Pub Date : 2024-09-12DOI: 10.1016/j.cllc.2024.09.001
Alexander S Watson, Harris B Krause, Andrew Elliott, Alex Farrell, Stephen V Liu, Patrick C Ma, Ari VanderWalde, George W Sledge, David Spetzler, Erin L Schenk, D Ross Camidge
Background: Gene copy number gain (CNG) is a continuous variable. The relevant cutpoint for HER2, KRAS and MET CNG in non-mall cell lung cancer remains uncertain. As de novo driver oncogenes are largely mutually exclusive, oncogene overlap analysis can be used to explore CNG thresholds.
Patient and methods: We retrospectively analysed NGS of DNA/RNA in 13,702 NSCLC adenocarcinoma samples. Alternate and same-gene driver oncogene co-occurrence with HER2, KRAS and MET CNG was examined. Overall survival (OS) from time of biopsy collection was correlated with CNG and pathogenic mutations in driver oncogenes (Driver+).
Results: The frequency of Driver+ tumors decreased with increasing CNG. Setting CNG thresholds by oncogene overlap and dataset size (CNA ≥ 6 for HER2, KRAS and ≥ 4 for MET), tumors considered relevantly amplified (Amp) for MET, HER2 and KRAS were significantly less likely to be Driver+ (P < .001). When Driver+ did overlap with Amp status, same-gene alterations (mutation and CNG) were significantly enriched for all 3 genes (HER2, KRAS and MET), while BRAF and EGFR mutations were more common in MET-Amp than in HER2- or KRAS-Amp tumors. A negative OS association with Amp status was independent of Driver+ status for HER2 and MET, however not KRAS.
Conclusion: Tissue NGS-based HER2, KRAS and MET CNG thresholds set by oncogene overlap identified potentially clinically relevant "Amp" subgroups with altered genetic profiles and decreased survival. Prospective research into targeted therapy benefit in these groups is encouraged.
背景：基因拷贝数增殖（CNG）是一个连续变量：基因拷贝数增殖（CNG）是一个连续变量。非小细胞肺癌中 HER2、KRAS 和 MET CNG 的相关切点仍不确定。由于新的驱动癌基因在很大程度上是相互排斥的，因此可以利用癌基因重叠分析来探索 CNG 临界点：我们回顾性地分析了13702份NSCLC腺癌样本中DNA/RNA的NGS。研究了HER2、KRAS和MET CNG的替代基因和同基因驱动癌基因共存情况。从活检采集时算起的总生存期（OS）与CNG和驱动癌基因的致病突变（Driver+）相关：结果：Driver+肿瘤的发生率随着CNG的增加而降低。根据癌基因重叠和数据集大小设定CNG阈值（HER2和KRAS的CNA≥6，MET的CNA≥4），MET、HER2和KRAS相关扩增（Amp）的肿瘤被认为是Driver+的可能性显著降低（P < .001）。当Driver+与Amp状态重叠时，同基因改变（突变和CNG）在所有3个基因（HER2、KRAS和MET）中都明显富集，而BRAF和表皮生长因子受体突变在MET-Amp肿瘤中比在HER2-或KRAS-Amp肿瘤中更常见。OS与Amp状态的负相关与HER2和MET的Driver+状态无关，但与KRAS无关：结论：基于组织 NGS 的 HER2、KRAS 和 MET CNG 阈值由癌基因重叠度设定，确定了具有潜在临床相关性的 "Amp "亚群，这些亚群的基因图谱发生改变，生存率降低。我们鼓励对这些群体的靶向治疗获益进行前瞻性研究。
{"title":"Use of Oncogene Overlap by Tissue-Based Next-Generation Sequencing to Explore the Mutational Landscape and Survival Impact of HER2, KRAS and MET Copy-Number Gain in Nonsmall Cell Lung Cancer.","authors":"Alexander S Watson, Harris B Krause, Andrew Elliott, Alex Farrell, Stephen V Liu, Patrick C Ma, Ari VanderWalde, George W Sledge, David Spetzler, Erin L Schenk, D Ross Camidge","doi":"10.1016/j.cllc.2024.09.001","DOIUrl":"https://doi.org/10.1016/j.cllc.2024.09.001","url":null,"abstract":"<p><strong>Background: </strong>Gene copy number gain (CNG) is a continuous variable. The relevant cutpoint for HER2, KRAS and MET CNG in non-mall cell lung cancer remains uncertain. As de novo driver oncogenes are largely mutually exclusive, oncogene overlap analysis can be used to explore CNG thresholds.