Spot Scanning Proton Therapy Research Articles

Dosimetric impact of systematic spot position errors in spot scanning proton therapy of head and neck tumor.

The spot position is an important beam parameter in the quality assurance of scanning proton therapy. In this study, we investigated dosimetric impact of systematic 15 spot position errors (SSPE) in spot scanning proton therapy using three types of optimization methods of head and neck tumor. The planning simulation was performed with ± 2 mm model SSPE in the X and Y directions. Treatment plans were created using intensity-modulated proton therapy (IMPT) and single-field uniform dose (SFUD). IMPT plans were created by two optimization methods: with worst-case optimization (WCO-IMPT) and without (IMPT). For clinical target volume (CTV), D95%, D50%, and D2cc were used for analysis. For organs at risk (OAR), Dmean was used to analyze the brain, cochlea, and parotid, and Dmax was used to analyze brainsetem, chiasm, optic nerve, and cord. For CTV, the variation (1 standard deviation) of D95% was ± 0.88%, 0.97% and 0.97% to WCO-IMPT, IMPT, and SFUD plan. The variation of D50% and D2cc of CTV showed <0.5% variation in all plans. The dose variation due to SSPE was larger in OAR, and worst-case optimization reduced the dose variation, especially in Dmax. The analysis results showed that SSPE has little impact on SFUD. We clarified the impact of SSPE on dose distribution for three optimization methods. SFUD was shown to be a robust treatment plan for OARs, and the WCO can be used to increase robustness to SSPE in IMPT.

Retrospective Analysis of Replan Frequency and Causes in Esophageal Cancer Patients Treated with Spot Scanned Proton Therapy

<h3>Purpose/Objective(s)</h3> For patients with esophageal cancer treated with intensity-modulated proton therapy (IMPT) at our institution, weekly verification CT scans are obtained to ensure that the plan is still acceptable. If unacceptable deviations from the intended dose are observed, replanning is performed. This study aims to investigate the frequency and causes of replans to determine the appropriate frequency of performing verification scans. <h3>Materials/Methods</h3> Data from a cohort of 205 esophageal cancer patients treated with IMPT between 2015 and 2020 were retrospectively analyzed. Patients were typically positioned head first supine with arms up in a vacuum immobilization device, and a four-dimensional CT (4DCT) simulation scan was obtained. The typical prescription was 50 Gy in 25 fractions over 5 weeks, with contours delineated as per consensus guidelines. For tumor motion ≤ 10 mm, patients were treated free-breathing with isolayer repainting, while for motion > 10 mm, gating was also added. Two posterior oblique beams were typically used, and single field optimization was performed. Robust optimization was utilized with 5-mm translational perturbations and 3% range uncertainty, with dose evaluation, also performed on the extreme respiratory phases. Weekly 4DCT verification scans in treatment position were acquired. Rigid image registration to the original planning CT image set was performed, and the care team reviewed the recalculated dose distributions to determine the need for replan. CTV (V95%) % was selected as a metric to compare the difference in target volume dose between verification scans that did [CTV_replan (V95%) %], versus did not [CTV_no-replan (V95%) %], lead to a replan. <h3>Results</h3> The primary tumor location was upper/middle esophagus (16%) or lower/gastroesophageal junction (83%). 21 patients (10%) required replanning, including 3 patients with 2 replans. Replans occurred during the 1^st (20%), 2^nd (33%), 3^rd (20%), or 4^th (25%) weeks of treatment. Primary reasons for replanning were a superior shift of the diaphragm baseline position affecting the range of the beams entering near this interface (46%), changes in tumor size or position (17%), new or resolving pleural effusion affecting the range of beams (13%), changes in stomach filling affecting the target geometry (13%), and patient setup reproducibility issues (13%). The average value of CTV_no-replan (V95%) % = 98% ± 3% vs. CTV_replan (V95%) % = 96% ± 1%. The modest size of this difference suggests that other factors, including poor fidelity of rigid CTV contours, also contribute to clinical decision-making. <h3>Conclusion</h3> In this large cohort of patients with esophageal cancer treated with robustly planned IMPT, the rate of adaptive replanning was 10% and resulted from 5 discrete changes as described above. Every other week frequency of verification scans should be considered.

