Beam Therapy Research Articles

Optimizing focused very-high-energy electron beams for radiation therapy based on Monte Carlo simulation.

A TOPAS-based optimization program has been developed to precisely concentrate the dose of focused very-high-energy electron (VHEE) beams on deep-seated targets. This is accomplished by optimizing the magnetic gradients, positions, and number of quadrupole magnets within TOPAS. Using only three quadrupole magnets, the program focuses 250MeV VHEE beams to achieve a maximum dose position deeper than 17cm, while maintaining entrance and exit doses within 25% and limiting the lateral dimensions to ≤ 1cm at the maximum dose location. The linear relationship between the magnetic gradient of the last quadrupole magnet and the maximum dose position enables dose location adjustments through gradient variation. Multiple positions were validated in TOPAS with errors within 1%. The spread-out electron peak (SOEP) is achieved by combining two VHEE beams with different maximum dose positions using the differential evolution method, covering a target depth of 12-17cm and attaining a dose flatness better than 99%. This pioneering program imposes constraints on entrance dose, exit dose, maximum dose position, and the lateral dimensions of dose deposition at the maximum dose position within phantom. This program may be a promising tool in the applications of focused VHEE in highly conformal treatment plans based on TOPAS.

Significant Effect of Carbon-Ion Radiation Therapy Combined With Androgen Deprivation on Biochemical Recurrence Rates in High-Risk Prostate Cancer Patients: A Two-Center Controlled Trial Compare With X-Ray External Beam Radiation Therapy.

To compare the effects of carbon-ion radiation therapy (CIRT) and external beam radiotherapy (EBRT) on the prognosis of patients with prostate cancer. The effects of initial prostate-specific antigen (iPSA), clinical Tumor (cT) stage, radiotherapy method, and other clinical factors on the prognosis of 577 patients with radiotherapy were analyzed. Cox regression analysis showed that CIRT (RR: 0.49, p = 0.0215), cT stage ≥ 3 (RR: 2.72, p = 0.0003), and iPSA ≥ 16 ng/mL (RR: 1.74, p = 0.0347) were independent predictors of biochemical recurrence (BCR). After propensity score matching (PSM), CIRT (RR: 0.42, p = 0.0147), cT stage ≥ 3 (RR: 2.55, p = 0.0092), and iPSA ≥ 16 ng/mL (RR: 2.12, p = 0.0366) were still the predictors of univariate analysis. In multivariate analysis, CIRT (RR: 0.42, p = 0.015) and cT stage≥ 3 (RR:2.21, p = 0.0332) were independent predictors of BCR. Among them, we used iPSA and cT stages to establish a new radiotherapy selection model based on BCR risk. Patients who met more than one factor (score ≥ 1) and underwent CIRT had significantly better BCR progression-free survival (PFS) than those who received EBRT (p ≤ 0.01). This was also confirmed by Kaplan-Meier analysis after PSM. CIRT patients exhibited lower 5-year BCR rates compared to the EBRT group. Patients with a risk score of our model ≥ 1 undergoing CIRT were more likely to experience BCR benefits compared to those receiving EBRT.

Assessment of pencil beam scanning proton therapy beam delivery accuracy through machine learning and log file analysis

PurposeComprehensive Quality Assurance (QA) protocols are necessary for complex beam delivery systems like Pencil Beam Scanning (PBS) proton therapy. This study focuses on automating the evaluation of beam delivery accuracy using irradiation log files and machine learning (ML) models. MethodsIrradiation log files of 935 clinical treatment fields and routine QA beams were analysed to evaluate spot parameters and Monitor Unit (MU) accuracy. ML models predicted spot size along the X, Y, major, and minor axes. In-house scripts automated log file analysis and spot size predictions. Predicted spot sizes were compared with expected baselines, and the accuracy of spot position, symmetry, and MU for each spot in the beam was evaluated. ResultsMore than 99.5 % of spot positions were accurate within a 1 mm. The mean and Standard Deviation (SD) of X positional error were −0.021 mm (SD: 0.181 mm), and for Y positional error, they were −0.002 mm (SD: 0.132 mm). ML models accurately predicted spot sizes, with over 95 % of spots demonstrating size variations within 10 % of the baseline. The Root Mean Squared Error (RMSE) of X and Y spot size differences were 0.15 mm and 0.16 mm, respectively. Spot symmetry was within 10 %, and MU accuracy showed 95 % of spots with MU per spot variation less than 2 %. ConclusionThis method can validate the vendor’s beam delivery safety interlock system and serve as a quick alternative to patient-specific QA in adaptive treatment, where time is limited, as well as for routine QA spot parameter evaluations.

