An uncertainty-incorporated method for fast beam angle selection in intensity-modulated proton therapy.

Purpose: to minimize the influence of ranger and patient setup uncertainties in intensity‐modulated proton therapy (IMPT), thus achieving the goal of “what you see is what you get” results in IMPT. Methods: A new efficient optimization scheme, which uses memory‐distributed parallelization on a multi‐processor system, is devised. Our method minimizes the possible hot spots in target volumes by penalizing not only underdosing but also overdosing in the target volumes in the objective function. Range and setup uncertainties are considered simultaneously with some simplifications. The optimization is done using the L‐BFGS method and parallelized with beamlet domain decomposition. Our approach is essentially not restrained by the memory available at one computing node and can easily be expanded to address more demanding problems in the future. Results: Compared with conventional treatment plans optimized based on planning target volumes (PTVs), our method yields plans that are considerably less sensitive to range and setup uncertainties and provides better protection for organs at risk. After robust optimization, the dose distribution is static to the CTV regardless of range and/or setup uncertainties, therefore reducing the sensitivity of the CTV coverage. This unique characteristic allows that the dose distribution is not necessarily conformal inside the whole volume of PTV, but rather a much smaller volume enclosing the CTV. Better normal tissue protection is thus accomplished by underdosing the margin of the PTV while not compromising the CTV coverage. Conclusions: Our results demonstrate the importance of robust optimization and challenge the effectiveness of the use of PTV to account for uncertainties in IMPT planning. Actually we can get some benefits rather than impediments from the sensitive dose distribution to uncertainties of IMPT. Thus, ideally all IMPT plans should be robustly optimized and our approach has great potential to make previously unreliable IMPT plans reliable.

The Potential Role of Intensity-modulated Proton Therapy in the Regional Nodal Irradiation of Breast Cancer: A Treatment Planning Study

Purpose:To evaluate the potential benefits of robust optimization in intensity modulated proton therapy(IMPT) treatment planning to account for inter‐fractional variation for Head Neck Cancer(HNC).Methods:One patient with bilateral HNC previous treated at our institution was used in this study. Ten daily CBCTs were selected. The CT numbers of the CBCTs were corrected by mapping the CT numbers from simulation CT via Deformable Image Registration. The planning target volumes(PTVs) were defined by a 3mm expansion from clinical target volumes(CTVs). The prescription was 70Gy, 54Gy to CTV1, CTV2, and PTV1, PTV2 for robust optimized(RO) and conventionally optimized(CO) plans respectively. Both techniques were generated by RayStation with the same beam angles: two anterior oblique and two posterior oblique angles. The similar dose constraints were used to achieve 99% of CTV1 received 100% prescription dose while kept the hotspots less than 110% of the prescription. In order to evaluate the dosimetric result through the course of treatment, the contours were deformed from simulation CT to daily CBCTs, modified, and approved by a radiation oncologist. The initial plan on the simulation CT was re‐replayed on the daily CBCTs followed the bony alignment. The target coverage was evaluated using the daily doses and the cumulative dose.Results:Eight of 10 daily deliveries with using RO plan achieved at least 95% prescription dose to CTV1 and CTV2, while still kept maximum hotspot less than 112% of prescription compared with only one of 10 for the CO plan to achieve the same standards. For the cumulative doses, the target coverage for both RO and CO plans was quite similar, which was due to the compensation of cold and hot spots.Conclusion:Robust optimization can be effectively applied to compensate for target dose deficit caused by inter‐fractional target geometric variation in IMPT treatment planning.