</p><p><strong>Patient and methods: </strong>We retrospectively analysed NGS of DNA/RNA in 13,702 NSCLC adenocarcinoma samples. Alternate and same-gene driver oncogene co-occurrence with HER2, KRAS and MET CNG was examined. Overall survival (OS) from time of biopsy collection was correlated with CNG and pathogenic mutations in driver oncogenes (Driver+).</p><p><strong>Results: </strong>The frequency of Driver+ tumors decreased with increasing CNG. Setting CNG thresholds by oncogene overlap and dataset size (CNA ≥ 6 for HER2, KRAS and ≥ 4 for MET), tumors considered relevantly amplified (Amp) for MET, HER2 and KRAS were significantly less likely to be Driver+ (P < .001). When Driver+ did overlap with Amp status, same-gene alterations (mutation and CNG) were significantly enriched for all 3 genes (HER2, KRAS and MET), while BRAF and EGFR mutations were more common in MET-Amp than in HER2- or KRAS-Amp tumors. A negative OS association with Amp status was independent of Driver+ status for HER2 and MET, however not KRAS.</p><p><strong>Conclusion: </strong>Tissue NGS-based HER2, KRAS and MET CNG thresholds set by oncogene overlap identified potentially clinically relevant \"Amp\" subgroups with altered genetic profiles and decreased survival. Prospective research into targeted therapy benefit in these groups is encouraged.</p>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388638","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}
Pub Date : 2024-09-06DOI: 10.1016/j.cllc.2024.08.017
Anna Graber-Naidich, Eunji Choi, Julie T Wu, Timothy J Ellis-Caleo, Joel Neal, Heather A Wakelee, Allison W Kurian, Summer S Han
Objective: Long-term breast cancer (BC) survivors are known to develop second malignancies, with second primary lung cancer (SPLC) one common type. Smoking was identified as a main risk factor for SPLC among BC survivors. These findings were limited to the U.S. and focused on smoking status, not incorporating cumulative smoking exposures (eg, pack-years). We examine SPLC incidence and evaluate the associations between SPLC risk and cumulative cigarette smoking exposures and other potential factors among BC survivors in a prospective European cohort.
Methods: Of 502,505 participants enrolled in the UK Biobank in 2006 to 2010, we identified 8429 patients diagnosed with BC between 2006 and 2016 and followed for second malignancies through 2016. Smoking information was collected at enrollment, and treatment data were collected using electronic health records. Multivariable cause-specific Cox regression (CSC) evaluated the association between each factor and SPLC risk.
Results: Of 8429 BC patients, 40 (0.47%) developed SPLC over 45,376 person-years. The 10-year cumulative SPLC incidence was 0.48% (95% CI = 0.33%-0.62%). The CSC analysis confirmed the association between SPLC and ever-smoking status (adjusted hazard-ratio (aHR) = 3.46 (P < .001). The analysis showed a 24% increment in SPLC risk per 10 smoking pack-years among BC survivors (aHR = 1.24 per-10 pack-years, P = .01). The associations between SPLC and other variables remained statistically insignificant. We applied the USPSTF lung cancer screening eligibility criteria and found that 80% of the 40 BC survivors who developed SPLC would have been ineligible for lung cancer screening.
Conclusion: In a large, European cohort, cumulative smoking exposure is significantly associated with SPLC risk among BC survivors.
