Beam Scanning Proton Therapy Research Articles

Mechanical Characterization and Validation of the Dynamic Collimation System Prototype for Proton Radiotherapy.

Radiation therapy is integral to cancer treatments for more than half of patients. Pencil beam scanning (PBS) proton therapy is the latest radiation therapy technology that uses a beam of protons that are magnetically steered and delivered to the tumor. One of the limiting factors of PBS accuracy is the beam cross-sectional size, similar to how a painter is only as accurate as the size of their brush allows. To address this, collimators can be used to shape the beam along the tumor edge to minimize the dose spread outside of the tumor. Under development is a dynamic collimation system (DCS) that uses two pairs of nickel trimmers that collimate the beam at the tumor periphery, limiting dose from spilling into healthy tissue. Herein, we establish the dosimetric and mechanical acceptance criteria for the DCS based on a functioning prototype and Monte Carlo methods, characterize the mechanical accuracy of the prototype, and validate that the acceptance criteria are met. From Monte Carlo simulations, we found that the trimmers must be positioned within ±0.5 mm and ±1.0 deg for the dose distributions to pass our gamma analysis. We characterized the trimmer positioners at jerk values up to 400 m/s3 and validated their accuracy to 50 μm. We measured and validated the rotational trimmer accuracy to ±0.5 deg with a FARO® ScanArm. Lastly, we calculated time penalties associated with the DCS and found that the additional time required to treat one field using the DCS varied from 25-52 s.

The Effects of Pencil Beam Scanning Proton Beam Therapy on a HeartMate 3 Left Ventricular Assist Device: Implications for Patient Safety.

The Effects of Pencil Beam Scanning Proton Beam Therapy on a HeartMate 3 Left Ventricular Assist Device: Implications for Patient Safety.

Factors Associated With Acute Toxicity in Pediatric Patients Treated With Proton Radiation Therapy: A Report From the Pediatric Proton Consortium Registry

PurposeLimited prospective information regarding acute toxicity in pediatric patients receiving proton therapy (PT) exists. In this study, Pediatric Proton Consortium Registry (PPCR) data was analyzed for factors associated with development of acute toxicity in children receiving passively scattered or pencil beam scanning PT. Methods and MaterialsPediatric patients treated with PT and enrolled on the PPCR from 2016 to 2017 at 7 institutions were included. Data were entered on presence versus absence of acute general, cardiac, endocrine, eye, gastrointestinal, genitourinary, hematologic, mouth, musculoskeletal, neurologic, psychological, respiratory, and skin toxicities before (baseline) and at the end of PT (acute). Associations between patient and treatment variables with development of acute toxicity were assessed with multivariable modeling. ResultsOf 422 patients included, PT technique was passively scattered in 241 (57%), pencil beam scanning in 180 (43%), and missing in 1 (<1%) patient. Median age was 9.9 years. Daily anesthesia for treatment was used in 169 (40%). Treatments were categorized as craniospinal irradiation (CSI; n = 100, 24%), focal central nervous system PT (n = 157, 38%), or body PT (n = 158, 38%). Passively scattered PT was associated with increased risk of hematologic toxicity compared with pencil beam scanning PT (odds ratio [OR]: 3.03; 95% confidence interval [CI], 1.38-6.70; P = .006). There were no other differences toxicities between PT techniques. Uninsured patients had increased risk of GI (OR: 2.71; 95% CI, 1.12-6.58; P = .027) and hematologic toxicity (OR: 10.67; 95% CI, 2.68-42.46; P <.001). Patients receiving concurrent chemotherapy were more likely to experience skin (OR: 2.45; 95% CI, 1.23-4.88; P = .011), hematologic (OR: 2.87; 95% CI, 1.31-6.25; P = .008), GI (OR: 2.37; 95% CI, 1.33-4.21; P = .003), and mouth toxicities (OR: 2.03; 95% CI, 1.10-3.73; P = .024). Patients receiving 49 to 55 Gy were more likely to experience skin (OR: 2.18; 95% CI, 1.06-4.44; P = .033) toxicity than those receiving <49 Gy. ConclusionsThe PPCR registry highlights broad differences in acute toxicity rates in children receiving PT, and identifies opportunities for improvements in prevention, monitoring, and treatment of toxicities.