Purpose: The passive scattering proton therapy (PSPT) technique is the commonly used radiotherapy technique for craniospinal irradiation (CSI). However, PSPT involves many numbers of junction shifts applied over the course of treatment to reduce the cold and hot regions caused by field mismatching. In this work, we introduced a robust planning approach to develop an optimal and clinical efficient techniques for CSI using intensity modulated proton therapy (IMPT) so that junction shifts can essentially be eliminated. Methods: The intra-fractional uncertainty, in which two overlapping fields shift in the opposite directions along the craniospinal axis, are incorporated into the robust optimization algorithm. Treatment plans with junction sizes 3,5,10,15,20,25 cm were designed and compared with the plan designed using the non-robust optimization. Robustness of the plans were evaluated based on dose profiles along the craniospinal axis for the plans applying 3 mm intra-fractional shift. The dose intra-fraction variations (DIV) at the junction are used to evaluate the robustness of the plans. Results: The DIVs are 7.9%, 6.3%, 5.0%, 3.8%, 2.8% and 2.2%, for the robustly optimized plans with junction sizes 3,5,10,15,20,25 cm. The DIV are 10% for the non-robustly optimized plans with junction size 25 cm. The dose profiles along the craniospinalmore » axis exhibit gradual and tapered dose distribution. Using DIVs less than 5% as maximum acceptable intrafractional variation, the overlapping region can be reduced to 10 cm, leading to potential reduced number of the fields. The DIVs are less than 5% for 5 mm intra-fractional shifts with junction size 25 cm, leading to potential no-junction-shift for CSI using IMPT. Conclusion: This work is the first report of the robust optimization on CSI based on IMPT. We demonstrate that robust optimization can lead to much efficient carniospinal irradiation by eliminating the junction shifts.« less

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.

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

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.

Purpose: 4D dose calculation can accurately predict the doses received by a deforming anatomy in the presence of the intra‐fraction respiratory motion. However, 4D dose calculation is time consuming since it requires a separate dose calculation for each phase of the 4D datasets. The purpose of this work is to develop and validate a method which can correctly predict the 4D dose distribution using fewer 4D datasets. Method and Materials: An n‐state 4D convolution dose calculation method was implemented to perform the 4D dose calculation in intensity modulated photon therapy (IMXT), passive scatteredproton therapy (PSPT) and intensity modulated proton therapy (IMPT). n‐state 4D convolution dose calculation was to calculate the doses at n selected phases of 4D CT and convolve the calculated doses with the deformation vectors for each phase obtained through a deformable image registration algorithm. One‐state 4D convolution dose calculation was compared with full 4D dose calculation for an IMRT plan. One and two‐state 4D convolved dose distributions was compared with full 4D dose distribution for a PSPT and an IMPT plan. Results: The dose volume histogram (DVH) was almost identical between one‐state 4D convolved dose and full 4D dose for the IMRT plan. One‐state 4D convolution dose calculation did not predict the target coverage well for the PSPT and IMPT plans. The DVHs was predicted reasonably well by two‐state 4D convolution dose calculation for PSPT plan but was not good enough for the IMPT plans. Conclusion: For proton and photon plans, the apparent dose could be different from the 4D dose. One‐state 4D convolved dose agrees well with full 4D dose, indicating the 4D dose calculation for the photon therapy could be obtained much faster. At least two‐state 4D convolution dose calculation was required for the proton therapy.

Adjuvant Radiation for Bladder Cancer: A Dosimetry Study

Purpose: For intensity‐modulated proton therapy (IMPT), spots (high dose regions around the Bragg peaks of beamlets) for a set of energies are arranged on a grid in the target volume. The spot spacing can have a significant impact on the quality and efficiency of an IMPT plan. The purpose of this research is to optimize spot spacing and lateral margin for IMPT. Method and Materials: Multiple treatment plans were generated for a group of prostate patients, varying spot spacing (2.5–10mm) and margin size (0–12mm). All plans employed two opposing fields which were individually optimized for uniform target coverage. Dose Volume Histograms were compared to evaluate rectal sparing and target dose homogeneity. Spot‐weight histograms were used to investigate the impact of delivery system constraints on low MUs per spot, on plan quality and robustness, and on optimization efficiency. Results: Dose homogeneity decreases with lateral margin size for a given spot spacing, with 5mm spacing showing comparable performance to current treatment protocols (10mm spacing and 12mm margin). Rectal dose increases with margin size and decreases with spot spacing. For small spot spacing and margin combinations, a large fraction of the spots are close to the minimum MU limit for the delivery system. Many of the spots below this limit are discarded during optimization. This effect decreases significantly above about 5mm spacing and margin. Conclusion: Lateral margins and spot spacing must be chosen to balance target dose homogeneity against avoidance of critical structures. While decreased spot spacing increases target dose homogeneity and lowers rectal dose, it also results in a large number of low‐intensity spots, decreasing plan robustness and optimization efficiency and increasing calculation time. The optimum combination that improves rectal sparing while maintaining comparable dose homogeneity, calculation time, and plan robustness is 5mm for spot spacing with 5mm for lateral margins.

