Cancer Center, Sichuan Taikang Hospital, Tianfu New Area, #881 Xiang He First Street, Chengdu, Sichuan Province, China.
Department of Radiation Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
Radiother Oncol. 2024 Aug;197:110334. doi: 10.1016/j.radonc.2024.110334. Epub 2024 May 25.
All known randomized trials of stereotactic radiotherapy (SRT) versus whole brain radiotherapy (WBRT) for brain metastases (BMs) comprise mixed histologies. The phase III HYBRID trial (NCT02882984) attempted to evaluate the non-inferiority of SRT vs. WBRT specifically for EGFR-mutated non-small cell lung cancer (EGFRm NSCLC) BMs.
Inclusion criteria were ≤ 5 BMs (any size) from treatment-naïve EGFRm NSCLC. All patients started a first-generation tyrosine kinase inhibitor on the first day of WBRT (37.5 Gy/15 fractions) or SRT (25-40 Gy/5 fractions per tumor volume). The primary endpoint was 18-month intracranial progression-free survival (iPFS; intention-to-treat).
The trial commenced in June 2015 and was closed in April 2021 after screening 208 patients but enrolling 85 (n = 41 WBRT, n = 44 SRT; median follow-up 31 and 36 months, respectively). Respectively, 9.5 % vs. 10.2 % of patients experienced intracranial progression at 18 months, and the median iPFS was 21.4 vs. 22.3 months (p > 0.05 for all). The SRT arm experienced higher overall survival and cognitive preservation (p < 0.05 for all). The most notable reason for low enrollment was patients not wishing to risk neurocognitive decline from WBRT.
Although this phase III trial was underpowered, there was no evidence that SRT yielded outcome detriments compared to WBRT for EGFRm NSCLC BMs. Lessons from prematurely closed trials are valuable, as they often provide important experiential perspectives for investigators designing/executing future trials. In the current era, randomized trials involving WBRT without cognitive sparing measures may be at high risk of underaccrual; trial investigators are encouraged to carefully consider our experience when attempting to design such trials. However, trials of molecular-/biologically-stratified patients are highly recommended as the notion of "individualized medicine/oncology" continues to expand.
所有已知的立体定向放射治疗（SRT）与全脑放疗（WBRT）治疗脑转移瘤（BMs）的随机试验均包含混合组织学。III 期 HYBRID 试验（NCT02882984）试图专门评估 SRT 与 WBRT 对表皮生长因子受体（EGFR）突变型非小细胞肺癌（EGFRm NSCLC）BMs 的非劣效性。
纳入标准为治疗初治的 EGFRm NSCLC 患者，BMs 数≤5 个（任何大小）。所有患者在 WBRT（37.5Gy/15 次分割）或 SRT（25-40Gy/5 次分割，每次分割对应一个肿瘤体积）的第一天开始使用第一代酪氨酸激酶抑制剂。主要终点为 18 个月颅内无进展生存期（iPFS；意向治疗）。
该试验于 2015 年 6 月开始，在筛选了 208 例患者后于 2021 年 4 月关闭，但仅入组了 85 例（n=41 例 WBRT，n=44 例 SRT；中位随访时间分别为 31 个月和 36 个月）。分别有 9.5%和 10.2%的患者在 18 个月时发生颅内进展，中位 iPFS 分别为 21.4 个月和 22.3 个月（所有比较均为 p>0.05）。SRT 组的总生存期和认知保存更好（所有比较均为 p<0.05）。入组率低的最主要原因是患者不愿意冒 WBRT 导致认知下降的风险。
尽管这项 III 期试验的效力不足，但没有证据表明 SRT 对 EGFRm NSCLC BMs 的治疗结果与 WBRT 相比存在损害。预先关闭的试验提供了有价值的经验，因为它们为研究者设计/执行未来的试验提供了重要的经验视角。在当前时代，不包括认知保护措施的 WBRT 随机试验可能存在入组不足的高风险；试验研究者在试图设计此类试验时，应仔细考虑我们的经验。然而，强烈推荐对分子/生物学分层患者进行随机试验，因为“个体化医学/肿瘤学”的概念不断扩大。
