[Biologic effects of high doses per fraction]. / Effets biologiques des hautes doses par fraction.

The radiobiological concepts described for conventional doses per fraction (1.8 to 2Gy) seem difficult to translate to high doses per fraction radiobiology. In fact, specific mechanisms are involved during high dose per fraction irradiation, involving vascular microenvironment damage and anti tumor immune response. The "5R's" of "classical" radiobiology (factors influencing the response of healthy or cancer cells to irradiation) seem to play a less important role in case of high doses per fraction. In addition, applicability of the linear quadratic model in this context is debated. It is therefore difficult to obtain reliable equivalent doses, hence the importance of including our patients in clinical trials, especially in case of concomitant systemic treatments. In addition to stereotactic radiotherapy, flash irradiations defined by a dose rate approximately 2000 times faster than "conventional" irradiation can also deliver high doses per fraction, with a much better tolerance for normal tissue without loss of anti tumor efficacy. Finally, availability of robust prospective data is a prerequisite to answer the question of short and long-term risk/benefit ratio of these different irradiation techniques.

Use of radiobiology in medical jurisprudence, with particular reference to delays in diagnosis and therapeutic onset.

OBJECTIVE: This paper considers aspects of radiobiology and cell and tissue kinetics applicable to legal disputations concerned with diagnostic and treatment onset delays. METHODS: Various models for tumour volume changes with time are reviewed for estimating volume ranges at earlier times, using ranges of kinetic parameters. Statistical cure probability methods, using Poisson statistics with allowances for parameter heterogeneity, are also described to estimate the significance of treatment delays, as well as biological effective dose (BED) estimations of radiation effectiveness. RESULTS: The use of growth curves, based on parameters in the literature but with extended ranges, can identify a window of earlier times when such tumour volumes would be amenable to a cure based on the literature for curability with stage (and dimensions). Also, where tumour dimensions are not available in a post-operative setting, higher cure probabilities can be achieved if treatment had been given at earlier times. CONCLUSION: The use of radiobiological modelling can provide useful insights, with quantitative assessments of probable prior conditions and future outcomes, and thus be of assistance to a Court in deciding the most correct judgement. ADVANCES IN KNOWLEDGE: This study collates prior knowledge about aspects of radiobiology that can be useful in the accumulation of sufficient proof within medicolegal claims involving diagnostic and treatment days.

Thirty-sixth Lauriston S. Taylor Lecture on radiation protection and measurements--from the field to the laboratory and back: the what ifs, wows, and who cares of radiation biology.

My scientific journey started at the University of Utah chasing fallout. It was on everything, in everything, and was distributed throughout the ecosystem. This resulted in radiation doses to humans and caused me great concern. From this concern I asked the question, "Are there health effects from these radiation doses and levels of radioactive contamination?" I have invested my scientific career trying to address this basic question. While conducting research, I got acquainted with many of the What ifs of radiation biology. The major What if in my research was, "What if we have underestimated the radiation risk for internally-deposited radioactive material?" While conducting research to address this important question, many other What ifs came up related to dose, dose rate, and dose distribution. I also encountered a large number of Wows. One of the first was when I went from conducting environmental fallout studies to research in a controlled laboratory. The activity in fallout was expressed as pCi L⁻¹, whereas it was necessary to inject laboratory animals with µCi g⁻¹ body weight to induce measurable biological changes, chromosome aberrations, and cancer. Wow! That is seven to nine orders of magnitude above the activity levels found in the environment. Other Wows have made it necessary for the field of radiation biology to make important paradigm shifts. For example, one shift involved changing from "hit theory" to total tissue responses as the result of bystander effects. Finally, Who cares? While working at U.S. Department of Energy headquarters and serving on many scientific committees, I found that science does not drive regulatory and funding decisions. Public perception and politics seem to be major driving forces. If scientific data suggested that risk had been underestimated, everyone cared. When science suggested that risk had been overestimated, no one cared. This result-dependent Who cares? was demonstrated as we tried to generate interactions by holding meetings with individuals involved in basic low-dose research, regulators, and the news media. As the scientists presented their "exciting data" that suggested that risk was overestimated, many of the regulators simply said, "We cannot use such data." The newspaper people said, "It is not possible to get such information by my editors." In spite of these difficulties, research results from basic science must be made available and considered by members of the public as well as by those that make regulatory recommendations. Public outreach of the data is critical and must continue to be a future focus to address properly the question of, "Who cares?" My journey in science, like many of yours, has been a mixture of chasing money, beatings, and the joys of unique and interesting research results. Perhaps through our experiences, we can improve research environments, funding, and use of the valuable information that is generated. Scientists that study at all levels of biological organization, from the environment to the laboratory and human epidemiology, must share expertise and data to address the What Ifs, Wows, and Who Cares of radiation biology.