Clinical lung cancer最新文献

{"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, Jonathan W Riess, Guneet Kaleka, Alexander Borowsky, John D McPherson, Luis A Godoy, Lorenzo Grego, Primo N Lara, Nicholas Mitsiades","doi":"10.1016/j.cllc.2025.01.005","DOIUrl":"https://doi.org/10.1016/j.cllc.2025.01.005","url":null,"abstract":"","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":" ","pages":""},"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}

{"title":"Elucidating the Role of EGFR^L858R in Brain Metastasis Among Patients With Advanced NSCLC Undergoing TKI Therapy.","authors":"Eduardo Rios-Garcia, Alberto Guijosa, Enrique Caballé-Perez, David Davila-Dupont, Carlos Izquierdo, Alicia Regino, Natalia Lozano-Vazquez, Andrea Solis, Luis Lara-Mejía, Jordi Remon, Bernardo Cacho-Díaz, Andrés F Cardona, Oscar Arrieta","doi":"10.1016/j.cllc.2025.01.004","DOIUrl":"https://doi.org/10.1016/j.cllc.2025.01.004","url":null,"abstract":"<p><strong>Introduction: </strong>Brain metastases (BM) are a prevalent and severe complication of non-small cell lung cancer (NSCLC) that significantly affects quality of life. Although several predictive factors for BM have been identified, the influence of EGFR mutation subtypes remains under-explored.</p><p><strong>Methods: </strong>We retrospectively examined patients with advanced NSCLC and EGFR mutations treated with first-line EGFR-TKIs. Our primary endpoint was intracranial progression-free survival (icPFS), defined as the time from the initiation of upfront treatment to the development of BM, the progression of existing brain lesions, or death. Additionally, we evaluated intracranial objective response rates (icORR) and disease control rates (icDCR) for patients with baseline BM. Subgroup and multivariate analyses were performed to adjust for relevant factors.</p><p><strong>Results: </strong>Of the 324 patients analyzed, 40.7% had baseline BM. Overall, the EGFR^L858R mutation was linked to a significantly shorter median icPFS of 13.9 months, compared to 23.4 months for those with EGFR^Δ19 (HR 1.60, P < .0001) For patients without baseline BM, icPFS was 14.3 months for EGFR^L858R versus 26.2 months (HR 1.65, P = .007), while with baseline BM, it was 13.9 versus 18.5 months (HR 1.59, P = .035); icORR was lower for EGFR^L858R (31.2% vs. 58.8%). Multivariate analysis showed EGFR^L858R was independently linked to worse icPFS in patients with (HR 1.634, P = .031) and without BM (HR 1.606, P = .008), and lower icORR (OR 3.511, P = .007) and icDCR (OR 4.443, P = .006).</p><p><strong>Conclusions: </strong>EGFR^L858R mutation significantly impacts BM development, intracranial progression, and response, emphasizing its critical role in therapy selection.</p>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188554","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":"Regimen Selection for Chemoimmunotherapy in Nonsquamous Non-Small Cell Lung Cancer with Low PD-L1 Expression: A Multicenter Retrospective Cohort Study.","authors":"Tae Hata, Tadaaki Yamada, Yasuhiro Goto, Akihiko Amano, Yoshiki Negi, Satoshi Watanabe, Naoki Furuya, Tomohiro Oba, Tatsuki Ikoma, Akira Nakao, Keiko Tanimura, Hirokazu Taniguchi, Akihiro Yoshimura, Tomoya Fukui, Daiki Murata, Kyoichi Kaira, Shinsuke Shiotsu, Makoto Hibino, Asuka Okada, Yusuke Chihara, Hayato Kawachi, Takashi Kijima, Koichi Takayama","doi":"10.1016/j.cllc.2025.01.002","DOIUrl":"https://doi.org/10.1016/j.cllc.2025.01.002","url":null,"abstract":"<p><strong>Background: </strong>Although chemoimmunotherapy is recommended for advanced nonsquamous non-small cell lung cancer (NSCLC) with low programmed cell death ligand 1 (PD-L1) expression, no head-to-head comparisons of immune checkpoint inhibitors (ICIs) have been performed. Therefore, we compared the effect and safety of regimens in these patients to guide evidence-based treatment.