JTO Clinical and Research Reports最新文献

{"title":"Combination Therapy With MET Tyrosine Kinase Inhibitor and EGFR Tyrosine Kinase Inhibitor in Patients With MET-Overexpressed EGFR-Mutant Lung Adenocarcinoma","authors":"Jia-Jun Wu MD ,&nbsp;Zhe-Rong Zheng MD ,&nbsp;Tse-Hsien Lo MD ,&nbsp;Cheng-Hsiang Chu MD ,&nbsp;Kun-Chieh Chen MD, PhD ,&nbsp;Gee-Chen Chang MD, PhD","doi":"10.1016/j.jtocrr.2025.100832","DOIUrl":"10.1016/j.jtocrr.2025.100832","url":null,"abstract":"<div><h3>Introduction</h3><div>Dysregulated <em>MET</em> signaling, such as MET overexpression or <em>MET</em> amplification (<em>MET</em>amp), is a important mechanism of resistance to EGFR tyrosine kinase inhibitors (TKIs) in patients with <em>EGFR</em>-mutant lung adenocarcinoma (LUAD). Combination therapy with EGFR TKIs and MET TKIs has revealed efficacy in these patients. This study aimed to analyze the real-world experience of TKI combination in patients with <em>EGFR</em>-mutant MET-overexpressed LUAD.</div></div><div><h3>Methods</h3><div>This retrospective cohort study included patients with advanced <em>EGFR</em>-mutant LUAD who progressed after EGFR TKIs and were treated with combination therapy of EGFR TKIs and MET TKIs (capmatinib or tepotinib). Immunohistochemistry was used to detect MET overexpression.</div></div><div><h3>Results</h3><div>This study included 27 patients, with a median age of 69 years; 40.7% of the patients were male individuals, and 88.9% never smoked. Overall, the treatment response of the TKI combination reported 29.6% (eight of 27) partial response, 55.6% (15 of 27) stable disease, a median progression-free survival of 7.3 months, and an overall survival of 26.9 months. The adverse events were mostly grade 1 to 2, with only one patient experiencing a grade 3 or greater event, which was peripheral edema. The most common adverse events were hypoalbuminemia (44.4%), increased creatinine (44.4%), and peripheral edema (44.4%). Eight patients underwent next-generation sequencing analysis, and two (25.0%) of them had <em>MET</em>amp. Three patients (37.5%) had <em>TP53</em> mutations, which were the most common concurrent alterations. Those with positive <em>MET</em>amp had significantly longer median progression-free survival than those without (25.3 versus 5.8 mo; <em>p</em> = 0.034).</div></div><div><h3>Conclusions</h3><div>The TKI combination reported clinical activities in patients with advanced <em>EGFR</em>-mutant LUAD resistant to EGFR TKIs and mild toxicity in those with MET overexpression.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 6","pages":"Article 100832"},"PeriodicalIF":3.0,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143912809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Outcomes in Patients With Resectable Stage III NSCLC Who Did Not Have Definitive Surgery After Neoadjuvant Treatment—A Retrospective Analysis of the SAKK Trials 16/96, 16/00, 16/01, 16/08, and 16/14: A Brief Report","authors":"Sabine Raimann MD ,&nbsp;Sämi Schär PhD ,&nbsp;Stefanie Hayoz PhD ,&nbsp;Matthias Guckenberger MD ,&nbsp;Tobias Finazzi MD, PhD ,&nbsp;Isabelle Opitz MD ,&nbsp;Sabine Schmid MD ,&nbsp;Michael Mark MD ,&nbsp;Alfredo Addeo MD ,&nbsp;Laetitia A. Mauti MD, PhD ,&nbsp;Daniel C. Betticher MD ,&nbsp;Hans-Beat Ris MD ,&nbsp;Roger Stupp MD ,&nbsp;Alessandra Curioni-Fontecedro MD ,&nbsp;Solange Peters MD, PhD ,&nbsp;Martin Früh MD ,&nbsp;Sacha I. Rothschild MD, PhD ,&nbsp;Miklos Pless MD ,&nbsp;David König MD","doi":"10.1016/j.jtocrr.2025.100834","DOIUrl":"10.1016/j.jtocrr.2025.100834","url":null,"abstract":"<div><h3>Introduction</h3><div>Neoadjuvant or perioperative treatment, including an immune checkpoint inhibitor (ICI), has emerged as a new standard for patients with resectable stage III NSCLC. Nevertheless, approximately 20% of patients who start neoadjuvant chemo-immunotherapy will not undergo definitive surgery. Little is known about these patients.