目的：众所周知，长期乳腺癌（BC）幸存者会罹患第二种恶性肿瘤，其中第二原发性肺癌（SPLC）是一种常见类型。吸烟被认为是乳腺癌幸存者罹患第二原发性肺癌的主要风险因素。这些研究结果仅限于美国，而且只关注吸烟状况，没有纳入累积吸烟暴露（如包年）。我们在一个前瞻性欧洲队列中研究了SPLC的发病率，并评估了BC幸存者中SPLC风险与累积吸烟暴露及其他潜在因素之间的关联：在2006年至2010年期间加入英国生物库的502,505名参与者中，我们确定了8429名在2006年至2016年期间被诊断为BC的患者，并对他们的第二次恶性肿瘤随访至2016年。入库时收集了吸烟信息，并通过电子健康记录收集了治疗数据。多变量特异性病因考克斯回归（CSC）评估了各因素与SPLC风险之间的关联：在 8429 名 BC 患者中，有 40 人（0.47%）在 45376 人年中患了 SPLC。10年累计SPLC发病率为0.48%（95% CI = 0.33%-0.62%）。CSC分析证实了SPLC与曾经吸烟状态之间的关系（调整后危险比值（aHR）= 3.46（P < .001））。分析表明，在 BC 存活者中，每吸烟 10 包年，SPLC 风险增加 24%（aHR = 1.24 per-10 pack-years，P = .01）。SPLC 与其他变量之间的关系在统计学上仍不显著。我们采用了 USPSTF 肺癌筛查资格标准，发现在 40 名患 SPLC 的 BC 幸存者中，有 80% 不符合肺癌筛查资格：结论：在一个大型欧洲队列中，累积吸烟暴露与 BC 幸存者的 SPLC 风险显著相关。
{"title":"Smoking and the Risk of Second Primary Lung Cancer Among Breast Cancer Survivors from the Population-Based UK Biobank Study.","authors":"Anna Graber-Naidich, Eunji Choi, Julie T Wu, Timothy J Ellis-Caleo, Joel Neal, Heather A Wakelee, Allison W Kurian, Summer S Han","doi":"10.1016/j.cllc.2024.08.017","DOIUrl":"https://doi.org/10.1016/j.cllc.2024.08.017","url":null,"abstract":"<p><strong>Objective: </strong>Long-term breast cancer (BC) survivors are known to develop second malignancies, with second primary lung cancer (SPLC) one common type. Smoking was identified as a main risk factor for SPLC among BC survivors. These findings were limited to the U.S. and focused on smoking status, not incorporating cumulative smoking exposures (eg, pack-years). We examine SPLC incidence and evaluate the associations between SPLC risk and cumulative cigarette smoking exposures and other potential factors among BC survivors in a prospective European cohort.</p><p><strong>Methods: </strong>Of 502,505 participants enrolled in the UK Biobank in 2006 to 2010, we identified 8429 patients diagnosed with BC between 2006 and 2016 and followed for second malignancies through 2016. Smoking information was collected at enrollment, and treatment data were collected using electronic health records. Multivariable cause-specific Cox regression (CSC) evaluated the association between each factor and SPLC risk.</p><p><strong>Results: </strong>Of 8429 BC patients, 40 (0.47%) developed SPLC over 45,376 person-years. The 10-year cumulative SPLC incidence was 0.48% (95% CI = 0.33%-0.62%). The CSC analysis confirmed the association between SPLC and ever-smoking status (adjusted hazard-ratio (aHR) = 3.46 (P < .001). The analysis showed a 24% increment in SPLC risk per 10 smoking pack-years among BC survivors (aHR = 1.24 per-10 pack-years, P = .01). The associations between SPLC and other variables remained statistically insignificant. We applied the USPSTF lung cancer screening eligibility criteria and found that 80% of the 40 BC survivors who developed SPLC would have been ineligible for lung cancer screening.</p><p><strong>Conclusion: </strong>In a large, European cohort, cumulative smoking exposure is significantly associated with SPLC risk among BC survivors.</p>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343011","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}
Pub Date : 2024-09-03DOI: 10.1016/j.cllc.2024.08.016
May-Lucie Meyer, Louis Gros, Natalie Décosterd, Marco Tagliamento, Arianna Marinello, David Planchard, David Combarel, Fabrice Barlesi, Jordi Remon, Benjamin Besse, Mihaela Aldea
{"title":"Brief Report: Targeted Therapies and Pancreatitis in Patients With Advanced Nonsmall Cell Lung Cancer.","authors":"May-Lucie Meyer, Louis Gros, Natalie Décosterd, Marco Tagliamento, Arianna Marinello, David Planchard, David Combarel, Fabrice Barlesi, Jordi Remon, Benjamin Besse, Mihaela Aldea","doi":"10.1016/j.cllc.2024.08.016","DOIUrl":"https://doi.org/10.1016/j.cllc.2024.08.016","url":null,"abstract":"","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142343010","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}
Pub Date : 2024-09-01DOI: 10.1016/j.cllc.2024.08.015
Kyle F. Concannon , Bonnie S. Glisson , Robert C. Doebele , Chao Huang , Marcelo Marotti , D. Ross Camidge , John V. Heymach
Introduction
Small cell lung cancer (SCLC) is known to express high levels of the proangiogenic factor vascular endothelial growth factor (VEGF). We assessed the safety and tolerability of cediranib, an oral inhibitor of VEGF receptor tyrosine kinases, in combination with etoposide and cisplatin as first-line therapy for extensive-stage (ES) SCLC or metastatic lung neuroendocrine cancer (NEC).
