Proton therapy delivers the same radiation dose to a tumor as standard radiation therapy with photons while delivering a much lower dose to surrounding tissue. But whether this reduced dose to healthy tissue results in decreased side effects for patients with head and neck cancer has yet to be proven in a randomized controlled trial. Such a trial is now under way to determine whether intensity-modulated proton therapy (IMPT) reduces adverse effects compared with photon therapy for patients with oropharyngeal cancer, one of the most common head and neck cancers.
The standard treatment for oropharyngeal cancer is intensity-modulated radiation therapy with photon beams (IMRT) used concurrently with chemotherapy. However, IMRT causes a high symptom burden because of the radiation dose delivered to surrounding healthy tissues.
“The standard photon-based radiation treatment delivers a lot of unnecessary radiation that causes collateral damage in the oral cavity, brain stem, salivary glands, and larynx,” said Steven Frank, M.D., a professor in the Department of Radiation Oncology and the medical director of the Proton Therapy Center at The University of Texas MD Anderson Cancer Center. “Proton therapy, which is more precisely targeted, provides a unique opportunity to target the cancer and eliminate the unnecessary radiation in head and neck cancer patients.”
Dr. Frank said that most patients who undergo IMRT for oropharyngeal cancer experience grade 3 or 4 adverse effects. These effects include dysphagia requiring a feeding tube, severe mucositis, loss of taste leading to malnutrition with weight loss and dehydration, loss of salivary function causing difficulty in eating, dental issues, trismus, and aspiration pneumonia. Furthermore, one or more of these adverse effects develop into chronic conditions in up to 12% of patients.
In an effort to reduce the occurrence and severity of adverse effects, IMPT is now being used to treat oropharyngeal cancer. Protons deliver most of their energy at the end of their targeted path, with only a low radiation dose delivered to the surrounding healthy tissue. According to Dr. Frank, IMPT for oropharyngeal cancer typically delivers a 25-Gy-lower radiation dose to healthy tissue than does IMRT throughout the course of treatment.
“How much is 25 Gy? That’s equivalent to 12,500 computed tomography scans or 5 million dental x-rays,” Dr. Frank said. “So when we talk about the amount of radiation that we have the ability to eliminate during a cancer patient’s treatment, it is not insignificant. Not only is it not insignificant, avoiding it can improve that patient’s quality of life.”
To quantify the differences in radiation doses delivered to critical structures by IMPT and IMRT, Dr. Frank and his colleagues compared the radiation plans for 50 patients with oropharyngeal cancer who received IMPT in a prior single-arm clinical trial to those for a case-matched cohort that received IMRT. IMPT resulted in significantly lower radiation doses to the oral cavity, hard palate, larynx, mandible, and esophagus and to central nervous system structures associated with nausea and vomiting. A subsequent analysis of patient outcomes found no survival differences between 50 patients with oropharyngeal cancer who received IMPT and a case-matched cohort that received IMRT, but the patients who received IMPT had lower rates of severe weight loss and feeding tube dependency.
Dr. Frank expects the evidence in favor of IMPT to be further supported by a phase II/III clinical trial (No. 2012-0825) that is currently enrolling patients with stage III, IVA, or IVB oropharyngeal cancer. In the multicenter trial, patients are randomly assigned to receive IMPT or IMRT. Patients in both treatment arms receive the same radiation dose to the tumor (70 Gy in 33 fractions over 6.5 weeks), with or without chemotherapy as recommended by the patients’ medical oncologists.
Dr. Frank, the trial’s principal investigator, said the trial’s primary objective is to determine whether IMPT can achieve treatment outcomes similar to those of IMRT with fewer adverse effects. Adverse effects are measured by questionnaires given at baseline and at regular intervals during and after treatment. Patients also undergo a modified barium swallow study at baseline, at the end of radiation therapy, and at regular intervals afterward to measure changes in swallowing function.
So far, more than 130 patients have been enrolled. As more centers have been added for the trial, the projected enrollment has been changed from 440 patients to 520.
“We are very excited about the trial,” Dr. Frank said. “It’s an opportunity to change the standard of care by eliminating unnecessary radiation.”
Value of proton therapy
Dr. Frank believes the ongoing trial can help define the value of proton therapy to individual patients and the health care system as a whole. Although IMPT for oropharyngeal cancer is more expensive than IMRT, a reduced adverse effect profile could save patients and insurance companies the cost of emergency department visits, hospitalization, and treatments such as feeding tubes.
Furthermore, patients who experience fewer adverse effects will likely require less time off from work. “Head and neck tumors are highly curable and can occur in relatively young individuals who may remain in the workforce, so it is important to reduce toxicities as much as possible,” Dr. Frank said. “We think proton therapy can result in better quality of life and better overall value.”
For more information, call Dr. Steven Frank at 713-563-8489. To learn more about the trial comparing proton therapy and standard radiation therapy for patients with oropharyngeal cancer, visit www.clinicaltrials.org and select study No. 2012-0825.
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Holliday EB, Kocak-Uzel E, Feng L, et al. Dosimetric advantages of intensity-modulated proton therapy for oropharyngeal cancer compared with intensity-modulated radiation: A case-matched control analysis. Med Dosim. 2016;41:189–194.
Sio TT, Lin HK, Shi Q, et al. Intensity-modulated proton therapy versus intensity-modulated photon radiation therapy for oropharyngeal cancer: First comparative results of patient-reported outcomes. Int J Radiat Oncol Biol Phys. 2016;95:1107–1114.
Thaker NG, Frank SJ, Feely TW. Comparative costs of advanced proton and photon radiation therapies: Lessons from time-driven activity-based costing in head and neck cancer. J Comp Eff Res. 2015;4:297–301.
Bryan Tutt contributed to this article.
OncoLog, March 2017, Volume 62, Issue 3