What's Changed in 75 Years of RadRes? - An Australian Perspective on Selected Topics.

Several scientific themes are reviewed in the context of the 75-year period relevant to this special platinum issue of Radiation Research. Two criteria have been considered in selecting the scientific themes. One is the exposure of the associated research activity in the annual meetings of the Radiation Research Society (RRS) and in the publications of the Society's Journal, thus reflecting the interest of members of RRS. The second criteria is a focus on contributions from Australian members of RRS. The first theme is the contribution of radiobiology to radiation oncology, featuring two prominent Australian radiation oncologists, the late Rod Withers and his younger colleague, Lester Peters. Two other themes are also linked to radiation oncology; preclinical research aimed at developing experimental radiotherapy modalities, namely microbeam radiotherapy (MRT) and Auger endoradiotherapy. The latter has a long history, in contrast to MRT, especially in Australia, given that the associated medical beamline at the Australian Synchrotron in Melbourne only opened in 2011. Another theme is DNA repair, which has a trajectory parallel to the 75-year period of interest, given the birth of molecular biology in the 1950s. The low-dose radiobiology theme has a similar timeline, predominantly prompted by the nuclear era, which is also connected to the radioprotector theme, although radioprotectors also have a long-established potential utility in cancer radiotherapy. Finally, two themes are associated with biodosimetry. One is the micronucleus assay, highlighting the pioneering contribution from Michael Fenech in Adelaide, South Australia, and the other is the γ-H2AX assay and its widespread clinical applications.

[Éditorial. La radiothérapie dix ans après]. / Éditorial. La radiothérapie dix ans après.

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[Radiotherapy for non-tumoral disorders : a brief history and indications in 2024]. / La radiothérapie des pathologies non tumorales : un bref historique et possibilités en 2024.

Radiotherapy for non-tumoral disorders has a long history. Lack of high-level evidence, therapeutic alternatives and fear of side effects (particularly radiation-induced cancer) reduced some indications to a trickle during the second half of the 20th century. Others were logically abandoned. There are two exceptions to this trend. On the one hand, some Central European countries (Germany in particular) still use radiotherapy regularly for diseases such as osteoarthritis, plantar fasciitis, chronic tendinopathies, Dupuytren's disease, etc. On the other hand, the development of stereotactic ablative radiotherapy has opened up new indications, whether cerebral (arteriovenous malformations, trigeminal neuralgia, obsessive-compulsive disorders) or cardiac (ventricular tachycardia). In this article, we present a non-exhaustive list of some indications (or rather possibilities) for radiotherapy in non-tumoral disorders in 2024.

La radiothérapie des pathologies non tumorales possède une longue histoire. L'absence de preuves d'un niveau élevé, les alternatives thérapeutiques et la peur d'effets secondaires (en particulier le cancer radio-induit) ont réduit certaines indications à peau de chagrin durant la seconde moitié du 20ème siècle. D'autres ont logiquement été abandonnées. Deux exceptions existent concernant cette diminution. D'une part, certains pays d'Europe centrale (l'Allemagne en particulier) continuent d'utiliser régulièrement la radiothérapie dans des pathologies telles que l'arthrose, la fasciite plantaire, les tendinopathies chroniques, la maladie de Dupuytren ... D'autre part, le développement de la radiothérapie stéréotaxique ablative a permis d'envisager de nouvelles indications qu'elles soient cérébrales (malformations artério-veineuses, névralgie du trijumeau, troubles obsessionnels compulsifs) ou cardiaques (tachycardie ventriculaire). Nous présentons, de façon non exhaustive, quelques indications (ou plutôt possibilités) de radiothérapie dans les pathologies non tumorales utilisées en 2024.

A Century of Fractionated Radiotherapy: How Mathematical Oncology Can Break the Rules.

Radiotherapy is involved in 50% of all cancer treatments and 40% of cancer cures. Most of these treatments are delivered in fractions of equal doses of radiation (Fractional Equivalent Dosing (FED)) in days to weeks. This treatment paradigm has remained unchanged in the past century and does not account for the development of radioresistance during treatment. Even if under-optimized, deviating from a century of successful therapy delivered in FED can be difficult. One way of exploring the infinite space of fraction size and scheduling to identify optimal fractionation schedules is through mathematical oncology simulations that allow for in silico evaluation. This review article explores the evidence that current fractionation promotes the development of radioresistance, summarizes mathematical solutions to account for radioresistance, both in the curative and non-curative setting, and reviews current clinical data investigating non-FED fractionated radiotherapy.

