JTO Clinical and Research Reports最新文献

{"title":"Next-Generation Sequencing Analysis on Image-Guided Biopsy Samples in Early-Stage Lung Cancer: Feasibility Study and Comparison With Surgical Samples","authors":"Louis Gros MD,&nbsp;Rowena Yip PhD, MPH,&nbsp;Arel Golombeck MD,&nbsp;David F. Yankelevitz MD,&nbsp;Claudia I. Henschke PhD, MD","doi":"10.1016/j.jtocrr.2024.100777","DOIUrl":"10.1016/j.jtocrr.2024.100777","url":null,"abstract":"<div><h3>Introduction</h3><div>Limited information exists on next-generation sequencing (NGS) success for lung tumors of 30 mm or less. We aimed to compare NGS success rates across biopsy techniques for these tumors, assess DNA sequencing quality, and verify reliability against surgical resection results.</div></div><div><h3>Methods</h3><div>We used data from the Initiative for Early Lung Cancer Research on Treatment study, including patients with lung tumors measuring 30 mm or less who had surgery and NGS on biopsies since 2016. We collected data on biopsy type, nodule characteristics, complications, sequencing feasibility, clinical actionable variants, surgery type, and TNM classification. We compared NGS feasibility and quality between biopsy methods and, for those with NGS on surgical samples, compared feasibility, quality, and detection of actionable variants.</div></div><div><h3>Results</h3><div>Among the 654 participants with lung tumors of 30 mm or less who underwent surgery, 70 had NGS on prior biopsies. The median age was 68.5; 51.4% were male individuals, and 75.7% were smokers. The mean diameter of biopsied nodules was 17.7 mm, with 67.1% fine-needle aspiration, 17.1% computed tomography–guided transthoracic core needle biopsies, and 17.1% endobronchial ultrasound–guided transbronchial needle aspiration. DNA sequencing was feasible in 97.1% of biopsy samples; 2.9% had low tumor cellularity. Coverage depth was achieved in 89.7% of biopsies. RNA sequencing was successful in 66.2% of biopsies, especially in core needle biopsies. Actionable alterations were found in 41.4% of patients. Among the participants, 30% had NGS on surgical samples. RNA sequencing was more feasible on surgical samples (95.2% versus 42.9% for biopsies). NGS on surgical samples matched biopsy results in 90% of patients, with 10% showing additional alterations.</div></div><div><h3>Conclusion</h3><div>DNA sequencing succeeded in 97.1% of biopsies of nodules 30 mm or less, whereas RNA sequencing feasibility was lower. NGS on biopsy samples is generally reliable but requires careful review.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 2","pages":"Article 100777"},"PeriodicalIF":3.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059497","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":"Epidemiology of SCLC in the United States From 2000 to 2019: A Study Utilizing the Surveillance, Epidemiology, and End Results Registry","authors":"Leah E. Wells MD ,&nbsp;Sean Cohen MD ,&nbsp;Benjamin Brennan MS ,&nbsp;Mousumi Banerjee PhD ,&nbsp;Gregory P. Kalemkerian MD","doi":"10.1016/j.jtocrr.2025.100799","DOIUrl":"10.1016/j.jtocrr.2025.100799","url":null,"abstract":"<div><h3>Introduction</h3><div>From the late 1980s to 2000, SCLC represented a decreasing proportion of lung cancer cases in the United States. Nevertheless, survival outcomes in SCLC did not improve, reflecting the paucity of treatment advances. We sought to determine whether these trends continued into more recent decades, before the Food and Drug Administration approval of immunotherapy for SCLC in 2019, by evaluating the incidence and survival of SCLC from 2000 to 2019 in the United States population, with attention to variance across gender and racial subgroups.</div></div><div><h3>Methods</h3><div>Using the United States Surveillance, Epidemiology, and End Results 17 database, we evaluated the incidence of SCLC and NSCLC from 2000 to 2019. Demographic, staging, and survival data were collected for patients with SCLC by comparing the incidence and outcomes across groups.</div></div><div><h3>Results</h3><div>The percentage of SCLC among all newly diagnosed lung cancer cases decreased from 14.5% in 2000 to 11.8% in 2019. A decrease in SCLC incidence was observed in all sex and racial subgroups but was earlier and steeper in men than in women. This has resulted in a shift in the male-to-female ratio from 1.14:1 in 2000 to 0.93:1 in 2019. Among the racial subgroups, the incidence of SCLC declined most slowly in non-Hispanic Whites and most rapidly in non-Hispanic Asians and Pacific Islanders. There was a decline in limited-stage SCLC at diagnosis, from 31.1% in 2000 to 26.4% in 2019. Minimal improvement was observed in survival regardless of patient characteristics or stage.