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

doi:10.1016/j.annonc.2022.04.074

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 journal › Article › peer-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 7^th 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 language	English
Pages (from-to)	804-813
Journal	Annals of Oncology
Volume	33
Issue number	8
Early online date	4 May 2022
DOIs	https://doi.org/10.1016/j.annonc.2022.04.074
Publication status	E-pub ahead of print - 4 May 2022

Keywords

CD103
Cetuximab
Head and neck cancer
human papillomavirus
oropharyngeal cancer

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.annonc.2022.04.074

Cite this

Rischin, D., Mehanna, H., Young, R. J., Bressel, M., Dunn, J., Corry, J., Soni, P., Fulton-lieuw, T., Iqbal, G., Kenny, L., Porceddu, S., Wratten, C., Robinson, M., & 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 randomised trials. Annals of Oncology, 33(8), 804-813. Advance online publication. https://doi.org/10.1016/j.annonc.2022.04.074

@article{b6ddebaa123743eb9514e0db0e661f49,

title = "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",

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.",

keywords = "CD103, Cetuximab, Head and neck cancer, human papillomavirus, oropharyngeal cancer",

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

year = "2022",

month = may,

day = "4",

doi = "10.1016/j.annonc.2022.04.074",

language = "English",

volume = "33",

pages = "804--813",

journal = "Annals of Oncology",

issn = "0923-7534",

publisher = "Oxford University Press",

number = "8",

}

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 2022, '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', Annals of Oncology, vol. 33, no. 8, pp. 804-813. https://doi.org/10.1016/j.annonc.2022.04.074

TY - JOUR

T1 - 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

AU - Rischin, D.

AU - Mehanna, H.

AU - Young, R.j.

AU - Bressel, M.

AU - Dunn, J.

AU - Corry, J.

AU - Soni, P.

AU - Fulton-lieuw, T.

AU - Iqbal, G.

AU - Kenny, L.

AU - Porceddu, S.

AU - Wratten, C.

AU - Robinson, M.

AU - Solomon, B.j.

PY - 2022/5/4

Y1 - 2022/5/4

N2 - 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.

AB - 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.

KW - CD103

KW - Cetuximab

KW - Head and neck cancer

KW - human papillomavirus

KW - oropharyngeal cancer

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U2 - 10.1016/j.annonc.2022.04.074

DO - 10.1016/j.annonc.2022.04.074

M3 - Article

SN - 0923-7534

VL - 33

SP - 804

EP - 813

JO - Annals of Oncology

JF - Annals of Oncology

IS - 8

ER -