Conformal Treatment 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 250 MeV VHEE beams to achieve a maximum dose position deeper than 17 cm, while maintaining entrance and exit doses within 25% and limiting the lateral dimensions to ≤ 1 cm 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 12–17 cm 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.

Optimization of three-dimensional esophageal tumor ablation by simultaneous functioning of multiple electrodes.

Radiofrequency ablation is a widely accepted minimal-invasive and effective local treatment for tumors. However, its current application in esophageal cancer treatment is limited to targeting thin and superficial lesions, such as Barrett's Esophagus. This study proposes an optimization method using multiple electrodes simultaneously to regulate the temperature field and achieve conformal ablation of tumors. A particle swarm optimization algorithm, coupled with a three-dimensional thermal ablation model, was developed to optimize the status of the functioning electrodes, the optimal voltage (Vopt), and treatment duration (ttre) for targeted esophageal tumors. This approach takes into account both the electrical and thermal interactions of the electrodes. The results indicate that for esophageal cancers at various stages, with thickness (c) ranging from 4.5mm to 10.0mm, major axis (a) ranging from 7.3mm to 27.3mm, and minor axis (b) equaling 7.3mm or 27.3mm, as well as non-symmetrical geometries, complete tumor coverage (over 99.5%) close to conformal can be achieved. This method illustrates possible precise conformal ablation of esophageal cancers and it may also be used for conformal treatments of other intraluminal lesions.

Characterizing devices for validation of dose, dose rate, and LET in ultra high dose rate proton irradiations.

Ultra high dose rate (UHDR) radiotherapy using ridge filter is a new treatment modality known as conformal FLASH that, when optimized for dose, dose rate (DR), and linear energy transfer (LET), has the potential to reduce damage to healthy tissue without sacrificing tumor killing efficacy via the FLASH effect. Clinical implementation of conformal FLASH proton therapy has been limited by quality assurance (QA) challenges, which include direct measurement of UHDR and LET. Voxel DR distributions and LET spectra at planning target margins are paramount to the DR/LET-related sparing of organs at risk. We hereby present a methodology to achieve experimental validation of these parameters. Dose, DR, and LET were measured for a conformal FLASH treatment plan involving a 250-MeV proton beam and a 3D-printed ridge filter designed to uniformly irradiate a spherical target. We measured dose and DR simultaneously using a 4D multi-layer strip ionization chamber (MLSIC) under UHDR conditions. Additionally, we developed an "under-sample and recover (USRe)" technique for a high-resolution pixelated semiconductor detector, Timepix3, to avoid event pile-up and to correct measured LET at high-proton-flux locations without undesirable beam modifications. Confirmation of these measurements was done using a MatriXX PT detector and by Monte Carlo (MC) simulations. MC conformal FLASH computed doses had gamma passing rates of>95% (3mm/3% criteria) when compared to MatriXX PT and MLSIC data. At the lateral margin, DR showed average agreement values within 0.3% of simulation at 100Gy/s and fluctuations ∼10% at 15Gy/s. LET spectra in the proximal, lateral, and distal margins had Bhattacharyya distances of<1.3%. Our measurements with the MLSIC and Timepix3 detectors shown that the DR distributions for UHDR scenarios and LET spectra using USRe are in agreement with simulations. These results demonstrate that the methodology presented here can be used effectively for the experimental validation and QA of FLASH treatment plans.

Hybrid ultra-high and conventional dose rate treatments with electrons and photons for the clinical transfer of FLASH-RT to deep-seated targets: A treatment planning study

