GRID Radiation Research Articles

The Radiosurgery Society Working Groups on GRID, LATTICE, Microbeam, and FLASH Radiotherapies: 2022 to 2023 Advancements Symposium and Subsequent Progress Made

PurposeSince the inaugural workshop “Understanding High-Dose, Ultra-High Dose Rate and Spatially Fractionated Radiotherapy.” hosted by the NCI and sponsored by the Radiosurgery Society (RSS), growing collaborations and investigations have ensued among experts, practitioners, and researchers. The RSS GRID, Lattice, Microbeam & FLASH (GLMF) Working Groups were formed as a framework for these efforts and have focused on advancing the understanding of the biology, technical/physical parameters, trial design, and clinical practice of these new radiation therapy modalities. Methods and MaterialsIn view of the steadily increasing clinical interest in SFRT and FLASH, a full-day symposium entitled “Advancements in GRID, LATTICE, and FLASH Radiotherapy Symposium” was established in 2022 that immediately preceded the RSS scientific meeting. This well-attended symposium focused on clinical, technical, and physics approaches for SFRT, while closely examining relevant radiobiological underpinnings. Practical clinical trial development was a highlighted discussion. An additional section reviewed proton therapy and other particle-based techniques for the delivery of GRID and Lattice therapy. A treatment planning and delivery tutorial for GRID, Lattice, and proton GRID/Lattice was directed towards the real-world considerations for the development of new clinical GRID or LATTICE programs. An overall similar approach was applied to the discussion of FLASH. This report summarizes the content of the first GLMF Symposium and related work of the RSS GLMF Working Groups in the field of heterogeneous and ultra-high dose rate irradiation, over approximately 2 years. ResultsThe GLMF Working Groups have continued to expand in membership and attendance, and several resultant trial concepts, research efforts, academic discussions, and peer-reviewed publications have followed as the number of institutions and practitioners utilizing SFRT and FLASH continues to grow. ConclusionsThe GLFM Working Groups and the RSS continue to demonstrate excellent progress in proliferating use of and improving understanding of SFRT and ultra-high dose rate radiotherapy techniques.

An inter-comparison between MCNPX and EGSnrc Monte Carlo codes in grid radiotherapy characterization using beta-emitting radionuclides

IntroductionThe applicability of MCNPX and EGSnrc Monte Carlo codes in dosimetric characterization of spatially fractionated radiotherapy (SFRT or grid radiotherapy, in other words) of superficial tumors using beta-emitting radionuclides has been assessed in the current study. Materials and methodsA grid block including 63 cubic holes was modeled by each Monte Carlo code. Then, the grid block was separately filled by four widely adopted beta-emitting radioisotopes for radionuclide-therapy purposes including 32P, 90Y, 166Ho, and 188Re. Finally, the depth dose distribution and transverse dose profiles at different depths were separately calculated for each radionuclide using both MCNPX and EGSnrc Monte Carlo codes. Obtained results were quantitatively compared by gamma analysis as well as an R-squared statistical test to evaluate the compatibility of acquired dosimetry results by each code. ResultsSimilar dosimetry results were obtained by both Monte Carlo codes, where no significant difference was observed among the obtained data by each code. The uniformity of dose distribution improved with increasing the depth inside the phantom for all radionuclides under investigation. ConclusionFrom the results, it can be concluded that MCNPX and EGSnrc Monte Carlo codes have similar performance in dosimetric characterization of grid radiotherapy using beta-emitting radionuclides. Small differences between the results acquired by employed codes originate from associated statistical uncertainty with the Monte Carlo data as well as differences in considered condense history scheme (CHS) during the electron transport inside the medium.

