Low-Dose Radiotherapy for Patients with Pneumonia Due to COVID-19: A Single-Institution Prospective Study.

PURPOSE: Results of the low-dose radiation therapy (LDRT) in patients with pneumonia due to COVID-19 has been presented. METHODS: Fifteen patients received a single-fraction radiation dose of 1 Gy to the bilateral lungs due to pre-ARDS pneumonia in the course of COVID-19. Follow-up was performed on days 1, 3, 5, 7, 14 after LDRT. RESULTS: Eleven patients (73%) were released up until day 28. Median hospitalization was 20 days; 28-day mortality was 13%. Median O2 saturation improved within 24 h after LDRT in 14/15, with median SpO2 values of 84.5% vs. 87.5% p = 0.016, respectively. At day 14 of hospitalization, 46% did not require oxygen supplementation. Significant decline in CRP and IL-6 was observed within 24 h post LDRT. No organ toxicities were noted. CONCLUSION: LDRT is feasible, well tolerated and may translate to early clinical recovery in patients with severe pneumonia. Further studies are needed to determine optimal candidate, time and dose of LDRT for COVID-19 patients with pneumonia.

Comparison of the dose distribution of the VMAT radiotherapy technique depending on the beam used: FFF-X10MV and FFF-X15MV.

Background: The aim of the study was to answer the question of whether flattening filter (FF) and flattening filter-free (FFF) beams can be used alternately in the volumetric modulated arc therapy (VMAT) treatment technique, regardless of the size of the irradiated volume [small (S) or large (L) planning target volume (PTV)]. Materials and methods: Two groups of patients were examined: a group with a S-PTV-laryngeal cancer and a group with a L-PTV - gynecological volume. For each patient, two treatment plans were made for beams (energies): FFF-X10MV and FF-X15MV. Then, a statistical analysis, nonparametric test, and independent groups were performed, comparing the beams' impact on the analyzed treatment plans. Results: In the case of laryngeal irradiation (S-PTV), there are no statistically significant differences between the energy used and the assessed parameters of the plan. In the case of gynecological volume (L-PTV), only statistically significant differences were noted for the number of monitor units depending on the energy used. For a large irradiated volume (gynecological case), the use of FFF beams increases the number of monitor units by 39,4% in relation to the FF beam. Conclusions: In the case of gynecological neoplasms, statistically significant differences were found in the number of monitor units. Therefore, in the case of irradiation of L-PTV, it is recommended that flattening-filtering beams are used due to the smaller number of monitors. In the case of S-PTV, no statistically significant differences were found between the types of beams used (FF or FFF) and the treatment plan parameters analyzed in the study.

Comparison of the Thermal Reaction of Patients after Conserving Procedures and after Mastectomy to the Radiation Dose Obtained during Radiotherapy.

The main aim of the study was to compare the temperature response of the body to the dose received during breast cancer radiotherapy. The control group consisted of 50 healthy volunteers. They underwent one thermographic examination and compared the temperatures between the left and right breasts. The research group consisted of 50 patients. Based on the treatment plan, the area PTV and isodose was marked on the thermograms. Five thermographs were performed in each patient (before radiotherapy and in each week of treatment). A qualitatively similar increase in mean temperature during treatment was observed in both subgroups in the analyzed areas. The highest increase in temperature was obtained in the third week of treatment. Compared with the value before treatment, the increase in the mean temperature in PTV in patients after partial surgery was 0.78 °C, these values are statistically significant p = 0.000055. In the case of post-mastectomy patients, 0.8 °C was obtained, these values are statistically significant p = 0.00369. In addition, strong correlation was calculated between isodoses read from treatment plans and isotherms obtained from the analysis of thermal images. In post-mastectomy patients for PTV r = 0.77, 30 Gy r = 0.94, 20 Gy r = 0.96, and 10 Gy r = 0.75. For patients after partial surgery for PTV r = 0.74, 30 Gy r = 0.89, 20 Gy r = 0.83, and 10 Gy r = 0.89. Infrared thermography seems to be a useful method of assessing the thermal response of the body to the dose received during radiotherapy of breast cancer and may be a clinically useful method of assessing the early skin response to radiation.

The Use of Infrared Thermography in the Assessment of Thermal Reaction of Patients Treated with Radiotherapy after Breast-Conserving Procedures.

