An efficient dose calculation strategy for intensity modulated proton therapy

Intensity-modulated proton therapy (IMPT) can achieve a better dose distribution than passive scattering or uniform scanning. For IMPT optimization, Monte Carlo (MC) is desired for spots dose calculations because of the high accuracy in heterogeneous cases. Due to its capability of computing linear energy transfer (LET), MC-based IMPT planning is preferred in biological optimization scheme. However, MC simulation is too slow to be used for this purpose. Although GPU-based MC engine has been developed, the achieved efficiency is still not ideal. The purpose of this work is to develop a new scheme to include GPU-based MC into IMPT. The conventional approach for this purpose is simply using MC repeatedly for each spot dose calculations. However, this is not the optimal approach, because of the unnecessary computations on spots that turned out to have very small weights after IMPT optimization. Memory writing conflict also poses a challenge, if one sequentially compute dose at each spot. To solve these problems, we have developed a new MC-based IMPT plan optimization framework that iteratively performs MC dose calculations and plan optimization. At each dose calculation step, the particles are sampled from different spots based on previously optimized spots intensity map with Metropolis sampling method. Simultaneous handling multiple spots also solves the memory writing conflict problem. We validated the proposed MC-based optimization schemes in one prostate case. It took 5-6 min of total computation time including both spots dose calculation and optimization with only one GPU card for the proposed method, whereas a conventional method naively using MC for spot dose calculations would be 2-3 times slower.KeywordsIMPTMonte Carloinverse plan optimizationGPU

The purpose of this study is to compare the dosimetric results between the uniform scanning proton therapy (USPT) and intensity modulated proton therapy (IMPT) plans for the prostate cancer in patients with a unilateral metallic hip prosthesis. Five prostate cancer cases with left (n = 3) and right (n = 2) metallic hip prostheses were included in this retrospective study. For each case, the USPT and IMPT plans were generated using two anterior-oblique beams and one lateral beam for a total dose of 79.2 Gy(RBE) to be delivered in 44 fractions. For a given case, the beam parameters, dose prescription, and delivery schema in the IMPT plan were kept identical to the ones in the USPT plan. The IMPT and USPT plans were compared for various dosimetric parameters. The mean dose to the target volume was comparable. Both the IMPT and USPT techniques achieved the target coverage goals. Dose homogeneity was found to be similar in the IMPT and USPT plans. For both the rectum and bladder, the IMPT plans produced favorable dosimetric results in the low-, medium-, and high-dose regions when compared to the USPT plans. For the high dose regions, the rectal V 70 was lower in the IMPT plans by about 3.89 cc when compared to the one in the USPT plans. The rectal V 80 in the IMPT plans (1.10 cc) was almost half than the one in the USPT plans (2.39 cc). In comparison to the USPT plans, the mean dose to the rectum, bladder, and femoral head were lower in the IMPT plans by about 8.91%, 4.15%, and 41.09%, respectively. Based on the preliminary results of five cases presented in this study, the IMPT plans provided slightly better dosimetric results compared to the USPT plans, especially in sparing the rectum and bladder in the low-, medium-, and high-dose regions, for the treatment of the prostate cancer in patients with a unilateral metallic hip prosthesis. Future studies need to address the impact of the setup uncertainties and intra-fraction prostate motion in the IMPT planning of the prostate cancer patients with prosthetic hip replacements.

