“…We observed that more 53BP1 foci were present at 24 hours after a 4-Gy proton dose in the HPV-positive UMSCC-47 cells than in the HPV-negative HN5 cells, and the HPVpositive UMSCC-47 cells showed greater tail moment in the neutral comet assay, suggesting that persistence of double-strand breaks may be one explanation for the greater sensitivity of HPV-positive cells to proton therapy compared with HPV-negative cells. 22 6 0.19) or continuous (1.10 6 0.18) 46 ; however, other factors that potentially influence the RBE of HNSCC need to be addressed. [39][40][41][42] Currently, clinical use of proton therapy is based largely on experience with XRT-based therapy.…”
“…We observed that more 53BP1 foci were present at 24 hours after a 4-Gy proton dose in the HPV-positive UMSCC-47 cells than in the HPV-negative HN5 cells, and the HPVpositive UMSCC-47 cells showed greater tail moment in the neutral comet assay, suggesting that persistence of double-strand breaks may be one explanation for the greater sensitivity of HPV-positive cells to proton therapy compared with HPV-negative cells. 22 6 0.19) or continuous (1.10 6 0.18) 46 ; however, other factors that potentially influence the RBE of HNSCC need to be addressed. [39][40][41][42] Currently, clinical use of proton therapy is based largely on experience with XRT-based therapy.…”
“…The proton RBE for tumor growth delay of NFSa (fibrosarcoma) in mice found a proton RBE of ~0.8 (at ~30 Gy relative to 180 kVp x rays; note that relative to 60 Co the RBE would be ~1.0) . The study of tumor growth delay of human hypopharyngeal squamous cell carcinoma cells in mice resulted in an RBE between 1.1 and 1.2 at ~20 Gy relative to 6 MV photons using a 23‐MeV proton beam . A study on the recurrence of mouse mammary carcinoma in mice resulted in an RBE of ~1.1 (at ~50 Gy relative to 60 Co) .…”
Section: Review Of Published Experimentsmentioning
confidence: 96%
“…The local dose rate also differs between scanned beam delivery and passively scattered delivery. Whether ultra‐high dose rates in excess of 20 Gy/s show differential responses between murine normal and tumor tissues in vivo is controversial, effects of ultra‐high dose rates on biological response have not been found in vitro.…”
Section: Assess Whether the Current Practice Of A Constant Rbe Shouldmentioning
The biological effectiveness of proton beams relative to photon beams in radiation therapy has been taken to be 1.1 throughout the history of proton therapy. While potentially appropriate as an average value, actual relative biological effectiveness (RBE) values may differ. This Task Group report outlines the basic concepts of RBE as well as the biophysical interpretation and mathematical concepts. The current knowledge on RBE variations is reviewed and discussed in the context of the current clinical use of RBE and the clinical relevance of RBE variations (with respect to physical as well as biological parameters).
The following task group aims were designed to guide the current clinical practice:
Assess whether the current clinical practice of using a constant RBE for protons should be revised or maintained.
Identifying sites and treatment strategies where variable RBE might be utilized for a clinical benefit.
Assess the potential clinical consequences of delivering biologically weighted proton doses based on variable RBE and/or LET models implemented in treatment planning systems.
Recommend experiments needed to improve our current understanding of the relationships among in vitro, in vivo, and clinical RBE, and the research required to develop models. Develop recommendations to minimize the effects of uncertainties associated with proton RBE for well‐defined tumor types and critical structures.
“…Of fundamental importance to gain insights into laser-driven particle biological effectiveness is, of course, in vivo work. From these studies, mainly limited to tumour growth delay as endpoint of clinical relevance and still too scarce for firm conclusions to be drawn, no enhancing effects have emerged for both protons and electrons [38][39][40].…”
A: Accelerated proton beams have become increasingly common for treating cancer. The need for cost and size reduction of particle accelerating machines has led to the pioneering investigation of optical ion acceleration techniques based on laser-plasma interactions as a possible alternative. Laser-matter interaction can produce extremely pulsed particle bursts of ultra-high dose rates (≥ 10 9 Gy/s), largely exceeding those currently used in conventional proton therapy. Since biological effects of ionizing radiation are strongly affected by the spatio-temporal distribution of DNA-damaging events, the unprecedented physical features of such beams may modify cellular and tissue radiosensitivity to unexplored extents. Hence, clinical applications of laser-generated particles need thorough assessment of their radiobiological effectiveness. To date, the majority of studies have either used rodent cell lines or have focussed on cancer cell killing being local tumour control the main objective of radiotherapy. Conversely, very little data exist on sub-lethal cellular effects, of relevance to normal tissue integrity and secondary cancers, such as premature cellular senescence. Here, we discuss ultra-high dose rate radiobiology and present preliminary 1Corresponding author.
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