Dosimetry in MRgPT: Impact of magnetic fields on TLD dose response during proton irradiation.

Proton beam therapy, when integrated with MRI guidance, presents complex dosimetric challenges due to interactions with magnetic fields. Prior research has emphasized the nuanced impact of magnetic fields on dosimetry. For thermoluminescent dosimeters (TLDs) the electron-return effect, alongside small air cavities surrounding the pellets, can lead to nonuniform dose distributions. Future MR-guided proton therapy will require reliable methods for end-to-end tests and dosimetric audits, which so far are often performed using TLDs equipped with phantoms. This implicates the necessity of accounting for theseinteractions. This study investigates the influence of magnetic fields on TLDs at two proton energies, using magnetic field strengths of 0, 0.25, and , aiming to clarify their impact on dose measurementaccuracy. The study was conducted at a synchrotron-based ion beam therapy beam line, enhanced by a resistive dipole magnet for creating magnetic fields up to to simulate MR-guided proton therapy. Individual correction factors were applied for TLD measurements. The impact of air gaps on the TLD signal was evaluated using three dedicated TLD holders with air gaps of 0.1, 0.25, and 0.5 mm surrounding the TLD pellets using the highest available proton energy of . Additionally, the influence of the magnetic field strength on the TLD response was evaluated for two proton energies of and . The study found no statistically significant variation in TLD dose response attributable to changes in the air gap or the presence of magnetic fields. A power analysis indicated an upper limit on a potential change in dose-response as small as 1.5%. The findings suggested that the impact of air gap variations and magnetic field strengths on the TLD response was below the detection threshold of TLD sensitivity. This emphasizes the suitability of TLDs for dose measurement in MR-guided proton therapy, indicating that additional correction factors may not be necessary despite the influence of magneticfields.

Real-time measurement of two-dimensional LET distributions of proton beams using scintillators.


The linear energy transfer (LET) of proton therapy beams increases rapidly from the Bragg peak to the end of the beam. Although the LET can be determined using analytical or computational methods, a technique for efficiently measuring its spatial distribution has not yet been established. Thus, the purpose of this study is to develop a technique to measure the two-dimensional LET distribution in proton therapy in real time using a combination of multiple scintillators with different quenching. Inorganic and organic scintillator sheets were layered and irradiated with proton beams. Two-color signals of the CMOS sensor were obtained from the scintillation light and calibration curves were generated using LET. LET was calculated using Monte Carlo simulations as LETt and LETd weighted by fluence and dose, respectively. The accuracy of the calibration curve was evaluated by comparing the calculated and measured LET values for the 200 MeV monoenergetic and spread-out Bragg peak (SOBP) beams. LET distributions were obtained from the calibration curves.
Main results:
The deviation between the calculated and measured LET values was evaluated. For both LETt and LETd, the deviation in the plateau region of the monoenergetic and SOBP beams tended to be larger than those in the peak region. The deviation was smaller for LETd. In the obtained LETd distribution, the deviation between the calculated and measured values agreed within 3% in the peak region, while the deviation was larger in other regions. The LET distribution can be measured with a single irradiation using two scintillator sheets. This method may be effective for verifying LET in daily clinical practice and for quality control.&#xD.

