Importance: Patients with oropharyngeal carcinoma (OPC) treated with radiotherapy often experience substantial toxic effects, even with modern techniques such as intensity-modulated radiation therapy (IMRT). Intensity-modulated proton therapy (IMPT) has a potential advantage over IMRT due to reduced dose to the surrounding organs at risk; however, data are scarce given the limited availability and use of IMPT.Objective: To compare toxic effects and oncologic outcomes among patients with newly diagnosed nonmetastatic OPC treated with IMPT vs IMRT with or without chemotherapy.Design, Setting, and Participants: This retrospective cohort study included patients aged 18 years or older with newly diagnosed nonmetastatic OPC who received curative-intent radiotherapy with IMPT or IMRT at a single-institution tertiary academic cancer center from January 1, 2018, to December 31, 2021, with follow-up through December 31, 2021.Exposures: IMPT or IMRT with or without chemotherapy.Main Outcomes and Measures: The main outcomes were the incidence of acute and chronic (present after ≥6 months) treatment-related adverse events (AEs) and oncologic outcomes, including locoregional recurrence (LRR), progression-free survival (PFS), and overall survival (OS). Fisher exact tests and χ² tests were used to evaluate associations between toxic effects and treatment modality (IMPT vs IMRT), and the Kaplan-Meier method was used to compare LRR, PFS, and OS between the 2 groups.Results: The study included 292 patients with OPC (272 [93%] with human papillomavirus [HPV]-p16–positive tumors); 254 (87%) were men, 38 (13%) were women, and the median age was 64 years (IQR, 58-71 years). Fifty-eight patients (20%) were treated with IMPT, and 234 (80%) were treated with IMRT. Median follow-up was 26 months (IQR, 17-36 months). Most patients (283 [97%]) received a dose to the primary tumor of 70 Gy. Fifty-seven of the patients treated with IMPT (98%) and 215 of those treated with IMRT (92%) had HPV-p16–positive disease. There were no significant differences 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 significantly higher for IMRT compared with IMPT for oral pain of grade 2 or greater (42 [72%] IMPT vs 217 [93%] IMRT; P < .001), xerostomia of grade 2 or greater (12 [21%] IMPT vs 68 [29%] IMRT; P < .001), dysgeusia of grade 2 or greater (16 [28%] IMPT vs 134 [57%] IMRT; P < .001), grade 3 dysphagia (4 [7%] IMPT vs 29 [12%] IMRT; P < .001), mucositis of grade 3 or greater (10 [53%] IMPT vs 13 [70%] IMRT; P = .003), nausea of grade 2 or greater (0 [0%] IMPT vs 18 [8%] IMRT; P = .04), and weight loss of grade 2 or greater (22 [37%] IMPT vs 138 [59%] IMRT; P < .001). There were no significant differences in chronic toxic effects except for xerostomia. Four patients receiving IMRT (2%) vs 0 receiving IMPT had a percutaneous endoscopic gastrostomy tube for longer than 6 months.Conclusions and Relevance: In this study, curative-intent radiotherapy with IMPT for nonmetastatic OPC was associated with a significantly reduced acute toxicity burden compared with IMRT, with few chronic toxic effects and favorable oncologic outcomes, including locoregional recurrence of only 5% at 2 years. Prospective randomized clinical trials comparing these 2 technologies and of patient-reported outcomes are warranted.