PurposeThis study explores the dosimetric feasibility and plan quality of hybrid ultra-high dose rate (UHDR) electron and conventional dose rate (CDR) photon (HUC) radiotherapy for treating deep-seated tumours with FLASH-RT. MethodsHUC treatment planning was conducted optimizing a broad UHDR electron beam (between 20–250 MeV) combined with a CDR VMAT for a glioblastoma, a pancreatic cancer, and a prostate cancer case. HUC plans were based on clinical prescription and fractionation schemes and compared against clinically delivered plans. Considering a HUC boost treatment for the glioblastoma consisting of a 15-Gy-single-fraction UHDR electron boost supplemented with VMAT, two scenarios for FLASH sparing were assessed using FLASH-modifying-factor-weighted doses. ResultsFor all three patient cases, HUC treatment plans demonstrated comparable dosimetric quality to clinical plans, with similar PTV coverage (V95% within 0.5 %), homogeneity, and critical OAR-sparing. At the same time, HUC plans delivered a substantial portion of the dose to the PTV (Dmedian of 50–69 %) and surrounding tissues at UHDR. For the HUC boost treatment of the glioblastoma, the first FLASH sparing scenario showed a moderate FLASH sparing magnitude (10 % for D2%,PTV) for the 15-Gy UHDR electron boost, while the second scenario indicated a more substantial sparing of brain tissues inside and outside the PTV (32 % for D2%,PTV, 31 % for D2%,Brain). ConclusionsFrom a planning perspective, HUC treatments represent a feasible approach for delivering dosimetrically conformal UHDR treatments, potentially mitigating technical challenges associated with delivering conformal FLASH-RT for deep-seated tumours. While further research is needed to optimize HUC fractionation and delivery schemes for specific patient cohorts, HUC treatments offer a promising avenue for the clinical transfer of FLASH-RT.

The Effect of Contrast Material in Three Dimensional Conformal and Helical Treatment Plans in Rectal Radiotherapy

The Effect of Contrast Material in Three Dimensional Conformal and Helical Treatment Plans in Rectal Radiotherapy

Evaluation and Comparison of the Dose Received by the Mandible, Maxilla, and Teeth in Two Methods of Three-dimensional Conformal Radiation Therapy and Helical Tomotherapy.

Using three-dimensional conformal radiation treatment (3D-CRT) and helical tomotherapy (HT), this study examines and contrasts the dosage received by the mandible, maxilla, and teeth. Sixteen patients with head-and-neck cancer (H and NC) were the subject of treatment planning at the Seyyed Al-Shohada Hospital in Isfahan, Iran. This study examined target coverage quality, exposure of healthy tissue, and radiation delivery effectiveness. In terms of a number of measures, including D2%, D50%, Dmean, V95%, conformity index (CI), and homogeneity index (HI) for the planning target volume (PTV) and D2%, D98%, Dmean, V95%, CI, and HI for the nodal PTV, HT showed considerable gains over 3D-CRT. The brainstem, D1cc, and D10cc received considerably lower maximum dosages in HT. Measurements of the right and left cochleas (Dmean, V55, and Dmax) revealed decreases in HT, with Dmean revealing the most significant variations. The Dmean and Dmax values for HT significantly decreased in constrictors as well. In terms of several HT-related indicators, the larynx, optic chiasm, optic nerves, oral cavity, mandible, thyroid, and parotid glands all showed considerable decreases. The findings of the comparison of the two treatment approaches revealed that the HT method was more than 50% more effective than the 3D-CRT method in sustaining organs at risk (OARs) and the target volume dose. In general, dosimetric coverage, homogeneity, conformity indices, and the absence of cold and hot patches showed that HT produced targets with greater accuracy than 3D-CRT. In addition, HT outperformed 3D-CRT in protecting important structures (OARs). HT as a result has the potential to be a more effective method of treatment for those with H and NC and involvement of regional lymph nodes.

Quantum chemical package Jaguar: A survey of recent developments and unique features.

This paper is dedicated to the quantum chemical package Jaguar, which is commercial software developed and distributed by Schrödinger, Inc. We discuss Jaguar's scientific features that are relevant to chemical research as well as describe those aspects of the program that are pertinent to the user interface, the organization of the computer code, and its maintenance and testing. Among the scientific topics that feature prominently in this paper are the quantum chemical methods grounded in the pseudospectral approach. A number of multistep workflows dependent on Jaguar are covered: prediction of protonation equilibria in aqueous solutions (particularly calculations of tautomeric stability and pKa), reactivity predictions based on automated transition state search, assembly of Boltzmann-averaged spectra such as vibrational and electronic circular dichroism, as well as nuclear magnetic resonance. Discussed also are quantum chemical calculations that are oriented toward materials science applications, in particular, prediction of properties of optoelectronic materials and organic semiconductors, and molecular catalyst design. The topic of treatment of conformations inevitably comes up in real world research projects and is considered as part of all the workflows mentioned above. In addition, we examine the role of machine learning methods in quantum chemical calculations performed by Jaguar, from auxiliary functions that return the approximate calculation runtime in a user interface, to prediction of actual molecular properties. The current work is second in a series of reviews of Jaguar, the first having been published more than ten years ago. Thus, this paper serves as a rare milestone on the path that is being traversed by Jaguar's development in more than thirty years of its existence.

