Neutron versus photon irradiation for unresectable salivary gland tumors: Final report of an RTOG-MRC randomized clinical trial

Purpose: To compare the efficacy of fast neutron radiotherapy versus conventional photon and/or electron radiotherapy for unresectable, malignant salivary gland tumors a randomized clinical trial comparing was sponsored by theRadiation Therapy Oncology Group in the United States and the Medical Research Council in Great Britain. Methods and Materials: Eligibility criteria included either inoperable primary or recurrent major or minor salivary gland tumors. Patients were stratified by surgical status (primary vs. recurrent), tumor size (less than or greater than 5 cm), and histology (squamous or malignant mixed versus other). After a total of 32 patients were entered onto this study, it appeared that the group receiving fast neutron radiotherapy had a significantly improved local/regional control rate and also a borderline improvement in survival and the study was stopped earlier than planned for ethical reasons. Twenty-five patients were study-eligible and analyzable. Results: Ten-year follow-up data for this study is presented. On an actuarial basis, there continues to be a statistically significant improvement in local/regional control for the neutron group (56% vs. 17%, p = 0.009) but there is no improvement in overall survival (15010 vs. 25010, p = n . s .). Patterns of failure are analyzed and it is shown that distant metastases account for the majority of failures on the neutron arm and local/regional failures account for the majority of failures on the photon arm. Long-term, treatment-related morbidity is analyzed and while the incidence of morbidity graded "severe" was greater on the neutron arm, there was no significant difference in "life-threatening" complications. This work is placed in the context of other series of malignant salivary gland tumors treated with definitive radiotherapy. Conclusions: Fast neutron radiotherapy appears to be the treatment-of-choice for patients with inoperable primary or recurrent malignant salivary gland tumors.