Purpose: To enhance an in-house graphic-processing-unit (GPU) accelerated virtual particle (VP)-b... more Purpose: To enhance an in-house graphic-processing-unit (GPU) accelerated virtual particle (VP)-based Monte Carlo (MC) proton dose engine (VPMC) to model aperture blocks in both dose calculation and optimization for pencil beam scanning proton therapy (PBSPT)-based stereotactic radiosurgery (SRS). Methods and Materials: A module to simulate VPs passing through patient-specific aperture blocks was developed and integrated in VPMC based on simulation results of realistic particles (primary protons and their secondaries). To validate the aperture block module, VPMC was first validated by an opensource MC code, MCsquare, in eight water phantom simulations with 3cm thick brass apertures: four were with aperture openings of 1, 2, 3, and 4cm without a range shifter, while the other four were with same aperture opening configurations with a range shifter of 45mm water equivalent thickness. Then, VPMC was benchmarked with MCsquare and RayStation MC for 10 patients with small targets (average...
6025 Background: To evaluate the severity of cetuximab-induced rash and its correlation with clin... more 6025 Background: To evaluate the severity of cetuximab-induced rash and its correlation with clinical outcome and late skin toxicity. Methods: The analysis included patients who received definitive CRT on RTOG 0522 (70 Gy + cisplatin and cetuximab) or postoperative CRT on RTOG 0234 (60–66 Gy + cetuximab and either docetaxel or cisplatin). Patients had to have received the loading dose and at least one concurrent dose of cetuximab. Results: Six hundred two patients were analyzed: 406 on RTOG 0522 and 196 on RTOG 0234; 386 patients (64.1%) developed Grade 2-4 cetuximab rash. Patients with Grade 2-4 rash had younger age (p<0.001), fewer pack-years smoking history (p<0.001), were male (p=0.03) and had an oropharynx primary site (p=0.002). Combined across treatment groups, patients with Grade 2-4 rash, when compared to those with Grade 0-1 rash, had increased OS (HR 0.58 [95%CI 0.44-0.76)], p<0.001), increased PFS (HR 0.76 [95%CI 0.60-0.97], p=0.03), and reduced incidence of distant metastasis (HR 0.63 [95%CI ...
International Journal of Radiation Oncology Biology Physics, Nov 1, 2021
PURPOSE/OBJECTIVE(S) We previously reported the two-year results of MC1273, a phase II trial eval... more PURPOSE/OBJECTIVE(S) We previously reported the two-year results of MC1273, a phase II trial evaluating 30-36 Gy of adjuvant radiation therapy (RT) for selected patients (pts) with HPV+ OPSCC. Herein we report the long-term disease control and toxicity rates for this de-escalated regimen. MATERIALS/METHODS Details for the MC1273 regimen have previously been published. All pts received surgery & neck dissection for a margin negative resection. Eligibility criteria included pts with HPV+OPSCC, ≤10 pack-year smoking history, and negative margins. Cohort A (≥T3, ≥N2, lymphovascular invasion, or perineural invasion) received 30 Gy delivered in 1.5 Gy b.i.d. over 12 days along with weekly docetaxel (15 mg/m2, days 1 & 8). Pts with +ECE were enrolled in Cohort B and received the same treatment plus a simultaneous integrated boost to nodal levels with ECE to 36 Gy in 1.8 Gy b.i.d. The primary endpoint was local/regional control (LRC) at 2 years with each cohort powered to detect a 10% locoregional failure rate with 85% confidence. Secondary endpoints included 2-yr progression free survival (PFS), overall survival (OS), toxicity, swallow function, and pt reported QOL. Follow-up was q3 mos for the first 2 years, q6 mo for year 3, and yearly until year 5. Based upon the 2-year MC1273 data, pts with pT4 disease were excluded from MC1675, the follow-up phase III trial randomizing pts to the 30-36 Gy regimen versus a standard 60 Gy regimen. RESULTS Accrual was from September 2013 to June 2016 (n = 80, 1 ineligible, Cohort A: 37, Cohort B: 43, median (range) age 61 years (25 - 77), male n = 71 (89.9%). Median follow-up for alive pts as of 2/22/21 was 52 mos (30 - 67). Late grade 2 or higher toxicity rates at 2, 3, and 5 years were 6.7%, 6.8%, and 5.0%, respectively, with the most common being dry mouth (1.7%, 3.4%, and 0.0% at years 2, 3, and 5) and dysphagia (3.3%, 0.0%, and 5.0% at years 2, 3, and 5). Grade 3 rates were 0.0%, 0.0%, and 1.2% at years 2, 3, and 5, respectively, with one pt who developed a malignant peripheral nerve sheath tumor in the brachial plexus at the edge of the neck volume 51 mo after RT. The 2, 3, and 5 year disease metrics for the entire study population, Cohort A, and Cohort B can be found in the Table, along with an unplanned subset analysis for pts qualifying for MC1675 (n = 72). CONCLUSION MC1273 maintained excellent long-term disease control rates comparable to historical controls, particularly in the intermediate risk cohort and pts qualifying for MC1675. Toxicity rates remained low long-term.
