Table 1. Studies investigating blood-based biomarkers for radiation oncology.

Authors (years)	n	PSA levels (ng/mL)	Gleason scores	TNM stage	Sample collection	Cytokines	Results
Johnke et al., 2009	37	<21	≤6	T1–2cN0M0	Prior to TAS, prior to RT, after 24 hours to the RT, and weekly during RT	IL-1β, IL-6 and TGF-β	Elevated level of IL-1β and IL-6 found during RT, but TGF-β decreased immediately following RT
Kovacs et al., 2003	37	<21	6	T1–2cN0M0	Prior to RT, intervals throughout the RT	IL-1α, TGF-β	Elevated plasma concentration of IL-1α, TGF-β found following RT
Christensen et al., 2009	42	>0.05	6, 7 and 9	T1c–3N0M0	Prior to RT and at every 5th fraction during IMRT and end of treatment	IFN-γ, TNF-α, IL-1α, IL-2, IL6, IL-8, IL-10, and IL-12p70	IFN-γ and IL-6 increased during RT and association was found between increased IL-2 and IL-1 and acute gastrointestinal and genitourinary toxicity
Tanji et al., 2015	30	N/A	N/A	N/A	Before and during RT	FGF-2, VEGF, G-CSF, GRO, TGF-β1 and TGF-β2	Levels of epidermal G-CSF, and IFN-γ, G-CSF, GRO, TGF-β1 and TGF-β2 were significantly increased during RT
Dirksen et al., 2014	35	N/A	N/A	N/A	Before and after RT	TNF-α, IL-1b, IL-1b, IL-6, IL-10, and IL-4	Elevated TNF-α was associated with depression, anxiety, urinary irritation, and bowel problems
Holliday et al., 2016	28	N/A	N/A	N/A	Before RT, 1 h after RT, end of week 3, end of week 5, and end of RT	IL-1a, IL-1b, TNF-α, IL-6, IL-8, IL-10	IL-6 increased during RT but not associated with fatigue scores or sleep disturbance
Feng et al., 2016	34	N/A	N/A	N/A	Before, the midpoint of EBRT, and 1 year following RT	IL-2 IL-3, IL-8, IL-9, IL-10, IL-16, IFN-γ, IFN-α2	Increased levels of IL-2 IL-3, IL-8, IL-9, IL-10, IL-16, IFN-γ, IFN-α2, were associated with worsening of fatigue
Michalaki et al., 2004	80	5.2–113	6, 8 and 10	T1–4N0M0	Prior to any treatment	IL-6 and TNF-α	Elevated levels of IL-6 and TNF-α were observed in patients with metastatic disease compared to localised disease. Both cytokines were also elevated at the point of PSA progression
Bedini et al., 2018	20	2.5–14.8	6 and 7	N/A	Before RT, after dose of 8 Gy, after 50 Gy, end of RT and one months after RT completion	CCL2, IL-b, IL-6, IL-8 PTX3 and TNF-α	CCL2 was found to significantly increase during IMRT. Patients exhibiting late rectal toxicity were found to have elevated CCL2 levels at the end of RT

TAS, total androgen suppression; RT, radiation treatment; and other abbreviations as in text; IL-1, interleukin 1; TGF-β, tumour growth factors-β; IFN-γ, interferon-γ; TNF-α, tumour necrosis factor-α; IL-12p70, interleukin-12p70; FGF-2, fibroblast growth factor-2; VEGF, vascular endothelial growth factor; G-CSF, granulocyte colony-stimulating factor; GRO, growth-related oncogene; IFN-α2, interferon-α2; PTX3, pentraxin; CCL2, chemokine ligand 2; TNM, tumour node metastasis.