A 25-year perspective on the evolution of radiation treatment of urologic cancers.

Advances in radiotherapy technology and technique over the last 3 decades have revolutionized radiation treatment options for genitourinary malignancies. The development of more focused and accurate radiation treatment has facilitated safe delivery of dose-escalated treatment that improves disease control and the development of shorter-duration hypofractionated treatment regimens that are more convenient for patients and improve access to treatment. The management of oligometastatic disease is evolving with ablative treatment of oligometastasis and the primary for select patients and shorter-duration palliative treatment regimens. Work is ongoing to personalize radiation treatment regimens for genitourinary malignancies based on molecular biomarkers.

Treating infections with ionizing radiation: a historical perspective and emerging techniques.

BACKGROUND: Widespread use and misuse of antibiotics have led to a dramatic increase in the emergence of antibiotic resistant bacteria, while the discovery and development of new antibiotics is declining. This has made certain implant-associated infections such as periprosthetic joint infections, where a biofilm is formed, very difficult to treat. Alternative treatment modalities are needed to treat these types of infections in the future. One candidate that has been used extensively in the past, is the use of ionizing radiation. This review aims to provide a historical overview and future perspective of radiation therapy in infectious diseases with a focus on orthopedic infections. METHODS: A systematic search strategy was designed to select studies that used radiation as treatment for bacterial or fungal infections. A total of 216 potentially relevant full-text publications were independently reviewed, of which 182 focused on external radiation and 34 on internal radiation. Due to the large number of studies, several topics were chosen. The main advantages, disadvantages, limitations, and implications of radiation treatment for infections were discussed. RESULTS: In the pre-antibiotic era, high mortality rates were seen in different infections such as pneumonia, gas gangrene and otitis media. In some cases, external radiation therapy decreased the mortality significantly but long-term follow-up of the patients was often not performed so long term radiation effects, as well as potential increased risk of malignancies could not be investigated. Internal radiation using alpha and beta emitting radionuclides show great promise in treating fungal and bacterial infections when combined with selective targeting through antibodies, thus minimizing possible collateral damage to healthy tissue. CONCLUSION: The novel prospects of radiation treatment strategies against planktonic and biofilm-related microbial infections seem feasible and are worth investigating further. However, potential risks involving radiation treatment must be considered in each individual patient.

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.

The madness of Princess Alice: Sigmund Freud, Ernst Simmel and Alice of Battenberg at Kurhaus Schloß Tegel.

During the winter of 1930, Princess Alice of Battenberg was admitted to Kurhaus Schloß Tegel, where she was diagnosed with schizophrenic paranoia. When Freud was consulted about her case by Ernst Simmel, the Sanatorium's Director, he recommended that the patient's ovaries be exposed to high-intensity X-rays. Freud's suggestion was not based on any psychoanalytic treatment principles, but rooted in a rejuvenation technique to which Freud himself had subscribed. In recommending that psychotic patients should be treated with physical interventions, Freud confirmed his conviction that the clinical applicability of psychoanalysis should not be extrapolated beyond the neuroses, yet he also asserted that a proper consideration of endocrinological factors in the aetiology and treatment of the psychoses should never be excluded.

Targeted Radionuclide Therapy: A Historical and Personal Review.