</div></div><div><h3>Conclusions</h3><div>In the preimmunotherapy era of 2000 to 2019, the incidence of SCLC continued to decline in both sexes and all racial subgroups. The male-to-female ratio continued to narrow with women outnumbering men in the most recent years. The proportion of patients with limited-stage disease continues to decline, likely because of improved staging procedures. The outcomes improved slightly but remained poor, highlighting the need for more effective treatment strategies.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 4","pages":"Article 100799"},"PeriodicalIF":3.0,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143508095","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":"Targeting DLL3: A New Weapon in Lung Neuroendocrine Tumors?","authors":"Mariona Riudavets MD, PhD ,&nbsp;David Planchard MD, PhD","doi":"10.1016/j.jtocrr.2025.100796","DOIUrl":"10.1016/j.jtocrr.2025.100796","url":null,"abstract":"","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 5","pages":"Article 100796"},"PeriodicalIF":3.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143697853","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":"PD-L1, Tumor Mutational Burden, and Outcomes in NSCLC With Brain Metastases: A Brief Report","authors":"Elio Adib MD ,&nbsp;Amin H. Nassar MD ,&nbsp;Elias Bou Farhat MD ,&nbsp;Shyam K. Tanguturi MD ,&nbsp;Rifaquat M. Rahman MD ,&nbsp;Daphne A. Haas-Kogan MD, MBA ,&nbsp;Wenya Linda Bi MD, PhD ,&nbsp;Omar Arnaout MD ,&nbsp;Patrick Y. Wen MD ,&nbsp;David J. Kwiatkowski MD, PhD ,&nbsp;Mark M. Awad MD, PhD ,&nbsp;Ayal A. Aizer MD","doi":"10.1016/j.jtocrr.2025.100797","DOIUrl":"10.1016/j.jtocrr.2025.100797","url":null,"abstract":"<div><h3>Introduction</h3><div>Patients with NSCLC and brain metastases have a poor prognosis. Combining brain-directed radiation therapy (RT) with immune checkpoint inhibitors (ICIs) may be synergistic. Nevertheless, predictors of response and toxicity are lacking.</div></div><div><h3>Methods</h3><div>This retrospective study conducted at Dana-Farber Brigham Cancer Center from 2015 to 2023 included patients with non-<em>EGFR</em> and non-<em>ALK</em>-altered NSCLC and newly diagnosed brain metastases starting ICI within 90 days of brain-directed RT. We assessed all-cause mortality, systemic and neurologic death, systemic and intracranial progression at the patient level, and local recurrence and radiation necrosis at the metastasis level.</div></div><div><h3>Results</h3><div>Among the 178 patients with 536 brain metastases, the median age was 64 years, and 53% were female individuals. The median number of brain metastases detected at diagnosis was three. Most patients received pembrolizumab (93%) and were treated with stereotactic radiation (81%). Higher programmed death-ligand 1 (PD-L1) expression was associated with improved all-cause mortality (median survival: PD-L1 less than 1%: 10.7 mo, 1%–49%: 14.3 mo, more or equal to 50%: 29.5 mo), driven by longer time to systemic death. Higher PD-L1 was also associated with improved systemic progression-free survival (<em>p</em>_{≥50% versus &lt;1%} = 0.02) and distant intracranial disease-free survival (<em>p</em>_{≥50% versus &lt;1%} = 0.02). The rate of local recurrence was low across all groups (1%–4% at 2 y). Patients with higher PD-L1 had numerically higher radiographic radiation necrosis rates (2.3%, 5.5%, 9.3% at 2 y for PD-L1 &lt;1%, 1%–49%, and ≥50%, respectively, <em>p</em>_{≥50% versus &lt;1%} = 0.08) and significantly higher symptomatic radiation necrosis rates (<em>p</em>_{≥50% versus &lt;1%} = 0.04).</div></div><div><h3>Conclusions</h3><div>The combination of brain-directed RT and ICI is effective in treating patients with NSCLC and brain metastases. Although high PD-L1 levels are associated with longer survival and improved intracranial control, radiation necrosis occurs more frequently in patients with high PD-L1 expression. Clinicians should be aware of long-term treatment-related toxicities in this population.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 4","pages":"Article 100797"},"PeriodicalIF":3.