Clinical lung cancer最新文献

{"title":"Induction Immunochemotherapy Followed by Hypo-Fractionated Radiotherapy in Unresectable Stage III Non-Small Cell Lung Cancer.","authors":"Zihao Zhu, Jianfeng Wu, Lijun Zhao, Ning Jiang, Yu Chen, Xue Song, Ming Li, Ming Jiang, Meiqi Shi, Shaorong Yu, Binhui Ren, Rong Yin, Feng Jiang, Li Wang, Cheng Kong, Xiangzhi Zhu","doi":"10.1016/j.cllc.2025.01.012","DOIUrl":"https://doi.org/10.1016/j.cllc.2025.01.012","url":null,"abstract":"<p><strong>Purpose: </strong>To evaluate the efficacy and safety of induction immunochemotherapy followed by hypo-fractionated radiotherapy (Hypo-RT) for locally advanced unresectable non-small cell lung cancer (LA-NSCLC).</p><p><strong>Methods: </strong>This retrospective analysis involved the data of 35 patients with unresectable stage III LA-NSCLC receiving immunotherapy plus Hypo-RT from January 1, 2019, to December 31, 2023. At least 2 cycles of induction immunochemotherapy were initially administered, followed by a definitive Hypo-RT at 4 Gy per fraction. The primary endpoint was overall survival (OS) and the secondary endpoints were progression-free survival (PFS) and grade ≥ 3 nonhematologic toxicities. Time-to-event outcomes for the entire cohort were calculated using the Kaplan-Meier method.</p><p><strong>Results: </strong>At a median follow-up of 31.5 months (95% confidence interval, 26.1 to 36.9 months), median OS did not reach, with 1, 2, and 3-year OS rates of 100.0%, 82.5%, and 77.3%, respectively. Disease progression or death was recorded in 18 (51.4%) patients, with a median PFS of 28.0 months (95% CI, 9.4 to 46.6 months). The 1, 2, and 3-year PFS rates were 74.3%, 55.7%, and 47.6%, respectively.</p><p><strong>Conclusion: </strong>Induction immunochemotherapy followed by Hypo-RT demonstrated promising efficacy and acceptable toxicity in patients with LA-NSCLC. Studies on Hypo-RT combined with induction and consolidation immunotherapies are warranted in the future.</p>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Safety of Atezolizumab in Chinese Patients With Advanced Thymic Carcinoma: A Multicenter, Single-Arm Phase 2 Study","authors":"Shun Lu ,&nbsp;Xuezhen Ma ,&nbsp;Lunxu Liu ,&nbsp;Qiang Li ,&nbsp;Jian Hu ,&nbsp;Changli Wang ,&nbsp;Jianxing He ,&nbsp;Xiufeng Hu ,&nbsp;Chun Chen ,&nbsp;Zhenzhou Yang ,&nbsp;Dandan Hu ,&nbsp;Yanjun Shi ,&nbsp;Yi Zhou ,&nbsp;Mo Chen","doi":"10.1016/j.cllc.2025.01.011","DOIUrl":"10.1016/j.cllc.2025.01.011","url":null,"abstract":"<div><h3>Introduction</h3><div>There are limited treatment options for thymic carcinoma. This study aimed to evaluate the efficacy and safety of atezolizumab for the treatment of advanced thymic carcinoma after failure with prior systemic therapy.</div></div><div><h3>Patients and Methods</h3><div>Patients aged ≥ 18 years with advanced thymic carcinoma after failure with prior systemic therapy were enrolled at 10 medical centers in China. Atezolizumab 1200 mg was administered on Day 1 (baseline) every 3 weeks until unacceptable toxicity/loss of clinical benefit. The primary efficacy endpoint was the confirmed objective response rate in the full analysis set.</div></div><div><h3>Results</h3><div>Between 29 July 2020 and 28 December 2022, 34 patients enrolled (median age, 54.5 years), and 16 (47.1%) had received ≥ 2 prior lines of therapy. At the cut-off date (July 16, 2023), the median follow-up duration was 19.1 months. The confirmed objective response rate (ORR) was 14.7% (95% confidence interval, 5.0%-31.1%); disease control rate, 58.8%; median progression-free survival (PFS), 3.2 months; 24-month OS rate, 63.2%; Better ORR and PFS were observed in PD-L1-positive patients versus PD-L1-negative patients (40.0% vs. 0% and 7.4 vs. 1.5 months, respectively). No correlation was observed with TMB. The incidence of adverse events (AEs) was 94.1%; serious AEs, 26.5%; immune-related AEs, 29.4%; and AEs leading to drug withdrawal, 2.9%.