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Review
. 2021 Jun 4;22(6):54.
doi: 10.1007/s11864-021-00847-y.

Proton Therapy for HPV-Associated Oropharyngeal Cancers of the Head and Neck: a De-Intensification Strategy

Nicolette Taku  1 , Li Wang  2 , Adam S Garden  1 , David I Rosenthal  1 , G Brandon Gunn  1 , William H Morrison  1 , C David Fuller  1 , Jack Phan  1 , Jay P Reddy  1 , Amy C Moreno  1 , Michael T Spiotto  1 , Gregory Chronowski  1 , Shalin J Shah  1 , Lauren L Mayo  1 , Neil D Gross  3 , Renata Ferrarotto  4 , X Ronald Zhu  5 , Xiaodong Zhang  5 , Steven J Frank  6
Affiliations
Review

Proton Therapy for HPV-Associated Oropharyngeal Cancers of the Head and Neck: a De-Intensification Strategy

Nicolette Taku et al. Curr Treat Options Oncol. .

Abstract

The rise in the incidence of human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPC), the relatively young age at which it is diagnosed, and its favorable prognosis necessitate the use of treatment techniques that reduce the likelihood of side effects during and after curative treatment. Intensity-modulated proton therapy (IMPT) is a form of radiotherapy that de-intensifies treatment through dose de-escalation to normal tissues without compromising dose to the primary tumor and involved, regional lymph nodes. Preclinical studies have demonstrated that HPV-positive squamous cell carcinoma is more sensitive to proton radiation than is HPV-negative squamous cell carcinoma. Retrospective studies comparing intensity-modulated photon (X-ray) radiotherapy to IMPT for OPC suggest comparable rates of disease control and lower rates of pain, xerostomia, dysphagia, dysgeusia, gastrostomy tube dependence, and osteoradionecrosis with IMPT-all of which meaningfully affect the quality of life of patients treated for HPV-associated OPC. Two phase III trials currently underway-the "Randomized Trial of IMPT versus IMRT for the Treatment of Oropharyngeal Cancer of the Head and Neck" and the "TOxicity Reduction using Proton bEam therapy for Oropharyngeal cancer (TORPEdO)" trial-are expected to provide prospective, level I evidence regarding the effectiveness of IMPT for such patients.

Keywords: Clinical trials; De-escalation; De-intensification; Head and neck; Oropharyngeal cancer; Proton therapy.

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Conflict of interest statement

Neil D. Gross was on the advisory board of PDS Biotechnology and Shattuck Labs and was a consultant for Intuitive Surgical. Renata Ferrarotto received personal fees from Regeneron-Sanofi, Ayala Pharmaceuticals, Prelude Pharmaceuticals, Bicara, Klus Pharma, Medscape, and Carevive; she declared institution conflicts of interest with Ayala Pharmaceuticals, AstraZeneca, Merck, Genentech, Pfizer, and Prelude Pharmaceuticals; and she was on the advisory boards of Ayala Pharmaceuticals, Prelude Pharmaceuticals, and Regeneron-Sanofi. Steven J. Frank received grants from C4 Imaging, Eli Lilly, and Hitachi; he received personal fees from Boston Scientific, C4 Imaging, and Varian; he was the founder/director of C4 Imaging; he was on the advisory board of Breakthrough Chronic Care and Varian; and he was a consultant for Boston Scientific and Varian. C. David Fuller received grants and personal fees from Elekta AB. Nicolette Taku received grants from Varian. Li Wang declares that she has no conflict of interest. Adam S. Garden declares that he has no conflict of interest. David I. Rosenthal declares that he has no conflict of interest. G. Brandon Gunn declares that he has no conflict of interest. William H. Morrison declares that he has no conflict of interest. Jack Phan declares that he has no conflict of interest. Jay P. Reddy declares that he has no conflict of interest. Amy C. Moreno declares that she has no conflict of interest. Michael Spiotto declares that he has no conflict of interest. Gregory Chronowski declares that he has no conflict of interest. Shalin J. Shah declares that he has no conflict of interest. Lauren L. Mayo declares that she has no conflict of interest. X. Ronald Zhu declares that he has no conflict of interest. Xiaodong Zhang declares that he has no conflict of interest.

Figures

Fig. 1
Fig. 1
Coronal (top) and sagittal (bottom) views of treatment plans used to assess dose distributions associated with intensity-modulated proton therapy (IMPT) (left) and intensity-modulated photon (X-ray) radiotherapy (IMXT) (middle). The images on the right illustrate the additional radiation dose associated with IMXT relative to IMPT. Reprinted from “Intensity Modulated Proton Therapy for Head and Neck Tumors: Gilding the Lily or Holy Grail?” by Steven J. Frank, International Journal of Radiation Oncology Biology Physics, volume 95, page no. 38, Copyright 2016, with permission from Elsevier.
See this image and copyright information in PMC

References

References and Recommended Reading

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