Course Of Radiation Treatment Research Articles

Modelling systematic anatomical uncertainties of head and neck cancer patients during fractionated radiotherapy treatment

Objective. Head and neck cancer patients experience systematic as well as random day to day anatomical changes during fractionated radiotherapy treatment. Modelling the expected systematic anatomical changes could aid in creating treatment plans which are more robust against such changes. Approach. Inter- patient correspondence aligned all patients to a model space. Intra- patient correspondence between each planning CT scan and on treatment cone beam CT scans was obtained using diffeomorphic deformable image registration. The stationary velocity fields were then used to develop B-Spline based patient specific (SM) and population average (AM) models. The models were evaluated geometrically and dosimetrically. A leave-one-out method was used to compare the training and testing accuracy of the models. Main results. Both SMs and AMs were able to capture systematic changes. The average surface distance between the registration propagated contours and the contours generated by the SM was less than 2 mm, showing that the SM are able to capture the anatomical changes which a patient experiences during the course of radiotherapy. The testing accuracy was lower than the training accuracy of the SM, suggesting that the model overfits to the limited data available and therefore, also captures some of the random day to day changes. For most patients the AMs were a better estimate of the anatomical changes than assuming there were no changes, but the AMs could not capture the variability in the anatomical changes seen in all patients. No difference was seen in the training and testing accuracy of the AMs. These observations were highlighted in both the geometric and dosimetric evaluations and comparisons. Significance. In this work, a SM and AM are presented which are able to capture the systematic anatomical changes of some head and neck cancer patients over the course of radiotherapy treatment. The AM is able to capture the overall trend of the population, but there is large patient variability which highlights the need for more complex, capable population models.

The process of changing the potency of chromosomes, disease nosodes and organ preparations. How does this change the nature of the course of diseases and the physiological state of the subjects?

The work identified “active” and “inactive” chromosomes and how “inactive” chromosomes become “active”. For this purpose, a device for resonance diagnostics and therapy was used, connected to a computer, and the resonance of creation was used to transform inactive chromosomes into active ones. We added the sum of potencies to the already existing chromosome values. So, for example, at the beginning of the study, the patient was tested with a low potency of chromosomes equal to cassette No. 3 and ended with testing with cassette No. 10. Next, we “added”, connected the potency found in cassette No. 32 with high potencies to cassette No. 10. As a result, testing now began with cassette No. 1, and ended with cassette No. 12, i.e. testing increased to 4 cassettes. In a 50-year-old man, in the initial state, testing of chromosome potency began with cassette No. 18, and ended with cassette No. 31, i.e. 13 cassettes were tested. After connecting a cassette with a sufficiently high potency (cassette No. 47) to cassette No. 31, the start of testing changed and took place on cassette No. 2, and ended on cassette No. 49. Cassette testing increased to 49 cassettes, i.e. more than 3 times. Is it possible to potentiate not only chromosomes, but also other structures of the body? Potentiation is possible not only with chromosomes, but also with disease nosodes and organ preparations. An 84-year-old patient had untreated calculous cholecystitis from which he suffered. However, after transforming the nosode, after potentiating the nosode by connecting large cassettes to the nosode “calculous cholecystitis,” the patient’s calculous cholecystitis was extremely effectively cured. Treatment of an 82-year-old patient with cribriform prostate cancer. 10 years ago, the patient underwent surgery to remove cribriform prostate cancer - radical prostatectomy. After 10 years, a relapse occurred, which was treated with radiotherapy. The patient underwent 36 procedures, 5 procedures per week. At the end of the course of radiotherapy treatment, testing of cribriform prostate cancer showed that the cancer was still being tested, i.e. treatment has not been completed. We treated this patient using resonance therapy with changing, increasing potency of the nosode “caribous prostate cancer.” We increased the potency of the nosode in the patient to the point where the cancer could no longer be tested, i.e. We have completed treatment for cribriform prostate cancer. Potentiation is possible not only of chromosomes, nosodes, but also of organ preparations. Potentiation of the organopreparation “brain” was carried out in a 72-year-old subject who complained of general weakness, uncertainty of movements, memory loss, and poor sleep. After potentiation of the human brain organopreparation, the patient’s condition improved - he stopped complaining about changes in his physiological state. Thus, as a result of transformations of chromosomes, nosodes and organ preparations, as a result of their potentiation (increase in potency) when connecting a cassette of large potency, patients develop a new higher quality of chromosomes, nosodes and organ preparations. The effectiveness of the treatment of various diseases was achieved by us by increasing the potency of the nosode of the disease from which the patient suffered and using this potency for treatment. Potentiation of the human brain organopreparation significantly improved the physiological state of the subjects.