</div></div><div><h3>Methods</h3><div>We analyzed outcomes of patients without definitive surgery from five Swiss Group for Clinical Cancer Research (SAKK) trials that investigated different neoadjuvant treatment modalities in patients with resectable stage III-N2 NSCLC. Study treatment included neoadjuvant cisplatin-docetaxel chemotherapy (with or without radiotherapy), either combined with peri-operative durvalumab in the SAKK 16/14 trial (n = 68) or without an ICI (non-ICI trials, n = 431).</div></div><div><h3>Results</h3><div>Of the 499 patients, 102 (20%) did not have definitive surgery. Cancellation of surgery occurred in a similar proportion of patients with or without neoadjuvant ICI (19% versus 21%, <em>p</em> = 0.9). Reasons were in non-ICI trials and SAKK 16/14: disease progression (47% and 54%), nonresectability (18% and 8%), medical reasons (17% and 31%), and unknown (18% and 8%), respectively. Of these patients, no patient in SAKK 16/14 and 17 patients (19%) in the non-ICI trials received curative-intended salvage therapy. Three-year overall survival was higher in patients who had definitive surgery compared with those who did not: 78% versus 32% (SAKK 16/14) and 54% versus 10% (non-ICI trials).</div></div><div><h3>Conclusions</h3><div>In our pooled analysis, patients with definitive surgery had higher survival rates than those without definitive surgery. Prognosis in patients without definitive surgery seems to have improved in the era of ICI.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 6","pages":"Article 100834"},"PeriodicalIF":3.0,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cost-Effectiveness of Adjuvant Osimertinib With and Without Chemotherapy for Surgically Resected NSCLC","authors":"Angelos Vasilopoulos BS ,&nbsp;Alexander Pohlman MD ,&nbsp;Ayham Odeh MD ,&nbsp;K. Robert Shen MD ,&nbsp;Julia M. Coughlin MD ,&nbsp;Zaid M. Abdelsattar MD, MS, FACS","doi":"10.1016/j.jtocrr.2025.100833","DOIUrl":"10.1016/j.jtocrr.2025.100833","url":null,"abstract":"<div><h3>Introduction</h3><div>Osimertinib is now approved as adjuvant therapy for stage IB to III NSCLC with <em>EGFR</em> mutations. Nevertheless, this treatment is lengthy and expensive. Its cost-effectiveness profile as monotherapy versus combination with chemotherapy is unknown. In this context, we investigate the cost-effectiveness of adjuvant osimertinib with and without chemotherapy for NSCLC.</div></div><div><h3>Methods</h3><div>A set of Markov models was established to predict the cost-effectiveness of these different regimens. Data were sourced from the ADAURA trial’s publications and protocols. Health outcomes were quantified as quality-adjusted life-years (QALYs). Costs and incremental cost-effectiveness ratios (ICERs) were estimated in U.S. dollars (USD) and USD per QALY, respectively. Deterministic and probabilistic sensitivity analyses were performed. Data from the Surveillance, Epidemiology, and End Results Program were used to predict additional costs to the U.S. health care system.</div></div><div><h3>Results</h3><div>Compared with treatment with chemotherapy alone, treatment with osimertinib plus chemotherapy yielded 5.86 QALYs with incremental costs of $414,607.69 (ICER = $380,347.85 per QALY). Treatment with osimertinib alone yielded 6.63 QALYs with an incremental cost of $402,224.32 (ICER = $213,447.59 per QALY). Osimertinib is only likely to be cost-effective if the willingness-to-pay threshold per QALY is $200,000 or more. The price of osimertinib had the strongest influence on cost-effectiveness. On the basis of Surveillance, Epidemiology, and End Results Program data, these practices may cost the U.S. health care system an additional 8.9 billion USD/year.</div></div><div><h3>Conclusions</h3><div>Adjuvant osimertinib alone is more cost-effective than combination therapy, but only if the willingness-to-pay is high. A reduction in the price of osimertinib would improve its cost-effectiveness profile.