Characterization of a real time dosimetry system using 2D nano and micro-coatings in proton and carbon therapeutic ion beams

Real-time radioluminescence two-dimensional coatings have potential as dosemeters in proton and carbon therapeutic beams. We investigated coatings made of nano and micro-(C44H38P2)MnCl4 and (C38H36P2)MnBr4 crystals mixed with a water-equivalent substrate. The response of the radioluminescence signal of the coatings along the Bragg curves presented an ionization quenching effect, but less prominent than what has been observed in our previous works using Al2O3:X (X = C and C,Mg) coatings. We hypothesize that this results from their lower crystal sizes and effective atomic number (Zeff). Combined experimental results and Monte Carlo simulations resulted in correction factors to address the linear energy transfer dependence and restore the constant response for particle therapy beams. The quenching correction method was applied to the studied proton and carbon ion beams and yielded the best results for the nano-(C44H38P2)MnCl4, coating, followed by the micro-(C44H38P2)MnCl4, nano-(C38H36P2)MnBr4, and micro-(C38H36P2)MnBr4.

A pictographic guide for decision making in surgery for pelvic bone sarcoma

Pelvic bone sarcoma surgery is challenging due to complex anatomy, proximity to major neurovascular structures, and, more importantly, the potential for complications. Decision-making is vital in offering patients the best oncological and functional outcomes after surgery. Multidisciplinary teams involved from the stage of diagnosis and treatment planning, followed by surgery by experienced teams have proven to be beneficial. Tumour-free margin clearance is essential, and surgical planning must be tailored to achieve the same. The choice of reconstruction needs to be decided based on the amount of bone resected and the available expertise and resources. Lesions isolated only to PI or PIII region may not need reconstruction. Though pedestal cups and Custom-made prosthesis are useful in reconstruction after periacetabular tumour resections, hip transposition surgery is also widely practiced by surgeons with favourable outcomes particularly after neo-adjuvant radiotherapy/proton beam therapy. Navigation has shown promise in achieving tumour-negative margins and disease-free progression particularly in chondrosarcoma. A flap-based approach can be considered for hindquarter amputations; however, patients need to be counseled regarding the complications following this surgery. This article, with proposed flowcharts, is aimed at providing practicing surgeons with a guide toward decision-making while planning pelvic bone sarcoma surgery.

Setting the Stage: Feasibility and Baseline Characteristics in the PARTIQoL Trial Comparing Proton Therapy Versus Intensity Modulated Radiation Therapy for Localized Prostate Cancer

Men with localized prostate cancer may receive either photon-based intensity modulated radiation therapy (IMRT) or proton beam therapy (PBT). The PARTIQoL trial (NCT01617161) demonstrates the feasibility of performing a large, multicenter phase 3 randomized trial comparing IMRT with PBT for localized prostate cancer. Here, we report baseline features of patients enrolled on this trial and present strategies to improve feasibility of other similar trials. Patients with low- or intermediate-risk prostate cancer were randomly assigned to either PBT or IMRT with stratification by institution, age, use of rectal spacer, and fractionation schedule (conventional fractionation: 79.2 Gy in 44 fractions vs moderate hypofractionation: 70.0 Gy in 28 fractions). The primary endpoint is a change from baseline bowel health using the Expanded Prostate Index Composite score 24 months after radiation therapy. Secondary objectives include treatment-related differences in urinary and erectile functions, adverse events, and efficacy endpoints. Between July 2012 and November 2021, 450 patients were successfully accrued. Patients were randomly assigned to either PBT (N = 226) or to IMRT (N = 224); 13 were ineligible or withdrew before treatment. The median age of 437 analyzed patients was 68 years (range, 46-89 years). A total of 41% of patients had low-risk and 59% had intermediate-risk disease. In total, 49% of patients were treated with conventional fractionation and 51% with moderately hypofractionation. 48% of patients used a rectal spacer. For patients receiving PBT, pencil beam scanning was used in 48%. PBT and IMRT arms were balanced for baseline variables. Despite significant challenges, the PARTIQoL trial demonstrated that, with targeted recruitment approaches, multicenter collaboration, payer engagement, and protocol updates to incorporate contemporary techniques, it is feasible to perform a large phase 3 randomized clinical trial to assess whether PBT improves outcomes. We will separately report primary results and continue to monitor participants for longer follow-up and secondary endpoints.