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143631884","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":"Recent Survival Gains in Stage IV NSCLC by Sociodemographic Strata","authors":"Oluwaseun F. Ayoade MD, MSHA ,&nbsp;Maureen E. Canavan PhD, MPH ,&nbsp;Emily J. Zolfaghari MD, MS ,&nbsp;Giorgio Caturegli MD ,&nbsp;So Yeon Kim MD ,&nbsp;Daniel J. Boffa MD, MBA","doi":"10.1016/j.jtocrr.2025.100798","DOIUrl":"10.1016/j.jtocrr.2025.100798","url":null,"abstract":"<div><h3>Introduction</h3><div>The management of stage IV NSCLC has been transformed by recent innovations. Nevertheless, access to medical innovations varies across sociodemographic groups in the United States, which may affect the rate of outcome improvements. Our objective was to evaluate the recent real-world gains in the survival of patients with stage IV NSCLC across sociodemographic groups.</div></div><div><h3>Methods</h3><div>The National Cancer Database was queried for treated patients diagnosed with stage IV NSCLC between 2010 and 2020. Data was analyzed in three eras (2010–2013, 2014–2017, and 2018–2020). Two-year survival was assessed using the Kaplan-Meier method. Adjusted mortality risk was calculated using stratified Cox analysis.</div></div><div><h3>Results</h3><div>A total of 393,586 patients with stage IV NSCLC received treatment. Chemotherapy administration decreased (from 64.8% to 25.1%), radiation therapy decreased (from 54.3% to 27.6%), and immunotherapy increased (from 2.0% to 51.8%). Between eras 1 and 3, median survival increased by 53.7% (6.7–10.3 mo); nevertheless, not all groups improved at the same pace. The median survival increased by 81% (from 8.3 to 15.0 mo) for Hispanic patients, by 54.7% (from 6.7 to 10.3 mo) for non-Hispanic Blacks, and by 46.7% (from 6.6 to 9.6 mo) for non-Hispanic Whites. The median survival of uninsured patients increased from 5.8 to 7.2 months (24.1%), whereas that of patients with private insurance increased from 8.6 to 14.7 months (70.9%).</div></div><div><h3>Conclusions</h3><div>The survival of patients with treated stage IV NSCLC has improved considerably over the past decade. Nevertheless, expected survival and the pace of improvement differed across sociodemographic groups. Further studies to understand this outcome variability may enhance the effectiveness and equity of NSCLC treatments.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 4","pages":"Article 100798"},"PeriodicalIF":3.0,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143679338","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":"Automated Measurement of Coronary Artery Calcifications and Routine Perioperative Blood Tests Predict Survival in Resected Stage I Lung Cancer","authors":"Federica Sabia MSc ,&nbsp;Camilla Valsecchi MSc ,&nbsp;Roberta Eufrasia Ledda MD ,&nbsp;Giorgio Bogani MD ,&nbsp;Riccardo Orlandi MD ,&nbsp;Luigi Rolli MD ,&nbsp;Michele Ferrari MD ,&nbsp;Maurizio Balbi MD ,&nbsp;Alfonso Marchianò MD ,&nbsp;Ugo Pastorino MD","doi":"10.1016/j.jtocrr.2025.100788","DOIUrl":"10.1016/j.jtocrr.2025.100788","url":null,"abstract":"<div><h3>Introduction</h3><div>Coronary artery calcification (CAC) is a well-known cardiovascular risk factor. In the past year, the CAC score has been investigated in lung cancer (LC) screening, suggesting promising results in terms of mortality risk assessment. Nevertheless, its role in patients with LC is still to be investigated. This study aimed to evaluate the performance of a fully automated CAC scoring alone and combined with a prognostic index on the basis of perioperative routine blood tests in predicting 5-year survival of patients with stage I LC.</div></div><div><h3>Methods</h3><div>This study included 536 consecutive patients with stage I LC who underwent preoperative chest computed tomography followed by surgical resection. The CAC score was measured by commercially available, fully automated artificial intelligence software. The primary outcome was the 5-year overall survival rate.</div></div><div><h3>Results</h3><div>A total of 110 patients (20.5%) had a CAC score greater than or equal to 400, 149 (27.8%) between 100 and 399, and 277 (51.7%) had less than 100. Male smokers had the highest CAC values: 32% compared with only 17% of nonsmokers. Females had lower CAC values compared with males both in smokers and nonsmokers: CAC greater than or equal to 400 only for 10% of smoking females and 0% in nonsmoking females. The 5-year survival was 80.3% overall, 84.7% in CAC less than 100, 77.5% in CAC 100 to 399, and 73.5% in CAC greater than or equal to 400 (<em>p</em> = 0.0047).