ESTRO 2022 - Abstract Book

S318

Abstract book

ESTRO 2022

Results Results: Based on this, 4 levels of biomarker response could be identified, with the following 5-year values for loco-regional failure (LRF) and disease-free survival (DFS):

LRF 87% 73% 53% 37%

DFS

Level 0: A ‘more hypoxic’ geneprofile, p16 neg, no nimorazole

6%

Level 1: High expression of CMET and SLC3A2:

17% 25%

Level 2: Intermediate expression of CMET and SLC3A2:

Level 3: Low expression of CMET and SLC3A2:

42% P<0.001 P<0.001

Hypoxia was not found to be of clinical importance in patients with less hypoxic gene profile, and/or p16 pos tumors, or given treatment with nimorazole. A multivariate analysis confirmed the value of the abovementioned levels 0-3 (HR: 0.62 [95%cf.l. 48-82] and significantly identified the additional importance of increasing tumor volume; HR: 1.53 [1.14-2.07], and HPV/p16; HR: 0.43 [0.28-0. 66]. Conclusion Conclusion: Tumor biomarkers are of key importance for the outcome after RT of HNSCC. Such individual biological information will be useful to select the right patients to receive a more effective RT. Therefore, to follow the theme of ESTRO 2022, and try to learn from every patient, in order to improve RT, we must in return apply the learned knowledge in form of a personalized adapted therapy to the individual future patient.

MO-0383 A validated prognostic genetic profile independent of smoking in HPV-positive oropharynx cancer

J. Lilja-Fischer 1,2 , M. Stougaard 3 , M.H. Kristensen 1 , T. Steiniche 4 , J.G. Eriksen 1 , J. Overgaard 1

1 Aarhus University Hospital, Department of Experimental Clinical Oncology, Aarhus, Denmark; 2 Aarhus University Hospital, Otolaryngology - Head & Neck Surgery, Aarhus, Denmark; 3 Aarhus University, Institute of Pathology, Aarhus, Denmark; 4 Aarhus University Hospital, Institute of Pathology, Aarhus, Denmark Purpose or Objective Prognosis after primary radiotherapy of oropharyngeal squamous cell carcinoma (OPSCC) is significantly better in patients with HPV+ disease, but previous smoking is associated with a worse prognosis. The reason is unknown, but in a previous study using patient-derived xenografts, we found differing radiosensitivity even in HPV+ OPSCC, pointing to a radiobiological cause. The aim of this study was to explore and validate tumor genetic differences in patients with HPV+ OPSCC with differing tobacco exposure, and test in an independent cohort whether these genetic differences hold prognostic information. Materials and Methods In the exploratory phase of the study, we analyzed tissue samples from 54 patients. Forty patients had HPV+ disease, and 20 of those had a history of significant tobacco smoking (>10 pack-years). Molecular analyses included targeted DNA-sequencing of more than 400 cancer-related genes in the exploratory phase. Patients were divided in to three groups according to HPV- and smoking status (HPV-positive non-smokers, HPV-positive smokers and HPV-negative). A genetic profile was developed according to differences between these groups. In the validation phase, we utilized a custom-made panel including 59 genes, and included 77 patients. Thirty-nine had HPV+ disease, 18 of these had a significant smoking history. Patients were assigned in to three groups according to their HPV-status and genetic profile (HPV+ high-risk, HPV+ low-risk, HPV-neg). All patients were contemporary patients with OPSCC identified in the DAHANCA database, and treated with curatively intended primary (chemo-)radiotherapy according to national guidelines. We compared event-free survival (EFS) and loco-regional failure (LRF) between groups. Results In the test-cohort we found that in patients with HPV+ disease, a history of tobacco smoking was associated with mutations in ATR, MET, RB1 and PIK3CA genes. In the validation-cohort, we were able to re-establish a distinct group of patients with HPV+ OPSCC who were characterized by one or more of these alterations (“HPV+ high-risk”). These patients had a worse prognosis in terms of LRF and EFS, than patients with HPV+ OPSCC without these changes (Figure). There was no difference in tobacco pack-years between HPV+ high-risk and HPV+ low-risk groups in the validation phase. Conclusion We were able to establish a group of patients with HPV+ OPSCC who are characterized by distinct genetic alterations. This profile was reproduced in an independent validation cohort, and was shown to confer a worse prognosis, approaching that of patients with HPV-negative disease, independent of smoking history.