Synchronized high-speed scintillation imaging of proton beams, generated by a gantry-mounted synchrocyclotron, on a pulse-by-pulse basis.

BACKGROUND: With the emergence of more complex and novel proton delivery techniques, there is a need for quality assurance tools with high spatiotemporal resolution to conveniently measure the spatial and temporal properties of the beam. In this context, scintillation-based dosimeters, if synchronized with the radiation beam and corrected for ionization quenching, are appealing. PURPOSE: To develop a synchronized high-speed scintillation imaging system for characterization and verification of the proton therapy beams on a pulse-by-pulse basis. MATERIALS AND METHODS: A 30 cm × 30 cm × 5 cm block of BC-408 plastic scintillator placed in a light-tight housing was irradiated by proton beams generated by a Mevion S250 proton therapy synchrocyclotron. A high-speed camera system, placed perpendicular to the beam direction and facing the scintillator, was synchronized to the accelerator's pulses to capture images. Opening and closing of the camera's shutter was controlled by setting a proper time delay and exposure time, respectively. The scintillation signal was recorded as a set of two-dimensional (2D) images. Empirical correction factors were applied to the images to correct for the nonuniformity of the pixel sensitivity and quenching of the scintillator. Proton range and modulation were obtained from the corrected images. RESULTS: The camera system was able to capture all data on a pulse-by-pulse basis at a rate of ∼504 frames per second. The applied empirical correction method for ionization quenching was effective and the corrected composite image provided a 2D map of dose distribution. The measured range (depth of distal 90%) through scintillation imaging agreed within 1.2 mm with that obtained from ionization chamber measurement. CONCLUSION: A high-speed camera system capable of capturing scintillation signals from individual proton pulses was developed. The scintillation imaging system is promising for rapid proton beam characterization and verification.

Spatially fractionated stereotactic body radiation therapy (Lattice) for large tumors.

PURPOSE: Stereotactic body radiation therapy (SBRT) has demonstrated clinical benefits for patients with metastatic and/or unresectable cancer. Technical considerations of treatment delivery and nearby organs at risk can limit the use of SBRT in large tumors or those in unfavorable locations. Spatially fractionated radiation therapy (SFRT) may address this limitation because this technique can deliver high-dose radiation to discrete subvolume vertices inside a tumor target while restricting the remainder of the target to a safer lower dose. Indeed, SFRT, such as GRID, has been used to treat large tumors with reported dramatic tumor response and minimal side effects. Lattice is a modern approach to SFRT delivered with arc-based therapy, which may allow for safe, high-quality SBRT for large and/or deep tumors. METHODS AND MATERIALS: Herein, we report the results of a dosimetry and quality assurance feasibility study of Lattice SBRT in 11 patients with 12 tumor targets, each ≥10 cm in an axial dimension. Prior computed tomography simulation scans were used to generate volumetric modulated arc therapy Lattice SBRT plans that were then delivered on clinically available Linacs. Quality assurance testing included external portal imaging device and ion chamber analyses. RESULTS: All generated plans met the standard SBRT dose constraints, such as those from the American Association of Physicists in Medicine Task Group 101. Additionally, we provide a step-by-step approach to generate and deliver Lattice SBRT plans using commercially available treatment technology. CONCLUSIONS: Lattice SBRT is currently being tested in a prospective trial for patients with metastatic cancer who need palliation of large tumors (NCT04553471, NCT04133415).

Does the sequence of high-dose rate brachytherapy boost and IMRT for prostate cancer impact early toxicity outcomes? Results from a single institution analysis.

BACKGROUND: We present the first report comparing early toxicity outcomes with high-dose rate brachytherapy (HDR-BT) boost upfront versus intensity modulated RT (IMRT) upfront combined with androgen deprivation therapy (ADT) as definitive management for intermediate risk or higher prostate cancer. METHODS AND MATERIALS: We reviewed all non-metastatic prostate cancer patients who received HDR-BT boost from 2014 to 2019. HDR-BT boost was offered to patients with intermediate-risk disease or higher. ADT use and IMRT target volume was based on NCCN risk group. IMRT dose was typically 45 Gy in 25 fractions to the prostate and seminal vesicles ± pelvic lymph nodes. HDR-BT dose was 15 Gy in 1 fraction, delivered approximately 3 weeks before or after IMRT. The sequence was based on physician preference. Biochemical recurrence was defined per ASTRO definition. Gastrointestinal (GI) and Genitourinary (GU) toxicity was graded per CTCAE v5.0. Pearson Chi-squared test and Wilcoxon tests were used to compare toxicity rates. P-value < 0.05 was significant. RESULTS: Fifty-eight received HDR-BT upfront (majority 2014-2016) and 57 IMRT upfront (majority 2017-2018). Median follow-up was 26.0 months. The two cohorts were well-balanced for baseline patient/disease characteristics and treatment factors. There were differences in treatment sequence based on the year in which patients received treatment. Overall, rates of grade 3 or higher GI or GU toxicity were <1%. There was no significant difference in acute or late GI or GU toxicity between the two groups. CONCLUSION: We found no significant difference in GI/GU toxicity in intermediate-risk or higher prostate cancer patients receiving HDR-BT boost upfront versus IMRT upfront combined with ADT. These findings suggest that either approach may be reasonable. Longer follow-up is needed to evaluate late toxicity and long-term disease control.