The aim of the study was to assess the usefulness of the infrared thermography method in the assessment of the body's thermal reaction in patients during radiotherapy. Studies have shown how the temperature distribution changes with the dose of radiation used in each treatment week. Fifty-four patients participated in the study. The control group consisted of healthy patients, among whom the difference in mean temperatures between the breasts was checked. The study group included patients after conserving procedures qualified for radiotherapy. Measurements were taken and analyzed for each patient during each week of treatment. The target area (marked by a doctor) and the 30 Gy, 20 Gy and 10 Gy isodoses (generated from the treatment plan) were transferred on thermograms and then analyzed. This way of defining the observed areas is the most accurate and individually adjusted to each treated patient. The analysis showed an increase in temperature in the tested body surface areas, whereas the highest average temperature value was achieved during the third week of treatment. The observations may be used to evaluate the skin reaction from radiation; however, they require further studies and new quantitative parameters.

Influence of optional measurement parameters in the Eclipse treatment planning system on the quality of the dosimetric model of the biomedical accelerator using the Acuros XB algorithm.

Background: To properly configure a treatment planning system, a measurement data set is needed, which consists of the values required for its configuration. The aim is to obtain a dosimetric model of the beam that is as compatible as possible with the measured values. The set of required data can be supplemented with optional values. The aim of the study was to assess the influence of optional measurement data on the compliance of the calculations with the measurements. Materials and methods: Dosimetric measurements, model configuration and dose distribution calculations were performed for the photon radiation beams generated by the VMS TrueBeam® linear accelerator. Beams were configured on an Eclipse™ v. 15.6 system using the Acuros v. 15.6 algorithm. The measured and calculated data were entered into the Alfard™ software for comparison with the calculated dose distributions. In the last stage, the absolute dose values at the designated points were also compared. The obtained data were statistically analysed with Statistica™ v. 13.3. Results: The work showed that the differences in the shape of the beam profile, depth dose and the dose value in points were not related to the use of optional data. Differences in dose distributions are within the tolerance. It cannot be determined under which conditions the use of optional data has a more favourable effect on the reflection of the actual dose values. Conclusions: The use of optional data in modelling photon radiation beams does not significantly improve the compliance of the calculated and measured dose values.

Long-Term Skin Temperature Changes after Breast Cancer Radiotherapy.

The aim of the study was to use thermal imaging to evaluate long-term chest temperature changes in patients who had previously been treated with radiotherapy. The examination with a thermal imaging camera involved 144 women-48 of them were patients after RT, 48 were females before breast cancer radiotherapy and the last group of participants were 48 healthy women. All patients (before and after radiotherapy) were divided into women after mastectomy and those after conservative surgery. In addition, the first group of women, those who had received radiotherapy, were divided into three other groups: up to 1 year after RT, over 1 year and up to 5 years after RT and over 5 years after RT. Due to this, it was possible to compare the results and analyse the differences between the temperature in the healthy and treated breasts. The comparison of obtained temperature results showed that the area treated by ionizing radiation is characterized by a higher temperature even a few years after the finished treatment. It is worth mentioning that despite the fact that the difference was visible on the thermograms, the patients had no observable skin lesion or change in color at the treatment site. For the results of the study provided for the group of healthy patients, there were no significant differences observed between the average temperatures in the breasts. The use of thermal imaging in the evaluation of skin temperature changes after radiotherapy showed that the average temperature in the treated breast area can change even a long time after treatment.

Twelve-Month Evaluation of Temperature Effects of Radiotherapy in Patients after Mastectomy.

The aim of this study was to verify the changes in the temperature distribution within the breast at twelve months after the end of radiotherapy for breast cancer. The study included twenty-four women. The first test group consisted of twelve women who underwent breast mastectomy and qualified for radiotherapy according to standard medical treatment procedures. The second group included twelve healthy women. The tests were conducted before treatment with radiation therapy and two months, six months, nine months, and one year after the end of treatment. The mean temperature values changed depending on the time that had elapsed since the end of treatment. The highest temperature increase in all patients was observed six months after the end of radiotherapy. This research has confirmed that the assessment of temperature changes in the breast area after radiotherapy can evaluate the severity and lesions in the time course of the radiation reaction.

