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Impact of Germline Genomic Alterations On Normal Tissue and Tumor Response to Radiation Therapy in Head and Neck Squamous Cell Carcinoma

A Hopper, L Sutton, P Sanghvi, X Ray, L Krockenberger, I Deichaite, V Moiseenko*, UC San Diego, La Jolla, CA

Presentations

PO-GePV-M-1 (Sunday, 7/10/2022)   [Eastern Time (GMT-4)]

ePoster Forums

Purpose: To investigate if germline genomic alterations impact incidence of adverse events (AE), overall, locoregional recurrence free, and metastases free survival (OS, LFS and MFS) in head and neck squamous cell carcinoma (HNSCC) patients receiving radiotherapy (RT).

Methods: 34 HNSCC patients treated with RT who had undergone genomic testing were evaluated. Age, disease site, stage, HPV status, pre-RT surgical resection, and RT dose were extracted from patient charts. AE, locoregional recurrence, metastasis, and last follow up or death data were collected. Patients were assigned to “supersensitive” or “insensitive” groups based on rates of mucositis, dysphagia and xerostomia and the relative dose they received compared to the group quartile values. Differences in patient characteristics were compared using Fisher’s exact test. Differences in OS, LFS and MFS were compared by Kaplan-Meier survival analysis.

Results: Prescribed doses ranged from 60 to 70 Gy. Median age at treatment was 62.5 years (range 37-85). Median follow up 42.5 months (range 7-205). 16 patients were categorized as RT supersensitive (Group A) and 18 in the insensitive subset (Group B). There was no significant difference in age, stage, site of origin, HPV status or pre-RT surgery between the groups. Kaplan-Meier survival analysis showed significant differences in OS between groups A and B (p = 0.017), LFS (p = 0.041) and MFS (p = 0.010). Multiple gene alterations were found with increased prevalence in Group A, alterations in TSC2 and HLA-A V91M being significantly more prevalent. Variants in HLA-DMB/DMA were associated with increased locoregional recurrence and were more common in Group B

Conclusion: Association between radiation-related AEs and differences in genomic alterations was observed, with further impact on OS, LFS and MFS. Although this patient group is small and heterogenous the data indicate that genomic analysis may play a role in treatment planning and prognosis in HNSCC.

Keywords

Not Applicable / None Entered.

Taxonomy

TH- Radiobiology(RBio)/Biology(Bio): Rbio - Outcome models combining dose, imaging, radiomics/radiogenomics and clinical factors: other than machine learning

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