Ultrahigh dose-rate radiotherapy (RT), or ‘FLASH’ therapy, has gained significant momentum following various in vivo studies published since 2014 which have demonstrated a reduction in normal tissue toxicity and similar tumor control for FLASH-RT when compared with conventional dose-rate RT. Subsequent studies have sought to investigate the potential for FLASH normal tissue protection and the literature has been since been inundated with publications on FLASH therapies. Today, FLASH-RT is considered by some as having the potential to ‘revolutionize radiotherapy’. FLASH-RT is considered by some as having the potential to ‘revolutionize radiotherapy’. The goal of this review article is to present the current state of this intriguing RT technique and to review existing publications on FLASH-RT in terms of its physical and biological aspects. In the physics section, the current landscape of ultrahigh dose-rate radiation delivery and dosimetry is presented. Specifically, electron, photon and proton radiation sources capable of delivering ultrahigh dose-rates along with their beam delivery parameters are thoroughly discussed. Additionally, the benefits and drawbacks of radiation detectors suitable for dosimetry in FLASH-RT are presented. The biology section comprises a summary of pioneering in vitro ultrahigh dose-rate studies performed in the 1960s and early 1970s and continues with a summary of the recent literature investigating normal and tumor tissue responses in electron, photon and proton beams. The section is concluded with possible mechanistic explanations of the FLASH normal-tissue protection effect (FLASH effect). Finally, challenges associated with clinical translation of FLASH-RT and its future prospects are critically discussed; specifically, proposed treatment machines and publications on treatment planning for FLASH-RT are reviewed.
Studies involving Monte Carlo simulations are common in both diagnostic and therapy medical physics research, as well as other fields of basic and applied science. As with all experimental studies, the conditions and parameters used for Monte Carlo simulations impact their scope, validity, limitations, and generalizability. Unfortunately, many published peer-reviewed articles involving Monte Carlo simulations do not provide the level of detail needed for the reader to be able to properly assess the quality of the simulations. The American Association of Physicists in Medicine Task Group #268 developed guidelines to improve reporting of Monte Carlo studies in medical physics research. By following these guidelines, manuscripts submitted for peer-review will include a level of relevant detail that will increase the transparency, the ability to reproduce results, and the overall scientific value of these studies. The guidelines include a checklist of the items that should be included in the Methods, Results, and Discussion sections of manuscripts submitted for peer-review. These guidelines do not attempt to replace the journal reviewer, but rather to be a tool during the writing and review process. Given the varied nature of Monte Carlo studies, it is up to the authors and the reviewers to use this checklist appropriately, being conscious of how the different items apply to each particular scenario. It is envisioned that this list will be useful both for authors and for reviewers, to help ensure the adequate description of Monte Carlo studies in the medical physics literature.
The authors have developed a treatment planning workflow for MC dose calculation of pencil beams and optimization for treatment planning of VHEE radiotherapy. The authors have demonstrated that VHEE plans resulted in similar or superior dose distributions for pediatric, lung, and prostate cases compared to clinical VMAT plans.
Secondary lymphedema is a common disorder associated with acquired functional impairment of the lymphatic system. The goal of this study was to evaluate the therapeutic efficacy of aligned nanofibrillar collagen scaffolds (BioBridge) positioned across the area of lymphatic obstruction in guiding lymphatic regeneration. In a porcine model of acquired lymphedema, animals were treated with BioBridge scaffolds, alone or in conjunction with autologous lymph node transfer as a source of endogenous lymphatic growth factor. They were compared with a surgical control group and a second control group in which the implanted BioBridge was supplemented with exogenous vascular endothelial growth factor-C (VEGF-C). Three months after implantation, immunofluorescence staining of lymphatic vessels demonstrated a significant increase in lymphatic collectors within close proximity to the scaffolds. To quantify the functional impact of scaffold implantation, bioimpedance was used as an early indicator of extracellular fluid accumulation. In comparison to the levels prior to implantation, the bioimpedance ratio was significantly improved only in the experimental BioBridge recipients with or without lymph node transfer, suggesting restoration of functional lymphatic drainage. These results further correlated with quantifiable lymphatic collectors, as visualized by contrast-enhanced computed tomography. They demonstrate the therapeutic potential of BioBridge scaffolds in secondary lymphedema.
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