/pembrolizumab treatment.</p></div><div><h3>Conclusions</h3><p>Afatinib and pembrolizumab were found to have modest activity associated with irAEs after PD on previous EGFR TKI setting. Proinflammatory changes in immune cell subsets in tissue and blood were detected and associated with antitumor activity and irAEs.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 10","pages":"Article 100706"},"PeriodicalIF":3.0,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364324000766/pdfft?md5=ce13645fd6b07f36ed9026d955d00ade&pid=1-s2.0-S2666364324000766-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141713891","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":"Identifying Novel Germline Mutations and Copy Number Variations in Patients With SCLC","authors":"Sami Ul Haq MSc ,&nbsp;Gregory Downs PhD ,&nbsp;Luna Jia Zhan MPH ,&nbsp;Sabine Schmid MD ,&nbsp;Devalben Patel BSc ,&nbsp;Danielle Sacdalan MD ,&nbsp;Janice J.N. Li BSc ,&nbsp;Dangxiao Cheng PhD ,&nbsp;Nicolas Meti MD ,&nbsp;Vivek Philip MSc, PhD ,&nbsp;Raymond H. Kim MD, PhD ,&nbsp;Geoffrey Liu MSc, MD ,&nbsp;Scott V. Bratman MD, PhD ,&nbsp;Peter J.B. Sabatini PhD ,&nbsp;Benjamin H. Lok MD","doi":"10.1016/j.jtocrr.2024.100702","DOIUrl":"10.1016/j.jtocrr.2024.100702","url":null,"abstract":"<div><h3>Introduction</h3><div>SCLC has traditionally been considered to arise from toxic exposure factors, such as smoking. Recent evidence has revealed that germline mutations may also affect the development of SCLC; however, these alterations remain understudied. We sought to identify novel germline mutations in SCLC including germline copy number variations (CNVs) in our cohort of patients.</div></div><div><h3>Methods</h3><div>We designed a custom hybrid-capture gene panel to evaluate germline alterations in 192 cancer-predisposition and frequently mutated genes in SCLC. We applied this panel to germline analysis of a treatment-naive cohort of 67 patients with SCLC at our institution. Subsequently, we annotated the variants using the American College of Medical Genetics criteria and further classified variants of uncertain significance using a set of in silico tools, including DeepMind AlphaMissense, MutationTaster, SIFT, and Polyphen2.</div></div><div><h3>Results</h3><div>We identified American College of Medical Genetics pathogenic or likely pathogenic alterations in seven of 67 patients. Five (71%) were novel alterations (<em>BCORL1</em>, <em>FANCC</em>, <em>ATR</em>, and <em>BBC3</em>) and a novel CNV (<em>SLFN11</em>) with two (29%) previously described mutations (<em>CHEK1</em> and <em>BRIP1</em>). We also identified 191 variants of uncertain significance in 60 of 67 patients, of which, depending on the in silico tool, 5% to 14% were predicted to be pathogenic. Patients with SCLC with the seven pathogenic alterations were observed to have a numerically longer overall survival (hazard ratio = 0.50) and progression-free survival (hazard ratio = 0.45) though not statistically significant compared with the remaining cohort.</div></div><div><h3>Conclusions</h3><div>Our study identifies novel germline alterations, including a CNV, and provides additional evidence that germline factors could be important contributing factors to the development of SCLC.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 12","pages":"Article 100702"},"PeriodicalIF":3.0,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142653718","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":"Combination of Cytologic Findings and Circulating Tumor DNA From Cerebrospinal Fluid Revealed SCLC Transformation in Patients With Leptomeningeal Metastases of Lung Adenocarcinoma","authors":"Jia-Xin Lin PhD ,&nbsp;Kai Yin PhD ,&nbsp;Li-Xu Yan PhD ,&nbsp;Mei-Mei Zheng PhD ,&nbsp;Yang-Si Li PhD ,&nbsp;Shi-Ling Zhang MS ,&nbsp;Kang-Hui Zeng MS ,&nbsp;Hong-Hong Yan MS ,&nbsp;Hai-Yan Tu PhD ,&nbsp;Zhi-Hong Chen MS ,&nbsp;Xu-Chao Zhang PhD ,&nbsp;Qing Zhou PhD ,&nbsp;Jin-Ji Yang PhD ,&nbsp;Ben-Yuan Jiang PhD ,&nbsp;Qing-Ling Zhang PhD ,&nbsp;Yi-Long Wu MD","doi":"10.1016/j.jtocrr.2024.100704","DOIUrl":"10.1016/j.jtocrr.2024.100704","url":null,"abstract":"<div><h3>Introduction</h3><p>Transformation to SCLC is a resistance mechanism to tyrosine kinase inhibitor in <em>EGFR</em>-mutated lung adenocarcinoma (LUAD). Nevertheless, the clinical and molecular features of SCLC transformation in LUAD with leptomeningeal metastases (LM) are scarce.