International Journal of Radiation Oncology Biology Physics, Nov 1, 2017
To evaluate whether historic risk categories and indications for adjuvant therapy in the pre-huma... more To evaluate whether historic risk categories and indications for adjuvant therapy in the pre-human papillomavirus (HPV) and pre-transoral surgery (TOS) era were associated with clinically significant relapse rates in HPV+ oropharyngeal squamous cell cancer patients undergoing TOS. A multi-institutional retrospective review of intermediate- and high-risk HPV+ oropharyngeal squamous cell cancer patients not receiving adjuvant therapy after TOS was performed. Perineural invasion, lymphovascular invasion, T3-T4, or ≥N2 disease were considered to be intermediate-risk factors, and extracapsular extension or positive margins were considered to be high-risk features, according to established risk categories. Median follow-up was 42.9 months. Among all 53 patients, the 3-year cumulative incidence of relapse was 26.0%. The 3-year cumulative incidence was 11.8% in the 37 intermediate-risk patients and 52.4% in the 16 high-risk patients. On univariate analysis only high-risk status was significantly associated with an increased risk of relapse (hazard ratio 3.9; P=.018). The salvage rate for relapse was 77%, with 10 of 13 patients undergoing salvage therapy. Risk category was associated with clinically significant relapse rates after TOS alone in HPV+ oropharyngeal cancer, comparable to historical data and traditional indications for adjuvant therapy for all oropharyngeal cancer.
6064 Background: RRT is offered as definitive (DRRT) or post-operative (PRRT) treatment for patie... more 6064 Background: RRT is offered as definitive (DRRT) or post-operative (PRRT) treatment for patients (pts) with loco-regionally recurrent (LRR) or new primary (NP) HNSCC in previously irradiated volumes. We report the results of a retrospective chart review of all consecutive pts with LRR and NP HNSCC treated with DRRT and PRRT at Mayo Clinic. Methods: We included LRR and NP HNSCC pts treated with DRRT/PRRT from 2003-2011 at all Mayo Clinic campuses. Patient and treatment related data were collected. Loco-regional recurrence rate (LR) and distant metastases rate (DM) at 2 years, and overall survival (OS) from end of RRT using Kaplan-Meier methods, were calculated. Results: We identified 89 pts (68 M, 21 F). 67 pts had LRR; 22 NP. Treatment included salvage surgery with PRRT (47 pts) and DRRT (42 pts). 30 pts received concurrent chemotherapy (CT) with PRRT; 33 DRRT pts received CT. Median prior RT dose was 66 Gy (26.4 – 79.2 Gy). Median PRRT dose was 60 Gy (11 – 70 Gy). Median DRRT dose was 69.6 Gy (18 – 7...
Surgical treatment of pelvic sarcoma involving the bone is the standard of care but is associated... more Surgical treatment of pelvic sarcoma involving the bone is the standard of care but is associated with several sequelae and reduced functional quality of life (QOL). Treatment with photon and proton radiotherapy is associated with relapse. Carbon ion radiotherapy (CIRT) may reduce both relapse rates and treatment sequelae. The PROSPER study is a tricontinental, nonrandomized, prospective, three-arm, pragmatic trial evaluating treatments of pelvic sarcoma involving the bone. Patients aged at least 15 years are eligible for inclusion. Participants must have an Eastern Cooperative Oncology Group Performance Status score of two or less, newly diagnosed disease, and histopathologic confirmation of pelvic chordoma, chondrosarcoma, osteosarcoma, Ewing sarcoma with bone involvement, rhabdomyosarcoma (RMS) with bone involvement, or non-RMS soft tissue sarcoma with bone involvement. Treatment arms include (1) CIRT (n = 30) delivered in Europe and Asia, (2) surgical treatment with or without a...
The purpose of this work is to investigate collimating individual proton beamlets from a dosimetr... more The purpose of this work is to investigate collimating individual proton beamlets from a dosimetric perspective and to introduce a new device concept, the spot scanning aperture (SSA). The SSA consists of a thin aperture with a small cylindrical opening attached to a robotics system, which allows the aperture to follow and align with individual beamlets during spot delivery. Additionally, a range shifter is incorporated (source-side) for treating shallow depths. Since the SSA trims beamlets spot by spot, the patient-facing portion of the device only needs to be large enough to trim a single proton beamlet. The SSA has been modelled in an open-source Monte-Carlo-based dose engine (MCsquare) to characterize its dosimetric properties in water at depths between 0 and 10 cm while varying the following parameters: the aperture material, thickness, distance to the water phantom, distance between the aperture and attached range shifter, and the aperture opening radius. Overall, the SSA grea...