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.

Stereotactic body radiation therapy (SBRT) of central lung tumors with photon or proton therapy has a risk of increased toxicity. Treatment planning studies comparing accumulated doses for state-of-the-art treatment techniques, such as MR-guided radiotherapy (MRgRT) and intensity modulated proton therapy (IMPT), are currently lacking. We conducted a comparison of accumulated doses for MRgRT, robustly optimized non-adaptive IMPT, and online adaptive IMPT for central lung tumors. A special focus was set on analyzing the accumulated doses to the bronchial tree, a parameter linked to high-grade toxicities. Data of 18 early-stage central lung tumor patients, treated at a 0.35T MR-linac in eight or five fractions, were analyzed. Three gated treatment scenarios were compared: (S1) online adaptive MRgRT, (S2) non-adaptive IMPT, and (S3) online adaptive IMPT. The treatment plans were recalculated or reoptimized on the daily imaging data acquired during MRgRT, and accumulated over all treatment fractions. Accumulated dose-volume histogram (DVH) parameters of the gross tumor volume (GTV), lung, heart, and organs-at-risk (OARs) within 2cm of the planning target volume (PTV) were extracted for each scenario and compared in Wilcoxon signed-rank tests between S1 & S2, and S1 & S3. The accumulated GTV D98% was above the prescribed dose for all patients and scenarios. Significant reductions (p < 0.05) of the mean ipsilateral lung dose (S2: -8%; S3: -23%) and mean heart dose (S2: -79%; S3: -83%) were observed for both proton scenarios compared to S1. The bronchial tree D0.1cc was significantly lower for S3 (S1: 48.1 Gy; S3: 39.2 Gy; p = 0.005), but not significantly different for S2 (S2: 45.0 Gy; p = 0.094), compared to S1. The D0.1cc for S2 and S3 compared to S1 was significantly (p < 0.05) smaller for OARs within 1-2cm of the PTV (S1: 30.2 Gy; S2: 24.6 Gy; S3: 23.1 Gy), but not significantlydifferent for OARs within 1cm of the PTV. A significant dose sparing potential of non-adaptive and online adaptive proton therapy compared to MRgRT for OARs in close, but not direct proximity of central lung tumors was identified. The near-maximum dose to the bronchial tree was not significantly different for MRgRT and non-adaptive IMPT. Online adaptive IMPT achieved significantly lower doses to the bronchial tree compared to MRgRT.

Purpose: To investigate the possible improvements in the dose conformity in intensity modulated proton therapy (IMPT) plans with multiple fields as compared to widely used single field optimized (SFO) plans with two lateral fields for spot scanned proton therapy (SSPT) and to verify the accuracy of the delivered dose using the Radiological Physics Center Proton Prostate Phantom (RPCPPP). Methods: The CT images of RPCPPP were used to design multiple IMPT plans using both SFO and multi field optimization (MFO) methods in the Varian Eclipse treatment planning system (TPS). The standard SFO clinical plan used two lateral fields going through the femoral heads. Non‐standard plans were generated using three or more oblique fields based on the SFO and MFO options of the TPS. The angles were carefully chosen to avoid bladder and rectum as much as possible. The RPC phantom containing films and TLDs was irradiated using the standard clinical SFO plan and the four field MFO plan to compare the planned and delivered dose. Results: Based on the DVHs, MFO plan with multiple oblique fields is found to have superior target conformity with reduced dose to organs at risk (OAR) and normal tissue, especially in the high dose regions, as compared to SFO plans. The point doses measured by TLDs and 2‐D dose distribution measured by GafChromic films in the RPCPPP irradiation passed the commonly used RPC acceptance criteria, namely +/− 7% agreement in point does and more than 85% of the voxels meeting the gamma index criteria of 7% dose or 4 mm distance agreement. Conclusion: The MFO SSPT plans for prostatic targets with multiple fields lead to better target conformity with lower doses to OARs as compared to SFO plans. The results of irradiations of the RPCPPP show that these plans can be delivered with acceptable accuracy