Radiosensitizing effects of heparinized magnetic iron oxide nanoparticles in colon cancer

The combination of radiation treatment and chemotherapy is currently the standard for management of cancer patients. However, safe doses do not often provide effective therapy, then pre-treated patients are forced to repeat treatment with often already increased tumor resistance to drugs and irradiation. One of the solutions we suggest is to improve primary course of radiation treatment via enhancing radiosensitivity of tumors by magnetic-guided iron oxide nanoparticles (magnetite). We obtained spherical heparinized iron oxide nanoparticles (hIONPs, ∼20 nm), characterized it by TEM, Infrared spectroscopy and DLS. Then hIONPs cytotoxicity was assessed for colon cancer cells (XTT assay) and cellular uptake of nanoparticles was analyzed with X-ray fluorescence.Combination of ionizing radiation (IR) and hIONPs in vitro caused an increase of G2/M arrest of cell cycle, mitotic errors and decrease in survival (compared with samples exposed to IR and hIONPs separately). The promising results were shown for magnetic-guided hIONPs in CT26-grafted BALB/C mice: the combination of intravenously administrated hIONPs and IR showed 20,8% T/C ratio (related to non-treated mice), while single radiation had no shown significant decrease in tumor growth (72,4%). Non-guided by magnets hIONPs with IR showed 57,9% of T/C. This indicates that ultra-small size and biocompatible molecule are not the key to successful nano-drug design, in each case, delivery technologies need to be improved when transferred to in vivo model.

Increasing the efficiency of cone-beam CT based delta-radiomics using automated contours to predict radiotherapy-related toxicities in prostate cancer

Extracting longitudinal image quantitative data, known as delta-radiomics, has the potential to capture changes in a patient’s anatomy throughout the course of radiation treatment for prostate cancer. Some of the major challenges of delta-radiomics studies are contouring the structures for individual fractions and accruing patients’ data in an efficient manner. The manual contouring process is often time consuming and would limit the efficiency of accruing larger sample sizes for future studies. The problem is amplified because the contours are often made by highly trained radiation oncologists with limited time to dedicate to research studies of this nature. This work compares the use of automated prostate contours generated using a deformable image-based algorithm to make predictive models of genitourinary and changes in total international prostate symptom score in comparison to manually contours for a cohort of fifty patients. Area under the curve of manual and automated models were compared using the Delong test. This study demonstrated that the delta-radiomics models were similar for both automated and manual delta-radiomics models.

Adaptive radiotherapy for head and neck cancer: Pitfalls and possibilities from the radiation oncologist's point of view.

Patients with head and neck cancer (HNC) may experience substantial anatomical changes during the course of radiotherapy treatment. The implementation of adaptive radiotherapy (ART) proves effective in managing the consequent impact on the planned dose distribution. This narrative literature review comprehensively discusses the diverse strategies of ART in HNC and the documented dosimetric and clinical advantages associated with these approaches, while also addressing the current challenges for integration of ART into clinical practice. Although based on mainly non-randomized and retrospective trials, there is accumulating evidence that ART has the potential to reduce toxicity and improve quality of life and tumor control in HNC patients treated with RT. However, several questions remain regarding accurate patient selection, the ideal frequency and timing of replanning, and the appropriate way for image registration and dose calculation. Well-designed randomized prospective trials, with a predetermined protocol for both image registration and dose summation, are urgently needed to further investigate the dosimetric and clinical benefits of ART.