</p><p><strong>Methods: </strong>This retrospective study included patients with advanced nonsquamous NSCLC with a PD-L1 tumor proportion score of 1% to 49% administered ICI combination platinum-based chemotherapy between May 2018 and May 2023 at 19 institutions in Japan. The main analysis compared survival outcomes and the incidence of grade ≥3 adverse events among regimens.</p><p><strong>Results: </strong>Among 316 included patients (median [range] age, 69 [36-89] years; 242 males; 41 never smokers), 200 (63%), 68 (22%), and 48 (15%) received chemotherapy combined with anti-programmed cell death protein 1 (PD-1), anti-PD-L1, and anti-PD-1/cytotoxic T-lymphocyte associated protein 4 (CTLA-4) antibodies, respectively. The median overall survival times were 28.6, 23.1, and 24.4 months (P = .41), and the median progression-free survival times were 9.4, 7.2, and 8.7 months (P = .28) in the anti-PD-1/Chemo, anti-PD-L1/Chemo and anti-PD-1/CTLA-4/Chemo groups, respectively. The anti-PD-1/CTLA-4/Chemo group had the lowest incidence of hematologic toxicity (P = .13) and the highest incidence of nonhematologic toxicity (P = .07). The incidence of grade ≥3 pneumonitis was significantly lower in the anti-PD-L1/Chemo group (P = .049).</p><p><strong>Conclusions: </strong>Despite comparable survival benefits, adverse events differed among three regimens in patients with low PD-L1 expression. Notably, anti-PD-L1 antibody combination chemotherapy may reduce the risk of severe pneumonitis.</p>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045756","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":"Clinical Characteristics and Management of Checkpoint Inhibitor Pneumonitis in Non–Small-Cell Lung Cancer Patients After Neoadjuvant Immunotherapy","authors":"Long Jiang ,&nbsp;Shanshan Jiang ,&nbsp;Wang Miao ,&nbsp;Yaofeng Shen ,&nbsp;Larisa Bolotina ,&nbsp;Hongda Zhu ,&nbsp;Ningyuan Zou ,&nbsp;Yu Tian ,&nbsp;Hanbo Pan ,&nbsp;Jia Huang ,&nbsp;Andrey Ryabov ,&nbsp;Qingquan Luo","doi":"10.1016/j.cllc.2024.10.012","DOIUrl":"10.1016/j.cllc.2024.10.012","url":null,"abstract":"<div><h3>Objective</h3><div>Neoadjuvant immunotherapy with checkpoint inhibitors has shown promising results for non–small-cell lung cancer (NSCLC) patients. However, it has been associated with immune-related adverse events (irAEs), including checkpoint inhibitor pneumonitis (CIP), which can be life-threatening.</div></div><div><h3>Methods</h3><div>This retrospective study analysed the medical records of 197 NSCLC patients who underwent neoadjuvant checkpoint inhibitor therapy to investigate the incidence, clinical characteristics, and management of CIP.</div></div><div><h3>Results</h3><div>Of the 197 patients, 24 (12.2%) developed CIP. The majority of patients presented with respiratory symptoms, and ground-glass opacities were the most common radiographic finding. Patients with CIP had a longer duration of immunotherapy and a higher baseline C-reactive protein level than those without CIP. Most cases were mild to moderate in severity (Grade 1: 11, Grade 2: 6, Grade 3: 5) and managed with corticosteroids, while 2 patients of Grade 4 developed severe respiratory failure requiring mechanical ventilation. No patient died due to respiratory failure.</div></div><div><h3>Conclusions</h3><div>CIP was identified as a potential complication of neoadjuvant treatment with checkpoint inhibitors in patients with resectable NSCLC. Therefore, close monitoring for CIP and prompt recognition and management of symptoms are essential for the safe use of checkpoint inhibitors in NSCLC patients. While the study also found that such neoadjuvant treatment can induce a major pathological response in a significant proportion of these patients, further research is required to fully understand and manage the risk factors of CIP in this patient population.