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

D. Rischin, H. Mehanna, R.j. Young, M. Bressel, J. Dunn, J. Corry, P. Soni, T. Fulton-lieuw, G. Iqbal, L. Kenny, S. Porceddu, C. Wratten, M. Robinson, B.j. Solomon

Research output: Contribution to journalArticlepeer-review

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 if quantification of ITIC CD103 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 randomised trials that compared CETUX/70GyRT with CIS/70GyRT in low risk HPV-associated OPSCC: AJCC 7th 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/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 were 93% (95% CI: 79-98%) in high CD103 and 74% (95% CI: 63-81%) in low CD103, adjusted HR 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: 76-92%) in low CD103, p<0.001. In patients treated with CIS/RT there was no significant difference in FFS.

Conclusion: 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.
Original languageEnglish
JournalAnnals of Oncology
Early online date4 May 2022
DOIs
Publication statusE-pub ahead of print - 4 May 2022

Keywords

  • Head and neck cancer
  • oropharyngeal cancer
  • human papillomavirus
  • CD103
  • Cetuximab

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