Postoperative Radiation Therapy for Parotid Pleomorphic Adenoma with Close or Positive Margins: Treatment Outcomes and Toxicities

Discussion

Benign pleomorphic adenomas are the most common neoplasms of the parotid gland. It is widely accepted that surgery (parotidectomy) is the primary treatment for pleomorphic adenoma. We demonstrated the efficacy and tolerability of PORT for patients with this disease with positive or close margins after resection. A review of several series revealed that the recurrence rate was greater than 20% among patients who underwent enucleation compared to 1% in patients who underwent total parotidectomy (7). Still, the question as to how much parotid tissue should be resected remains and thus superficial, sub-total and total parotidectomy remain viable surgical options that can reduce the risk of local recurrence when compared to enucleation (3).

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Figure 1.

Actuarial relapse-free survival.

The role of PORT in the treatment of benign pleomorphic adenomas is controversial and some clinicians believe that radiation therapy should be avoided in the majority of these cases (6, 8-10). In malignant salivary gland tumors, matched-pair analysis with historical controls revealed no statistically significant benefit in local control in patients treated with PORT compared to surgery alone; however, Armstrong et al. (11) did find that PORT resulted in a significant improvement in survival and a benefit in local control in stage III and IV tumors. In malignant salivary gland neoplasms, there are factors other than stage that have been recognized as indicators for PORT, including close or positive surgical margins, perineural or perilymphatic invasion, intraparotid or regional nodal metastases and recurrent disease(12-15). Given the strength of evidence behind these factors, it would stand to reason that some of them may also represent applicable indicators for PORT in benign pleomorphic adenomas.

There have been a number of retrospective reviews of PORT for pleomorphic adenomas. Armitstead et al. (16) reported the first study that demonstrated the value of PORT in salivary pleomorphic adenomas. They reviewed 76 patients with a primary pleomorphic salivary adenoma treated with simple extra-capsular enucleation and high-energy radiation between 1963 and 1976. Only 1 patient had developed a recurrence after radiation. This study demonstrated the importance of PORT in cases where incomplete resections are performed.

Dawson et al. (17) reported on 29 patients with recurrent pleomorphic adenomas (mixed tumors) of the parotid treated with excision and PORT. In this study, 18 of 20 (90%) patients with a first recurrence achieved local control comparing favorably with series employing surgery alone. PORT was thus found to be beneficial in cases of recurrent disease.

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Figure 2.

Actuarial overall survival.

Samson et al. reviewed 21 cases of recurrent pleomorphic adenoma treated with subtotal excision and facial nerve preservation, followed by PORT (8). Of the 17 patients with microscopic residual tumor at completion of surgery, 16 (94%) remained free of recurrence at 6 years whereas only one of four patients (25%) with a large postoperative tumor load remained free of disease. Importantly, facial nerve function was normal in 20 of 21 patients. The authors recommended that facial nerve preservation with PORT should be considered as an alternative to nerve sacrifice in selected cases of recurrent pleomorphic adenoma. Liu reviewed 76 patients with pleomorphic adenoma of the parotid of which 55 received PORT between 1970 and 1987 at the Princess Margaret Hospital (9). These patients had been treated with total parotidectomy with facial nerve preservation. With a median follow up of 12.5 years, relapse-free survival was 62% and 93% for patients with gross residual disease and microscopic disease, respectively. While PORT was found to be most useful in cases of recurrent disease, the authors also recommended that it be considered in cases of tumor spillage or residual disease. Of note, no patient developed a secondary malignancy.

In another study, Barton et al. revealed the importance of immediate PORT vs. delayed radiation after an observed recurrence (18). They followed 187 patients with incomplete removal or tumor spillage of parotid pleomorphic adenomas treated with PORT. One hundred fifteen patients had radiotherapy immediately after their first resection while 72 patients underwent PORT after surgical treatment of one or more recurrences. Radiation was initially delivered with a radium needle implant prior to the 1960s and then with external beam. At a median follow-up of 14 years, recurrence rates were 0.9% (1/115) and 12.5% (9/115) in the immediate and delayed arms, respectively. The authors concluded that patients having an unsatisfactory surgery due to spill at operation or residual tumor should undergo PORT immediately because of the increased morbidity and higher incidence of a second recurrence with delayed radiation.

In an update on their experience with radiation for pleomorphic adenoma of the parotid, Wallace et al. reviewed 25 patients of which 23 were treated with resection followed by PORT (19). At a median follow-up of 10.5 years, local control was achieved in 13 (75%) of 16 patients with subclinical disease and 5 (56%) of 9 patient with gross disease. Two out of the 25 patients underwent definitive radiation therapy without resection and both experienced local recurrence, revealing yet again the oncologic necessity for surgical resection prior to radiation therapy.

The local control rates in the above studies are in general concordance with our findings; however, in our study, we focused solely on the patients with close or positive margins who received PORT after resection.

Malard et al. performed a retrospective review of 32 patients with parotid pleomorphic adenoma treated with resection at their institution with a 20-year follow-up (10). Eleven patients were treated with PORT. In contrast to prior studies, Malard et al. found no significant reduction in local recurrence with PORT but did note a delay in time-to-recurrence in cases of multifocal tumors. They noted that their sample size of patients receiving PORT was small (n=11) and this likely contributed to their findings.

One reason for the reluctance to use radiation therapy is the fear of inducing a second malignant tumor in the remaining gland or in other organs of the head and neck. However, series reviewing the outcomes of patients who underwent PORT for benign pleomorphic adenoma have found that the incidence of second primary tumors is low (18, 20, 21). We did not find any secondary malignancies in our patient cohort following radiation therapy.

Another concern with using PORT is the development of acute and late toxicities. As presented in our study, treatment toxicity was minimal. All significant acute toxicities resolved within 3 months of treatment completion and the only late toxicity was xerostomia, which was experienced by 2 (10%) of our patients.

There are minimal data on the toxicity of parotidectomy alone, but the available data suggest that radiation therapy does not add substantially to this toxicity (22). Chaushu et al. (23) reviewed salivary flow rates in preoperative and postoperative settings and reported decreased flow proportional to the volume of parotid resected. Nitzan et al. reported on 53 patients with parotidectomy and found that 11 (21%) patients developed xerostomia (24). While it would be difficult in our series to separate late grade 1 xerostomia induced by resection, postoperative radiation, or both, this toxicity did not appear to be a major clinical problem in our cohort.

We believe that our levels of toxicity were low as a direct correlation to the limited anatomic contouring volumes (parotid bed with a modest margin) used to guide our treatment plans and because of the technology employed in treating the majority of these patients. IMRT has been found to decrease toxicity when used to treat parotid lesions in comparison to 3DCRT (25), and three fourths of our patient cohort was treated with IMRT. Because of our findings, we believe that the prospect of developing treatment-related toxicity should not sway the practitioner away from postoperative radiation in warranted cases.

There are certain limitations to our study. It is a retrospective study with a relatively small number of patients. While the median follow-up period was significant, longer follow-up would be needed to ensure that our local control rates and toxicity profiles are maintained.