Division of Endocrinology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
Division of General Internal Medicine, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
PLoS One. 2022 Nov 15;17(11):e0263911. doi: 10.1371/journal.pone.0263911. eCollection 2022.
Randomized controlled trials (RCTs) have demonstrated a survival benefit for adjuvant platinum-based chemotherapy after resection of locoregional non-small cell lung cancer (NSCLC). The relative benefits and harms and optimal approach to treatment for NSCLC patients who have major comorbidities (chronic obstructive pulmonary disease [COPD], coronary artery disease [CAD], and congestive heart failure [CHF]) are unclear, however.
We used a simulation model to run in-silico comparative trials of adjuvant chemotherapy versus observation in locoregional NSCLC in patients with comorbidities. The model estimated quality-adjusted life years (QALYs) gained by each treatment strategy stratified by age, comorbidity, and stage. The model was parameterized using outcomes and quality-of-life data from RCTs and primary analyses from large cancer databases.
Adjuvant chemotherapy was associated with clinically significant QALY gains for all patient age/stage combinations with COPD except for patients >80 years old with Stage IB and IIA cancers. For patients with CHF and Stage IB and IIA disease, adjuvant chemotherapy was not advantageous; in contrast, it was associated with QALY gains for more advanced stages for younger patients with CHF. For stages IIB and IIIA NSCLC, most patient groups benefited from adjuvant chemotherapy. However, In general, patients with multiple comorbidities benefited less from adjuvant chemotherapy than those with single comorbidities and women with comorbidities in older age categories benefited more from adjuvant chemotherapy than their male counterparts.
Older, multimorbid patients may derive QALY gains from adjuvant chemotherapy after NSCLC surgery. These results help extend existing clinical trial data to specific unstudied, high-risk populations and may reduce the uncertainty regarding adjuvant chemotherapy use in these patients.
随机对照试验（RCT）已经证明，局部区域非小细胞肺癌（NSCLC）切除术后辅助铂类化疗有生存获益。然而，对于患有重大合并症（慢性阻塞性肺疾病[COPD]、冠状动脉疾病[CAD]和充血性心力衰竭[CHF]）的 NSCLC 患者，其相对益处和危害以及最佳治疗方法尚不清楚。
我们使用模拟模型在患有合并症的局部区域 NSCLC 患者中进行辅助化疗与观察的虚拟比较试验。该模型根据年龄、合并症和分期，对每种治疗策略的质量调整生命年（QALY）获益进行了估计。该模型使用 RCT 的结果和生活质量数据以及大型癌症数据库的主要分析进行了参数化。
辅助化疗与所有 COPD 患者的所有年龄/分期组合相关，除了 80 岁以上的 IB 期和 IIA 期癌症患者，都具有显著的 QALY 获益。对于 CHF 和 IB 期和 IIA 期疾病患者，辅助化疗没有优势；相反，对于年龄较小的 CHF 患者的更晚期，它与 QALY 获益相关。对于 IIB 和 IIIA 期 NSCLC，大多数患者群体受益于辅助化疗。然而，一般来说，患有多种合并症的患者从辅助化疗中获益不如患有单一合并症的患者，而年龄较大的女性合并症患者从辅助化疗中获益比男性患者更多。
患有多种合并症的老年患者可能从 NSCLC 手术后的辅助化疗中获得 QALY 获益。这些结果有助于将现有的临床试验数据扩展到特定的未研究的高危人群，并减少这些患者使用辅助化疗的不确定性。