Physical parameters in thermal imaging of basal cell cancer patients treated with high-dose-rate brachytherapy - first study.

Background: The basal cell carcinoma (BCC) is often treated by surgery or radiotherapy using ionizing radiation. While there is an established diagnostic path before treatment and also for the follow-up there are no good noninvasive methods objectifying irradiated area evolution during treatment. The main goal of preliminary studies was to try to answer if there are any useful information that can be derived from temperature effects of high-dose-rate (HDR) brachytherapy in treatment of BCC. Moreover, the temperature gradient was introduced as a physical parameter characterizing the thermal map of the lesion, its surroundings and reference area, which provided information about cancer tissue thermal reaction to brachytherapy. Materials and methods: Thirty-three patients suffering from BCC were monitored with thermovision during the brachytherapy treatment. All lesions were diagnosed as superficial and were confirmed with histopathology examination. Results: Results of the study showed two groups of patients characterized with two thermal maps and temperature gradient describing the lesion and surrounding area of BCC. The first group was characterized by higher temperature of the lesion than the surrounding tissue temperature (mean dT = 0,41°) whereas the other one, with lower lesion temperature (mean dT = -0.42°). It seems that the temperature changes observed in designated areas before and after therapy may provide physicians with additional information which could be useful in planning the treatment process, especially when considering temperature gradient changes during therapy. Conclusions: Although the data obtained indicate the possibilities of temperature distribution in pre-irradiation cases, further research is required for estimation of clinical effects of treatment.

The Use of Thermal Imaging in the Evaluation of Temperature Effects of Radiotherapy in Patients after Mastectomy-First Study.

The aim of the study was to evaluate the temperature parameter of the breast area in patients undergoing radiotherapy at various intervals. The relationship between temperature changes on the patient's skin and the time after the end of radiotherapy was studied. Measurements with a thermal imaging camera were performed in a group of twelve volunteers. Six of them were healthy women who did not have thermal asymmetry between the breasts, whereas six were diagnosed with breast cancer and underwent mastectomy due to the advanced stage of the disease. The patients were qualified for radiation therapy. Thermographic examinations were performed before treatment, two months later and then six months after the end of the treatment. Temperature differences between the healthy breasts and the treated areas were assessed. Additionally, the correlation between a patient's skin temperature changes and the time after the end of radiotherapy was analyzed. The highest skin temperature increase (1.47 °C) was observed 6 months after the end of RT compared to the measurement before treatment. It seems that thermovision may bring a new tool for quantitative analyses of the temperature effects of radiotherapy.

Advanced dose calculation algorithm in superficial brachytherapy - the impact of tissue inhomogeneity on treatment plan dosimetry.

PURPOSE: Given tissue inhomogeneity and lack of backscatter media, superficial brachytherapy necessitates more accurate dosimetry than TG-43 formalism. However, the introduction of modern model-based dose calculation algorithms into clinical practice should be carefully evaluated. The aim of this work was to compare dose distributions calculated with TG-43 and advanced collapsed cone engine (ACE) algorithms for individual multi-catheter moulds, and investigate the impact of target size and the lack of bolus to differences between plans. MATERIAL AND METHODS: Eleven treatment plans for individual mould multi-catheter high-dose-rate brachytherapy (IMM HDR) were selected for retrospective analysis. All treatment plans were initially calculated with TG-43 formula and re-calculated using ACE algorithm. Plan re-calculation with ACE was repeated for each plan in order to assess the impact of bolus. To evaluate differences between TG-43 and ACE dose distributions, dose-volume histogram (DVH) parameters for each ROI were compared. Dmax (maximal point dose), D0.1cc, and D2cc were calculated for each risk's organ (OARs) and for external contour. For clinical target volume (CTV), D98, D90, D50, CTV coverage (CTV-V100), and dose delivered to reference point were compared between the plans. RESULTS: A significantly lower values (p < 0.05) of CTV parameters were observed for treatment plans calculated with ACE algorithm comparing to TG-43. Further analysis showed that differences between CTV-V100 for ACE and TG-43 plans depended on CTV volume. Dosimetric parameters for OARs were significantly lower in ACE plans than those of TG-43. Only D2cc for external and D0.1cc for both eye lenses in ACE plans were insignificantly different comparing to TG-43 plans. CONCLUSIONS: Results show that differences between dosimetric parameters are statistically significant. However, their clinical relevance is still undetermined. Careful re-evaluation of the clinical results based on long-term research on TG-43 is necessary to safely introduce modern algorithms to clinical practice.