BackgroundIn proton therapy dose calculation, Monte Carlo (MC) simulations are superior in accura... more BackgroundIn proton therapy dose calculation, Monte Carlo (MC) simulations are superior in accuracy but more time consuming, compared to analytical calculations. Graphic processing units (GPUs) are effective in accelerating MC simulations but may suffer thread divergence and racing condition in GPU threads that degrades the computing performance due to the generation of secondary particles during nuclear reactions.PurposeA novel concept of virtual particle (VP) MC (VPMC) is proposed to avoid simulating secondary particles in GPU‐accelerated proton MC dose calculation and take full advantage of the computing power of GPU.MethodsNeutrons and gamma rays were ignored as escaping from the human body; doses of electrons, heavy ions, and nuclear fragments were locally deposited; the tracks of deuterons were converted into tracks of protons. These particles, together with primary and secondary protons, are considered to be the realistic particles. Histories of primary and secondary protons ...
BackgroundBoth dose and linear energy transfer (LET) could play a substantial role in adverse eve... more BackgroundBoth dose and linear energy transfer (LET) could play a substantial role in adverse event (AE) initialization of cancer patients treated with pencil‐beam‐scanning (PBS) proton therapy. However, not all the voxels within the AE regions are directly induced from the dose and LET effect. It is important to study the synergistic effect of dose and LET in AE initialization by only including a subset of voxels that are dosimetrically important.PurposeTo perform exploratory investigation of the dose and LET effects upon AE initialization in PBS using seed spots analysis.MethodsA total of 113 head‐and‐neck (H&N) cancer patients receiving curative PBS were included. Among them, 20 patients experienced unanticipated CTCAEv4.0 grade ≥3 AEs (AE group) and 93 patients did not (control group). Within the AE group, 13 AE patients were included in the seed spot analysis to derive the descriptive features of AE initialization and the remaining 7 mandible osteoradionecrosis patients and 93 ...
PurposeTo develop an online graphic processing unit (GPU)‐accelerated Monte Carlo‐based adaptive ... more PurposeTo develop an online graphic processing unit (GPU)‐accelerated Monte Carlo‐based adaptive radiation therapy (ART) workflow for pencil beam scanning (PBS) proton therapy to address interfraction anatomical changes in patients treated with PBS.Methods and MaterialsA four‐step workflow was developed using our in‐house developed GPU‐accelerated Monte Carlo‐based treatment planning system to implement online Monte Carlo‐based ART for PBS. The first step conducts diffeomorphic demon‐based deformable image registration (DIR) to propagate contours on the initial planning CT (pCT) to the verification CT (vCT) to form a new structure set. The second step performs forward dose calculation of the initial plan on the vCT with the propagated contours after manual approval (possible modifications involved). The third step triggers a reoptimization of the plan depending on whether the verification dose meets the clinical requirements or not. A robust evaluation will be done for both the veri...