Risk-Tailoring Radiotherapy for Endometrial Cancer: A Narrative Review.

Endometrial cancer is the most common gynecologic cancer in the United States and it contributes to the second most gynecologic cancer-related deaths. With upfront surgery, the specific characteristics of both the patient and tumor allow for risk-tailored treatment algorithms including adjuvant radiotherapy and systemic therapy. In this narrative review, we discuss the current radiation treatment paradigm for endometrial cancer with an emphasis on various radiotherapy modalities, techniques, and dosing regimens. We then elaborate on how to tailor radiotherapy treatment courses in combination with other cancer-directed treatments, including chemotherapy and immunotherapy. In conclusion, this review summarizes ongoing research that aims to further individualize radiotherapy regimens for individuals in an attempt to improve patient outcomes.

MR-guided stereotactic radiation therapy for head and neck cancers

PurposeMR-guided radiotherapy (MRgRT) has the advantage of utilizing high soft tissue contrast imaging to track daily changes in target and critical organs throughout the entire radiation treatment course. Head and neck (HN) stereotactic body radiation therapy (SBRT) has been increasingly used to treat localized lesions within a shorter timeframe. The purpose of this study is to examine the dosimetric difference between the step-and-shot intensity modulated radiation therapy (IMRT) plans on Elekta Unity and our clinical volumetric modulated arc therapy (VMAT) plans on Varian TrueBeam for HN SBRT. MethodFourteen patients treated on TrueBeam sTx with VMAT treatment plans were re-planned in the Monaco treatment planning system for Elekta Unity MR-Linac (MRL). The plan qualities, including target coverage, conformity, homogeneity, nearby critical organ doses, gradient index and low dose bath volume, were compared between VMAT and Monaco IMRT plans. Additionally, we evaluated the Unity adaptive plans of adapt-to-position (ATP) and adapt-to-shape (ATS) workflows using simulated setup errors for five patients and assessed the outcomes of our treated patients. ResultsMonaco IMRT plans achieved comparable results to VMAT plans in terms of target coverage, uniformity and homogeneity, with slightly higher target maximum and mean doses. The critical organ doses in Monaco IMRT plans all met clinical goals; however, the mean doses and low dose bath volumes were higher than in VMAT plans. The adaptive plans demonstrated that the ATP workflow may result in degraded target coverage and OAR doses for HN SBRT, while the ATS workflow can maintain the plan quality. ConclusionThe use of Monaco treatment planning and online adaptation can achieve dosimetric results comparable to VMAT plans, with the additional benefits of real-time tracking of target volume and nearby critical structures. This offers the potential to treat aggressive and variable tumors in HN SBRT and improve local control and treatment toxicity.

Study on the radiotherapy effect and serum neutral granulocyte lymphocyte ratio and inflammatory factor expression of nasopharyngeal carcinoma.

To compare target area delineation schemes in intensity-modulated radiotherapy (IMRT) effect on patients with locally advanced nasopharyngeal carcinoma (NPC). A total of 88 NPC patients received IMRT and were assigned into control group (n = 44) and observation group (n = 44) based on MRI and CT imaging. In the control group, the treatment range was determined as the clinical target volume (CTV) as the gross tumor volume (GTV) + 5 mm. In the observation group, high-risk target areas CTVp1 was GTVp + 5 mm, lymphatic drainage area CTVn1 was GTVn + 5 mm, medium-risk CTVp2 was CTVp1 + 5 mm margin + the whole nasopharyngeal area, CTVn2 was CTVn1 + 5 mm. Radiotherapy treatment course was 6-8 weeks, four times a week. The observation group had higher total effective rate, with fewer complications. Neutrophil lymphocyte ratio (NLR), interleukin (IL)-6, and tumor necrosis factor (TNF)-α levels were lower after radiotherapy in both groups compared to before radiotherapy, with the observation group demonstrating lower levels than the control group. The effective group exhibited lower serum NLR, IL-6, and TNF-α compared to the non-effective group. T stage, target location, serum NLR, IL-6, and TNF-α were risk factors for the effect of radiotherapy. Serum NLR, IL-6, and TNF-α have predictive significance for radiotherapy effect.