Optimising craniospinal irradiation for medulloblastoma: a dosimetric comparison of two VMAT planning methods.

Craniospinal irradiation (CSI) poses a challenging planning process because of the complex target volume. Traditional 3D conformal CSI does not spare any critical organs, resulting in toxicity in patients. Here the dosimetric advantages of volumetric-modulated arc therapy (VMAT) using partial arc and avoidance sectors are compared with each other in planning in adult patients undergoing CSI to develop a clinically feasible technique that is both effective and efficient. Eight adult patients treated with CSI were retrospectively identified. In total 16 plans were made. We generated two plans for each patient: 1. VMAT plan using partial arc, namely VMAT_pa. 2. VMAT plan using avoidance sectors, namely VMAT_as. The dose prescribed was 36 Gy in 20 fractions. The dose-volume histogram for planning target volume (PTV) and organs at risk (OAR) (lens, eye, heart, thyroid, lungs, liver, gonads and kidneys) were analysed and compared. Dose parameters of mean dose, V95%, and V107% for the PTV were evaluated. The median length of PTV is 65.58 cm (45.8-79.5). The volume of PTV receiving 95% of the dose (V95%) in both the plans are 97.51% (VMAT_as) and 97.99% (VMAT_pa) (p = 0.121) while V107% are 0.733 and 0.742 for VMAT_as and VMAT_pa, respectively (p = 0.969). The doses of OARs such as lens, eye, liver and gonads were comparable. The mean heart dose was 10.4 and 9.0 Gy in VMAT_as and VMAT_pa plans, respectively (p = 0.005). Significant lower doses to the thyroid, kidneys and lungs were seen in VMAT plans using avoidance sectors. This study provides a practically useful VMAT planning method for the treatment of CSI and illustrates the ability of VMAT using avoidance sectors to generate highly conformal and homogeneous treatment plans for CSI, while limiting the dose to the relevant OARs.

1533: New cyclotron-based proton therapy facility development to achieve conformal FLASH treatment plans

1533: New cyclotron-based proton therapy facility development to achieve conformal FLASH treatment plans

A comprehensive study of massive compact star admitting conformal motion under bardeen geometry

This article primarily investigates the existence of the charged compact star under the conformal motion treatment within the context of f(Q) gravity. We have developed two models by implementing the power-law and linear form of conformal factor, enabling an in-depth comparison in our study. We have selected the MIT Bag model equation of state to describe the connection between pressure and energy density and matched the interior spherically symmetric space-time with the Bardeen space-time. In addition, the present research examines various physically valid characteristics of realistic stars, such as PSR J1614−2230, PSR J1903+327, Vela X-1, Cen X-3, and SMC X-1. We compare two constructed models by attributing the behavior of density, pressure, equilibrium conditions, and the adiabatic index. We have additionally included a brief analysis of the scenario involving Reissner-Nordstrom spacetime as an external geometry for the matching condition. In contrast to the Reissner-Nordstrom instance, the Bardeen model with the extra term in the asymptotic representations yields a more intriguing and viable result. The current analysis reveals that the resulting compact star solutions are physically acceptable and authentic when considering the presence of charge with conformal motion in f(Q) gravity.

Treatment planning with high-resolution 3D dose maps in preclinical and translational synchrotron microbeam radiation therapy

Background and PurposeMicrobeam Radiation Therapy (MRT) aims to deliver higher doses to the target while minimizing radiation damage to healthy tissues using synchrotron x-ray microbeams. Translational MRT research has now started, driven by promising results from preclinical studies. This study aimed to propose a first dose-outcome model by analyzing micrometric dose distributions obtained with high-resolution 3D dose calculations, accounting for the inherent physical dose distribution complexity in MRT. The feasibility of integrating penMRT, our full Monte Carlo multiscale dose calculation algorithm based on PENELOPE into translational research on veterinary patients was also investigated. Material and MethodsMicrometric dose distributions were calculated in tumor-bearing rats and for a veterinary patient with penMRT, for conformal multi-directional MRT treatment plans. Absorbed dose maps were obtained with 0.005 × 0.005 × 1 mm3 voxel sizes. High-resolution dose-volume histograms were extracted and analyzed against radiobiology studies. ResultsThe complexity of the MRT dose distribution was properly rendered at a micrometer scale on 3D dose maps, with well separated dose regions observed on the differential dose-volume histograms. The median survival time of glioma-bearing rats varied linearly with the volume fraction of the planning target volume that received doses higher than 50 Gy (R2 = 0.98). The feasibility of using penMRT for treatment planning in large volumes has been shown on a veterinary patient. ConclusionsThis study demonstrated the significant added value of penMRT for planning and prescribing MRT treatments. It also shed light on the correlation between the high-resolution 3D dose distributions and the treatment outcome.

