original article a model for the relative biological effectiveness of protons: the tissue specific parameter a/b of photons is a predictor for the sensitivity to let changes abstract Background. The biological effects of particles are often expressed in relation to that of photons through the concept of relative biological effectiveness, RbE. in proton radiotherapy, a constant RbE of 1.1 is usually assumed. However, there is experimental evidence that RbE depends on various factors. The aim of this study is to develop a model to predict the RbE based on linear energy transfer (LET), dose, and the tissue specific parameter a/b of the linear-quadratic model for the reference radiation. Moreover, the model should capture the basic features of the RbE using a minimum of assumptions, each supported by experimental data. Material and methods. The a and b parameters for protons were studied with respect to their dependence on LET. an RbE model was proposed where the dependence of LET is affected by the (a/b) phot ratio of photons. Published cell survival data with a range of well-defined LETs and cell types were selected for model evaluation rendering a total of 10 cell lines and 24 RbE values. Results and Conclusion. a statistically significant relation was found between a for protons and LET. Moreover, the strength of that relation varied significantly with (a/b) phot . in contrast, no significant relation between b and LET was found. On the whole, the resulting RbE model provided a significantly improved fit (p-value  0.01) to the experimental data compared to the standard constant RbE. by accounting for the a/b ratio of photons, clearer trends between RbE and LET of protons were found, and our results suggest that late responding tissues are more sensitive to LET changes than early responding tissues and most tumors. an advantage with the proposed RbE model in optimization and evaluation of treatment plans is that it only requires dose, LET, and (a/b) phot as input parameters. Hence, no proton specific biological parameters are needed. Oncologica, 2013; 52: 580-588 iSSn 0284-186X print/iSSn 1651-226X online Acta

New radiobiological models are used to describe tumour and normal tissue reactions and to account for their dependence on the irradiated volume and inhomogeneities of the delivered dose distribution and cell sensitivity. The probability of accomplishing complication-free tumour control is maximized by an iterative algorithm. The algorithm is demonstrated by applying it to a one-dimensional (1D) tumour model but also to a more clinically relevant 2D case. The new algorithm is n-dimensional so it could simultaneously optimize the dose delivery in a 3D volume and in principle also select the ideal beam orientations, beam modalities (photons, electrons, neutrons, etc) and optimal spectral distributions of the corresponding modalities. To make calculation time reasonable, 2D-3D problems are most practical, and suitable beam orientations are preselected by the choice of irradiation kernel. The energy deposition kernel should therefore be selected in order to avoid irradiation through organs at risk. Clinically established dose response parameters for the tissues of interest are used to make the optimization as relevant as possible to the clinical problems at hand. The algorithm can be used even with a poorly selected kernel because it will always, as far as possible, avoid irradiating organs at risk. The generated dose distribution will be optimal with respect to the spatial distribution and assumed radiobiological properties of the tumour and normal tissues at risk for the kernel chosen. More specifically the probability of achieving tumour control without fatal complications in normal tissues is maximized. In the clinical examples a reduced tumour dose is seen at the border to sensitive organs at risk, but instead an increased dose just inside the tumour border is generated. The increased tumour dose has the effect that the dose fall-off is as steep as possible at the border to organs at risk.

BACKGROUNDIt is well recognized that many patients with head and neck carcinoma have problems with food intake and malnutrition. The objective of the current study was to determine the clinical pattern of patients with nonneoplastic stricture of the upper esophagus after radiotherapy for head and neck carcinoma.METHODSA retrospective chart study of 22 patients with stricture of the proximal esophagus diagnosed between 1993 and 1999 at Karolinska Hospital was performed. The dose volume histograms of the first 2 cm and 5 cm, respectively, of the proximal esophagus were calculated.RESULTSFive of the patients (23%) had total obliteration. The first 2 cm of the esophagus received at least 60 grays (Gy) in > 80% of the volume. Radiation injury was not reported to occur at doses < 60 Gy. There was a correlation found between dysphagia during radiotherapy and the development of proximal esophageal stricture. Stricture was diagnosed 1–60 months (median, 6 months) after radiotherapy. In 18 patients, the stricture was treated with single or repeated endoscopic dilation. These treatments allowed a nearly normal diet in 78% of the patients.CONCLUSIONSStricture of the upper esophagus is one deglutition disorder that is reported to occur after radiotherapy for head and neck carcinoma. In the current study, the authors emphasize the importance of knowing the tolerance of the normal esophagus to irradiation as well as early diagnosis of stricture of the proximal esophagus because this condition may lead to physical and emotional distress. Cancer 2003;97:1693–700. © 2003 American Cancer Society.DOI 10.1002/cncr.11236

Developments in radiation therapy planning have improved the information about the three-dimensional dose distribution in the patient. Isodose graphs, dose volume histograms and most recently radiobiological models can be used to evaluate the dose distribution delivered to the irradiated organs and volumes of interest. The concept of a biologically effective uniform dose (D) assumes that any two dose distributions are equivalent if they cause the same probability for tumour control or normal tissue complication. In the present paper the D concept both for tumours and normal tissues is presented, making use of the fact that probabilities averaged over both dose distribution and organ radiosensitivity are more relevant to the clinical outcome than the expected number of surviving clonogens or functional subunits. D can be calculated in complex target volumes or organs at risk either from the 3D dose matrix or from the corresponding dose volume histograms of the dose plan. The value of the D concept is demonstrated by applying it to two treatment plans of a cervix cancer. Comparison is made of the D concept with the effective dose (Deff ) and equivalent uniform dose (EUD) that have been suggested in the past. The value of the concept for complex targets and fractionation schedules is also pointed out.