SIOG2021-0136 - Institutional audit of geriatric patients treated with pencil beam scanning (PBS) proton beam therapy(PBT) – Toxicities and early outcomes

SIOG2021-0136 - Institutional audit of geriatric patients treated with pencil beam scanning (PBS) proton beam therapy(PBT) – Toxicities and early outcomes

Simulation study using the spots deletion technique in spot scanning proton beam therapy for prostate cancers.

The aim of the present study was to investigate the effects on the dose distribution and beam delivery time in spot scanning proton beam therapy (PBT) incorporating the spot deletion technique. A spot scanning plan was created for 30 patients with prostate cancer. The plan was then modified via two processes: Spots with lower weighting depositions were deleted (process A) and spots that were distant from the clinical target volume (CTV) were deleted (process B). The dose distribution to the organs at risk (OAR), the expanded CTV (exCTV), which was defined by a uniform expansion of the CTV by a radius of 5 mm, and the beam delivery time were compared among initial and modified plans. The V50 Gy [relative biological effectiveness (RBE)] to the rectum and bladder, and V60 Gy(RBE) to the urethral bulb, inhomogeneity index (INH) of the exCTV showed a difference (P=1.1x10-14, P=6.4x10-14, P=2.7x10-7, P=3.2x10-17), although only changes by process B were significant. Modified plan by process B showed the V50 Gy(RBE) to the rectum and bladder decreased by -2.4±1.6 and -2.3±1.4%, and the V60 Gy (RBE) to the urethral bulb decreased by -15.9±19.4%. The INH of the exCTV increased by 0.05±0.03%. On the other hand, modification of the initial plan by process A did not affect the dose of the OAR, exCTV or beam delivery time. In spot scanning PBT, modification of the initial radiotherapy plan by systemic deletion of spots distant from the CTV could result in a dose reduction to the OAR.

Comparative In Silico Analysis of Intensity Modulated Scanning Beam Proton Therapy (IMPT) and Volumetric Modulated Arc Photon Radiotherapy (VMAT) for the Post-Operative Treatment of Prostate Cancer

Limited data exist regarding the dosimetric techniques and potential advantages of modern scanning beam proton therapy relative to conventional photon therapy modalities for prostate cancer patients in the post-operative setting. Our purpose was to evaluate the dosimetric differences in IMPT versus IMRT for the post-operative treatment of prostate cancer.The 3DCT data of 7 consecutive, post-prostatectomy patients treated at our institution with adjuvant or salvage IMPT in 2020 were used to generate VMAT and IMPT plans using 3 different beam arrangements: 2-field (opposed laterals), 3-field (opposed laterals inferiorly matched to posterior beam superiorly), and 4-field (opposed laterals inferiorly matched superiorly to 2 posterior oblique beams). Prescription was 50 Gy in 2 Gy fractions delivered to elective pelvic nodal regions (i.e., whole pelvis) and 20 Gy in 2 Gy fractions delivered to the prostate bed for a total dose of 70 Gy in 35 fractions. PT doses are reported in Gy (RBE) = 1.1 Gy. Dose goals for target and relevant organs at risk (OAR), as well as dose-volume histogram parameters were assessed. The paired 2-sided Wilcoxon signed-rank test was used to compare the 4-field IMPT versus VMAT plans, with P < .05 indicating statistical significance.CTV coverage met pre-specified dose goals for all plans with 99% of CTVs receiving ≥ 100% of the prescription doses. The 2-, 3-, and 4-field IMPT plans showed similar doses to the bladder and bladder minus CTV (bladderless-CTV), while the 4-field IMPT plan showed the lowest mean and low to intermediate doses to the bowel cavity and rectum. For example, mean bowel cavity V15 and V45 for the 2-, 3-, and 4-field IMPT plans were respectively 549.2 ± 282.6 cc and 110.7 ± 39.8 cc, 303.0 ± 102.0 cc and 92.7 ± 32.6 cc, and 263.4 ± 97.3 cc and 90.6 ± 40.6 cc. Mean rectum V50 and V60 for the 2-, 3-, and 4-field IMPT plans were 26.8 ± 8.9% and 18.7 ± 7.4%, 28.9 ± 10.5% and 19.5 ± 8.0%, 24.3 ± 4.8% and 16.7 ± 4.1% respectively. When comparing the 4-field IMPT and VMAT plans, the rectal, bowel, and bladder parameters in Table 1 differed significantly.The 4-field IMPT beam arrangement showed the greatest reductions in dose to the bowel cavity and rectum compared to VMAT and the 2- and 3-field IMPT arrangements. These data can inform the future clinical management and delivery of proton therapy for prostate cancer in the post-prostatectomy setting.