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 6","pages":"Article 100833"},"PeriodicalIF":3.0,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The United States’ Early Experience With Lung Cancer Screening—Creation of a National Data Linkage: A Brief Report","authors":"V. Paul Doria-Rose DVM, PhD ,&nbsp;Gerard A. Silvestri MD, MS ,&nbsp;Danielle D. Durham PhD ,&nbsp;Philip Connor BS ,&nbsp;Lenka Goldman MSE ,&nbsp;Lindsey Enewold PhD, MPH ,&nbsp;Farhood Farjah MD, MPH ,&nbsp;Eric A. Miller PhD, MSPH ,&nbsp;Michael Simanowith MD ,&nbsp;Robert A. Smith PhD ,&nbsp;Louise M. Henderson PhD, MSPH ,&nbsp;Raymond U. Osarogiagbon M.B.B.S., FASCO ,&nbsp;Ella A. Kazerooni MD, MS ,&nbsp;Andrew Ward PhD, MPH ,&nbsp;Paul Pinsky PhD","doi":"10.1016/j.jtocrr.2025.100825","DOIUrl":"10.1016/j.jtocrr.2025.100825","url":null,"abstract":"<div><h3>Introduction</h3><div>Lung cancer screening has been recommended by the United States Preventive Services Taskforce since 2013. The Centers for Medicare and Medicaid Services coverage decision in early 2015 required data submission to a Centers for Medicare and Medicaid Services–approved registry for facilities to receive payment for screening. Only the American College of Radiology’s Lung Cancer Screening Registry (LCSR) received approval for this purpose. Some LCSR elements, such as race, ethnicity, downstream diagnostic procedures, and cancer outcomes, were underreported.</div></div><div><h3>Methods</h3><div>To address underreporting, we linked data from the LCSR to Medicare and Surveillance, Epidemiology, and End Results cancer registry data from 2015 to 2021. We created two different cohorts of individuals aged 65 years and older: (1) those who were enrolled in Medicare fee-for-service plans with parts A and B coverage at the time of at least one LCSR-reported screen, and (2) Medicare beneficiaries (regardless of whether fee-for-service or managed care) living within a Surveillance, Epidemiology, and End Results catchment area at the time of at least one LCSR-reported screen. We compared the characteristics of individuals in the linked cohorts with those of all individuals in the LCSR aged 65 years and over.</div></div><div><h3>Results</h3><div>Demographic, smoking history, and screening examination data elements in the linked data were generally similar to those in the overall LCSR.</div></div><div><h3>Conclusions</h3><div>On the basis of these results, the linked populations seem to be generally representative of older individuals in the LCSR. These unique data linkages provide an unprecedented opportunity to better understand the early implementation of lung cancer screening in the United States.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 6","pages":"Article 100825"},"PeriodicalIF":3.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intensity-Modulated Radiotherapy for Locally Advanced Lung Cancer in the Immunotherapy Era: A Prospective Study WJOG12019L","authors":"Hideyuki Harada MD, PhD ,&nbsp;Akito Hata MD ,&nbsp;Masahiro Konno PhD ,&nbsp;Nobuaki Mamesaya MD, PhD ,&nbsp;Kiyoshi Nakamatsu MD, PhD ,&nbsp;Koji Haratani MD, PhD ,&nbsp;Takaya Yamamoto MD, PhD ,&nbsp;Ryota Saito MD, PhD ,&nbsp;Hiroshi Mayahara MD, PhD ,&nbsp;Masaki Kokubo MD, PhD ,&nbsp;Yuki Sato MD ,&nbsp;Nobuki Imano MD, PhD ,&nbsp;Takeshi Masuda PD, PhD ,&nbsp;Haruyuki Fukuda MD, PhD ,&nbsp;Toshikatsu Sado MD, PhD ,&nbsp;Kenichi Yoshimura PhD ,&nbsp;Yasumasa Nishimura MD, PhD ,&nbsp;Kazuhiko Nakagawa MD, PhD ,&nbsp;Isamu Okamoto MD, PhD ,&nbsp;Nobuyuki Yamamoto MD, PhD","doi":"10.1016/j.jtocrr.2025.100828","DOIUrl":"10.1016/j.jtocrr.2025.100828","url":null,"abstract":"<div><h3>Introduction</h3><div>Chemoradiotherapy (CRT) followed by durvalumab is the standard of care for unresectable locally advanced NSCLC. Limited prospective data have been reported on intensity-modulated radiotherapy (IMRT)–adapted CRT in the immunotherapy era.