JTO Clinical and Research Reports最新文献

{"title":"Impact of the COVID-19 Pandemic on Diagnosis and Multidisciplinary Treatment of NSCLC in Ontario, Canada","authors":"Kirstin Perdrizet MD ,&nbsp;Lisa W. Le MSc ,&nbsp;Anthea Lau BSc ,&nbsp;Xiaochen Tai MSc ,&nbsp;Mary R. Rabey BMBS ,&nbsp;Jennifer H. Law MSc ,&nbsp;Donna Maziak MD ,&nbsp;Natasha Leighl MD","doi":"10.1016/j.jtocrr.2025.100869","DOIUrl":"10.1016/j.jtocrr.2025.100869","url":null,"abstract":"<div><h3>Introduction</h3><div>The coronavirus disease 2019 pandemic disrupted cancer care delivery globally, with many jurisdictions reporting reductions in lung cancer diagnoses and delays in treatment. In Ontario, Canada, both institutional and provincial data have reported mixed trends in NSCLC presentation and care. This study aimed to assess the short-term impact of the coronavirus disease 2019 pandemic on NSCLC diagnoses and treatment pathways across Ontario using population-level data from Cancer Care Ontario administrative health databases.</div></div><div><h3>Methods</h3><div>We conducted a retrospective cohort study of patients diagnosed with NSCLC in Ontario between January 1, 2019 and December 31, 2020. The cohort was created using relevant diagnostic codes and linked provincial databases to evaluate diagnostic trends and access to surgical, medical, and radiation oncology services. Statistical analyses included Poisson regression to assess changes in diagnosis rates and multivariable linear regressions to evaluate wait times, adjusting for age, sex, income quintile, and geographic region.</div></div><div><h3>Results</h3><div>A total of 13,407 NSCLC cases were identified. There was a 6% overall decline in diagnoses in 2020, with a 31% drop during quarter 2 (April–June 2020). The mean wait times for surgical consultation and treatment and also medical and radiation oncology consults improved or remained stable. No delays were found in systemic therapy initiation. Multivariable analyses confirmed these findings.</div></div><div><h3>Conclusions</h3><div>NSCLC care delivery in Ontario remained stable during the early pandemic period. Declines in diagnosis warrant further investigation using longer-term data. Real-time data systems are essential for future pandemic preparedness and response.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 9","pages":"Article 100869"},"PeriodicalIF":3.5,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144830548","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":"BRAF Fusion as Resistance Mechanism to Osimertinib in EGFR-Mutated NSCLC: A Case Report and Review of Literature","authors":"Marianna Peroni MD ,&nbsp;Alessandro Leonetti MD, PhD ,&nbsp;Roberta Minari MSc, PhD ,&nbsp;Michela Verzè MSc ,&nbsp;Letizia Gnetti MD ,&nbsp;Lorena Bottarelli MSc, PhD ,&nbsp;Cinzia Azzoni MSc, PhD ,&nbsp;Marco Galaverni MD ,&nbsp;Nicola Simoni MD ,&nbsp;Gabriele Missale MD ,&nbsp;Elisabetta Biasini MD ,&nbsp;Marcello Tiseo MD, PhD","doi":"10.1016/j.jtocrr.2025.100867","DOIUrl":"10.1016/j.jtocrr.2025.100867","url":null,"abstract":"<div><div>Despite the efficacy of osimertinib in the first-line treatment of advanced <em>EGFR</em>-mutated NSCLC, the development of resistance is nearly inevitable. <em>BRAF</em> mutations and fusions are reported in 1% to 3% of patients with <em>EGFR</em>-mutated NSCLC receiving osimertinib and represent potential targetable alterations.</div><div>In this case report, we discuss the rationale for EGFR-MEK co-inhibition in a patient with <em>EGFR</em>-mutated NSCLC treated with osimertinib that developed a <em>CTNNA</em><em>1-BRAF</em> fusion at progression. In addition, we provide a brief overview of the current evidence of <em>BRAF</em> fusions as an acquired resistance mechanism to osimertinib and potential treatment strategies.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 8","pages":"Article 100867"},"PeriodicalIF":3.