A Single-Institution Prospective Study to Evaluate the Safety and Efficacy of Real-Time-Image Gated Spot-Scanning Proton Therapy (RGPT) for Prostate Cancer

<h3>Purpose/Objective(s)</h3> Since 2014, RGPT that corrects the positional change of the prostate during treatment using gold fiducial markers placed in the prostate has been in use, but there are concerns about the effect of the metal marker on the proton dose distribution. Therefore, we conducted a prospective study to evaluate the safety and short-term clinical outcome of RGPT for prostate cancer. <h3>Materials/Methods</h3> Prostate cancer patients with ECOG performance status 0 to 2 and no lymph node or distant metastasis were enrolled in this study. In all cases, 3-4 pure gold fiducial markers of 1.5 mm diameter were inserted in the prostate. To reduce the influence of the markers on the dose distribution, the proton beam was delivered from 3 or 4 directions. The prescribed dose was 70 Gy (RBE) in 30 fractions over 7.5 weeks, and 3 years of hormone therapy was recommended for patients with high or very high risk of recurrence according to the National Comprehensive Cancer Network classification. Adverse events (AE) were evaluated weekly during the treatment, and monthly after the treatment until 3 months and every 3 months thereafter. The primary endpoint was the frequency of an early AE of Grade 2 or higher within 90 days after the end of the proton therapy, and the secondary endpoint was the biological relapse-free survival rate (BRFS) and the frequency of late AE. Based on the previous report (Nihei et al., 2011) that the frequency of Grade 2 or higher AE was 12.6%, the frequency of early AE of RGPT was assumed to be 7.6% and the non-inferiority margin was set at 10%; the threshold AE occurrence rate was set at 22.6%. Since the required number of cases was calculated to be 43 using the one-sample binomial test by the SWOG statistical tools with the one-sided significance level of 2.5% and power 80%, the target number of cases was set to 45. Based on this assumption, the non-inferiority of early safety of RGPT would be verified if the number of Grade 2 or higher early AE occurrence cases is 5 or less. <h3>Results</h3> Forty-five cases were enrolled between March 2015 and May 2017. The number of patients with Low, Favorable intermediate, Unfavorable intermediate, and High/Very high risk was 9, 7, 12, and 17, respectively. Hormone therapy was used with 17 patients and all patients completed the treatment protocol. The frequency of a Grade 2 or higher early AE was 8.9% (4/45 cases), and the non-inferiority of early safety of RGPT was verified. The median follow-up period was 63.0 months (51.3 to 79.3 months) and the overall 5-year BRFS was 88.9%. As late AE: rectal bleeding (Grade 1 in 13 cases (28.9%), Grade 2 in 8 cases (17.8%)), and bladder bleeding (Grade 1 in 2 cases (4.4%)) were observed. <h3>Conclusion</h3> The results here allow the conclusion that the RGPT for prostate cancer was as safe as conventional proton beam therapy in early AE, and its efficacy was suggested to be comparable with previous studies.

Treatment planning of total marrow irradiation with intensity-modulated spot-scanning proton therapy.

PurposeThe goal of this study is to investigate treatment planning of total marrow irradiation (TMI) using intensity-modulated spot-scanning proton therapy (IMPT). The dosimetric parameters of the intensity-modulated proton plans were evaluated and compared with the corresponding TMI plans generated with volumetric modulated arc therapy (VMAT) using photon beams.MethodsIntensity-modulated proton plans for TMI were created using the Monte Carlo dose-calculation algorithm in the Raystation 11A treatment planning system with spot-scanning proton beams from the MEVION S250i Hyperscan system. Treatment plans were generated with four isocenters placed along the longitudinal direction, each with a set of five beams for a total of 20 beams. VMAT-TMI plans were generated with the Eclipse-V15 analytical anisotropic algorithm (AAA) using a Varian Trilogy machine. Three planning target volumes (PTVs) for the bones, ribs, and spleen were covered by 12 Gy. The dose conformity index, D80, D50, and D10, for PTVs and organs at risk (OARs) for the IMPT plans were quantified and compared with the corresponding VMAT plans.ResultsThe mean dose for most of the OARs was reduced substantially (5% and more) in the IMPT plans for TMI in comparison with VMAT plans except for the esophagus and thyroid, which experienced an increase in dose. This dose reduction is due to the fast dose falloff of the distal Bragg peak in the proton plans. The conformity index was found to be similar (0.78 vs 0.75) for the photon and proton plans. IMPT plans provided superior superficial dose coverage for the skull and ribs in comparison with VMAT because of increased entrance dose deposition by the proton beams.ConclusionTreatment plans for TMI generated with IMPT were superior to VMAT plans mainly due to a large reduction in the OAR dose. Although the current IMPT-TMI technique is not clinically practical due to the long overall treatment time, this study presents an enticing alternative to conventional TMI with photons by providing superior dose coverage of the targets, increased sparing of the OARs, and enhanced radiobiological effects associated with proton therapy.