Comprehensive validation of halcyon 2.0 plans and the implementation of patient specific QA with multiple detector platforms.

PURPOSE: To perform a comprehensive validation of plans generated on a preconfigured Halcyon 2.0 with preloaded beam model, including evaluations of new features and implementing the patient specific quality assurance (PSQA) process with multiple detectors. METHODS: A total of 56 plans were generated in Eclipse V15.6 (Varian Medical System) with a preconfigured Halcyon treatment machine. Ten plans were developed via the AAPM TG-119 test suite with both IMRT and VMAT techniques. 34 clinically treated plans using C-arm LINAC from 24 patients were replanned on Halcyon using IMRT or VMAT techniques for a variety of sites including: brain, head and neck, lung, breast, abdomen, and pelvis. Six of those plans were breast VMAT plans utilizing the extended treatment field technique available with Halcyon 2.0. The dynamically flattened beam (DFB), another new feature on Halcyon 2.0, was also used for an AP/PA spine and four field box pelvis, as well as ten 3D breast plans. All 56 plans were measured with an ion chamber (IC), film, portal dosimetry (PD), ArcCHECK, and Delta4. Tolerance and action limits were calculated and compared to the recommendations of TG-218. RESULTS: TG-119 IC and film confidence limits met those set by the task group, except for IMRT target point dose. Forty-four of 46 clinical plans were within 3% for IC measurements. Average gamma passing rates with 3% dose difference and 2mm distance-to-agreement for IMRT/VMAT plans were: Film - 96.8%, PD - 99.9%, ArcCHECK - 99.1%, and Delta4 - 99.2%. Calculated action limits were: Film - 86.3%, PD - 98.4%, ArcCHECK - 96.1%, and Delta4 - 95.7%. Extended treatment field technique was fully validated and 3D plans with DFB had similar results to IMRT/VMAT plans. CONCLUSION: Halcyon plan deliveries were verified with multiple measurement devices. New features of Halcyon 2.0 were also validated. Traditional PSQA techniques and process specific tolerance and action limits were successfully implemented.

Injectable Hydrogels for Localized Chemotherapy and Radiotherapy in Brain Tumors.

Overall survival of patients with newly diagnosed glioblastoma (GBM) remains dismal at 16 months with state-of-the-art treatment that includes surgical resection, radiation, and chemotherapy. GBM tumors are highly heterogeneous, and mechanisms for overcoming tumor resistance have not yet fully been elucidated. An injectable chitosan hydrogel capable of releasing chemotherapy (temozolomide [TMZ]) while retaining radioactive isotopes agents (iodine, [131I]) was used as a vehicle for localized radiation and chemotherapy, within the surgical cavity. Release from hydrogels loaded with TMZ or 131I was characterized in vitro and in vivo and their efficacy on tumor progression and survival on GBM tumors was also measured. The in vitro release of 131I was negligible over 42 days, whereas the TMZ was completely released over the first 48 h. 131I was completely retained in the tumor bed with negligible distribution in other tissues and that when delivered locally, the chemotherapy accumulated in the tumor at 10-fold higher concentrations than when delivered systemically. We found that the tumors were significantly decreased, and survival was improved in both treatment groups compared to the control group. Novel injectable chemo-radio-hydrogel implants may potentially improve the local control and overall outcome of aggressive, poor prognosis brain tumors.

FMEA of manual and automated methods for commissioning a radiotherapy treatment planning system.

PURPOSE: To evaluate the level of risk involved in treatment planning system (TPS) commissioning using a manual test procedure, and to compare the associated process-based risk to that of an automated commissioning process (ACP) by performing an in-depth failure modes and effects analysis (FMEA). METHODS: The authors collaborated to determine the potential failure modes of the TPS commissioning process using (a) approaches involving manual data measurement, modeling, and validation tests and (b) an automated process utilizing application programming interface (API) scripting, preloaded, and premodeled standard radiation beam data, digital heterogeneous phantom, and an automated commissioning test suite (ACTS). The severity (S), occurrence (O), and detectability (D) were scored for each failure mode and the risk priority numbers (RPN) were derived based on TG-100 scale. Failure modes were then analyzed and ranked based on RPN. The total number of failure modes, RPN scores and the top 10 failure modes with highest risk were described and cross-compared between the two approaches. RPN reduction analysis is also presented and used as another quantifiable metric to evaluate the proposed approach. RESULTS: The FMEA of a MTP resulted in 47 failure modes with an RPNave of 161 and Save of 6.7. The highest risk process of "Measurement Equipment Selection" resulted in an RPNmax of 640. The FMEA of an ACP resulted in 36 failure modes with an RPNave of 73 and Save of 6.7. The highest risk process of "EPID Calibration" resulted in an RPNmax of 576. CONCLUSIONS: An FMEA of treatment planning commissioning tests using automation and standardization via API scripting, preloaded, and pre-modeled standard beam data, and digital phantoms suggests that errors and risks may be reduced through the use of an ACP.

