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Reports of Practical Oncology and... 2017Recent advances in the technology of radiotherapy have enabled the development of new therapeutic modalities that deliver radiation with very high accuracy, reduced... (Review)
Review
Recent advances in the technology of radiotherapy have enabled the development of new therapeutic modalities that deliver radiation with very high accuracy, reduced margins and high dose conformation, allowing the reduction of healthy tissue irradiated and therefore minimizing the risk of toxicity. The next step was to increase the total tumor dose using conventional fractionation (which remains the best way to relatively radioprotect healthy tissues when large volumes are treated) or to use new fractionation schemes with greater biological effectiveness. Based on the experience gained in radiosurgery, the latter way was chosen for small and well-defined tumors in the body. Stereotactic body radiotherapy delivers high doses of radiation to small and well-defined targets in an extreme hypofractionated (and accelerated) scheme with a very high biological effectiveness obtaining very good initial clinical results in terms of local tumor control and acceptable rate of late complications. In fact, we realize a posteriori that it was not feasible to administer such biologically equivalent dose in a conventional fractionation because the treatment could last several months. So far, these new therapeutic modalities have been developed due to technologic advances in image guidance and treatment delivery but without a solid biological basis. It is the role of traditional radiobiology (and molecular radiobiology) to explain the effects of high doses of ionizing radiation on tumor and normal tissues. Only through a better understanding of how high doses of ionizing radiation act, clinicians will know exactly what we do, allowing us in the future to refine our treatments. This article attempts to describe through simple and understandable concepts the known aspects of the biological action of high doses of radiation on tumor and normal tissues, but it is clear that we need much more basic research to better understand the biology of high doses of radiation.
PubMed: 28490978
DOI: 10.1016/j.rpor.2017.02.010 -
International Journal of Molecular... Mar 2022The continuously evolving field of radiotherapy aims to devise and implement techniques that allow for greater tumour control and better sparing of critical organs.... (Review)
Review
The continuously evolving field of radiotherapy aims to devise and implement techniques that allow for greater tumour control and better sparing of critical organs. Investigations into the complexity of tumour radiobiology confirmed the high heterogeneity of tumours as being responsible for the often poor treatment outcome. Hypoxic subvolumes, a subpopulation of cancer stem cells, as well as the inherent or acquired radioresistance define tumour aggressiveness and metastatic potential, which remain a therapeutic challenge. Non-conventional irradiation techniques, such as spatially fractionated radiotherapy, have been developed to tackle some of these challenges and to offer a high therapeutic index when treating radioresistant tumours. The goal of this article was to highlight the current knowledge on the molecular and radiobiological mechanisms behind spatially fractionated radiotherapy and to present the up-to-date preclinical and clinical evidence towards the therapeutic potential of this technique involving both photon and proton beams.
Topics: Dose Fractionation, Radiation; Humans; Neoplasms; Photons; Radiation Oncology; Radiobiology; Radiotherapy
PubMed: 35328787
DOI: 10.3390/ijms23063366 -
Cancers Sep 2021Vestibular schwannomas (VS) are benign tumors arising from cranial nerve VIII that account for 8-10% of all intracranial tumors and are the most common tumors of the... (Review)
Review
Vestibular schwannomas (VS) are benign tumors arising from cranial nerve VIII that account for 8-10% of all intracranial tumors and are the most common tumors of the cerebellopontine angle. These tumors are typically managed with observation, radiation therapy, or microsurgical resection. Of the VS that are irradiated, there is a subset of tumors that are radioresistant and continue to grow; the mechanisms behind this phenomenon are not fully understood. In this review, the authors summarize how radiation causes cellular and DNA injury that can activate (1) checkpoints in the cell cycle to initiate cell cycle arrest and DNA repair and (2) key events that lead to cell death. In addition, we discuss the current knowledge of VS radiobiology and how it may contribute to clinical outcomes. A better understanding of VS radiobiology can help optimize existing treatment protocols and lead to new therapies to overcome radioresistance.
