Acute and long-term toxicity of whole pelvis proton radiation therapy for definitive or adjuvant management of gynecologic cancers.

OBJECTIVE: To characterize long-term toxicity and disease outcomes with whole pelvis (WP) pencil beam scanning proton radiation therapy (PBS PRT) for gynecologic malignancies. METHODS: We reviewed 23 patients treated from 2013 to 2019 with WP PBS PRT for endometrial, cervical, and vaginal cancer. We report acute and late Grade (G)2+ toxicities, graded by Common Terminology Criteria for Adverse Events, Version 5. Disease outcomes were assessed by Kaplan-Meier method. RESULTS: Median age was 59 years. Median follow up was 4.8 years. 12 (52.2%) had uterine cancer, 10 (43.5%) cervical, 1 (4.3%) vaginal. 20 (86.9%) were treated post-hysterectomy. 22 (95.7%) received chemotherapy, 12 concurrently (52.2%). The median PBS PRT dose was 50.4GyRBE (range, 45-62.5). 8 (34.8% had para-aortic/extended fields. 10 (43.5%) received brachytherapy boost. Median follow up was 4.8 years. 5-year actuarial local control was 95.2%, regional control 90.9%, distant control 74.7%, both disease control and progression-free survival 71.2%. Overall survival was 91.3%. In the acute period, 2 patients (8.7%) had G2 genitourinary (GU) toxicity, 6 (26.1%) had gastrointestinal (GI) G2-3 toxicity, 17 (73.9%) had G2-4 hematologic (H) toxicity. In the late period, 3 (13.0%) had G2 GU toxicity, 1 (4.3%) had G2 GI toxicity, 2 (8.7%) had G2-3H toxicity. The mean small bowel V15Gy was 213.4 cc. Mean large bowel V15 Gy was 131.9 cc. CONCLUSIONS: WP PBS PRT for gynecologic malignancies delivers favorable locoregional control. Rates of GU and GI toxicity are low. Acute hematologic toxicity was most common, which may be related to the large proportion of patients receiving chemotherapy.

Five-Year Outcomes of a Phase 1/2 Trial of Accelerated Partial Breast Irradiation Using Proton Therapy for Women With Stage 0-IIA Breast Cancer.

Purpose: We report the results of a phase 1/2 trial of external beam partial breast radiation using proton therapy. Methods and Materials: Eligible patients included stage 0-IIA breast cancer pTis-T2, N0, and size ≤3 cm. Proton beam radiation was used to deliver 3.85 Gy twice daily to 38.5 Gy. The phase 1 portion determined feasibility based on criteria of successful plan creation, treatment delivery, and acute toxicity grade ≥3 in ≤20% of patients. The phase 2 portion had efficacy goals of acute toxicity grade ≥3 in ≤20% of patients and observing physician-rated cosmesis of excellent or good >85% of patients at 2 years. Results: From April 2013 to March 2015, there were 12 patients enrolled onto the phase 1 portion, and the preplanned analysis of feasibility was met in all 4 required criteria. From July 2015 through December 2019 there were 28 patients with 29 treated breasts (1 bilateral) enrolled onto the phase 2 portion of the trial out of 45 originally planned. The trial was closed to accrual because of the coronavirus pandemic and not reopened. Thirty-eight breasts were treated with double-scattering and 3 pencil-beam scanning protons. The median follow-up of the 40 patients is 5.4 years (range, 2.3-8.6 years). There was 1 local recurrence. There was no grade ≥3 acute or late toxicity. At baseline all patients had physician-rated cosmesis good or excellent but at 2 years was excellent in 56%, good in 19%, and fair in 25%. Conclusions: Proton-accelerated partial breast irradiation delivered with a twice-daily fractionation was feasible and associated with very low acute and long-term toxicity. However, the trial did not meet goals for cosmesis outcomes and was closed prematurely. Future study is needed to determine whether pencil-beam scanning protons or different fractionation could improve these outcomes.

Validation and application of a fast Monte Carlo algorithm for assessing the clinical impact of approximations in analytical dose calculations for pencil beam scanning proton therapy.

PURPOSE: Monte Carlo (MC) dose calculation is generally superior to analytical dose calculation (ADC) used in commercial TPS to model the dose distribution especially for heterogeneous sites, such as lung and head/neck patients. The purpose of this study was to provide a validated, fast, and open-source MC code, MCsquare, to assess the impact of approximations in ADC on clinical pencil beam scanning (PBS) plans covering various sites. METHODS: First, MCsquare was validated using tissue-mimicking IROC lung phantom measurements as well as benchmarked with the general purpose Monte Carlo TOPAS for patient dose calculation. Then a comparative analysis between MCsquare and ADC was performed for a total of 50 patients with 10 patients per site (including liver, pelvis, brain, head-and-neck, and lung). Differences among TOPAS, MCsquare, and ADC were evaluated using four dosimetric indices based on the dose-volume histogram (target Dmean, D95, homogeneity index, V95), a 3D gamma index analysis (using 3%/3 mm criteria), and estimations of tumor control probability (TCP). RESULTS: Comparison between MCsquare and TOPAS showed less than 1.8% difference for all of the dosimetric indices/TCP values and resulted in a 3D gamma index passing rate for voxels within the target in excess of 99%. When comparing ADC and MCsquare, the variances of all the indices were found to increase as the degree of tissue heterogeneity increased. In the case of lung, the D95s for ADC were found to differ by as much as 6.5% from the corresponding MCsquare statistic. The median gamma index passing rate for voxels within the target volume decreased from 99.3% for liver to 75.8% for lung. Resulting TCP differences can be large for lung (≤10.5%) and head-and-neck (≤6.2%), while smaller for brain, pelvis and liver (≤1.5%). CONCLUSIONS: Given the differences found in the analysis, accurate dose calculation algorithms such as Monte Carlo simulations are needed for proton therapy, especially for disease sites with high heterogeneity, such as head-and-neck and lung. The establishment of MCsquare can facilitate patient plan reviews at any institution and can potentially provide unbiased comparison in clinical trials given its accuracy, speed and open-source availability.

A Javascript library that uses Windows Script Host (WSH) to analyze prostate motion data fragmented across a multitude of Excel files by the Calypso 4D Localization System.

The Calypso 4D Localization System records prostate motion continuously during radiation treatment. It stores the data across thousands of Excel files. We developed Javascript (JScript) libraries for Windows Script Host (WSH) that use ActiveX Data Objects, OLE Automation and SQL to statistically analyze the data and display the results as a comprehensible Excel table. We then leveraged these libraries in other research to perform vector math on data spread across multiple access databases.