Background: The use of stereotactic body radiation therapy (SBRT) is widely utilized for treatment of localized prostate cancer. Magnetic-resonance-guided radiotherapy (MRgRT) was introduced in 2014 and has recently been implemented in SBRT for prostate cancer as it provides an opportunity for smaller margins and adaptive daily planning. Currently, the only publications of MRgRT for prostate SBRT describe European clinical experiences which utilized adaptive planning. However, adaptive planning adds significantly to the time required for daily treatment. Objectives: Since prostate SBRT has demonstrated acceptable toxicity for several years, we did not consider daily adaptation critical to the process of prostate SBRT. After Institutional Review Board approval, we analyzed and now report our experience using MRgRT without adaptation. Methods: Between 25 September 2019 and 21 December 2020, 35 consecutive patients were treated with MRgRT prostate SBRT at our center. Patients treated with MRgRT included favorable intermediate risk (43%) and unfavorable intermediate risk (54%), and only one patient had low-risk prostate cancer. Nine patients (25%) received adjuvant leuprolide for a median of 4.5 months (range 4–6 m). Our clinical pathway allows for a maximum prostate gland volume of 60 cc; median prostate volume of this cohort was 35.0 cc (range 17–58.4 cc). Median pre-treatment PSA was 6.30 (range 2.55–16.77). Each patient was treated with 36.25 Gy delivered in five fractions over 2 weeks with urethral sparing to a maximal dose of 35 Gy. Target volumes included the prostate gland and proximal seminal vesicles with a 3 mm margin. Results: Median follow-up as of 26 May 2021 was 11.97 months (range 4.37–19.80). First follow-up data are available for all patients, with a median of 1.10 month from completion of treatment (0.63–3.40). The median PSA at first visit was 2.75 (range 0.02–9.00) with a median AUA symptom score of 9 (range 1–24). Second follow-up data are available for 34 patients at a median of 4.45 months (range 2.57–8.90). At second follow-up, the median PSA was 1.60 (range 0.02–5.40) with a median AUA symptom score of 6 (range 1–33). Seventeen patients had third follow-up data with a median of 9.77 months (range 4.70–12.33) after SBRT. The median PSA was 1.13 (range 0.02–4.73) with an AUA score of 9 (2–22) at the third follow-up. We observed a statistically significant decrease in PSA between pre-treatment and at first follow-up (p < 0.005). The most common toxicity was grade 2 urethritis, managed in all cases by tamsulosin. One patient developed grade 2 tenesmus relieved by topical steroids. No cases of grade ≥ 3 toxicity were seen in our patient population. Conclusions: By avoiding the extra time required for plan adaptation, MRgRT without daily adaptation allows for successful prostate SBRT with manageable toxicity. We continue to reserve our limited adaptive treatment slots for preoperative pancreatic and ultra-central lung SBRT patients, which require time-intensive respiratory gating and adaptive planning.

Background: Standard of care treatment for anal squamous cell carcinoma (SCC) is concurrent chemoradiation (CRT). However, the necessity of CRT over radiation alone for T1-2N0 disease is less certain. Methods: The National Cancer Database (NCDB) was queried to identify patients who received CRT, defined as initiation of chemo and RT within 14 days of each other, or RT alone (without any chemo during initial treatment phase) for cT1-2N0M0 SCC of the anus. The cohort was limited to patients less than 70 years old with Charlson-Deyo Comorbidity Index of 0, receiving a radiation dose range of 4,500–5,940 cGy. Univariable and multivariable logistic regression were performed to assess for predictors of CRT usage. Five-year overall survival (OS) was analyzed using the Kaplan-Meier method with the log rank test both for the full cohort and then on the subsets of T1 and T2 patients. Results: We identified 4,564 patients, of whom 4,371 (95.8%) received CRT and 193 (4.2%) received RT alone. Median follow up was 49.8 months. About 33.5% of patients had cT1N0 disease, while 66.5% of patients had cT2N0 disease. On multivariable logistic regression, patients were more likely to receive CRT if they had T2 disease [OR 2.318 (1.732–3.102), P<0.0001]. Five-year OS was 86.6% for CRT and 79.1% for RT (P=0.001). For T1 patients, 5-year OS was 90.3% with CRT and 84.7% with RT (P=0.114). For T2 patients, 5-year OS was 84.7% with CRT and 72.8% with RT (P<0.0001). Multivariable Cox regression analysis confirmed association between OS and CRT use [HR 0.588 (95% CI: 0.430–0.804), P=0.001]. Conclusions: The vast majority of patients under age 70 without significant comorbidities are treated with CRT over radiation alone for early stage anal SCC, with better survival associated with CRT.

A 79-year-old HIV-negative Caucasian man with a medical history of smoking 20 pack-years (quit 40 years prior), early-stage non-small cell lung cancer status post-lobectomy 13 years earlier at an outside hospital without evidence of recurrence, and benign prostatic hypertrophy was diagnosed with synchronous very high-risk prostate adenocarcinoma and early-stage anal basaloid squamous cell carcinoma. He proceeded to undergo concurrent treatment for these tumors, consisting of androgen deprivation therapy, external beam radiation therapy, and a brachytherapy boost for the prostate adenocarcinoma; for the anal carcinoma, he was treated with definitive chemoradiation. Over 3.5 years since the completion of radiotherapy, he remains in clinical and biochemical remission.