Establishment of local diagnostic reference levels for breast cancer CT protocols in radiotherapy in a single Moroccan center

The objective of this study was to establish local diagnostic reference levels (LDRLs) for breast cancer computed tomography imaging in radiotherapy (CT-RT) at a single hospital in Morocco. Data were collected from 106 adult breast cancer patients aged between 33 and 78 yr during five months. Data were obtained using a Hitachi Supria 16-slice CT simulator at a regional oncology center in Morocco. CT-RT images are intended for 3D conformal radiotherapy treatment planning. Dose length product (DLP) and volumetric computed tomography dose index (CTDIvol) were evaluated by determining the 75th percentile as diagnostic reference levels for CT-RT breast cancer. LDRLs for CT-RT breast cancer have been determined in terms of DLP and CTDIvol, and they were 330.4 mGy.cm and 6.8 mGy, respectively. The DRLs were compared with other Europeans study. DRLs for this study were lower than those for the United Kingdom (UK), Croatia and Slovenia. The results of this study can be a reference for the establishment of local and national DRLs in Morocco and the optimization of CT-RT breast cancer procedures.

Efficacy of the collapsed cone algorithm calculated radiotherapy plans in intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT): A comparative dosimetric study in tumors of thorax.

In this study, efficacy of collapsed cone algorithm-generated intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) were evaluated for treatment of thoracic esophageal cancer. Ten previously treated patients with VMAT were considered for evaluation. The planning parameters were evaluated in terms of max dose, mean dose, Homogeneity Index, Conformity Index for planning target volume, and organ at risk doses. Total monitor unit, treatment time, and gamma passing index were also reported. The target dose coverage of the VMAT and IMRT plans achieved the clinical dosimetric criteria for all ten patients in the evaluation. Under the condition of equivalent target dose distribution, the VMAT plan's Conformity Index, monitor unit, treatment time, and gamma passing index rate were superior than in the IMRT plan, and the result was statistically significant. Collapsed cone algorithm-based VMAT can have a more effective and better approach for esophageal cancer than IMRT.

Preparation of Preformed Submicron Crosslinked Polymer Coils for Conformance Control in Low-Permeability Reservoirs.

With the increasing development of low-permeability reservoirs, the significance of conformance control treatment has risen considerably. To address the conflict between injectability and plugging performance, as well as to enhance the deep migration capacity of conformance control agents, preformed submicron crosslinked polymer coils (SCPCs) have been manufactured using aqueous solution dispersion polymerization. Fourier transform infrared and scanning electron microscopy were employed to examine the chemical structure and micromorphology, while particle size distribution, zeta potential, rheological, and filtration properties were analyzed. The effectiveness of conformance control was confirmed through the parallel core displacement. The effective particle size of SCPCs was at a submicron level (500~800 nm). SCPCs exhibit a transitional threshold concentration between gel and sol states (0.25 wt%~0.5 wt%). SCPCs can efficiently block the 1.2 μm microporous filter membrane. The filtration time is up to 67.8 min. SCPCs can improve the water absorption rate of lower permeability cores from 21.21% to 57.89% with a permeability difference of 5. Therefore, SCPCs have good injectability, plugging performance, and deep migration capacity and can be used for conformance control in low-permeability reservoirs.

Stereotactic radiotherapy for advanced canine anal sac adenocarcinoma: an exploratory study.