Methods
Patients received up to six 21-day cycles of etoposide (100 mg/m2, days 1-3) and cisplatin (80 mg/m2, day 1) with once-daily cediranib until disease progression or unacceptable toxicity. Cediranib dosing started at 30 mg with de-escalation cohorts planned based on cycle 1 dose-limiting toxicities (DLTs). An expansion cohort of 12 patients was enrolled at the recommended phase II dose.
Results
Twenty-two patients (18 with ES SCLC, 4 with NEC) received treatment. Only 4 patients were enrolled at the 30 mg cediranib dose before other studies established 20 mg/day as the recommended dose with chemotherapy. Among the 18 patients enrolled at the 20-mg dose, common adverse events included nausea/vomiting, neutropenia, and diarrhea; 8 patients (44%) had grade 1 or 2 hypertension, and 2 (11%) had grade 3 hemoptysis. For all 18 patients, the objective response rate and median progression-free survival duration were 67% and 7.9 months. Plasma levels of VEGF were significantly higher, and those of soluble VEGFR2 were significantly lower, on day 22 than at baseline but were not correlated with tumor shrinkage.
Conclusions
Cediranib (20 mg) plus etoposide and cisplatin is well tolerated and has promising clinical activity.
众所周知，小细胞肺癌（SCLC）表达高水平的促血管生成因子血管内皮生长因子（VEGF）。我们评估了血管内皮生长因子受体酪氨酸激酶口服抑制剂西地尼布联合依托泊苷和顺铂作为广泛期（ES）SCLC或转移性肺神经内分泌癌（NEC）一线疗法的安全性和耐受性。患者最多接受6个21天周期的依托泊苷（100毫克/米，第1-3天）和顺铂（80毫克/米，第1天）治疗，同时每天服用一次西地尼布，直到疾病进展或出现不可接受的毒性。西地尼布的剂量从 30 毫克开始，并根据第一周期的剂量限制性毒性（DLT）计划降级队列。12名患者组成的扩大队列以推荐的II期剂量入组。22 名患者（18 名 ES SCLC 患者，4 名 NEC 患者）接受了治疗。在其他研究确定20毫克/天为化疗推荐剂量之前，只有4名患者以30毫克西地尼布剂量入组。在18名接受20毫克剂量治疗的患者中，常见的不良反应包括恶心/呕吐、中性粒细胞减少和腹泻；8名患者（44%）出现1级或2级高血压，2名患者（11%）出现3级咯血。所有18名患者的客观反应率和中位无进展生存期分别为67%和7.9个月。与基线时相比，第22天的血浆VEGF水平明显升高，可溶性VEGFR2水平明显降低，但与肿瘤缩小无关。塞地拉尼（20 毫克）加依托泊苷和顺铂的耐受性良好，临床活性也很好。
{"title":"A Phase I Open-Label Study of Cediranib Plus Etoposide and Cisplatin as First-Line Therapy for Patients With Extensive-Stage Small-Cell Lung Cancer or Metastatic Neuroendocrine Non–Small-Cell Lung Cancer","authors":"Kyle F. Concannon , Bonnie S. Glisson , Robert C. Doebele , Chao Huang , Marcelo Marotti , D. Ross Camidge , John V. Heymach","doi":"10.1016/j.cllc.2024.08.015","DOIUrl":"10.1016/j.cllc.2024.08.015","url":null,"abstract":"<div><h3>Introduction</h3><div>Small cell lung cancer (SCLC) is known to express high levels of the proangiogenic factor vascular endothelial growth factor (VEGF). We assessed the safety and tolerability of cediranib, an oral inhibitor of VEGF receptor tyrosine kinases, in combination with etoposide and cisplatin as first-line therapy for extensive-stage (ES) SCLC or metastatic lung neuroendocrine cancer (NEC).</div></div><div><h3>Methods</h3><div>Patients received up to six 21-day cycles of etoposide (100 mg/m<sup>2</sup>, days 1-3) and cisplatin (80 mg/m<sup>2</sup>, day 1) with once-daily cediranib until disease progression or unacceptable toxicity. Cediranib dosing started at 30 mg with de-escalation cohorts planned based on cycle 1 dose-limiting toxicities (DLTs). An expansion cohort of 12 patients was enrolled at the recommended phase II dose.