This review traces the development of targeted radionuclide therapy (TRT) (the Magic Bullet) from the discovery of radioactivity in nature and the subsequent discovery of artificial radioactivity (the production of radioactive isotopes of stable elements) to the current status of TRT in the medical literature and clinical practice. With the availability of radioisotopes of iodine, initially to study thyroidal iodine kinetics, it was soon observed that sufficient amounts of radiation could control thyroid hyperfunction. Shortly thereafter, when radioiodine was administered to a patient with differentiated thyroid carcinoma whose hypermetabolism was secondary to excess thyroid hormone production, it was observed that radioiodine also had an antitumor effect. The concept of the Magic Bullet has since been extended to other disease states such as (1) 131I-meta-iodobenzylguanidine (131I-MIBG) to treat malignant and metastatic pheochromocytomas and paragangliomas; (2) 131I-tositumomab, a radioiodinated anti-CD20 IgG to treat CD20 expressing non-Hodgkins lymphoma. In recent years, other ß-emitting radionuclides, Yttrium-90 (90Y) and Lutetium-177 (177Lu), have been added to this list. These radiometals have different physical properties that were thought to be possibly more effective than radioiodine. 90Y was initially used to radio-label somatostatin analogues to treat metastatic neuroendocrine tumors but has virtually been replaced by 177Lu since the physical characteristics of the latter appear to be better suited to effectively irradiate the micrometastases of neuroendocrine tumors. A similar evolution is taking place in the development of a targeted radionuclide therapeutic that recognizes prostate-specific membrane antigen (PSMA), an epitope expressed in increased amounts in prostate carcinoma. Both an anti-PSMA immunoglobulin (J591) and a small molecule glutamase ligand are currently being evaluated as targeted radionuclide therapy agents. Radionuclides that have affinity for the calcium hydroxyapatite in bone have been used to relieve bone pain due to tumor metastases based on increased deposition of the bone seeking radiometals at the osteoblastic interface of the tumor metastases and boney matrix. Most of these trials have been in patients with metastatic prostate cancer since there are few other options. In this regard, targeted radionuclide therapy has come full circles as the most recent addition to this anti-tumor arsenal is a radioisotope of Radium, 223Ra, an alpha emitter which has a greater radiobiologic effect but limited range in tissue thus adding an element of safety when treating marrow metastases. Other alpha emitting radiometals are currently being evaluated as alternative radiometals in place of 90Y and 177Lu to label targeting molecules.

Radiotherapy in India: History, current scenario and proposed solutions.

The history and current status of a biomedical discipline in a country or region provide important health system indicators. During the last one hundred years, radiotherapy has established its position as a vital specialty in cancer management. It has proved to be one of the most cost effective ways of treating cancer providing both radical and palliative treatments depending on patient stage and performance status. However, access to radiotherapy for cancer patients in India is limited by several factors including physical proximity of centre, cost and availability of required technology. This article gives an outline of the history, existing radiotherapy facilities and future trends related to radiotherapy practice in India.

Repeat Resection and Intraoperative Radiotherapy for Malignant Gliomas of the Brain: A History and Review of Current Techniques.

The degree of primary resection of malignant brain gliomas (MBGs) has correlated positively with progression-free and overall survival. The indications for surgery and reoperation in MBG relapse remain controversial. Surgery will not be curative and should be followed by adjuvant treatment. We reviewed the reported studies with respect to repeat resection and the various methods of intraoperative radiotherapy for MBGs from the initial experience with high-energy linear accelerators in Japan to modern, integrated brachytherapy solutions using solid and balloon applicators. Because of the findings from our review, we have begun to research into the use of intraoperative balloon brachytherapy for recurrent MBGs.

Development of Targeted Alpha Therapy from Bench to Bedside.

This review briefly describes recent promising developments of alpha emitter labelled compounds for targeted alpha therapy of bladder cancer, brain tumours, neuroendocrine tumours, and prostate cancer.

Synchrotron radiation biomedical imaging and radiotherapy: from the UK to the Antipodes.

Although the general public might think of 'X-rays' as they are applied to imaging (radiography) and for the treatment of disease (radiotherapy), the use of synchrotron radiation (SR) X-ray beams in these areas of science was a minor activity 50 years ago. The largest gains in science from SR were seen to be in those areas where signals were weakest in laboratory instruments, such as X-ray diffraction and spectroscopy. As the qualities of SR X-rays were explored and more areas of science adopted SR-based methods, this situation changed. About 30 years ago, the clinical advantages of using SR X-ray beams for radiography, radiotherapy and clinical diagnostics started to be investigated. In the UK, a multi-disciplinary group, consisting of clinicians, medical physicists and other scientists working mainly with the Synchrotron Radiation Source (SRS) in Cheshire, started to investigate techniques for diagnosis and potentially a cure for certain cancers. This preliminary work influenced the design of new facilities being constructed around the world, in particular the Imaging and Medical Beam Line on the Australian Synchrotron in Melbourne. Two authors moved from the UK to Australia to participate in this exciting venture. The following is a personal view of some of the highlights of the early-year SRS work, following through to the current activities on the new facility in Australia. This article is part of the theme issue 'Fifty years of synchrotron science: achievements and opportunities'.

Radiation protection biology then and now.