PURPOSE Due to the employment of quadratic programming using soft constraints to implement dose v... more PURPOSE Due to the employment of quadratic programming using soft constraints to implement dose volume constraints and the "trial-and-error" procedure needed to achieve a clinically acceptable plan, conventional dose volume constraints (upper limit) are not adequately effective in controlling small and isolated hot spots in the dose/linear energy transfer (LET) distribution. Such hot spots can lead to adverse events. In order to mitigate the risk of brain necrosis, one of the most clinically significant adverse events in patients receiving intensity-modulated proton therapy (IMPT) for base of skull (BOS) cancer, we propose per-voxel constraints to minimize hot spots in LET-guided robust optimization. METHODS AND MATERIALS Ten BOS cancer patients treated with IMPT were carefully selected by meeting one of the following conditions: 1) diagnosis of brain necrosis during follow-up; 2) considered high risk for brain necrosis by not meeting dose constraints to the brain. An optimizing structure (BrainOPT) and an evaluating structure (BrainROI) that both contained the aforementioned hot dose regions in the brain were generated for optimization and evaluation, respectively. Two plans were generated for every patient: one using conventional dose-only robust optimization, the other using LET-guided robust optimization. The impact of LET was integrated into the optimization via a term of extra biological dose (xBD). A novel optimization tool of per-voxel constraints to control small and isolated hot spots in either the dose, LET, or combined (dose/LET) distribution was developed and used to minimize dose/LET hot spots of the selected structures. Indices from dose-volume histogram (DVH) and xBD dose-volume histogram (xBDVH) were used in the plan evaluation. A newly developed tool of the dose-LET-volume histogram (DLVH) was also adopted to illustrate the underlying mechanism. Wilcoxon signed-rank test was used for statistical comparison of the DVH and xBDVH indices between the conventional dose-only and the LET-guided robustly optimized plans. RESULTS Per-voxel constraints effectively and efficiently minimized dose hot spots in both dose-only and LET-guided robust optimization and LET hot spots in LET-guided robust optimization. Compared to the conventional dose-only robust optimization, the LET-guided robust optimization could generate plans with statistically lower xBD hot spots in BrainROI (VxBD,50Gy[RBE], P = 0.009; VxBD,60Gy[RBE], P = 0.025; xBD1cc, P = 0.017; xBD2cc, P = 0.022) with comparable dose coverage, dose hot spots in the target, and dose hot spots in BrainROI. DLVH analysis indicated that LET-guided robust optimization could either reduce LET at the same dose level or redistribute high LET from high dose regions to low dose regions. CONCLUSION Per-voxel constraint is a powerful tool to minimize dose/LET hot spots in IMPT. The LET-guided robustly optimized plans outperformed the conventional dose-only robustly optimized plans in terms of xBD hot spots control. This article is protected by copyright. All rights reserved.
PURPOSE To evaluate the accuracy of the RayStation Monte Carlo dose engine (RayStation MC) in mod... more PURPOSE To evaluate the accuracy of the RayStation Monte Carlo dose engine (RayStation MC) in modeling small-field block apertures in proton pencil beam scanning. Furthermore, we evaluate the suitability of MCsquare as a 2nd check for RayStation MC. METHODS We have enhanced MCsquare to model block apertures. To test the accuracy of both RayStation MC and the newly enhanced MCsquare, we compare the dose predictions of each to in-water dose measurements obtained using diode detectors and radiochromic film. Nine brass apertures with openings of 1, 2, 3, 4, and 5 cm and either 2 cm or 4 cm thickness were used in the irradiation of a water phantom. Two measurement setups were used, one with a range shifter and 119.7 MeV proton beam energy and the other with no range shifter and 147 MeV proton beam energy. To further test the validity of RayStation MC and MCsquare in modeling block apertures and to evaluate MCsquare as a 2nd check tool, ten small-field (average target volume 8.3 cm3 ) patient treatment plans were calculated by each dose engine followed by a statistical comparison. RESULTS Comparing to the absolute dose measurements in water, RayStation MC differed by 1.2% ± 1.0% while MCsquare differed by -1.8% ± 3.7% in the plateau region of a pristine Bragg peak. Compared to the in-water film measurements, RayStation MC and MCsquare both performed well with an average 2D-3D gamma passing rate of 99.4% and 99.7% (3%/3mm) respectively. A t-test comparing the agreement with the film measurements between RayStation MC and MCsquare suggested that the relative spatial dose distributions calculated by MCsquare and RayStation MC were statistically indistinguishable. Directly comparing the dose calculations between MCsquare and RayStation MC over ten patients resulted in an average 3D-3D gamma passing rates of 98.5% (3%/3mm) and 94.1% (2%/2mm) respectively. CONCLUSION The validity of RayStation MC algorithm for use with patient-specific apertures has been expanded to include small apertures. MCsquare has been enhanced to model apertures and was found to be an adequate 2nd check of RayStation MC in this scenario. This article is protected by copyright. All rights reserved.
ObjectiveDiagnostic delay in human papillomavirus–associated oropharynx squamous cell carcinoma (... more ObjectiveDiagnostic delay in human papillomavirus–associated oropharynx squamous cell carcinoma (HPV(+)OPSCC) is common due to nonspecific symptoms. We aim to describe the disease burden and oncologic outcomes of patients with HPV(+)OPSCC diagnosed >12 months after symptom onset.Study DesignThis is a retrospective cohort study of HPV(+)OPSCC patients receiving intent‐to‐cure treatment (including surgery ± adjuvant therapy or primary chemoradiation).Setting2006‐2016, tertiary care center.MethodsTumor stage was compared between patients with and without delayed diagnosis using χ2 tests. Kaplan‐Meier survival analysis with univariate and multivariable Cox regressions were used to determine the effect of diagnostic delay on oncologic outcomes.ResultsIn total, 664 patients were included. Compared to patients diagnosed <12 months from symptom onset (n = 601), those diagnosed at >12 months (n = 63) were more likely to have T4 disease and higher overall American Joint Committee on ...