</div></div><div><h3>Results</h3><div>Twenty-two patients (18 with ES SCLC, 4 with NEC) received treatment. Only 4 patients were enrolled at the 30 mg cediranib dose before other studies established 20 mg/day as the recommended dose with chemotherapy. Among the 18 patients enrolled at the 20-mg dose, common adverse events included nausea/vomiting, neutropenia, and diarrhea; 8 patients (44%) had grade 1 or 2 hypertension, and 2 (11%) had grade 3 hemoptysis. For all 18 patients, the objective response rate and median progression-free survival duration were 67% and 7.9 months. Plasma levels of VEGF were significantly higher, and those of soluble VEGFR2 were significantly lower, on day 22 than at baseline but were not correlated with tumor shrinkage.</div></div><div><h3>Conclusions</h3><div>Cediranib (20 mg) plus etoposide and cisplatin is well tolerated and has promising clinical activity.</div></div>","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"25 7","pages":"Pages 601-611"},"PeriodicalIF":3.3,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267783","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}
Pub Date : 2024-08-31DOI: 10.1016/j.cllc.2024.08.013
Qin Chen, Xinyue Wang, Richeng Jiang
{"title":"Response to Editor: Commentary on “Influence of Tumor Cavitation on Assessing the Clinical Benefit of Anti-PD1 or PD-L1 Inhibitors in Advanced Lung Squamous Cell Carcinoma”","authors":"Qin Chen, Xinyue Wang, Richeng Jiang","doi":"10.1016/j.cllc.2024.08.013","DOIUrl":"https://doi.org/10.1016/j.cllc.2024.08.013","url":null,"abstract":"","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"1 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267786","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}
Pub Date : 2024-08-31DOI: 10.1016/j.cllc.2024.08.014
Kalyani Narra, Bassam Ghabach, Vivek Athipatla, James-Michael Blackwell, Kari J. Teigen, Jolonda C. Bullock, Anna Diaz, David E. Gerber, Mitchell S. von Itzstein
Advances in the testing and treatment of patients with nonsmall cell lung cancer (NSCLC) harboring oncogenic drivers have improved outcomes. Little is known about testing and treatment patterns in the diverse patient populations. We conducted a retrospective study in a diverse cohort of patients treated in the John Peter Smith safety net healthcare system. We determined patterns of blood- and tissue-based testing and treatment of patients with and alterations. Cox proportional-hazards regression models were used to assess the impact of and testing. A total of 220 patients were included, 97 (44%) were non-Hispanic White, 72 (33%) were Black, 28 (13%) were Hispanic, and 23(10%) were Asian. and testing increased over time from 55% and 52%, respectively, in 2017 to 87% and 82%, respectively, in 2021. Frequency of alterations were highest in Asian patients (45%) and comparable among other groups (6-13%). Frequency of alterations were highest in Hispanic (13%), and Asian (11%) patients, and were 2% for both Black and non-Hispanic White patients. In a multivariate model, lack of testing was associated with worse survival (aHR 1.6; = .003) and testing positive for (aHR 0.43; = .01) or (aHR 0.28; = .04) was associated with improved survival. Race and ethnicity were not associated with survival differences. As molecular testing for oncogenic mutations in NSCLC increases, druggable alterations such as and can be identified in all race-ethnicity groups and are associated with improved outcomes.
