Oropharyngeal squamous cell carcinoma (OPC) is one of themost common head and neck cancers. Despite its rising incidence and prevalence,an increasing proportion of OPC is associated with human papillomavirus (HPV),with a favorable prognosis. Currently, the standard nonsurgical management ofnonmetastatic OPC is definitive radiotherapy with or without chemotherapy.Long-term sequelae and quality of life (QOL) are important considerations inthe treatment of OPC since patients with OPC are generally young at diagnosiswith a potential for long-term survival. Despite the advanced dose conformityprovided by the current standard intensity-modulated radiation therapy (IMRT),long-term sequelae may persist or progress over time and adversely impact QOLin survivors.
Proton beams have fundamental physical advantages overphoton beams, providing a moderate entrance dose, uniform high dose within thetumor, and minimal exit dose with steep distal dose gradients. These uniquedose distributions allow the proton beams to deliver prescription doses to thetumor while sparing nearby normal tissues, whereas the conventional photonbeams still deliver a moderate amount of radiation to normal tissues alongtheir path. The use of intensity modulated proton therapy (IMPT) in thetreatment of OPC has been reported in several studies that showed increasednormal-tissue sparing and reduced symptom burden compared with IMRT.
In this study, authors Irini Youssef et al examined a cohortof patients with nonmetastatic OPC who were treated with curative-intent IMPTor IMRT to compare the toxicity profiles and survival outcomes.
This retrospective cohort study included patients aged 18years or older with newly diagnosed nonmetastatic OPC who receivedcurative-intent radiotherapy with IMPT or IMRT at a single-institution tertiaryacademic cancer center from January 1, 2018, to December 31, 2021, withfollow-up through December 31, 2021. The main outcomes were the incidence ofacute and chronic (present after 6 months) treatment-related adverse events(AEs) and oncologic outcomes, including locoregional recurrence (LRR), progression-freesurvival (PFS), and overall survival (OS).
The study included 292 patients with OPC (272 [93%] withhuman papillomavirus [HPV]- p16–positive tumors). Fifty-eight patients (20%)were treated with IMPT, and 234 (80%) were treated with IMRT. Median follow-upwas 26 months (IQR, 17-36 months).
Most patients [97%] received a dose to the primary tumor of70 Gy. Fifty-seven of the patients treated with IMPT (98%) and 215 of thosetreated with IMRT (92%) had HPV-p16–positive disease. There were no significantdifferences in 3-year OS (97% IMPT vs 91% IMRT; P = .18), PFS (82% IMPT vs 85%IMRT; P = .62), or LRR (5% IMPT vs 4% IMRT; P = .59).
The incidence of acute toxic effects was significantlyhigher for IMRT compared with IMPT for oral pain of grade 2 or greater (72%IMPT vs 93% IMRT; P < .001), xerostomia of grade 2 or greater (21% IMPT vs29% IMRT; P < .001), dysgeusia of grade 2 or greater (28% IMPT vs 57% IMRT;P < .001), grade 3 dysphagia (7%] IMPT vs 29 [12%] IMRT; P < .001), mucositisof grade 3 or greater (53% IMPT vs 70% IMRT; P = .003), nausea of grade 2 orgreater (0 IMPT vs 8% IMRT; P = .04), and weight loss of grade 2 or greater (37%IMPT vs 59% IMRT; P < .001).
There were no significant differences in chronic toxiceffects of grade 3 or greater, although there was a significant difference forchronic xerostomia of grade 2 or greater (6 IMPT [11%] vs 22 IMRT [10%]; P <.001). Four patients receiving IMRT (2%) vs 0 receiving IMPT had a percutaneousendoscopic gastrostomy tube for longer than 6 months.
The key findings of this study showed that IMPT treatmentwas significantly associated with reduced treatment-related toxic effects,particularly acute toxic effects. As grade 3 or higher toxic effects usuallymean severe symptoms requiring extensive medical intervention withhospitalization and limiting self-care activities of daily living, thereduction of toxic effects and improvement of QOL associated with IMPTtreatment could potentially lead to significant savings on health careresources. It is important to note that most patients in the current cohortreceived deescalated elective neck doses (30 GyE), suggesting that improvementsin acute toxic effects associated with IMPT persisted despite a deescalatedstrategy with an overall lower expected toxicity burden.
In this cohort study, primary IMPT for nonmetastatic OPC wassignificantly associated with a reduced acute toxicity burden compared withIMRT, with few severe chronic adverse effects and favorable oncologic outcomes.In particular, PEG tube placement was significantly reduced in patientsreceiving IMPT during the acute phase and absent during the chronic phase. Thefindings suggest that IMPT is well tolerated in the setting of nonmetastatic,de novo OPC. Prospective randomized clinical trials along with patient-reportedoutcomes are warranted to optimize patient selection for IMPT in nonmetastaticOPC, especially given that many of these patients have a potential for longtermsurvival.
Source: Irini Youssef, MD; Jennifer Yoon, MD; Nader Mohamed;JAMA Network Open. 2022;5(11):e2241538. doi:10.1001/jamanetworkopen.2022.41538