</div></div><div><h3>Methods</h3><div>In this multicenter prospective observational study, patients underwent IMRT-adapted CRT (platinum-doublet chemotherapy plus 60 Gy IMRT in 30 fractions under a prespecified radiation protocol), followed by consolidative durvalumab. The primary outcome was the durvalumab introduction rate within 42 days post-CRT.</div></div><div><h3>Results</h3><div>Thirty-two patients with unresectable locally advanced NSCLC were enrolled between November 2019 and February 2021. Among the 28 evaluable cases, durvalumab was introduced in 24 (85.7%, 90% confidence interval: 70.2%–95.0%) of 28 patients after CRT, achieving the primary end point. All 29 patients who received IMRT completed the scheduled 60 Gy radiotherapy dose. One year of durvalumab treatment was completed in 12 of 24 patients (50%). In the 24 patients who were durvalumab-introduced, the median progression-free survival and overall survival were 20.9 (95% confidence interval: 6.9–not evaluable) months and not reached, respectively. Two-year progression-free survival and overall survival rates were 44% and 73%, respectively. Among the 29 patients in the safety analysis set, there were no treatment-related deaths or grade 4 nonhematological adverse events. Pneumonitis grade 1 was observed in 13 patients (45%), grade 2 in seven (24%), and grade 3 in one (3%).</div></div><div><h3>Conclusions</h3><div>High durvalumab introduction rate was reported after the completion of IMRT-adapted CRT under a prespecified radiation protocol. Its efficacy has been suggested, with favorable safety profiles, including a low incidence of severe pneumonitis.</div></div><div><h3>Trial Registration</h3><div>University Hospital Medical Information Network database ID: UMIN000038366</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 6","pages":"Article 100828"},"PeriodicalIF":3.0,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143855762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to ‘Humanized Mouse Models for Immuno-Oncology Research: A Review and Implications in Lung Cancer Research’ [JTO Clinical and Research Reports Volume 6 Issue 3 (2025) 100781]","authors":"Cheol-Kyu Park MD, PhD ,&nbsp;Maryam Khalil BSc ,&nbsp;Nhu-An Pham PhD ,&nbsp;Stephanie Wong BSc ,&nbsp;Dalam Ly PhD ,&nbsp;Adrian Sacher MD, FRCPC ,&nbsp;Ming-Sound Tsao MD, FRCPC","doi":"10.1016/j.jtocrr.2025.100824","DOIUrl":"10.1016/j.jtocrr.2025.100824","url":null,"abstract":"","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 5","pages":"Article 100824"},"PeriodicalIF":3.0,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143705770","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":"Incidence and Outcomes of Brain Metastasis in Pleural Mesothelioma in the Era of Immunotherapy","authors":"Margaret Stalker MD ,&nbsp;Suzanne L. Walker PhD, CRNP, AOCN, BC ,&nbsp;Emily Lebow MD ,&nbsp;Emily Ling-Lin Pai MD, PhD ,&nbsp;Alex Watts MS ,&nbsp;Wei-Ting Hwang PhD ,&nbsp;Amir Banihashemi MD ,&nbsp;Evan Anderson MSN ,&nbsp;Leonid Roshkovan MD ,&nbsp;Sharyn I. Katz MD ,&nbsp;Leslie Litzky MD ,&nbsp;Andrew R. Haas MD, PhD ,&nbsp;Sunil Singhal MD ,&nbsp;Corey J. Langer MD ,&nbsp;Keith Cengel MD, PhD ,&nbsp;Melina E. Marmarelis MD, MSCE","doi":"10.1016/j.jtocrr.2025.100823","DOIUrl":"10.1016/j.jtocrr.2025.100823","url":null,"abstract":"<div><h3>Introduction</h3><div>Immunotherapy (IO) has reported efficacy in pleural mesothelioma (PM). Brain metastases (BMs) in PM are rare; thus, surveillance brain imaging is not included in the guidelines. We evaluated the incidence of BM by treatment type.</div></div><div><h3>Methods</h3><div>In this retrospective analysis, patients with PM treated at the University of Pennsylvania between January 1, 2015, and August 31, 2023, were included. Demographic and clinical data were extracted from the medical records. The treatment categories included chemotherapy, single-agent IO, and dual-agent IO. A two-tailed Z score was used to determine a difference in the proportion of BM. Overall survival (OS) was analyzed using the Kaplan-Meier method. Of those with BM, available brain tissue was further analyzed.