A Prospective Study of Mucosal Sparing Proton Beam Therapy in Resected Oropharyngeal Cancer Patients

Purpose/Objective(s) Oropharyngeal cancer (OPC) patients (pts) undergoing postoperative radiation therapy (RT) are routinely treated to the postoperative primary site and neck(s) after transoral surgery (TOS). Elimination of the postoperative primary site from the radiation target in select cases may not increase the risk of local recurrence and improve tolerability of RT. We report the results of a prospective study utilizing mucosal sparing proton beam therapy (PBT). Materials/Methods From 3/2016-5/2019, 64 pts were enrolled at our multi-site institution on an IRB approved prospective trial with a primary 2 year (yr) local control (LC) endpoint. AJCC 7th edition stage III/IVA pT1-2 N1-3M0 p16+ OPC pts underwent TOS (negative margins) with neck dissection with indications for adjuvant RT due to pathologic N2 or extranodal extension. PBT was delivered to at risk nodal regions, excluding the primary mucosal site. Secondary to insurance denial for PBT, IMRT was allowed. CTCAE v5.0, EORTC HN-QLQ 35 survey (QOL), and modified barium swallowing impairment profiles (MBSImP) were obtained at baseline prior to RT, then 3 months (mo) and 12 mo post RT. Kaplan-Meier estimates were calculated for time-to-event clinical outcomes and repeated measures mixed models were utilized for explore changes in QOL over time. Results There were 61 evaluable pts with a median follow up of 38 mo (range, 10 – 64 mo.). The majority were males (93.4%) and received adjuvant PBT (72.2%). Two yr LC is 98.4% with one local recurrence reported at 9 mo after RT. Two yr locoregional control (LRC) is 96.7%. Two yr overall survival (OS), progression free survival (PFS), and distant metastasis free survival (DMFS) are 100%, 94.9%, and 98.1%, respectively. Six pts reported treatment related grade 3 adverse events (AEs) during treatment (5, dermatitis and 1, nausea) with no grade ≥ 3 reported at 3 mo post PBT and beyond. Two IMRT pts required PEG tube placement during treatment secondary to significant nausea due to dysgeusia. Pts noted significant QOL improvement over time in the pain, swallowing, senses, speech, contact, mouth opening domains (all p < 0.05). MBSImP overall severity score as well as oral and pharyngeal impairment scores showed stability with no significant change over time. Dosimetric analysis of incidental PBT dose to the hypothetical CTV of the primary mucosal site revealed a mean D95 of 963 cGy (SD±930). Conclusion Mucosal sparing PBT is tolerated well in select resected HPV related OPC with a low risk of recurrence at the mucosal primary site and reduced toxicity burden. Oropharyngeal cancer (OPC) patients (pts) undergoing postoperative radiation therapy (RT) are routinely treated to the postoperative primary site and neck(s) after transoral surgery (TOS). Elimination of the postoperative primary site from the radiation target in select cases may not increase the risk of local recurrence and improve tolerability of RT. We report the results of a prospective study utilizing mucosal sparing proton beam therapy (PBT). From 3/2016-5/2019, 64 pts were enrolled at our multi-site institution on an IRB approved prospective trial with a primary 2 year (yr) local control (LC) endpoint. AJCC 7th edition stage III/IVA pT1-2 N1-3M0 p16+ OPC pts underwent TOS (negative margins) with neck dissection with indications for adjuvant RT due to pathologic N2 or extranodal extension. PBT was delivered to at risk nodal regions, excluding the primary mucosal site. Secondary to insurance denial for PBT, IMRT was allowed. CTCAE v5.0, EORTC HN-QLQ 35 survey (QOL), and modified barium swallowing impairment profiles (MBSImP) were obtained at baseline prior to RT, then 3 months (mo) and 12 mo post RT. Kaplan-Meier estimates were calculated for time-to-event clinical outcomes and repeated measures mixed models were utilized for explore changes in QOL over time. There were 61 evaluable pts with a median follow up of 38 mo (range, 10 – 64 mo.). The majority were males (93.4%) and received adjuvant PBT (72.2%). Two yr LC is 98.4% with one local recurrence reported at 9 mo after RT. Two yr locoregional control (LRC) is 96.7%. Two yr overall survival (OS), progression free survival (PFS), and distant metastasis free survival (DMFS) are 100%, 94.9%, and 98.1%, respectively. Six pts reported treatment related grade 3 adverse events (AEs) during treatment (5, dermatitis and 1, nausea) with no grade ≥ 3 reported at 3 mo post PBT and beyond. Two IMRT pts required PEG tube placement during treatment secondary to significant nausea due to dysgeusia. Pts noted significant QOL improvement over time in the pain, swallowing, senses, speech, contact, mouth opening domains (all p < 0.05). MBSImP overall severity score as well as oral and pharyngeal impairment scores showed stability with no significant change over time. Dosimetric analysis of incidental PBT dose to the hypothetical CTV of the primary mucosal site revealed a mean D95 of 963 cGy (SD±930). Mucosal sparing PBT is tolerated well in select resected HPV related OPC with a low risk of recurrence at the mucosal primary site and reduced toxicity burden.