Departments of Radiation Oncology, Harold C. Simmons Comprehensive Cancer Center at the University of Texas Southwestern Medical Center, Dallas.
Department of Internal Medicine (Hematology-Oncology), Harold C. Simmons Comprehensive Cancer Center at the University of Texas Southwestern Medical Center, Dallas.
JAMA Oncol. 2018 Jan 11;4(1):e173501. doi: 10.1001/jamaoncol.2017.3501.
Patterns-of-failure studies suggest that in metastatic non-small-cell lung cancer (NSCLC) sites of gross disease at presentation are the first to progress when treated with chemotherapy. This knowledge has led to increased adoption of local ablative radiation therapy in patients with stage IV NSCLC, though prospective randomized evidence is limited.
To determine if intervening with noninvasive stereotactic ablative radiotherapy (SAbR) prior to maintenance chemotherapy in patients with non-progressive limited metastatic NSCLC after induction therapy led to significant improvements in progression-free survival (PFS).
DESIGN, SETTING, AND PARTICIPANTS: This is a single-institution randomized phase 2 study of maintenance chemotherapy alone vs SAbR followed by maintenance chemotherapy for patients with limited metastatic NSCLC (primary plus up to 5 metastatic sites) whose tumors did not possess EGFR-targetable or ALK-targetable mutations but did achieve a partial response or stable disease after induction chemotherapy.
Maintenance chemotherapy or SAbR to all sites of gross disease (including SAbR or hypofractionated radiation to the primary) followed by maintenance chemotherapy.
The primary end point was PFS; secondary end points included toxic effects, local and distant tumor control, patterns of failure, and overall survival.
A total of 29 patients (9 women and 20 men) were enrolled; 14 patients (median [range] age, 63.5 [51.0-78.0] years) were allocated to the SAbR-plus-maintenance chemotherapy arm, and 15 patients (median [range] age, 70.0 [51.0-79.0] years) were allocated to the maintenance chemotherapy-alone arm. The trial was stopped to accrual early after an interim analysis found a significant improvement in PFS in the SAbR-plus-maintenance chemotherapy arm of 9.7 months vs 3.5 months in the maintenance chemotherapy-alone arm (P = .01). Toxic effects were similar in both arms. There were no in-field failures with fewer overall recurrences in the SAbR arm while those patients receiving maintenance therapy alone had progression at existing sites of disease and distantly.
Consolidative SAbR prior to maintenance chemotherapy appeared beneficial, nearly tripling PFS in patients with limited metastatic NSCLC compared with maintenance chemotherapy alone, with no difference in toxic effects. The irradiation prevented local failures in original disease, the most likely sites of first recurrence. Furthermore, PFS for patients with limited metastatic disease appeared similar to those patients with a greater metastatic burden, further arguing for the potential benefits of local therapy in limited metastatic settings.
clinicaltrials.gov Identifier: NCT02045446.
失败模式研究表明，在转移性非小细胞肺癌（NSCLC）中，接受化疗时，最初出现的明显疾病部位首先进展。这一认识导致了局部消融放疗在 IV 期 NSCLC 患者中的应用增加，尽管前瞻性随机证据有限。
确定在诱导治疗后，非进展性局限性转移性 NSCLC 患者在接受维持化疗前，采用非侵入性立体定向消融放疗（SAbR）干预，是否能显著提高无进展生存期（PFS）。
设计、地点和参与者：这是一项单中心、随机的 2 期研究，比较单独接受维持化疗与 SAbR 联合维持化疗的疗效，研究对象为局限性转移性 NSCLC 患者（原发灶加最多 5 个转移灶），其肿瘤不具有 EGFR 靶向或 ALK 靶向突变，但在诱导化疗后获得部分缓解或疾病稳定。
对所有明显疾病部位（包括原发灶的 SAbR 或低分割放疗）行 SAbR 治疗，然后进行维持化疗。
主要终点为 PFS；次要终点包括毒性作用、局部和远处肿瘤控制、失败模式和总生存期。
共纳入 29 例患者（9 例女性和 20 例男性），其中 14 例（中位[范围]年龄，63.5[51.0-78.0]岁）患者被分配至 SAbR 联合维持化疗组，15 例（中位[范围]年龄，70.0[51.0-79.0]岁）患者被分配至单纯维持化疗组。在中期分析发现 SAbR 联合维持化疗组的 PFS 显著改善（9.7 个月），而单纯维持化疗组为 3.5 个月后，试验提前停止入组。
SAbR 联合维持化疗组毒性作用与单纯维持化疗组相似。SAbR 组无局部复发，远处复发较少，而单纯维持化疗组的疾病存在部位有进展。
与单纯维持化疗相比，在维持化疗前进行巩固性 SAbR 治疗似乎有益，可将局限性转移性 NSCLC 患者的 PFS 提高近 3 倍，且毒性作用无差异。放疗预防了原发病灶的局部失败，这是最有可能的首次复发部位。此外，局限性转移疾病患者的 PFS 与转移负担更大的患者相似，进一步证明了局部治疗在局限性转移环境中的潜在益处。
clinicaltrials.gov 标识符：NCT02045446。
