Radiation oncology is vital to the management of patients with cancer of the head and neck, and for certain patients, proton therapy may offer significant benefit over intensity-modulated radiation therapy, according to Walter J. Curran, MD, Executive Director of the Winship Cancer Institute of Emory University, Georgia Research Alliance Eminent Scholar in Cancer Research, and NRG Oncology Group Chair.

“There’s no question intensity-modulated radiation therapy provides significant advantage over three-dimensional or two-dimensional radiotherapy, but the sequelae associated with it are still significant,” he said at a symposium hosted by the Winship Cancer Institute and Emory University: Updates in the Management of Head and Neck Cancer.¹ Proton therapy may be superior to other modalities because it can increase the possibility of controlling a tumor and reduce the possibility of long-term complications. “If you know where the target is, deliver the radiation there, and don’t deliver it where the target isn’t,” he explained.

[Clinical trials are needed to establish any superiority of proton therapy over intensity-modulated radiation therapy,] but the important takeaway is its potential lower toxicity to patients.

— Walter J. Curran, MD

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Proton therapy is still concentrated in certain centers and is not yet widely used, so clinical trials are needed to establish any superiority of proton therapy over intensity-modulated radiation therapy. “But the important takeaway is its potential lower toxicity to patients,” said Nabil F. Saba, MD, Professor in the Department of Hematology and Medical Oncology at Emory University School of Medicine and Director of the Head and Neck Medical Oncology Program at the Winship Cancer Institute. “That’s why you go to the trouble of creating a proton center—to benefit patients.”

“As of now, there are no large-scale studies looking into it, but it certainly is a window into the future,” Dr. Saba told The ASCO Post.

Radiation Oncology Evolves

Intensity-modulated radiation therapy has advantages over three-dimensional radiotherapy in terms of lowering the dose to salivary tissue (which does not contain cancer), therefore reducing the risk of xerostomia. “It offers enhanced tumor control at least retrospectively, but there have not been many randomized trials using this technology,” noted Dr. Curran. Further, patient-reported outcomes, critical in the realm of head and neck cancer, are generally improved with intensity-modulated radiation therapy, he added. For example, in areas where targets are near the optic apparatus, it appears there is a reduction in blindness, fewer treatment interruptions, and a reduction in severe late effects² and acute toxicities with intensity-modulated radiation therapy.³

Protons display a variable penetration range in human tissue, and this range is proportional to the proton energy. “In photon, or conventional, radiation, there tends to be a radiation dose beyond the target,” he said. “But proton therapy can be modulated around the tumor.”

With proton therapy, the unwanted side effects of irradiating healthy tissue (eg, in a growing child) can be reduced, added Dr. Curran, noting the use of proton therapy in children has increased significantly over the past 5 years.

Current Research

Ongoing and developing multi-institutional trials of proton therapy include a trial evaluating proton vs intensity-modulated radiation therapy for prostate cancer (Massachusetts General Hospital, University of Pennsylvania, and others), several open and accruing NRG Oncology randomized trials comparing proton therapy with intensity-modulated radiation therapy in the treatment of various malignancies, and a number of Children’s Oncology Group trials. He noted that one NRG phase III randomized trial comparing protons to intensity-modulated radiation therapy and chemotherapy for patients with stage III lung cancer should yield particularly interesting results.

“One of the reasons lung cancer is an area of -interest in proton therapy is there’s a significant reduction of contralateral dose to the heart as compared to intensity-modulated radiation therapy,” declared Dr. Curran. “Heart dose appears to be associated with poor outcome, and perhaps protons can reduce this.”

In the treatment of head and neck cancer, proton therapy is a fairly well-established modality in skull base tumors. “Good preliminary data with intensity-modulated proton therapy has come out of MD Anderson, particularly in oropharyngeal cancer, and there are plans for a randomized phase II trial there,” he added. “There’s a reduction in the dose to the oral cavity and the neck with proton therapy; when nontarget areas get less dose, there are fewer complications.”

Early data comparing proton therapy and intensity-modulated radiation therapy in head and neck cancer patients show promise. A study of 81 patients at MD Anderson resulted in better patient-reported outcomes in the proton-treated group.⁴ Patients cited a decrease in reduction in taste, difficulty swallowing, and overall symptom burden. Similar results have been shown in other disease sites.

According to Dr. Curran, the Winship Cancer Institute is working to develop an Emory Proton Therapy Center and aims to open it for use and clinical trial testing in the next few years. Tremendous technical progress has been made in the treatment of head and neck cancer with radiation therapy, and NRG Oncology and other trials will illuminate forthcoming progress in proton therapy, stated Dr. Curran. ■

DISCLOSURE: Drs. Curran and Saba reported no conflicts of interest.

REFERENCES

1. Curran WJ: Proton therapy in head and neck cancer: Is the future bright enough? 2017 Winship Cancer Institute of Emory University Updates in the Management of Head and Neck Cancer Symposium. Presented April 22, 2017.

2. Machtay M, Moughan J, Trotti A, et al: Factors associated with severe late toxicity after concurrent chemoradiation for locally advanced head and neck cancer: An RTOG analysis. J Clin Oncol 26:3582-3589, 2008.

3. Rosenthal DI, Chambers MS, Fuller CD, et al: Beam path toxicities to non-target structures during intensity-modulated radiation therapy for head and neck cancer. Int J Radiat Oncol Biol Phys 72:747-755, 2008.

4. 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 95:1107-1114, 2016.