Background: Different modern radiation therapy treatment solutions for breast cancer (BC) and regional nodal irradiation (RNI) have been proposed. In this study, we evaluate the potential reduction in radiation-induced skin morbidity obtained by intensity modulated proton therapy (IMPT) compared with intensity modulated photon therapy (IMXT) for left-side BC and RNI.Material and Methods: Using CT scans from 10 left-side BC patients, treatment plans were generated using IMXT and IMPT techniques. A dose of 50 Gy (or Gy [RBE] for IMPT) was prescribed to the target volume (involved breast, the internal mammary, supraclavicular, and infraclavicular nodes). Two single filed optimization IMPT (IMPT1 and IMPT2) plans were calculated without and with skin optimization. For each technique, skin dose-metrics were extracted and normal tissue complication probability (NTCP) models from the literature were employed to estimate the risk of radiation-induced skin morbidity. NTCPs for relevant organs-at-risk (OARs) were also considered for reference. The non-parametric Anova (Friedman matched-pairs signed-rank test) was used for comparative analyses.Results: IMPT improved target coverage and dose homogeneity even if the skin was included into optimization strategy (HIIMPT2 = 0.11 vs. HIIMXT = 0.22 and CIIMPT2 = 0.96 vs. CIIMXT = 0.82, p < .05). A significant relative skin risk reduction (RR = NTCPIMPT/NTCPIMXT) was obtained with IMPT2 including the skin in the optimization with a RR reduction ranging from 0.3 to 0.9 depending on the analyzed skin toxicity endpoint/model. Both IMPT plans attained significant OARs dose sparing compared with IMXT. As expected, the heart and lung doses were significantly reduced using IMPT. Accordingly, IMPT always provided lower NTCP values.Conclusions: IMPT guarantees optimal target coverage, OARs sparing, and simultaneously minimizes the risk of skin morbidity. The applied model-based approach supports the potential clinical relevance of IMPT for left-side BC and RNI and might be relevant for the setup of cost-effectiveness evaluation strategies based on NTCP predictions, as well as for establishing patient selection criteria.

Adjuvant Radiation for Bladder Cancer: A Dosimetry Study

Proton therapy (PT) improves outcomes in patients with nasal cavity (NC) and paranasal sinus (PNS) cancers. Herein, the authors have reported to their knowledge the largest series to date using intensity-modulated proton therapy (IMPT) in the treatment of these patients. Between 2013 and 2018, a total of 86 consecutive patients (68 of whom were radiation-naive and 18 of whom were reirradiated) received PT to median doses of 70grays and 67grays relative biological effectiveness, respectively. Approximately 53% received IMPT. The median follow-up was 23.4months (range, 1.7-69.3months) for all patients and 28.1months (range, 2.3-69.3months) for surviving patients. The 2-year local control (LC), distant control, disease-free survival, and overall survival rates were 83%, 84%, 74%, and 81%, respectively, for radiation-naive patients and 77%, 80%, 54%, and 66%, respectively for reirradiated patients. Among radiation-naive patients, when compared with 3-dimensional conformal proton technique, IMPT significantly improved LC (91% vs 72%; P<.01) and independently predicted LC (hazard ratio, 0.14; P=.01). Sixteen radiation-naive patients (24%) experienced acute grade 3 toxicities; 4 (6%) experienced late grade 3 toxicities (osteoradionecrosis, vision loss, soft-tissue necrosis, and soft tissue fibrosis) (grading was performed according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 5.0]). Slightly inferior LC was noted for patients undergoing reirradiation with higher complications: 11% experienced late grade 3 toxicities (facial pain and brain necrosis). Patients treated with reirradiation had more grade 1 to 2 radionecrosis than radiation-naive patients (brain: 33% vs 7% and osteoradionecrosis: 17% vs 3%). PT achieved remarkable LC for patients with nasal cavity and paranasal sinus cancers with lower grade 3 toxicities relative to historical reports. IMPT has the potential to improve the therapeutic ratio in these malignancies and is worthy of further investigation.

Explore the Potential Clinical and Dosimetric Improvements for Brain Cancer Proton Beam Treatment Based on the New Delivery and Planning Technique Developments - Collimator Based Intensity Modulated Proton Therapy and Spot-Scanning Proton Arc Therapy

