Predictors of severe late radiotherapy-related toxicity after hyperfractionated radiotherapy with or without concomitant cisplatin in locally advanced head and neck cancer. Secondary retrospective analysis of a randomized phase III trial (SAKK 10/94).
OBJECTIVE
This secondary analysis was performed to identify predictive factors for severe late radiotherapy (RT)-related toxicity after treatment with hyperfractionated RT +/- concomitant cisplatin in locally advanced head and neck cancer.


METHODS
Patients were retrospectively analyzed from the previously reported randomized phase III trial: SAKK 10/94. Severe late RT-related toxicity was defined as late RTOG ≥ grade 3 toxicity starting 3 months after end of RT and/or potential treatment-related death within 3 years of randomization.


RESULTS
Two hundred and thirteen randomized patients were analyzed; 84 (39%) experienced severe late RT-related toxicity. With median follow-up of 9.7 years (range, 0.4-15.4 years), median time to severe late RT-related toxicity was 9.6 years. In the univariate Cox proportional hazards model the following variables were associated with severe late RT-related toxicity: advanced N-classification (p<0.001); technically unresectable disease (p=0.04); weight loss ratio (p=0.003); supportive measures (p=0.009) and severe acute dysphagia (p=0.001). In the subsequent multivariate analysis all variables except use of supportive measures remained statistically significant.


CONCLUSIONS
Chemotherapy did not appear to affect severe late RT-related toxicity, but advanced N-classification, technically unresectable disease, weight loss ratio, and severe acute dysphagia were independent predictive factors for severe late RT-related toxicity.
Department of Radiation Oncology, Inselspital, Bern University Hospital, Bern, Switzerland. pirus.ghadjar@insel.ch
Pirus
P
Ghadjar
Mathew
M
Simcock
Frank
F
Zimmermann
Michael
M
Betz
Stephan
S
Bodis
Jacques
J
Bernier
Gabriela
G
Studer
Daniel M
DM
Aebersold
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy / Q000009:adverse effects* / Q000379:methods*; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects; D016001:Confidence Intervals; D019583:Dose Fractionation, Radiation; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005500:Follow-Up Studies; D006258:Head and Neck Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011832:Radiation Injuries / Q000175:diagnosis* / Q000209:etiology / Q000517:prevention & control; D011879:Radiotherapy Dosage; D012189:Retrospective Studies; D018570:Risk Assessment; D013997:Time Factors; D016896:Treatment Outcome
D002945:Cisplatin