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144632070","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":"Phase 3 Trials of Neoadjuvant, Perioperative, and Adjuvant Chemoimmunotherapy for Resectable, Early-Stage NSCLC: Comprehensive Review and Detailed Analysis","authors":"Jay M. Lee MD ,&nbsp;Alessandro Brunelli MD ,&nbsp;Amy L. Cummings MD ,&nbsp;Enriqueta Felip MD, PhD ,&nbsp;Catherine A. Shu MD ,&nbsp;Benjamin J. Solomon M.B.B.S., PhD ,&nbsp;Masahiro Tsuboi MD ,&nbsp;Heather Wakelee MD ,&nbsp;Anjali Saqi MD ,&nbsp;Yi-Long Wu MD ,&nbsp;Pao-Chen Li PhD ,&nbsp;Barbara J. Gitlitz MD","doi":"10.1016/j.jtocrr.2025.100866","DOIUrl":"10.1016/j.jtocrr.2025.100866","url":null,"abstract":"<div><div>Phase 3 trials of neoadjuvant, perioperative, and adjuvant immune checkpoint inhibitors combined with chemotherapy (ICI-CT) in resectable early-stage NSCLC (eNSCLC) have reported that all three approaches confer an event-free or disease-free survival benefit over CT alone, with acceptable safety profiles. All three strategies are approved standards of care for eNSCLC. This review provides a detailed analysis of these phase 3 ICI-CT trials and addresses the considerations regarding the selection of each approach, including protocol schema and baseline patient and tumor differences, preoperative staging, surgical outcomes, efficacy end points, safety, treatment disposition, and the programmed death-ligand 1 (PD-L1) efficacy biomarker. The differences between regimens and study populations among these ICI-CT trials hamper cross-trial comparisons and highlight the need for head-to-head trials. Patients achieving pathologic complete response with neoadjuvant ICI-CT have better survival outcomes irrespective of subsequent treatment, but the optimal number of preoperative ICI-CT cycles needed to achieve pathologic complete response has not been defined. The choice between a neoadjuvant or perioperative versus adjuvant treatment approach involves a risk-benefit assessment of the potential for preoperative attrition to surgery, postoperative attrition to ICI-CT, and the anticipated toxicity profile. Current limitations of invasive lymph node staging mean that adjuvant ICI remains an important treatment strategy, but preoperative node staging is imperative. Future studies that identify the safety and toxicity contributions of each treatment phase in perioperative trials will confirm whether a pre- or postoperative ICI approach is superior, whether there is added benefit to adjuvant after neoadjuvant ICI-CT, and which patients will benefit the most from each approach.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 9","pages":"Article 100866"},"PeriodicalIF":3.5,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144725044","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":"Incorporating High-Risk Individuals Beyond Smoking History Into Lung Cancer Screening in Hong Kong: A Cost-Effectiveness Study","authors":"Herbert Ho-fung Loong MBBS, FRCP ,&nbsp;Xuanqi Pan PhD ,&nbsp;Carlos K.H. Wong PhD ,&nbsp;Chao-Hua Chiu MD ,&nbsp;Szu-Chun Yang MD ,&nbsp;Matthew Shing Hin Chung BSc ,&nbsp;Molly Siu Ching Li MBBS ,&nbsp;Lisa de Jong PhD ,&nbsp;Harry Groen MD, PhD ,&nbsp;Maarten J. Postma PhD ,&nbsp;Pan-Chyr Yang MD, PhD","doi":"10.1016/j.jtocrr.2025.100860","DOIUrl":"10.1016/j.jtocrr.2025.100860","url":null,"abstract":"<div><h3>Introduction</h3><div>Lung cancer (LC) accounts for 26.4% of all cancer deaths in Hong Kong (HK). Lung cancer screening (LCS) with low-dose computed tomography (LDCT) can reduce LC mortality. The cost-effectiveness of LDCT screening in high-risk individuals on the basis of smoking history has previously been investigated. However, nearly half of patients with LC in HK never smoke, indicating a different LC epidemiology compared with Western countries, where most LC cases are associated with smoking. We conducted a cost-effectiveness analysis for LCS, utilizing local data and expanding the target population to include we not only high-risk individuals identified on the basis of smoking history but also those identified through other risk factors.</div></div><div><h3>Methods</h3><div>A decision tree combined with a state-transition Markov model was developed to simulate identification, diagnosis, and treatments for high-risk individuals, from a health care provider perspective. The selection criteria and screening effectiveness for high-risk individuals on the basis of smoking history were obtained from the Dutch-Belgian Lung Cancer Screening Study, targeting heavy smokers aged 50 to 74 years; whereas the Taiwan Lung Cancer Screening in Never-Smoker Trial was used to model high-risk individuals on the basis of factors other than smoking history. Local LC survival and cost data were used to populate the model. The willingness-to-pay threshold used in the study was US$24,302 to US$40,202 per quality-adjusted life-year (QALY).