Using beam profile inflection point in process of treatment planning system verification.

BACKGROUND: The comparison between profiles during the commissioning of the treatment planning system is an essential procedure. It is impossible to designate a field size for off-axis, wedged, and FFF beams directly by using the definition of the on-axis symmetric field size. This work proposes the use of different characteristic points as indicators of the field size for commissioning and QA purposes. This work aimed to search for the beam profile's characteristic points and use them for the TPS commissioning purposes. MATERIALS AND METHODS: The proposal is to use profile inflection points as the beam profile characteristic points. The usage of dedicated software allowed for comparing distances between inflection points and between points of 50% intensity. For the off-axis, wedged, and FFF fields, comparisons were made to the nominal field sizes. RESULTS: Distances between inflection points proved to be different by less than 1 mm from nominal field sizes for all kinds of investigated beams. CONCLUSIONS: Inflection points are convenient for comparing the off-axis, wedged, and FFF field sizes because of their independence from profile normalization. With finite accuracy, the inflection points could be used for the above kind of beam sizes designation.

Correlation between Isotherms and Isodoses in Breast Cancer Radiotherapy-First Study.

The study is focused on correlation of isotherms derived from thermal images with an isodoses describing treatment plan for patients with breast cancer treated by radiotherapy. The irradiated area covered the part of the body after mastectomy. The study included patients diagnosed with breast cancer who were qualified for radiotherapy treatment. All patients were monitored during each treatment week during the entire radiotherapy process. The measurements were made under strictly defined conditions. In the treatment planning system (TPS), the specific plan was created for each patient. Spatial dose distribution in the patient's body was obtained and presented by the isodoses (lines connecting points with the same dose values). The following areas from the treatment planning system were plotted on the thermograms: target (tumor area) and isodose: 45 Gy, 40 Gy, 30 Gy, 20 Gy and 10 Gy. The obtained results indicated a high correlation between magnitude of the dose represented as the isodose and the temperature of the treated skin. Moreover, preliminary analysis showed a repeatable increase of the mean temperature in the irradiated area during the treatment.

Portal dosimetry in radiotherapy repeatability evaluation.

The accuracy of radiotherapy is the subject of continuous discussion, and dosimetry methods, particularly in dynamic techniques, are being developed. At the same time, many oncology centers develop quality procedures, including pretreatment and online dose verification and proper patient tracking methods. This work aims to present the possibility of using portal dosimetry in the assessment of radiotherapy repeatability. The analysis was conducted on 74 cases treated with dynamic techniques. Transit dosimetry was made for each collision-free radiation beam. It allowed the comparison of summary fluence maps, obtained for fractions with the corresponding summary maps from all other treatment fractions. For evaluation of the compatibility in the fluence map pairs (6798), the gamma coefficient was calculated. The results were considered in four groups, depending on the used radiotherapy technique: stereotactic fractionated radiotherapy, breath-hold, free-breathing, and conventionally fractionated other cases. The chi2 or Fisher's exact test was made depending on the size of the analyzed set and also Mann-Whitney U-test was used to compare treatment repeatability of different techniques. The aim was to test whether the null hypothesis of error-free therapy was met. The patient is treated repeatedly if the P-value in all the fluence maps sets is higher than the level of 0.01. The best compatibility between treatment fractions was obtained for the stereotactic technique. The technique with breath-holding gave the lowest percentage of compliance of the analyzed fluence pairs. The results indicate that the repeatability of the treatment is associated with the radiotherapy technique. Treated volume location is also an essential factor found in the evaluation of treatment accuracy. The EPID device is a useful tool in assessing the repeatability of radiotherapy. The proposed method of fluence maps comparison also allows us to assess in which therapeutic session the patient was treated differently from the other fractions.

Tandem autologous hematopoietic cell transplantation with sequential use of total marrow irradiation and high-dose melphalan in multiple myeloma.