PurposeTo systematically compare fully automated planning for 36-field discrete proton arc therapy (36PAT) with: (1) intensity-modulated proton therapy (IMPT) with 4- and 6-field clinical beam-angle class solutions (4CS, 6CS), (2) IMPT with patient-specific, computer-optimized beam-angle configurations with 6, 8 or 10 fields (6BAO, 8BAO, 10BAO), and (3) 36-field equiangular ‘‘Utopia’’ IMPT (36Utopia; total focus on dosimetric quality, no delivery time considerations) for oropharyngeal cancer patients.Materials and MethodsAll automated plan generations were performed with Erasmus-iCycle. An energy layer (EL) reduction algorithm was developed in Erasmus-iCycle to balance plan quality with delivery time in discrete PAT planning. Patient-tailored beam-angle configurations for BAO plans were obtained with the earlier published iCycle-pBAO. In 36Utopia plans, no EL reductions were applied. While beam configurations varied among approaches, all final plans were automatically generated using the published wish-list driven SISS-MCO optimizer with dosimetry-based sparsity-induced spot selection (SISS), followed by multi-criterial spot weight optimization (MCO) and resulting in Pareto-optimality in spot weights. The same wish-list for all delivery approaches prevented planning bias across approaches.Results36PAT plans achieved organs at risk (OAR) doses and normal tissue complication probability (NTCP) approaching 36Utopia plans. Relative to CS plans, 36PAT plans reduced normal tissue dose, decreasing xerostomia and dysphagia NTCPs. Compared to 4CS, 36PAT reduced summed NTCPs for grade 2 toxicity by 6.1%-point (P = .002) and grade 3 by 2.1%-point (P = .002). For 6CS, reductions were 4.7%-point (P = .002) and 1.2%-point (P = .01), respectively. 36PAT plans also outperformed BAO plans with 6 and 8 fields but were comparable to 10BAO in OAR doses and NTCPs for similar EL numbers and Monitor Units (MU).ConclusionPAT demonstrated superior dosimetric quality over clinical class solutions for oropharyngeal cancer and approached Utopia. Ten-field IMPT with personalized beam angles could be an alternative to 36-field PAT with similar expected toxicity, ELs and MUs, but a lower number of fields.

We aimed to assess the dosimetric impact of advanced delivery radiotherapy techniques using either intensity modulated x-ray beams (IMXT), volumetric modulated arc therapy (VMAT), or intensity modulated proton therapy (IMPT), for high-risk prostate cancer patients with sentinel nodes in the pararectal region. Twenty high-risk prostate cancer patients were included in a prospective trial evaluating sentinel nodes on pelvic SPECT acquisition. To be eligible for the dosimetric study, patients had to present with pararectal sentinel nodes usually not included in the clinical target volume encompassing the pelvic lymph nodes. Radiotherapy-plans including the prostate, the seminal vesicles, and the pelvic lymph nodes with the pararectal sentinel nodes were optimized for 6 eligible patients. IMXT and IMPT were delivered with 7 and 3 beams respectively and VMAT with 2 arcs. Results were assessed with Dose-Volume Histograms and predictive normal tissue complication probabilities (NTCPs) models between the three competing treatment modalities aiming to deliver a total dose of 50.4 Gy in 1.8 Gy daily fractions. Target coverage was optimized with IMPT when compared to IMXT and VMAT. Coverage of the sentinel node was slightly better with IMXT (D98% 5 57.3 ± 5.1 Gy) when compared with VMAT (D98% 5 56.2 ± 4.1 Gy). The irradiation of rectal, bladder, small bowel, and femoral heads volumes was significantly reduced with IMPT when compared to IMXT and VMAT. NTCPs rates for rectal and bladder ≥ grade-3 late toxicity were better with IMPT (0.4 ± 0.0% and 0.0 ± 0.0%) compared with IMXT (4.6 ± 3.3% and 1.4 ± 1.1%), and VMAT (4.5 ± 4.0% and 1.6 ± 1.6%), respectively. Acceptable dose-volume distributions and low rectal and urinary NTCPs were estimated to geometrically complex pelvic volumes such as the ones proposed in this study using IMXT, VMAT and IMPT. IMPT succeeded, however, to propose the best physical and biological treatment plans compared to both X-ray derived plans.