Trans-Tasman Radiation Oncology Group, De-ESCALaTE HPV Trial Group (Including: Rischin, D., Mehanna, H., Young, R. J., Bressel, M., Dunn, Janet A., Corry, J., Soni, P., Fulton-Lieuw, T., Iqbal, G., Kenny, L., Porceddu, S., Wratten, C., Robinson, M. and Solomon, B. J.). (2022) 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. Annals of Oncology, 33 (8). pp. 804-813. doi:10.1016/j.annonc.2022.04.074 ISSN 0923-7534.

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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.

Item Type:	Journal Article
Subjects:	R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Divisions:	Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Pharynx -- Cancer -- Prognosis, Neck -- Cancer -- Prognosis, Papillomaviruses, Dendritic cells, Cetuximab, Cisplatin
Journal or Publication Title:	Annals of Oncology
Publisher:	Elsevier
ISSN:	0923-7534
Official Date:	1 August 2022
Dates:	Date Event 1 August 2022 Published 4 May 2022 Available 19 April 2022 Accepted
Volume:	33
Number:	8
Page Range:	pp. 804-813
DOI:	10.1016/j.annonc.2022.04.074
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
Date of first compliant deposit:	13 July 2022
RIOXX Funder/Project Grant:	Project/Grant ID RIOXX Funder Name Funder ID 1175929 National Health and Medical Research Council http://dx.doi.org/10.13039/501100000925

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