Lee Howard J, Boscardin John, Walter Louise C, Smith Alexander K, Cohen Harvey J, Giri Smith, Williams Grant R, Presley Carolyn J, Singhal Surbhi, Huang Li-Wen, Velazquez Ana I, Gubens Matthew A, Blakely Collin M, Mulvey Claire K, Cheng Michael L, Sakoda Lori C, Kushi Lawrence H, Quesenberry Charles, Liu Raymond, Fleszar-Pavlovic Sara, Eskandar Caroline, Cutler Edward, Mercurio Anne Marie, Wong Melisa L
Division of Hematology/Oncology, University of California, San Francisco, San Francisco, CA 94143, United States.
Division of Geriatrics, University of California, San Francisco and San Francisco Veterans Affairs Health Care System, San Francisco, CA 94143, United States.
Oncologist. 2025 Aug 4;30(8). doi: 10.1093/oncolo/oyae349.
Among older adults with cancer receiving chemotherapy, frailty indices predict OS and toxicity. Given the increased use of immunotherapy and targeted therapy for advanced non-small cell lung cancer (aNSCLC), we evaluated frailty and Karnofsky Performance Status (KPS) among older adults with aNSCLC receiving chemotherapy, immunotherapy, and/or targeted therapy.
Patients aged ≥ 65 with aNSCLC starting systemic therapy with non-curative intent underwent geriatric assessments over 6 months. We developed a deficit-accumulation frailty index to categorize patients as robust, pre-frail, or frail. To evaluate associations between frailty and KPS with OS, we used Cox proportional hazards models adjusted for race, insurance, and treatment. We used logistic regression to evaluate hospitalizations, functional decline, and severe toxicity.
Among 155 patients (median age 73), 45.8% were robust, 36.1% pre-frail, and 18.2% frail; 34.8% had a KPS ≥ 90, 32.9% had a KPS of 80, and 32.3% had a KPS ≤ 70. The median OS was 17.9 months. Pre-frail/frail patients had worse OS compared to robust patients (adjusted hazard ratio [HR] 2.09, 95% CI, 1.31-3.34) and were more likely to be hospitalized (adjusted odds ratio [OR] 2.21, 95% CI, 1.09-4.48), functionally decline (adjusted OR 2.29, 95% CI, 1.09-4.78), and experience grade ≥ 3 hematologic toxicity (adjusted OR 5.18, 95% CI, 1.02-26.03). KPS was only associated with OS.
Our frailty index was associated with OS, hospitalization, functional decline, and hematologic AEs among older adults with aNSCLC receiving systemic therapies, while KPS was only associated with OS. Pretreatment frailty assessment may help identify older adults at risk for poor outcomes to optimize decision-making and supportive care.
在接受化疗的老年癌症患者中，衰弱指数可预测总生存期（OS）和毒性。鉴于免疫疗法和靶向疗法在晚期非小细胞肺癌（aNSCLC）中的使用增加，我们评估了接受化疗、免疫疗法和/或靶向疗法的老年aNSCLC患者的衰弱情况和卡诺夫斯基体能状态（KPS）。
年龄≥65岁、开始进行非根治性全身治疗的aNSCLC患者在6个月内接受了老年评估。我们制定了一个缺陷累积衰弱指数，将患者分为健康、衰弱前期或衰弱。为了评估衰弱和KPS与OS之间的关联，我们使用了经种族、保险和治疗因素调整的Cox比例风险模型。我们使用逻辑回归来评估住院情况、功能衰退和严重毒性。
在155例患者（中位年龄73岁）中，45.8%为健康，36.1%为衰弱前期，18.2%为衰弱；34.8%的KPS≥90，32.9%的KPS为80，32.3%的KPS≤70。中位OS为17.9个月。与健康患者相比，衰弱前期/衰弱患者的OS更差（调整后风险比[HR]为2.09，95%置信区间[CI]为1.31 - 3.34），且更有可能住院（调整后优势比[OR]为2.21，95% CI为1.09 - 4.48）、出现功能衰退（调整后OR为2.29，95% CI为1.09 - 4.78）以及经历≥3级血液学毒性（调整后OR为5.18，95% CI为1.02 - 26.03）。KPS仅与OS相关。
我们的衰弱指数与接受全身治疗的老年aNSCLC患者的OS、住院情况、功能衰退和血液学不良事件相关，而KPS仅与OS相关。治疗前的衰弱评估可能有助于识别预后不良风险较高的老年患者，以优化决策和支持性治疗。