Proton reirradiation for recurrent or new primary breast cancer in the setting of prior breast irradiation

Background and purposeLate local recurrences and second primary breast cancers are increasingly common. Proton beam therapy (PBT) reirradiation (reRT) may allow safer delivery of a second definitive radiotherapy (RT) course. We analyzed outcomes of patients with recurrent or new primary breast cancer who underwent reRT. Materials and methodsIn an IRB-approved retrospective study, patient/tumor characteristics, treatment parameters, outcomes, and toxicities were collected for all consecutive patients with recurrent or new primary non-metastatic breast cancer previously treated with breast or chest wall RT who underwent PBT reRT. ResultsForty-six patients received reRT using uniform (70%) or pencil beam (30%) scanning PBT. Median first RT, reRT, and cumulative doses were 60 Gy (range 45–66 Gy), 50.4 Gy(RBE) (40–66.6 Gy(RBE)), and 110 Gy(RBE) (96.6–169.4 Gy(RBE)), respectively. Median follow-up was 21 months. There were no local or regional recurrences; 17% developed distant recurrence. Two-year DMFS and OS were 92.0% and 93.6%, respectively. Nine of 13 (69.2%) patients who underwent implant or flap reconstruction developed capsular contracture, 3 (23.1%) requiring surgical intervention. One (7.7%) patient developed grade 3 breast pain requiring mastectomy after breast conserving surgery. No acute or late grade 4–5 toxicities were seen. Increased body mass index (BMI) was protective of grade ≥ 2 acute toxicity (OR = 0.84, 95%CI = 0.70–1.00). ConclusionIn the largest series to date of PBT reRT for breast cancer recurrence or new primary after prior definitive breast or chest wall RT, excellent locoregional control and few high-grade toxicities were encountered. PBT reRT may provide a relatively safe and highly effective salvage option. Additional patients and follow-up are needed to correlate composite normal tissue doses with toxicities and assess long-term outcomes.

Proton Reirradiation for Recurrent or New Primary Breast Cancer in the Setting of Prior Breast Irradiation

Local breast cancer recurrences and new primary breast cancers are an increasingly common clinical challenge without clear treatment guidelines. To date, photon reirradiation (reRT) has not been widely adopted due to concerns for toxicities. Proton beam therapy (PBT) can optimize normal tissue sparing and may allow for safer delivery of a second definitive radiotherapy (RT) course. We hypothesize salvage PBT reRT can be safely delivered, and we present clinical outcomes and toxicities of patients with recurrent or new primary non-metastatic breast cancer who received prior RT and PBT reRT.In an IRB-approved retrospective study, all consecutive patients with recurrent or new primary non-metastatic breast cancer treated with breast or chest wall (CW) RT and PBT reRT from a single institution were identified. Patient and tumor characteristics, treatment parameters, clinical outcomes and toxicities were collected. Distant metastasis-free survival (DMFS) and overall survival (OS) were defined from PBT reRT start to date of distant recurrence, death or last follow-up and estimated using Kaplan-Meier methodology.Forty-six consecutive patients were assessed. Eight patients (17.4%) were reirradiated to an intact breast, 13 (28.3%) to CW without reconstruction, 20 (43.5%) to CW with reconstruction, and 5 (10.9%) to regional lymph nodes (LN) alone. PBT reRT was delivered with uniform (70%) or pencil beam (30%) scanning PBT. Median first course dose was 60Gy (45-66Gy); median PBT reRT dose was 50.4Gy (RBE) (40-66.6Gy); median cumulative dose was 108.9Gy2, a/b = 3(RBE) (95.0-168.8 Gy2, a/b = 3 (RBE)). When regional LN were retreated, median first course dose was 50.4 Gy (48.6-66.6Gy) and median PBT reRT dose was 50 Gy2, a/b = 3 (46.7-66.0Gy2, a/b = 3). Four patients had significant brachial plexus overlap with cumulative doses up to 99.0 Gy. At a median follow-up of 21 months, there were no local or regional recurrences; 8 patients (17%) developed distant recurrence, of whom three died. Estimated 3-year DMFS and OS were 60% and 88%, respectively. Grade 3 acute toxicities were limited exclusively to RT dermatitis (30.4%). Grade 3 late toxicities occurred in 4 patients (8.7%) (3 capsular contracture requiring surgical intervention, 1 breast pain requiring mastectomy). Two patients developed rib fracture. No cases of neuropathies, skin ulceration or other acute or late grade ≥3 toxicities occurred.In the largest series to date of PBT reRT for breast cancer recurrence or new primary after prior definitive breast or CW RT, PBT reRT provided excellent locoregional control with a low rate of high-grade toxicities limited to target tissue not amenable to sparing from full reRT dose. These data are encouraging and suggest PBT reRT may provide patients with a relatively safe and highly effective salvage option. Longer follow-up and additional patients are needed to correlate composite normal tissue doses with toxicities and assess long-term outcomes.

