Novel treatment planning approaches to enhance the therapeutic ratio: targeting the molecular mechanisms of radiation therapy

Protopapa, Maria; Kouloulias, Vassilis; Kougioumtzopoulou, Andromachi; Liakouli, Zoi; Papadimitriou, C.; Zygogianni, Anna

doi:10.1007/s12094-019-02165-0

Cited by 5 publications

(7 citation statements)

References 115 publications

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“…LRT can be used to induce immune responses through its high-dose component, including abscopal effects and bystander effects. The presence of a bystander in GRID has been experimentally documented by a significant decrease in clonogenic survival and an increase in the expression of DNA damage genes in bystander cells [22][23] . Larger tumours may release more antigens in response to irradiation, which potentially intensifies the abscopal effects 24 .…”

Section: Discussionmentioning

confidence: 99%

Feasibility of lattice radiotherapy using proton and carbon ion pencil beam for sinonasal adenoid cystic carcinoma

Yang

et al. 2021

Preprint

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Background: Adenoid cystic carcinomas (ACCs) are extremely rare, but they are a treatment challenge because they are highly radioresistant and are surrounded by several organs at risk (OARs). We aimed to investigate the feasibility of lattice radiotherapy (LRT) using pencil beam scanning (PBS) proton or carbon ion beams in the treatment of sinonasal ACC.Patients and methods: Ten patients with nonoperative, bulky, and radioresistant ACCs were enrolled. Spherical vertices with a 1-cm diameter and average centre-to-centre distance of 3.51 cm were delineated within the gross tumour volumes. The prescription was 15 Gy (relative biological effectiveness [RBE]) to vertices and 3–3.5 Gy (RBE) to the periphery as clinical boost target volumes (CTVboosts) in one fraction. Photon, proton, and carbon-ion LRT plans were generated based on this. Peak-to-valley ratios (PVDRs) and dose delivered to the vertices, CTVboost, and OARs were compared among the three plans. The OAR doses were also compared between LRT plans and one fraction of clinical boost plans. Results: The mean for photon, proton, and carbon-ion LRT plans were 4.78 (range: 4.34–5.36), 4.82 (range: 4.15–5.37), and 4.69 (range: 4.31–5.28), respectively. The mean for the same plans were 3.42 (range: 3.15–3.79), 2.93 (range: 2.19–3.74), and 3.58 (range: 3.09–4.68), respectively, with no significant differences in both. The brain stem, chiasm, optic nerve, parotids, spinal cord, and brain were better protected in proton and carbon-ion LRT plans than in photon LRT plans. Further, these plans did not introduce more doses to the OARs compared to the one-fraction clinical boost plan, with a significant difference. Conclusion: Despite the minimal difference in PVDR between proton and carbon-ion LRT plans and photon LRT plans, the former can better protect OARs than photon LRT plans. Therefore, PBS proton and carbon-ion LRT can be used for sinonasal ACC.

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Section: Discussionmentioning

confidence: 99%

Feasibility of lattice radiotherapy using proton and carbon ion pencil beam for sinonasal adenoid cystic carcinoma

Yang

et al. 2021

Preprint

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“…The logic of developing Manganese Superoxide Dismutase (MnSOD) gene therapy arose from the challenge to provide better normal tissue protection during clinical radiotherapy [1][2][3][4]. The basic principles of effective radiotherapy rely upon the concept of the therapeutic ratio: the greater relative level of tumor cytoreduction compared to normal tissue damage [5][6][7]. The principles of clinical radiotherapy also rely upon attention to detail regarding the physical parameters associated with an effective therapeutic ratio, including (1) minimizing the volume of normal tissue irradiated; (2) not exceeding the necessary therapeutic dose delivered; (3) the fraction size (dose given per day over a multiday/multiweek course of radiotherapy); (4) the overall duration (time course in days to weeks) of each particular treatment program.…”

Section: Introductionmentioning

confidence: 99%

“…Clinical radiation oncology has evolved, as a medical specialty with its primary goal to provide optimization of the therapeutic ratio to prevent acute and late toxicity [5][6][7]. The ability to shape a radiation field around a cancer target volume, while protecting normal tissues, has been greatly facilitated by improvement in the physical parameters of therapy machines.…”