Microdosimetric measurements for LET monitoring in proton therapy. The development of engineered mini-TEPCs for clinical applications: First results

Innovative Treatment Planning Systems (TPS) in proton therapy based on a variable radiation quality with depth with respect to the conventional one with a fixed Relative Biological Effectiveness (RBE) of 1.1 are under study. Experimental methods are needed to verify the consistency between what is planned and what is delivered in terms of radiation quality. Microdosimetry studies the stochastics of the energy deposition process at micrometric and sub-micrometric level which is known to be related to the biological effectiveness of ionising radiation fields. For this reason, it is recognised by the scientific community that it is a useful tool to monitor the radiation quality of hadron therapy beams where the effectiveness varies with the penetration depth in patients. Detectors are needed to perform a microdosimetric characterization of a clinical beam and they need to satisfy specific requirements to enter the clinical practice as instruments for the Quality Assurance (QA). With this aim, at the Legnaro National Laboratories of the Italian National Institute for Nuclear Physics (LNL-INFN) a technological transfer project was carried out with the final goal of developing engineered miniaturized Tissue Equivalent Proportional Counters (mini-TEPCs) for clinical applications. This work presents the characterization performed on the new detectors and the results obtained in neutron and proton fields.

In Silico Comparison of Three Different Beam Arrangements for Intensity-Modulated Proton Therapy for Postoperative Whole Pelvic Irradiation of Prostate Cancer.

Background and purpose: Proton therapy has been shown to provide dosimetric benefits in comparison with IMRT when treating prostate cancer with whole pelvis radiation; however, the optimal proton beam arrangement has yet to be established. The aim of this study was to evaluate three different intensity-modulated proton therapy (IMPT) beam arrangements when treating the prostate bed and pelvis in the postoperative setting. Materials and Methods: Twenty-three post-prostatectomy patients were planned using three different beam arrangements: two-field (IMPT2B) (opposed laterals), three-field (IMPT3B) (opposed laterals inferiorly matched to a posterior-anterior beam superiorly), and four-field (IMPT4B) (opposed laterals inferiorly matched to two posterior oblique beams superiorly) arrangements. The prescription was 50 Gy radiobiological equivalent (GyE) to the pelvis and 70 GyE to the prostate bed. Comparisons were made using paired two-sided Wilcoxon signed-rank tests. Results: CTV coverages were met for all IMPT plans, with 99% of CTVs receiving ≥ 100% of prescription doses. All organ at risk (OAR) objectives were met with IMPT3B and IMPT4B plans, while several rectum objectives were exceeded by IMPT2B plans. IMPT4B provided the lowest doses to OARs for the majority of analyzed outcomes, with significantly lower doses than IMPT2B +/- IMPT3B for bladder V30-V50 and mean dose; bowel V15-V45 and mean dose; sigmoid maximum dose; rectum V40-V72.1, maximum dose, and mean dose; femoral head V37-40 and maximum dose; bone V40 and mean dose; penile bulb mean dose; and skin maximum dose. Conclusion: This study is the first to compare proton beam arrangements when treating the prostate bed and pelvis. four-field plans provided better sparing of the bladder, bowel, and rectum than 2- and three-field plans. The data presented herein may help inform the future delivery of whole pelvis IMPT for prostate cancer.

Using Scorecards to Tune Ethos Directive Templates: An Adaptive Radiation Therapy Individualized Approach-Cervix Dosimetric Planning Study

The Adaptive Radiation Therapy Individualized Approach-Cervix clinical trial uses predefined clinical directive templates (CDTs) combined with RapidPlan dose-volume histogram estimations (DVHe) to guide plan optimization in the Ethos treatment planning system. The dosimetric scorecard is a scoring tool that quantifies improvements in plan quality after physicians have precisely expressed their complete clinical intent. To our knowledge, this is the first study to use the dosimetric scorecard tool to tune an Ethos CDT to improve resulting plan quality. Iterative replanning was used to modify the draft CDT (CDT-1) in Ethos 1.1 to generate a new CDT (CDT-2) that maximized the clinical consensus scorecard's total score compared with CDT-1. CDT-2 was established, and resulting plans were compared with and without a DVHe. Additional fixed field intensity modulated radiation therapy beam geometries were compared between CDT-1 and CDT-2, both with DVHe. After obtaining favorable results when comparing CDT-1 versus CDT-2 for 2 test cases, 10 additional cases were retrospectively identified and tested. CDT-2 reduced organ at risk doses without compromising planning target volume coverage in the initial test cases. When combined with DVHe, CDT-2 marginally outperformed CDT-1. Plan quality further improved with a 19-field geometry. In the expanded analysis, CDT-2 achieved higher scores than CDT-1 in most cases, with the 19-field approach showing superiority. Optimization and calculation time increased by 1.9 minutes, monitor unit (MU)/field decreased by 44.4, whereas beam-on time increased by 2.8 minutes when increasing fields to 19 from 9. Reoptimization with Ethos 1.1 Maintenance Release 1 resulted in decreased MU and minimal score changes. The scorecard is an effective tool to adjust an Ethos CDT to improve the average calculated plan quality. It also allowed for easy evaluation of the dosimetric impact of other planning parameters (beam arrangements and use of DVHe) to identify the best approach. Using a finely tuned CDT is expected to improve planning efficiency and decrease intrainstitutional plan quality variability, benefiting cone beam computed tomography-guided adaptive radiation therapy.

