Steven J Frank, associate professor of radiation therapy and medical director of the MD Anderson Proton Therapy Center and colleagues reported the early outcomes of 15 consecutive patients enrolled in a progressive study. After a median of 28 months, all patients were alive, 14 were cancer-free, and none had required hospitalization as a result of treatment. "The study provides additional evidence that proton therapy for head-and-neck cancers is safe and effective," he said. MD Anderson has treated approximately 300 such patients since it initiated MFO-IMPT in 2010 (Int. J. Radiat. Oncol. Biol. Phys. 89 846).

"In the United States, more than 100,000 cases of head-and-neck cancer are diagnosed annually, making it the sixth most common form of cancer. The rising incidence of human papillomavirus (HPV)-associated oropharyngeal tumours in the United States and Europe has reached epidemic proportions. In Asia, the Epstein-Barr virus is driving a huge increase in nasopharynx cancer," Frank stated. "While cure rates are high, patients may suffer with a range of acute and often late morbidities that can be the cause of substantial misery for decades."

IMRT is the current standard of treatment for head-and-neck cancer because of its ability to tightly conform the dose to target volume, sparing normal structures such as the parotid glands. IMPT further refines treatment by avoiding high doses of radiation to normal tissue structures. Because of this, neurocognitive function, vision, swallowing, hearing, taste and speech can be better preserved.

Compared to photon radiotherapy, proton therapy has the potential to deliver superior dose distributions, due to the shape of the dose deposition curve of a proton pencil beam. IMPT offers more precise delivery of photons than passive scattering beam techniques, and is used when the dose must be sculpted away from a nearby critical structure. Scanning beam proton therapy with MFO can further shape the dose in cases that involve treatment of such complex targets as the bilateral aspects of the neck. The question has been whether IMPT is as safe and effective as IMRT for the treatment of head-and-neck cancers.

Clinical experience

The study included 10 patients with squamous cell carcinoma (SCC), who had tumours located in the oropharynx (eight patients), nasopharynx (one patient) and one unknown with cervical metastases. All had comprehensive proton therapy extending from the base of the skull to the clavicle. Five patients with adenoid cystic carcinoma (ACC) were treated with concurrent chemotherapy and MFO-IMPT for unresectable disease and received 70 Gy (RBE) in 33 fractions to gross disease with margin but no treatment to the regional lymphatics. For all patients, proton beam energies ranged from 72.5 to 221.8 MeV.

All patients experienced grade 1 to grade 3 xerostomia and mucositis. Other toxicities experienced by some patients included dysgeusia, dysphagia, vomiting, radiation dermatitis and weight loss. Toxicities were less severe than those experienced by patients who underwent IMRT. With the exception of one patient with ACC who was being re-irradiated for a recurrent paranasal sinus tumour, all patients had a clinical complete response.

MD Anderson Proton Therapy Center was one of the first in the world to offer MFO-IMPT treatment. But Frank says that with the new generation of proton therapy systems, he expects this to become a standard offering at all proton therapy centres. Although the treatment delivery is more expensive compared to IMRT, when the episodic costs of care are considered, proton therapy may be less expensive.

Frank explained: "We performed a cost analysis of treatment for the first two patients of a randomized trial comparing outcomes of IMPT-treated patients versus IMRT-treated patients, using actual costs and time-driven activity-based costing analysis. What we were able to demonstrate was that while the incremental cost of delivery of protons was more, the curves cross at about 31 days. The IMRT-treated patient experienced more toxicity that required emergency department visits, hospitalization and feeding tubes." And this cost analysis did not include costs incurred by the patient (transportation costs, loss of income or health insurance co-payment), which would have been greater for IMRT.

Due to the steep dose fall-off of a photon beam, IMPT is more sensitive to treatment planning errors than IMRT. Frank told medicalphysicsweb that his team is continuing to improve internally developed robust optimization software that identifies, arranges and analyses uncertainties in the treatment planning and delivery process. Active investigation of robust analysis, image guidance, optimal beam angle selection, advanced mobilization techniques and adaptive planning are also ongoing.

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