</div></div><div><h3>Conclusions</h3><div>We observed that the CAC score predicted the 5-year overall survival in patients with resected stage I LC, both alone and combined with the modified routine blood test score. These results open new prospects for the prevention of noncancer mortality in patients with early-stage LC.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 3","pages":"Article 100788"},"PeriodicalIF":3.0,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143173714","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":"Temporal Trends in the Utilization and Survival Outcomes of Lobar, Segmental, and Wedge Resection for Early-Stage NSCLC, 2004 to 2020","authors":"Eden Z. Deng BS ,&nbsp;Xiaofei Wang PhD ,&nbsp;Jianrong Zhang MD, MPH ,&nbsp;Thomas E. Stinchcombe MD ,&nbsp;Chi-Fu (Jeffrey) Yang MD ,&nbsp;Nasser Altorki MD","doi":"10.1016/j.jtocrr.2025.100794","DOIUrl":"10.1016/j.jtocrr.2025.100794","url":null,"abstract":"<div><h3>Introduction</h3><div>Although lobectomy has long been the standard of surgical treatment for early-stage NSCLC, segmental and wedge resections have become another option often used over the past two decades.</div></div><div><h3>Methods</h3><div>To examine the trends over time in the utilization, quality, and overall survival (OS) differences of lobectomy, segmentectomy, and wedge resection, we performed an observational, population-level study of 76,466 patients with T1 or T2 N0M0 NSCLC tumors 2 cm or less in size in the National Cancer Database, from 2004 to 2020. To compare the OS of the three treatments, we used inverse probability of treatment weighting to analyze a subgroup of cases with nodal examination and minimal comorbidity burden.</div></div><div><h3>Results</h3><div>From 2004 to 2020, the use of lobectomy decreased from 75.2% to 67.6% of resections, wedge remained relatively stable (20.5%–22.8%), and segmentectomy increased from 4.3% to 9.7%. The likelihood of nodal assessments and negative margins has increased for all treatments. Younger patients, patients with low comorbidity burden, and patients with smaller tumors have become increasingly likely to receive segmental and wedge resections. Five-year OS of segmentectomy (80.6%, 95% confidence interval [CI]: 78.1%–83.2%) remained noninferior to lobectomy (83.6%, 95% CI: 83.1%–84.1%]), whereas wedge resection was inferior until 2016 to 2019 (five-y OS = 79.9%, 95% CI: 75.9%–83.8%).</div></div><div><h3>Conclusions</h3><div>Sublobar resections, particularly segmentectomies, have increased in frequency and quality. The growing use of sublobar resections for younger and healthier patients highlights the need for additional clinical evidence demonstrating whether these trends do indeed lead to better outcomes.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 3","pages":"Article 100794"},"PeriodicalIF":3.0,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143348352","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":"Impact of Immune Checkpoint Inhibitors and Local Radical Treatment on Survival Outcomes in Synchronous Oligometastatic NSCLC","authors":"Mandy Jongbloed MD ,&nbsp;Valentina Bartolomeo MD ,&nbsp;Martina Bortolot MD ,&nbsp;Shahan Darwesh MD ,&nbsp;Jarno W.J. Huijs MD ,&nbsp;Safiye Dursun MD ,&nbsp;Juliette Degens MD, PhD ,&nbsp;Ben E.E.M. van den Borne MD, PhD ,&nbsp;Maggy Youssef-El Soud MD, PhD ,&nbsp;Marcel Westenend MD, PhD ,&nbsp;Cordula Pitz MD, PhD ,&nbsp;Dirk K.M. De Ruysscher MD, PhD ,&nbsp;Lizza E.L. Hendriks MD, PhD","doi":"10.1016/j.jtocrr.2025.100790","DOIUrl":"10.1016/j.jtocrr.2025.100790","url":null,"abstract":"<div><h3>Introduction</h3><div>The impact of an immune checkpoint inhibitor (ICI)–based systemic treatment strategy with or without local radical treatment (LRT) on outcomes for patients with NSCLC and synchronous oligometastatic disease (sOMD) is unknown.</div></div><div><h3>Methods</h3><div>Multicenter retrospective study including adequately staged patients, with sOMD NSCLC (maximum five metastases in three organs [European Organization for Research and Treatment of Cancer definition]) between January 1, 2015 and December 31, 2022, treated with a first-line ICI-based versus chemotherapy-only regimen. Primary end points were progression-free survival and overall survival (OS) for an ICI-based versus chemotherapy-only strategy. Subgroup analyses were performed for patients who were deemed candidates for LRT in the multidisciplinary meeting and those proceeding to LRT.