Artificial Intelligence in Medicine Program, Mass General Brigham, Harvard Medical School, Boston, Massachusetts.
Department of Radiation Oncology, Dana Farber Cancer Institute, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
JAMA Oncol. 2024 Jun 1;10(6):773-783. doi: 10.1001/jamaoncol.2024.1120.
The association between body composition (BC) and cancer outcomes is complex and incompletely understood. Previous research in non-small-cell lung cancer (NSCLC) has been limited to small, single-institution studies and yielded promising, albeit heterogeneous, results.
To evaluate the association of BC with oncologic outcomes in patients receiving immunotherapy for advanced or metastatic NSCLC.
DESIGN, SETTING, AND PARTICIPANTS: This comprehensive multicohort analysis included clinical data from cohorts receiving treatment at the Dana-Farber Brigham Cancer Center (DFBCC) who received immunotherapy given alone or in combination with chemotherapy and prospectively collected data from the phase 1/2 Study 1108 and the chemotherapy arm of the phase 3 MYSTIC trial. Baseline and follow-up computed tomography (CT) scans were collected and analyzed using deep neural networks for automatic L3 slice selection and body compartment segmentation (skeletal muscle [SM], subcutaneous adipose tissue [SAT], and visceral adipose tissue). Outcomes were compared based on baseline BC measures or their change at the first follow-up scan. The data were analyzed between July 2022 and April 2023.
Hazard ratios (HRs) for the association of BC measurements with overall survival (OS) and progression-free survival (PFS).
A total of 1791 patients (878 women [49%]) with NSCLC were analyzed, of whom 487 (27.2%) received chemoimmunotherapy at DFBCC (DFBCC-CIO), 825 (46.1%) received ICI monotherapy at DFBCC (DFBCC-IO), 222 (12.4%) were treated with durvalumab monotherapy on Study 1108, and 257 (14.3%) were treated with chemotherapy on MYSTIC; median (IQR) ages were 65 (58-74), 66 (57-71), 65 (26-87), and 63 (30-84) years, respectively. A loss in SM mass, as indicated by a change in the L3 SM area, was associated with worse oncologic outcome across patient groups (HR, 0.59 [95% CI, 0.43-0.81] and 0.61 [95% CI, 0.47-0.79] for OS and PFS, respectively, in DFBCC-CIO; HR, 0.74 [95% CI, 0.60-0.91] for OS in DFBCC-IO; HR, 0.46 [95% CI, 0.33-0.64] and 0.47 [95% CI, 0.34-0.64] for OS and PFS, respectively, in Study 1108; HR, 0.76 [95% CI, 0.61-0.96] for PFS in the MYSTIC trial). This association was most prominent among male patients, with a nonsignificant association among female patients in the MYSTIC trial and DFBCC-CIO cohorts on Kaplan-Meier analysis. An increase of more than 5% in SAT density, as quantified by the average CT attenuation in Hounsfield units of the SAT compartment, was associated with poorer OS in 3 patient cohorts (HR, 0.61 [95% CI, 0.43-0.86] for DFBCC-CIO; HR, 0.62 [95% CI, 0.49-0.79] for DFBCC-IO; and HR, 0.56 [95% CI, 0.40-0.77] for Study 1108). The change in SAT density was also associated with PFS for DFBCC-CIO (HR, 0.73; 95% CI, 0.54-0.97). This was primarily observed in female patients on Kaplan-Meier analysis.
The results of this multicohort study suggest that loss in SM mass during systemic therapy for NSCLC is a marker of poor outcomes, especially in male patients. SAT density changes are also associated with prognosis, particularly in female patients. Automated CT-derived BC measurements should be considered in determining NSCLC prognosis.
体成分 (BC) 与癌症结局之间的关联复杂且尚未完全阐明。先前在非小细胞肺癌 (NSCLC) 中的研究仅限于小型、单机构研究，得出了有希望的、但存在异质性的结果。
评估 BC 与接受免疫治疗的晚期或转移性 NSCLC 患者的肿瘤学结局之间的关联。
设计、设置和参与者： 这项综合多队列分析包括在达纳-法伯布列根癌症中心 (DFBCC) 接受治疗的队列的临床数据，这些队列接受了单独或联合化疗的免疫治疗，并前瞻性地收集了来自 1/2 期研究 1108 期和 3 期 MYSTIC 试验化疗臂的数据。收集并使用深度神经网络分析基线和随访 CT 扫描，以进行 L3 切片选择和身体腔室分割（骨骼肌 [SM]、皮下脂肪组织 [SAT] 和内脏脂肪组织）。根据基线 BC 测量值或第一次随访扫描时的变化来比较结局。数据在 2022 年 7 月至 2023 年 4 月之间进行分析。
用于评估 BC 测量值与总生存期 (OS) 和无进展生存期 (PFS) 之间关联的风险比 (HR)。
共分析了 1791 名 NSCLC 患者（878 名女性 [49%]），其中 487 名（27.2%）在 DFBCC 接受了化疗免疫治疗（DFBCC-CIO），825 名（46.1%）在 DFBCC 接受了 ICI 单药治疗（DFBCC-IO），222 名（12.4%）在 1108 期接受了 durvalumab 单药治疗，257 名（14.3%）在 MYSTIC 接受了化疗；中位（IQR）年龄分别为 65（58-74）、66（57-71）、65（26-87）和 63（30-84）岁。SM 质量的损失（由 L3 SM 区域的变化表示）与所有患者群体的肿瘤学结局较差相关（OS 和 PFS 的 HR 分别为 0.59 [95%CI，0.43-0.81] 和 0.61 [95%CI，0.47-0.79]，在 DFBCC-CIO 中；在 DFBCC-IO 中 OS 的 HR 为 0.74 [95%CI，0.60-0.91]；在 1108 期中 OS 和 PFS 的 HR 分别为 0.46 [95%CI，0.33-0.64] 和 0.47 [95%CI，0.34-0.64]；在 MYSTIC 试验中 PFS 的 HR 为 0.76 [95%CI，0.61-0.96]）。这种关联在男性患者中最为明显，在 MYSTIC 试验和 DFBCC-CIO 队列的 Kaplan-Meier 分析中，女性患者的关联不显著。SAT 密度的增加（通过 Hounsfield 单位测量的 SAT 隔室的平均 CT 衰减来量化）超过 5%与 3 个患者队列的 OS 较差相关（在 DFBCC-CIO 中 HR 为 0.61 [95%CI，0.43-0.86]；在 DFBCC-IO 中 HR 为 0.62 [95%CI，0.49-0.79]；在 1108 期中 HR 为 0.56 [95%CI，0.40-0.77]）。SAT 密度的变化也与 DFBCC-CIO 的 PFS 相关（HR，0.73；95%CI，0.54-0.97）。这主要在 Kaplan-Meier 分析中的女性患者中观察到。
这项多队列研究的结果表明，NSCLC 系统性治疗期间 SM 质量的损失是预后不良的标志物，尤其是在男性患者中。SAT 密度的变化也与预后相关，尤其是在女性患者中。自动 CT 衍生的 BC 测量值应在确定 NSCLC 预后中考虑。