Institutional Audit of Adaptive Re-Planning With Pencil Beam Scanning Proton Beam Therapy

Pencil beam scanning proton beam therapy (PBS-PBT) dose distributions are extremely sensitive to tissue deformation. We conducted a retrospective audit of 190 consecutive patients treated with image guided PBS-PBT over a period of 1.5 years, to analyze the incidence, causes and trigger for adaptive re-planning.Patients were treated with daily image guidance with either KV X-rays or Cone beam CT scan (CBCT) or both. Patients underwent quality assurance imaging either with a CT (QA-CT) or MRI after every 5-10 fractions or earlier based on CBCT. The nominal plans were overlaid on the QA-CT and the doses were recalculated to assess dose perturbations and need for adaptive re-planning. The thresholds for re-planning were based on the physician's choice. The trigger for re-planning was also recorded and classified as elective QA-CT, QA-CT based on CBCT trigger or based on clinical triggers. After the initial 6-9 months of the study several measures were implemented with regards to simulation and planning such as skin rind evaluation for head neck patients, modified planning techniques, avoidance of certain beam angles and changes to class solutions.At least 3 QA images were acquired for each patient. A total of58 patients (30.52 %) required adaptive re-planning, of which 9 (15%) underwent re-planning more than once. Of the patients undergoing re-planning, 44.8%were of head neck,15.5%brain, 10.3%pelvic,5.2%skull base, 5.2% CSI, and 12.3% were of thoracic subsite.68% of Head neck and 66% of thoracic patients underwent adaptive re-planning. The number of patients undergoing adaptive re-planning in week 1,2,3,4,5&6 were 11, 10, 18, 8, 7 and 4 respectively. Most common cause for adaptive planning was deformation of target (23.07%) and beam path changes (23.07%) followed by persistent set up errors (9.23%), OAR deformation (7.69%) and combination of either of the factors in 26.15%. 59% of plans were adapted due to overdose in OARs, 29.7% were due to under-coverage of target while 10.8% had both. The average dose perturbation in the high dose target was higher than the intermediate dose target. Of the first 70 patients 43% underwent plan adaptation while after implementation of measures to reduce the adaptive re-planning, in next 120 patients only 23.3% required the same. Trigger for adaptive re-planning was elective QA-CT in 15%, CBCT trigger in 78%, and clinical triggers in 7% of patients.Our retrospective audit showed that the need for adaptive re-planning for patients treated with PBS-PBT is significantly high especially for head neck and thoracic tumors. The most common causes for adaptive re-planning were target deformations and beam path changes which in a majority of cases are picked up by CBCT imaging. Innovative simulation and planning approaches could potentially reduce the need for adaptive re-planning.

Incidence of Symptomatic Brain Injury Following Pencil Beam Scanning Proton Beam Therapy for Management of Central Nervous System Tumors

