Toxicity with proton therapy for oral and/or oropharyngeal cancers: A scoping review

Abstract

BackgroundOral and/or oropharyngeal cancers account for approximately 2% of all malignancies, with variation across age groups, genders, and geographic locations. Treatments for oral and/or oropharyngeal cancers usually consist of a combination of surgical excision most commonly followed by radiotherapy ± chemotherapy and/or immunotherapy/biotherapy depending on the nature of the malignancy. The significant morbidity caused by high‐dose radiotherapy to the head and neck region is widely observed. Proton therapy is a promising treatment option that localises a proton beam to direct radiation at a specific target, with reduced irradiation to adjacent structures.MethodThe objective was to explore the toxicity associated with proton therapy for adults with oral and/or oropharyngeal cancer. Eligibility criteria included full‐text articles, English articles, published between up till 7 January 2023. Databases included PubMed, Scopus, Web of Science, Embase, and Scopus.ResultsThe systematic search identified 345 studies and a total of 18 studies were included after two independent reviewers completed title, abstract, and full‐text screening. Included studies were from four countries, and median participant age range was 53.3 to 66 years. The most commonly reported acute toxic effects included dysphagia, radiation dermatitis, oral mucositis, dysgeusia, and alopecia.ConclusionProton therapy is an evolving cancer treatment technique that has diverse advantages over conventional radiotherapy and chemotherapy. This review provides evidence that supports that proton therapy has an improved acute toxicity profile compared to radiotherapy to treat oral and/or oropharyngeal cancer individuals.

Toxicity with proton therapy for oral and/or oropharyngeal cancers

“…This rate was 45.8% with PT-based HNC chemoradiotherapy in the recent study by Gentile et al 3 It was found that dose (per Gy increase) to temporomandibular joints (TMJs) was associated with patient-reported RIT [Hazard ratio (HR): 1.14, p = 0.02], objective trismus (HR: 1.12, p = 0.04) and magnitude of decline in 2-year maximum interincisional opening ( p = 0.01). Interpreting Gentile's results together with those presented herein by Sethi et al 1 is of particular importance for the facts that (1) RIT is a common early-onset toxicity that also affects nearly half of all patients treated with PT; (2) it is mandatory to set dosevolume constraints for the masticatory apparatus components, including the TMJs, to avoid RIT in patients treated with PT; and (3) RIT is a devastating but underestimated complication in PT studies, as evidenced by the lack of emphasis on this complication in the 18 studies involved in this meta-analysis. Therefore, it is sensible to recommend the analysis of RIT in future PT research, which could aid in the development of preventative measures against it and its debilitating effects on the quality of life of the affected patient.…”

“…Second, although the ORNJ has been presented as one of the acute PT toxicities by Sethi et al, 1 it is typically a late-onset complication of RT since it usually manifests after 6-months of RT in the absence of predisposing risk factors like previous mandibular surgery. Confirming this note, the median time to ORNJ development was 27 months (range: 2-127 months) in the study reported by Kubota and colleagues.…”

Oral Complications from Oropharyngeal Cancer Therapy

“…Overall, the incidence ranges from 59% to 100%, with severe oral mucositis ranging from 23% to 81% [ 4 , 5 ]. While proton therapy has been associated with a reduction in severe oral mucositis by minimizing integral doses, the incidence of oral mucositis still ranges from 11% to 58% [ 6 , 7 ].…”

“…The mucins found in saliva serve several important functions within the oral cavity. These functions include (1) making it less susceptible to abrasive trauma; (2) flushing the oral cavity to reduce debris and microorganisms; (3) dissolving tastants (see Taste Dysfunction section); (4) containing digestive enzymes; (5) neutralizing acids; (6) providing protection of the dentition (see Caries section); (7) containing proteins and peptides with antibacterial, antiviral, and antifungal effects; and (8) providing factors that enhance wound healing [35]. The parotid and submandibular glands contribute equally to about 90% of total daily saliva production, while the minor salivary glands supply the remaining amount.…”