For dogs with anal sac adenocarcinoma (ASAC), metastasis to intra-abdominal and pelvic lymph nodes occurs early in the disease course. Death is usually related to locoregional progression. Surgical excision is the treatment of choice, but may not be possible in advanced cases. Dogs treated with RT in the gross disease setting showed a 38%-75% overall response rate, but side effects to organs at risk in this area (especially the colon, bladder, and spinal cord) were reported. Stereotactic radiation therapy (SRT) utilizes highly conformal treatment planning with rapid dose fall-off and hypofractionation. SRT may help to reduce the risk of late side effects of radiation while also creating a larger biological effect on ASACs. A primary aim of this prospective, descriptive, exploratory study was to describe the safety and feasibility of an SRT protocol in a small sample of dogs with ASAC, using objective and subjective measures to monitor acute and late side effects. A secondary aim was to describe the anti-tumor response of the SRT protocol using CT at 3- and 6 months posttreatment. Five dogs completed the radiation protocol. Four had follow-up CT characteristics of complete response (1), partial response (2), and stable disease (1). Minimal acute side effects were observed. Despite some large tumor volumes, constraints for OAR were achieved in all but the spinal cord for one patient. Findings indicated that SRT is a safe and feasible treatment for dogs with ACAC. Future studies are warranted to compare patient outcomes for SRT versus other treatments.

End-to-end validation of fiducial tracking accuracy in robotic radiosurgery using MRI-only simulation imaging.

Image-guided radiation-therapy (IGRT)-based robotic radiosurgery using magnetic resonance imaging (MRI)-only simulation could allow for improved target definition with highly conformal radiotherapy treatments. Fiducial marker (FM)-based alignment is used with robotic radiosurgery treatments of sites such as the prostate because it aids in accurate target localization. Synthetic CT (sCT) images are generated in the MRI-only workflow but FMs used for IGRT appear as signal voids in MRIs and do not appear in MR-generated sCTs, hindering the ability to use sCTs for fiducial-based IGRT. In this study we evaluate the fiducial tracking accuracy for a novel artificial fiducial insertion method in sCT images that allows for fiducial marker tracking in robotic radiosurgery, using MRI-only simulation imaging (MRI-only workflow). Artificial fiducial markers were inserted into sCT images at the site of the real marker implantation as visible in MRI. Two phantoms were used in this study. A custom anthropomorphic pelvis phantom was designed to validate the tracking accuracy for a variety of artificial fiducials in an MRI-only workflow. A head phantom containing a hidden target and orthogonal film pair inserts was used to perform end-to-end tests of artificial fiducial configurations inserted in sCT images. The setup and end-to-end targeting accuracy of the MRI-only workflow were compared to the computed tomography (CT)-based standard. Each phantom had six FMs implanted with a minimum spacing of 2cm. For each phantom a bulk-density sCT was generated, and artificial FMs were inserted at the implantation location. Several methods of FM insertion were tested including: (1) replacing HU with a fixed value (10000HU) (voxel-burned); (2) using a representative fiducial image derived from a linear combination of fiducial templates (composite-fiducial); (3) computationally simulating FM signal voids using a digital phantom containing FMs and inserting the corresponding signal void into sCT images (simulated-fiducial). All tests were performed on a CyberKnife system (Accuray, Sunnyvale, CA). Treatment plans and digital-reconstructed-radiographs were generated from the original CT and sCTs with embedded fiducials and used to align the phantom on the treatment couch. Differences in the initial phantom alignment (3D translations/rotations) and tracking parameters between CT-based plans and sCT-based plans were analyzed. End-to-end plans for both scenarios were generated and analyzed following our clinical protocol. For all plans, the fiducial tracking algorithm was able to identify the fiducial locations. The mean FM-extraction uncertainty for the composite and simulated FMs was below 48% for fiducials in both the anthropomorphic pelvis and end-to-end phantoms, which is below the 70% treatment uncertainty threshold. The total targeting error was within tolerance (<0.95mm) for end-to-end tests of sCT images with the composite and head-on simulated FMs (0.26, 0.44, and 0.35mm for the composite fiducial in sCT, head-on simulated fiducial in sCT, and fiducials in original CT, respectively. MRI-only simulation for robotic radiosurgery could potentially improve treatment accuracy and reduce planning margins. Our study has shown that using a composite-derived or simulated FM in conjunction with sCT images, MRI-only workflow can provide clinically acceptable setup accuracy in line with CT-based standards for FM-based robotic radiosurgery.

UVB pretreatment of β-lactoglobulin affects the temperature-induced formation of functional amyloid-like aggregates and promotes oxidative degradation.