Although proton beam therapy (PBT) results in decreased dose to non-target tissue compared to modern photon therapy, there are concerns of rare CNS injury occurring following PBT due in part to RBE/LET uncertainties. Such uncertainties can be further exacerbated when delivering PBT using pencil beam scanning (PBS) technology. The primary objective of this study was to report the incidence of CNS toxicities in a large cohort of adult brain tumor patients treated with PBS at a single academic proton center. We hypothesized that PBS can be safely delivered for treatment of CNS tumors.A single-institution retrospective IRB-approved analysis was conducted of all patients with CNS tumors treated with PBT at our institution between February 2016 and April 2020. Patients were excluded if follow up was less than one month. Kaplan-Meier estimates of treatment toxicities were calculated, accounting for death and local recurrence as competing risks. Multivariate analysis (MVA) was performed using the Cox proportional hazard model to determine risk factors associated with symptomatic toxicity.A total of 283 consecutive patients with CNS toxicities (116 [41%] males, 167 [59%] females) completed a course of definitive-intent PBT; 116 patients had meningiomas/pituitary adenomas, 92 patients had gliomas/GBM, and 75 patients had other histologies (chordoma, paraganglioma, ependymoma, medulloblastoma, pineal tumor). Median age was 52 years old (range 18-91). Median dose of PBT was 51.3 Gy (RBE = 1.1, [range 20.4 - 78.8 Gy RBE]). Median dose per fraction was 1.8 Gy/fx (range 1.1-3.8 Gy/fx). Sixty patients [21%] had received some form of prior intracranial RT. Concurrent systemic therapy was delivered in 49 patients [17%]. Median follow-up time was 20 months. The 2-year incidence of symptomatic-treatment toxicity was 8.7%. Symptomatic radiation necrosis occurred in 13 patients including optic neuritis [N = 2], seizure [N = 3], neurologic deficit [N = 9], stroke [N = 1] and brainstem necrosis [N = 2]. Two patients had symptoms with no radiation-related imaging changes including stroke [N = 1] and seizure [N = 1]. MVA identified prior intracranial irradiation (HR 3.901, 95% CI 1.42, 10.73, P = 0.008) and increasing EQD2 of proton radiation (HR 1.077 per Gray, 95% CI 1.00, 1.15, P = 0.036) as predictive factors for increased incidence of adverse events including symptomatic toxicity and asymptomatic radiation necrosis. No PBT treatment planning parameters were found to correlate with toxicity risk.This is the largest series to date reporting outcomes for patients with CNS tumors treated with pencil beam scanning PBT. Our analysis indicates that pencil beam scanning PBT in this setting is well-tolerated with a toxicity profile similar to modern photon therapy. Future studies correlating toxicity-risk with LET are warranted.B. Savla: None. G.S. Alexander: None. K. Sun: None. S.M. Bentzen: Travel Expenses; University of Copenhagen. S. Mossahebi: None. Y. Kwok: None. W.F. Regine: None. M.V. Mishra: Employee; Orthofix. Research Grant; ASTRO, Keep Punching. Advisory Board; Patient Centers Outcomes Research Institute (PCORI. Travel Expenses; Patient Centers Outcomes Research Institute (PCORI.

Toxicity Outcomes of Hypofractionated Image Guided Pencil Beam Scanning Proton Beam Therapy for Spinal Chordomas

To evaluate acute and late toxicities in patients of chordoma treated with hypofractionated, image guided pencil beam scanning proton beam therapy.Consecutive patients diagnosed with spinal chordomas treated at our center with pencil beam scanning proton beam therapy (part of a prospective SCCORE- Sarcoma, Chordoma, Chondrosarcoma registry) were included in this study. Among all patients, high risk CTV (CTV-HR) was treated to a dose of 70.4CGE/32fractions and intermediate risk CTV (CTV-IR) was treated to a dose of 57.6-64CGE/32fractions. Patients underwent clinical, radiological (including metabolic- DCE MRI imaging) and QOL (EORTC QOL QC-30) evaluations at baseline and 6 monthly thereafter. Acute and late toxicities were recorded at each clinical visit as per CTCAE V4.0 and LENT SOMA scales respectively. Clinical and radiological outcomes are being reported in this study.Consecutive 23 patients with a median age of 38 years (range 4-64 years) with histologically proven chordoma (20 classical chordomas, 1 chondroid chordomas and 2 de-differentiated chordomas were analyzed. Among patients with skull base and dorsal chordomas (15 patients) all patients underwent surgery at least once, 21% underwent surgery twice, 14% underwent thrice and 7% underwent more than 3 times. Among patients with sacral chordomas (8 patients), 63% underwent surgery at least once and 50% underwent more than once. 17% patients (2 clival and 2 sacral) underwent prior radiation with photons (IMRT technique) with 13% receiving more than once. Mean volumes of CTV HR and for skull base chordomas was 32.4cc (0.83-132cc) and for sacral chordomas was 855cc (96.1-1740cc). Two patients had acute grade 3 dermatitis, 1 patient had acute grade 3 oropharyngeal mucositis and 1 patient had acute grade 3 gastrointestinal mucositis. 28.5% of patients with Clival and 50% of patients with Sacral lesions had grade 2 acute toxicities. 1 patient had late grade 3 toxicity requiring tracheostomy. None of patients had any late grade 2/3 gastrointestinal or genitourinary toxicities. With a median follow up of 17 months (9-23 months), 21 patients (91%) remained radiologically stable with favorable metabolic response in all the 10 patients (43%) where metabolic imaging was available. Only 1 patient had in-field radiological progression and 1 patient had distant bone metastases.Pencil beam scanning proton beam therapy is feasible in patients with spinal chordomas. Despite high doses, large treatment volumes and large number of patients receiving prior treatments, the acute and late toxicities were relatively low in this cohort.