Results of Treatment of Patients with Progression of Primary Highly Malignant Brain Gliomas During a Repeated Course of Radiation Therapy. Own Experience

Purpose: To determine the most effective option for repeated radiation therapy in patients with continued growth of primary high-grade brain glioma, taking into account the isodose distribution during the initial course of radiation therapy. Material and methods: As a result of a retrospective analysis, the results of treatment of 100 patients with confirmed progression of high-grade glioma treated at the Chelyabinsk Regional Center for Oncology and Nuclear Medicine in the period from 2010 to 2020 were evaluated. The ratio of men and women was approximately equal (56 men and 44 women). The mean age of patients of both sexes was 47.2±11.9 years. According to the histological conclusion, patients with glioblastomas (GB) prevailed (n = 58), 42 patients were diagnosed with anaplastic astrocytoma (AA). Reoperation was performed in 26 patients. Repeated radiation therapy in an independent variant was performed in 76 patients of them: 17 patients received a course of neuronal therapy in mono mode and in 17 patients in combination with external beam radiation therapy; 23 patients underwent stereotactic radiotherapy (SRS) using the CyberKnife device; in 19 cases, remote radiation therapy. In 24 cases, a chemotherapeutic component was added in addition to radiation treatment. Results: Mean time to relapse was 23 months. The median overall survival (OS) for all patients was 35 months. (DI 26.2–43.7). Indicators of 1-year OS — 85.6 %; 3-year-old — 44.1 %, 5-year-old — 26.5 %. Depending on the type of radiation therapy: the highest progression-free survival (PFS) was found with SPLT and combined photon-neutron therapy (SPNT) as in the group of patients with recurrent EH for 15, 17, and AA 24 and 40 months, respectively. Among the patients included in our study, the majority of patients (42 people) had central recurrences (in which 95 % or more of the volume of the recurrent tumor was within 100-95 % of the initial isodose), 6 had marginal relapses (20 to 80 % of the recurrent volume is within the surface of 95 % isodose), and in 2 cases a distant recurrence was recorded (less than 20 % of the recurrent volume was within 95 % of the isodose). Distant recurrences (marginal and distant) occurred within an average of 12 months, while central recurrences were diagnosed on average 26 months after the end of the course of radiation (chemoradiation) treatment. Conclusion: Thus, when analyzing our data, in all patients with continued growth of primary high-grade brain gliomas, the method of choice for a repeated course of radiation therapy is stereotactic radiation therapy or a combined course of photon-neutron therapy, which allows to overcome the existing radioresistance.

Simulating tumor volume dynamics in response to radiotherapy: Implications of model selection

From the beginning of the usage of radiotherapy (RT) for cancer treatment, mathematical modeling has been integral to understanding radiobiology and for designing treatment approaches and schedules. There has been extensive modeling of response to RT with the inclusion of various degrees of biological complexity. In this study, we compare three models of tumor volume dynamics: (1) exponential growth with RT directly reducing tumor volume, (2) logistic growth with direct tumor volume reduction, and (3) logistic growth with RT reducing the tumor carrying capacity with the objective of understanding the implications of model selection and informing the process of model calibration and parameterization. For all three models, we: examined the rates of change in tumor volume during and RT treatment course; performed parameter sensitivity and identifiability analyses; and investigated the impact of the parameter sensitivity on the tumor volume trajectories. In examining the tumor volume dynamics trends, we coined a new metric – the point of maximum reduction of tumor volume (MRV) – to quantify the magnitude and timing of the expected largest impact of RT during a treatment course. We found distinct timing differences in MRV, dependent on model selection. The parameter identifiability and sensitivity analyses revealed the interdependence of the different model parameters and that it is only possible to independently identify tumor growth and radiation response parameters if the underlying tumor growth rate is sufficiently large. Ultimately, the results of these analyses help us to better understand the implications of model selection while simultaneously generating falsifiable hypotheses about MRV timing that can be tested on longitudinal measurements of tumor volume from pre-clinical or clinical data with high acquisition frequency. Although, our study only compares three particular models, the results demonstrate that caution is necessary in selecting models of response to RT, given the artifacts imposed by each model.