</div></div><div><h3>Conclusions</h3><div>In patients with advanced thymic carcinoma who had failed prior systemic therapy, atezolizumab was well-tolerated with a manageable toxicity profile and showed encouraging the antitumor activity, especially in patients with PD-L1-positive tumors.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"26 3","pages":"Pages 244-252.e2"},"PeriodicalIF":3.3,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Sarcopenia With Toxicity and Survival in Patients With Lung Cancer, a Multi-Institutional Study With External Dataset Validation.","authors":"Anurag Saraf, John He, Kee-Young Shin, Jakob Weiss, Mark M Awad, Justin Gainor, Benjamin H Kann, David C Christiani, Hugo J W L Aerts, Raymond H Mak","doi":"10.1016/j.cllc.2025.01.010","DOIUrl":"https://doi.org/10.1016/j.cllc.2025.01.010","url":null,"abstract":"<p><strong>Introduction: </strong>Sarcopenia is associated with worse survival in non-small cell lung cancer (NSCLC), but less studied in association with toxicity. Here, we investigated the association between imaging-assessed sarcopenia with toxicity in patients with NSCLC.</p><p><strong>Methods: </strong>We analyzed a \"chemoradiation\" cohort (n = 318) of patients with NSCLC treated with chemoradiation, and an external validation \"chemo-surgery\" cohort (n = 108) who were treated with chemotherapy and surgery from 2002 to 2013 at a different institution. A deep-learning pipeline utilized pretreatment computed tomography scans to estimate SM area at the third lumbar vertebral level. Sarcopenia was defined by dichotomizing SM index, (SM adjusted for height and sex). Primary endpoint was NCI CTCAE v5.0 grade 3 to 5 (G3-5) toxicity within 21-days of first chemotherapy cycle. Multivariable analyses (MVA) of toxicity endpoints with sarcopenia and baseline characteristics were performed by logistic regression, and overall survival (OS) was analyzed using Cox regression.</p><p><strong>Results: </strong>Sarcopenia was identified in 36% and 36% of patients in the chemoradiation and chemo-surgery cohorts, respectively. On MVA, sarcopenia was associated with worse G3-5 toxicity in chemoradiation (HR 2.00, P < .01) and chemo-surgery cohorts (HR 2.95, P = .02). In the chemoradiation cohort, worse OS was associated with G3-5 toxicity (HR 1.42, P = .02) but not sarcopenia on MVA. In chemo-surgery cohort, worse OS was associated with sarcopenia (HR 2.03, P = .02) but not G3-5 toxicity on MVA.</p><p><strong>Conclusion: </strong>Sarcopenia, assessed by an automated deep-learning system, was associated with worse toxicity and survival outcomes in patients with NSCLC. Sarcopenia can be utilized to tailor treatment decisions to optimize adverse events and survival.</p>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Effectiveness of Nivolumab and Ipilimumab Plus Chemotherapy Versus Pembrolizumab Plus Chemotherapy in PD-L1 Negative Metastatic Non-Small Cell Lung Cancer Patients.","authors":"Marjon V Verschueren, Dagmar T A Hiensch, Peter M J Plomp, Lisanne A Kastelijn, Ewoudt M W van de Garde, Bas J M Peters","doi":"10.1016/j.cllc.2025.01.009","DOIUrl":"https://doi.org/10.1016/j.cllc.2025.01.009","url":null,"abstract":"<p><strong>Background: </strong>Recently, the combination of nivolumab, ipilimumab and chemotherapy (NIC) became available for the treatment of metastatic non-small cell lung cancer (mNSCLC) patients, introducing a new treatment option. This study aimed to compare the treatment response and real-world outcomes of NIC with the current standard of care pembrolizumab plus chemotherapy (PC) in PD-L1 negative mNSCLC patients treated in clinical practice and to compare these outcomes with the results of the Checkmate-9LA trial.