Department of Radiation Oncology, Wake Forest Medical University, Winston-Salem, North Carolina.
Department of Radiation Oncology, SUNY Upstate Medical University, Syracuse, New York.
JAMA Netw Open. 2024 Oct 1;7(10):e2440673. doi: 10.1001/jamanetworkopen.2024.40673.
The impact of patient-specific, disease-related, and social factors on outcomes in limited-stage small cell lung cancer (LS-SCLC) is not well defined. A post hoc secondary analysis of such factors from the Cancer and Leukemia Group B (CALGB) 30610-Radiation Therapy Oncology Group (RTOG) 0538 trial may impact future trial design.
To assess the comprehensive demographic, disease-related, treatment-related, and social factors for potential associations with survival outcomes and understand whether specific subpopulations may benefit from radiotherapy (RT) dose escalation in LS-SCLC.
DESIGN, SETTING, AND PARTICIPANTS: This post hoc secondary analysis of a randomized clinical trial included 638 adults with LS-SCLC treated at 186 unique treatment sites with at least 1 accrual for all patients from March 15, 2008, to December 1, 2019; 313 patients were randomized to receive RT twice daily to a dosage of 45 Gy for 3 weeks and 325 to receive RT once daily to a dosage of 70 Gy for 7 weeks. Data were locked February 28, 2022, and analyzed from November 28, 2022, to June 4, 2024.
Twice-daily RT or once-daily RT.
Multivariable Cox proportional hazards models evaluated the association of treatment groups and other risk factors with progression-free survival (PFS) and overall survival (OS). Patient-specific factors included age, sex, and Eastern Cooperative Oncology Group performance status. Disease-related factors included tumor, nodal, and overall cancer stages. Treatment-related factors included type of chemotherapy, timing of concurrent RT, RT technique, and prophylactic cranial irradiation. Social factors included marital status and treatment center accrual volume.
Among 507 patients (260 [51.3%] female and 247 [48.7%] male; mean [SD] age, 62.6 [7.9] years) included in the multivariate survival analysis, with a median follow-up of 4.7 (IQR, 3.7-7.1) years, female sex was associated with improved OS (hazard ratio [HR], 0.73 [95% CI, 0.58-0.91]; P = .006), while being 70 years or older was associated with decreased OS (HR, 1.50 [95% CI, 1.14-1.98]; P = .004). Neither age nor sex was associated with PFS. When compared with those with N1 disease, OS and PFS were worse in patients with N2 (HRs, 1.64 [95% CI, 1.19-2.26]; P = .002 and 1.36 [95% CI, 1.02-1.81]; P = .04, respectively) and N3 (HRs, 2.03 [95% CI, 1.40-2.93]; P < .001 and 1.63 [95% CI, 1.17-2.26]; P = .004) disease. Compared with stage II cancer, OS was worse for stage IIIA (HR, 1.65 [95% CI, 1.17-2.31]; P = .004) and stage IIIB (HR, 1.94 [95% CI, 1.34-2.83]; P < .001). Compared with high-volume accrual centers, treatment at low- or middle-volume accrual centers was associated with worse PFS (HRs, 1.94 [95% CI, 1.33-2.82; P < .001] and 1.44 [95% CI, 1.15-1.82; P = .002], respectively) and worse OS (HRs, 1.55 [95% CI, 1.03-2.32; P = .03] and 1.33 [95% CI, 1.04-1.70; P = .02], respectively).
This secondary analysis of the CALGB 30610-RTOG 0538 randomized clinical trial of patients with LS-SCLC found associations between female sex or being younger than 70 years and improved overall survival and between advanced nodal stage or treatment at low- or middle-volume accrual centers and worse outcomes. These findings suggest that stratification by nodal stage, clinical stage, and age should be considered in future randomized trials.
ClinicalTrials.gov Identifier: NCT00632853.
患者特异性、疾病相关和社会因素对局限期小细胞肺癌（LS-SCLC）患者的预后的影响尚未明确。对癌症和白血病组 B（CALGB）30610-放射治疗肿瘤组（RTOG）0538 试验中这些因素的事后二次分析可能会影响未来的试验设计。
评估与生存结果相关的综合人口统计学、疾病相关、治疗相关和社会因素，并了解特定亚组患者是否可能从 LS-SCLC 的放疗（RT）剂量递增中获益。
设计、地点和参与者：这是一项对随机临床试验的事后二次分析，共纳入 186 个治疗场所的 638 名 LS-SCLC 成年患者，所有患者至少有 1 名入组，入组时间为 2008 年 3 月 15 日至 2019 年 12 月 1 日；313 名患者随机接受每日两次 RT，剂量为 45 Gy，共 3 周；325 名患者接受每日一次 RT，剂量为 70 Gy，共 7 周。数据锁定日期为 2022 年 2 月 28 日，分析日期为 2024 年 6 月 4 日至 2024 年 6 月 4 日。
每日两次 RT 或每日一次 RT。
多变量 Cox 比例风险模型评估了治疗组和其他风险因素与无进展生存期（PFS）和总生存期（OS）的关系。患者特异性因素包括年龄、性别和东部肿瘤协作组表现状态。疾病相关因素包括肿瘤、淋巴结和癌症总体分期。治疗相关因素包括化疗类型、同期 RT 的时机、RT 技术和预防性颅脑照射。社会因素包括婚姻状况和治疗中心入组量。
在纳入多变量生存分析的 507 名患者（260 名女性[51.3%]和 247 名男性[48.7%]；平均[SD]年龄为 62.6[7.9]岁）中，中位随访时间为 4.7（IQR，3.7-7.1）年，女性与 OS 改善相关（风险比[HR]，0.73[95%CI，0.58-0.91]；P=0.006），而 70 岁或以上与 OS 降低相关（HR，1.50[95%CI，1.14-1.98]；P=0.004）。年龄和性别均与 PFS 无关。与 N1 疾病相比，N2（HR，1.64[95%CI，1.19-2.26]；P=0.002）和 N3（HR，2.03[95%CI，1.40-2.93]；P<0.001）疾病患者的 OS 和 PFS 更差，而 N3（HR，1.63[95%CI，1.02-1.81]；P=0.04）疾病患者的 OS 和 PFS 更差。与 II 期癌症相比，III A 期（HR，1.65[95%CI，1.17-2.31]；P=0.004）和 III B 期（HR，1.94[95%CI，1.34-2.83]；P<0.001）癌症患者的 OS 更差。与高容量入组中心相比，低容量或中容量入组中心治疗与较差的 PFS（HRs，1.94[95%CI，1.33-2.82；P<0.001]和 1.44[95%CI，1.15-1.82；P=0.002]）和较差的 OS（HRs，1.55[95%CI，1.03-2.32；P=0.03]和 1.33[95%CI，1.04-1.70；P=0.02]）相关。
对 LS-SCLC 患者的 CALGB 30610-RTOG 0538 随机临床试验的二次分析发现，女性或年龄小于 70 岁与总体生存改善相关，而淋巴结分期较晚或在低或中容量入组中心治疗与预后较差相关。这些发现表明，在未来的随机试验中，应考虑按淋巴结分期、临床分期和年龄进行分层。
ClinicalTrials.gov 标识符：NCT00632853。