The goal of this phase II trial was to evaluate safety and efficacy of a tandem autologous hematopoietic cell transplantation (auto-HCT) using sequentially total marrow irradiation (TMI) at the dose of 12 Gy (4 Gy on days -3, -2, and -1) and melphalan 200 mg/m2 for patients with multiple myeloma (MM). TMI was performed using helical tomotherapy. Additional "boosts" (total 24 Gy) were applied for patients with active lesions as revealed by PET-FDG. Fifty patients with median age 58 years (41-64 years) were included and received tandem auto-HCT. TMI resulted in absolute neutropenia in all patients. Grade 3 infections were reported in 30% patients. Other toxicities were rare. Proportion of patients who achieved at least very good partial response increased from 46% before the first auto-HCT to 82% after tandem transplantation. Complete remission rates changed from 10% to 42%, respectively. The probabilities of overall and progression-free survival at 5 years were 74% and 55%, respectively. No patient died without progression. We conclude that conditioning with TMI ± PET-guided "boosts" represents personalized treatment approach in MM and is characterized by very good toxicity profile. Tandem auto-HCT using TMI in sequence with high-dose melphalan appears safe with encouraging early efficacy.

IMRT/VMAT dose distributions generated for HD ® and Millennium ® collimators TrueBeam ® and Clinac ® accelerators.

AIM: The aim of this study is to answer the question whether the calculated dose distributions for HD and Millennium collimators (Varian Medical Systems) are equivalent for large treatment volumes. BACKGROUND: Modern biomedical linacs are equipped with multileaf collimators where leaves can be of different widths. Thinner leaves allow better fit to desired (tumor) shape. At the same time, however, the maximum size of the field that can be obtained with the collimator is also reduced. Varian Medical Systems HD and Millennium collimators can be a good sample. They have 40 cm or 22 cm × 40 cm maximal field size at the isocenter, respectively. MATERIALS AND METHODS: This paper presents the comparison of selected statistical and dosimetric parameters achieved for treatment plans where the beams for a HD collimator had to be merged because of the size of the tumor volume. RESULTS AND DISCUSSION: Achieved results show that, independently from irradiated volume, there is no statistically significant difference for calculated dose distributions, integral doses, MU values and coefficients evaluating dose distributions for HD and Millennium collimators. CONCLUSIONS: Results show that both types of collimators can be used interchangeably for preparing the treatment plans for large tumor volume without quality reduction of the prepared treatment plan.

In silico assessment of the dosimetric quality of a novel, automated radiation treatment planning strategy for linac-based radiosurgery of multiple brain metastases and a comparison with robotic methods.

BACKGROUND: To appraise the dosimetric features and the quality of the treatment plan for radiosurgery of multiple brain metastases optimized with a novel automated engine and to compare with plans optimized for robotic-based delivery. METHODS: A set of 15 patients with multiple brain metastases was selected for this in silico study. The technique under investigation is the recently introduced HyperArc. For all patients, three treatment plans were computed and compared: i: a HyperArc; ii: a standard VMAT; iii) a CyberKnife. Dosimetric features were computed for the clinical target volumes as well as for the healthy brain tissue and the organs at risk. RESULTS: The data showed that the best dose homogeneity was achieved with the VMAT technique. HyperArc allowed to minimize the volume of brain receiving 4Gy (as well as for the mean dose and the volume receiving 12Gy, although not statistically significant). The smallest dose on 1 cm3 volume for all organs at risk is for CK techniques, and the biggest for VMAT (p < 0.05). The Radiation Planning Index coefficient indicates that, there are no significant differences among the techniques investigated, suggesting an equivalence among these. CONCLUSION: At treatment planning level, the study demonstrates that the use of HyperArc technique can significantly improve the sparing of the healthy brain while maintaining a full coverage of the target volumes.

FDXR is a biomarker of radiation exposure in vivo.

Previous investigations in gene expression changes in blood after radiation exposure have highlighted its potential to provide biomarkers of exposure. Here, FDXR transcriptional changes in blood were investigated in humans undergoing a range of external radiation exposure procedures covering several orders of magnitude (cardiac fluoroscopy, diagnostic computed tomography (CT)) and treatments (total body and local radiotherapy). Moreover, a method was developed to assess the dose to the blood using physical exposure parameters. FDXR expression was significantly up-regulated 24 hr after radiotherapy in most patients and continuously during the fractionated treatment. Significance was reached even after diagnostic CT 2 hours post-exposure. We further showed that no significant differences in expression were found between ex vivo and in vivo samples from the same patients. Moreover, potential confounding factors such as gender, infection status and anti-oxidants only affect moderately FDXR transcription. Finally, we provided a first in vivo dose-response showing dose-dependency even for very low doses or partial body exposure showing good correlation between physically and biologically assessed doses. In conclusion, we report the remarkable responsiveness of FDXR to ionising radiation at the transcriptional level which, when measured in the right time window, provides accurate in vivo dose estimates.