</p><p><strong>Methods: </strong>All mNSCLC patients with PD-L1<1% treated with NIC or PC at 2 large teaching hospitals in the Netherlands between 2019 and 2023 were included. The objective response rate (ORR) and progression-free survival (PFS) and treatment characteristics of patients treated with NIC were compared to those of patients treated with PC. Additionally, the real-world outcomes of NIC were compared to the results from the CheckMate 9LA trial. A multivariate Cox regression was used to calculate PFS hazard ratios (HR).</p><p><strong>Results: </strong>PD-L1 negative mNSCLC patients treated with NIC had a higher ORR than those treated with PC (41% versus 27%, P = .08). The PFS was slightly longer for patients treated with NIC versus PC (5.5 vs. 4.5 months, aHR = 0.91 [95% CI 0.59-1.58]), although not statistically significant. The treatment discontinuation rates were comparable between the real-world NIC and PC cohorts (72% vs. 68%), mostly due to disease progression (67% vs. 64%). The outcomes for patients treated with NIC in clinical practice were comparable to the Checkmate-9LA trial.</p><p><strong>Conclusion: </strong>For mNSCLC patients with <1% PD-L1 expression, the treatment responses to NIC were numerically better than to PC. Larger cohorts with longer follow-up periods and overall survival endpoints are needed to further establish the role of NIC in PD-L1 negative patients.</p>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunotherapy for Early-Stage Non–Small Cell Lung Cancer: A Practical Guide of Current Controversies","authors":"William J. Phillips ,&nbsp;Ashley Jackson ,&nbsp;Biniam Kidane ,&nbsp;Gerald Lim ,&nbsp;Vishal Navani ,&nbsp;Paul Wheatley-Price","doi":"10.1016/j.cllc.2025.01.006","DOIUrl":"10.1016/j.cllc.2025.01.006","url":null,"abstract":"<div><div>The role of immunotherapy as systemic therapy for nonmetastatic non–small cell lung cancer (NSCLC) has evolved rapidly over the last decade. There are several well-conducted phase 3 clinical trials evaluating immunotherapy in the neoadjuvant, perioperative, adjuvant and nonoperative setting. In this narrative review, we summarize the data from these studies and discuss ongoing controversies in applying these data to clinical practice. These controversies relate to the value of the adjuvant component of perioperative immunotherapy, treatment of patients with PDL1 negative tumors, defining resectability, optimal use of operative versus nonoperative management, the role of stereotactic radiation therapy for very early lung cancers, and management of tumors with an oncogenic driver.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"26 3","pages":"Pages 179-190"},"PeriodicalIF":3.3,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Retrospective Evaluation of PD-L1 Expression and Heterogeneity in Early-Stage Non-Small Cell Lung Cancer (REPLICA)","authors":"Eleni C. Josephides ,&nbsp;Daniel Smith ,&nbsp;Andrea Bille ,&nbsp;Akshay Patel ,&nbsp;Hannah L. Rush ,&nbsp;Roberta Dunn ,&nbsp;Daniel J. Hughes ,&nbsp;Sarah Hunter ,&nbsp;Phillipe Taniere ,&nbsp;Danielle Crawley ,&nbsp;Maria Monroy-Iglesias ,&nbsp;Annie-Rose Henry ,&nbsp;Ana Montes ,&nbsp;Mieke Van Hemelrijck ,&nbsp;James Spicer ,&nbsp;Debra Josephs ,&nbsp;George Santis ,&nbsp;Daisuke Nonaka ,&nbsp;Eleni M. Karapanagiotou","doi":"10.1016/j.cllc.2025.01.008","DOIUrl":"10.1016/j.cllc.2025.01.008","url":null,"abstract":"<div><h3>Background</h3><div>Immune checkpoint inhibitors have improved survival in patients with non-small cell lung cancer (NSCLC). Whilst PD-L1 expression is a useful predictive biomarker, data on concordance of expression between primary tumor and nodal metastases in the surgical setting are sparse.</div></div><div><h3>Methods</h3><div>We assessed PD-L1 expression in paired primary tumor and involved lymph node samples from 451 consecutive patients with stage IIB-IIIB NSCLC who underwent curative lung resection and lymphadenectomy at our institution between 2009 and 2018, to assess intertumor heterogeneity. Clinical records were examined to determine survival outcomes, and relationship to PD-L1 expression was explored.