The impact of individual in vivo repair of DNA double-strand breaks on oral mucositis in adjuvant radiotherapy of head-and-neck cancer.
OBJECTIVE
To evaluate the impact of individual in vivo DNA double-strand break (DSB) repair capacity on the incidence of severe oral mucositis in patients with head-and-neck cancer undergoing adjuvant radiotherapy (RT) or radiochemotherapy (RCT).


METHODS
Thirty-one patients with resected head-and-neck cancer undergoing adjuvant RT or RCT were examined. Patients underwent RT of the primary tumor site and locoregional lymph nodes with a total dose of 60-66 Gy (single dose 2 Gy, five fractions per week). Chemotherapy consisted of two cycles of cisplatin and 5-fluorouracil. To assess DSB repair, γ-H2AX foci in blood lymphocytes were quantified before and 0.5 h, 2.5 h, 5 h, and 24 h after in vivo radiation exposure (the first fraction of RT). World Health Organization scores for oral mucositis were documented weekly and correlated with DSB repair.


RESULTS
Sixteen patients received RT alone; 15 patients received RCT. In patients who developed Grade≥3 mucositis (n=18) the amount of unrepaired DSBs 24 h after radiation exposure and DSB repair half-times did not differ significantly from patients with Grade≤2 mucositis (n=13). Patients with a proportion of unrepaired DSBs after 24 h higher than the mean value + one standard deviation had an increased incidence of severe oral mucositis.


CONCLUSIONS
Evaluation of in vivo DSB repair by determination of γ-H2AX foci loss is feasible in clinical practice and allows identification of patients with impaired DSB repair. The incidence of oral mucositis is not closely correlated with DSB repair under the evaluated conditions.
Department of Radiotherapy and Radiation Oncology, Saarland University Medical School, Homburg, Germany. rajfle@uks.eu
Jochen
J
Fleckenstein
Martin
M
Kühne
Katharina
K
Seegmüller
Sarah
S
Derschang
Patrick
P
Melchior
Stefan
S
Gräber
Andreas
A
Fricke
Claudia E
CE
Rübe
Christian
C
Rübe
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D059248:Chemoradiotherapy / Q000009:adverse effects; D002945:Cisplatin / Q000008:administration & dosage; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair / Q000502:physiology*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D006657:Histones / Q000097:blood*; D006801:Humans; D015994:Incidence; D015182:Lymphatic Irradiation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011836:Radiation Tolerance; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects; D013280:Stomatitis / Q000453:epidemiology / Q000235:genetics*; D013997:Time Factors
D015415:Biomarkers; C468783:H2AX protein, human; D006657:Histones; D002945:Cisplatin; D005472:Fluorouracil