389 Initial Experience of Spatially Fractionated GRID Radiotherapy In Indonesia

389 Initial Experience of Spatially Fractionated GRID Radiotherapy In Indonesia

O 42 - Commissioning of collimating brass aperture for spot-scanning proton GRID radiotherapy

O 42 - Commissioning of collimating brass aperture for spot-scanning proton GRID radiotherapy

Beam quality and the mystery behind the lower percentage depth dose in grid radiation therapy

Grid therapy recently has been picking momentum due to favorable outcomes in bulky tumors. This is being termed as Spatially Fractionated Radiation Therapy (SFRT) and lattice therapy. SFRT can be performed with specially designed blocks made with brass or cerrobend with repeated holes or using multi-leaf collimators where dosimetry is uncertain. The dosimetric challenge in grid therapy is the mystery behind the lower percentage depth dose (PDD) in grid fields. The knowledge about the beam quality, indexed by TPR20/10 (Tissue Phantom Ratio), is also necessary for absolute dosimetry of grid fields. Since the grid may change the quality of the primary photons, a new kq,q0\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\\mathbf{k}}_{\\mathbf{q},{\\mathbf{q}}_{0}}$$\\end{document} should be evaluated for absolute dosimetry of grid fields. A Monte Carlo (MC) approach is provided to resolving the dosimetric issues. Using 6 MV beam from a linear accelerator, MC simulation was performed using MCNPX code. Additionally, a commercial grid therapy device was used to simulate the grid fields. Beam parameters were validated with MC model for output factor, depth of maximum dose, PDDs, dose profiles, and TPR20/10. The electron and photon spectra were also compared between open and grid fields. The dmax is the same for open and grid fields. The PDD with grid is lower (~ 10%) than the open field. The difference in TPR20/10 of open and grid fields is observable (~ 5%). Accordingly, TPR20/10 is still a good index for the beam quality in grid fields and consequently choose the correct kq,q0\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${\\mathbf{k}}_{\\mathbf{q},{\\mathbf{q}}_{0}}$$\\end{document} in measurements. The output factors for grid fields are 0.2 lower compared to open fields. The lower depth dose with grid therapy is due to lower depth fluence with scatter radiation but it does not impact the dosimetry as the calibration parameters are insensitive to the effective beam energies. Thus, standard dosimetry in open beam based on international protocol could be used.

Utilization of spatially fractionated radiotherapy in the management of a patient with inoperable uterine leiomyosarcoma

Utilization of spatially fractionated radiotherapy in the management of a patient with inoperable uterine leiomyosarcoma

How much should you worry about contaminant neutrons in spatially fractionated grid radiation therapy?

Neutron contamination in radiation therapy is of concern in treatment with high-energy photons (> 10 MV). With the development of new radiotherapy modalities such as spatially fractionated grid radiation therapy (SFGRT) or briefly grid radiotherapy, more studies are required to evaluate the risks associated with neutron contamination. In 15 MV SFGRT, high-Z materials such as lead and cerrobend are used as the block on the tray of linear accelerator (linac) which can probably increase the photoneutron production. On the other hand, the high-dose fractions (10-20 Gy) used in SFGRT can induce high neutron contamination. The current study was devoted to addressing these concerns via compression of neutron fluence (Φn) and ambient dose equivalent ([Formula: see text]) at the patient table and inside the maze between SFGRT and conventional fractionated radiation therapy (CFRT). The main components of the 15 MV Siemens Primus equipped with different grids and located inside a typical radiotherapy bunker were simulated by the MCNPX® Monte Carlo code. Evidence showed that the material used for grid construction does not significantly increase neutron contamination inside the maze. However, at the end of the maze, neutron contamination in SFGRT is significantly higher than in CFRT. In this regard, a delay time of 15 minutes after SFGRT is recommended for all radiotherapy staff before entering the maze. It can be also concluded that [Formula: see text] at the patient table is at least 10 times more pronounced than inside the maze. Therefore, the patient is more at risk of neutrons compared to the staff. The [Formula: see text] at the isocenter in SFGRT with grids made of lead and cerrobend was nearly equal to CFRT. Nevertheless, it was dramatically lower than in CFRT by 30% if the brass grid is used. Accordingly, SFGRT with the brass grid is recommended, from radiation protection aspects.