Analysis of the Rate of Re-planning in Spot-Scanning Proton Therapy.

PurposeFinite proton range affords improved dose conformality of radiation therapy when patient regions-of-interest geometries are well characterized. Substantial changes in patient anatomy necessitate re-planning (RP) to maintain effective, safe treatment. Regularly planned verification scanning (VS) is performed to ensure consistent treatment quality. Substantial resources, however, are required to conduct an effective proton plan verification program, which includes but is not limited to, additional computed tomography (CT) scanner time and dedicated personnel: radiation therapists, medical physicists, physicians, and medical dosimetrists.Materials and MethodsVerification scans (VSs) and re-plans (RPs) of 711 patients treated with proton therapy between June 2015 and June 2018 were studied. All treatment RP was performed with the intent to maintain original plan integrity and coverage. The treatments were classified by anatomic site: brain, craniospinal, bone, spine, head and neck (H&N), lung or chest, breast, prostate, rectum, anus, pelvis, esophagus, liver, abdomen, and extremity. Within each group, the dates of initial simulation scan, number of VSs, number of fractions completed at the time of VS, and the frequency of RP were collected. Data were analyzed in terms of rate of RP and individual likelihood of RP.ResultsA total of 2196 VSs and 201 RPs were performed across all treatment sites. H&N and lung or chest disease sites represented the largest proportion of plan modifications in terms of rate of re-plan (RoR: 54% and 58%, respectively) and individual likelihood of RP on a per patient basis (likelihood of RP [RP%]: 46% and 39%, respectively). These sites required RP beyond 4 weeks of treatment, suggesting continued benefit for frequent, periodic VS. Disease sites in the lower pelvis demonstrated a low yield for RP per VS (0.01-0.02), suggesting that decreasing VS frequency, particularly late in treatment, may be reasonable.ConclusionsA large degree of variation in RoR and individual RP% was observed between anatomic treatment sites. The present retrospective analysis provides data to help develop anatomic site–based VS protocols.

Spot-scanning proton therapy for targets with adjacent cardiac implantable electronic devices - Strategies for breast and head & neck cancer.

Cardiac implantable electronic device (CIED) malfunctions can be induced by secondary neutron dose from spot-scanning proton therapy. A recent in-vitro study investigating secondary neutron dose to CIEDs up to 7mSv per fraction found that exposure of secondary neutrons in this range was clinically manageable. This study presents decision algorithms proposed by a national expert group for selection of patients with breast and head & neck (H&N) cancer with CIEDs adjacent to target for proton therapy based on the 7mSv threshold. Ten patients with breast cancer and five with H&N cancer were included in the study. Five patients with breast cancer received photon therapy with CIED and proton plans were retrospectively created. The remaining patients received proton therapy without CIED and a worst-case position of a virtual CIED was retrospectively delineated. Secondary neutron dose was estimated as ambient dose equivalent H*(10) using Monte Carlo simulations. For patients with breast cancer and with contralateral CIED, the secondary neutron dose to the CIED was below 7mSv per fraction for CTV<1500cm3 in 2Gy fractions and CTV<1000cm3 in 2.67Gy fractions. The secondary neutron dose to the CIED was below 7mSv per fraction for all patients with H&N cancer. Simulations of neutron exposure suggest that proton therapy is feasible for most patients with CIED adjacent to target. This forms the basis for decision algorithms for selection of patients with CIED for proton therapy.

Performance prediction of gamma electron vertex imaging (GEVI) system for interfractional range shift detection in spot scanning proton therapy

The maximum dose delivery at the end of the beam range provides the main advantage of using proton therapy. The range of the proton beam, however, is subject to uncertainties, which limit the clinical benefits of proton therapy and, therefore, accurate in vivo verification of the beam range is desirable. For the beam range verification in spot scanning proton therapy, a prompt gamma detection system, called as gamma electron vertex imaging (GEVI) system, is under development and, in the present study, the performance of the GEVI system in spot scanning proton therapy was predicted with Geant4 Monte Carlo simulations in terms of shift detection sensitivity, accuracy and precision. The simulation results indicated that the GEVI system can detect the interfractional range shifts down to 1 mm shift for the cases considered in the present study. The results also showed that both the evaluated accuracy and precision were less than 1–2 mm, except for the scenarios where we consider all spots in the energy layer for a local shifting. It was very encouraging results that the accuracy and precision satisfied the smallest distal safety margin of the investigated beam energy (i.e., 4.88 mm for 134.9 MeV).