</div></div><div><h3>Results</h3><div>Using PD-L1 expression categories of &lt; 1%, 1% to 49% and ≥ 50% there was heterogeneity of PD-L1 expression between the primary and corresponding lymph node metastases in 24% of cases with only moderate positive correlation (Spearman's coefficient 0.7). 46% of early-stage primary tumors expressed PD-L1, although only 11% demonstrated a high (&gt; 50%) level. It was more common for PD-L1 expression to be higher in the primary tumor than its metastatic lymph node than the converse. PD-L1 expression irrespective of site, had no significant impact on disease-free or overall survival.</div></div><div><h3>Conclusion</h3><div>Our study confirms the heterogeneity of PD-L1 expression in early-stage NSCLC and suggests that a biopsy specimen from a single site may not be a comprehensive representation of PD-L1 expression. The proportion of tumours with high PD-L1 expression appears lower in early-stage NSCLC than in advanced disease.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"26 3","pages":"Pages e223-e231"},"PeriodicalIF":3.3,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143363925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CNS Outcomes of Osimertinib Plus Chemotherapy in Patients With EGFR Mutation Positive Lung Cancer Beyond Osimertinib Progression","authors":"Wesley K.Y. Wong ,&nbsp;Kevin K.S. Mok ,&nbsp;Giselle P.C. Tsui ,&nbsp;Olivia H. Chen ,&nbsp;Herbert H.F. Loong ,&nbsp;Landon L. Chan ,&nbsp;Kelvin Yan ,&nbsp;Frankie Mo ,&nbsp;Kirsty W.C. Lee ,&nbsp;K.C. Lam ,&nbsp;Florence S.T. Mok ,&nbsp;David Johnson ,&nbsp;Allen C.C. Chen ,&nbsp;Benjamin Lam ,&nbsp;Matthew Lee ,&nbsp;Tony S.K. Mok ,&nbsp;Molly S.C. Li","doi":"10.1016/j.cllc.2025.01.007","DOIUrl":"10.1016/j.cllc.2025.01.007","url":null,"abstract":"<div><h3>Background</h3><div>Central nervous system (CNS) metastases are common among patients with epidermal growth factor receptor (<em>EGFR</em>) mutation positive non–small cell lung cancer (NSCLC). Osimertinib in combination with chemotherapy beyond osimertinib progression may minimize CNS progression.</div></div><div><h3>Method</h3><div>In this retrospective analysis, patients with advanced <em>EGFR</em> mutation positive NSCLC and brain metastases who received platinum-based chemotherapy (PbChT) after disease progression on osimertinib were enrolled. The primary endpoint was real-world CNS progression-free survival (rwCNS-PFS) between patients who received PbChT with and without osimertinib continuation. Secondary endpoints included competing risk analysis of CNS progression and incidence of salvage radiotherapy to brain.</div></div><div><h3>Results</h3><div>A total of 101 patients were analyzed, out of which, 39 (39%) continued osimertinib with chemotherapy (OSI+ cohort) and 62 (61%) received chemotherapy alone (OSI- cohort). Median rwCNS-PFS was significantly longer in the OSI+ cohort (9.0 months, 95% CI 6.6-11.4) than the OSI- cohort (5.7 months, 95% CI 4.6-6.9) (HR 0.37, 95% CI 0.18-0.76, <em>P =</em> .007). This remained significant after adjustment for <em>EGFR</em> mutation, line of osimertinib treatment, prior radiotherapy to brain, and CNS progression on osimertinib monotherapy. Estimated probability of CNS progression at 6 months was 5.6% in OSI+ cohort versus 20.9% in OSI- cohort. Incidence of salvage radiotherapy to brain was lower in the OSI+ cohort (15%) compared to OSI- cohort (24%).</div></div><div><h3>Conclusion</h3><div>In patients with <em>EGFR</em> mutation positive NSCLC and brain metastases, continuing osimertinib with chemotherapy after progression on osimertinib significantly reduced risk of CNS progression. Prospective studies are warranted to define the optimal treatment strategy for this patient population.