A Prospective Study of Mucosal Sparing Radiation Therapy in Resected Oropharyngeal Cancer Patients.

PURPOSE: Our objective was to report the prospective results of mucosal sparing radiation therapy in human papillomavirus-related oropharyngeal squamous cell carcinoma. METHODS AND MATERIALS: From March 2016 through May 2019, patients were enrolled in this institutional review board-approved prospective cohort study at a multisite institution. Inclusion criteria included p16+ American Joint Committee on Cancer seventh edition pathologic T1 or T2, N1 to N3, and M0 oropharyngeal cancers. Proton therapy (PT) was delivered to at-risk nodal regions, excluding the primary mucosal site. Secondary to insurance denial for PT, intensity modulated radiation therapy (IMRT) was allowed. European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck Module and Patient-Reported Outcomes Measurement Information System surveys (quality of life [QOL]) and modified barium swallowing impairment profiles (MBSImP) were obtained at baseline before radiation therapy, then 3 and 12 months after radiation therapy. Kaplan-Meier estimates were calculated for time-to-event clinical outcomes, and repeated measures mixed models were used to explore changes in QOL over time. A comparison of QOL and swallowing outcomes with standard-of-care treatment was analyzed. RESULTS: There were 61 evaluable patients with a median follow-up of 38 months (range, 10-64); 44 (72%) were treated with PT and 17 (28%) were treated with IMRT. The 2-year local control, locoregional control, distant metastasis-free survival, and overall survival were 98%, 97%, 98%, and 100%, respectively. There were 6 grade ≥3 events related to treatment. Two IMRT patients required percutaneous endoscopic gastrostomy tube placement during treatment secondary to significant nausea due to dysgeusia. Patients noted significant QOL improvement over time in the pain, swallowing, speech, social eating, social contact, mouth opening, and use of pain medication domains (all P < .02). The MBSImP overall severity score as well as oral and pharyngeal impairment scores showed stability with no significant change over time. For the 44 patients treated with PT, the mean D95 to the primary target was 10.7 Gy (standard deviation = 12.5 Gy). CONCLUSIONS: Mucosal sparing radiation is well tolerated in select resected human papillomavirus-related oropharyngeal squamous cell carcinoma with a low risk of recurrence at the mucosal primary site, a low rate of percutaneous endoscopic gastrostomy tube placement, and few radiation-related grade ≥3 adverse events.

The Number of Radiographically Positive Lymph Nodes Further Stratifies Patient Survival Among Clinical N1 Patients With Human Papillomavirus-Associated Oropharyngeal Cancer.

Purpose: Human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPV[+]OPSCC) requires further study to optimize the existing clinical staging system and guide treatment selection. We hypothesize that incorporation of the number of radiographically positive lymph nodes will further stratify patients with clinical N1 (cN1) HPV(+)OPSCC. Methods and Materials: A post hoc analysis from 2 prospective clinical trials at a high-volume referral center was conducted. Patients underwent primary tumor resection and lymphadenectomy, followed by either standard-of-care radiation therapy (60 Gy in 30 fractions) with or without cisplatin (40 mg/m2 weekly) or de-escalated radiation therapy (30 Gy in 20 twice-daily fractions) with concomitant 15 mg/m2 docetaxel once weekly. Imaging studies were independently reviewed by a blinded neuroradiologist classifying radiographic extranodal extension (rENE) and the number and maximal size of involved lymph nodes. Patients without pathologic data available for assessment were excluded. Results: A total of 260 patients were included. Of these, 216 (83%) were cN1. Patients had a median of 2 radiographically positive lymph nodes (range, 0-12), and 107 (41%) had rENE. For cN1 patients, stratifying by radiographically positive lymph nodes (1-2 vs 3-4 vs >4) was predictive of progression-free survival (PFS) (P = .017), with 2-year PFS rates of 96%, 88%, and 81%, respectively. More than 2 radiographically positive lymph nodes was identified as a significant threshold for PFS (P = .0055) and overall survival (P = .029). Radiographic ENE and lymph node size were not predictive of PFS among cN1 patients. Conclusions: The number of radiographically positive lymph nodes is predictive of PFS and overall survival and could be used to meaningfully subcategorize cN1 patients with HPV(+)OPSCC. We recommend further validation of our proposal that cN1 patients with 1 to 2 radiologically positive lymph nodes be categorized as cN1a, patients with 3 to 4 radiologically positive lymph nodes categorized as cN1b, and patients with >4 radiographically positive lymph nodes categorized as cN1c.

How to design, fabricate, and validate a customized COMS-style eye plaque: Illustrated with a narrow-slotted plaque example.

PURPOSE: A customized Collaborative Ocular Melanoma Study (COMS)-style eye plaque may provide superior dosimetric coverage compared with standard models for certain intraocular tumor locations and shapes. This work provides a recipe for developing and validating such customized plaques. METHODS AND MATERIALS: The concept-into-clinical treatment process for a customized COMS-style eye plaque begins with a CAD model design that meets the specifications of the radiation oncologist and surgeon based on magnetic resonance, ultrasound, and clinical measurements, as well as a TG-43 hybrid heterogeneity-corrected dose prediction to model the dose distribution. Next, a 3D printed plastic prototype is created and reviewed. After design approval, a Modulay plaque is commercially fabricated. Quality assurance (QA) is subsequently performed to verify the physical measurements of the Modulay and Silastic and also includes dosimetric measurement of the calibration, depth dose, and dose profiles. Sterilization instructions are provided by the commercial fabricator. This customization procedure and QA methodology is demonstrated with a narrow-slotted plaque that was recently constructed for the treatment of a circumpapillary (e.g., surrounding the optic disk) ocular tumor. RESULTS: The production of a customized COMS-style eye plaque is a multistep process. Dosimetric modeling is recommended to ensure that the design will meet the patient's needs, and QA is essential to confirm that the plaque has the proper dimensions and dose distribution. The customized narrow-slotted plaque presented herein was successfully implemented in the clinic, and provided superior dose coverage of juxtapapillary and circumpapillary tumors compared with standard or notched COMS-style plaques. Plaque development required approximately 30 h of physicist time and a fabrication cost of $1500. CONCLUSION: Customized eye plaques may be used to treat intraocular tumors that cannot be adequately managed with standard models. The procedure by which a customized COMS-style plaque may be designed, fabricated, and validated was presented along with a clinical example.