Evaluation of Visualizing the Prostatic Urinary Tract in MRI With a Super Resolution Deep Learning Model for Urethra Sparing Radiotherapy

<h3>Purpose/Objective(s)</h3> In the treatment planning for urethra-sparing radiation therapy in localized prostate cancer, it is important to visualize the prostatic urinary tract to reduce the risk of urinary symptoms linked to the urethral dose. We developed a methodology for visualizing the prostatic urinary tract by post-urination magnetic resonance imaging (PU-MRI) without using a urethral catheter for urethra-sparing radiotherapy. Several super-resolution (SR) deep learning models were proposed for improving image quality. This study investigated whether these SR deep learning models improve the visibility of the prostatic urinary tract in PU-MRI. <h3>Materials/Methods</h3> We enrolled 30 patients who had previously undergone real-time-image-gated spot scanning proton therapy (RGPT) by inserting fiducial markers at our institution from October 2019 to October 2020. PU-MRI was performed using a non-contrast high-resolution two-dimensional T2-weighted turbo spin-echo (TSE) imaging sequence. Four different SR deep learning models were constructed: the EDSR (enhanced deep SR network), WDSR (widely activated SR network), SRGAN (SR generative adversarial network), and RDN (residual dense network). All models were trained using a diverse 2K resolution high-quality image dataset. We imported PU-MRIs as low-resolution images and exported four SR images that were enlarged using one of the models each. To assess the performance of the proposed SR image compared to PU-MRI, we used the complex wavelet structural similarity index measure (CW-SSIM) as the quantitative metric. A 1-to-5 scale was used to subjectively evaluate the visibility of the prostatic urinary tract by two radiation oncologists. <h3>Results</h3> The mean (± standard deviation) of the CW-SSIM in the EDSR, WDSR, SRGAN, and RDN were 0.999 ± 0.001, 0.999 ± 0.002, 0.993 ± 0.002, and 0.997 ± 0.002, respectively. The mean prostatic urinary tract visibility scores for oncologist 1 and 2 were 3.70 ± 0.64 and 3.53 ± 0.99 for PU-MRI, 3.67 ± 0.60 and 2.70 ± 0.82 for EDSR, 3.70 ± 0.53 and 2.73 ± 0.81 for WDSR, 3.67 ± 0.65 and 2.73 ± 0.81 for SRGAN, and 4.37 ± 0.61 and 3.73 ± 0.93 for RDN, respectively. <h3>Conclusion</h3> This study investigated whether the combination of PU-MRI and SR deep learning models improves visibility of the prostatic urinary tract. The results suggest that SR images using RDN are highly similar to the original image and subjectively improve the visibility of the prostatic urinary tract.

Retrospective Review of Patients With Cardiac Implantable Electronic Devices Treated With Spot Scanning Proton Therapy

There is limited data on the effects of intensity modulated proton therapy (IMPT) on cardiac implantable electronic devices (CIEDs) such as pacemakers or defibrillators. Neutron scatter could affect CIED function and great caution needs to be taken when treating patients (pts) with CIEDs with IMPT. The purpose of this retrospective study was to review our experience treating CIED pts with IMPT.We retrospectively reviewed 50 pts age ≥18 years with CIEDs underwent IMPT for esophageal (11), H&N (10), other GI (7), NSCLC (6), prostate (6), brain (3), and breast (2) cancers, 4 pts with sarcomas and 1 pt with metastatic disease to bone between June 2015 and July 2020 at our institution on this IRB approved study. Thirty-seven pts were male and the average age (range) was 74 years (25-91). CIED manufacturers were Medtronic (21), Boston Scientific (15), Abbott (10), Biotronik (3) and Sorin (1). Forty-three pts had pacemakers and 7 had defibrillators. Eight pts were pacemaker dependent. Prior to treating the first CIED pt with IMPT, a multidisciplinary team including radiation oncology, cardiology, anesthesiology and nursing was established to develop guidelines for safe treatment and monitoring before, during and after IMPT. We implemented a risk-based decision tree for monitoring during treatment based on CIED dependence and underlying heart rate. We report with descriptive statistics pt demographics, cancer diagnosis, dose and distance from CIED, and CIED events and outcomes (CIED malfunctions, resets, battery depletion).Thirteen pts had intensive monitoring of their CIED during IMPT and the remaining 37 pts had reduced monitoring. Overall, 619 fractions were analyzed. The median prescribed proton dose (range) of radiation was 50 GyRBE1.1 in 25 fractions (25-75 GyRBE1.1). 46 pts had zero proton dose to the CIED. Those who had dose to the CIED had an average dose of 0.85 GyRBE1.1 (range of 0.03-2.18 GyRBE1.1). The average distance from CIED was 16.4cm (range: 2.4- > 50cm). There were no major CIED events related to the IMPT. There were three pts who had pacemaker programming resets to manufacturer settings, and all three of these pts had Biotronik CIEDs. These three pts had 6, 1 and 3 resets, and their CIED were 4cm, 7cm and 9cm from the 80% isodose line, respectively. No clinical cardiac events were related to these resets, and the CIEDS were reprogrammed to original settings uneventfully. Routine CIED battery depletion occurred in 2 pts, one of whom underwent CIED replacement during treatment. Projected CIED battery longevity decreased by 1-4 yrs in five pts.Treating pts with CIEDs undergoing IMPT seems to be safe as long as pts are carefully monitored. Infrequent CIED resets may occur. Frequent CIED monitoring may be associated with reduced projected CIED battery longevity. Long term outcomes will be reviewed and reported at the meeting.