Purpose: Pediatric craniopharyngioma, adult base-of-skull sarcoma and chordoma cases are all regarded as priority candidates for proton therapy. In this study, a dosimetric comparison between volumetric modulated arc therapy (VMAT) and intensity modulated proton therapy (IMPT) was first performed. We then investigated the impact of physical and biological uncertainties. We assessed whether IMPT plans remained dosimetrically superior when such uncertainty estimates were considered, especially with regards to sparing organs at risk (OARs).Methodology: We studied 10 cases: four chondrosarcoma, two chordoma and four pediatric craniopharyngioma. VMAT and IMPT plans were created according to modality-specific protocols. For IMPT, we considered (i) variable RBE modeling using the McNamara model for different values of (α/β)x, and (ii) robustness analysis with ±3 mm set-up and 3.5% range uncertainties.Results: When comparing the VMAT and IMPT plans, the dosimetric advantages of IMPT were clear: IMPT led to reduced integral dose and, typically, improved CTV coverage given our OAR constraints. When physical robustness analysis was performed for IMPT, some uncertainty scenarios worsened the CTV coverage but not usually beyond that achieved by VMAT. Certain scenarios caused OAR constraints to be exceeded, particularly for the brainstem and optical chiasm. However, variable RBE modeling predicted even more substantial hotspots, especially for low values of (α/β)x. Variable RBE modeling often prompted dose constraints to be exceeded for critical structures.Conclusion: For base-of-skull and pediatric craniopharyngioma cases, both physical and biological robustness analyses should be considered for IMPT: these analyses can substantially affect the sparing of OARs and comparisons against VMAT. All proton RBE modeling is subject to high levels of uncertainty, but the clinical community should remain cognizant possible RBE effects. Careful clinical and imaging follow-up, plus further research on end-of-range RBE mitigation strategies such as LET optimization, should be prioritized for these cohorts of proton patients.

The role of breath hold intensity modulated proton therapy for a case of left-sided breast cancer with IMN involvement. How protons compare with other conformal techniques?

Purpose: In Proton therapy, especially intensity modulated proton therapy(IMPT), the dose distribution shape is very sensitive to errors due to sharp dose gradients at the Bragg peaks. The concept of the conventional margin is based on the assumption that dose distribution is shifted rather than deformed due to geometrical uncertainties. The goal of this study is to access the validity of the margin concept as well as propose a new approach using Dose Volume Population Histogram (DVPH) in evaluating IMPT plans. Methods: For a prostate case, an intensity modulated proton therapy is optimized based on the conventional PTV based objective function. The plan is evaluated based on the PTV DVH and CTV DVPH (dose volume population histogram) which explicitly taking into account geometric uncertainties. The DVPH is calculated based on 2197 dose distributions at different CTV possible positions for both random and systematic errors. The DVPH with a 90% confidence level is used for the comparison. Results: The minimum dose of the CTV DVPH with a 90% confidence level is only about 18% of the prescribed dose, while the minimum dose of the PTV is 95%. For bladder DVHs, the D50 and D35 is 26% and 30%, compared to 65% and 70% of the prescribed dose from the bladder DVPH with 90% confidence level. Conclusion: The results showed that the PTV concept for ensuring the prescribed dose actually delivered to the CTV is invalid in proton therapy. The good PTV DVH might Result in an underdose to the target and should not be used for IMPT optimization. For OARs, the conventional evaluation approach underestimates dose volume end points. The new concept DVPH has been proved to provide a more accurate DVH evaluation in proton therapy.