Early Experience Using Proton Beam Therapy for Extremity Soft Tissue Sarcoma: A Multi-Institution Study

<h3>Purpose/Objective(s)</h3> Proton beam therapy (PBT) may provide an advantage when planning selected patients with extremity soft tissue sarcoma (STS), especially for larger and anatomically challenging cases. We analyzed our early experience with PBT on toxicity and outcomes. <h3>Materials/Methods</h3> A retrospective study was performed of 20 consecutive patients with extremity STS treated between June 2016 and September 2020, with pencil beam scanning PBT at two institutions with a median age 51.5 years (range, 19-78 years). Demographic, tumor, treatment, and toxicity characteristics were gathered from baseline to end of follow-up or death. Surgery was performed for all patients; chemotherapy and intraoperative electron radiotherapy boost were included for selected patients. Wound complications were defined as secondary operation for wound repair (debridement, drainage, skin graft, and muscle flap) or non-operative management requiring hospitalization. Dermatitis was graded according to the CTCAE scale. Analysis was performed with statistical software. <h3>Results</h3> All patients completed the prescribed course of PBT to a median dose of 5000 cGY RBE (range: 3000 – 6600 cGY RBE). Tumor presentation was primary (n = 17) or recurrent after prior combined modality therapy (n = 3). Tumor location was either lower extremity (n = 13) or upper extremity (n = 7). Median pre-treatment tumor size was 9.2 cm (range: 1.3 – 30.0 cm). Baseline staging for patients prior to PBT follows: 2 (10%) IA, 7 (35%) IB, 4 (20%) II, 3 (15%) IIIA, 3 (15%) IIIB, and 1 (5%) IV. Radiation was delivered pre-operatively in most patients (n = 18). Median follow-up was 13.7 months (range, 1.7 – 48.1 months). Nineteen patients (90%) were alive at the end of follow-up. Locoregional control was 100%. Four patients (20%) had developed metastatic disease by end of follow-up. Acute dermatitis was maximum grade 2 (n = 8, 40%) and grade 3 (n = 3, 15 %). After pre-operative radiation and surgical resection, acute wound complications occurred in 7 patients (39%). Intraoperative debridement and I&D, unplanned skin graft, muscle flap, and IV antibiotic use requiring hospitalization was required in 5 (25%), 3 (15%), 1 (5%), and 2 (10%), respectively. Tumor size was larger in patients with wound complications compared to no complications (median 15.3 cm [range 1.6-30.0 cm] vs 6.9cm [1.3-14.4 cm], <i>P</i> = 0.045). Factors such as patient age, tumor location, histology, chemotherapy, or IORT were not associated with wound complications. Rates of chronic G2+ pain, neuropathy, fibrosis, and lymphedema were 25%, 15%, 5%, and 5% respectively. <h3>Conclusion</h3> This early study of PBT for challenging extremity STS cases demonstrates good local control, similar acute toxicity profile, and wound complication rate comparable to photons. Long term follow-up and further dosimetric analyses will provide further insight into potential advantages of PBT in this patient population.