Recurrent Axis Chordoma after Carbon ion Therapy Necessitating Reconstructive Surgery with Osteocutaneous Radial Forearm Free Flap: A Case Report

AbstractChordomas originate from remnant tissue of the notochord during embryonic development, with a relatively low incidence rate. Furthermore, chordomas, being resistant to radiotherapy, are primarily treated by resection; however, in some cases, particularly in those that involve the skull base or upper cervical spine, chordomas are unresectable. In recent years, carbon ion/proton beam therapy has shown significant efficacy in such cases. However, it is not sufficiently curative and is commonly associated with recurrence. Moreover, there is no consensus regarding the treatment of recurrent cases, resulting in several uncertainties pertaining to it. Here, we present the case of a 55-year-old male patient with axial chordoma who experienced recurrence after carbon ion therapy and underwent tumor reduction surgery for a longer life span. Two months postoperatively, dehiscence was found in the posterior pharyngeal wall, probably due to heavy ion therapy. Salvage surgery was performed using an osteocutaneous radial forearm free flap, and the patient's postoperative course was uneventful.

Hypofractionated proton and carbon ion beam radiotherapy for sacrococcygeal chordoma (ISAC): An open label, randomized, stratified, phase II trial

IntroductionSacrococcygeal chordomas have high recurrence rates and are challenging to treat. MethodsIn this phase II prospective, randomized, stratified trial, the safety and feasibility of hypofractionated ion radiation therapy were investigated. The primary focus was monitored through the incidence of Grade 3–5 NCI-CTC-AE toxicity. Secondary endpoints included local progression-free (LPFS) and overall survival (OS). ResultsThe study enrolled 82 patients with primary (87 %) and recurrent (13 %) inoperable or incompletely resected sacral chordomas from January 2013 to July 2022, divided equally into proton therapy (Arm A) and carbon ion beam therapy (Arm B) groups, each receiving a total dose of 64 Gy (RBE) in 16 fractions, 5–6 fractions per week. Overall 74 % of patients received no previous surgery and 66 % of tumors were confirmed by a brachyury staining. The mean and median Gross Tumor Volume at the time of treatment (GTV) was 407 ml and 185 ml, respectively. The median follow-up of the surviving patients was 44.7 months, and the 2-year and 4-year OS rates were 96 % and 81 %, respectively. Factors such as smaller GTV and younger age trended towards better OS. The LPFS after 2-year and 4-year was 84 % and 70 %, respectively. Male gender emerged as a significant predictor of LPFS. There was no significant difference between the treatment groups. We observed five grade 4 wound healing disorders (6 %). ConclusionThe initial response rates were promising; however local control was not sustained. More comparative research on fractionation schemes is essential to refine treatment approaches for inoperable sacral chordoma.

A Bibliometric Analysis of the 20 Most Cited Articles on Sacrococcygeal Chordomas.