</p></div><div><h3>Methods</h3><p>We retrospectively collected 237 patients with NSCLC who underwent lumbar puncture owing to suggestion of LM. All SCLC transformation in cerebrospinal fluid (CSF) was confirmed by two experienced pathologists using cytologic evaluation. CSF circulating tumor DNA (ctDNA) was tested by next-generation sequencing.</p></div><div><h3>Results</h3><p>Tumor cells in CSF samples were found in 111 patients (111 of 237, 46.8%), and eight cases (eight of 111, 7.2%) were identified as having SCLC cells in CSF. Seven patients carried the <em>EGFR</em> mutation, including four patients with <em>EGFR exon 19 deletion</em> and three patients with <em>EGFR</em> <em>exon</em> <em>21 L858R</em> mutation. Another patient harbored <em>ERBB2</em> insertion. Seven of these patients were resistant to targeted therapy. CSF ctDNA analysis reported that <em>TP53</em> and <em>RB1</em> mutations were common. The median time from the diagnosis of advanced NSCLC to SCLC transformation found in CSF was 9.7 months (95% confidence interval [CI]: 4.0–17.5 mo). The median overall survival since the initial diagnosis of metastatic NSCLC was 15.3 months (95% CI: 1.2–29.4 mo). The median overall survival after SCLC transformation detected in CSF was 5.0 months (95% CI: 4.0–5.9 mo).</p></div><div><h3>Conclusions</h3><p>SCLC transformation may be revealed in CSF by both cytologic evaluation and ctDNA, not just in tissue that underwent rebiopsy. SCLC transformation of CSF is informative for resistance mechanism in patients with LUAD with LM on tyrosine kinase inhibitor progression, which was associated with poor survival.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 9","pages":"Article 100704"},"PeriodicalIF":3.0,"publicationDate":"2024-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364324000742/pdfft?md5=870ec4f4f2918aac97890cf20e833f5f&pid=1-s2.0-S2666364324000742-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141710322","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":"Reproducibility of Assessment of Lepidic (Noninvasive) Patterns in Lung Adenocarcinoma With Cytokeratin Immunostain Compared With Hematoxylin and Eosin and the Proposed New International Association for the Study of Lung Cancer (IASLC) Algorithm","authors":"Ellen Yang MD, FRCPC ,&nbsp;Najd Alshamlan MD ,&nbsp;Katrina Hueniken MSc ,&nbsp;Jessica Weiss MSc ,&nbsp;Michael Cabanero MD ,&nbsp;Ming-Sound Tsao MD, FRCPC","doi":"10.1016/j.jtocrr.2024.100682","DOIUrl":"10.1016/j.jtocrr.2024.100682","url":null,"abstract":"<div><h3>Introduction</h3><p>Lepidic growth is considered noninvasive in lung nonmucinous adenocarcinoma, whereas other patterns are invasive. Considerable interobserver variability in assessing “invasion” has been reported. We assessed the utility of cytokeratin 7 (CK7) stain and recently proposed International Association for the Study of Lung Cancer criteria to improve assessment of noninvasion in lung adenocarcinoma.</p></div><div><h3>Methods</h3><p>Four pathologists (two staff, two trainees) assessed 158 hematoxylin and eosin (HE)- and CK7-stained slides of 108 pT1N0-2 nonmucinous lung adenocarcinoma cases. Scoring took place in four rounds. First, sections were independently scored for percentage of noninvasive or probable noninvasive and invasive or probable invasive patterns. Second, after a consensus scoring algorithm for CK7 was formulated, the slides were rescored. Subsequent third-round scoring was conducted only on HE slides using the 2023 International Association for the Study of Lung Cancer proposed criteria, and fourth-round scoring on both HE and CK7 slides simultaneously. Intraclass correlation coefficient (ICC) was calculated for each round. Recurrence-free survival was assessed using Cox proportional hazards regression methods.</p></div><div><h3>Results</h3><p>In the first two rounds, interobserver concordance was consistently higher with CK7 (ICC range = 0.44–0.6) than HE (range = 0.24–0.49) scores. The IASLC proposed algorithm improved ICC of HE scores to 0.60 (95% confidence interval: 0.52–0.67), and round 4 HE and CK7 combined improved ICC to 0.75 (95% confidence interval: 0.70–0.80). Continuous measures of averaged noninvasive and probable noninvasive scores on HE were associated with improved recurrence-free survival (hazard ratio: 0.83–0.86).</p></div><div><h3>Conclusions</h3><p>CK7 staining consistently increased interobserver concordance in assessment of invasive versus noninvasive patterns than HE. Combining CK7 with the 2023 IASLC criteria for morphologic features of invasion may further improve the interobservers’ concordance for the recognition of lepidic growth in nonmucinous lung adenocarcinoma.