Arms positioning in post-mastectomy proton radiation: Feasibility and development of a new arms down contouring atlas.

BACKGROUND AND PURPOSE: Breast cancer patients receiving radiation are traditionally positioned with both arms up, but this may not be feasible or comfortable for all patients. We evaluated the treatment planning and positioning reproducibility differences between the arms up and arms down positions for patients receiving post-mastectomy radiation therapy (PMRT) using proton pencil beam scanning (PBS). MATERIALS AND METHODS: Ten PMRT patients who were scheduled to receive PBS underwent CT-based treatment planning in both an arms down and a standard arms up position. An arms down contouring atlas was developed for consistency in treatment planning. Treatment plans were performed on both scans. A Wilcoxon test was applied to compare arms up and arms down metrics across patients. Five patients received treatment in the arms-down position at our institution while others were treated with the arms up. Residual set-up errors were recorded for each patient's treatment fractions and compared between positions. RESULTS: Target structure coverage remained consistent between the arms up and arms down positions. In regard to the OAR, the heart mean and maximum doses were statistically significantly lower in the arms up position versus the arms down position, however, the absolute differences were modest. Patients demonstrated similar setup errors, less than 0.5 mm differences, in all directions. CONCLUSIONS: PBS for PMRT in the arms down position appeared stable and reproducible compared to the traditional arms up positioning. The degree of OAR sparing in the arms down group was minimally less robust but still far superior to conventional photon therapy.

Phase II Study of Proton Beam Radiation Therapy for Patients With Breast Cancer Requiring Regional Nodal Irradiation.

PURPOSE: To evaluate the safety and efficacy of proton beam radiation therapy (RT) for patients with breast cancer who require regional nodal irradiation. METHODS: Patients with nonmetastatic breast cancer who required postoperative RT to the breast/chest wall and regional lymphatics and who were considered suboptimal candidates for conventional RT were eligible. The primary end point was the incidence of grade 3 or higher radiation pneumonitis (RP) or any grade 4 toxicity within 3 months of RT. Secondary end points were 5-year locoregional failure, overall survival, and acute and late toxicities per Common Terminology Criteria for Adverse Events (version 4.0). Strain echocardiography and cardiac biomarkers were obtained before and after RT to assess early cardiac changes. RESULTS: Seventy patients completed RT between 2011 and 2016. Median follow-up was 55 months (range, 17 to 82 months). Of 69 evaluable patients, median age was 45 years (range, 24 to 70 years). Sixty-three patients (91%) had left-sided breast cancer, two had bilateral breast cancer, and five had right-sided breast cancer. Sixty-five (94%) had stage II to III breast cancer. Sixty-eight (99%) received systemic chemotherapy. Fifty (72%) underwent immediate reconstruction. Median dose to the chest wall/breast was 49.7 Gy (relative biological effectiveness) and to the internal mammary nodes, 48.8 Gy (relative biological effectiveness), which indicates comprehensive coverage. Among 62 surviving patients, the 5-year rates for locoregional failure and overall survival were 1.5% and 91%, respectively. One patient developed grade 2 RP, and none developed grade 3 RP. No grade 4 toxicities occurred. The unplanned surgical re-intervention rate at 5 years was 33%. No significant changes in echocardiography or cardiac biomarkers after RT were found. CONCLUSION: Proton beam RT for breast cancer has low toxicity rates and similar rates of disease control compared with historical data of conventional RT. No early cardiac changes were observed, which paves the way for randomized studies to compare proton beam RT with standard RT.

Evaluation of a 3D surface imaging system for deep inspiration breath-hold patient positioning and intra-fraction monitoring.