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"26 1","pages":"Pages e91-e98"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692733","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":"Implementation and Retrospective Examination of a Lung Cancer Survivorship Clinic in a Comprehensive Cancer Center","authors":"Sarah N. Price ,&nbsp;Alana R. Willis ,&nbsp;Amy Hensley ,&nbsp;Jill Hyson ,&nbsp;Stephanie J. Sohl ,&nbsp;Ralph B. D'Agostino Jr ,&nbsp;Michael Farris ,&nbsp;W. Jeffrey Petty ,&nbsp;Alberto de Hoyos ,&nbsp;Kathryn E. Weaver ,&nbsp;Stacy Wentworth","doi":"10.1016/j.cllc.2024.09.008","DOIUrl":"10.1016/j.cllc.2024.09.008","url":null,"abstract":"<div><h3>Purpose</h3><div>The number of early-stage lung cancer survivors (LCS) is increasing, yet few survivorship programs address their specific needs. We developed a workflow to transition early-stage LCS to dedicated lung survivorship care and comprehensively identify and address their needs using electronic patient-reported outcomes (ePROs).</div></div><div><h3>Methods</h3><div>A lung cancer multidisciplinary team developed a workflow (eg, referrals, survivorship care plan delivery, documentation, orders, tracking, ePROs, and surveillance) for a survivorship clinic staffed by Advanced Practice Providers (APPs). ePROs included the NCCN Distress Thermometer, PROMIS-29, and investigator-developed patient satisfaction items. Patient characteristics, ePROs, and referrals are described; chi-square and t-tests examined ePRO completion by patient characteristics and compared PROMIS-29 domains by treatment modality and to a national sample.</div></div><div><h3>Results</h3><div>From January 2020-March 2023, 315 early-stage LCS completed a survivorship orientation visit. Patient satisfaction was high; 75% completed ePROs. Females were overall less likely to complete ePROs than males; male, age 65+, Black or other race, and rural patients were more likely to complete ePROs in clinic versus online. Patients reported lower symptom burden compared to a general population of early-stage LCS in the United States; scores were similar regardless of treatment modality. Rates of moderate-severe symptoms ranged from 6% (depression) to 42% (poor physical function); ≤ 20% had a referral placed.</div></div><div><h3>Conclusions</h3><div>A referral-based, APP-staffed survivorship clinic model for early-stage LCS which includes ePROs to identify specific needs is acceptable to patients. Future work should include outreach to female LCS and increasing supportive care referrals and acceptability to further address early-stage LCS reported needs.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"26 1","pages":"Pages e41-e54"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567650","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":"Phrenic Nerve Palsy after Stereotactic Body Radiotherapy for Central Lung Cancer: A Case Report","authors":"James C.H. Chow,&nbsp;Jeannie Y.K. Chik,&nbsp;Ka Man Cheung,&nbsp;Luke T.Y. Lee,&nbsp;Kam Hung Wong,&nbsp;Kwok Hung Au","doi":"10.1016/j.cllc.2024.10.006","DOIUrl":"10.1016/j.cllc.2024.10.006","url":null,"abstract":"<div><div><ul><li><span>•</span><span><div>Radiation-induced phrenic nerve palsy is an uncommon complication of stereotactic body radiotherapy (SBRT) for central lung tumor. The resultant paralysis of hemidiaphragm can be symptomatic and compromise respiratory function.</div></span></li><li><span>•</span><span><div>The phrenic nerve can be delineated on planning computed tomography images using landmarks of the surrounding mediastinal structures. It should be considered a standard organ at-risk in thoracic SBRT where the planning target volume is in close proximity.</div></span></li><li><span>•</span><span><div>The dose-toxicity relationship of radiation-induced phrenic nerve palsy remains unclear. Nevertheless, the risk of palsy may be reduced by careful plan optimization, hotspot control within the planning target volume, respiratory motion management, and robust treatment verification.