S673
Clinical – Head & neck
ESTRO 2026
proposed by Scott et. al. [1]. By weighing the delivered dose with the RSI, the method produces a Genomic Adjusted Radiation Dose (GARD) value. Further clinical validation of the method is still required.This analysis tested whether the GARD stratifies locoregional failure in Danish HNSCC patients in the DAHANCA19 randomized controlled trial. Material/Methods: Analyses were performed on tumor specimens from HNSCC patients from the DAHANCA19 trial [2]. From paraffin-embedded tumor sections (8-µm) mRNA extraction was extracted, reverse-transcribed to complementary DNA (cDNA) and analyzed by quantitative polymerase chain reaction (qPCR). Gene expression levels were determined using robust assays targeting each specific gene used for RSI estimation. Each cycle-threshold (Ct) measurement was normalized within patient to the average Ct of three in-house reference genes. Normalized Ct values were then used to rank genes based on expression levels. Based on the RSI values assessed on each patient we calculated Genomic Adjusted Radiation Dose (GARD) using clinical data on each patient’s RT dose. Methods for calculation of GARD values were adopted from existing literature [1, 3]. Patients were ranked and divided into tertiles based on GARD values. The primary outcome was locoregional failure within 3 years as defined by previous publications [2]. Results: We found RSI values to display an approximate normal distribution, as seen in figure 1, with median RSI 0.66and median GARD13.5 Gy, respectively. Distribution of patient RSI values translating into GARD values supported tiering of patients for proposed radioresistance stratification. Among 188 patients (94 HPV-positive, 94 HPV-negative), HPV-positive disease arose exclusively in the oropharynx; HPV-negative primaries were larynx (n=47), hypopharynx (n=39), and oral cavity (n=8). Patients received 66 Gy/33 fx (n=107), 68 Gy/34 fx (n=75), or 76 Gy/56 fx (n=6). Cisplatin 40 mg/m2 was given concomitantly to majority of patients (n=144). Locoregional failures clustered in the intermediate tier, while patients with radioresistant tumors experienced fewer events over the first 2-3 years of follow-up. We found no evidence that GARD- based stratification predicted clinical outcomes.
Conclusion: In this cohort of older pts with HPV-related OPC treated with radical RT, only disease-related factors such as ECOG PS and TNM seemed to be strongly associated with survival outcomes, rather than age subgroup or comorbidity scores. Further analyses are needed to confirm results and to better undestrand optimal patient selection. Keywords: Older patients, comorbidity, Oropharyngeal cancer Digital Poster 5090 Verification study of Genomic Adjusted Radiation Dose (GARD) in HNSCC patients from the DAHANCA19 trial Anders Frederiksen 1 , Jacob Kinggaard Lilja-Fischer 2 , Morten Horsholt Kristensen 1 , Jesper Grau Eriksen 1 , Jens Overgaard 1 1 Department of Experimental Clincal Oncology, Aarhus University Hospital, Aarhus, Denmark. 2 Department of Otolaryngology, Head and Neck Surgery, Aarhus University Hospital, Aarhus, Denmark Purpose/Objective: Radiotherapy (RT) for head and neck squamous cell carcinoma (HNSCC) remains uniformly prescribed based on tumor site rather than tumor genomics. The Genomic Adjusted Radiation Dose assay has shown promising results in stratification of tumor radiosensitivity and may enable personalized risk- adapted dosing. The genome-based radiosensitivity index (RSI) based on cellular radiosensitivity has been
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