Dosimetric Verification of Grid Radiotherapy Using Three Ionization Chamber Detectors o Dosimetry

This study aims to provide verification between measured and calculated radiation dose using three different ionization chamber detectors in Grid plans to select the best ones To the best of our knowledge, this is the first practical experiment in such subject. Grid radiotherapy is an unconventional method for bulky tumors treatment. It is characterized by a single-fraction and high radiation dose. Ten cases (scenarios) were selected to achieve Grid plans by MLCs, with a single dose of 1500-2000 cGy. Three ionization detectors were employed to measure the maximum, mean, and point doses (cGy), and match them with those calculated by the linear accelerator used in this study. The results showed significant differences among the three detectors in measuring the maximum and mean doses, with p-value = 0.0016 and 0.06, respectively. While the differences among the measured three detectors and calculated doses for the point dose were non-significant, p = 0.12. The variation in the results of the corresponding percentage between calculated and measured doses depended on the type and position of the detector, the scattering, and the leakage of the radiation. In conclusions, the Semi-flex chamber gives the best results.

A case report on the abscopal effect of liver-directed GRID radiotherapy

GRID radiotherapy is a form of spatially fractionated radiotherapy that allows delivery of high radiation doses to bulky tumours. A grid splits the beam into multiple beamlets to give a heterogenous dose to the tumour, while stimulating the immune system to improve tumour response through the abscopal effect. However, this has fallen out of favour in recent times due to the presence of more modern techniques. Here we present a case of a large liver metastasis from a rectal neuroendocrine primary treated with GRID radiotherapy with an abscopal response seen in a portal vein tumour thrombus.

Biological Evaluation of Grid versus 3D Conformal Radiotherapy in Bulky Head and Neck Cancer.

Grid radiotherapy is one of the treatment techniques applied to treat patients with advanced bulky tumors.Purpose:This study aims to estimate the difference in biological and dosimetric parameters of the grid radiotherapy technique for the treatment of bulky head and neck (H and N) tumors and compare it with conventional conformal radiotherapy.Subjects and Methods:Three-dimensional conformal and grid radiotherapy were designed by the Monaco treatment planning system (TPS). Eight bulky tumors of (H and N) cases were selected, using a single fraction 15–20 Gy. Dose-volume histogram of the tumors and organs at risk (OARs) used to calculate the equivalent uniform dose (EUD) (Gy) by Matlab program. Furthermore, dosimetric parameters of the tumors from the TPS were compared for two techniques (grid radiotherapy and the conventional conformal radiotherapy).Results:Grid attained a lower EUD (Gy) in tumors and OARs as compared to conformal therapy, as Grid principle protects about half of the tumor area from the radiation leads to less coverage of the tumor. Also, where OARs in closed with tumors and the shielding by multi-leaf (1 cm) were more effective than other techniques, lead to a decrease of radiobiological values according to its definition by Niemierko. Radiobiological results showed significant differences between the two methods, and dosimetric data obtained by the TPS for tumours for two plans were P < 0.05.Conclusions:The grid plan achieves lower values of EUDs than the conformal technique for OARs. Hence, it achieves more sparing and fewer complications for these organs.

Feasibility of 18-MV grid therapy from radiation protection aspects: unwanted dose and fatal cancer risk caused by photoneutrons and scattered photons