PURPOSE: To determine the accuracy of a surface guided radiotherapy (SGRT) system for positioning of breast cancer patients in breath-hold (BH) with respect to cone-beam computed tomography (CBCT). Secondly, to evaluate the thorax position stability during BHs with SGRT, when using an air-volume guidance system. METHODS AND MATERIALS: Eighteen left-sided breast cancer patients were monitored with SGRT during CBCT and treatment, both in BH. CBCT scans were matched on the target volume and the patient surface. The setup error differences were evaluated, including with linear regression analysis. The intra-fraction variability and stability of the air-volume guided BHs were determined from SGRT measurements. The variability was determined from the maximum difference between the different BH levels within one treatment fraction. The stability was determined from the difference between the start and end position of each BH. RESULTS: SGRT data correlated well with CBCT data. The correlation was stronger for surface-to-CBCT (0.61) than target volume-to-CBCT (0.44) matches. Systematic and random setup error differences were ≤ 2 mm in all directions. The 95% limits of agreement (mean ± 2SD) were 0.1 ± 3.0, 0.6 ± 4.1 and 0.4 ± 3.4 mm in the three orthogonal directions, for the surface-to-CBCT matches. For air-volume guided BHs, the variability detected with SGRT was 2.2, 2.8 and 2.3 mm, and the stability - 1.0, 2.1 and 1.5 mm, in three orthogonal directions. Furthermore, the SGRT system could detect unexpected patient movement, undetectable by the air-volume BH system. CONCLUSION: With SGRT, left-sided breast cancer patients can be positioned and monitored continuously to maintain position errors within 5 mm. Low intra-fraction variability and good stability can be achieved with the air-volume BH system, however, additional patient position information is available with SGRT, that cannot be detected with air-volume BH systems.

Tattoo free setup for partial breast irradiation: A feasibility study.

PURPOSE: Patients undergoing external beam accelerated partial breast irradiation (APBI) receive permanent tattoos to aid with daily setup alignment and verification. With the advent of three-dimensional (3D) body surface imaging and two-dimensional (2D) x-ray imaging-based matching to surgical clips, tattoos may not be necessary to ensure setup accuracy. We compared the accuracy of conventional tattoo-based setups to a patient setup without tattoos. MATERIALS/METHODS: Twenty consecutive patients receiving APBI at our institution from July 10, 2017 to February 13, 2018 were identified. All patients received tattoos per standard of care. Ten patients underwent setup using tattoos for initial positioning followed by surface imaging and 2D matching of surgical clips. The other ten patients underwent positioning using surface imaging followed by 2D matching without reference to tattoos. Overall setup time and orthogonal x-ray-based shifts after surface imaging per fraction were recorded. Shift data were used to calculate systematic and random error. RESULTS: Among ten patients in the "no tattoo" group, the average setup time per fraction was 6.83 min vs 8.03 min in the tattoo cohort (P < 0.01). Mean 3D vector shifts for patients in the "no tattoo" group were 4.6 vs 5.9 mm in the "tattoo" cohort (P = NS). Mean systematic errors in the "no tattoo" group were: 1.2 mm (1.5 mm SD) superior/inferior, 0.5 mm (1.6 mm SD) right/left, and 2.3 mm (1.9 mm SD) anterior/posterior directions. Mean systematic errors in the "tattoo" group were: 0.8 mm (2.2 mm SD) superior/inferior, 0.3 mm (2.5 mm SD) right/left, and 1.4 mm (4.4 mm SD) anterior/posterior directions. The random errors in the "no tattoo" group ranged from 0.6 to 0.7 mm vs 1.2 to 1.7 mm in the "tattoo" group. CONCLUSIONS: Using both surface imaging and 2D matching to surgical clips provides excellent accuracy in APBI patient alignment and setup verification with reduced setup time relative to the tattoo cohort. Skin-based tattoos may no longer be warranted for patients receiving external beam APBI.

Reducing X-ray imaging for proton postmastectomy chest wall patients.

PURPOSE: Proton postmastectomy radiation therapy (PMRT) patients are positioned daily using surface imaging with additional x-ray imaging for confirmation. This study aims to investigate whether weekly x-ray imaging with daily surface imaging, as performed for photon treatment, is sufficient to maintain PMRT patient positioning fidelity. METHODS AND MATERIALS: Calculated radiographic corrections and surface imaging residual setup errors were analyzed at the treatment angle for 28 PMRT patients (with and without breast implant, left and right sided). The temporal repartition of radiographic translations >3 mm occurring after surface imaging positioning was studied as well as their impact on the final patient position, defined as the comparison between the treatment angle surface image and the planning computed tomography scan. To compare both sets of images, the traditional bony anatomy landmarks on the digitally reconstructed radiographs were replaced by 3 radiopaque markers placed over the patient's skin tattoos. The temporal variation of the distances between these skin markers was analyzed, as were the surface imaging statistics. RESULTS: Discrepancies between surface imaging and x-ray imaging were more frequent for patients without breast implants and among reconstructed patients with large implants. One-quarter of studied patients exhibited calculated radiographic translations >3 mm during the last week of treatment. In most circumstances, applying radiographic corrections did not affect patient position, which remained within 3 mm/2° robustness tolerances. One patient's implant shifted following computed tomography planning; this shift would not have been detected without x-ray imaging. CONCLUSION: Initial and weekly x-ray acquisition combined with daily surface imaging seems adequate both for routine PMRT positioning and to monitor potential changes in the treatment area. The limits of the surface imaging system, however, need to be better specified among patients without breast implants or in those with large implant reconstructions.