This study aims to summarize sacrococcygeal chordoma literature through bibliometric analysis and to offer insights into key studies to guide clinical practices and future research. The Web of Science database was searched using the terms "sacral chordoma", "chordomas of the sacrum", "chordomas of the sacral spine", "chordomas of the sacrococcygeal region", "coccygeal chordoma", and "coccyx chordoma". Articles were analyzed for citation count, authorship, publication date, journal, research area tags, impact factor, and evidence level. The median number of citations was 75 (range: 53-306). The primary publication venue was the International Journal of Radiation Oncology, Biology, Physics. Most works, published between 1999 and 2019, featured a median journal impact factor of 3.8 (range: 2.1-7) and predominantly fell under the research area tag, radiation, nuclear medicine, and imaging. Of these articles, 19 provided clinical data with predominantly level III evidence, and one was a literature review. This review highlights the increasing volume of sacrococcygeal chordoma publications over the past two decades, indicating evolving treatment methods and interdisciplinary patient care. Advances in radiation, particularly intensity-modulated radiation therapy (IMRT) and proton beam therapy, are believed to be propelling research growth, and the lack of level I evidence underscores the need for more rigorous studies to refine treatment protocols for sacrococcygeal chordomas.

Stereotactic body radiation therapy (SBRT) for prostate cancer: Improving treatment delivery efficiency and accuracy

PurposeIn stereotactic body radiation therapy (SBRT) for prostate cancer, intrafraction motion is an important source of treatment uncertainty as it could not be completely smoothed through fractionation. Herein, we compared different arrangements and beam qualities for extreme hypofractionated treatments to minimize beam delivery time and so intrafractional errors. MethodsA retrospective dataset of 11 patients was used. Three volumetric modulated arc therapy (VMAT) beam arrangements were compared for a prescription dose of 40 Gy/5 fractions: two full arcs, 6 MV flattening filter free (FFF); one full arc, 6 MV FFF; one full arc, 10 MV FFF. A plan quality index was defined to compare achievement of the planning goals. Plan complexity was evaluated with the modulation factor. Dose delivery accuracy and efficiency were measured with patient-specific quality assurance plans. ResultsAll treatment plans fulfilled all dose objectives. No statistical differences were found both in plan quality and complexity. Very accurate dose delivery was achieved with the three arrangements, with mean γ passing rates >96.5 % (2 %/2 mm criteria). Slightly but significantly higher γ passing rates were observed with single-arc 6 MV FFF. Contrariwise, statistically significant reductions of the delivery time were obtained with single-arc geometries: the average delivery times were 1.6 min (−46.1 %) and 1.3 min (−56.2 %) for 6 and 10 MV FFF respectively. ConclusionsThe high-quality, very fast and accurate dose delivery of single-arc plans confirmed the suitability of this arrangement for prostate SBRT. In particular, the significant reduction of delivery time would improve treatment robustness against intrafraction prostate motion.

Reduced Risk of Severe Radiation-Induced Lymphopenia in Carbon Ion Radiation Therapy for Locally Advanced Pancreatic Cancer: A Comparative Analysis of Carbon Versus Photon Therapy

Radiation-induced lymphopenia (RIL) is associated with poor prognosis in patients with locally advanced pancreatic cancers. However, there are no reports comparing the effects of carbon ion radiation therapy (CIRT) and photon beam radiation therapy (RT) on the development of RIL. Differences in RIL after CIRT or photon beam RT and predictive factors for RIL in patients with locally advanced pancreatic cancer were investigated. This retrospective study cohort included 834 patients who received concurrent chemoradiotherapy (CCRT) in 2 separate institutions: 337 and 497 in the CIRT and photon beam RT groups, respectively. Severe RIL was defined as an absolute lymphocyte count (ALC) <0.5 × 109 cells/L. A 1:1 propensity score-matching analysis was performed between the CIRT and photon beam RT groups. Patients were categorized into 3 groups according to the development of recovery from severe RIL: no severe RIL (Group A), recovery from severe RIL (Group B), and no recovery from severe RIL (Group C). Logistic regression analysis was performed to identify the predictive value of severe RIL. The prognostic factors of overall survival (OS) were determined using Cox regression analysis. After propensity score matching, the baseline ALC and planning target volume of the CIRT and photon beam RT groups were comparable. During CCRT, the ALC of the entire cohort decreased and was significantly lower in the photon beam RT group than in the CIRT group (P < .001). Multivariate logistic regression analysis showed that CIRT reduced severe RIL more than photon beam RT. After adjusting for other factors, the RT modality and RIL were significantly associated with OS. Photon beam RT showed a significantly worse OS than CIRT, and Group C showed a significantly worse OS than Group A. CIRT seems to reduce the development of severe RIL. The RT modality and development/recovery from severe RIL were associated with OS in patients who received CCRT for locally advanced pancreatic cancer. The reduction of severe RIL through optimized RT may be essential for improving treatment outcomes.