</div></div><div><h3>Results</h3><div>Screening led to additional early LC detected, and LC mortality reduction, compared with no screening. Over a lifetime horizon, the incremental cost-effectiveness ratio for high-risk individuals on the basis of smoking history was US$14,122 per QALY. The incremental cost-effectiveness ratio for high-risk individuals on the basis of factors other than smoking history was lower at US$9610 per QALY.</div></div><div><h3>Conclusion</h3><div>LCS with LDCT can be considered cost-effective in HK for high-risk individuals on the basis of smoking history and factors other than smoking history, contributing to the health benefits of the population. Our findings support a population-based LCS for all high-risk individuals identified through criteria beyond smoking history.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 10","pages":"Article 100860"},"PeriodicalIF":3.5,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145046211","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":"CANOPY-N: A Phase 2 Study of Canakinumab or Pembrolizumab, Alone or in Combination, as Neoadjuvant Therapy in Patients With Resectable, Stage IB–IIIA NSCLC","authors":"Jay M. Lee MD ,&nbsp;Jean-Louis Pujol MD, PhD ,&nbsp;Jun Zhang MD, PhD ,&nbsp;Oleg Leonov MD, PhD ,&nbsp;Masahiro Tsuboi MD, PhD ,&nbsp;Edward S. Kim MD, MBA ,&nbsp;Calvin Ng MD ,&nbsp;Nicolas Moreno-Mata MD, PhD ,&nbsp;Amy Cummings MD, PhD ,&nbsp;Ilhan Hacibekiroglu MD ,&nbsp;Abidin Sehitogullari MD ,&nbsp;Nirmal Veeramachaneni MD ,&nbsp;Cathy Spillane PhD ,&nbsp;Jiawei Duan PhD ,&nbsp;Claudia Bossen PhD ,&nbsp;Alexander Savchenko MD, PhD ,&nbsp;Chiara Lobetti-Bodoni MD, PhD ,&nbsp;Tony Mok MD ,&nbsp;Pilar Garrido MD","doi":"10.1016/j.jtocrr.2025.100859","DOIUrl":"10.1016/j.jtocrr.2025.100859","url":null,"abstract":"<div><h3>Introduction</h3><div>Canakinumab is a human monoclonal anti–interleukin-1β antibody with the potential to enhance the activity of programmed death-ligand 1 inhibitors by inhibiting protumor inflammation.</div></div><div><h3>Methods</h3><div>CANOPY-N was a randomized, phase 2 study to evaluate safety and efficacy of neoadjuvant canakinumab (200 mg subcutaneous once every three weeks) and pembrolizumab (200 mg intravenous once every three weeks), either in combination or alone, in patients with early-stage (stage Ib–IIIa) NSCLC. The primary end point was major pathologic response (MPR) rates (≤10% of residual tumor cells) by central pathology review in the arms containing canakinumab. Secondary end points included overall response rates, safety, pharmacokinetics, surgical feasibility rates, and MPR rate in the pembrolizumab arm. The impact of treatment on surgical outcomes was assessed as an exploratory outcome.</div></div><div><h3>Results</h3><div>In total, 88 patients were enrolled: 35 to the canakinumab arm, 35 to the canakinumab + pembrolizumab arm, and 18 to the pembrolizumab arm. One patient (2.9%) in the canakinumab arm (95% confidence interval [CI]: 0.07–14.92), six patients (17.1%) in the canakinumab + pembrolizumab arm (95% CI: 6.56–33.65), and three patients (16.7%) in the pembrolizumab arm (95% CI: 3.58–41.42) achieved MPR. No unexpected safety signals were observed. Of the 84 patients (95.5%) who underwent operation, the prespecified 6-week window was achieved for 72 patients (85.7%).</div></div><div><h3>Conclusions</h3><div>Neoadjuvant treatment with canakinumab alone or combined with pembrolizumab did not improve MPR rates compared with pembrolizumab alone. No unexpected safety signals were observed and canakinumab did not adversely affect surgical outcomes. Intraoperative perihilar or perilobular fibrosis after neoadjuvant immunotherapy was rare.