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

Rischin, D; Mehanna, H; Young, RJ; Bressel, M; Dunn, J; Corry, J; Soni, P; Fulton-Lieuw, T; Iqbal, G; Kenny, L; Porceddu, S; Wratten, C; Robinson, M; Solomon, BJ; Trans-Tasman Radiation Oncology Group; De-ESCALaTE HPV Trial Group

Author(s): Rischin, D; Mehanna, H; Young, RJ; Bressel, M; Dunn, J; Corry, J; Soni, P; Fulton-Lieuw, T; Iqbal, G; Kenny, L; Porceddu, S; Wratten, C; Robinson, M; Solomon, BJ; Trans-Tasman Radiation Oncology Group; De-ESCALaTE HPV Trial Group;
Details: Publication Year 2022-08,Volume 33,Issue #8,Page 804-813
Journal Title: Annals of Oncology
Publication Type: Research article
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.
Keywords: Cetuximab; *Head and Neck Neoplasms/complications; Humans; *Oropharyngeal Neoplasms/pathology; Papillomaviridae; *Papillomavirus Infections/complications; Prognosis; Randomized Controlled Trials as Topic; Cd103; cisplatin; head and neck cancer; human papillomavirus; oropharyngeal cancer
Department(s): Medical Oncology; Laboratory Research; Biostatistics and Clinical Trials; Pathology
PubMed ID: 35525376
Publisher's Version: https://doi.org/10.1016/j.annonc.2022.04.074
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2025-03-07 05:57:20

Last Modified: 2025-03-07 06:00:21