Human spaceflight is associated with several health-related issues as a result of long-term exposure to microgravity, ionizing radiation, and higher levels of psychological stress. Frequent reported skin problems in space include rashes, itches, and a delayed wound healing. Access to space is restricted by financial and logistical issues; as a consequence, experimental sample sizes are often small, which limits the generalization of the results. Earth-based simulation models can be used to investigate cellular responses as a result of exposure to certain spaceflight stressors. Here, we describe the development of an in vitro model of the simulated spaceflight environment, which we used to investigate the combined effect of simulated microgravity using the random positioning machine (RPM), ionizing radiation, and stress hormones on the wound-healing capacity of human dermal fibroblasts. Fibroblasts were exposed to cortisol, after which they were irradiated with different radiation qualities (including X-rays, protons, carbon ions, and iron ions) followed by exposure to simulated microgravity using a random positioning machine (RPM). Data related to the inflammatory, proliferation, and remodeling phase of wound healing has been collected. Results show that spaceflight stressors can interfere with the wound healing process at any phase. Moreover, several interactions between the different spaceflight stressors were found. This highlights the complexity that needs to be taken into account when studying the effect of spaceflight stressors on certain biological processes and for the aim of countermeasures development.
Purpose: To quantify the effects of the Bragg peak degradation due to lung tissue on treatment plans of lung cancer patients with spot scanning proton therapy and to give a conservative approximation of these effects. Methods and materials: Treatment plans of five lung cancer patients (tumors of sizes 2.7–46.4 cm3 at different depths in the lung) were optimized without consideration of the Bragg peak degradation. These treatment plans were recalculated with the Monte Carlo code TOPAS in two scenarios: in a first scenario, the treatment plans were calculated without including the Bragg peak degradation to reproduce the dose distribution predicted by the treatment-planning system (TPS). In a second scenario, the treatment plans were calculated while including the Bragg peak degradation. Subsequently, the plans were compared by means of Dmean, D98% and D2% in the clinical target volume (CTV) and organs at risk (OAR). Furthermore, isodose lines were investigated and a gamma index analysis was performed. Results: The Bragg peak degradation leads to a lower dose in the CTV and higher doses in OARs distal to the CTV compared to the prediction from the TPS. The reduction of the mean dose in the CTV was − 5% at maximum and − 2% on average. The deeper a tumor was located in the lung and the smaller its volume the bigger was the effect on the CTV. The enhancement of the mean dose in OARs distal to the CTV was negligible for the cases investigated. Conclusions: Effects of the Bragg peak degradation due to lung tissue were investigated for lung cancer treatment plans in proton therapy. This study confirms that these effects are clinically tolerable to a certain degree in the current clinical context considering the various more critical dose uncertainties due to motion and range uncertainties in proton therapy.
Charged particle therapy with protons or heavier ions is one of the most effective radiotherapy techniques, but uncertainties in the beam range can limit its efficacy. Radioactive ion beams are ideal for image-guided particle therapy because isotopes that undergo β+ decay can be visualized with positron emission tomography. This allows spatial localization of the particle distribution in vivo, which can be correlated with the expected dose deposition for online beam range verification. Here we report the successful treatment of a mouse osteosarcoma using a radioactive 11C-ion beam. The tumour was located in the neck, close to the spinal cord, where deviations of even a few millimetres in the beam range could lead to unintended dose deposition in the spine and radiation-induced myelopathy, an injury to the spinal cord. We achieved complete tumour control with the highest dose of 20 Gy while avoiding paralysis. Low-grade neurological side effects were correlated to the activity measured by positron emission tomography in the spine. The biological washout of the activity from the tumour volume was dependent on the dose, indicating a potential component of vascular damage at high doses. This experiment marks a step towards future clinical applications of radioactive ion beams.