PurposePhotoneutron production is a common concern when using 18-MV photon beams in radiation therapy. In Spatially Fractionated Grid Radiation Therapy (SFGRT), the grid block in the collimation system modifies the neutron production, photon scattering, and electron contamination in and out of the radiation field. Such an effect was studied with grids made of different high-Z materials by Monte Carlo simulations. The results were also used to evaluate the lifetime risk of fatal cancers. MethodsMCNPX® code (2.7.0 extensions) was employed to simulate an 18-MV LINAC (Varian 2100 C/D). Three types of grid made of brass, cerrobend, and lead were used to study the neutron and electron fluence. Output factors for each grid with different field sizes were calculated. A revised female MIRD phantom with an 8-cm spherical tumor inside the liver was used to estimate the dose to the tumor and the critical organs. A 20-Gy SFGRT plan with Anterior Posterior (AP) - Posterior Anterior (PA) grid beams was compared with a Conventional Fractionated Radiation Therapy (CFRT) plan which delivered 40-Gy to the tumor by AP-PA open beams. Neutron equivalent dose, photon equivalent dose, as well as lifetime risks of fatal cancer were calculated in the organs at risk. ResultsThe grid blocks reduced the fluence of contaminant electrons inside the treatment field by more than 50%. The neutron fluences per electron-history in SFGRT plans with brass, cerrobend and lead were on average 55%, 31% and 31% less than that of the CFRT plan, respectively. However, when converting to fluences per delivered dose (Gy), the cerrobend and lead grid may incur higher neutron dose for 20 × 20 cm2 field size and above. The changes in neutron mean energy, as well as the correlated radiation weighting factors, were insignificant. The total risk due to the photoneutrons in the SFGRT plans was 87% or lower than that in the CFRT plans. In both SFGRT and CFRT plans, the contribution of the primary and scattered photons to the fatal cancer risk was 2 times or more than the photoneutrons. The total risks from photons in SFGRT with brass, cerrobend, and lead blocks were 1.733, 1.374, and 1.260%, respectively, which were less than 30% of the total photon-risk in CFRT (5.827%). ConclusionIn the brass, cerrobend, and lead grids, the attenuation of photoneutrons outweighs its photoneutron production in 18-MV SFGRT. The total cancer risks from photons and photoneutrons in the SFGRT plans were 30% or less of the risks in the CFRT plans (5.911%). Using 18 MV photon beams with brass, cerrobend, and lead grid blocks is still a feasible option for SFGRT.

Dosimetric Parameters Associated With Pathologic Response in Patients Undergoing Preoperative Spatially Fractionated Radiotherapy (GRID) for Soft Tissue Sarcoma

<h3>Purpose/Objective(s)</h3> Spatially fractionated radiotherapy, or GRID radiotherapy, is a technique utilizing multiple beamlets of high dose radiotherapy in a heterogeneous grid pattern to treat tumor non-uniformly with megavoltage X-rays while maintaining normal tissue tolerance. We sought to characterize associations between GRID dosimetric parameters and pathologic response in patients undergoing preoperative GRID radiotherapy for high grade soft tissue sarcoma. <h3>Materials/Methods</h3> We analyzed 26 patients with high grade soft tissue sarcomas undergoing GRID radiotherapy. Dosimetric parameters included mean dose to GTV, maximum dose to 0.01 cc, maximum dose to 0.03 cc, D5, D10, D20, D50, D90, D100, V5, V10, V20, V50, V90, V100, total area under the curve, maximum tumor length, maximum tumor width, tumor volume, equivalent uniform dose to GTV, minimum surface to tumor distance, maximum surface to tumor distance, maximum tumor depth, maximum dose outside GTV, maximum dose to skin, number of beamlets, peak to valley ratio, and peak to peak distance. <h3>Results</h3> The dosimetric parameters most closely associated with pathologic response were maximum dose to 0.01 cc and maximum dose to 0.03 cc (Spearman coefficient of 0.685, <i>P</i>-value of 0.01). Mean dose to GTV, V90, and V100 showed weak associations that weaker associations that were not significant (Spearman coefficient of 0.442, 0.510, and 0.504 with <i>P</i>-values of 0.08, 0.09, 0.09). <h3>Conclusion</h3> This study showed an association between the dosimetric parameters maximum dose to 0.01 cc and maximum dose to 0.03 cc and pathologic response in patients undergoing preoperative GRID radiotherapy for high grade soft tissue sarcoma.

Stem Cell Migration: A Possible Mechanism for the Tissue-Sparing Effect of Spatially Fractionated Radiation.

