Reduced radiation-induced toxicity by using proton therapy for the treatment of oropharyngeal cancer

Abstract

Patients with squamous cell carcinoma of the oropharynx are generally treated with (chemo) radiation. Patients with oropharyngeal cancer have better survival than patients with squamous cell carcinoma of other head and neck subsites, especially when related to human papillomavirus. However, radiotherapy results in a substantial percentage of survivors suffering from significant treatment-related side-effects. Late radiation-induced side-effects are mostly irreversible and may even be progressive, and particularly xerostomia and dysphagia affect health-related quality of life. As the risk of radiation-induced side-effects highly depends on dose to healthy normal tissues, prevention of radiation-induced xerostomia and dysphagia and subsequent improvement of health-relatedquality of life can be obtained by applying proton therapy, which offers the opportunity to reduce the dose to both the salivary glands and anatomic structures involved in swallowing.This review describes the results of the first cohort studies demonstrating that proton therapy results in lower dose levels in multiple organs at risk, which translates into reduced acute toxicity (i.e. up to 3 months after radiotherapy), while preserving tumour control. Next to reducing mucositis, tube feeding, xerostomia and distortion of the sense of taste, protons can improve general well-being by decreasing fatigue and nausea. Proton therapy results in decreased rates of tube feeding dependency and severe weight loss up to 1 year after radiotherapy, and may decrease the risk of radionecrosis of the mandible. Also, the model-based approach for selecting patients for proton therapy in the Netherlands is described in this review and future perspectives are discussed.

Figure 1.

Proton and photon dose distribution of a patient with cT4N0M0 oropharyngeal cancer This 47-year-old patient presented with a cT4N0M0 oropharyngeal cancer (p16+/HPV+) involving the base of the tongue, mobile tongue and floor of the mouth. He was treated with chemoradiation: the primary tumour was treated up to 70 Gy in 35 fractions of 2 Gy; the elective neck Level I-IVa bilaterally was treated with 54.25 Gy in 35 fractions of 1.55 Gy. (A) Mean dose to the superior pharyngeal constrictor is 40.6 Gy for protons vs 51.9 Gy for photons. The superior pharyngeal constrictor is delineated in red, indicated by the white arrow. (B) Mean dose to the inferior pharyngeal constrictor is 12.7 Gy for protons vs 26.2 Gy for photons. The inferior pharyngeal constrictor is delineated in blue, indicated by the white arrow. (C) Mean dose to the cricopharyngeal muscle is 9.6 Gy for protons vs 27.6 Gy for photons. The cricopharyngeal muscle is delineated in red, indicated by the white arrow. (D) Mean dose to the right parotid gland is 16.4 Gy for protons vs 24.1 Gy for photons. The right parotid gland is delineated in olive and, indicated by the white arrow. (E) Mean dose to the brainstem is 2.1 Gy for protons vs 19.4 Gy for photons. The brainstem is delineated in yellow and is indicated with the white arrow. The red line represents the 70 Gy CTV and the pink line represents the 54.25 Gy CTV. CTV,clinical target volume; HPV, humanpapillomavirus.

Figure 2.

Proton and photon dose distribution of a patient with a cT1N3M0 oropharyngeal cancer This 66-year-old patient presented with a cT1N3M0 squamous cell carcinoma of the left tonsil (p16+/HPV+). He was treated with concurrent chemoradiation. The primary tumour on the left side and the pathological lymph nodes in Level II, III and IV in the left neck were treated with 35 fractions of 2 Gy to a total dose of 70 Gy. The elective neck Level II-IVa on the right side and Level I-V and Level VII on the left side were treated with 54.25 Gy in 35 fractions of 1.55 Gy. (A) Mean dose to the oral cavity is 17.7 Gy for protons vs 44.4 Gy for photons. The oral cavity is delineated in green and is indicated with the white arrow. (B) Mean dose to the superior pharyngeal constrictor is 49.1 Gy for protons vs 56.6 Gy for photons. The superior pharyngeal constrictor is delineated in red and is indicated with the white arrow. (C) Mean dose to the inferior pharyngeal constrictor is 17.7 Gy for protons vs 27.5 Gy for photons. The inferior pharyngeal constrictor is delineated in blue and is indicated with the white arrow. (D) Mean dose to the cricopharyngeal muscle is 12.1 Gy for protons vs 20.0 Gy for photons. The cricopharyngeal muscle is delineated in red and is indicated with the white arrow. (E) Mean dose to the right parotid gland is 11.5 Gy for protons vs 18.8 Gy for photons. The right parotid gland is delineated in olive and is indicated with the white arrow. The red line represents the 70 Gy CTV and the pink line represents the 54.25 Gy CTV. CTV,clinical target volume; HPV, humanpapillomavirus.

Figure 3.

Estimated radiation-induced toxicity rates of treatment with protons vs photons for a patient with cT4N0M0 oropharyngeal cancer Dose distribution of radiation with protons vs photons and dose to several organs at risk for this patient are shown in Figure 1. By using proton therapy, the lower dose to organs at risk translates into a decreased risk of tube dependency (11.2%). So, this patient was treated with proton therapy. Abbreviations: NTCP, normal tissue complication probability; ∑, sum; ∆, absolute difference.

Figure 4.

Estimated radiation-induced toxicity rates of treatment with protons vs photons for a patient with cT1N3M0 oropharyngeal cancer Dose distribution of radiation with protons vs photons and dose to several organs at risk for this patient are shown in Figure 2. By using proton therapy, the lower dose to organs at risk translates into a decreased risk of both Grade 2 and Grade 3 radiation-induced toxicity. So, this patient was treated with proton therapy. Abbreviations: NTCP, normal tissue complication probability; ∑, sum; ∆, absolute difference.

Figure 5.

Results of the plan comparison in 42 p16-positive OPC patients between VMAT (photons) and IMPT (protons). Both plans were optimised based on NTCP-models for moderate-to-severe patient-rated xerostomia (contralateral parotid gland), Grade ≥2 dysphagia (oral cavity and superior pharyngeal constrictor) and tube feeding dependence (superior and inferior pharyngeal constrictor, cricopharyngeal muscle and contralateral parotid gland). Abbreviations: IMPT, intensity-modulated proton therapy; PCM, pharyngeal constrictor muscle; VMAT, volumetric modulated arc therapy.