The world's first single-room proton therapy facility: Two-year experience.

PURPOSE: This is a review of our 2-year experience with the first single-gantry proton therapy (PT) system. METHODS AND MATERIALS: All patients were consented to participate on an institutional review board-approved prospective patient registry between December 2013 and December 2015. PT was delivered in a single-room facility using a synchrocyclotron with proton beam energy of 250 MeV. The dataset was interrogated for demographics, diagnosis, treatment modality, and clinical trial involvement. Cases were classified as simple or complex based on fields used and immobilization. The volume of photon patients treated in our department was collected between January 2011 and December 2015 to evaluate the impact of PT on our photon patient volume. RESULTS: A total of 278 patients were treated with PT, including 228 (82%) adults and 50 (18%) pediatric cases. PT patients traveled a mean distance of 83.3 miles compared with 47.4 miles for photon patients queried in 2015. Rationale for treatment included reirradiation (20%), involvement in prospective clinical trial (14%), and proximity to critical structures to maximally spare organs at risk (66%). Forty patients were enrolled on 5 adult and 3 pediatric prospective clinical trials. The most common histologies treated were glioma (27%) and non-small cell lung cancer (18%) in adults, and medulloblastoma (22%) and low-grade glioma (24%) in pediatric patients. Prostate cancer composed 6% of PT. Complex cases composed 45% of our volume. Our photon patient volume increased yearly between 2011 and 2015, with 2780 patients completing photon treatment in 2011 and 3385 patients in 2015. PT composed 4% of overall patients treated with external beam radiation. CONCLUSIONS: The installation of our single-gantry proton facility has expanded the treatment options within our cancer center, helping to increase the number of patients we see. Patients travel from twice as far away to receive this treatment, many for typical PT indications such as pediatrics or to participate in prospective clinical trials.

Commissioning and initial experience with the first clinical gantry-mounted proton therapy system.

The purpose of this study is to describe the comprehensive commissioning process and initial clinical experience of the Mevion S250 proton therapy system, a gantry-mounted, single-room proton therapy platform clinically implemented in the S. Lee Kling Proton Therapy Center at Barnes-Jewish Hospital in St. Louis, MO, USA. The Mevion S250 system integrates a compact synchrocyclotron with a C-inner gantry, an image guidance system and a 6D robotic couch into a beam delivery platform. We present our commissioning process and initial clinical experience, including i) CT calibration; ii) beam data acquisition and machine characteristics; iii) dosimetric commissioning of the treatment planning system; iv) validation through the Imaging and Radiation Oncology Core credentialing process, including irradiations on the spine, prostate, brain, and lung phantoms; v) evaluation of localization accuracy of the image guidance system; and vi) initial clinical experience. Clinically, the system operates well and has provided an excellent platform for the treatment of diseases with protons.

Salvage radioembolization of liver-dominant metastases with a resin-based microsphere: initial outcomes.

PURPOSE: The use of radioembolization of hepatic metastases with yttrium-90 ((90)Y) microspheres is increasing. The present report describes the outcomes in a cohort of patients with metastatic liver tumors treated with a resin-based microsphere agent. MATERIALS AND METHODS: Thirty patients with colon (n = 13), breast (n = 7), and other primary cancers (n = 10) were treated after the failure of first- and second-line therapy. Overall survival (OS), time to progression (TTP), and time to treatment failure (TTTF) were calculated from the first treatment. Response was measured according to Response Evaluation Criteria In Solid Tumors at interval follow-up imaging. RESULTS: Thirty patients underwent 56 infusions of (90)Y, and 18 remained alive at the end of the study. Fourteen patients (47%) had a partial response or stable disease. OS (604 vs 251 days), TTP (223 vs 87 days), and TTTF (363 vs 87 days) were all significantly longer for patients who had a partial response or stable disease (P < .05). Median OS, TTP, and TTTF for patients with colorectal carcinoma were 357, 112, and 107 days, respectively, versus 638, 118, and 363 days in patients with other metastatic sources. Median survival was not reached for patients with breast carcinoma, and the TTP and TTTF were each 282 days. One patient (3%) experienced grade 3 toxicity (gastrointestinal ulceration). CONCLUSIONS: (90)Y microsphere therapy produced promising survival rates compared with systemic salvage options, with minimal toxicity.