Final report of a randomized trial on altered-fractionated radiotherapy innasopharyngeal carcinoma prematurely terminated by significant increase inneurologic complications

Purpose: The aim of the present study was to compare the survival, local co ntrol and complications of conventional/accelerated-hyperfractionate radiot herapy and conventional radiotherapy in nonmetastatic nasopharyngeal carcin oma (NPC). Methods and Materials: From February 1993 to October 1995, 159 patients wit h newly diagnosed nonmetastatic (M0) NPC with N0 or 4 cm or less N1 disease (Ho's N-stage classification, 1978) were randomized to receive either conv entional radiotherapy (Arm I, n = 82) or conventional/accelerated-hyperfrac tionate radiotherapy (Arm II, n = 77). Stratification was according to the T stage. The biologic effective dose (10 Grays) to the primary and the uppe r cervical lymphatics were 75.0 and 73.1 for Arm I and 84.4 and 77.2 for Ar m II, respectively. Results: With comparable distribution among the T stages between the two ar ms, the free from local failure rate at 5 years after radiotherapy was not significantly different between the two arms (85.3%; 95% confidence interva l, 77.2-93.4% for Arm I; and 88.9%; 95% confidence interval, 81.7-96.2% for Arm II). The two arms were also comparable in overall survival, relapse-fr ee survival, and rates of distant metastasis and regional relapse. Conventi onal/accelerated-hyperfractionated radiotherapy was associated with signifi cantly increased radiation-induced damage to the central nervous system (in cluding temporal lobe, cranial nerves, optic nerve/ chiasma, and brainstem/ spinal cord) in Arm II. Although insignificant, radiation-induced cranial n erve(s) palsy (typically involving WI-XII), trismus, neck soft tissue fibro sis, and hypopituiturism and hypothyroidism occurred more often in Arm II. In addition, the complications occurred at significantly shorter intervals after radiotherapy in Arm II. Conclusion: Accelerated hyperfractionation when used in conjunction with a two-dimensional radiotherapy planning technique, in this case the Ho's tech nique, resulted in increased radiation damage to the central nervous system without significant improvement in efficacy. (C) 2000 Elsevier Science Inc .