MC1635: Randomized Phase III Trial of Hypofractionated Radiotherapy to the Whole Breast After Breast Conserving Surgery

Hypofractionated radiation therapy (RT) for localized breast cancer improves patient convenience and reduces treatment cost. Here, we report the early results of MC1635 randomized trial.Between 04/04/2018 and 02/11/2020, patients with localized breast cancer (T1-T3, N0-N1, M0) managed with breast conserving surgery (BCS) were enrolled. Patients were randomized to receive whole breast RT with moderate hypofractionation to 40 Gy in 15 fractions (Arm A) or extreme hypofractionation to 25 Gy in 5 fractions (Arm B). An optional concurrent integrated boost to 48 Gy on Arm A or 30 Gy on Arm B was allowed. All patients were treated daily (Monday-Friday). Analysis of early toxicity (< 3 months), late toxicity (> 3 months), quality of life (QOL), cosmesis, and Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) were done. QOL was assessed with patient-reported outcomes measurement information system (PROMIS), overall Linear Analogue Self-Assessment (LASA), and The Breast Cancer Treatment Outcome Scale (BCTOS). Deterioration of cosmesis was defined as going from excellent/good to fair/poor or from fair to poor according to the Harvard Cosmesis Scale.One hundred seven patients were randomized to either Arm A (n = 54) or Arm B (n = 53). Median follow-up was 20 months. Patient characteristics included: IDC 55%, ILC 20%, mixed 7%, DCIS 16%, other 3%; grade 1 or 2 72%, grade 3 28%; triple negative 9%, ER/PR+ 84%, and Her2+ 7%. Treatment characteristics included: sentinel lymph node biopsy 68%, axillary lymph node dissection 32%; spot scanned proton therapy 50%, 3D conformal x-rays 50%; and an integrated boost 21%. No significant differences in any characteristics were noted between the two arms. No grade 3 toxicities occurred on either arm. Grade 2 toxicities were seen in 7.4% of Arm A and 7.5% of Arm B. This primarily consisted of radiation dermatitis (6 patients) with 1 patient with fibrosis and 1 patient with lymphedema. Deterioration in cosmesis ≥ 3 months after RT was seen in 1.6% of Arm A and 1.7% of Arm B (P = 0.4). The average Harvard Cosmesis score was similar between arms at all timepoints. QOL was similar between arms, as well. Patient-reported radiation skin burns of 'moderate to severe' as assessed by PRO-CTCAE were more commonly reported in Arm A (58.7%) vs Arm B (27.9%) (odds ratio 3.7, CI 1.5-8.9; P = 0.004). Patient satisfaction with treatment was very high with more than 98% of patients in both arms saying that they would do RT again. No cancer recurrences or deaths have been seen in either arm.Our early analysis of our randomized study suggests that extreme hypofractionation using 25 Gy in 5 fractions is well-tolerated and as safe as moderate hypofractionation. Patient-reported radiation skin burns were 3.7 times less likely with 25 Gy in 5 fractions. Further follow-up is warranted.

