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Table 1 Biomarkers predicting outcome and toxicity in radiotherapy for NSCLC

From: Precision radiotherapy for non-small cell lung cancer

Types of Biomarkers Outcome predictors Toxicity predictors
 Genomics Genomic predicting scores: Radiosensitiviy Index (RSI), Genomic-adjusted radiation dose (GARD)
Lung adenocarcinoma associated gene: KRAS
Squamous cell carcinoma associated genes: KEAP1, NFE2L2
DAN repair genes: ATM
Other mutated genes: PTEN, RB1, TP53 …
 SNPs DNA repair gene sites: XRCC1, BRCA1, and ERCC1 DNA repair gene sites: ATM, RAD51, XRCC family, LIG4, MTHFR
Inflammatory gene sites: TGFβ1
Immune modulated gene sites: CBLB
 Epigenetics DNA methylation profile, IGFBP-3
Micro RNA: p53 regulation, RAD51 regulation (MiR-34a)
 Proteome /Metabolome Serum inflammatory biomarkers: TGFβ, IL-1, KL-6, IL-6 IL-8, PDGF, TGFα, TNFα, CXCL10 (IP-10), CCL2 (MCP-1), Eotaxin, and TIMP-1
Novel proteins identified by mass spectroscopy:C4BPA, VTN, α2M, CO4A, CO5
 Immunological markers Neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), neutrophil count, lymphocyte count Neutrophil-to-lymphocyte ratio (NLR)
 CT scan Post SABR local recurrence prediction: enlarging opacity at 12 months after SABR, bulging margin, loss of linear margin and air bronchogram lossPost SABR recurrence free survival: tumor size, pleural retraction, vessel attachment
For adaptive RT during chemoradiation: LARTIA trial
Combination of radiomic signatures predict radiation pneumonitis
 PET FDG-PET: Max SUV, metabolic volume, total lesion glycolysis
FLT-PET: sensitive than FDG-PET to predict tumor response
F-MISO-PET: identify radioresistant area for adaptive treatment
FLT-PET: predict hematological toxicity (bone marrow)
 Dosiomics   Dosiomic information + dosimetric information (DVH) + clinical factors better predict radiation pneumonitis
  1. Abbreviations: NSCLC Non-small cell lung cancer. CT Computed tomography. PET Positron emission tomography. SABR Stereotactic ablative radiotherapy. DVH Dose volume histogram