FLASH radiotherapy: Considerations for multibeam and hypofractionation dose delivery

Current interest in ultra-high-dose-rate radiation therapy (FLASH) has arisen from the observed protection of various normal tissues exposed to high single doses in preclinical studies [1]. In this context ‘ultra-high-dose-rate’ is considered to be ≥40 Gy/s (c.f. a conventional (CONV) dose-rate ≥ 0.01 Gy/s) [2,3] (Fig. 1). While existing preclinical and clinical application of FLASH has used only a single beam, some proponents of FLASH have suggested the use of multiple beams to achieve the same conformal dose distributions obtainable using advanced radiotherapy techniques such as scanned beam proton therapy with conventional radiation dose-rates [4].

PO-1460 Adaptive re-planning with image guided pencil beam scanning proton beam therapy

PO-1460 Adaptive re-planning with image guided pencil beam scanning proton beam therapy

PO-1419 Toxicity outcomes of hypofractionated pencil beam scanning proton beam therapy for spinal Chordomas

PO-1419 Toxicity outcomes of hypofractionated pencil beam scanning proton beam therapy for spinal Chordomas

Abstract PO-009: Targeting a unique electrochemical vulnerability in a pediatric brain tumor to potentiate proton beam radiotherapy

Abstract Medulloblastoma (MB) is the most common malignant (WHO Grade IV) primary brain cancer in children, adolescents, and young adults. Radiotherapy (RT) is a mainstay of MB treatment, as it is for most childhood and adult cancers. RT dose and frequency needed to achieve efficacy in MB patients severely impacts survival outcomes and is the cause of long-term cognitive deficits. To improve on short-term side effects and long-term complications, scanning beam proton therapy is employed, when available. While this recent technological advance significantly reduces damage to surrounding healthy brain tissue, survivors continue to experience induced radiation damage, including neurocognitive sequelae. To impact survivors’ health-related quality of life and caregivers’ emotional and financial burden, it is critical to identify approaches that reduce RT dose to mitigate side-effects without impacting RT effectiveness. We are investigating targeting a unique MB electrochemical vulnerability as a means to sensitize MB tumor cells to RT. There are four MB molecular subgroups: wingless, sonic-hedgehog, Group 3, and Group 4. Our analysis of 763 MB tumor transcriptomes reveals that all Group 3 MB tumors share an enhanced expression of genes-coding for subunits of the Type-A GABA receptor (GABAAR), a chloride channel. Using patch-clamp electrophysiology, we found that GABAARs conduct Cl− in MB cells and that a brain-penetrant benzodiazepine (BZ) enhances this effect and triggers cytotoxic responses commensurate with mitochondrial depolarization. We find that BZ combined with RT, even at a sub-lethal dose, is highly effective in impairing the viability of MB tumor cells, greater than RT alone. Our BZis capable of penetrating the blood-brain barrier in minutes, is metabolically stable, and showed no toxicity in a primate model. We are investigating its suitability to be used concomitant with proton beam radiotherapy, replacing standard of care vincristine, to reduce radiation-induced brain toxicity experienced by MB patients and survivors while not decreasing RT effectiveness. Citation Format: Daniel Pomeranz Krummel, Laura Kallay, Debanjan Bhattacharya, Vaibhavkumar Gawali, Kamdem T. Donatien, Taukir Ahmed, James M. Cook, Michael Lamba, Susanne Wells, Ralph E. Vatner, Mathieu Sertorio, Dan T. Ionascu, Soma Sengupta. Targeting a unique electrochemical vulnerability in a pediatric brain tumor to potentiate proton beam radiotherapy [abstract]. In: Proceedings of the AACR Virtual Special Conference on Radiation Science and Medicine; 2021 Mar 2-3. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(8_Suppl):Abstract nr PO-009.

Results of an independent dosimetry audit for scanned proton beam therapy facilities

PurposeAn independent dosimetry audit based on end-to-end testing of the entire chain of radiation therapy delivery is highly recommended to ensure consistent treatments among proton therapy centers. This study presents an auditing methodology developed by the MedAustron Ion Beam Therapy Center (Austria) in collaboration with the National Physical Laboratory (UK) and audit results for five scanned proton beam therapy facilities in Europe. MethodsThe audit procedure used a homogeneous and an anthropomorphic head phantom. The phantoms were loaded either with an ionization chamber or with alanine pellets and radiochromic films. Homogeneously planned doses of 10Gy were delivered to a box-like target volume in the homogeneous phantom and to two clinical scenarios with increasing complexity in the head phantom. ResultsFor all tests the mean of the local differences of the absolute dose to water determined with the alanine pellets compared to the predicted dose from the treatment planning system installed at the audited institution was determined. The mean value taken over all tests performed was −0.1±1.0%. The measurements carried out with the ionization chamber were consistent with the dose determined by the alanine pellets with a mean deviation of −0.5±0.6%. ConclusionThe developed dosimetry audit method was successfully applied at five proton centers including various “turn-key” Cyclotron solutions by IBA, Varian and Mevion. This independent audit with extension to other tumour sites and use of the correspondent anthropomorphic phantoms may be proposed as part of a credentialing procedure for future clinical trials in proton beam therapy.