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 8","pages":"Article 100859"},"PeriodicalIF":3.0,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144579962","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":"Occult Node Detection With Lobectomy Versus Segmentectomy for Stage IA NSCLC","authors":"Yota Suzuki MD ,&nbsp;Rajeev Dhupar MD ,&nbsp;Inderpal S. Sarkaria MD, MBA ,&nbsp;Ian G. Christie MD ,&nbsp;Summer N. Mazur BS ,&nbsp;Arjun Pennathur MD ,&nbsp;James D. Luketich MD ,&nbsp;Ryan M. Levy MD ,&nbsp;Rodney J. Landreneau MD ,&nbsp;Matthew J. Schuchert MD","doi":"10.1016/j.jtocrr.2025.100861","DOIUrl":"10.1016/j.jtocrr.2025.100861","url":null,"abstract":"<div><h3>Objective</h3><div>Besides the discussion on parenchymal margin, data on the extent of lymph node (LN) dissection are scarce, especially in segmentectomy. This study aimed to investigate the extent of LN dissection and detection of occult disease in segmentectomy compared with lobar resection.</div></div><div><h3>Methods</h3><div>We performed a single-institution, retrospective analysis for patients who underwent segmentectomy or lobectomy for clinical T1N0M0 (≤3 cm) NSCLC from 2012 to 2022. The extent of LN dissection and the rate of detection of occult LN disease were compared. N1 nodes were further classified as collected as a specimen during the operation (N1 dissection) and the nodes retrieved from lung specimens by pathologists (N1 lung specimen).</div></div><div><h3>Results</h3><div>During the study period, 957 lobectomies and 402 segmentectomies were performed for clinical T1N0M0 NSCLC. The median number of sampled LNs was significantly higher in the lobectomy group (18 versus 12; <em>p</em> &lt; 0.001). This tendency was similar across all node groups, including N2 nodes (7 versus 5), N1 dissection nodes (6 versus 4), and most significantly N1 lung specimen nodes (4 versus 0; all <em>p</em> &lt; 0.001) There was a significant difference in N1 occult nodes (13.3% versus 3.7%; <em>p</em> &lt; 0.001), whereas the difference was not significant in N2 occult nodes (5.5% versus 3.2%; <em>p</em> = 0.074).</div></div><div><h3>Conclusions</h3><div>Segmentectomy was associated with less LN sampling, which translated into lower detection of occult nodal metastasis in N1 LNs. Although standardized pathologic dissection could potentially improve detection, there is likely an inevitable inferiority in LN sampling with segmentectomy.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 8","pages":"Article 100861"},"PeriodicalIF":3.0,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144588218","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":"Role of Quality of Life in Daily Functioning, Communication with Care Teams, and Treatment Decisions in Patients with <i>ALK</i>+ NSCLC.","authors":"Heather Law, Huamao M Lin, Eileen Curran, Annette Szumski, Jacinta Wiens, Jennifer Blender, Emily S Venanzi, Erin L Schenk, Jessica J Lin, Jennifer C King","doi":"10.1016/j.jtocrr.2025.100863","DOIUrl":"10.1016/j.jtocrr.2025.100863","url":null,"abstract":"<p><strong>Introduction: </strong>This study investigated quality of life (QoL) and its role in treatment decision making among patients with anaplastic lymphoma kinase (<i>ALK</i>)+ NSCLC.</p><p><strong>Methods: </strong>Adult patients with self-reported <i>ALK</i>+ NSCLC residing in the United States from the Lung Cancer Registry from GO2 for Lung Cancer were included. Measures included a core patient survey derived from Quality of Life Questionnaire - Core 30 items (QLQ-C30) and QLQ - lung cancer module 29 items domains and an <i>ALK+</i> NSCLC module (ALK module). Associations were assessed between key domains and module questions using polyserial or Spearman's correlations and Cochran-Mantel-Haenszel tests.</p><p><strong>Results: </strong>Seventy-one patients with <i>ALK</i>+ NSCLC completed the ALK module. Most patients (85%) felt their current therapy helped stop cancer growth, helped them live longer, and was worth taking despite side effects; however, 80% reported some cancer scan-related anxiety and only 32% reported having received \"quite a bit\" or \"very much\" mental health support information from their care team. Most patients (75%) reported QoL as a top concern in treatment decisions, regardless of responses to other ALK module questions (all associations <i>p</i> ≥ 0.50). Although most patients (87%) perceived their physicians as interested in their QoL, only 51% reported their physicians discussed QoL as a top concern in treatment decisions. QLQ-C30 composite global health status-QoL score had significant moderate to strong correlations with all other QLQ-C30 and lung cancer module 29 items domains (<i>p</i> ≤ 0.004) and some components of communication with care teams, treatment confidence, and impact on daily life.