Can surface imaging improve the patient setup for proton postmastectomy chest wall irradiation?

PURPOSES/OBJECTIVES: For postmastectomy radiation therapy by proton beams, the usual bony landmark based radiograph setup technique is indirect because the target volumes are generally superficial and far away from major bony structures. The surface imaging setup technique of matching chest wall surface directly to treatment planning computed tomography was evaluated and compared to the traditional radiograph-based technique. METHODS AND MATERIALS: Fifteen postmastectomy radiation therapy patients were included, with the first 5 patients positioned by standard radiograph-based technique; radiopaque makers, however, were added on the patient's skin surface to improve the relevance of the setup. AlignRT was used to capture patient surface images at different time points along the process, with the calculated position corrections recorded but not applied. For the remaining 10 patients, the orthogonal x-ray imaging was replaced by the AlignRT setup procedure followed by a beamline radiograph at the treatment gantry angle only as confirmation. The position corrections recorded during all fractions for all patients (28-31 each) were analyzed to evaluate the setup accuracy. The time spent on patient setup and treatment delivery was also analyzed. RESULTS: The average position discrepancy over the treatment course relative to the planning computed tomography was significantly larger in the radiograph only group, particularly in translations (3.2 ± 2.0 mm in vertical, 3.1 ± 3.0 mm in longitudinal, 2.6 ± 2.5 mm in lateral), than AlignRT assisted group (1.3 ± 1.3 mm in vertical, 0.8 ± 1.2 mm in longitudinal, 1.5 ± 1.4 mm in lateral). The latter was well within the robustness limits (±3 mm) of the pencil beam scanning treatment established in our previous studies. The setup time decreased from an average of 11 minutes using orthogonal x-rays to an average of 6 minutes using AlignRT surface imaging. CONCLUSIONS: The use of surface imaging allows postmastectomy chest wall patients to be positioned more accurately and substantially more efficiently than radiograph only-based techniques.

A novel approach to postmastectomy radiation therapy using scanned proton beams.

PURPOSE: Postmastectomy radiation therapy (PMRT), currently offered at Massachusetts General Hospital, uses proton pencil beam scanning (PBS) with intensity modulation, achieving complete target coverage of the chest wall and all nodal regions and reduced dose to the cardiac structures. This work presents the current methodology for such treatment and the ongoing effort for its improvements. METHODS AND MATERIALS: A single PBS field is optimized to ensure appropriate target coverage and heart/lung sparing, using an in-house-developed proton planning system with the capability of multicriteria optimization. The dose to the chest wall skin is controlled as a separate objective in the optimization. Surface imaging is used for setup because it is a suitable surrogate for superficial target volumes. In order to minimize the effect of beam range uncertainties, the relative proton stopping power ratio of the material in breast implants was determined through separate measurements. Phantom measurements were also made to validate the accuracy of skin dose calculation in the treatment planning system. Additionally, the treatment planning robustness was evaluated relative to setup perturbations and patient breathing motion. RESULTS: PBS PMRT planning resulted in appropriate target coverage and organ sparing, comparable to treatments by passive scattering (PS) beams but much improved in nodal coverage and cardiac sparing compared to conventional treatments by photon/electron beams. The overall treatment time was much shorter than PS and also shorter than conventional photon/electron treatment. The accuracy of the skin dose calculation by the planning system was within ±2%. The treatment was shown to be adequately robust relative to both setup uncertainties and patient breathing motion, resulting in clinically satisfying dose distributions. CONCLUSIONS: More than 25 PMRT patients have been successfully treated at Massachusetts General Hospital by using single-PBS fields. The methodology and robustness of both the setup and the treatment have been discussed.