PROTON BEAM RADIOTHERAPY FOR SINONASAL MALIGNANCIES

February 26, 2010 — For patients with locally advanced sinonasal malignancies, proton-beam radiation therapy might be an effective treatment.

According to research presented at the 2010 Multidisciplinary Head and Neck Cancer Symposium in Chandler, Arizona, local control rates were 87% at 5 years after treatment with proton-beam therapy. The overall survival rate at 5 years was 57%, with distant metastasis being the primary cause of relapse.

Sinonasal malignant neoplasms are rare tumors and are difficult to treat because of their anatomical location. Conventional radiation therapy results in very poor local control and is associated with significant acute and long-term treatment-related toxicities, explained Louis Harrison, MD, chair of radiation oncology at Beth Israel Medical Center in New York City, who moderated the press briefing that highlighted the results of this study.

"The proximity of these tumors to vital structures such as the brain stem and optic nerves can make treatment challenging," Dr. Harrison told Medscape Oncology. "The challenge is to deliver high doses of radiation, but it could also be a source of significant morbidity to the patient."

The management of sinonasal tumors can include surgery and/or radiation therapy. Unfortunately, patients generally present with advanced-stage disease, according to lead author Annie Chan, MD, a radiation oncologist at Massachusetts General Hospital in Boston. "The prognosis has been less than optimal," she said, noting that recent studies show a range of 20% to 50% for 5-year local control of sinonasal malignancies.

Compared with conventional radiotherapy, proton-beam radiation therapy has better dose-distribution properties — allowing higher doses to be delivered to the tumor and lower doses to be delivered to the surrounding normal tissue — than is feasible with any photon technique, according to the authors.

In this study, Dr. Chan and colleagues sought to determine the long-term treatment outcome and prognostic factors in patients with locally advanced sinonasal malignancy who received proton-beam radiation therapy.

Improved Local Control

The cohort consisted of 99 patients with newly diagnosed sinonasal malignancy who were treated with proton-beam radiation therapy at the Massachusetts General Hospital between 1991 and 2003. In this group, 65% had T4b disease, 67% had undergone surgery prior to radiation, and 2% had received concurrent chemotherapy.

The most common histological subtype was squamous cell carcinoma (n = 32), followed by esthesioneuroblastoma/neuroendocrine tumors (n = 30), adenoid cystic carcinoma (n = 20), sarcoma (n = 11), and adenocarcinoma (n = 6).

The median total dose of radiation to the primary tumor was 72.8 GyE (range, 59.4 - 79.4 GyE), and the median percentage of protons was 57% (range, 22% - 84%). More than three quarters of the patients (79%) received elective nodal irradiation, and 82% received twice-daily radiation.

At a median follow-up of 92.6 months for all surviving patients, the authors found local control rates to be 87% at 5 years and 83% at 8 years. The overall survival rates at 5 and 8 years were 57% and 46%, respectively.

They also note that there were no statistically significant differences in local control rates when broken down by histological subtype or T stage. But in a multivariate analysis, T4b disease (P = .001), squamous cell carcinoma (P = .002), and a Karnofsky performance status of 80 or less (P = .005) were associated with decreased overall survival rates.

Distant metastasis accounted for 56% of all relapses, and the distant-metastasis-free survival rate at both 5 and 8 years was 69%. In multivariate analysis, the authors found that only T4b disease was significantly associated with a decreased distant-metastasis-free survival rate (P = .024).

Most patients in the study remained free of late high-grade toxicity. At 5 years, the rates of grade 3 or higher late toxicity was 29% in patients who had undergone surgery prior to proton-beam radiation therapy, and 7% in patients who had not had surgery (P = .07). The most common event was soft-tissue toxicity, reported in 9% of all patients at 5 years.

More Studies Needed, Therapy Not Widely Available

"Compared with other studies, our results are encouraging," said Dr. Chan. "This study showed very encouraging results for these patients, and now prospective multi-institutional studies are being planned to further study the use of proton therapy in the treatment of this rare but aggressive malignancy."

Dr. Harrison acknowledged that although these results are very promising, proton-beam radiation therapy is not widely available yet and is very expensive. This can make recruitment into trials more difficult, he explained, and limit the number of potential participants.

2010 Multidisciplinary Head and Neck Cancer Symposium (MHNCS): Abstract 3. Presented February 25, 2010.