</div></div><div><h3>Results</h3><div>A total of 416 patients were included, treated with chemotherapy-ICI (n = 138) or chemotherapy-only (n = 278), 319 out of 416 were deemed candidates by multidisciplinary meetings for LRT, whereas 192 (60%) proceeded to LRT. The median OS was significantly longer in the chemotherapy-ICI compared with the chemotherapy-only group (33.6 versus 15.9 mo, hazard ratio [HR] = 0.5, 95% confidence interval [CI]: 0.4–0.7, <em>p</em> &lt; 0.001), in the subgroups who were candidate for LRT (36.1 versus 17.2 mo, HR = 0.5, 95% CI: 0.4–0.7, <em>p</em> &lt; 0.001) and those proceeding to LRT (not reached versus 23.1 mo, HR = 0.4, 95% CI: 0.2–0.7, <em>p</em> &lt; 0.001). In multivariate analysis, an ICI-based strategy was associated with improved survival in the total group (HR = 0.6, 95% CI: 0.4–0.9, <em>p</em> &lt; 0.001), in those with intention of LRT (HR = 0.6, 95% CI: 0.4–0.9, <em>p</em> = 0.02) and those who proceeded to LRT (HR = 0.3, 95% CI: 0.1–0.6, <em>p</em> = 0.002).</div></div><div><h3>Conclusions</h3><div>An ICI-based systemic treatment strategy (±LRT) is associated with improved survival compared with chemotherapy-only (±LRT) for patients with sOMD NSCLC. Prospective randomized trial data are necessary to identify patients most likely to benefit from adding LRT.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 3","pages":"Article 100790"},"PeriodicalIF":3.0,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143173716","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":"Cannabidiol Vaping–Associated Multifocal NSCLC in a 24-Year-Old Female: A Case Report","authors":"Mansi Barthwal MD ,&nbsp;Nataliya Moldovan MD ,&nbsp;Shantanu Banerji MD ,&nbsp;Julian O. Kim MD","doi":"10.1016/j.jtocrr.2025.100789","DOIUrl":"10.1016/j.jtocrr.2025.100789","url":null,"abstract":"<div><div>Vaping use among Canadian youth is rising but the long-term sequelae of cannabidiol (CBD) vaping are not yet elucidated. Vaping aerosols contain carcinogens; however, owing to the latency period between carcinogen exposure and clinical presentation of malignancies, at present, there is a paucity of reported CBD vaping–associated lung cancers. We present the case of a 24-year-old female with nonspecific respiratory symptoms who developed multifocal NSCLC attributable to extensive CBD vaping.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 3","pages":"Article 100789"},"PeriodicalIF":3.0,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143174197","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":"Novel PLEC-EML4-ALK Double Fusion Underlying Crizotinib Resistance in a Metastatic Inflammatory Myofibroblastic Tumor: A Case Report","authors":"Alessandra Maleddu MD ,&nbsp;Trista K. Hinz MS ,&nbsp;Margaret A. Black MD ,&nbsp;Dara L. Aisner MD, PhD ,&nbsp;Carrie B. Marshall MD ,&nbsp;Anthony D. Elias MD ,&nbsp;Breelyn A. Wilky MD ,&nbsp;Lynn E. Heasley PhD ,&nbsp;Kurtis D. Davies PhD","doi":"10.1016/j.jtocrr.2025.100791","DOIUrl":"10.1016/j.jtocrr.2025.100791","url":null,"abstract":"<div><div><em>ALK</em> fusions are frequent oncogenic drivers in inflammatory myofibroblastic tumors. Treatment with crizotinib is effective in fusion-positive patients; however, acquired resistance remains a challenge. Here, we present a case of <em>EML4-ALK</em>-positive metastatic inflammatory myofibroblastic tumor that initially responded to crizotinib but developed resistance. The progressing lesion revealed the acquisition of a “double fusion” event in which <em>EML4-ALK</em> was additionally fused to <em>PLEC</em> to create a <em>PLEC-EML4-ALK</em> transcript. The double fusion was associated with an increase in <em>ALK</em> expression, mimicking the <em>ALK</em> fusion amplification that is a known mechanism of resistance to crizotinib in lung cancer. On transition to the more potent ALK inhibitor alectinib, the patient exhibited a dramatic response. Thus, the formation of a double fusion represents a novel and targetable mechanism of resistance to crizotinib.</div></div>","PeriodicalId":17675,"journal":{"name":"JTO Clinical and Research Reports","volume":"6 5","pages":"Article 100791"},"PeriodicalIF":3.0,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143697855","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}