Researchers at the University of Texas MD Anderson Cancer Center have published the first clinical experience and toxicity of multifield optimization intensity modulated proton therapy (MFO-IMPT) for patients with head and neck tumors.
Intensity modulated radiation therapy (IMRT) is the current standard of treatment for head-and-neck cancer, since its ability to adjust the dose to target volume leaves normal structures, such as the parotid glands, untouched. However, IMPT has the potential to further improve treatment by avoiding high doses of radiation to normal tissue structures, preserving neurocognitive function, vision, swallowing, hearing, taste and speech. Additionally, proton therapy can provide superior dose distribution and a more precise delivery of photons than scattering beam techniques, especially in conjunction with MFO.
This is extremely relevant in cases that involve treatment of complex structures, such as the bilateral aspects of the neck. However, the question so far has been the safety and effectiveness of IMPT for the treatment of head-and-neck cancers.
To answer this question, a team of scientists led by Steven J. Frank, assistant professor of radiation therapy and medical director of the MD Anderson Proton Therapy Center, followed 15 consecutive patients with different types of head and neck tumors who underwent MFO-IMPT active scanning beam proton therapy.
“This study provides additional evidence that proton therapy for head-and-neck cancers is safe and effective”, said Prof. Frank. “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. 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,” he added.
Among the 15 patients studied, 10 had squamous cell carcinoma (SCC), 8 had tumors located in the oropharynx, 1 had a nasopharynx tumor, and 1 had an unknown tumor with cervical metastases. All of the subjects had comprehensive proton therapy ranging from 72.5 to 221.8 MeV and covering the area between the base of the skull and the clavicle. Five patients who had adenoid cystic carcinoma (ACC) simultaneously received chemotherapy and MFO-IMPT for unresectable disease, receiving 70 Gy (RBE) in 33 fractions to gross disease with margin but no treatment to the regional lymphatics.
All patients experienced grade 1 to grade 3 xerostomia (reduced saliva) and mucositis (inflammation of the mucous membranes lining the digestive tract), as well as vomiting and radiation dermatitis. Other toxicities experienced by some patients included altered sense of taste, difficulty in swallowing, vomiting and weight loss. However, these toxicities were not as severe as those reported by patients who underwent IMRT.
All 15 patients were able to complete treatment with MFO-IMPT, with no need for treatment breaks or hospitalizations. No treatment-related deaths were registered, and with a median follow-up time of 28 months the overall clinical complete response rate was an encouraging 93.3%.
MD Anderson has treated approximately 300 such patients since it initiated MFO-IMPT in 2010 and the MD Anderson Proton Therapy Center was one of the first in the world to offer MFO-IMPT treatment. However, with the new generation of proton therapy systems, this technique can become a standard procedure at all proton therapy centers.
Even though the treatment delivery is more expensive compared to IMRT, when the episodic costs of care are considered, proton therapy may prove to be less expensive.
“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.” Said Prof. Frank.
Furthermore, due to its increased energy, the photon beam has a rapid dose fall-off, making IMPT more sensitive to treatment planning errors than IMRT.
The research team has been undergoing studies aiming to improve internally developed robust optimization software that identifies, arranges, and analyzes uncertainties in the treatment planning and delivery process.
Future investigation of proton therapy in prospective clinical trials can have potential implications in the treatment and life quality of patients suffering from head and neck tumors as well as patients diagnosed with other types of solid tumors.
The MD Anderson team includes Steven J.Frank, MD, James Fox, MD, Michael Gillin, MD, Radhe Mohan, PhD, Adam Garden, MD, David Rosenthal, MD, G. Brandon Gunn, MD, Randal S. Weber, MD, Merrill S. Kies, MD, Jan S. Lewin, PhD, Mark F. Munsell, MS, Matthew B. Palmer, BS, Narayan Sahoo, PhD, Xiaodong Zhang, PhD, Wei Liu, PhD and X. Ronald Zhu, PhD.