Section: Introductionmentioning

confidence: 99%

“…A third category of physical parameters for improvements in radiotherapy involves dose and fraction size [5][6][7]. Hypofractionation (reduced number of treatments including stereotactic radiotherapy and stereotactic body radiotherapy) with higher dose per treatment was tested and found in some cases to produce the same outcome as found with more cumbersome multiweek conventional fractionation schedules, which traditionally deliver 1.8-2.0 Gy per day.…”

Section: Introductionmentioning

confidence: 99%

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Gene Therapy for Systemic or Organ Specific Delivery of Manganese Superoxide Dismutase

2021

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Manganese superoxide dismutase (MnSOD) is a dominant component of the antioxidant defense system in mammalian cells. Since ionizing irradiation induces profound oxidative stress, it was logical to test the effect of overexpression of MnSOD on radioresistance. This task was accomplished by introduction of a transgene for MnSOD into cells in vitro and into organs in vivo, and both paradigms showed clear radioresistance following overexpression. During the course of development and clinical application of using MnSOD as a radioprotector, several prominent observations were made by Larry Oberley, Joel Greenberger, and Michael Epperly which include (1) mitochondrial localization of either manganese superoxide dismutase or copper/zinc SOD was required to provide optimal radiation protection; (2) the time required for optimal expression was 12–18 h, and while acceptable for radiation protection, the time delay was impractical for radiation mitigation; (3) significant increases in intracellular elevation of MnSOD activity were required for effective radioprotection. Lessons learned during the development of MnSOD gene therapy have provided a strategy for delivery of small molecule SOD mimics, which are faster acting and have shown the potential for both radiation protection and mitigation. The purpose of this review is to summarize the current status of using MnSOD-PL and SOD mimetics as radioprotectors and radiomitigators.

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“…The complexity of cancer patients and the rapid changes in terms of technological evolution that characterize RO as a discipline, require that all involved professionals have to remain updated on scientific progress and trained in interdependent skills of their specific professional area [9]. Scientific research in RO has historically relied on two principal professional figures: the radiation oncologist and the medical physicist [10].…”

Section: Introductionmentioning

confidence: 99%

Radiation therapy technologists’ involvement and opinion in research: A national survey in Italy

Piro

Boldrini

Cornacchione

et al. 2020

Technical Innovations & Patient Support in Radiation Oncolo

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Introduction: This survey describes Italian RTTs' involvement and opinions in research activities related to radiation oncology. Primary aim was to assess the degree of involvement of the national RTTs community in research and to describe how RTTs can integrate their skills collaborating with other professionals. Materials and methods: A ten-items multiple-choice questionnaire, with 2-8 possible responses, was developed by a steering committee and generated on a survey platform. Links were sent via email to Italian RTTs.The questions were divided in 3 domains: demographic data; scientific research and activity; opinions about RTTs role in scientific research. The survey started on October 1, 2018 and ended on January 31, 2019.Results: One hundred thirty-five out of 509 (26.5%) RTTs responded to the questionnaire at its expiring date; 97.73% think to be valid contributors in radiation oncology research, expressing clear interest in ''data collection" tasks (52.71%); 38.64% feel unsupported by other professionals in the research team and 59.85% of the respondents are not members in any scientific society. Conclusions: The role of Italian RTTs in research is heterogeneous. Mainly RTTs in the age range from 30 to 40 years responded to the survey showing their interest in scientific research. This might be related to different informatics and educational skills as well as to personal attitudes. RTTs particular skills, like data management and technical hypothesis generation abilities, are of benefit to realize research projects. Therefore, engaging RTTs in research activities is strongly suggested.

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Novel treatment planning approaches to enhance the therapeutic ratio: targeting the molecular mechanisms of radiation therapy

Cited by 5 publications

References 115 publications

Feasibility of lattice radiotherapy using proton and carbon ion pencil beam for sinonasal adenoid cystic carcinoma

Feasibility of lattice radiotherapy using proton and carbon ion pencil beam for sinonasal adenoid cystic carcinoma

Gene Therapy for Systemic or Organ Specific Delivery of Manganese Superoxide Dismutase

Radiation therapy technologists’ involvement and opinion in research: A national survey in Italy

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