Prediction of Radiation Treatment Response for Locally Advanced Rectal Cancer via a Longitudinal Trend Analysis Framework on Cone-Beam CT.

Locally advanced rectal cancer (LARC) presents a significant challenge in terms of treatment management, particularly with regards to identifying patients who are likely to respond to radiation therapy (RT) at an individualized level. Patients respond to the same radiation treatment course differently due to inter- and intra-patient variability in radiosensitivity. In-room volumetric cone-beam computed tomography (CBCT) is widely used to ensure proper alignment, but also allows us to assess tumor response during the treatment course. In this work, we proposed a longitudinal radiomic trend (LRT) framework for accurate and robust treatment response assessment using daily CBCT scans for early detection of patient response. The LRT framework consists of four modules: (1) Automated registration and evaluation of CBCT scans to planning CT; (2) Feature extraction and normalization; (3) Longitudinal trending analyses; and (4) Feature reduction and model creation. The effectiveness of the framework was validated via leave-one-out cross-validation (LOOCV), using a total of 840 CBCT scans for a retrospective cohort of LARC patients. The trending model demonstrates significant differences between the responder vs. non-responder groups with an Area Under the Curve (AUC) of 0.98, which allows for systematic monitoring and early prediction of patient response during the RT treatment course for potential adaptive management.

Early Prediction of Radiation Treatment Response via Longitudinal Analysis of CBCT Radiomic Features for Locally Advanced Rectal Cancer.

Patients respond to the same radiation treatment course differently due to inter- and intra- patient variability in radiosensitivity. Despite widespread use of AI/ML in radiation oncology, there is a lack of monitoring strategies used during treatment courses to evaluate early predictors of treatment response in a systematic fashion. This work advances a straightforward, yet effective, method for the early detection of treatment response through systematically analyzing daily CBCT radiomic features. The goal is to aid clinicians in assessing the treatment efficacy routinely with a view towards optimizing personalized treatment. We included a cohort of 30 patients diagnosed with locally advanced rectal cancer who underwent neo-adjuvant fractionated radiation treatment (RT) with a prescription dose of 50.4 Gy (28 fractions), followed by total mesorectal excision surgery after completion of ChemoRT. Daily IGRT imaging was acquired prior to each fraction resulting in a total of 840 CBCTs. Patients were divided into responder (14 patients) and non-responder (16 patients) groups based on post-RT pathological response. Mutual information algorithms were utilized to rigorously register daily CBCT images to the planning CT, and longitudinal radiomic features of the target were extracted from the daily CBCTs during the entire treatment course. All longitudinal features for a given patient were standardized with Z-Score normalization, followed by linear fitting using the least square method, resulting in radiomic feature trends (RFT) represented by slope values. Statistical significance was established via a two-sample U test and P-value with a threshold of 0.05. Logistic regression was performed to eliminate RFT with accuracy rates lower than 0.5. The final trending model was developed using random forest. For each patient at fraction N, our investigation involved independent 27 group experiments, where each experiment considered image group from fraction #1 to N, to confirm the effectiveness and stability of the model. The proposed RFT demonstrated a high level of precision and consistency for post-RT response based on longitudinal CBCT images for LARC patients. The trending model yielded an accuracy of 0.9556, 95% CI (0.94, 0.972) when each daily image was considered, the prediction consistency was 0.964. Given the first 14 experiments (considering group images of fraction #1-15), the prediction accuracy was 0.9357, 95% CI (0.915, 0.956) and the prediction consistency was 0.952. A strategy for monitoring and early prediction of LARC patients' radioresponse was evaluated via longitudinal CBCT assessment. Our trending models demonstrate a significant difference between the responder vs non-responder groups as early as the 15th fraction. Our strategy achieved superior accuracy and consistency to predict post-RT response of LARC patients.