Purpose: To enhance an in-house graphic-processing-unit (GPU) accelerated virtual particle (VP)-b... more Purpose: To enhance an in-house graphic-processing-unit (GPU) accelerated virtual particle (VP)-based Monte Carlo (MC) proton dose engine (VPMC) to model aperture blocks in both dose calculation and optimization for pencil beam scanning proton therapy (PBSPT)-based stereotactic radiosurgery (SRS). Methods and Materials: A module to simulate VPs passing through patient-specific aperture blocks was developed and integrated in VPMC based on simulation results of realistic particles (primary protons and their secondaries). To validate the aperture block module, VPMC was first validated by an opensource MC code, MCsquare, in eight water phantom simulations with 3cm thick brass apertures: four were with aperture openings of 1, 2, 3, and 4cm without a range shifter, while the other four were with same aperture opening configurations with a range shifter of 45mm water equivalent thickness. Then, VPMC was benchmarked with MCsquare and RayStation MC for 10 patients with small targets (average...
6025 Background: To evaluate the severity of cetuximab-induced rash and its correlation with clin... more 6025 Background: To evaluate the severity of cetuximab-induced rash and its correlation with clinical outcome and late skin toxicity. Methods: The analysis included patients who received definitive CRT on RTOG 0522 (70 Gy + cisplatin and cetuximab) or postoperative CRT on RTOG 0234 (60–66 Gy + cetuximab and either docetaxel or cisplatin). Patients had to have received the loading dose and at least one concurrent dose of cetuximab. Results: Six hundred two patients were analyzed: 406 on RTOG 0522 and 196 on RTOG 0234; 386 patients (64.1%) developed Grade 2-4 cetuximab rash. Patients with Grade 2-4 rash had younger age (p<0.001), fewer pack-years smoking history (p<0.001), were male (p=0.03) and had an oropharynx primary site (p=0.002). Combined across treatment groups, patients with Grade 2-4 rash, when compared to those with Grade 0-1 rash, had increased OS (HR 0.58 [95%CI 0.44-0.76)], p<0.001), increased PFS (HR 0.76 [95%CI 0.60-0.97], p=0.03), and reduced incidence of distant metastasis (HR 0.63 [95%CI ...
International Journal of Radiation Oncology Biology Physics, Nov 1, 2021
PURPOSE/OBJECTIVE(S) We previously reported the two-year results of MC1273, a phase II trial eval... more PURPOSE/OBJECTIVE(S) We previously reported the two-year results of MC1273, a phase II trial evaluating 30-36 Gy of adjuvant radiation therapy (RT) for selected patients (pts) with HPV+ OPSCC. Herein we report the long-term disease control and toxicity rates for this de-escalated regimen. MATERIALS/METHODS Details for the MC1273 regimen have previously been published. All pts received surgery & neck dissection for a margin negative resection. Eligibility criteria included pts with HPV+OPSCC, ≤10 pack-year smoking history, and negative margins. Cohort A (≥T3, ≥N2, lymphovascular invasion, or perineural invasion) received 30 Gy delivered in 1.5 Gy b.i.d. over 12 days along with weekly docetaxel (15 mg/m2, days 1 & 8). Pts with +ECE were enrolled in Cohort B and received the same treatment plus a simultaneous integrated boost to nodal levels with ECE to 36 Gy in 1.8 Gy b.i.d. The primary endpoint was local/regional control (LRC) at 2 years with each cohort powered to detect a 10% locoregional failure rate with 85% confidence. Secondary endpoints included 2-yr progression free survival (PFS), overall survival (OS), toxicity, swallow function, and pt reported QOL. Follow-up was q3 mos for the first 2 years, q6 mo for year 3, and yearly until year 5. Based upon the 2-year MC1273 data, pts with pT4 disease were excluded from MC1675, the follow-up phase III trial randomizing pts to the 30-36 Gy regimen versus a standard 60 Gy regimen. RESULTS Accrual was from September 2013 to June 2016 (n = 80, 1 ineligible, Cohort A: 37, Cohort B: 43, median (range) age 61 years (25 - 77), male n = 71 (89.9%). Median follow-up for alive pts as of 2/22/21 was 52 mos (30 - 67). Late grade 2 or higher toxicity rates at 2, 3, and 5 years were 6.7%, 6.8%, and 5.0%, respectively, with the most common being dry mouth (1.7%, 3.4%, and 0.0% at years 2, 3, and 5) and dysphagia (3.3%, 0.0%, and 5.0% at years 2, 3, and 5). Grade 3 rates were 0.0%, 0.0%, and 1.2% at years 2, 3, and 5, respectively, with one pt who developed a malignant peripheral nerve sheath tumor in the brachial plexus at the edge of the neck volume 51 mo after RT. The 2, 3, and 5 year disease metrics for the entire study population, Cohort A, and Cohort B can be found in the Table, along with an unplanned subset analysis for pts qualifying for MC1675 (n = 72). CONCLUSION MC1273 maintained excellent long-term disease control rates comparable to historical controls, particularly in the intermediate risk cohort and pts qualifying for MC1675. Toxicity rates remained low long-term.
