Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York.
Ligue Nationale Contre le Cancer Meta-Analysis Plateform, Service de Biostatistique et d'Epidémiologie, Gustave Roussy, Université Paris-Saclay, Villejuif, France.
Cancer. 2020 Dec 15;126(24):5263-5273. doi: 10.1002/cncr.33212. Epub 2020 Oct 5.
This study was designed to test the hypothesis that the effectiveness of intensive treatment for locoregionally advanced head and neck cancer (LAHNC) depends on the proportion of patients' overall event risk attributable to cancer.
This study analyzed 22,339 patients with LAHNC treated in 81 randomized trials testing altered fractionation (AFX; Meta-Analysis of Radiotherapy in Squamous Cell Carcinomas of Head and Neck [MARCH] data set) or chemotherapy (Meta-Analysis of Chemotherapy in Head and Neck Cancer [MACH-NC] data set). Generalized competing event regression was applied to the control arms in MARCH, and patients were stratified by tertile according to the ω score, which quantified the relative hazard for cancer versus competing events. The classifier was externally validated on the MACH-NC data set. The study tested for interactions between the ω score and treatment effects on overall survival (OS).
Factors associated with a higher ω score were a younger age, a better performance status, an oral cavity site, higher T and N categories, and a p16-negative/unknown status. The effect of AFX on OS was greater in patients with high ω scores (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.85-0.99) and medium ω scores (HR, 0.91; 95% CI, 0.84-0.98) versus low ω scores (HR, 0.97; 95% CI, 0.90-1.05; P for interaction = .086). The effect of chemotherapy on OS was significantly greater in patients with high ω scores (HR, 0.81; 95% CI, 0.75-0.88) and medium ω scores (HR, 0.86; 95% CI, 0.78-0.93) versus low ω scores (HR, 0.96; 95% CI, 0.86-1.08; P for interaction = .011).
LAHNC patients with a higher risk of cancer progression relative to competing mortality, as reflected by a higher ω score, selectively benefit from more intensive treatment.
本研究旨在检验以下假设，即局部区域晚期头颈部癌症（LAHNC）强化治疗的有效性取决于患者总体事件风险中归因于癌症的比例。
本研究分析了 81 项随机试验中 22339 例 LAHNC 患者的数据，这些试验检测了改变分割（AFX；头颈部鳞状细胞癌放射治疗荟萃分析 [MARCH]数据集）或化疗（头颈部癌症化疗荟萃分析 [MACH-NC]数据集）。广义竞争事件回归应用于 MARCH 的对照臂，根据 ω 评分对患者进行分层，该评分量化了癌症与竞争事件的相对危险度。该分类器在 MACH-NC 数据集上进行了外部验证。该研究检测了 ω 评分与总生存（OS）治疗效果之间的交互作用。
与较高的 ω 评分相关的因素包括年龄较小、较好的表现状态、口腔部位、较高的 T 和 N 类别，以及 p16 阴性/未知状态。AFX 对 OS 的影响在 ω 评分较高（风险比 [HR]，0.92；95%置信区间 [CI]，0.85-0.99）和中等 ω 评分（HR，0.91；95% CI，0.84-0.98）的患者中大于 ω 评分较低（HR，0.97；95% CI，0.90-1.05；交互作用 P 值=0.086）的患者。化疗对 OS 的影响在 ω 评分较高（HR，0.81；95% CI，0.75-0.88）和中等 ω 评分（HR，0.86；95% CI，0.78-0.93）的患者中显著大于 ω 评分较低（HR，0.96；95% CI，0.86-1.08；交互作用 P 值=0.011）的患者。
与竞争死亡率相比，癌症进展风险较高的 LAHNC 患者（反映为较高的 ω 评分）可选择性地从更强化的治疗中获益。