{"title":"Identification and Treatment of Lung Cancer Oncogenic Drivers in a Diverse Safety Net Setting","authors":"Kalyani Narra, Bassam Ghabach, Vivek Athipatla, James-Michael Blackwell, Kari J. Teigen, Jolonda C. Bullock, Anna Diaz, David E. Gerber, Mitchell S. von Itzstein","doi":"10.1016/j.cllc.2024.08.014","DOIUrl":"https://doi.org/10.1016/j.cllc.2024.08.014","url":null,"abstract":"Advances in the testing and treatment of patients with nonsmall cell lung cancer (NSCLC) harboring oncogenic drivers have improved outcomes. Little is known about testing and treatment patterns in the diverse patient populations. We conducted a retrospective study in a diverse cohort of patients treated in the John Peter Smith safety net healthcare system. We determined patterns of blood- and tissue-based testing and treatment of patients with and alterations. Cox proportional-hazards regression models were used to assess the impact of and testing. A total of 220 patients were included, 97 (44%) were non-Hispanic White, 72 (33%) were Black, 28 (13%) were Hispanic, and 23(10%) were Asian. and testing increased over time from 55% and 52%, respectively, in 2017 to 87% and 82%, respectively, in 2021. Frequency of alterations were highest in Asian patients (45%) and comparable among other groups (6-13%). Frequency of alterations were highest in Hispanic (13%), and Asian (11%) patients, and were 2% for both Black and non-Hispanic White patients. In a multivariate model, lack of testing was associated with worse survival (aHR 1.6; = .003) and testing positive for (aHR 0.43; = .01) or (aHR 0.28; = .04) was associated with improved survival. Race and ethnicity were not associated with survival differences. As molecular testing for oncogenic mutations in NSCLC increases, druggable alterations such as and can be identified in all race-ethnicity groups and are associated with improved outcomes.","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"49 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267784","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}
Pub Date : 2024-08-31DOI: 10.1016/j.cllc.2024.08.011
Christopher M. Kapp, Chelsi Green, Jeffrey Thiboutot, Jeremy Kim, Mary M. Pasquinelli, Benjamin Aronson, A. Christine Argento
Lung cancer remains the leading cause of cancer death in the United States. There is an association between certain social determinants of health (SDOH) and adverse cancer outcomes. These include Black race and low-income, which are associated with poorer adherence to lung cancer screening and presentation at a later stage of disease. We conducted a retrospective review of all patients with a diagnosis of lung cancer at a single urban, academic center from 2015 to 2021. Demographic data including race and clinical data including time taken to progress through various checkpoints (ie, concerning CT scan to diagnosis, diagnosis to treatment) were collected. Income data was approximated based on population medians at patient's home address zip code. A total of 550 patients were included in the final analysis. The study population was 57.4% Black and 61.2% of patients presenting with a household income of $40,000 US Dollars or lower based on approximated median household income. The time from CT scan to first treatment for the entire cohort was 121.3 days with no statistically significant variance by race. However, among patients presenting at stage IV, 72.7% were black and 76.0% resided in a zip code with a median income < $40,000. This study demonstrated no significant delays in progressing through checkpoints of lung cancer diagnosis and treatment on the basis of race or income approximation. Black patients and patients in low-income households were diagnosed with lung cancer at a more advanced stage. Efforts to close the gap in lung cancer disparities should be focused on targeting screening and early identification toward social groups that may be at highest risk of late presentation. Institutional focus on patient navigation through these stages should be paramount. There were no delays in progression to lung cancer diagnostic and therapeutic milestones based on race or income approximation.
{"title":"Understanding the Social Risk Factors That Avert Equitable Lung Cancer Care","authors":"Christopher M. Kapp, Chelsi Green, Jeffrey Thiboutot, Jeremy Kim, Mary M. Pasquinelli, Benjamin Aronson, A. Christine Argento","doi":"10.1016/j.cllc.2024.08.011","DOIUrl":"https://doi.org/10.1016/j.cllc.2024.08.011","url":null,"abstract":"Lung cancer remains the leading cause of cancer death in the United States. There is an association between certain social determinants of health (SDOH) and adverse cancer outcomes. These include Black race and low-income, which are associated with poorer adherence to lung cancer screening and presentation at a later stage of disease. We conducted a retrospective review of all patients with a diagnosis of lung cancer at a single urban, academic center from 2015 to 2021. Demographic data including race and clinical data including time taken to progress through various checkpoints (ie, concerning CT scan to diagnosis, diagnosis to treatment) were collected. Income data was approximated based on population medians at patient's home address zip code. A total of 550 patients were included in the final analysis. The study population