Predictive second cancer risk models based on peripheral neutron dosimetry of patients undergoing radiotherapy

Resumen

The study of Secondary Malignant Neoplasms (SMNs) after radiotherapy is becoming a topic of interest nowadays, as a consequence of the higher healing rates and life expectancy accomplished with current diagnose procedures and radiotherapy treatments. In the case of modern techniques, there is a tendency to prefer low (i.e. 6 MV) energies to high ones (e.g. 15 or 18 MV), sometimes to the detriment of treatment conformity, as the latter are known to increase equivalent dose to patients due to neutron production. The Medical Physics Group of the University of Seville, pioneered the development of a simple and universal methodology for the estimation of peripheral neutron doses, based on the correlation between readings of a SRAM-based detector (in a reference location, far from the patient) and those of passive detectors, located inside an adult anthropomorphic phantom. This correspondence model directly links detector readings (referring to thermal neutron fluence in the room) to equivalent neutron doses at specific organs in the patient. One of the main problems of this methodology was the need of using the specific SRAM-based digital detector for the characterization of every facility. In addition, the passive behavior of plastic and thermoluminiscent devices used for ‘in-phantom’ measurements, together with their limitations in these environments, restricted the repetition and reliability of some critical points. The acquisition of a new prototype of a miniaturized active thermal neutron detector, initially designed for nuclear purposes, opened the possibility of improving the existing peripheral neutron dose estimation methodology in high-energy radiotherapy. The goal of this work was the use of these devices for the validation, improvement and generalization of the existing models, in order to make the real time estimation of peripheral neutron doses directly available in any facility. The online disposal of thermal neutron fluence estimations from the new TNRD detectors (Thermal Neutron Rate Detector), allowed the simplification and generalization of this procedure. Thus, making it feasible with any thermal neutron detector following a simple characterization procedure. Additionally, their active and miniaturized behavior permitted their use in both locations ‘in-phantom’ and external (for patient measurements). In order to enhace the existing models, further and more precise measurements of real radiotherapy treatments were performed with TNRD detectors, ensuring that the two existing model locations (i.e. H&N and abdomen) are general enough to cover any specific treatment. We thought that at this stage, patient age and anatomy was an important aspect that should be taken into account for second cancer risk estimations, being of special importance for children, whose life expectancy and radiosensibility are greater. For that, measurements with the new miniaturized active devices were performed for three different phantom sizes (child, teen and adult). Once these results were implemented, this new methodology was applied to 510 patients, starting the generation of an improved database that would allow a more patient specific analysis of second cancer risk, as a consequence of neutron contamination. Besides, the analytical peripheral photon model simultaneously developed by our group, has allowed the generation of a piece of software for the estimation of both peripheral doses. This has enabled a quick assessment of photon and neutron peripheral doses in clinical routine, from readily available parameters. Estimations of these doses were finally evaluated for some of the most common tumor locations, comparing conventional techniques and fractionations (3D-CRT, IMRT, VMAT) to newer ones (SBRT, FFF), regarding the three main linac manufacturers and energies (6, 10, and 15 MV). As a general pattern, hypofractionated modality, 10 MV photon energy and FFF irradiation mode have shown as the best alternatives in terms of peripheral dose reduction. Thus, a combined use of these options would imply a decrease of second cancer probability. Second cancer risk estimations could be easily performed from the here presented procedures by the direct use of the existing risk models, established by the international organisms (i.e. ICRP or BEIR). The universal methodology presented aims to provide an objective additional criterion (Second Cancer Probability, SCP), to be used in combination wih the previously existing radiobiological parameters as Tumor Control Prrobability (TCP) and Normal Tissue Complication Probability (NTCP), for the choice of the best radiotherapy strategy, thanks to its easy implementation in Treatment Planning Systems.