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"26 3","pages":"Pages e214-e222.e5"},"PeriodicalIF":3.3,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Imaging Findings Related to Lung Tract Sealant Use in Percutaneous CT-guided Lung Biopsy","authors":"Mohamed M. Soliman ,&nbsp;Blake Gershon ,&nbsp;Deirdre Sullivan RA ,&nbsp;Joanna G. Escalon ,&nbsp;Lauren K. Groner ,&nbsp;Meghan Cahill ,&nbsp;Gulce Askin ,&nbsp;Brian W. Sullivan ,&nbsp;Bradley B. Pua","doi":"10.1016/j.cllc.2025.01.003","DOIUrl":"10.1016/j.cllc.2025.01.003","url":null,"abstract":"<div><h3>Purpose</h3><div>This study examines the imaging findings and malignancy suspicion associated with hydrogel lung tract sealants (h-LTS) used after CT-guided lung biopsy (CTLB).</div></div><div><h3>Materials and Methods</h3><div>Charts of patients who underwent CTLB from 01/2016 to 01/2020 were reviewed for biopsy date, h-LTS use, resection, and imaging follow-up. Exclusion criteria included resection &lt;3 months postbiopsy, no imaging ≥3 months, and pleural nodules. Postbiopsy imaging was analyzed for abnormalities at the biopsy tract. Out of 164 patients who underwent CTLB with h-LTS, a random subset of 64 patients (Group A) was anonymized and compared with another randomly selected, anonymized group of 64 patients who underwent CTLB without h-LTS during the study period (Group B) to assess inter-reader agreement. Two cardiothoracic radiologists reviewed the anonymized intraprocedural biopsy CT and follow-up imaging at multiple intervals (3-6, 6-12, 12-24, &gt;24months) for abnormalities along the biopsy tract and associated malignancy suspicion (Categories 1-5 [low-high]).</div></div><div><h3>Results</h3><div>A serpiginous lesion was observed along the biopsy tract in 60% (99/164) of patients who received h-LTS, lasting an average of 23.3 months (Range: 3-67). Moderate inter-reader agreement was seen for abnormalities in Group A patients at all follow-up intervals. FDG-PET/CT showed mild uptake for up to 5 years in 46% of patients. At initial follow-up, 17% of h-LTS scars were rated Category 3 or higher suspicion for malignancy. Most h-LTS scars maintained or decreased in suspicion in later follow-ups.</div></div><div><h3>Conclusion</h3><div>h-LTS is associated with a serpiginous scar, which may be mildly hypermetabolic and last up to 5 years.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"26 3","pages":"Pages 236-243"},"PeriodicalIF":3.3,"publicationDate":"2025-01-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Kirsten Rat Sarcoma Virus Mutations Effect On Tumor Doubling Time And Prognosis Of Solid Dominant Stage I Lung Adenocarcinoma","authors":"Riccardo Tajè ,&nbsp;Vincenzo Ambrogi ,&nbsp;Federico Tacconi ,&nbsp;Filippo Tommaso Gallina ,&nbsp;Gabriele Alessandrini ,&nbsp;Daniele Forcella ,&nbsp;Simonetta Buglioni ,&nbsp;Paolo Visca ,&nbsp;Alexandro Patirelis ,&nbsp;Fabiana Letizia Cecere ,&nbsp;Enrico Melis ,&nbsp;Antonello Vidiri ,&nbsp;Isabella Sperduti ,&nbsp;Federico Cappuzzo ,&nbsp;Silvia Novello ,&nbsp;Mauro Caterino ,&nbsp;Francesco Facciolo","doi":"10.1016/j.cllc.2025.01.001","DOIUrl":"10.1016/j.cllc.2025.01.001","url":null,"abstract":"<div><h3>Introduction</h3><div>To analyze the impact of Kirsten-Rat-Sarcoma Virus (<em>KRAS</em>) mutations on tumor-growth as estimated by tumor-doubling-time (TDT) among solid-dominant clinical-stage I lung adenocarcinoma. Moreover, to evaluate the prognostic role of <em>KRAS</em> mutations, TDT and their combination in completely-resected pathologic-stage I adenocarcinomas.</div></div><div><h3>Methods</h3><div>In this single-center retrospective analysis, completely resected clinical-stage I adenocarcinomas presenting as solid-dominant nodules (consolidation-to-tumor ratio &gt; 0.5) in at least 2 preoperative computed-tomography scans were enrolled. Nodules’ growth was scored as fast (TDT &lt; 400 days) or slow (TDT &gt; 400 days). <em>KRAS</em>-mutated adenocarcinomas were identified with next-generation sequencing. Logistic- and Cox-regressions were used to identify predictors of fast-growth and disease-free survival (DFS), respectively.</div></div><div><h3>Results</h3><div>Among 151 patients, 83 (55%) had fast-growing nodules and 64 (42.4%) were <em>KRAS</em>-mutated.