was 57.4% Black and 61.2% of patients presenting with a household income of $40,000 US Dollars or lower based on approximated median household income. The time from CT scan to first treatment for the entire cohort was 121.3 days with no statistically significant variance by race. However, among patients presenting at stage IV, 72.7% were black and 76.0% resided in a zip code with a median income < $40,000. This study demonstrated no significant delays in progressing through checkpoints of lung cancer diagnosis and treatment on the basis of race or income approximation. Black patients and patients in low-income households were diagnosed with lung cancer at a more advanced stage. Efforts to close the gap in lung cancer disparities should be focused on targeting screening and early identification toward social groups that may be at highest risk of late presentation. Institutional focus on patient navigation through these stages should be paramount. There were no delays in progression to lung cancer diagnostic and therapeutic milestones based on race or income approximation.","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"35 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267785","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}
Pub Date : 2024-08-30DOI: 10.1016/j.cllc.2024.08.009
Julie Wu, Theodore Thomas, Hannah F. Tavalire, Frances Vecchio, Tassos C. Kyriakides, Kristina Crothers, Michael J. Kelley, Drew Moghanaki, Scott Shofer, Fred Hendler, Lawrence Feldman
{"title":"Letter to the Editor in Response to “Adherence to Annual Lung Cancer Screening in a Centralized Academic Program”","authors":"Julie Wu, Theodore Thomas, Hannah F. Tavalire, Frances Vecchio, Tassos C. Kyriakides, Kristina Crothers, Michael J. Kelley, Drew Moghanaki, Scott Shofer, Fred Hendler, Lawrence Feldman","doi":"10.1016/j.cllc.2024.08.009","DOIUrl":"https://doi.org/10.1016/j.cllc.2024.08.009","url":null,"abstract":"","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"209 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267787","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}
Pub Date : 2024-08-24DOI: 10.1016/j.cllc.2024.08.012
Sanuki Tissera, Baki Billah, Margaret Brand, Md Nazmul Karim, Phillip Antippa, Robert Blum, Michelle Caldecott, Matthew Conron, Wasek Faisal, Susan Harden, Inger Olesen, Phil Parente, Gary Richardson, Evangeline Samuel, Katharine See, Craig Underhill, Gavin Wright, John Zalcberg, Rob G. Stirling
Lung cancer in Australia contributes 9% of all new cancer diagnoses and is the leading cause of cancer death and burden. Clinical practice guidelines provide evidence-based treatment recommendations for best practice management. We aimed to determine the extent of delivery of guideline-concordant treatment (GCT) and to identify modifiable variables influencing receipt of GCT and survival. Data was sourced from the Victorian Lung Cancer Registry (VLCR) in Victoria, Australia. Descriptive statistics were used to summarize patient and disease characteristics according to treatment type: GCT versus non-GCT versus no/declined treatment. Statistical analyses included multiple logistic regression, multiple COX regression and Kaplan-Meier survival estimates. 52% of patients were treated with GCT, 32.8% non-GCT and 15.2% declined or received no treatment. GCT treated patients were younger, never smoked, had no comorbidities, had better performance status, had early stage cancer, were discussed at a multidisciplinary meeting or had treatment at a higher volume hospital. Overall, patients that received GCT had a 24% lower risk of mortality compared to patients that received non-GCT. Modifiable variables impacting likelihood of receiving GCT included age, smoking status and treating hospital characteristics. Several modifiable variables were identified with positive impacts on survival including increased treatment of the elderly, smoking cessation, delivery of GCT, and treatment in higher volume hospitals. The measurement and reporting of delivery of GCT has positive impacts on survival and therefore merits consideration as an evidence-based quality indicator in the reporting of lung cancer quality and safety outcomes.
{"title":"Stage-Specific Guideline Concordant Treatment Impacts on Survival in Nonsmall Cell Lung Cancer: A Novel Quality Indicator","authors":"Sanuki Tissera, Baki Billah, Margaret Brand, Md Nazmul Karim, Phillip Antippa, Robert Blum, Michelle Caldecott, Matthew Conron, Wasek Faisal, Susan Harden, Inger Olesen, Phil Parente, Gary Richardson, Evangeline Samuel, Katharine See, Craig Underhill, Gavin Wright, John Zalcberg, Rob G. Stirling","doi":"10.1016/j.cllc.2024.08.012","DOIUrl":"https://doi.org/10.1016/j.cllc.2024.08.012","url":null,"abstract":"Lung cancer in Australia contributes 9% of all new cancer diagnoses and is the leading cause of cancer death and burden. Clinical practice guidelines provide evidence-based treatment recommendations for best practice management. We aimed to determine the extent of delivery of guideline-concordant treatment (GCT) and to identify modifiable variables influencing receipt of GCT and survival. Data was sourced from the Victorian Lung Cancer Registry (VLCR) in Victoria, Australia. Descriptive statistics were used to summarize patient and disease characteristics according to treatment type: GCT versus non-GCT versus no/declined treatment. Statistical analyses included multiple logistic regression, multiple COX regression and Kaplan-Meier survival estimates. 