Initial experience and patient tolerance of proton stereotactic body radiotherapy.

Purpose: To review our initial experience with proton-based SBRT to evaluate the planning outcomes and initial patient tolerance of treatment. Patients and methods: From Sep. 2019 to Dec. 2020, 52 patients were treated with proton SBRT to 62 lesions. Fractionation varied by indication and site with a median of 5 fractions and median fractional dose of 8 Gy. Planning outcomes, including plan heterogeneity, conformity, and PTV volume receiving 100% of the prescription dose (PTV V100%) were evaluated. Acute toxicities were prospectively recorded, and patient reported outcomes were assessed prior to and at completion of treatment using the MD Anderson Symptom Inventory (MDASI) and EQ-5D5L visual analogue score (VAS). Results: All treated patients completed their course of proton-based SBRT. The mean conformity index was 1.05 (range 0.51-1.48). R50% values were comparable to ideal photon parameters. PTV V100% was 89.9% on average (40.44% - 99.76%). 5 patients (10%) required plan modification due to setup or tumor changes. No patients developed a new grade 3 or greater toxicity during treatment. Comparing pretreatment to end of treatment timepoints, there was a significant improvement in the mean VAS (65 to 75, p = 0.014), with no significant change in the mean MDASI symptom (1.7, 1.8; p = 0.79) or interference (2.3, 2.4; p = 0.452) scores. Conclusion: Proton-based SBRT can achieve dosimetric goals required by major clinical photon trials. It was well-tolerated with no decrement in patient reported outcomes and a mean 10-point improvement in VAS at the conclusion of SBRT. Further follow-up is necessary for tumor control and late effects analysis.

Immune System Dose With Proton Versus Photon Radiotherapy for Treatment of Locally Advanced NSCLC.

Purpose: Emerging data have illuminated the impact of effective radiation dose to immune cells (EDIC) on outcomes in patients with locally advanced, unresectable non-small cell lung cancer (NSCLC) treated with intensity-modulated radiotherapy (IMRT). Hypothesizing that intensity-modulated proton therapy (IMPT) may reduce EDIC versus IMRT, we conducted a dosimetric analysis of patients treated at our institution. Materials and Methods: Data were retrospectively collected for 12 patients with locally advanced, unresectable NSCLC diagnosed between 2019 and 2021 who had physician-approved IMRT and IMPT plans. Data to calculate EDIC from both Jin et al (PMID: 34944813) and Ladbury et al's (PMID: 31175902) models were abstracted. Paired t tests were utilized to compare the difference in mean EDIC between IMPT and IMRT plans. Results: IMPT decreased EDIC for 11 of 12 patients (91.7%). The mean EDIC per the Jin model was significantly lower with IMPT than IMRT (3.04 GyE vs 4.99 Gy, P < .001). Similarly, the mean EDIC per the Ladbury model was significantly lower with IMPT than IMRT (4.50 GyE vs 7.60 Gy, P < .002). Modeled 2-year overall survival was significantly longer with IMPT than IMRT (median 71% vs 63%; P = .03). Conclusion: IMPT offers a statistically significant reduction in EDIC compared to IMRT. Given the emergence of EDIC as a modifiable prognostic factor in treatment planning, our dosimetric study highlights a potential role for IMPT to address an unmet need in improving oncologic outcomes in patients with locoregionally advanced NSCLC.

Institution-level Patterns of Care for Early-stage Oropharynx Cancers in the United States.

OBJECTIVES: The adoption of transoral robotic surgery and shifting epidemiology in oropharyngeal squamous cell cancer have stimulated debate over upfront and adjuvant treatment. Institutional variation in practice patterns can be obscured in patient-level analyses. We aimed to characterize institutional patterns of care as well as identify potential associations between patterns of care and survival. METHODS: This was a retrospective cohort study of patients identified from 2004-2015 in the National Cancer Database. We analyzed 42,803 cases of oropharyngeal squamous cell cancer Stage cT1-2N0-2bM0 (AJCC 7th edition) treated with curative intent surgery and/or radiotherapy. We defined facility-4-year periods to account for changing institutional practice patterns. The 42,803 patients were treated within 2578 facility-4-year periods. We assessed institutional practice patterns, including the ratio of upfront surgery to definitive radiotherapy, case volumes, use of adjuvant therapies (radiotherapy or chemoradiotherapy), and margin positivity rates. Survival associations with institutional practice patterns were estimated with Cox regression. RESULTS: The ratio of upfront surgery to definitive radiotherapy ranged from 80-to-1 to 1-to-23. The institution-level median rate of adjuvant radiotherapy was 69% (IQR 50%-100%), adjuvant chemoradiotherapy was 44% (IQR 0%-67%), and margin-positive resection was 33% (IQR 0%-50%). On patient-level MVA, worse overall survival was not significantly associated with institutional case volume, adjuvant radiotherapy, or adjuvant chemoradiotherapy utilization. CONCLUSIONS: High rates of multimodal therapy and positive margins underscore the importance of multidisciplinary care and highlight variable patterns of care across institutions. Further work is warranted to explore indicators of high-quality care and to optimize adjuvant therapy in the HPV era.

Intensity-Modulated Reirradiation Therapy With Nivolumab in Recurrent or Second Primary Head and Neck Squamous Cell Carcinoma: A Nonrandomized Controlled Trial.