Evaluation of Biological Dose Enhancement in Mucosal Surfaces of Oropharyngeal Cancer Patients Treated With Ipsilateral Discrete Spot-Scanning Proton Therapy

Proton therapy plans for head and neck cancer patients receiving ipsilateral neck radiotherapy have limited angle options given desired avoidance of contralateral tissue and other at-risk organs. This may lead to dose enhancement at the mucosal surfaces at the end of range. Herein, we study the relationship between potential areas of mucosal toxicity and biological dose (BD).The patient cohort comprised of 5 patients with oropharyngeal carcinoma treated between 2019 and 2020 with adjuvant proton therapy to doses of 60-66 Gy in 30-33 fractions to the tumor bed with/without ipsilateral neck treatment after radical resection. Monte-Carlo based linear energy transfer (LET), relative biological effectiveness (RBE), and BD distributions of clinical plans were generated using the research version of a commercial treatment planning system. BD and RBE were calculated using the McNamara (MCN) model, which includes dependencies with dose-weighted LET (LETd), alpha/beta ratio, and physical dose (PD). α/β = 3.1 Gy and a reference dose of 2 Gy per fraction, were used to perform RBE computations. 10 mm rings around the mucosal targets were used to quantify biological dose enhancement outside the target structure. Mean and max RBE, LETd Volume Histograms, as well as D2cc and near-maximum (D1%) values in comparison to conventional PD × 1.1 were analyzed.As summarized in Table 1, the rings showed an increase of 8-10 % when comparing D2cc numbers between conventional PD × 1.1 and BD. The RBE predicted by the McNamara model showed an average of 1.207 and a maximum (RBE1%) of 1.358 for this group of patients. LETd2cc and LETd1% had average values of 5.998 and 6.413 keV/µm, respectively.BD enhancement was observed at the periphery of mucosal targets in these patients. An additional study is needed to evaluate the correlation of this dose enhancement with clinical/radiologic outcomes. In the future, use of additional beam angles and/or incorporating LET in treatment planning may mitigate this effect.

Experimental Simulation of Volume Repainting Technique at Proton Synchrotron in Context of Spot Scanning Proton Therapy

Experimental Simulation of Volume Repainting Technique at Proton Synchrotron in Context of Spot Scanning Proton Therapy

PH-0599 Three-dimensional dosimetric verification of spot-scanning proton therapy in a breast-shaped phantom

PH-0599 Three-dimensional dosimetric verification of spot-scanning proton therapy in a breast-shaped phantom

Monte Carlo framework for commissioning a synchrotron-based discrete spot scanning proton beam system and treatment plan verification

This study aimed to develop a Monte Carlo (MC) framework for commissioning the narrow proton beams (spot size sigma, 5.2 mm 2 mm at isocenter for 69.4 MeV-221.3 MeV for the main beam option and 4.1 mm 1.3 mm for the minibeam option respectively) of a synchrotron-based proton therapy system and design an independent absolute dose calculation engine for intensity-modulated proton treatments. A proton therapy system (Hitachi PROBEAT-V) was simulated using divergent and convergent beam models at the nozzle entrance. The innovative source weighting scheme for the MC simulation with TOPAS (TOol for PArticle Simulations) was implemented using dose output data for the absolute dose calculations. The results of the MC simulation were compared to the experimental data, analyzed and used to commission the treatment planning system. Two MC models, divergent and convergent beams were implemented. The convergent beam model produced a high level of agreement when MC and measurements were analyzed. The beam ellipticity did not result in significant differences between MC simulated and treatment planning system calculated doses. A model of a synchrotron-based spot scanning proton therapy system has been developed and implemented in the TOPAS MC transport code framework. The dose computation engine is useful for treatment plan verification with primary and minibeam beam option.

Spot Scanning Proton Therapy for Sinonasal Malignant Tumors.

PurposeTreatment of sinonasal malignant tumors is challenging, and evidence to establish a standard treatment is limited. Our objective was to evaluate the efficacy and safety of spot scanning proton therapy (SSPT) for sinonasal malignant tumors.Patients and MethodsWe retrospectively analyzed patients with sinonasal malignant tumors (T1-4bN0-2M0) who underwent SSPT between May 2014 and September 2019. The prescription dose was typically either 60 GyRBE in 15 fractions or 60.8 GyRBE in 16 fractions for mucosal melanoma and 70.2 GyRBE in 26 fractions for other histologic subtypes. Endpoints included local control (LC), progression-free survival, overall survival (OS), and incidence of toxicity. Prognostic factors were analyzed using the Kaplan-Meier method and log-rank test.ResultsOf 62 enrolled patients, the common histologic subtypes were mucosal melanoma (35%), squamous cell carcinoma (27%), adenoid cystic carcinoma (16%), and olfactory neuroblastoma (10%). Locally advanced stages were common (T3 in 42% and T4 in 53%). Treatment-naïve tumors and postsurgical recurrent tumors accounted for 73% and 27%, respectively. No patient had previous radiotherapy. The median follow-up was 17 months (range, 6-66) for all patients and 21.5 months (range, 6-66) for survivors. The 2-year LC, progression-free survival, and OS rates of all patients were 92%, 50%, and 76%, respectively. Univariate analysis revealed histology as a prognostic factor for OS, being higher in adenoid cystic carcinoma and olfactory neuroblastoma than in other tumors. Sixteen grade ≥3 late toxicities were observed in 12 patients (19%), including 11 events resulting in visual impairment; the most common was cataract. There was 1 grade 4 toxicity, and there were no grade 5 toxicities.ConclusionSSPT was well tolerated and yielded good LC for sinonasal malignant tumors. Although we consider SSPT to be a leading treatment modality, further studies are required to establish its status as a standard treatment.