International Journal of Radiation Oncology Biology Physics, Nov 1, 2017
To evaluate whether historic risk categories and indications for adjuvant therapy in the pre-huma... more To evaluate whether historic risk categories and indications for adjuvant therapy in the pre-human papillomavirus (HPV) and pre-transoral surgery (TOS) era were associated with clinically significant relapse rates in HPV+ oropharyngeal squamous cell cancer patients undergoing TOS. A multi-institutional retrospective review of intermediate- and high-risk HPV+ oropharyngeal squamous cell cancer patients not receiving adjuvant therapy after TOS was performed. Perineural invasion, lymphovascular invasion, T3-T4, or ≥N2 disease were considered to be intermediate-risk factors, and extracapsular extension or positive margins were considered to be high-risk features, according to established risk categories. Median follow-up was 42.9 months. Among all 53 patients, the 3-year cumulative incidence of relapse was 26.0%. The 3-year cumulative incidence was 11.8% in the 37 intermediate-risk patients and 52.4% in the 16 high-risk patients. On univariate analysis only high-risk status was significantly associated with an increased risk of relapse (hazard ratio 3.9; P=.018). The salvage rate for relapse was 77%, with 10 of 13 patients undergoing salvage therapy. Risk category was associated with clinically significant relapse rates after TOS alone in HPV+ oropharyngeal cancer, comparable to historical data and traditional indications for adjuvant therapy for all oropharyngeal cancer.
6064 Background: RRT is offered as definitive (DRRT) or post-operative (PRRT) treatment for patie... more 6064 Background: RRT is offered as definitive (DRRT) or post-operative (PRRT) treatment for patients (pts) with loco-regionally recurrent (LRR) or new primary (NP) HNSCC in previously irradiated volumes. We report the results of a retrospective chart review of all consecutive pts with LRR and NP HNSCC treated with DRRT and PRRT at Mayo Clinic. Methods: We included LRR and NP HNSCC pts treated with DRRT/PRRT from 2003-2011 at all Mayo Clinic campuses. Patient and treatment related data were collected. Loco-regional recurrence rate (LR) and distant metastases rate (DM) at 2 years, and overall survival (OS) from end of RRT using Kaplan-Meier methods, were calculated. Results: We identified 89 pts (68 M, 21 F). 67 pts had LRR; 22 NP. Treatment included salvage surgery with PRRT (47 pts) and DRRT (42 pts). 30 pts received concurrent chemotherapy (CT) with PRRT; 33 DRRT pts received CT. Median prior RT dose was 66 Gy (26.4 – 79.2 Gy). Median PRRT dose was 60 Gy (11 – 70 Gy). Median DRRT dose was 69.6 Gy (18 – 7...
Surgical treatment of pelvic sarcoma involving the bone is the standard of care but is associated... more Surgical treatment of pelvic sarcoma involving the bone is the standard of care but is associated with several sequelae and reduced functional quality of life (QOL). Treatment with photon and proton radiotherapy is associated with relapse. Carbon ion radiotherapy (CIRT) may reduce both relapse rates and treatment sequelae. The PROSPER study is a tricontinental, nonrandomized, prospective, three-arm, pragmatic trial evaluating treatments of pelvic sarcoma involving the bone. Patients aged at least 15 years are eligible for inclusion. Participants must have an Eastern Cooperative Oncology Group Performance Status score of two or less, newly diagnosed disease, and histopathologic confirmation of pelvic chordoma, chondrosarcoma, osteosarcoma, Ewing sarcoma with bone involvement, rhabdomyosarcoma (RMS) with bone involvement, or non-RMS soft tissue sarcoma with bone involvement. Treatment arms include (1) CIRT (n = 30) delivered in Europe and Asia, (2) surgical treatment with or without a...
The purpose of this work is to investigate collimating individual proton beamlets from a dosimetr... more The purpose of this work is to investigate collimating individual proton beamlets from a dosimetric perspective and to introduce a new device concept, the spot scanning aperture (SSA). The SSA consists of a thin aperture with a small cylindrical opening attached to a robotics system, which allows the aperture to follow and align with individual beamlets during spot delivery. Additionally, a range shifter is incorporated (source-side) for treating shallow depths. Since the SSA trims beamlets spot by spot, the patient-facing portion of the device only needs to be large enough to trim a single proton beamlet. The SSA has been modelled in an open-source Monte-Carlo-based dose engine (MCsquare) to characterize its dosimetric properties in water at depths between 0 and 10 cm while varying the following parameters: the aperture material, thickness, distance to the water phantom, distance between the aperture and attached range shifter, and the aperture opening radius. Overall, the SSA grea...