Probability of normal tissue complications for hematologic and gastrointestinal toxicity in postoperative whole pelvic radiotherapy for gynecologic malignancies using intensity-modulated proton therapy with robust optimization.

This retrospective treatment-planning study was conducted to determine whether intensity-modulated proton therapy with robust optimization (ro-IMPT) reduces the risk of acute hematologic toxicity (H-T) and acute and late gastrointestinal toxicity (GI-T) in postoperative whole pelvic radiotherapy for gynecologic malignancies when compared with three-dimensional conformal radiation therapy (3D-CRT), intensity-modulated X-ray (IMXT) and single-field optimization proton beam (SFO-PBT) therapies. All plans were created for 13 gynecologic-malignancy patients. The prescribed dose was 45 GyE in 25 fractions for 95% planning target volume in 3D-CRT, IMXT and SFO-PBT plans and for 99% clinical target volume (CTV) in ro-IMPT plans. The normal tissue complication probability (NTCP) of each toxicity was used as an in silico surrogate marker. Median estimated NTCP values for acute H-T and acute and late GI-T were 0.20, 0.94 and 0.58 × 10-1 in 3D-CRT; 0.19, 0.65 and 0.24 × 10-1 in IMXT; 0.04, 0.74 and 0.19 × 10-1 in SFO-PBT; and 0.06, 0.66 and 0.15 × 10-1 in ro-IMPT, respectively. Compared with 3D-CRT and IMXT plans, the ro-IMPT plan demonstrated significant reduction in acute H-T and late GI-T. The risk of acute GI-T in ro-IMPT plan is equivalent with IMXT plan. The ro-IMPT plan demonstrated potential clinical benefits for reducing the risk of acute H-T and late GI-T in the treatment of gynecologic malignances by reducing the dose to the bone marrow and bowel bag while maintaining adequate dose coverage to the CTV. Our results indicated that ro-IMPT may reduce acute H-T and late GI-T risk with potentially improving outcomes for postoperative gynecologic-malignancy patients with concurrent chemotherapy.

Voxel-Level Dosimetry for Combined Iodine 131 Radiopharmaceutical Therapy and External Beam Radiation Therapy Treatment Paradigms for Head and Neck Cancer

PurposeTargeted radiopharmaceutical therapy (RPT) in combination with external beam radiotherapy (EBRT) shows promise as a method to increase tumor control and mitigate potential high-grade toxicities associated with re-treatment for patients with recurrent head and neck cancer. This work establishes a patient-specific dosimetry framework that combines Monte Carlo based dosimetry from the two radiation modalities at the voxel level using deformable image registration (DIR) and radiobiological constructs for patients enrolled in a phase I clinical trial combining EBRT and RPT. MethodsSerial SPECT/CT patient scans performed at approximately 24, 48, 72, and 168 hours post-injection of 577.2 MBq/m2 (15.6 mCi/m2) iodine-131 containing RPT agent called XXX 131. Clinical EBRT treatment plans were created on a treatment planning CT (TPCT) using RayStation; SPECT/CT images were deformably registered to the TPCT using the Elastix DIR module in 3D Slicer and assessed by measuring mean activity concentrations and absorbed doses. Monte Carlo EBRT dosimetry was computed using EGSnrc. RPT dosimetry was conducted using a GEANT4 based RPT dosimetry platform named XXX. Radiobiological metrics (BED, EQD2) were utilized to combine the two radiation modalities. ResultsThe DIR method provided good agreement for the activity concentrations and calculated absorbed dose in the tumor volumes for the SPECT/CT and TPCT; the maximum mean absorbed dose difference was -11.2%. Based on the RPT absorbed dose calculations, two to four EBRT fractions were removed from patients’ EBRT treatments. From the combined treatment, the absorbed dose to target volumes ranged from 57.14 – 75.02 Gy. When including partial volume corrections (PVC), the mean EQD2 to the PTV from EBRT+RPT was -3.11% to 1.40% different compared to EBRT alone. ConclusionThis work demonstrated the clinical feasibility of performing combined EBRT+RPT dosimetry on TPCTs. Dosimetry guides treatment decisions for EBRT and this work provides a bridge for the same paradigm to be implemented within the rapidly emerging clinical RPT space.