</div></span></li></ul></div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"26 1","pages":"Pages e1-e4"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602166","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":"Transarterial Embolization for the Management of Emergent Hemoptysis in Patients With Primary and Metastatic Lung Tumors","authors":"Ruben Geevarghese ,&nbsp;Elena N. Petre ,&nbsp;Etay Ziv ,&nbsp;Ernesto Santos ,&nbsp;Lee Rodriguez ,&nbsp;Ken Zhao ,&nbsp;Vlasios S. Sotirchos ,&nbsp;Stephen B. Solomon ,&nbsp;Erica S. Alexander","doi":"10.1016/j.cllc.2024.11.008","DOIUrl":"10.1016/j.cllc.2024.11.008","url":null,"abstract":"<div><h3>Objectives</h3><div>To evaluate the role of systemic arterial embolization in patients with primary and metastatic lung tumors presenting with hemoptysis requiring emergent management.</div></div><div><h3>Patients and Methods</h3><div>This retrospective single-center study evaluated patients undergoing transarterial embolization for emergent hemoptysis. Endpoints included technical success, clinical success and overall survival. Clinical success was divided into partial or complete, and defined as absence (complete) or subtotal (partial) reduction in frequency and/or volume of hemoptysis in the first 24-hours following embolization. Predictive factors for clinical outcomes were evaluated using univariate analysis. Adverse events were graded according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0.</div></div><div><h3>Results</h3><div>Thirty-seven patients were identified, including 21/37 (56.8%) patients with primary lung cancer. Clinical success was achieved in 31/37 (83.8%) patients. Median overall survival was 18 days (95% CI, 10-95). Median hemoptysis-free survival was 270 days (95% CI 7 to not reached). No significant predictors of hemoptysis-free survival were identified. Prior chemotherapy (HR 2.69, 95% CI, 1.08-6.67<em>; P = .</em>03) was associated with poorer overall survival. History of primary lung tumor (vs. metastatic tumor) was associated with improved overall survival (HR 0.45, 95% CI, 0.21-0.95; <em>P</em> = 0.04). No serious adverse events (CTCAE Grade ≥ 3) were found to be directly attributable to the embolization.</div></div><div><h3>Conclusion</h3><div>Hemoptysis requiring emergent management in patients with lung malignancy carries a poor prognosis. Transarterial embolization is feasible, safe and may be an effective management option, although further research is warranted to identify which patients are likely to derive the greatest benefit.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"26 1","pages":"Pages 45-51.e5"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791171","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":"Treatment Patterns and Clinical Outcomes in Patients With EGFR-Mutated Non–Small-Cell Lung Cancer After Progression on Osimertinib","authors":"Nathaniel D. Robinson ,&nbsp;Maureen E. Canavan ,&nbsp;Peter L. Zhan ,&nbsp;Brooks V. Udelsman ,&nbsp;Ranjan Pathak ,&nbsp;Daniel J. Boffa ,&nbsp;Sarah B. Goldberg","doi":"10.1016/j.cllc.2024.09.006","DOIUrl":"10.1016/j.cllc.2024.09.006","url":null,"abstract":"<div><h3>Introduction</h3><div>For patients with advanced epidermal growth factor receptor (<em>EGFR</em>)-mutated non–small-cell lung cancer (NSCLC) who progress on first-line osimertinib, the optimal second-line treatment regimen after progression is not known. We sought to assess practice patterns and evaluate the association between different therapies and survival in patients with <em>EGFR</em>-mutated NSCLC following progression on first-line osimertinib.</div></div><div><h3>Methods</h3><div>Retrospective cohort study of patients who received first-line treatment with osimertinib using a population-based, multicenter nationwide electronic health record-derived deidentified database.</div></div><div><h3>Results</h3><div>We identified 2373 patients who received first-line osimertinib. The majority (n = 2279) received osimertinib monotherapy. A total of 538 patients received first-line osimertinib and had second-line treatment data available. Second-line treatment regimens were varied: 65% (n = 348) included chemotherapy, 37% (n = 197) included an immune checkpoint inhibitor (ICI), and 44% (n = 234) included an <em>EGFR</em> tyrosine kinase inhibitor (TKI).