</div></div><div><h3>Results</h3><div>In total, 251 patients were included; the median age of the participants was 73 years (range: 35–92 y), 79% were male individuals, 91% were white, and 73% had epithelioid histology. In the study, 102 (40.6%) were treated with chemotherapy, 100 (39.8%) with single-agent IO, and 49 (19.5%) with dual-agent IO. The median OS (mOS) was 21.6 months (95% confidence interval: 17.7–25.5) and did not differ between treatment groups (<em>p</em> = 0.774). A higher proportion of patients treated with IO developed BM than those treated with chemotherapy (6/149 [4%] versus 0/102 [0%]; Z score <em>p</em> = 0.04). The mOS from BM diagnosis was 95 days (range: 16–1025 d). The histomorphology of three patients with available brain tissue were similar to the primary site and reported substantial edema and hemorrhage.</div></div><div><h3>Conclusions</h3><div>In this retrospective study, clinically significant BM was most prevalent in those exposed to IO and not seen in those receiving chemotherapy despite similar mOS between the groups. Brain imaging should be considered before starting IO in patients with PM.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 5","pages":"Article 100823"},"PeriodicalIF":3.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791223","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":"Tumor-Induced Osteomalacia in a Patient With FGF23-Amplified Lung Adenocarcinoma and FGF23-Deleted SCLC: Case Report","authors":"Marcello Moro Queiroz MD ,&nbsp;Ricardo Dahmer Tiecher MD ,&nbsp;João Felipe Lima Feldmann MD ,&nbsp;Elisangela Monteiro Coser BSc ,&nbsp;Mariana Vargas Cruz PhD ,&nbsp;Livia Loureiro PhD ,&nbsp;Gabriela Franco Katz MD ,&nbsp;Marina Henkin Behar MD ,&nbsp;João Victor Machado Alessi MD ,&nbsp;Leonardo de Abreu Testagrossa PhD ,&nbsp;Anamaria Aranha Camargo PhD ,&nbsp;Paula Fontes Asprino PhD ,&nbsp;Fabiana Bettoni PhD ,&nbsp;Artur Katz MD","doi":"10.1016/j.jtocrr.2025.100822","DOIUrl":"10.1016/j.jtocrr.2025.100822","url":null,"abstract":"<div><div>Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by ectopic fibroblast growth factor-23 (FGF23) production. We report a unique case of a 78-year-old female patient with refractory hypophosphatemia, ultimately diagnosed as TIO, in the context of two metastatic primary lung cancers: adenocarcinoma and SCLC. Molecular analyses of tumor samples highlighted <em>FGF23</em> amplification in one adenocarcinoma sample and <em>FGF23</em> deletion in one SCLC sample, suggesting a potential link between tumor <em>FGF23</em> molecular alterations and elevated serum FGF23 levels. This case underscores the complexity of diagnoses and management of TIO when associated with solid tumors and highlights the need for awareness of this condition to prevent diagnostic delays. Future research should explore the mechanisms linking <em>FGF23</em> alterations and cancer progression and evaluate targeted therapies for TIO in the context of resistant metastatic cancers.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 6","pages":"Article 100822"},"PeriodicalIF":3.0,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143921998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Phase II Clinical Trial of Neoadjuvant Concurrent Chemoradiotherapy for Locally Advanced High-Grade Thymic Tumors","authors":"Ning Xu MD ,&nbsp;Changlu Wang MD ,&nbsp;Qin Zhang MD ,&nbsp;Xiuxiu Hao MD ,&nbsp;Teng Mao MD ,&nbsp;Jianxin Shi MD ,&nbsp;Zhitao Gu MD ,&nbsp;Lanting Gao MD ,&nbsp;Yan Shen MD ,&nbsp;Lei Zhu MD ,&nbsp;Xuefei Zhang MD ,&nbsp;Yuan Liu MD ,&nbsp;Wentao Fang MD","doi":"10.1016/j.jtocrr.2025.100821","DOIUrl":"10.1016/j.jtocrr.2025.100821","url":null,"abstract":"<div><h3>Introduction</h3><div>Optimal management of locally advanced thymic tumors remains controversial. We conducted a clinical trial (ChiCTR-TNC-10001204) to investigate the safety and efficacy of neoadjuvant concurrent chemoradiotherapy in patients with locally advanced thymic tumors.