It has been long known that patients treated with ionizing radiation carry a risk of developing a second cancer in their lifetimes. Factors contributing to the recently renewed concern about the second cancer include improved cancer survival rate, younger patient population as well as emerging treatment modalities such as intensity-modulated radiation treatment (IMRT) and proton therapy that can potentially elevate secondary exposures to healthy tissues distant from the target volume. In the past 30 years, external-beam treatment technologies have evolved significantly, and a large amount of data exist but appear to be difficult to comprehend and compare. This review article aims to provide readers with an understanding of the principles and methods related to scattered doses in radiation therapy by summarizing a large collection of dosimetry and clinical studies. Basic concepts and terminology are introduced at the beginning. That is followed by a comprehensive review of dosimetry studies for external-beam treatment modalities including classical radiation therapy, 3D-conformal x-ray therapy, intensity-modulated x-ray therapy (IMRT and tomotherapy) and proton therapy. Selected clinical data on second cancer induction among radiotherapy patients are also covered. Problems in past studies and controversial issues are discussed. The needs for future studies are presented at the end.

/pdf/a-review-of-dosimetry-studies-on-external-beam-radiation-399oilxd6q.pdf

A review of dosimetry studies on external-beam radiation treatment with respect to second cancer induction

Charged particle therapy has been largely driven and influenced by nuclear physics. The increase in energy deposition density along the ion path in the body allows reducing the dose to normal tissues during radiotherapy compared to photons. Clinical results of particle therapy support the physical rationale for this treatment, but the method remains controversial because of the high cost and of the lack of comparative clinical trials proving the benefit compared to x-rays. Research in applied nuclear physics, including nuclear interactions, dosimetry, image guidance, range verification, novel accelerators and beam delivery technologies, can significantly improve the clinical outcome in particle therapy. Measurements of fragmentation cross-sections, including those for the production of positron-emitting fragments, and attenuation curves are needed for tuning Monte Carlo codes, whose use in clinical environments is rapidly increasing thanks to fast calculation methods. Existing cross sections and codes are indeed not very accurate in the energy and target regions of interest for particle therapy. These measurements are especially urgent for new ions to be used in therapy, such as helium. Furthermore, nuclear physics hardware developments are frequently finding applications in ion therapy due to similar requirements concerning sensors and real-time data processing. In this review we will briefly describe the physics bases, and concentrate on the open issues.

https://iopscience.iop.org/article/10.1088/0034-4885/79/9/096702/pdf

Nuclear physics in particle therapy: a review.

(1987). Atoms, Radiation and Radiation Protection. International Journal of Radiation Biology and Related Studies in Physics, Chemistry and Medicine: Vol. 51, No. 5, pp. 951-951.

Atoms, Radiation and Radiation Protection

The influence of dose and dose rate on the oncogenic effectiveness of 1-MeV neutrons, 5-MeV neutrons, 250-kVp x-rays, and60 Co gamma-rays was investigated in male and female RF mice exposed to various doses of whole-body radiation at dose rates of 10-6 to $10^{2}\ \text{rads}/{\rm min}$, beginning at 10 weeks of age. Incidence of myeloid leukemia and of thymic lymphoma increased with dose, also varying with dose rate of gamma-rays but not of neutrons. Neutrons were equally or slightly less leukemogenic than x- or gamma-rays at high dose rates but several times as leukemogenic as gamma-rays at low dose rates. Incidence of ovarian tumors also varied as a function of dose and dose rate in gamma-irradiated mice, but relatively few such tumors were induced by neutrons. The cumulative incidence of nonthymic lymphomas and lung tumors was increased by gamma-irradiation at low dose rates but was decreased at high dose rates, the decrease being greater and less dependent on intensity with neutrons than with x- and ...

The dose rate of irradiation, induction of neoplasia.

Biological Considerations When Comparing Proton Therapy. With Photon Therapy

This paper presents so-called radiation effectiveness factors that are intended to represent the biological effectiveness of different radiation types, relative to high-energy Co gamma rays, for the purpose of estimating cancer risks and probability of causation of radiogenic cancers in identified individuals. Radiation effectiveness factors are expressed as subjective probability distributions to represent uncertainty that arises from uncertainties in estimates of relative biological effectiveness obtained from radiobiological studies of stochastic endpoints, limited data on biological effectiveness obtained from human epidemiological studies, and other judgments involved in evaluating the applicability of available information to induction of cancers in humans. Primarily on the basis of reviews and evaluations of available data by experts, probability distributions of radiation effectiveness factors are developed for the following radiation types: neutrons of energy less than 10 keV, 10-100 keV, 0.1-2 MeV (including fission neutrons), 2-20 MeV, and greater than 20 MeV; alpha particles of any energy emitted by radionuclides; photons of energy 30-250 keV and less than 30 keV; and electrons of energy less than 15 keV. Photons of energy greater than 250 keV and electrons of energy greater than 15 keV are assumed to have the same biological effectiveness as reference Co gamma rays and are assigned a radiation effectiveness factor of unity, without uncertainty. For neutrons and alpha particles, separate probability distributions of radiation effectiveness factors are developed for solid tumors and leukemias, and small corrections to represent an inverse dose-rate effect are applied to those distributions in cases of chronic exposure. A radiation effectiveness factor different from unity for 15-60 keV electrons is discussed but is not adopted due to a lack of relevant radiobiological data. Radiation effectiveness factors presented in this paper are incorporated in the Interactive RadioEpidemiological Program and were developed for use by The National Institute for Occupational Safety and Health and U.S. Department of Labor in evaluating claims for compensation for radiogenic cancers by workers at U.S. Department of Energy facilities.

Radiation effectiveness factors for use in calculating probability of causation of radiogenic cancers.

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Radiation effectiveness factors for use in calculating probability of causation of radiogenic cancers.