</p><p><strong>Conclusions: </strong>QoL is important in treatment decision making for patients with <i>ALK+</i> NSCLC. These findings highlight areas for improvement in mental health support and patient-provider communication.</p>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 9","pages":"100863"},"PeriodicalIF":3.5,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12354805/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144873869","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":"Midkine Expression as a Candidate Biomarker to Predict the Recurrence of Stage IA Lung Adenocarcinoma","authors":"Xiao Yang PhD,&nbsp;Shuo Sun BSc,&nbsp;Xunjie Kuang BSc,&nbsp;Xianfeng Lu MM,&nbsp;He Xiao MM,&nbsp;Yi Duan BSc,&nbsp;Yanli Xiong MM,&nbsp;Di Zhang BSc,&nbsp;Yu Xu PhD,&nbsp;Jianwu Zhu PhD,&nbsp;Mengxia Li PhD","doi":"10.1016/j.jtocrr.2025.100858","DOIUrl":"10.1016/j.jtocrr.2025.100858","url":null,"abstract":"<div><h3>Background</h3><div>Early recurrence limits the long-term survival of postoperative patients with stage IA lung adenocarcinoma (LUAD). This study aims to risk-stratify postoperative stage IA LUAD by means of the expression of Midkine (MDK).</div></div><div><h3>Materials and Methods</h3><div>We collected surgical samples from 62 patients with stage IA LUAD, of which 30 patients had early recurrence and others without. Intratumoral and peritumoral MDK expression were measured by immunohistochemistry staining. We also analyzed the MDK expression of stage IA LUAD from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus repository.</div></div><div><h3>Results</h3><div>The intratumoral MDK was significantly overexpressed in patients with early recurrence (<em>p</em> &lt; 0.001). Kaplan-Meier survival analysis revealed that patients with higher intratumoral MDK expression had poor recurrence-free survival (<em>p</em> &lt; 0.001) and overall survival (<em>p</em> = 0.004). Univariate Cox regression analysis indicated that intratumoral MDK expression significantly increased the risk of recurrence (hazard ratio [HR] 1.408 (1.076–1.842), <em>p</em> = 0.013) and death (HR 1.888 [1.127–3.162], <em>p</em> = 0.016). Stepwise Cox regression analysis revealed that smoking (HR 2.944 [1.419–6.107], <em>p</em> = 0.004), intratumoral MDK expression (HR 1.316 [1.037–1.669], <em>p</em> = 0.024), and <em>EGFR</em> mutation (HR 2.407 [1.110–5.221], <em>p</em> = 0.026) were independent prognostic factors for early recurrence. In TCGA data set, the MDK expression significantly increased the risk of recurrence (HR 1.559 [1.035–2.349], <em>p</em> = 0.034), and patients with higher MDK expression had worse disease-free survival (<em>p</em> = 0.024). In GSE31210, the MDK expression significantly increased the risk of recurrence (HR 2.617 [1.791–3.824], <em>p</em> &lt; 0.001) and death (HR 2.495 [1.429–4.356], <em>p</em> = 0.001), whereas patients with higher MDK expression also had worse recurrence-free survival (<em>p</em> = 0.006) and overall survival (<em>p</em> &lt; 0.001).</div></div><div><h3>Conclusion</h3><div>MDK was considered a putative candidate for predicting early recurrence in patients with stage IA LUAD.