Fast neutron radiotherapy for inoperable salivary gland tumors: Is it the treatment of choice?

Abstract

Salivary gland tumors a.re relatively rare, comprising approximately l-3% of all head and neck malignancies. They can arise in a variety of different sites (e.g., parotid gland, submandibular gland, sublingual gland, minor salivary glands) and consist of diverse histologies having varying potential for aggressive local behavior and distant spread. Reported series thus tend to be small and difficult to compare with each other. Moreover, the series tend to cover many years of treatment with changes both in treatment equipment and technique occurring over the time span in question. With these constraints, it is understandable why the role of radiotherapy for malignant tumors of the salivary gland is still in an unsettled state. Classically these tumors have been considered as “radioresistant” and surgery has been the primary treatment modality. Subsequently a review of the literature by Reddy et al. I4 showed that postoperative radiotherapy could appreciably reduc:e the local recurrence rates in patients having a high risk: of microscopic residual disease. The situation is not so favorable for inoperable tumors or for tumors recurrent after an initial surgical resection. The situation for low linear energy transfer (LET) photon or electron irradiation alone is summarized in Table 1 which represents a fairly extensive review of the literature. Patients treated postoperatively for microscopic residual disease or in a palliative manner with low doses of radiation are not included in the table. The long term local control rate based upon a total of 188 patients is only 28%. Note that the often quoted work by Ring and Fletcher” showing an 8 1% local control rate is not included in Table 1 because in reality it considers mostly patients treated postope:ratively for microscopic residual disease. Given the combination of a relatively poor outlook with conventional treatlment and the superficial location of the tumors, salivary gland malignancies were a natural tumor system for early neutron radiotherapy studies. The initial work was largely done using neutron generators built primarily for physics research purposes and subsequently adapted to medical use. They were primitive and their beams often had penetrating properties more like old-fashioned, orthovoltage units than modem megavoltage linear accelerators or “Co units. Nevertheless, while there is still considerable controversy in the efficacy of fast neutrons for the treatment of most malignancies, there is nearly unanimous agreement that for salivary gland tumors, the results are much better than could be obtained with conventional radiotherapy. The first radiobiological evidence that neutrons should be particularly effective in the treatment of salivary gland tumors is due to Batterman et al.’ who measured the relative biological effectiveness (RBE) relative to 6oCo radiation for neutrons produced by d - T reactions using human tumors metastatic to lung. They determined the RBE for growth delay in terms of the time required for tumor mass to return to its pre-irradiation volume as evaluated on serial radiographs. Patients having two or more metastases had lesions simultaneously treated with the two types of radiation. A wide range of RBE’s was found but an adenoidcystic carcinoma from a parotid gland primary was found to be among the highest: RBE = 5.7 for a single radiation dose and RBE = 8.0 for multiple radiation fractions such as would correspond to clinical treatment schemes. For most other tumors, the RBE’s were in the range of 2.5-4.0. Clinical results overwhelmingly support this conclusion. The local control rates for salivary gland tumors treated with fast neutrons are summarized in Table 2. The Fermi laboratory work reported by Saroja et al.,” in this issue, is the largest single series to date. It comprises 113 evaluable patients with gross tumors treated with fast neutron radiotherapy between September 1976 and December 1984. Ten patients were re-irradiated for a recurrence in a region that had already received postoperative low LET radiotherapy. The local control rate as 67% for