基于 TROG 12.01 和 De-ESCALaTE 随机试验中治疗的 HPV 相关口咽癌患者 CD103 免疫细胞丰度的预后分层。

Prognostic stratification of HPV-associated oropharyngeal cancer based on CD103 immune cell abundance in patients treated on TROG 12.01 and De-ESCALaTE randomized trials.

机构信息

Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia.

Institute of Head and Neck Studies and Education (InHANSE), University of Birmingham, Birmingham, UK.

出版信息

Ann Oncol. 2022 Aug;33(8):804-813. doi: 10.1016/j.annonc.2022.04.074. Epub 2022 May 4.

DOI:10.1016/j.annonc.2022.04.074

PMID:35525376

Abstract

BACKGROUND

High CD103 intratumoral immune cell (ITIC) abundance is associated with better prognosis in unselected patients with human papilloma virus-associated oropharyngeal squamous cell carcinoma (HPV-associated OPSCC) treated with cisplatin and radiotherapy (CIS/RT). Substituting cetuximab (CETUX) for CIS with RT in HPV-associated OPSCC resulted in inferior efficacy. Our aim was to determine whether quantification of CD103 ITIC could be used to identify a population of HPV-associated OPSCC with superior prognosis.

PATIENTS AND METHODS

We pooled data from the TROG 12.01 and De-ESCALaTE randomized trials that compared CETUX/70GyRT with CIS/70GyRT in low-risk HPV-associated OPSCC: American Joint Committee on Cancer 7 stage III (excluding T1-2N1) or stage IV (excluding N2b-c if smoking history >10 pack-years and/or distant metastases), including all patients with available tumor samples. The primary endpoint was failure-free survival (FFS) in patients receiving CETUX/RT comparing CD103 ITIC high (≥30%) versus low (<30%). High and low CD103 were compared using Cox regression adjusting for age, stage and trial.

RESULTS

Tumor samples were available in 159/182 patients on TROG 12.01 and 145/334 on De-ESCALaTE. CD103 ITIC abundance was high in 27% of patients. The median follow-up was 3.2 years. The 3-year FFS in patients treated with CETUX/RT was 93% [95% confidence interval (CI) 79% to 98%] in high CD103 and 74% (95% CI 63% to 81%) in low CD103 [adjusted hazard ratio = 0.22 (95% CI 0.12-0.41), P < 0.001]. The 3-year overall survival in patients treated with CETUX/RT was 100% in high CD103 and 86% (95% CI 76% to 92%) in low CD103, P < 0.001. In patients treated with CIS/RT, there was no significant difference in FFS.

CONCLUSIONS

CD103 ITIC expression separates CETUX/RT-treated low-risk HPV-associated OPSCC into excellent and poor prognosis subgroups. The high CD103 population is a rational target for de-intensification trials.

摘要

背景

在接受顺铂和放疗（CIS/RT）治疗的未选择的人类乳头瘤病毒相关口咽鳞状细胞癌（HPV 相关 OPSCC）患者中，高 CD103 肿瘤内免疫细胞（ITIC）丰度与更好的预后相关。在 HPV 相关 OPSCC 中用西妥昔单抗（CETUX）替代 CIS/RT 导致疗效降低。我们的目的是确定定量 CD103 ITIC 是否可用于鉴定 HPV 相关 OPSCC 中具有更好预后的人群。

患者和方法

我们汇集了 TROG 12.01 和 De-ESCALaTE 随机试验的数据，这些试验比较了 CETUX/70GyRT 与 CIS/70GyRT 在低危 HPV 相关 OPSCC 中的疗效：美国癌症联合委员会 7 期 III 期（不包括 T1-2N1）或 IV 期（如果吸烟史> 10 包年且/或有远处转移，则不包括 N2b-c），包括所有有可用肿瘤样本的患者。主要终点是接受 CETUX/RT 治疗的患者的无失败生存率（FFS），比较 CD103 ITIC 高（≥30%）与低（<30%）。使用 Cox 回归比较高和低 CD103，调整年龄、分期和试验。

结果

在 TROG 12.01 中，159/182 例患者和 De-ESCALaTE 中 145/334 例患者的肿瘤样本可用于分析。27%的患者 CD103 ITIC 丰度高。中位随访时间为 3.2 年。接受 CETUX/RT 治疗的患者的 3 年 FFS 在高 CD103 患者中为 93%（95%CI79%至 98%），在低 CD103 患者中为 74%（95%CI63%至 81%）[调整后的危险比=0.22（95%CI0.12-0.41），P<0.001]。接受 CETUX/RT 治疗的患者的 3 年总生存率在高 CD103 患者中为 100%，在低 CD103 患者中为 86%（95%CI76%至 92%），P<0.001。在接受 CIS/RT 治疗的患者中，FFS 无显著差异。