Simple SummaryChemoradiation with photon radiotherapy is very effective as a locally advanced cervical cancer (LACC) treatment. However, the majority of women with LACC experience treatment-related toxicity involving the gastrointestinal and urogenital tracts and the immune system. Compared to that of photon therapy, proton therapy substantially reduces undesired dose to the organs around the tumor, leading to a decrease in radiotherapy-related side-effects. At present, few studies on proton therapy in patients with LACC will be conducted. The PROTECT trial aims to evaluate the differences in side effects between photon therapy and proton therapy, both combined with chemotherapy, for LACC. Fifteen patients will be enrolled per treatment group. Information will be collected on the differences in dose to the organs around the tumor, treatment-related side effects, and the impact on the immune system. This information will be used to assess the potential of proton therapy as an innovative treatment for LACC.External beam radiation therapy (EBRT) with concurrent chemotherapy followed by brachytherapy is a very effective treatment for locally advanced cervical cancer (LACC). However, treatment-related toxicity is common and reduces the patient’s quality of life (QoL) and ability to complete treatment or undergo adjuvant therapies. Intensity modulated proton therapy (IMPT) enables a significant dose reduction in organs at risk (OAR), when compared to that of standard intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT). However, clinical studies evaluating whether IMPT consequently reduces side effects for LACC are lacking. The PROTECT trial is a nonrandomized prospective multicenter phase-II-trial comparing clinical outcomes after IMPT or IMRT/VMAT in LACC. Thirty women aged >18 years with a histological diagnosis of LACC will be included in either the IMPT or IMRT/VMAT group. Treatment includes EBRT (45 Gy in 25 fractions of 1.8 Gy), concurrent five weekly cisplatin (40 mg/m2), and 3D image (MRI)-guided adaptive brachytherapy. The primary endpoint is pelvic bones Dmean and mean bowel V15Gy. Secondary endpoints include dosimetric parameters, oncological outcomes, health-related QoL, immune response, safety, and tolerability. This study provides the first data on the potential of IMPT to reduce OAR dose in clinical practice and improve toxicity and QoL for patients with LACC.

Simple SummaryThe role of proton therapy as a radiation treatment option for locally advanced sinonasal cancer patients has increased in the last years, showing promising results in terms of clinical outcomes. Definition of strategies to identify patients who would benefit the most from proton therapy in terms of reduced toxicity is highly desirable, due to limited availability and higher costs of this treatment option. The novelty of our in silico study relies on assessing the suitability of a mixed dose volume histograms and normal tissue complication probability model-based approach, aiming at providing, to the scientific community, a patient selection criteria possibly leading the therapeutic choice between proton therapy and advanced photon techniques.(1) Background: In this work, we aim to provide selection criteria based on normal tissue complication probability (NTCP) models and additional explanatory dose-volume histogram parameters suitable for identifying locally advanced sinonasal cancer patients with orbital invasion benefitting from proton therapy. (2) Methods: Twenty-two patients were enrolled, and two advanced radiation techniques were compared: intensity modulated proton therapy (IMPT) and photon volumetric modulated arc therapy (VMAT). Plans were optimized with a simultaneous integrated boost modality: 70 and 56 Gy(RBE) in 35 fractions were prescribed to the high risk/low risk CTV. Several endpoints were investigated, classified for their severity and used as discriminating paradigms. In particular, when NTCP models were already available, a first selection criterion based on the delta-NTCP was adopted. Additionally, an overall analysis in terms of DVH parameters was performed. Furthermore, a second selection criterion based on a weighted sum of the NTCP and DVH was adopted. (3) Results: Four patients out of 22 (18.2%) were suitable for IMPT due to NTCP > 3% for at least one severe toxicity, 4 (18.2%) due to NTCP > 20% for at least three concurrent intermediate toxicities and 16 (72.7%) due to the mixed sum of NTCP and DVH criterion. Since, for some cases, both criteria were contemporary fulfilled, globally 17/22 patients (77.3%) would benefit from IMPT. (4) Conclusions: For this rare clinical scenario, the use of a strategy including DVH parameters and NTCPs when comparing VMAT and IMPT is feasible. We showed that patients affected by sinonasal cancer could profit from IMPT compared to VMAT in terms of optical and central nervous system organs at risk sparing.

Purpose: The aim of this work was to evaluate the feasibility of cone-beam computed tomography (CBCT) and deformable image registration (DIR)–based “dose of the day” calculations for adaptive proton therapy. Methods: Intensity-modulated radiation therapy (IMRT) and proton therapy plans were designed for 3 head and neck patients that required replanning, and hence had a replan computed tomography (CT). Proton plans were generated for different beam arrangements and optimizations: intensity modulated proton therapy and single-field uniform dose. We used an in-house DIR software implemented at our institution to generate a deformed CT, by warping the planning CT onto the daily CBCT. This CBCT had a similar patient geometry to the replanned CT. Dose distributions on the replanned CT were considered the gold standard for “dose of the day” calculations, and were compared with doses on deformed CT (our method) and directly on the calibrated CBCT and rigidly aligned planning CT (alternative methods) in t...