52% of patients were treated with GCT, 32.8% non-GCT and 15.2% declined or received no treatment. GCT treated patients were younger, never smoked, had no comorbidities, had better performance status, had early stage cancer, were discussed at a multidisciplinary meeting or had treatment at a higher volume hospital. Overall, patients that received GCT had a 24% lower risk of mortality compared to patients that received non-GCT. Modifiable variables impacting likelihood of receiving GCT included age, smoking status and treating hospital characteristics. Several modifiable variables were identified with positive impacts on survival including increased treatment of the elderly, smoking cessation, delivery of GCT, and treatment in higher volume hospitals. The measurement and reporting of delivery of GCT has positive impacts on survival and therefore merits consideration as an evidence-based quality indicator in the reporting of lung cancer quality and safety outcomes.","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"20 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142267788","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}
Patient-generated health data (PGHD), which includes patient-reported outcomes (PROs) and wearable device data, may have prognostic value for cancer patients. We tested that hypothesis using data from several prospective trials where patients with locally advanced non-small cell lung cancer (LA-NSCLC) were treated with definitive chemoradiotherapy. Cox proportional hazards models were utilized to identify the baseline patient-reported symptom that best predicted progression-free survival (PFS) duration in a trial that involved PRO-CTCAE collection (Cohort 1). Using data from trials that included EORTC QLQ-C30 questionnaires and wearable devices (Cohort 2), the same symptom was tested as a predictor of PFS. Baseline physical inactivity was also tested as a predictor of PFS. A simple risk stratification tool utilizing PROs and physical activity was proposed. In Cohort 1 (n = 50), anorexia was the only pretreatment PRO that was significantly associated with PFS after Bonferroni correction (HR = 3.94, = .002). In Cohort 2 (n = 58), baseline anorexia was also significantly associated with PFS (HR = 2.48, = .018), as was physical inactivity (HR = 3.11, < .001). Median PFS duration for patients in Cohort 2 with anorexia or physical inactivity was 6 months, compared to 18 months for other patients (HR = 3.08, < .001). Median overall survival duration for patients with anorexia or physical inactivity was 19 months, compared to 65 months for other patients (HR = 2.44, = .021). PGHD, including PROs and wearable device data, can provide valuable prognostic information for LA-NSCLC patients treated with definitive chemoradiotherapy. These findings should be validated using larger datasets.
{"title":"Untapping the Prognostic Value of Patient-Generated Health Data in Locally Advanced Non-small Cell Lung Cancer","authors":"Nitin Ohri, William Bodner, Madhur Garg, Brendon Stiles, Balazs Halmos, Shalom Kalnicki","doi":"10.1016/j.cllc.2024.08.010","DOIUrl":"https://doi.org/10.1016/j.cllc.2024.08.010","url":null,"abstract":"Patient-generated health data (PGHD), which includes patient-reported outcomes (PROs) and wearable device data, may have prognostic value for cancer patients. We tested that hypothesis using data from several prospective trials where patients with locally advanced non-small cell lung cancer (LA-NSCLC) were treated with definitive chemoradiotherapy. Cox proportional hazards models were utilized to identify the baseline patient-reported symptom that best predicted progression-free survival (PFS) duration in a trial that involved PRO-CTCAE collection (Cohort 1). Using data from trials that included EORTC QLQ-C30 questionnaires and wearable devices (Cohort 2), the same symptom was tested as a predictor of PFS. Baseline physical inactivity was also tested as a predictor of PFS. A simple risk stratification tool utilizing PROs and physical activity was proposed. In Cohort 1 (n = 50), anorexia was the only pretreatment PRO that was significantly associated with PFS after Bonferroni correction (HR = 3.94, = .002). In Cohort 2 (n = 58), baseline anorexia was also significantly associated with PFS (HR = 2.48, = .018), as was physical inactivity (HR = 3.11, < .001). Median PFS duration for patients in Cohort 2 with anorexia or physical inactivity was 6 months, compared to 18 months for other patients (HR = 3.08, < .001). Median overall survival duration for patients with anorexia or physical inactivity was 19 months, compared to 65 months for other patients (HR = 2.44, = .021). PGHD, including PROs and wearable device data, can provide valuable prognostic information for LA-NSCLC patients treated with definitive chemoradiotherapy. These findings should be validated using larger datasets.","PeriodicalId":10490,"journal":{"name":"Clinical lung cancer","volume":"5 1","pages":""},"PeriodicalIF":3.6,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142222837","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}
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