</div><div>We then analyzed the 333 patients with performance status 0-2 who received chemotherapy with osimertinib (n = 107, 32%) versus chemotherapy without osimertinib (n = 226, 68%). The continuation of osimertinib with chemotherapy was associated with superior progression-free survival (PFS; median: 10.1 versus 5.9 months, Hazard Ratio [HR]: 0.48, 95% Confidence Interval [CI]: [0.34, 0.68], <em>P</em> &lt; .001) and overall survival (OS; median: 17.0 versus 12.8 months, HR: 0.64, 95% CI: [0.44, 0.93], <em>P</em> = .018) compared to other chemotherapy approaches without osimertinib. This effect was most pronounced in patients with an <em>EGFR</em> exon 19 deletion.</div></div><div><h3>Conclusions</h3><div>Following progression on osimertinib, a wide variety of treatment regimens were used. The continuation of osimertinib with chemotherapy in the second line was associated with increased PFS and OS.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"26 1","pages":"Pages 9-17.e3"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142496437","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":"Comment on ``Prognostic Impact of TP53 Mutations in Metastatic Nonsquamous Non-small-cell Lung Cancer''","authors":"Laurent Mathiot,&nbsp;Judith Raimbourg","doi":"10.1016/j.cllc.2024.10.011","DOIUrl":"10.1016/j.cllc.2024.10.011","url":null,"abstract":"","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"26 1","pages":"Pages e20-e21"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142681071","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 Poor Prognostic ALK Phenotype: A Review of Molecular Markers of Poor Prognosis in ALK Rearranged Nonsmall Cell Lung Cancer","authors":"Sze  Wah  Samuel Chan ,&nbsp;Joy Zeng ,&nbsp;Jack Young ,&nbsp;Samir  H. Barghout ,&nbsp;Faisal Al-Agha ,&nbsp;Stavroula Raptis ,&nbsp;M.  Catherine Brown ,&nbsp;Geoffrey Liu ,&nbsp;Rosalyn Juergens ,&nbsp;Kevin Jao","doi":"10.1016/j.cllc.2024.10.009","DOIUrl":"10.1016/j.cllc.2024.10.009","url":null,"abstract":"<div><h3>Background</h3><div>Patients with nonsmall cell lung cancer with anaplastic lymphoma kinase (<em>ALK</em>) rearrangements derive a significant and durable clinical benefit from tyrosine kinase inhibitors (TKIs). However, early progression/death on treatment occurs in a subset of patients, which we term the poor prognostic ALK phenotype. This review aims to summarize the known molecular mechanisms that underlie this phenotype with a focus on variant 3 and <em>TP53</em> mutations.</div></div><div><h3>Methods</h3><div>A scoping review was performed using scientific databases such as Ovid Medline, Ovid Embase, and Cochrane Central Register of Controlled Trials. Studies included molecular markers of poor prognosis, with a focus on <em>TP53</em> mutations, variant 3 re-arrangements, and poor clinical response to TKIs.</div></div><div><h3>Results</h3><div>Of 4371 studies screened, 108 were included. Numerous studies implicated a negative prognostic role of variant 3, likely mediated through the acquisition of on-target resistance mutations and <em>TP53</em> mutations which are associated with greater chromosomal instability and mutational burden. Co-occurring variant 3 and <em>TP53</em> mutations were associated with even worse survival. Other mediators of early resistance development include aberrations in cell cycle regulators and mutations in cell signaling pathways. Comprehensive genomic analysis from first-line TKI clinical trial data was unable to identify a singular genomic signature that underlies the poor prognostic phenotype but implicated a combination of pathways.</div></div><div><h3>Conclusions</h3><div>This scoping review highlights that the poor prognostic ALK phenotype is likely composed of a heterogeneous variety of genomic factors. There remains an unmet need for a genomic assay to integrate these various molecular markers to predict this ALK phenotype.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"26 1","pages":"Pages e22-e32.e2"},"PeriodicalIF":3.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692721","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}