Deep Inspiration Breath-Hold (DIBH) for Locoregional Breast Irradiation using Volumetric Modulated Arc Therapy (VMAT) and Intensity Modulated Proton Therapy (IMPT): A Dosimetric Comparison to Cardiac Substructure

To determine the effect of dose calculation accuracy on inverse linear energy transfer (LET) optimization for intensity-modulated proton therapy, and to determine whether adding more beams would improve the plan robustness to different dose calculation engines. Two sets of intensity-modulated proton therapy plans using two, four, six, and nine beams were created for 10 prostate cancer patients: one set was optimized with dose constraints (DoseOpt) using the pencil beam (PB) algorithm, and the other set was optimized with additional LET constraints (LETOpt) using the Monte Carlo (MC) algorithm. Dose distributions of DoseOpt plans were then recalculated using the MC algorithm, and the LETOpt plans were recalculated using the PB algorithm. Dosimetric indices of targets and critical organs were compared between the PB and MC algorithms for both sets of plans. For DoseOpt plans, dose differences between the PB and MC algorithms were minimal. However, the maximum dose differences in LETOpt plans were 11.11% and 15.85% in the dose covering 98% and 2% (D2) of the clinical target volume, respectively. Furthermore, the dose to 1cc of the bladder differed by 11.42Gy (relative biological effectiveness). Adding more beams reduced the discrepancy in target coverage, but the errors in D2 of the structure were increased with the number of beams. High modulation of LET requires high dose calculation accuracy during the optimization and final dose calculation in the inverse treatment planning for intensity-modulated proton therapy, and adding more beams did not improve the plan robustness to different dose calculation algorithms.

To achieve a superior balance between dosimetry and the delivery efficiency of intensity-modulated proton therapy (IMPT) using as few beams as possible in a single fraction, we optimally vary beams in different fractions. In the optimization, 400~800 feasible noncoplanar beams were included in the candidate pool. For each beam, the doses of all scanning spots covering the target volume and a margin were calculated. The fraction-variant beam orientation optimization (FVBOO) problem was formulated to include three terms: two quadratic dose fidelity terms to penalize the deviation of planning target volume fractional dose and organs at risk (OAR) cumulative doses from prescription, respectively; an L2,1/2-norm group sparsity term to control the number of active beams per fraction to between 1 and 4. The Fast Iterative Shrinkage-Thresholding Algorithm (FISTA) was applied to solve this problem. FVBOO was tested on a patient with base-of-skull (BOS) tumor of 5 fractions (5f) and 30 fractions (30f) with an average number of active beams per fraction varying between 4 and 1. In addition, one bilateral head-and-neck (H&N) patient, and one esophageal cancer (ESG) patient of 30f were tested with about three active beams per fraction. The results were compared with IMPT plans that use fixed beams in each fraction. The fixed beams were selected using the group sparsity term with a fraction-invariant BOO (FIBOO) constraint. Varying beams were chosen in either the 5f or 30f FVBOO plans. While similar number of beams per fraction was selected as the FIBOO plan, the FVBOO plans were able to spare the OARs better, with an average reduction of [Dmean, Dmax] from the FIBOO plans by [0.85, 2.08] Relative Biological Effective Gy (GyRBE) in the 5f plan and [1.87, 4.06]GyRBE in the 30f plans. While reducing the number of beams per fraction in the BOS patient, a three-beam/fraction 5f FVBOO plan performs comparably as the four-beam FIBOO plan and a two-beam/fraction 30f FVBOO plan still provides superior dosimetry. Fraction-variant beam orientation optimization allows the utilization of a larger beam solution space for superior dose distribution in IMPT while maintaining a practical number of beams in each fraction.