Impact of COVID-19 on the performance of a radiation oncology department at a major comprehensive cancer centre in Poland during the first ten weeks of the epidemic.

The outbreak of SARS-CoV-2 coronavirus rapidly altered radiotherapy service delivery around the world. AIM: The main objective of this study was to assess the impact of precautionary measures implemented in response to the COVID-19 pandemic on the performance of a radiation oncology departments and on mitigation the risk of COVID-19 contagion between and among patients and staff. METHODS: The study period was from March 15 until May 22, 2020. We evaluated total number of patients irradiated and those who initiated treatments, taking into account tumours localisations. We assessed the relationship of potential risk of contagion with patients' domiciles locations in regions with high number of COVID19 case. RESULTS AND CONCLUSIONS: The number of patients treated with radiotherapy during the study period decreased due to precautionary measures. After five weeks, the number of radiotherapy treatments began to increase. Just over half of the radiotherapy patients (53.5%) treated at the GPCC reside in the city of Poznan or in one of the ten surrounding counties where COVID19 incidence was low and reached at the end of the study period cumulative number of cases n = 204. The precautionary measures were effective qRT-PCR tests were performed in 1545 individuals (patients and hospital staff) revealing four staff members and none patient with a positive PCR result. Immunoglobulin testing was performed in 1132 individuals (patients and hospital staff). A total of 63 individuals were positive for antibodies.

Low dose out-of-field radiotherapy, part 2: Calculating the mean photon energy values for the out-of-field photon energy spectrum from scattered radiation using Monte Carlo methods.

PURPOSE: During radiotherapy, leakage from the machine head and collimator expose patients to out-of-field irradiation doses, which may cause secondary cancers. To quantify the risks of secondary cancers due to out-of-field doses, it is first necessary to measure these doses. Since most dosimeters are energy-dependent, it is essential to first determine the type of photon energy spectrum in the out-of-field area. The aim of this study was to determine the mean photon energy values for the out-of-field photon energy spectrum for a 6 MV photon beam using the GEANT 4-Monte Carlo method. MATERIAL AND METHODS: A specially-designed large water phantom was simulated with a static field at gantry 0°. The source-to-surface distance was 92cm for an open field size of 10×10cm2. The photon energy spectra were calculated at five unique positions (at depths of 0.5, 1.6, 4, 6, 8, and 10cm) along the central beam axis and at six different off-axis distances. RESULTS: Monte Carlo simulations showed that mean radiation energy levels drop rapidly beyond the edge of the 6 MV photon beam field: at a distance of 10cm, the mean energy level is close to 0.3MeV versus 1.5MeV at the central beam axis. In some cases, the energy level actually increased even as the distance from the field edge increased: at a depth of 1.6cm and 15cm off-axis, the mean energy level was 0.205MeV versus 0.252MeV at 20cm off-axis. CONCLUSION: The out-of-field energy spectra and dose distribution data obtained in this study with Monte Carlo methods can be used to calibrate dosimeters to measure out-of-field radiation from 6MV photons.

Low dose out-of-field radiotherapy, part 1: Measurement of scattered doses.

PURPOSE: To measure out-of-field doses in a phantom model to better quantify this radiation. MATERIAL AND METHODS: The individual contribution of photons and neutrons to the total out-of-field dose for 6 MV and 20 MV photons at open beam were measured in a purpose-designed water phantom. Radiation doses were measured at seven separate points (P1-P7) in the phantom with thermoluminescent detectors (TLD 100, 600, and 700) and GAFchromic™ EBT films. RESULTS: At a prescribed dose of 75Gy to the isocentre, the photon dose level in the close-to-field area (P2) ranged from 2.0-2.5Gy for 6 MV and 1.5-2.0Gy for 20 MV; the total out-of-field doses at P2 and P7, respectively, were estimated to be as follows: for 6 MV: TLD 100 (<3.23% and<0.14%); radiochromic film (<2.52% and <0.03%); and for 20 MV: TLD 100 (<2.94% and <0.78%); TLD 700 (<2.02% and <0.14%); and radiochromic film (<1.73% and <0.01%). Although the dose decreased rapidly as the distance from the central beam axis increased, even distant doses could be as high as several centigrays. The neutron dose for 20 MV photons at a distance of 25cm from the isocentre was 4.0mSv/Gy. CONCLUSION: Our results show that in the close-to-field area, the dose level could be as high as 1.5Gy assuming a prescribed dose of 75Gy to the isocentre. By contrast, the doses delivered to more distant areas from the planning target volume were much lower (centigrays). These findings show that both 6 MV and 20 MV photons could produce dosimetrically important dose levels outside of the field. The data reported here may be of value to study the potential impact of even very low doses of radiation on human tissues.