PubMed: 34572805
DOI: 10.3390/cancers13184575 -
Strahlentherapie Und Onkologie : Organ... Dec 2023The number of patients treated with charged-particle radiotherapy as well as the number of treatment centers is increasing worldwide, particularly regarding protons.... (Review)
Review
The number of patients treated with charged-particle radiotherapy as well as the number of treatment centers is increasing worldwide, particularly regarding protons. However, high-linear energy transfer (LET) particles, mainly carbon ions, are of special interest for application in radiotherapy, as their special physical features result in high precision and hence lower toxicity, and at the same time in increased efficiency in cell inactivation in the target region, i.e., the tumor. The radiobiology of high-LET particles differs with respect to DNA damage repair, cytogenetic damage, and cell death type, and their increased LET can tackle cells' resistance to hypoxia. Recent developments and perspectives, e.g., the return of high-LET particle therapy to the US with a center planned at Mayo clinics, the application of carbon ion radiotherapy using cost-reducing cyclotrons and the application of helium is foreseen to increase the interest in this type of radiotherapy. However, further preclinical research is needed to better understand the differential radiobiological mechanisms as opposed to photon radiotherapy, which will help to guide future clinical studies for optimal exploitation of high-LET particle therapy, in particular related to new concepts and innovative approaches. Herein, we summarize the basics and recent progress in high-LET particle radiobiology with a focus on carbon ions and discuss the implications of current knowledge for charged-particle radiotherapy. We emphasize the potential of high-LET particles with respect to immunogenicity and especially their combination with immunotherapy.
Topics: Humans; Linear Energy Transfer; Ions; Heavy Ion Radiotherapy; Radiobiology; Carbon; Relative Biological Effectiveness
PubMed: 37872399
DOI: 10.1007/s00066-023-02158-7 -
Clinical Oncology (Royal College of... Nov 2021Microbeam radiotherapy (MRT) is the delivery of spatially fractionated beams that have the potential to offer significant improvements in the therapeutic ratio due to... (Review)
Review
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.
Topics: Humans; Radiation Oncology; Radiobiology; Radiotherapy
PubMed: 34454806
DOI: 10.1016/j.clon.2021.08.011 -
Cancers Feb 2021Clinical use of proton radiation has massively increased over the past years. The main reason for this is the beneficial depth-dose distribution of protons that allows... (Review)
Review
Clinical use of proton radiation has massively increased over the past years. The main reason for this is the beneficial depth-dose distribution of protons that allows to reduce toxicity to normal tissues surrounding the tumor. Despite the experience in the clinical use of protons, the radiobiology after proton irradiation compared to photon irradiation remains to be completely elucidated. Proton radiation may lead to differential damages and activation of biological processes. Here, we will review the current knowledge of proton radiobiology in terms of induction of reactive oxygen species, hypoxia, DNA damage response, as well as cell death after proton irradiation and radioresistance.
PubMed: 33546432
DOI: 10.3390/cancers13040604 -
Radiation and Environmental Biophysics May 2014The principle of biodosimetry is to utilize changes induced in the individual by ionizing radiation to estimate the dose and, if possible, to predict or reflect the... (Review)
Review
The principle of biodosimetry is to utilize changes induced in the individual by ionizing radiation to estimate the dose and, if possible, to predict or reflect the clinically relevant response, i.e., the biological consequences of the dose. Ideally, the changes should be specific for ionizing radiation, and the response should be unaffected by prior medical or physiological variations among subjects, including changes that might be caused by the stress and trauma from a radiation event. There are two basic types of biodosimetry with different and often complementary characteristics: those based on changes in biological parameters such as gene activation or chromosomal abnormalities and those based on physical changes in tissues (detected by techniques such as EPR). In this paper, we consider the applicability of the various techniques for different scenarios: small- and large-scale exposures to levels of radiation that could lead to the acute radiation syndrome and exposures with lower doses that do not need immediate care, but should be followed for evidence of long-term consequences. The development of biodosimetry has been especially stimulated by the needs after a large-scale event where it is essential to have a means to identify those individuals who would benefit from being brought into the medical care system. Analyses of the conventional methods officially recommended for responding to such events indicate that these methods are unlikely to achieve the results needed for timely triage of thousands of victims. Emerging biodosimetric methods can fill this critically important gap.
