The literature is reviewed to identify the main clinical and dose-volume predictors for acute and late radiation-induced heart disease. A clear quantitative dose and/or volume dependence for most cardiac toxicity has not yet been shown, primarily because of the scarcity of the data. Several clinical factors, such as age, comorbidities and doxorubicin use, appear to increase the risk of injury. The existing dose-volume data is presented, as well as suggestions for future investigations to better define radiation-induced cardiac injury.

The biological effectiveness of proton beams relative to photon beams in radiation therapy has been taken to be 1.1 throughout the history of proton therapy. While potentially appropriate as an average value, actual relative biological effectiveness (RBE) values may differ. This Task Group report outlines the basic concepts of RBE as well as the biophysical interpretation and mathematical concepts. The current knowledge on RBE variations is reviewed and discussed in the context of the current clinical use of RBE and the clinical relevance of RBE variations (with respect to physical as well as biological parameters). The following task group aims were designed to guide the current clinical practice: Assess whether the current clinical practice of using a constant RBE for protons should be revised or maintained. Identifying sites and treatment strategies where variable RBE might be utilized for a clinical benefit. Assess the potential clinical consequences of delivering biologically weighted proton doses based on variable RBE and/or LET models implemented in treatment planning systems. Recommend experiments needed to improve our current understanding of the relationships among in vitro, in vivo, and clinical RBE, and the research required to develop models. Develop recommendations to minimize the effects of uncertainties associated with proton RBE for well‐defined tumor types and critical structures.

Each year, 500,000 patients are treated with radiotherapy for head and neck cancer, resulting in relatively high survival rates. However, in 40% of patients, quality of life is severely compromised because of radiation-induced impairment of salivary gland function and consequent xerostomia (dry mouth). New radiation treatment technologies enable sparing of parts of the salivary glands. We have determined the parts of the major salivary gland, the parotid gland, that need to be spared to ensure that the gland continues to produce saliva after irradiation treatment. In mice, rats, and humans, we showed that stem and progenitor cells reside in the region of the parotid gland containing the major ducts. We demonstrated in rats that inclusion of the ducts in the radiation field led to loss of regenerative capacity, resulting in long-term gland dysfunction with reduced saliva production. Then we showed in a cohort of patients with head and neck cancer that the radiation dose to the region of the salivary gland containing the stem/progenitor cells predicted the function of the salivary glands one year after radiotherapy. Finally, we showed that this region of the salivary gland could be spared during radiotherapy, thus reducing the risk of post-radiotherapy xerostomia.

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Background and Purpose Brain radiotherapy is limited in part by damage to white matter, contributing to neurocognitive decline. We utilized diffusion tensor imaging (DTI) with multiple b-values (diffusion weightings) to model the dose-dependency and time course of radiation effects on white matter. Materials and Methods Fifteen patients with high-grade gliomas treated with radiotherapy and chemotherapy underwent MRI with DTI prior to radiotherapy, and after months 1, 4-6, and 9-11. Diffusion tensors were calculated using three weightings (high, standard, and low b-values) and maps of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (λ‖), and radial diffusivity (λ⊥) were generated. The region of interest was all white matter. Results MD, λ‖, and λ⊥increased significantly with time and dose, with corresponding decrease in FA. Greater changes were seen at lower b-values, except for FA. Time-dose interactions were highly significant at 4-6 months and beyond (p < .001), and the difference in dose response between high and low b-values reached statistical significance at 9-11 months for MD, λ‖, and λ⊥ (p < .001, p < .001, p = .005 respectively) as well as at 4-6 months for λ‖ (p = .04). Conclusions We detected dose-dependent changes across all doses, even <10 Gy. Greater changes were observed at low b-values, suggesting prominent extracellular changes possibly due to vascular permeability and neuroinflammation.