Validation of dose distribution for liver tumors treated with real-time-image gated spot-scanning proton therapy by log data based dose reconstruction.

In spot scanning proton therapy (SSPT), the spot position relative to the target may fluctuate through tumor motion even when gating the radiation by utilizing a fiducial marker. We have established a procedure that evaluates the delivered dose distribution by utilizing log data on tumor motion and spot information. The purpose of this study is to show the reliability of the dose distributions for liver tumors treated with real-time-image gated SSPT (RGPT). In the evaluation procedure, the delivered spot information and the marker position are synchronized on the basis of log data on the timing of the spot irradiation and fluoroscopic X-ray irradiation. Then a treatment planning system reconstructs the delivered dose distribution. Dose distributions accumulated for all fractions were reconstructed for eight liver cases. The log data were acquired in all 168 fractions for all eight cases. The evaluation was performed for the values of maximum dose, minimum dose, D99, and D5–D95 for the clinical target volumes (CTVs) and mean liver dose (MLD) scaled by the prescribed dose. These dosimetric parameters were statistically compared between the planned dose distribution and the reconstructed dose distribution. The mean difference of the maximum dose was 1.3% (95% confidence interval [CI]: 0.6%—2.1%). Regarding the minimum dose, the mean difference was 0.1% (95% CI: −0.5%—0.7%). The mean differences of D99, D5–D95 and MLD were below 1%. The reliability of dose distributions for liver tumors treated with RGPT-SSPT was shown by the evaluation of the accumulated dose distributions.

Empirical quenching correction in radiochromic silicone-based three-dimensional dosimetry of spot-scanning proton therapy.

Background and purposeThree-dimensional dosimetry of proton therapy (PT) with chemical dosimeters is challenged by signal quenching, which is a lower dose-response in regions with high ionization density due to high linear-energy-transfer (LET) and dose-rate. This study aimed to assess the viability of an empirical correction model for 3D radiochromic silicone-based dosimeters irradiated with spot-scanning PT, by parametrizing its LET and dose-rate dependency.Materials and methodsTen cylindrical radiochromic dosimeters (Ø50 and Ø75 mm) were produced in-house, and irradiated with different spot-scanning proton beam configurations and machine-set dose rates ranging from 56 to 145 Gy/min. Beams with incident energies of 75, 95 and 120 MeV, a spread-out Bragg peak and a plan optimized to an irregular target volume were included. Five of the dosimeters, irradiated with 120 MeV beams, were used to estimate the quenching correction factors. Monte Carlo simulations were used to obtain dose and dose-averaged-LET (LETd) maps. Additionally, a local dose-rate map was estimated, using the simulated dose maps and the machine-set dose-rate information retrieved from the irradiation log-files. Finally, the correction factor was estimated as a function of LETd and local dose-rate and tested on the different fields.ResultsGamma-pass-rates of the corrected measurements were >94% using a 3%-3 mm gamma analysis and >88% using 2%-2 mm, with a dose deviation of <5.6 ± 1.8%. Larger dosimeters showed a 20% systematic increase in dose-response, but the same quenching in signal when compared to the smaller dosimeters.ConclusionThe quenching correction model was valid for different dosimeter sizes to obtain relative dosimetric maps of complex dose distributions in PT.

Are simple verbal instructions sufficient to ensure that bladder volume does not deteriorate prostate position reproducibility during spot scanning proton therapy?