Disease and toxicity outcomes for a modern cohort of patients with squamous cell carcinoma of cutaneous origin involving the parotid gland: Comparison of volumetric modulated arc therapy and pencil beam scanning proton therapy

ObjectivesWe sought to describe outcomes for locally advanced cutaneous squamous cell carcinoma (SCC) involving the parotid treated with volumetric modulated arc therapy (VMAT) versus pencil beam scanning proton beam therapy (PBT). Materials and MethodsPatients were gathered from 2016 to 2022 from 5 sites of a large academic RT department; included patients were treated with RT and had parotid involvement by: direct extension of a cutaneous primary, parotid regional spread from a previously or contemporaneously resected but geographically separate cutaneous primary, or else primary parotid SCC (with a cutaneous primary ostensibly occult). Acute toxicities were provider-reported (CTCAE v5.0) and graded at each on treatment visit. Statistical analyses were conducted. ResultsMedian follow-up was 12.9 months (1.3 – 72.8); 67 patients were included. Positive margins/extranodal extension were present in 34 cases; gross disease in 17. RT types: 39 (58.2 %) VMAT and 28 (41.8 %) PBT. Concurrent systemic therapy was delivered in 10 (14.9 %) patients. There were 17 treatment failures (25.4 %), median time of 168 days. Pathologically positive neck nodes were associated with locoregional recurrence (p = 0.015). Oral cavity, pharyngeal constrictor, and contralateral parotid doses were all significantly lower for PBT. Median weight change was −3.8 kg (-14.1 – 5.1) for VMAT and −3 kg (-16.8 – 3) for PBT (p = 0.013). Lower rates of ≥ grade 1 xerostomia (p = 0.002) and ≥ grade 1 dysguesia (p < 0.001) were demonstrated with PBT. ConclusionsCutaneous SCC involving the parotid can be an aggressive clinical entity despite modern multimodal therapy. PBT offers significantly lower dose to organs at risk compared to VMAT, which seemingly yields diminished acute toxicities.

Evaluation of superficial xenograft volume estimation by ultrasound and caliper against MRI in a longitudinal pre-clinical radiotherapeutic setting.

Accurate tumor volume estimation is important for evaluating the response to radionuclide therapy and external beam radiotherapy as well as to other pharmaceuticals. A common method for monitoring the growth of subcutaneous tumors in pre-clinical models and assessing the treatment response is to measure the tumor length and width by external calipers to estimate its volume. This procedure relies on an assumption of a spheroidal tumor shape wherein the tumor depth equals the width and can yield considerably inaccuracies. Ultrasound imaging is a non-invasive technique that can measure all three axes of the tumor and might be an alternative to caliper measurement with potentially greater accuracy and comparable ease-of-use and throughput. Both 2D and 3D ultrasound imaging are possible, the former offering short scan times without the need for anesthesia and heating-valuable factors for longitudinal studies in large animal cohorts. Nevertheless, tumor volume estimation accuracy by 2D ultrasound imaging has seen limited investigation. In this study we have evaluated the accuracy of tumor volume estimation by caliper and 2D ultrasound with comparisons to reference measurements by magnetic resonance imaging (MRI) in a pre-clinical model of prostate cancer treated with either external beam radiotherapy, radionuclide therapy, or no treatment. Tumor volumes were measured longitudinally in 29 mice by caliper, ultrasound, and MRI before and after external beam radiotherapy, [177Lu]Lu-PSMA-617 radionuclide therapy, or no treatment. Caliper measurements had a marked bias, overestimating the tumor volumes by a median of 150% compared to MRI. Ultrasound measurements were markedly more accurate, with a median bias of -21% compared to MRI. Ultrasound imaging is a reliable and accurate method for tumor volume estimation in pre-clinical models of radiotherapy, whereas caliper measurements are prone to overestimation.