Topics: Animals; Environmental Exposure; Humans; Radiation Dosage; Radiobiology; Radiometry
PubMed: 24519326
DOI: 10.1007/s00411-014-0522-0 -
Seminars in Nuclear Medicine Mar 2020As a treatment modality that is fundamentally different from other therapies against cancer, radiopharmaceutical therapy with alpha-particle emitters has drawn the... (Review)
Review
As a treatment modality that is fundamentally different from other therapies against cancer, radiopharmaceutical therapy with alpha-particle emitters has drawn the attention of the therapy community and also the biopharmaceutical industry. Alpha-particles cause a preponderance of complex DNA double-strand breaks (DSBs). This provides an opportunity to either enhance cell kill by using DNA DSB repair inhibitors or identify patients who are likely to be high responders to alpha-emitter RPT. The short-range and high potency of alpha-particles requires special dosimetry considerations. These are reviewed in light of recent updates to the phantoms and associated dosimetric quantities used for dosimetry calculations. A formalism for obtaining the necessary microscale pharmacokinetic information from patient nuclear medicine imaging is presented. Alpha-emitter based radiopharmaceutical therapy is an exciting cancer therapy modality that is being revisited. Further development of imaging and dosimetric methods specific to alpha-particle emitters, coupled with standardization of the methods and rigorous evidence that dosimetry applied to alphaRPT improves patient care are needed moving forward.
Topics: Alpha Particles; Humans; Radiobiology; Radiometry; Radiopharmaceuticals
PubMed: 32172797
DOI: 10.1053/j.semnuclmed.2019.11.002 -
Journal of Nuclear Medicine Technology Dec 2017The purpose of this paper is to review basic radiation biology and associated terminology to impart a better understanding of the importance of basic concepts of... (Review)
Review
The purpose of this paper is to review basic radiation biology and associated terminology to impart a better understanding of the importance of basic concepts of ionizing radiation interactions with living tissue. As health care workers in a field that utilizes ionizing radiation, nuclear medicine technologists are concerned about the possible acute and chronic effects of occupational radiation exposure. Technologists should have a clear understanding of what they are exposed to and how their safety could be affected. Furthermore, technologists should be knowledgeable about radiation effects so that they can adequately assuage possible patient fears about undergoing a nuclear medicine procedure. After reading this article, the nuclear medicine technologist will be familiar with basic radiation biology concepts; types of interactions of radiation with living tissue, and possible effects from that exposure; theoretic dose-response curves and how they are used in radiation biology; stochastic versus nonstochastic effects of radiation exposure, and what these terms mean in relation to both high- and low-dose radiation exposure; and possible acute and chronic radiation exposure effects.
Topics: Cells; Dose-Response Relationship, Radiation; Humans; Radiation Exposure; Radiobiology; Terminology as Topic
PubMed: 29203550
DOI: 10.2967/jnmt.117.195230 -
Frontiers in Medicine 2021Targeted alpha therapy (TAT) using alpha particle-emitting radionuclides is in the spotlight after the approval of RaCl for patients with metastatic castration-resistant... (Review)
Review
Targeted alpha therapy (TAT) using alpha particle-emitting radionuclides is in the spotlight after the approval of RaCl for patients with metastatic castration-resistant prostate cancer and the development of several alpha emitter-based radiopharmaceuticals. It is acknowledged that alpha particles are highly cytotoxic because they produce complex DNA lesions. Hence, the nucleus is considered their critical target, and many studies did not report any effect in other subcellular compartments. Moreover, their physical features, including their range in tissues (<100 μm) and their linear energy transfer (50-230 keV/μm), are well-characterized. Theoretically, TAT is indicated for very small-volume, disseminated tumors (e.g., micrometastases, circulating tumor cells). Moreover, due to their high cytotoxicity, alpha particles should be preferred to beta particles and X-rays to overcome radiation resistance. However, clinical studies showed that TAT might be efficient also in quite large tumors, and biological effects have been observed also away from irradiated cells. These distant effects are called bystander effects when occurring at short distance (<1 mm), and systemic effects when occurring at much longer distance. Systemic effects implicate the immune system. These findings showed that cells can die without receiving any radiation dose, and that a more complex and integrated view of radiobiology is required. This includes the notion that the direct, bystander and systemic responses cannot be dissociated because DNA damage is intimately linked to bystander effects and immune response. Here, we provide a brief overview of the paradigms that need to be revisited.
PubMed: 34386508
DOI: 10.3389/fmed.2021.692436