EPRO Use in Men Receiving Radiotherapy for Localized Prostate Cancer

Describe real-time reporting of localized prostate cancer and patient-reported cancer/radiation treatment symptoms via mobile app or computer-based system. Patients (n = 177) who received standard-of-care treatment at an academic specialty care hospital in Finland from Jan. 2015 through Dec. 2020 and used a proprietary ePRO tool at least once during their course of radiotherapy were included in this study. The Clinical Care Team (CCT) utilized bidirectional software to administer an electronic questionnaire that included CTCAE (v5) items to report disease and/or treatment symptoms at least once during treatment and at 1 month and 3 months posttreatment. Patients could also complete the questionnaire ad hoc. The questionnaire is enhanced with programmed "emergency" and "urgent" clinical alerts which are used for two purposes: sending pre-programmed recommendations to patients and triaging patients by symptom severity on the CCT's dashboard in order to facilitate patient follow-up. Data were analyzed descriptively. Patients tended to be older (M = 73.16 years, SD = 6.86) and lived outside the city (n = 119, 67.23%). The average course of radiation treatment was over one month in duration (M = 39.21 days, SD = 16.96); relatively few patients received surgery (n = 21, 6.78%) and/or hormone therapy (n = 20, 11.30%). Almost all patients completed the module during treatment (response rate = 92.09%) and at posttreatment (response rate = 94.92%). Ad hoc reports were submitted by 18.07% of patients during treatment (78 submissions) and 28.24% of patients posttreatment (182 submissions). The most frequently reported symptoms during and after treatment were urination-related (during treatment = 73.44%; post treatment = 60.45%), diarrhea/constipation (during treatment = 50.84%; post treatment = 31.63%), and sexual function (during treatment = 44.63%; post treatment = 57.06%). Systematizing real-time collection of patient-reported symptoms is increasingly acknowledged as an adjunct to improving patient experience. The high usage observed in this study is a behavioral indicator that ePRO use is accepted and valued by patients. Perhaps the most interesting finding is the use of the ad hoc reporting function. During radiotherapy, patients have almost daily access to the CCT and can easily communicate symptoms; nevertheless, they still used the ePRO platform to report cancer/treatment effects. Understandably, in the posttreatment period, where scheduled contact with the CCT is less frequent, ad hoc usage was higher. These findings suggest that ePRO use (scheduled and ad hoc) helps address an unmet need and has the potential to empower patients throughout their cancer journey.

Proliferation Saturation Index to Simulate Adaptive Radiation Fractionation in HPV-Associated Oropharyngeal Cancer