Stem cell responses in tissues after exposure to radiation are of significance for maintaining tissue functions. From the point of view of stem cell characteristics, this article seeks to illustrate some contributions of microbeam research to spatially fractionated radiotherapy (SFRT), such as grid radiotherapy and microbeam radiotherapy. Although the tissue-sparing response after SFRT was first reported more than a century ago, current radiation dose-volume metrics are still unable to accurately predict such tissue-level changes in response to spatially fractionated radiation fields. However, microbeam approaches could contribute to uncovering the mechanisms of tissue response, significantly improving the outcomes of SFRT and reducing its adverse effects. Studies with microbeams have shown that the testicular tissue-sparing effect for maintaining spermatogenesis after exposure to spatially fractionated radiation depends on biological parameters, such as the radiation dose distribution at the microscale level for tissue-specific stem cells and the microenvironment, or niche. This indicates that stem cell survival, migration, and repopulation are involved in the tissue-level changes during or after SFRT. The illustration of microbeam applications in this article focuses on the stem cell migration as a possible mechanism of the tissue-sparing effect for preserving functionality.

A Brief Overview of the Preclinical and Clinical Radiobiology of Microbeam Radiotherapy

Microbeam radiotherapy (MRT) is the delivery of spatially fractionated beams that have the potential to offer significant improvements in the therapeutic ratio due to the delivery of micron-sized high dose and dose rate beams. They build on longstanding clinical experience of GRID radiotherapy and more recently lattice-based approaches. Here we briefly overview the preclinical evidence for MRT efficacy and highlight the challenges for bringing this to clinical utility. The biological mechanisms underpinning MRT efficacy are still unclear, but involve vascular, bystander, stem cell and potentially immune responses. There is probably significant overlap in the mechanisms underpinning MRT responses and FLASH radiotherapy that needs to be further defined.

PO-1616 Dosimetry of MLC based GRID radiotherapy using EBT – XD film

PO-1616 Dosimetry of MLC based GRID radiotherapy using EBT – XD film

SP-0722: Spatially fractionated GRID radiotherapy - rationale and promise

SP-0722: Spatially fractionated GRID radiotherapy - rationale and promise

A simple dosimetric approach to spatially fractionated GRID radiation therapy using the multileaf collimator for treatment of breast cancers in the prone position.

The purpose of this study was to explore the treatment planning methods of spatially fractionated radiation therapy (SFRT), commonly referred to as GRID therapy, in the treatment of breast cancer patients using multileaf collimator (MLC) in the prone position. A total of 12 patients with either left or right breast cancer were retrospectively chosen. The computed tomography (CT) images taken for the whole breast external beam radiation therapy (WB‐EBRT) were used for GRID therapy planning. Each GRID plan was made by using two portals and each portal had two fields with 1‐cm aperture size. The dose prescription point was placed at the center of the target volume, and a dose of 20 Gy with 6‐MV beams was prescribed. Dose‐volume histogram (DVH) curves were generated to evaluate dosimetric properties. A modified linear‐quadratic (MLQ) radiobiological response model was used to assess the equivalent uniform doses (EUD) and therapeutic ratios (TRs) of all GRID plans. The DVH curves indicated that these MLC‐based GRID therapy plans can deliver heterogeneous dose distribution in the target volume as seen with the conventional cerrobend GRID block. The plans generated by the MLC technique also demonstrated the advantage for accommodating different target shapes, sparing normal structures, and reporting dose metrics to the targets and the organs at risks. All GRID plans showed to have similar dosimetric parameters, implying the plans can be made in a consistent quality regardless of the shape of the target and the size of volume. The mean dose of lung and heart were respectively below 0.6 and 0.7 Gy. When the size of aperture is increased from 1 to 2 cm, the EUD and TR became smaller, but the peak/valley dose ratio (PVDR) became greater. The dosimetric approach of this study was proven to be simple, practical and easy to be implemented in clinic.

Photon GRID Radiation Therapy: A Physics and Dosimetry White Paper from the Radiosurgery Society (RSS) GRID/LATTICE, Microbeam and FLASH Radiotherapy Working Group.