Low dose out-of-field radiotherapy, part 3: Qualitative and quantitative impact of scattered out-of-field radiation on MDA-MB-231 cell lines.

PURPOSE: Patients who undergo external beam radiotherapy are at risk of developing second tumours due to scattered radiation outside the path of the primary beam. The aim of this study was to experimentally determine the in vitro radiobiological effects of scattered radiation in cells located outside the primary photon beam and to compare this to the effects that occur in cells inside the primary beam. The comparison was performed by assessing cell viability, DNA damage, and apoptosis. MATERIAL AND METHODS: Cells from the human breast cancer line MDA-MB-231 were inserted in a water phantom and irradiated at varying doses (1.5, 2.0, 2.5, and 3.0Gy). The cells were placed at two geometrical points: in the central beam axis and at 10cm out-of-field. The dose was constant in both geometrical points. Survival fraction, number of DNA double strand-breaks, and cleaved poly-(ADP-ribose) polymerase (PARP) levels were determined by clonogenic assay and flow cytometry. RESULTS: A slight, non-significant decrease of 3 to 5% in cell survival fraction was observed in cells irradiated outside the primary field. The number of PARP-positive cells and DNA double strand-breaks both increased after out-of-field irradiation. CONCLUSION: Scattered irradiation appears to induce an in vitro biological response on out-of-field cells that is stronger than the effect of primary radiation on in-field cells, independent of the bystander effect. These findings suggest that the biological response of healthy tissues outside the primary beam might be higher than previously believed.

Gene-modified tumor vaccine secreting a designer cytokine Hyper-Interleukin-6 is an effective therapy in mice bearing orthotopic renal cell cancer.

Although renal cell cancer (RCC) is known to be immunogenic, clinical efficacy of various immunotherapeutic approaches remains unsatisfactory. Novel targeted therapies showing cytostatic rather than cytotoxic activity are unable to cure RCC patients. In our studies, we evaluated the therapeutic efficacy of whole-cell vaccine based on irradiated murine RENCA cells genetically modified to secrete designer cytokine--Hyper-IL6 (H6)--comprising IL-6 and soluble IL-6 receptor. An orthotopic RCC model based on a subcapsular implantation of RENCA cells into kidneys of Balb/C mice was employed. The efficacy of RENCA-H6 vaccine was compared with control vaccine (RENCA-wt) in relation to naive (non-immunized) animals. Three sets of vaccination experiments were carried out in a (i) protective, (ii) palliative and (iii) adjuvant (following nephrectomy) setting. The influence of vaccination on survival of RCC-bearing animals was analyzed. Specificity of vaccine-induced immune response was studied using model antigen-GFP. RCC-bearing animals immunized with RENCA-H6 vaccine showed prolonged survival compared with other groups. In palliative and adjuvant settings the survival RENCA-H6-immunized animals exceeded 75%. Administration of RENCA-H6 inhibited formation and recruitment of Treg cells (CD4+CD25+Foxp3+) and increased maturation of DCs. RENCA tumors in RENCA-H6- vaccinated animals contained large populations of NK cells and activated CD4+, CD8+ T cells. In addition, in mice vaccinated with RENCA-H6 cells large population of CD4+ and CD8+ memory cells (CD62Llow) were detected. In the orthotopic RCC model, RENCA-H6 vaccine showed high therapeutic potential, which resulted from modulation of numerous immunological mechanisms.