Unfolding in combination with or without acid hydrolysis is crucial for the formation of functional amyloid (fibrillar) or amyloid-like (worm-like) β-lactoglobulin (BLG) aggregates, which can be induced through temperature treatment for several hours at pH 2-4. A preceding conformational destabilization of BLG might affect its aggregation. We investigated ultraviolet (UV) B radiation as conformational perturbing treatment to facilitate temperature-induced protein aggregation. 2-h UVB pretreated BLG (UV-BLG) exhibited an accelerated worm-like aggregation at pH 3.5, while at pH 2 the formation of fibrils was decelerated. The UV-induced conformational destabilization lowered the thermal stability and thus facilitates unfolding during thermal treatment. Thereby, the formation of covalent and non-covalent intermolecular interactions was favored, which promoted assembly of intact proteins resulting in worm-like aggregates. The oxidative degradation of UV-BLG was suggested to alter fibrillation-prone protein regions and thereby impede peptide assembly.

Clinical Sequalae of Initial Insurance Denials in a Large Academic Radiation Oncology Center

The objective of this study is to investigate the clinical sequalae of initial radiation oncology insurance denials. The hypothesis is that while the majority of initial insurance case denials are ultimately overturned, there are potential clinical implications to these initial denials. Data were extracted from an institutional registry of patient cases initially denied authorization by their insurers from January 2022 to December 2022. Chi-Square tests using statistical software were employed. Two hundred six cases from November 2021 to December 2022 were identified. The majority (n = 199 [96.6%]) of insurers were commercial payers, while 7 (3.4%) were Medicare/Medicare Advantage. 161 (78.1%) patients were <65 years of age, and 45 (21.8%) 65 or older. One hundred forty-one (68.4%) cases were metastatic, 60 (29.1%) definitive, and 5 (2.4%) were recurrent. Of the 206 cases, 127 (61.6%) cases were ultimately successful in authorization of the ordered treatment without any change to the requested treatment technique or prescription dose after P2P (Peer to Peer review), second-level appeal, comparison plan submission, employer request, insurance carrier change, and/or external appeal, and 56 (27.2%) cases were authorized though with insurer-requested modification to radiation treatment technique and/or prescription dose. Of 21 cases with a requested change in prescription dose, the median decrease in biologically effective dose (BED) was 24 Gy (range: 2.3-51). Of 58 cases with requested change in RT technique, 20 (34.5%) changed from IMRT to 3D-CRT, 16 (27.6%) SBRT to 3D, 15 (25.9%) SBRT to IMRT, 6 (10.3%) SBRT to 2D, and 1 (1.7%) 3D-CRT to 2D. 19 (9.2%) cases remained unauthorized by the insurer but proceeded with treatment via departmental administrative clearance. Of 196 cases which went on to treatment, 72 (36.7%) cases were delayed for a mean of 7.8 days and median of 5 days (range: 1-49). P2P was performed by the treating radiation oncologist in 169 (82.0%) cases, of which 78 (46.1%) were successful in authorization of the ordered treatment. Of the 91 unsuccessful cases, 62 (68.1%) second-level appeals were performed, of which 39 (62.9%) were successful in overturning denied authorization. Of the 23 cases not authorized either through P2P or second-level appeal, 3 (13.0%) cases were successful in authorization of the requested treatment via employer request, external appeal through an independent review organization, or insurance carrier change. Our institutional analysis suggests that while the majority of initial insurance case denials are ultimately overturned without any change to the requested treatment technique or prescription dose through a number of requests made by the insurer to the radiation oncologist, there are clinical implications with a significant percentage of case denials leading to treatment delays, decrease in prescription BED, and less conformal treatment technique.

A Novel Planning and Delivery Technology: Dose, Dose Rate and Linear Energy Transfer (LET) Optimization Based on Spot-Scanning Proton Arc Therapy FLASH (SPLASHLET)

