Hyperthermia with radiotherapy reduces tumour alpha/beta: Insights from trials of thermoradiotherapy vs radiotherapy alone. (September 2019)

• Record Type: Journal Article
• Authors: Datta, Niloy R.; Bodis, Stephan
• Is Part Of: Radiotherapy and oncology. Volume 138(2019)
• Page Start: 1
• Page End: 8
• Publication Date: 2019-09
• Subjects: BED biological effective dose -- BEDHTRT biological effective dose with thermoradiotherapy -- BEDRT biological effective dose with radiotherapy alone -- CR complete response -- D total radiotherapy dose -- d radiotherapy dose per fraction -- HTRT thermoradiotherapy -- LACC locally advanced cancer cervix -- LAHNC locally advanced head and neck cancer -- L-Q linear-quadratic -- n number of fractions -- ns not significant -- OR odds ratio -- RcBC recurrent breast cancer -- RD risk difference -- RR risk ratio -- RT radiotherapy -- α/βHTRT tumour α/β values with thermoradiotherapy -- α/βRT tumour α/β values with radiotherapy alone; Hyperthermia -- Radiobiology -- Radiation -- Alpha/beta -- Randomized clinical trial -- Meta-analysis; Oncology -- Periodicals; Radiotherapy -- Periodicals; Tumors -- Periodicals; Medical Oncology -- Periodicals; Neoplasms -- radiotherapy -- Periodicals; Radiotherapy -- Periodicals; Radiothérapie -- Périodiques; Cancérologie -- Périodiques; Tumeurs -- Périodiques; Electronic journals; 616.9940642
• DOI: 10.1016/j.radonc.2019.05.002
• Languages: English
• ISSNs: 0167-8140

Abstract

Graphical abstract: Highlights: Hyperthermia is known to inhibit postirradiation DNA damage repair. This could alter the α/β values in tumours. α/β were estimated from 12 clinical trials of thermoradiotherapy vs radiotherapy. α/β with thermoradiotherapy was computed as 2.25 Gy (95% CI: 1.8–2.7). This should guide in optimizing thermoradiotherapy dose-fractionation schedules. Abstract: Purpose: 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/βHTRT 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). Methods: 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 (BEDRT ) was computed assuming an α/βRT of 10 Gy. As outcomes were favourable with HTRT, thermoradiobiological BED (BEDHTRT ) was calculated as a product of BEDRT and %CRHTRT /%CRRT . The α/βHTRT was estimated as Dd/(BEDHTRT – D). Results: 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 BEDRT and BEDHTRT were 64.7 Gy (SD: ±15.5) and 109.5 Gy (SD: ±32.1) respectively and global α/βHTRT was 2.25 Gy (SD: ±0.79). Mean α/βHTRT for RcBC, LAHNC and LACC were 2.05 Gy, 1.74 Gy and 3.03 Gy respectively. On meta-regression, α/βHTRT was the sole predictor for the corresponding risk differences of the studies (coefficient = −0.096; p = 0.03). Conclusion: 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.