Importance: Intensity-modulated radiation therapy (IMRT) reirradiation of nonmetastatic recurrent or second primary head and neck squamous cell carcinoma (HNSCC) results in poor progression-free survival (PFS) and overall survival (OS). Objective: To investigate the tolerability, PFS, OS, and patient-reported outcomes with nivolumab (approved standard of care for patients with HNSCC) during and after IMRT reirradiation. Design, Setting, and Participants: In this multicenter nonrandomized phase 2 single-arm trial, the treatment outcomes of patients with recurrent or second primary HNSCC who satisfied recursive partitioning analysis class 1 and 2 definitions were evaluated. Between July 11, 2018, and August 12, 2021, 62 patients were consented and screened. Data were evaluated between June and December 2023. Intervention: Sixty- to 66-Gy IMRT in 30 to 33 daily fractions over 6 to 6.5 weeks with nivolumab, 240 mg, intravenously 2 weeks prior and every 2 weeks for 5 cycles during IMRT, then nivolumab, 480 mg, intravenously every 4 weeks for a total nivolumab duration of 52 weeks. Main Outcomes and Measures: The primary end point was PFS. Secondary end points included OS, incidence, and types of toxic effects, including long-term treatment-related toxic effects, patient-reported outcomes, and correlatives of tissue and blood biomarkers. Results: A total of 62 patients were screened, and 51 were evaluable (median [range] age was 62 [56-67] years; 42 [82%] were male; 6 [12%] had p16+ disease; 38 [75%] had salvage surgery; and 36 [71%.] had neck dissection). With a median follow-up of 24.5 months (95% CI, 19.0-25.0), the estimated 1-year PFS was 61.7% (95% CI, 49.2%-77.4%), rejecting the null hypothesis of 1-year PFS rate of less than 43.8% with 1-arm log-rank test P = .002 within a 1-year timeframe. The most common treatment-related grade 3 or higher adverse event (6 [12%]) was lymphopenia with 2 patients (4%) and 1 patient each (2%) exhibiting colitis, diarrhea, myositis, nausea, mucositis, and myasthenia gravis. Functional Assessment of Cancer Therapy-General and Functional Assessment of Cancer Therapy-Head and Neck Questionnaire quality of life scores remained stable and consistent across all time points. A hypothesis-generating trend favoring worsening PFS and OS in patients with an increase in blood PD1+, KI67+, and CD4+ T cells was observed. Conclusions and Relevance: This multicenter nonrandomized phase 2 trial of IMRT reirradiation therapy and nivolumab suggested a promising improvement in PFS over historical controls. The treatment was well tolerated and deserves further evaluation. Trial Registration: ClinicalTrials.gov Identifier: NCT03521570.

Assessing survival outcomes of patients with oral tongue squamous cell carcinoma: Focus on age, sex, and stage.

BACKGROUND: The purpose of this study was to provide further insights into whether age and/or sex are associated with prognosis in oral tongue squamous cell carcinoma. METHODS: This was a retrospective cohort study utilizing hospital registry data from 2006 to 2016 obtained from the National Cancer Database. Identified patients were divided into various cohorts based on age, sex, and staging. A descriptive analysis was performed using chi-square tests and overall survival rates were estimated using Kaplan-Meier method. RESULTS: A total of 17 642 patients were included in the study. The 5-year overall survival rates were 82.0% (95% CI: 79.8%-84.0%) in younger patients versus 67.5% (95% CI: 66.7%-68.3%, p-value <0.0001) older patients. The median overall survival for females was 143.4 months (95% CI: 133.2-NA) versus 129.8 (95% CI: 125.4-138.7, p-value <0.0001) in males. CONCLUSIONS: Our analysis suggests that younger age and female sex are both predictors of improved survival in oral tongue squamous cell carcinoma.

A retrospective study on the investigation of potential dosimetric benefits of online adaptive proton therapy for head and neck cancer.

PURPOSE: Proton therapy is sensitive to anatomical changes, often occurring in head-and-neck (HN) cancer patients. Although multiple studies have proposed online adaptive proton therapy (APT), there is still a concern in the radiotherapy community about the necessity of online APT. We have performed a retrospective study to investigate the potential dosimetric benefits of online APT for HN patients relative to the current offline APT. METHODS: Our retrospective study has a patient cohort of 10 cases. To mimic online APT, we re-evaluated the dose of the in-use treatment plan on patients' actual treatment anatomy captured by cone-beam CT (CBCT) for each fraction and performed a templated-based automatic replanning if needed, assuming that these were performed online before treatment delivery. Cumulative dose of the simulated online APT course was calculated and compared with that of the actual offline APT course and the designed plan dose of the initial treatment plan (referred to as nominal plan). The ProKnow scoring system was employed and adapted for our study to quantify the actual quality of both courses against our planning goals. RESULTS: The average score of the nominal plans over the 10 cases is 41.0, while those of the actual offline APT course and our simulated online course is 25.8 and 37.5, respectively. Compared to the offline APT course, our online course improved dose quality for all cases, with the score improvement ranging from 0.4 to 26.9 and an average improvement of 11.7. CONCLUSION: The results of our retrospective study have demonstrated that online APT can better address anatomical changes for HN cancer patients than the current offline replanning practice. The advanced artificial intelligence based automatic replanning technology presents a promising avenue for extending potential benefits of online APT.