In current clinical practice for fractionated radiotherapy (RT) patients receive a fixed fractionation protocol throughout radiation course. Radiation oncology has not yet moved toward adaptive fractionation to change RT fractionation based on individual patients' response dynamics. We have previously introduced a novel mathematical and imaging biomarker, proliferation saturation index (PSI), to simulate and evaluate tumor volume dynamics during therapy. Robust tumor volume reduction was associated with lower PSI, and PSI has been utilized to select fractionation schedules for the first mathematical model informed clinical trial. Here we simulate the possibility of adapting the selection of RT fractionation on a week-by-week basis by utilizing a dynamic weekly estimation of PSI. We generated a cohort of in silico patients by sampling from distributions of PSI, radiosensitivity, and growth rate parameters. These distributions were by pre-treatment and on-treatment tumor volume dynamics from a prospective clinical trial (NCT03656133), where 49 HPV+ OPC patients were treated with either 2 Gy daily fractions up to a total of 70 Gy if PS<0.75, or hyperfractionation at 1.2 Gy b.i.d. up to a total of 66 Gy for patients with PSI ≥ 0.75. We then simulated standard (2 Gy q.d.) and hyperfractionated (1.2 Gy b.i.d) for 1-8 weeks of RT to build a library of response dynamics for the different parameter combinations and treatment durations. This library was then used to estimate optimal adaptive fractionation schedules for the in silico patients that maximized tumor volume reduction and minimized total RT dose. We found that PSI evolved towards lower values (i.e., higher proliferative fractions) over the fractionation RT treatment course. For patients that began treatment with standard fractionation, no adaption was found to be superior to uniform fractionation. For selected patients who began treatment with hyperfractionation, however, the optimal fractionation schedule included a period of upfront hyperfractionated RT followed by a switch to standard fractionation at different times during their treatment course. The results of this study suggest that in addition to selecting the best initial fractionation schedule, a novel approach to personalize RT for OPC patients may include adapting the fractionation based on early treatment response dynamics. These results motivate validation in prospective clinical trials.

Proton Re-Irradiation with Concurrent Hyperthermia in Patients with Recurrent Breast Cancer

The aim of this study is to evaluate the safety and effectiveness of proton re-irradiation with concurrent hyperthermia in the treatment of recurrent breast cancer. We retrospectively identified patients previously treated with photon whole breast or chest wall irradiation for a primary breast cancer at our institution, who subsequently developed a histologically-confirmed locoregional recurrence or new ipsilateral primary breast cancer and underwent proton chest wall re-irradiation with concurrent hyperthermia as part of definitive treatment. Acute toxicity was evaluated once weekly while on-treatment and at 2 weeks and 3 months post-treatment. Toxicities were graded according to CTCAE v4.0. Fifteen patients received proton re-irradiation with concurrent superficial hyperthermia at our institution from August 2018 to December 2022. Median interval between radiation treatment courses was 7.7 years (range 1-30 years). Four patients (26%) had gross, unresected disease at the time of re-treatment. The median initial radiation dose, re-irradiation dose, and cumulative EQD2 was 60.4 Gy (50.6-61.2 Gy), 60 Gy (RBE) (45-66 Gy (RBE)), and 120 Gy (RBE) (103-126 Gy (RBE)), respectively. Patients received a median of 9 (3-14) concurrent hyperthermia treatments delivered twice weekly, and 13 patients (87%) received seven or more hyperthermia treatments. Median toxicity follow-up was 9 months (0-36 months). Acute grade 3 toxicities included two patients (13%) with grade 3 dermatitis, both of which resolved with conservative management within 3 months of treatment completion. Chronic grade 2 or higher toxicities included two grade 2 hyperpigmentation, one grade 3 induration, one grade 2 telangiectasia, and one grade 2 rib fracture. There were no grade 4-5 acute or late toxicities. There was one in-field local recurrence and one regional recurrence outside of the re-irradiation field. Both patients had gross, unresected disease at the time of re-irradiation. Two patients (13%) developed distant disease. Proton re-irradiation with concurrent hyperthermia is feasible and well-tolerated in the re-treatment of breast cancer. Further studies are warranted to determine long-term toxicity and oncologic outcomes.

Palliative radiotherapy for children: Symptom response and treatment-associated toxicity according to radiation therapy dose and fractionation.