BackgroundIn proton therapy dose calculation, Monte Carlo (MC) simulations are superior in accura... more BackgroundIn proton therapy dose calculation, Monte Carlo (MC) simulations are superior in accuracy but more time consuming, compared to analytical calculations. Graphic processing units (GPUs) are effective in accelerating MC simulations but may suffer thread divergence and racing condition in GPU threads that degrades the computing performance due to the generation of secondary particles during nuclear reactions.PurposeA novel concept of virtual particle (VP) MC (VPMC) is proposed to avoid simulating secondary particles in GPU‐accelerated proton MC dose calculation and take full advantage of the computing power of GPU.MethodsNeutrons and gamma rays were ignored as escaping from the human body; doses of electrons, heavy ions, and nuclear fragments were locally deposited; the tracks of deuterons were converted into tracks of protons. These particles, together with primary and secondary protons, are considered to be the realistic particles. Histories of primary and secondary protons ...
BackgroundBoth dose and linear energy transfer (LET) could play a substantial role in adverse eve... more BackgroundBoth dose and linear energy transfer (LET) could play a substantial role in adverse event (AE) initialization of cancer patients treated with pencil‐beam‐scanning (PBS) proton therapy. However, not all the voxels within the AE regions are directly induced from the dose and LET effect. It is important to study the synergistic effect of dose and LET in AE initialization by only including a subset of voxels that are dosimetrically important.PurposeTo perform exploratory investigation of the dose and LET effects upon AE initialization in PBS using seed spots analysis.MethodsA total of 113 head‐and‐neck (H&N) cancer patients receiving curative PBS were included. Among them, 20 patients experienced unanticipated CTCAEv4.0 grade ≥3 AEs (AE group) and 93 patients did not (control group). Within the AE group, 13 AE patients were included in the seed spot analysis to derive the descriptive features of AE initialization and the remaining 7 mandible osteoradionecrosis patients and 93 ...
PurposeTo develop an online graphic processing unit (GPU)‐accelerated Monte Carlo‐based adaptive ... more PurposeTo develop an online graphic processing unit (GPU)‐accelerated Monte Carlo‐based adaptive radiation therapy (ART) workflow for pencil beam scanning (PBS) proton therapy to address interfraction anatomical changes in patients treated with PBS.Methods and MaterialsA four‐step workflow was developed using our in‐house developed GPU‐accelerated Monte Carlo‐based treatment planning system to implement online Monte Carlo‐based ART for PBS. The first step conducts diffeomorphic demon‐based deformable image registration (DIR) to propagate contours on the initial planning CT (pCT) to the verification CT (vCT) to form a new structure set. The second step performs forward dose calculation of the initial plan on the vCT with the propagated contours after manual approval (possible modifications involved). The third step triggers a reoptimization of the plan depending on whether the verification dose meets the clinical requirements or not. A robust evaluation will be done for both the veri...