Objectives:The purpose of this study is to investigate whether verbal instructions are sufficient for bladder volume (BV) control not to deteriorate prostate position reproducibility in image-guided spot scanning proton therapy (SSPT) for localized prostate cancer.Methods:A total of 268 treatment sessions in 12 consecutive prostate cancer patients who were treated with image-guided SSPT with fiducial markers were retrospectively analyzed. In addition to strict rectal volume control procedures, simple verbal instructions to void urine one hour before the treatment were used here. The BV was measured by a Bladder Scan just before the treatment, and the prostate motion was measured by intraprostatic fiducial markers and two sets of X-ray fluoroscopy images. The correlation between the BV change and prostate motion was assessed by linear mixed-effects models and systematic and random errors according to the reproducibility of the BV.Results:The mean absolute BV change during treatment was from −98.7 to 86.3 ml (median 7.1 ml). The mean absolute prostate motion of the patients in the left-right direction was −1.46 to 1.85 mm; in the cranial-caudal direction it was −6.10 to 3.65 mm, and in the anteroposterior direction −1.90 to 5.23 mm. There was no significant relationship between the BV change and prostate motion during SSPT. The early and late genitourinary and gastrointestinal toxicity was minimal with a minimum follow up of 4.57 years.Conclusions:Simple verbal instructions about urination was suggested to be sufficient to control the BV not to impact on the prostate motion and clinical outcomes in image-guided SSPT. Careful attention to BV change is still needed when the seminal vesicle is to be treated.Advances in knowledge:Our data demonstrated that there was no apparent relationship between BV changes and prostate position reproducibility and simple verbal instruction about urination could be sufficient for image-guided SSPT.

Impact of interfractional target motion in locally advanced cervical cancer patients treated with spot scanning proton therapy using an internal target volume strategy.

Background and purposeThe more localized dose deposition of proton therapy (PT) compared to photon therapy might allow a reduction in treatment-related side effects but induces additional challenges to address. The aim of this study was to evaluate the impact of interfractional motion on the target and organs at risk (OARs) in cervical cancer patients treated with spot scanning PT using an internal target volume (ITV) strategy.Methods and materialsFor ten locally advanced cervical cancer patients, empty and full bladder planning computed tomography (pCT) as well as 25 daily cone beam CTs (CBCTs) were available. The Clinical Target Volume (CTV), the High Risk CTV (CTVHR) (gross tumor volume and whole cervix), the non-involved uterus as well as the OARs (bowel, bladder and rectum) were contoured on the daily CBCTs and transferred to the pCT through rigid bony match. Using synthetic CTs derived from pCTs, four-beam spot scanning PT plans were generated to target the patient-specific ITV with 45 Gy(RBE) in 25 fractions. This structure was defined based on pre-treatment MRI and CT to anticipate potential target motion throughout the treatment. D98% of the targets and V40Gy(RBE) of the OARs were extracted from the daily anatomies, accumulated and analyzed. In addition, the impact of bladder volume deviations from planning values on target and bowel dose was investigated.ResultsThe ITV strategy ensured a total accumulated dose >42.75 Gy(RBE) to the CTVHR for all ten patients. Two patients with large bladder-related uterus motion had accumulated dose to the non-involved uterus of 35.7 Gy(RBE) and 41.1 Gy(RBE). Variations in bowel V40Gy(RBE) were found to be correlated (Pearson r = −0.55; p-value <0.0001) with changes in bladder volume during treatment.ConclusionThe ITV concept ensured adequate dose to the CTVHR, but was insufficient for the non-involved uterus of patients subject to large target interfractional motion. CBCT monitoring and occasional replanning is recommended along the same lines as with photon radiotherapy in cervical cancer.

Implementation of a Compact Spot-Scanning Proton Therapy System in a GPU Monte Carlo Code to Support Clinical Routine

The purpose of this work was to implement a fast Monte Carlo dose calculation tool, Fred, in the Maastro proton therapy center in Maastricht (Netherlands) to complement the clinical treatment planning system. Fred achieves high accuracy and computation speed by using physics models optimized for radiotherapy and extensive use of GPU technology for parallelization. We implemented the beam model of the Mevion S250i proton beam and validated it against data measured during commissioning and calculated with the clinical TPS. The beam exits the accelerator with a pristine energy of around 230 MeV and then travels through the dynamically extendable nozzle of the device. The nozzle contains the range modulation system and the multi-leaf collimator system named adaptive aperture. The latter trims the spots laterally over the 20 × 20 cm2 area at the isocenter plane. We use a single model to parameterize the longitudinal (energy and energy spread) and transverse (beam shape) phase space of the non-degraded beam in the default nozzle position. The range modulation plates and the adaptive aperture are simulated explicitly and moved in and out of the simulation geometry dynamically by Fred. Patient dose distributions recalculated with Fred were comparable with the TPS and met the clinical criteria. Calculation time was on the order of 10–15 min for typical patient cases, and future optimization of the simulation statistics is likely to improve this further. Already now, Fred is fast enough to be used as a tool for plan verification based on machine log files and daily (on-the-fly) dose recalculations in our facility.