ESTRO 2024 - Abstract Book

S5269 ESTRO 2024 of cases. The most abundant category of biomarkers was DNA-based (83%), with proteins (8%), microbiota (6%) and others (3%) being less common. Among the 1531 extracted individual biomarker-toxicity associations, acute mucositis (51%) and dysphagia (20%) were the most commonly assessed side effects. When limiting analysis to statistically-significant results, REACTOME pathway analysis of biomarkers assignable to a gene symbol yielded statistically-significant enrichment in pathways of neutrophil degranulation (p<0.001), innate immune system (p< 0.001), activation of matrix metalloproteinases (p=0.003), immune system (p=0.02) and insulin-like growth factor (p=0.04). Table 1 shows a selection of mucositis related biomarkers that were statistically significant in multivariable models, accounting for confounders. Concerning data quality, only 52% of publications reported AJCC stage for all patients and similarly, a mere 41% and 36% had complete information about T- and N-stage, respectively. TNM version was mentioned in 49% of studies. 92% of biomarkers were mentioned in only one included publication (single nucleotide polymorphisms were translated to gene level for this analysis). Markers with the most replicated studies were albumin (n=8), hemoglobin (n=8) and XRCC1 (n=7), all associated with endpoint mucositis. Radiobiology - Normal tissue radiobiology

Table 1: Selection of biomarkers that were statistically significant in multivariable models for association with mucositis

Biomarker category

Biomarker subcategory (gene/protein name)

Biomarker specification

Early/late toxicity

Prediction measure

Prediction value (p value)

level of significance (adjusted for multiple

PMID

Year publica

testing yes/no) 0.05 (no)

DNA / SNP

XRCC1

rs25487

early

HR

1.72 (0.035) 6.9 (0.007) 4.68 (0.039) 0.455 (<0.001) 4.55 (<0.0001)

21704413

2011

rs1799782

early

OR

0.05 (no)

31997432

2020

ABCC1

rs45511401

early

OR

0.05 (no)

30973677

2019

Dietary factor

vitamin

vitamin C

early

OR

0.05 (no)

33300654

2021

Hematological parameter

blood cells

Neutrophil to lymphocyte ratio (NLR) Granulicatella

early

OR

0.05 (no)

34640462

2021

Microbiota

oral microbiome

early

HR

2.71 (0.04)

0.05 (no)

32888342

2020

Conclusion:

Our study was able to identify a wide range of markers associated with toxicities under and after RT for HNSCC. Generally, publications were suffering from incomplete data and a lack of replication studies. The best-evaluated markers were clinical routine blood parameters and genetic variants in the DNA repair pathway.

Keywords: systematic review, head/neck cancer, biomarkers

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