To achieve a high conformal dose with Linear Energy Transfer (LET) optimized FLASH proton therapy, we introduced a new planning and delivery technique concept, the voxel-wised optimization of LET distribution and dose rate based on scanning arc therapy (SPLASHLET) MATERIALS/METHODS: The algorithm optimizes (1) the clinical dose-volume constraint based on dose distribution and (2) the clinical LET-volume constraint based on LET distribution using Alternating Direction Method of Multipliers (ADMM) with Limited-memory BFGS solver by minimizing the monitor unit (MU) constraint on spot weight and (3) the effective dose-average dose rate by minimizing the accelerator's beam current sequentially. Such optimization framework enables the high dose conformal dynamic arc therapy with the capability of LET painting with voxel-based FLASH dose rate in an open-source proton planning platform (MatRad, Department of Medical Physics in Radiation Oncology, German Cancer Research Center-DKFZ). It aiming to minimize the overall cost function value combined with plan quality and voxel-based LET and dose rate constraints. Three representative cases (brain, liver and prostate cancer) were used for testing purposes. Dose-volume histogram (DVH), LET volume histogram (LVH) dose rate volume histogram (DRVH) and dose rate map were assessed compared to the original SPArc plan (SPArcoriginal). SPLASHLET plan could offer comparable plan quality compared to SPArcoriginal plan. The DRVH results indicated that SPArcoriginal could not achieve FLASH using the clinic beam current configuration, while SPLASHLET could significantly not only improve V40Gy/s in target and region of interest (ROI) but also improve the mean LET in the target and reduce the high LET in organ at risk (OAR) in comparison with SPArcoriginal (Table 1). SPLASHLET offers the first LET painting with voxel-based ultra-dose-rate and high-dose conformity treatment using proton beam therapy. Such technique has the potential to take full vantage of LET painting, FLASH and SPArc.

Escalating SBRT Dose to Hypoxic Centers of Large Pulmonary Tumors via Simultaneous Integrated Boost Confers Effective Local Control with Minimal Toxicity

Hypoxia confers radio-resistance to tumor cells and drives malignant disease progression. SBRT treatment of large (>5.0 cm) pulmonary tumors pose significant dosimetric challenges in minimizing dose to adjacent organs at risk (OARs). Here, we detail the use of SBRT with simultaneous integrated boost (SIB) to the hypoxic centers of large pulmonary masses with effective local control and minimal normal tissue toxicity. Highly conformal treatment plans utilized 3-4 non-coplanar VMAT arcs with 6MV-FFF (1400 MU/min) and 4D-CT on TrueBeam to deliver 50 Gy in 5 fractions to the planning target volume (PTV). SIB dose of 60 Gy was delivered to a 1-cm internal margin from the gross tumor volume (GTV). Dose was calculated using Acuros-based engine. Pre-treatment Conebeam CT imaging was used for patient setup and verification. Treatments were delivered in < 15 minutes. Patients underwent post-treatment clinical evaluation and CT imaging in 3-month intervals to assess changes in tumor size and post-radiation sequelae. Clinical outcomes reported include treatment response and toxicity. Twenty-six patients with large, centrally (n = 13) or peripherally (n = 13) located tumors were evaluated; this included 16 NSCLC patients with T2-T3N0 disease and 5 with pulmonary metastases from distant sites. One patient had declined surgery, while 25/26 (96.1%) were deemed medically inoperable. All plans met RTOG-0813 requirements for target coverage and dose to OARs. Median follow-up interval was 11 months (0 to 23 months). Twenty-one of 26 (80.7%) patients received post-treatment CT imaging within 6 months of SBRT. Local control was achieved in 20/21 (95.2%) patients; one patient with a peripherally located tumor progressed outside the treatment field. Acute toxicity profile amongst the 25 patients assessed included grade 1 fatigue (n = 2), grade 1 rib pain (n = 1), and grade 2 pulmonary fibrosis (n = 1). Otherwise, 22/25 (88%) patients reported no radiation induced toxicities. Subgroup analysis was performed on patients with centrally located tumors, defined as located <2 cm from the hilum, heart, or bronchial trees. One of 13 (7.6%) patients with central tumors reported grade 1 rib pain; otherwise, no radiation induced adverse effects were observed. All patients with centrally located lung tumors experienced local control on surveillance imaging. SBRT with SIB to the hypoxic centers of large pulmonary masses is a safe, efficacious treatment that confers improved local control while maintaining dose to adjacent OARs. This study demonstrates the feasibility of delivering doses up to 60 Gy to the hypoxic centers of large lung tumors, while decreasing local tumor burden, minimizing treatment mobility, and improving clinic workflow. SBRT with SIB shortens treatment course to 5 fractions (in contrast to the traditional daily 30 fractions), thus improving patient comfort and compliance.