2 June 2024

Body Composition in Advanced Non-Small Cell Lung Cancer Treated With Immunotherapy

(JAMA Oncology, IF: 28.4)

  • Tafadzwa L. Chaunzwa, MD; Jack M. Qian, MD; Qin Li, PhD; Biagio Ricciuti, MD; Leonard Nuernberg, BS; JustinW. Johnson, BS; JakobWeiss, MD; Zhongyi Zhang, BS; Jamie MacKay,MD, PhD; Ioannis Kagiampakis, PhD; Damian Bikiel, PhD; Alessandro Di Federico, MD; Joao V. Alessi, MD; Raymond H. Mak, MD; Etai Jacob, PhD; Mark M. Awad, MD; Hugo J.W. L. Aerts, PhD



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.




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.

这项综合性多队列分析纳入了在Dana-Farber Brigham癌症中心(DFBCC)接受治疗的队列的临床数据,这些队列接受单独或联合化疗的免疫疗法,以及从1/2期研究1108例患者和3期MYSTIC试验的化疗组前瞻性收集的数据。使用深度神经网络收集并分析基线和随访的计算机断层扫描(CT)扫描,用于自动L3切片选择和身体区域分割(骨骼肌[SM]、皮下脂肪组织[SAT]和内脏脂肪组织)。根据基线BC测量或第一次随访扫描时的变化对结果进行比较。数据分析时间为2022年7月至2023年4月。



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.

共分析了1791名NSCLC患者(878名女性[49%]),其中487人(27.2%)在DFBCC接受了化学免疫治疗,825人(46.1%)在DFBC接受了ICI单药治疗,222人(12.4%)在研究1108中接受了度伐利尤单抗单药治疗;257人(14.3%)在MYSTIC接受了化疗;中位(IQR)年龄分别为65岁(58-74岁)、66岁(57-71岁)、65岁(26-87岁)和63岁(30-84岁)。在L3 SM区域的变化表明,SM质量的损失与患者组的肿瘤学结果较差有关(在研究1108中,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-IO中,OS的HR为0.74[95%CI、0.60-0.91];OS和PFS分别为0.46[95%CI和0.34-0.64];在MYSTIC试验中,PFS的HR为0.66[95%CI,0.61-0.96])。在Kaplan-Meier分析的MYSTIC试验和DFBCC-CIO队列中,这种关联在男性患者中最为显著,但在女性患者之间的关联不显著。通过SAT中以Hounsfield单位的平均CT衰减来量化,SAT密度增加超过5%与3个患者队列中较差的OS相关(DFBCC-CIO的HR为0.61[95%CI,0.43-0.86];DFBCC-IO的HR为0.62[9%CI,0.49-0.79];研究1108的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)。这些主要在Kaplan-Meier分析的女性患者中观察到。



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.