Dataset Information

Associations of GWAS-Identified Risk Loci with Progression, Efficacy and Toxicity of Radiotherapy of Head and Neck Squamous Cell Carcinoma Treated with Radiotherapy.

ABSTRACT:

Background

Head and neck squamous cell carcinoma (HNSCC) ranks the sixth most common cancer worldwide. This study aims to evaluate the associations of GWAS-identified HNSCC risk loci with progression, efficacy and toxicity of radiotherapy of HNSCC treated with radiotherapy.

Methods

Six GWAS-identified risk loci were genotyped and evaluated. Multivariate logistic regression was used to determine the associations of these SNPs with progression, efficacy and toxicity of radiotherapy of HNSCC treated with radiotherapy.

Results

We found that rs259919 was significantly associated with higher TNM stage (allele A vs G: OR=1.49; 95% CI: 1.09-2.03; P=0.012), while rs3135001 was significantly associated with better efficacy of radiotherapy (allele T vs C: OR=1.80, 95% CIs=1.19-2.73, P=0.005). Both SNP rs1265081 (allele A vs C: OR=1.41, 95% CIs=1.08-1.86, P=0.012) and rs3135001 (allele T vs allele C: OR=0.53, 95% CIs=0.35-0.79, P=0.002) were significantly associated with the occurrence of grade 3-4 oral mucositis.

Conclusion

We identified that three GWAS-identified HNSCC risk loci were significantly associated with progression, efficacy and toxicity of radiotherapy of HNSCC. Our findings strengthen the understanding of the essential role of genetic background in the progression and therapeutic effects of HNSCC.

SUBMITTER: Li Q

PROVIDER: S-EPMC8464356 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceMajor weight loss is common in patients with head and neck squamous cell carcinoma (HNSCC) who undergo radiotherapy (RT). How baseline and posttreatment body composition affects outcome is unknown.ObjectiveTo determine whether lean body mass before and after RT for HNSCC predicts survival and locoregional control.Design, setting, and participantRetrospective study of 2840 patients with pathologically proven HNSCC undergoing curative RT at a single academic cancer referral center from October 1, 2003, to August 31, 2013. One hundred ninety patients had computed tomographic (CT) scans available for analysis of skeletal muscle (SM). The effect of pre-RT and post-RT SM depletion (defined as a CT-measured L3 SM index of less than 52.4 cm2/m2 for men and less than 38.5 cm2/m2 for women) on survival and disease control was evaluated. Final follow-up was completed on September 27, 2014, and data were analyzed from October 1, 2014, to November 29, 2015.Main outcomes and measuresPrimary outcomes were overall and disease-specific survival and locoregional control. Secondary analyses included the influence of pre-RT body mass index (BMI) and interscan weight loss on survival and recurrence.ResultsAmong the 2840 consecutive patients who underwent screening, 190 had whole-body positron emission tomography-CT or abdominal CT scans before and after RT and were included for analysis. Of these, 160 (84.2%) were men and 30 (15.8%) were women; their mean (SD) age was 57.7 (9.4) years. Median follow up was 68.6 months. Skeletal muscle depletion was detected in 67 patients (35.3%) before RT and an additional 58 patients (30.5%) after RT. Decreased overall survival was predicted by SM depletion before RT (hazard ratio [HR], 1.92; 95% CI, 1.19-3.11; P = .007) and after RT (HR, 2.03; 95% CI, 1.02-4.24; P = .04). Increased BMI was associated with significantly improved survival (HR per 1-U increase in BMI, 0.91; 95% CI, 0.87-0.96; P < .001). Weight loss without SM depletion did not affect outcomes. Post-RT SM depletion was more substantive in competing multivariate models of mortality risk than weight loss-based metrics (Bayesian information criteria difference, 7.9), but pre-RT BMI demonstrated the greatest prognostic value.Conclusions and relevanceDiminished SM mass assessed by CT imaging or BMI can predict oncologic outcomes for patients with HNSCC, whereas weight loss after RT initiation does not predict SM loss or survival.