</div><div>Fast-growing nodules outnumbered in the <em>KRAS</em>-mutated group (n = 45; 70.3%), median TDT 95-days (interquartile range, IQR 43.5-151.5) compared to the <em>KRAS</em> wild-type group (38, 43.7%), median TDT 138-days (IQR 70.3-278.5). <em>KRAS</em>-mutations predicted faster-growth at multivariable analysis (<em>P = .</em>009).</div><div>In a subgroup analysis including 108 pathologic-stage I adenocarcinomas, neither <em>KRAS</em>-mutations (<em>P = .</em>081) nor fast-growing pattern (<em>P = .</em>146) affected DFS. Nevertheless, the association of <em>KRAS</em>-mutations and fast-growing pattern identified a subgroup of patients with worse DFS (<em>P = .</em>02). The combination of fast-growing and <em>KRAS</em>-mutations (hazard-ratio 2.97 [95%CI 1.22-7.25]; <em>P = .</em>017) and average nodule diameter at diagnosis (hazard-ratio 1.08 [95%CI 1.03-1.14]; <em>P = .</em>004) were independent predictors of worse DFS.</div></div><div><h3>Conclusion</h3><div><em>KRAS</em> mutations are associated to faster growth, in clinical-stage I adenocarcinoma presenting at diagnosis as solid-dominant nodules undergoing complete resection. Moreover, faster-growth identifies a subgroup of pathologic-stage I <em>KRAS</em>-mutated adenocarcinomas with higher recurrences.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"26 3","pages":"Pages 210-220.e1"},"PeriodicalIF":3.3,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143037384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"POLE Mutation Associated With Microsatellite Instability and High Tumor Mutational Burden Confers Exquisite Sensitivity to Immune Checkpoint Inhibitor Therapy in Non–Small Cell Lung Cancer: A Case Report and Genomic Database Analysis","authors":"Matthew S. Lara ,&nbsp;Jonathan W. Riess ,&nbsp;Guneet Kaleka ,&nbsp;Alexander Borowsky ,&nbsp;John D. McPherson ,&nbsp;Luis A. Godoy ,&nbsp;Lorenzo Grego ,&nbsp;Primo N Lara Jr. ,&nbsp;Nicholas Mitsiades","doi":"10.1016/j.cllc.2025.01.005","DOIUrl":"10.1016/j.cllc.2025.01.005","url":null,"abstract":"<div><div><ul><li><span>•</span><span><div>DNA polymerase epsilon (<em>POLE</em>) mutations have emerged as a potential predictive biomarker for response to immunotherapy in advanced solid tumors, but are uncommon in non–small cell lung cancer (NSCLC). Here we present a patient with <em>POLE</em>-mutated NSCLC with high tumor mutational burden (TMB) and microsatellite instability (MSI), who experienced a complete response to a chemoimmunotherapy regimen that included an immune checkpoint inhibitor. Publicly available genomic sequencing databases were also queried for the prevalence of <em>POLE</em> mutations in NSCLC.</div></span></li><li><span>•</span><span><div>We describe the case of a 68-year-old male never smoker who was diagnosed with cT3 N0 M0 adenocarcinoma of the lung with a hypermutated phenotype characterized by a pathogenic <em>POLE</em> mutation, MSI-high, and very high TMB (572 mutations/megabase) as determined by next generation sequencing. Following completion of 4 cycles of neoadjuvant nivolumab with carboplatin and pemetrexed, the patient underwent left upper lobectomy and mediastinal lymph node dissection, and was found to have had a complete pathologic response.</div></span></li><li><span>•</span><span><div>Analysis of DNA sequencing databases confirmed that pathogenic <em>POLE</em> mutations, while very uncommon in NSCLC, appear to be associated with a hypermutated phenotype resulting in high TMB. This clinical vignette illustrates the potential for profound response to immunotherapy in NSCLCs harboring this phenotype. Further work is necessary to characterize <em>POLE</em> mutational status as a potential beneficial predictive biomarker.</div></span></li></ul></div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"26 3","pages":"Pages e207-e213"},"PeriodicalIF":3.3,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}