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 7","pages":"Article 100682"},"PeriodicalIF":3.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364324000523/pdfft?md5=505547fe19126cb010ec9fc15e678934&pid=1-s2.0-S2666364324000523-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141042571","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":"Successful Lorlatinib Rechallenge After Severe Drug-Induced Psychosis in ALK-Positive Metastatic NSCLC: A Case Report","authors":"","doi":"10.1016/j.jtocrr.2024.100689","DOIUrl":"10.1016/j.jtocrr.2024.100689","url":null,"abstract":"<div><p>Neurocognitive adverse events (NAEs) have been reported in up to 60% of patients on lorlatinib, a potent central nervous system–active ALK inhibitor. Manifestations may include psychotic, mood, speech, and cognitive symptoms. Current guidance recommends permanent discontinuation of lorlatinib in cases of grade IV NAEs. Here, we report a case of successful rechallenge of dose-reduced lorlatinib after recovery of grade IV psychosis in a patient with ALK-positive NSCLC.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 7","pages":"Article 100689"},"PeriodicalIF":3.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364324000596/pdfft?md5=258aef7abde42af0bb09cd23862cb12a&pid=1-s2.0-S2666364324000596-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141033806","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":"Trophoblast Cell Surface Antigen 2 Expression in Thymic Carcinoma: Brief Report","authors":"Kana Kurokawa MD, PhD ,&nbsp;Tetsuhiko Asao MD, PhD ,&nbsp;Takuo Hayashi MD, PhD ,&nbsp;Satsuki Kishikawa MD, PhD ,&nbsp;Koichiro Kanamori MD, PhD ,&nbsp;Takehito Shukuya MD, PhD ,&nbsp;Yosuke Miyashita MD ,&nbsp;Ikuko Nakamura MD, PhD ,&nbsp;Taichi Miyawaki MD, PhD ,&nbsp;Ryota Kanemaru MD, PhD ,&nbsp;Tomoyasu Mimori MD, PhD ,&nbsp;Yoichiro Mitsuishi MD, PhD ,&nbsp;Ken Tajima MD, PhD ,&nbsp;Naoko Shimada MD, PhD ,&nbsp;Fumiyuki Takahashi MD, PhD ,&nbsp;Kazuya Takamochi MD, PhD ,&nbsp;Kenji Suzuki MD, PhD ,&nbsp;Kazuhisa Takahashi MD, PhD","doi":"10.1016/j.jtocrr.2024.100693","DOIUrl":"https://doi.org/10.1016/j.jtocrr.2024.100693","url":null,"abstract":"<div><h3>Introduction</h3><p>Trophoblast cell surface antigen 2 (TROP2) is a transmembrane glycoprotein overexpressed in various cancer types. Although TROP2-targeting therapy is currently attracting attention, little is known about TROP2 expression in thymic carcinoma.</p></div><div><h3>Methods</h3><p>TROP2 gene expression in thymic epithelial tumors was analyzed using RNA-sequencing (RNA-seq) data for 122 cases obtained from The Cancer Genome Atlas. Immunohistochemistry (IHC) staining with anti-TROP2 antibody (SP295) was performed in 26 cases of thymic carcinoma tissues surgically resected at Juntendo University.</p></div><div><h3>Results</h3><p>RNA-seq data analysis from The Cancer Genome Atlas revealed that <em>TACSTD2</em> (gene encoding TROP2) expression was significantly higher in thymic carcinoma than in thymoma (adjusted <em>p</em> = 6.64e-05). There was also a trend of increasing expression in the order of thymoma type B1, B2, B3, and thymic carcinoma. As for IHC in thymic carcinoma, TROP2 expression was localized to the membrane of cancer cells. Intensity 0, 1, and 2 was observed in six (23.1%), 11 (42.3%), and nine (34.6%) cases, respectively, leading to TROP2 positivity in 20 cases (76.9%). The median proportion of TROP2-positive tumor cells and the median H-score were 25.0% (range: 0%–100%) and 25.0 (range: 0–200), respectively. No relevant factors were identified in the analysis of TROP2 expression and patient background. Although not significant, high TROP2 expression (H-score ≥ 50) tended to be associated with shorter survival.</p></div><div><h3>Conclusions</h3><p>TROP2 expression in thymic carcinoma was confirmed by both RNA-seq and IHC, with high expression observed in IHC for intensity (76.9%) and proportion. TROP2 could be a potential target in thymic carcinoma.</p></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"5 7","pages":"Article 100693"},"PeriodicalIF":3.0,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666364324000638/pdfft?md5=1a7346fac754e5d1a82e44a3087f356b&pid=1-s2.0-S2666364324000638-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141480251","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}