Can high dose rates used in cancer radiotherapy change therapeutic effectiveness?

Current cancer radiotherapy relies on increasingly high dose rates of ionising radiation (100-2400 cGy/min). It is possible that changing dose rates is not paralleled by treatment effectiveness. Irradiating cancer cells is assumed to induce molecular alterations that ultimately lead to apoptotic death. Studies comparing the efficacy of radiation-induced DNA damage and apoptotic death in relation to varying dose rates do not provide unequivocal data. Whereas some have demonstrated higher dose rates (single dose) to effectively kill cancer cells, others claim the opposite. Recent gene expression studies in cells subject to variable dose rates stress alterations in molecular signalling, especially in the expression of genes linked to cell survival, immune response, and tumour progression. Novel irradiation techniques of modern cancer treatment do not rely anymore on maintaining absolute constancy of dose rates during radiation emission: instead, timing and exposure areas are regulated temporally and spatially by modulating the dose rate and beam shape. Such conditions may be reflected in tumour cells' response to irradiation, and this is supported by the references provided.

Integral dose: Comparison between four techniques for prostate radiotherapy.

AIM: Comparisons of integral dose delivered to the treatment planning volume and to the whole patient body during stereotactic, helical and intensity modulated radiotherapy of prostate. BACKGROUND: Multifield techniques produce large volumes of low dose inside the patient body. Delivered dose could be the result of the cytotoxic injuries of the cells even away from the treatment field. We calculated the total dose absorbed in the patient body for four radiotherapy techniques to investigate whether some methods have a potential to reduce the exposure to the patient. MATERIALS AND METHODS: We analyzed CyberKnife plans for 10 patients with localized prostate cancer. Five alternative plans for each patient were calculated with the VMAT, IMRT and TomoTherapy techniques. Alternative dose distributions were calculated to achieve the same coverage for PTV. Integral Dose formula was used to calculate the total dose delivered to the PTV and whole patient body. RESULTS: Analysis showed that the same amount of dose was deposited to the treated volume despite different methods of treatment delivery. The mean values of total dose delivered to the whole patient body differed significantly for each treatment technique. The highest integral dose in the patient's body was at the TomoTherapy and CyberKnife treatment session. VMAT was characterized by the lowest integral dose deposited in the patient body. CONCLUSIONS: The highest total dose absorbed in normal tissue was observed with the use of a robotic radiosurgery system and TomoTherapy. These results demonstrate that the exposure of healthy tissue is a dosimetric factor which differentiates the dose delivery methods.

Antioxidant activity and protective effects against oxidative damage of human cells induced by X-radiation of phenolic glycosides isolated from pepper fruits Capsicum annuum L.

The antioxidant and radioprotective effects of the phenolic glycosides from Capsicum annuum L. were examined. There were: sinapoyl-E-glucoside, quercetin-3-O-rhamnoside-7-O-glucoside, quercetin-3-O-rhamnoside and luteolin-7-O-(2-apiosyl)-glucoside. To the best of our knowledge, this is the first study to assay these compounds for their radioprotective effect on human cell lymphocytes in response to oxidative damage induced by X radiation and their antioxidant abilities. Investigated compounds showed weaker antiradical activities, but their radioprotective potentials were higher than those of their aglycones. Quercetin-3-O-rhamnoside showed the highest radioprotective activity (50% according to control). Furthermore, quercetin and luteolin derivatives, in contrast to free aglycones, were not cytotoxic against human lymphocytes for all concentrations tested. The best correlation between radioprotective and antiradical activities of the investigated compounds was observed in the relationship to O2(-) generated using the NADH/PMS method (R(2)=0.859). Thus, we propose that superoxide radical scavenging activity is a useful method for screening for compounds with promising radioprotective potential.