Technical Note: First report on an in vivo range probing quality control procedure for scanned proton beam therapy in head and neck cancer patients.

The capability of proton therapy to provide highly conformal dose distributions is impaired by range uncertainties. The aim of this work is to apply range probing (RP), a form of a proton radiography-based quality control (QC) procedure for range accuracy assessment in head and neck cancer (HNC) patients in a clinical setting. This study included seven HNC patients. RP acquisition was performed using a multi-layer ionization chamber (MLIC). Per patient, two RP frames were acquired within the first two weeks of treatment, on days when a repeated CT scan was obtained. Per RP frame, integral depth dose (IDD) curves of 81 spots around the treatment isocenter were acquired. Range errors are determined as a discrepancy between calculated IDDs in the treatment planning system and measured residual ranges by the MLIC. Range errors are presented relative to the water equivalent path length of individual proton spots. In addition to reporting results for complete measurement frames, an analysis, excluding range error contributions due to anatomical changes, is presented. Discrepancies between measured and calculated ranges are smaller when performing RP calculations on the day-specific patient anatomy rather than the planning CT. The patient-specific range evaluation shows an agreement between calculated and measured ranges for spots in anatomically consistent areas within 3% (1.5 standard deviation). The results of an RP-based QC procedure implemented in the clinical practice for HNC patients have been demonstrated. The agreement of measured and simulated proton ranges confirms the 3% uncertainty margin for robust optimization. Anatomical variations show a predominant effect on range accuracy, motivating efforts towards the implementation of adaptive radiotherapy.

Comparative in Silico Analysis of Pre-Operative Scanning Beam Proton Therapy, Intensity Modulated Photon Radiation Therapy, and 3D Conformal Photon Radiation Therapy in Adult Soft Tissue Sarcoma

Comparative in Silico Analysis of Pre-Operative Scanning Beam Proton Therapy, Intensity Modulated Photon Radiation Therapy, and 3D Conformal Photon Radiation Therapy in Adult Soft Tissue Sarcoma

4D strategies for lung tumors treated with hypofractionated scanning proton beam therapy: Dosimetric impact and robustness to interplay effects

PurposeTo investigate the impact of four-dimensional robust optimization (4DRO) on dose delivered to lung cancer patients in pencil beam scanning proton therapy. Methods and materials2 strategies were compared for 20 lung cancer patients, using a different number of breathing phases of the reconstructed 4D computed tomography (CT) included in the plan optimization problem. In the restricted approach combined with gating, only 3 phases close to reference end-exhale were considered instead of the whole breathing cycle. The prescribed dose was 60 Gy(RBE) in 10 fractions. Target coverage (D98%) and dose to healthy tissues were evaluated using Wilcoxon signed-rank test.To assess the robustness against interfractional anatomical and respiratory variations, the optimized plans were recalculated on re-evaluation 4DCTs.To compare the sensitivity of both strategies to interplay effects, we implemented an end-to-end test with a home-made heterogeneous moving phantom and ionization chambers measurements. Robustly optimized plans with prescription doses of 6 Gy(RBE) were delivered in different dynamic conditions. ResultsBoth 4D robustly optimized plans reached the same target coverage (p = 0.56), while a statistically significant decrease of the homolateral lung dose was observed using the restricted approach (p < 0.0001).Plan recalculations within 15 days from the treatment simulation showed the same robustness of target D98% against interfractional variations (p = 0.48), with an average decrease of approximately 3 Gy(RBE).Phantom measurements confirmed the delivery accuracy of the restricted approach (mean dose deviations <5%). Higher deviations were found for ungated full 4DRO and larger motion amplitude. ConclusionThe restricted approach combined with gating improved normal tissue sparing and was shown to be more robust to single fraction deliveries and large motion amplitude.