Objective Radiation proctitis (RP) is a complication of pelvic radiotherapy which affects both the host and microbiota. Herein we assessed the radiation effect on microbiota and its relationship to tissue damage using a rectal radiation mouse model. Design We evaluated luminal and mucosa-associated dysbiosis in irradiated and control mice at two postradiation time points and correlated it with clinical and immunological parameters. Epithelial cytokine response was evaluated using bacterial-epithelial co-cultures. Subsequently, germ-free (GF) mice were colonised with postradiation microbiota and controls and exposed to radiation, or dextran sulfate-sodium (DSS). Interleukin (IL)-1β correlated with tissue damage and was induced by dysbiosis. Therefore, we tested its direct role in radiation-induced damage by IL-1 receptor antagonist administration to irradiated mice. Results A postradiation shift in microbiota was observed. A unique microbial signature correlated with histopathology.

Radiation therapy, in conjunction with surgical implant fixation, is a common combined treatment in cases of bone metastases. However, metal implants generally used in orthopedic implants perturb radiation dose distributions. Carbon‐Fiber Reinforced Polyetheretherketone (CFR‐PEEK) material has been recently introduced for production of intramedullary nails and plates. The purpose of this work was to investigate the perturbation effects of the new CFR‐PEEK screws on radiotherapy dose distributions and to evaluate these effects in comparison with traditional titanium screws. The investigation was performed by means of Monte Carlo (MC) simulations for a 6 MV photon beam. The project consisted of two main stages. First, a comparison of measured and MC calculated doses was performed to verify the validity of the MC simulation results for different materials. For this purpose, stainless steel, titanium, and CFR‐PEEK plates of various thicknesses were used for attenuation and backscatter measurements in a solid water phantom. For the same setup, MC dose calculations were performed. Next, MC dose calculations for titanium, CFR‐PEEK screws, and CFR‐PEEK screws with ultrathin titanium coating were performed. For the plates, the results of our MC calculations for all materials were found to be in good agreement with the measurements. This indicates that the MC model can be used for calculation of dose perturbation effects caused by the screws. For the CFR‐PEEK screws, the maximum dose perturbation was less than 5%, compared to more than 30% perturbation for the titanium screws. Ultrathin titanium coating had a negligible effect on the dose distribution. CFR‐PEEK implants have good prospects for use in radiotherapy because of minimal dose alteration and the potential for more accurate treatment planning. This could favorably influence treatment efficiency and decrease possible over‐ and underdose of adjacent tissues. The use of such implants has potential clinical advantages in the treatment of bone metastases.

Radiotherapy induces immune-related responses in cancer patients by various mechanisms. Here, we investigate the immunomodulatory role of tumor-derived microparticles (TMPs)-extracellular vesicles shed from tumor cells-following radiotherapy. We demonstrate that breast carcinoma cells exposed to radiation shed TMPs containing elevated levels of immune-modulating proteins, one of which is programmed death-ligand 1 (PD-L1). These TMPs inhibit cytotoxic T lymphocyte (CTL) activity both in vitro and in vivo, and thus promote tumor growth. Evidently, adoptive transfer of CTLs pre-cultured with TMPs from irradiated breast carcinoma cells increases tumor growth rates in mice recipients in comparison with control mice receiving CTLs pre-cultured with TMPs from untreated tumor cells. In addition, blocking the PD-1-PD-L1 axis, either genetically or pharmacologically, partially alleviates TMP-mediated inhibition of CTL activity, suggesting that the immunomodulatory effects of TMPs in response to radiotherapy is mediated, in part, by PD-L1. Overall, our findings provide mechanistic insights into the tumor immune surveillance state in response to radiotherapy and suggest a therapeutic synergy between radiotherapy and immune checkpoint inhibitors.

A major therapeutic obstacle in clinical oncology is intrinsic or acquired resistance to therapy, leading to subsequent relapse. We have previously shown that systemic administration of different cytotoxic drugs can induce a host response that contributes to tumor angiogenesis, regrowth and metastasis. Here we characterize the host response to a single dose of local radiation, and its contribution to tumor progression and metastasis. We show that plasma from locally irradiated mice increases the migratory and invasive properties of colon carcinoma cells. Furthermore, locally irradiated mice intravenously injected with CT26 colon carcinoma cells succumb to pulmonary metastasis earlier than their respective controls. Consequently, orthotopically implanted SW480 human colon carcinoma cells in mice that underwent radiation, exhibited increased metastasis to the lungs and liver compared to their control tumors. The irradiated tumors exhibited an increase in the colonization of macrophages compared to their respective controls; and macrophage depletion in irradiated tumor-bearing mice reduces the number of metastatic lesions. Finally, the anti-tumor agent, dequalinium-14, in addition to its anti-tumor effect, reduces macrophage motility, inhibits macrophage infiltration of irradiated tumors and reduces the extent of metastasis in locally irradiated mice. Overall, this study demonstrates the adverse effects of local radiation on the host that result in macrophage-induced metastasis.

Aims: To evaluate how common radiation therapy techniques perform in the setting of the new European Society for Radiotherapy and Oncology-Advisory Committee in Radiation Oncology Practice (ESTRO-ACROP) delineation recommendations for immediate breast reconstruction (IBR). Materials and methods: Seven Danish radiation therapy centres and six international European centres participated in this project. Two breast cancer cases (one left-sided and one right-sided) with a retropectoral implant were chosen for radiation therapy planning using deep-inspiration breath-hold. Target volumes were delineated according to ESTRO-ACROP delineation recommendations. The centres were asked to plan the cases using any radiation therapy technique according to the Danish Breast Cancer Group plan objectives.