Purpose: Radiation biology is a branch of the radiation research field which focuses on studying radiation effects in cells and organisms. Radiation can be used in biological investigations for two, mutually non-exclusive reasons: (1) to study biological processes by perturbing their functioning (qualitative approach) and (2) to assess consequences of radiation-induced damage (quantitative approach). While the former approach has a basic research character, the latter has an applied character that is driven by needs of medical applications and radiological protection. Radiation protection biology is defined in the sense of the second approach. The aim of the article is to provide a historical review of how radiation protection biology developed and how it influences radiological protection. Conclusions: While radiobiological investigations started immediately after the discovery of X-rays, the qualitative approach dominated until the end of World War II. After 1945, the nuclear weapons race and nuclear energy programs initiated quantitative radiobiological research. Radiation protection biology does not provide results from which radiation risks can be directly derived. Rather, it provides data that is necessary for understanding the nature of risks. Most recent years have seen, especially in Europe, a growing interest in coordinated studies on the effects of low radiation doses.

Chemical radiosensitizers: the Journal history.

Purpose: To review the Journal's coverage of chemical radiosensitizers. Methods: I have reviewed all the possibly-relevant papers that appeared in the Journal prior to 1970 and since 2010, plus the most highly-cited papers from the intervening years. I excluded papers that dealt only with oxygen as a sensitizer, that referred to sensitization of phototoxicity or hyperthermia, or that described interactions with antineoplastic agents unless they clearly distinguish between additive toxicity and radiosensitization. My definition of 'chemical' was very broad, so the coverage includes everything from classical hypoxic cell sensitizers to gold nanoparticles. Results: A literature search identifies ∼600 Journal articles as involving 'radiation sensitizing agents'; these articles are not common in Journals' first years but take off after 1970 with a peak in the late 1980s. Half of the highly-cited radiosensitizer papers were published between 1969 and 1974; the two most-cited radiosensitizer papers were 1969 and 1979 papers on hypoxic cell sensitizers. The third most-cited radiosensitizer paper would not come for two more decades, and it would use a physical rather than a chemical approach to radiosensitization. Conclusion: The development of an agent that would differentially sensitize tumors to irradiation remains a 'holy grail' of clinically-oriented radiobiology. Approaches to this goal have been a major feature of the Journal since its first decade, but we have yet to find such an agent. Perhaps we should be discouraged, but personally, I remain optimistic that we (or our students) will succeed.

The 42nd Lauriston S. Taylor Lecture: Radiation Dosimetry Research for Medicine and Protection-A European Journey.

The assessment of doses related to exposures to ionizing radiation is an essential part of all applications of ionizing radiation including radiation medicine, radiation protection, radiation biology, radiation epidemiology, and also industrial uses of radiation. Absorbed dose is generally considered to be the fundamental quantity of radiation dosimetry. It is a metrologically sound quantity for which even primary standards exist for some materials, and it is used routinely in practice. However, there is no unique correlation between absorbed dose and the radiation-induced biological effect considered. There are also different objectives of radiation dosimetry for different applications. In radiation protection, quantities are required to set meaningful exposure limits and to implement the principle of optimization. In radiation therapy, the dependence of clinical outcomes on temporal aspects of the irradiations must be accounted for. In radiation diagnostics, quantities are needed to enable and monitor optimization of radiation dose and image quality. In radiation protection and in therapy with high linear-energy-transfer radiations, appropriate methods and parameters are needed to account for differences in radiation quality. These limitations of the quantity absorbed dose have led to the use of a multiplicity of dose quantities and dose modification factors. Radiation dosimetry continues, therefore, to be a field of active research regarding fundamental and conceptual aspects, taking account of advances in technologies, of novel methods in radiation therapy and diagnostics, and of progress in computational dosimetry. Dosimetry of high-energy radiations such as cosmic radiation encountered at flight altitudes and during space missions as well as at high-energy accelerators has become an important issue. In Europe, collaboration and coordination of radiation research in general, and dosimetry research in particular, are playing an important role. Dedicated research programs of the European Commission have been and still are very valuable and include collaborations with institutes in Eastern Europe and non-European countries. Several current and recent research topics in radiation dosimetry are addressed based on research carried out within European research programs, at European research centers including the European Organization for Nuclear Research (known as CERN), in European particle therapy projects, and at national metrological institutes. One focus is the quantification of radiation quality in radiation protection and in high linear-energy-transfer radiation therapy with emphasis on measurements with low-pressure proportional counters. Another focus is dosimetry of high-energy radiations with respect to measurements of cosmic radiation and at CERN's high-energy accelerators.