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 9","pages":"Article 100858"},"PeriodicalIF":3.0,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144695429","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":"Acquisition of FGFR1 and NSD3 Amplifications During the Transformation of EGFR-Mutated Lung Adenocarcinoma into Squamous Cell Carcinoma: A Case Report","authors":"Naoki Fukunaga MD ,&nbsp;Hideki Terai MD, PhD ,&nbsp;Rui Nomura MD ,&nbsp;Yutaka Kurebayashi MD, PhD ,&nbsp;Kohei Nakamura MD, PhD ,&nbsp;Ryutaro Kawano MD ,&nbsp;Kohei Shigeta MD, PhD ,&nbsp;Koji Okabayashi MD ,&nbsp;Katsuhito Kinoshita MD ,&nbsp;Akihiko Ogata MD ,&nbsp;Lisa Shigematsu MD ,&nbsp;Fumimaro Ito MD ,&nbsp;Hatsuyo Takaoka MD ,&nbsp;Takahiro Fukushima MD ,&nbsp;Shigenari Nukaga MD, PhD ,&nbsp;Keiko Ohgino MD, PhD ,&nbsp;Hiroyuki Yasuda MD, PhD ,&nbsp;Hiroshi Nishihara MD, PhD ,&nbsp;Yuko Kitagawa MD, PhD ,&nbsp;Koichi Fukunaga MD, PhD","doi":"10.1016/j.jtocrr.2025.100862","DOIUrl":"10.1016/j.jtocrr.2025.100862","url":null,"abstract":"<div><div>Histologic transformation from adenocarcinoma to SCLC is a recognized mechanism of resistance in lung cancer. However, the transformation into squamous cell carcinoma is less common, and the associated genomic alterations remain unclear. Here, we present a case of lung adenocarcinoma harboring an EGFR (<em>EGFR</em>) mutation that transformed into squamous cell carcinoma. Although <em>EGFR</em> L858R mutation was detected throughout the transformation, genomic analyses were performed during the disease course, revealing the amplification of <em>FGFR1</em> and <em>NSD3</em>, which have recently been proposed as potential driver oncogenes in lung squamous cell carcinoma. This case report highlights the genomic alterations observed in repeatedly biopsied specimens, along with a review of the relevant literature.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 9","pages":"Article 100862"},"PeriodicalIF":3.5,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144739622","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 Study of Cabozantinib in Patients With MET-Altered Lung Cancers","authors":"Guilherme Harada MD ,&nbsp;Fernando C. Santini MD ,&nbsp;Clare J. Wilhelm PhD ,&nbsp;Rebecca W. Repetti NP ,&nbsp;Jason C. Chang MD ,&nbsp;Soo-Ryum Yang MD ,&nbsp;Yun-Te Lin MSc ,&nbsp;Khadeja A. Moses BA ,&nbsp;Christina Falcon MPH, PMP ,&nbsp;Michelle Goldstein MSW ,&nbsp;Alex Makhnin MA ,&nbsp;Michelle S. Ginsberg MD ,&nbsp;Andrew J. Plodkowski MD ,&nbsp;Mark G. Kris MD ,&nbsp;Alexander Drilon MD","doi":"10.1016/j.jtocrr.2025.100857","DOIUrl":"10.1016/j.jtocrr.2025.100857","url":null,"abstract":"<div><h3>Introduction</h3><div>Only type I MET tyrosine kinase inhibitors (TKIs) are approved for treating <em>MET</em>-altered NSCLCs. Preclinically, type II TKIs, such as cabozantinib, can rescue progression on type I TKIs. This phase 2 trial (NCT01639508) evaluated the activity of cabozantinib in patients with MET-dependent lung cancers, including TKI-pretreated cancers.</div></div><div><h3>Methods</h3><div>This phase 2 trial with a Simon two-stage minimax design treated patients with metastatic, <em>MET</em>-altered lung cancers with cabozantinib (60 mg daily) until progression or intolerable toxicity. The primary end point was objective response rate (ORR). We prespecified that cabozantinib would be considered a useful agent if at least a 20% ORR was observed. Secondary end points included progression-free survival, overall survival, and safety.</div></div><div><h3>Results</h3><div>We enrolled 28 patients, 23 patients (82%) with only a <em>MET</em> exon 14 alteration, two patients (7%) with <em>MET</em> amplification, and three patients (11%) with concurrent <em>MET</em> exon 14 alteration and amplification. There were 24 patients (86%) previously treated with a type I MET TKI. The ORR was 20% (5/25 assessable patients; 95% confidence interval [CI]: 8.9%–39.1%), with five partial responses (duration ranged from 4 to 39 mo). Four of five responders were type I MET TKI pretreated. The median progression-free survival and overall survival were 4.5 (95% CI: 3.3–5.7) months and 7.2 (95% CI: 2.9–11.5) months, respectively. Dose modification and discontinuation occurred in 64% (18/28) and 7% (2/28) of patients, respectively.</div></div><div><h3>Conclusion</h3><div>This trial met its primary end point. Importantly, we demonstrated that cabozantinib, a type II MET TKI, could benefit patients with MET-altered lung cancers previously treated with type I MET TKIs.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 8","pages":"Article 100857"},"PeriodicalIF":3.0,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144549819","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}