PURPOSE Due to the employment of quadratic programming using soft constraints to implement dose v... more PURPOSE Due to the employment of quadratic programming using soft constraints to implement dose volume constraints and the "trial-and-error" procedure needed to achieve a clinically acceptable plan, conventional dose volume constraints (upper limit) are not adequately effective in controlling small and isolated hot spots in the dose/linear energy transfer (LET) distribution. Such hot spots can lead to adverse events. In order to mitigate the risk of brain necrosis, one of the most clinically significant adverse events in patients receiving intensity-modulated proton therapy (IMPT) for base of skull (BOS) cancer, we propose per-voxel constraints to minimize hot spots in LET-guided robust optimization. METHODS AND MATERIALS Ten BOS cancer patients treated with IMPT were carefully selected by meeting one of the following conditions: 1) diagnosis of brain necrosis during follow-up; 2) considered high risk for brain necrosis by not meeting dose constraints to the brain. An optimizing structure (BrainOPT) and an evaluating structure (BrainROI) that both contained the aforementioned hot dose regions in the brain were generated for optimization and evaluation, respectively. Two plans were generated for every patient: one using conventional dose-only robust optimization, the other using LET-guided robust optimization. The impact of LET was integrated into the optimization via a term of extra biological dose (xBD). A novel optimization tool of per-voxel constraints to control small and isolated hot spots in either the dose, LET, or combined (dose/LET) distribution was developed and used to minimize dose/LET hot spots of the selected structures. Indices from dose-volume histogram (DVH) and xBD dose-volume histogram (xBDVH) were used in the plan evaluation. A newly developed tool of the dose-LET-volume histogram (DLVH) was also adopted to illustrate the underlying mechanism. Wilcoxon signed-rank test was used for statistical comparison of the DVH and xBDVH indices between the conventional dose-only and the LET-guided robustly optimized plans. RESULTS Per-voxel constraints effectively and efficiently minimized dose hot spots in both dose-only and LET-guided robust optimization and LET hot spots in LET-guided robust optimization. Compared to the conventional dose-only robust optimization, the LET-guided robust optimization could generate plans with statistically lower xBD hot spots in BrainROI (VxBD,50Gy[RBE], P = 0.009; VxBD,60Gy[RBE], P = 0.025; xBD1cc, P = 0.017; xBD2cc, P = 0.022) with comparable dose coverage, dose hot spots in the target, and dose hot spots in BrainROI. DLVH analysis indicated that LET-guided robust optimization could either reduce LET at the same dose level or redistribute high LET from high dose regions to low dose regions. CONCLUSION Per-voxel constraint is a powerful tool to minimize dose/LET hot spots in IMPT. The LET-guided robustly optimized plans outperformed the conventional dose-only robustly optimized plans in terms of xBD hot spots control. This article is protected by copyright. All rights reserved.
PURPOSE To evaluate the accuracy of the RayStation Monte Carlo dose engine (RayStation MC) in mod... more PURPOSE To evaluate the accuracy of the RayStation Monte Carlo dose engine (RayStation MC) in modeling small-field block apertures in proton pencil beam scanning. Furthermore, we evaluate the suitability of MCsquare as a 2nd check for RayStation MC. METHODS We have enhanced MCsquare to model block apertures. To test the accuracy of both RayStation MC and the newly enhanced MCsquare, we compare the dose predictions of each to in-water dose measurements obtained using diode detectors and radiochromic film. Nine brass apertures with openings of 1, 2, 3, 4, and 5 cm and either 2 cm or 4 cm thickness were used in the irradiation of a water phantom. Two measurement setups were used, one with a range shifter and 119.7 MeV proton beam energy and the other with no range shifter and 147 MeV proton beam energy. To further test the validity of RayStation MC and MCsquare in modeling block apertures and to evaluate MCsquare as a 2nd check tool, ten small-field (average target volume 8.3 cm3 ) patient treatment plans were calculated by each dose engine followed by a statistical comparison. RESULTS Comparing to the absolute dose measurements in water, RayStation MC differed by 1.2% ± 1.0% while MCsquare differed by -1.8% ± 3.7% in the plateau region of a pristine Bragg peak. Compared to the in-water film measurements, RayStation MC and MCsquare both performed well with an average 2D-3D gamma passing rate of 99.4% and 99.7% (3%/3mm) respectively. A t-test comparing the agreement with the film measurements between RayStation MC and MCsquare suggested that the relative spatial dose distributions calculated by MCsquare and RayStation MC were statistically indistinguishable. Directly comparing the dose calculations between MCsquare and RayStation MC over ten patients resulted in an average 3D-3D gamma passing rates of 98.5% (3%/3mm) and 94.1% (2%/2mm) respectively. CONCLUSION The validity of RayStation MC algorithm for use with patient-specific apertures has been expanded to include small apertures. MCsquare has been enhanced to model apertures and was found to be an adequate 2nd check of RayStation MC in this scenario. This article is protected by copyright. All rights reserved.
ObjectiveDiagnostic delay in human papillomavirus–associated oropharynx squamous cell carcinoma (... more ObjectiveDiagnostic delay in human papillomavirus–associated oropharynx squamous cell carcinoma (HPV(+)OPSCC) is common due to nonspecific symptoms. We aim to describe the disease burden and oncologic outcomes of patients with HPV(+)OPSCC diagnosed >12 months after symptom onset.Study DesignThis is a retrospective cohort study of HPV(+)OPSCC patients receiving intent‐to‐cure treatment (including surgery ± adjuvant therapy or primary chemoradiation).Setting2006‐2016, tertiary care center.MethodsTumor stage was compared between patients with and without delayed diagnosis using χ2 tests. Kaplan‐Meier survival analysis with univariate and multivariable Cox regressions were used to determine the effect of diagnostic delay on oncologic outcomes.ResultsIn total, 664 patients were included. Compared to patients diagnosed <12 months from symptom onset (n = 601), those diagnosed at >12 months (n = 63) were more likely to have T4 disease and higher overall American Joint Committee on ...
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