The limits of radiation tolerance, which often deter the use of large doses, have been a major challenge to the treatment of bulky primary and metastatic cancers. A novel technique using spatial modulation of megavoltage therapy beams, commonly referred to as spatially fractionated radiation therapy (SFRT) (e.g., GRID radiation therapy), which purposefully maintains a high degree of dose heterogeneity across the treated tumor volume, has shown promise in clinical studies as a method to improve treatment response of advanced, bulky tumors. Compared to conventional uniform-dose radiotherapy, the complexities of megavoltage GRID therapy include its highly heterogeneous dose distribution, very high prescription doses, and the overall lack of experience among physicists and clinicians. Since only a few centers have used GRID radiation therapy in the clinic, wide and effective use of this technique has been hindered. To date, the mechanisms underlying the observed high tumor response and low toxicity are still not well understood. To advance SFRT technology and planning, the Physics Working Group of the Radiosurgery Society (RSS) GRID/Lattice, Microbeam and Flash Radiotherapy Working Groups, was established after an RSS-NCI Workshop. One of the goals of the Physics Working Group was to develop consensus recommendations to standardize dose prescription, treatment planning approach, response modeling and dose reporting in GRID therapy. The objective of this report is to present the results of the Physics Working Group's consensus that includes recommendations on GRID therapy as an SFRT technology, field dosimetric properties, techniques for generating GRID fields, the GRID therapy planning methods, documentation metrics and clinical practice recommendations. Such understanding is essential for clinical patient care, effective comparisons of outcome results, and for the design of rigorous clinical trials in the area of SFRT. The results of well-conducted GRID radiation therapy studies have the potential to advance the clinical management of bulky and advanced tumors by providing improved treatment response, and to further develop our current radiobiology models and parameters of radiation therapy design.

Photon and photon–neutron experimental dosimetry in Grid therapy with 18 MV photon beams

AbstractPropose:Spatially fractionated Grid radiation therapy (SFGRT) in an effective technique for bulky and radio-sensitive tumours. SFGRT using a constructed block has been used to evaluate the photon and photo-neutron (PN) dose measurement in 18-MV photon beam energy.Methods and materials:A mounted Grid block on to a Varian Clinac 2100c linear accelerator was used to perform photon dosimetry. The percentage depth dose, in-plane and cross-plane beam profile and output factor was measured by ionization chamber in water. The PN contamination was measured after photon dosimetry using the combination of thermoluminescence dosimetry types 600 and 700, and Polycarbonate Film dosimeters on the surface and in the maximum depth dose (dmax) of solid water™ slabs.Results:The valley-to-peak ration for 6 and 18 MV photon beams obtained from the beam profiles was ~35 and 72%, respectively. Fast and thermal PN equivalent dose decreased in the Grid field compared to an open field (without Grid).Conclusion:The Grid therapy dosimetry compared to the conventional radiotherapy (without the grid) the production of fast and thermal neutrons were reduced. Using of a Grid block in high-energy photon beams for a long period of the treatment continuously might be a new source of contamination due to the interaction of photon beam resulting the activation of the Grid block

History and current perspectives on the biological effects of high-dose spatial fractionation and high dose-rate approaches: GRID, Microbeam & FLASH radiotherapy.

The effects of various forms of ionising radiation are known to be mediated by interactions with cellular and molecular targets in irradiated and in some cases non-targeted tissue volumes. Despite major advances in advanced conformal delivery techniques, the probability of normal tissue complication (NTCP) remains the major dose-limiting factor in escalating total dose delivered during treatment. Potential strategies that have shown promise as novel delivery methods in achieving effective tumour control whilst sparing organs at risk involve the modulation of critical dose delivery parameters. This has led to the development of techniques using high dose spatial fractionation (GRID) and ultra-high dose rate (FLASH) which have translated to the clinic. The current review discusses the historical development and biological basis of GRID, microbeam and FLASH radiotherapy as advanced delivery modalities that have major potential for widespread implementation in the clinic in future years.