Hyperthermia with radiotherapy reduces tumour alpha/beta: Insights from trials of thermoradiotherapy vs radiotherapy alone.

Abstract

Hyperthermia inhibits the repair of irradiation-induced DNA damage and thereby could alter the α/β values of tumours. This study estimates the clinical α/β_HTRT values from clinical trials of thermoradiotherapy (HTRT) vs radiotherapy (RT) in recurrent breast (RcBC), head and neck (III/IV) (LAHNC) and cervix cancers (IIB-IVA) (LACC). Three recently published meta-analyses for HTRT vs RT in RcBC, LAHNC and LACC were evaluated for complete response (CR). Studies with specified RT dose (D), dose/fraction (d) and corresponding CRs were selected. Tumour biological effective dose (BED) for each study with RT (BED_RT) was computed assuming an α/β_RT of 10 Gy. As outcomes were favourable with HTRT, thermoradiobiological BED (BED_HTRT) was calculated as a product of BED_RT and %CR_HTRT/%CR_RT. The α/β_HTRT was estimated as Dd/(BED_HTRT - D). 12 trials with 864 patients were shortlisted - RcBC (3 studies, n = 259), LAHNC (5 studies, n = 338) and LACC (4 studies, n = 267). Overall risk difference of 0.28 favoured HTRT (p < 0.001). Mean BED_RT and BED_HTRT were 64.7 Gy (SD: ±15.5) and 109.5 Gy (SD: ±32.1) respectively and global α/β_HTRT was 2.25 Gy (SD: ±0.79). Mean α/β_HTRT for RcBC, LAHNC and LACC were 2.05 Gy, 1.74 Gy and 3.03 Gy respectively. On meta-regression, α/β_HTRT was the sole predictor for the corresponding risk differences of the studies (coefficient = -0.096; p = 0.03). Thermoradiobiological effects on the repair of RT induced DNA damage results in reduction in α/β values of tumours. This should be considered to effectively optimize HTRT dose-fractionation schedules in the clinic.