</div></div><div><h3>Methods</h3><div>The trial was conducted at the Shanghai Chest Hospital in patients with potentially unresectable high-grade thymic tumors. Induction consisted of chemotherapy (docetaxel and cisplatin) and concurrent radiation (40 Gy). The primary end point was objective response rate (ORR).</div></div><div><h3>Results</h3><div>A total of 33 patients were accrued, including 11 with thymomas, 20 with thymic carcinomas, and two with neuroendocrine thymic tumors. ORR was 48.5%, with 16 patients having partial response. The other 17 had stable disease (SD). Thymomas had higher ORR (63.6%) than carcinomas (40.9%). A total of 13 patients (39.4%) experienced grades 3 to 4 toxicity. Surgical resection was feasible after induction in 23 patients (69.7%), among which 19 (82.6%) had complete resection. A higher rate of surgery (87.5% versus 52.9%, <em>p</em> = 0.057) and a significantly higher rate of R0 resection rate (81.3% versus 35.3%, <em>p</em> = 0.024) were observed in patients with partial response than in those with SD. Five-year overall survival and progression-free survival for the whole group were 63.5% and 44.9%, respectively. Patients with thymomas had significantly higher 5-year progression-free survival than the others (81.8% versus 25.6%, <em>p</em> = 0.012). Cumulative incidence of progression was significantly lower in patients with surgery than in those without (5-y CIP: 38.2% versus 80.0%, <em>p</em> = 0.045).</div></div><div><h3>Conclusions</h3><div>Neoadjuvant concurrent chemoradiotherapy is well tolerated and effective for patients with potentially unresectable high-grade thymic tumors, especially for patients with thymomas. Effective induction chemoradiation may help increase the chance of surgical resection and prolonged disease control. Future studies are in need to find more effective treatment approaches for patients with thymic carcinomas.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 6","pages":"Article 100821"},"PeriodicalIF":3.0,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143906075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discordant Response to Nivolumab Plus Ipilimumab and Identification of BRAF V600E Mutation in Biphasic Malignant Pleural Mesothelioma: Case Report","authors":"Olivia Wilkins DO ,&nbsp;Adedamola Omogbehin MD ,&nbsp;Peter J. Bergquist MD ,&nbsp;Chul Kim MD, MPH ,&nbsp;Stephen V. Liu MD ,&nbsp;Joshua E. Reuss MD","doi":"10.1016/j.jtocrr.2025.100820","DOIUrl":"10.1016/j.jtocrr.2025.100820","url":null,"abstract":"<div><div>Therapeutic advancement for malignant pleural mesothelioma (MPM) has been limited. Combination immunotherapy with nivolumab plus ipilimumab is a frontline treatment option for advanced MPM that is typically deployed for patients with sarcomatoid or biphasic MPM. Here, we present a case of biphasic MPM that exhibited a unique response pattern to first-line treatment with nivolumab plus ipilimumab, with brisk response in pleural and mediastinal sites of disease, but rapid progression in osseous/soft tissue sites of disease complicated by pathologic spinal cord compression. Pathologic findings from bony metastasis at progression found pure epithelioid histology without any evidence of sarcomatoid differentiation. Next-generation sequencing of this specimen revealed a <em>BRAF</em> V600E mutation, and the patient was subsequently treated with dabrafenib plus trametinib, achieving ongoing clinical and imaging response in all sites of the disease, including bones. This case supports the use of next-generation sequencing profiling in MPM, particularly in circumstances in which novel discordant response patterns are observed.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 5","pages":"Article 100820"},"PeriodicalIF":3.0,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143697854","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}