Radiotherapy is an effective palliative treatment in advanced cancer. Shorter palliative treatment courses are recommended for adults, though pediatric data addressing treatment efficacy and toxicity according to radiation therapy (RT) dose and fractionation are limited. Total 213 patients aged 21years or younger receiving 422 palliative radiotherapy treatment courses from 2003 to 2016 were included. Symptom response and treatment-associated toxicity were recorded and analyzed in relationship to demographic and treatment variables. Common diagnoses included sarcoma (32.5%), neuroblastoma (24.9%), leukemia/lymphoma (14.9%), and central nervous system tumors (10.9%). The most common indication for treatment was pain (46.7%). Patients received a median of 10 fractions, 2.5Gy dose per fraction, and 21Gy total dose. Number of RT fractions was five or less in 166 (39.3%), six to 10 fractions in 117 (27.2%), and 10 or more fractions in 139 (32.9%) of courses. Complete or partial pain relief was achieved in 85% (151 of 178 evaluable patients), including 77.8% receiving five or less fractions and 89.6% receiving more than five fractions. Highest toxicity was grade 1 in 159 (38.9%), grade 2 in 26 (6.4%), and grade 3 in two (0.5%) treatments. On multivariable analysis, RT delivered 30 or more days from death (OR 12.13, 95% CI: 2.13-69.2, p=.005) and no adjuvant chemotherapy (OR 0.14, 95% CI: 0.03-0.54, p=.005) were significantly associated with pain response, and five or less fractions were significantly associated with lower toxicity (OR 0.24, 95% CI: 0.06-0.97, p=.045). Palliative RT courses of five or less fractions result in high rates of pain control and are associated with low toxicity in pediatric patients with cancer.

Established and new horizons in radiotherapy for breast cancer.

Modern advances in diagnostics, surgery, systemic therapies, and radiotherapy (RT) have drastically revolutionized treatment strategies for breast cancer. This review outlines current and evolving treatment paradigms for RT in the breast-conserving therapy and post-mastectomy setting. In early-stage breast cancer, there is active investigation in expanding eligibility for omission of RT in women with more biologically favorable tumors and growing options to effectively irradiate less breast tissue and shorten RT treatment courses. For locally advanced breast cancer, we discuss several patient cohorts in which the necessity of post-mastectomy RT (PMRT) is commonly debated. Ongoing efforts to better refine indications for PMRT and evaluate the feasibility of hypofractionated PMRT are being studied. Metastasis-directed therapy with ablative RT is an emerging topic of interest in many cancers, including its role and impact in oligometastatic breast cancer. In this review, we will discuss the rationale for current standard of care and address in greater detail the aforementioned concepts.

Assessment of I-CAM1, V-CAM1, and E-selectin Serum Levels in Patients with Breast and Pelvic Cancer: A Case Control Study

Background: Breast and pelvic cancers are the most prevalent cancers among women globally. Several studies have reported on the effect of cell adhesion molecules on the growth, multiplication, invasion, and metastasis of tumor cells as well as inflammatory biomarkers, which are responsible for harmful inflammatory processes. Objectives: The purpose of the current study was to assess the serum levels of adhesion molecules intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-selectin in patients with cancer before and after radiotherapy, compare these with the levels of healthy subjects, and consider the relationship of these levels with the tumor origin. Methods: The present case-control study investigated 14 patients with breast cancer and 14 patients with pelvic cancer who had been referred to Omid Teaching Hospital’s oncology clinic, Mashhad, Iran between 2015 and 2017. Evaluated by the ELISA method for ICAM-1, VCAM-1, and E-selectin were the serum samples of these 28 cancer patients before and after their course of radiotherapy treatment and the serum samples of the 28 healthy subjects who had no history of cancer, radiotherapy or the risk factor of coronary artery disease. Results: The ICAM-1, VCAM-1, and E-selectin serum levels of all patients with cancer before and after a course of radiotherapy were significantly higher than those of the control group (P-value ≤ 0.5). There was no significant difference between the two cancer groups before and after radiotherapy (P-value ≥ 0.05). Conclusions: The current study demonstrated that the serum levels of adhesion molecules in patients with cancer before and after radiotherapy increase significantly regardless of the initial location of the tumor.

The content of VEGF, COX-2 and PGE-2 in the blood serum of patients with non-small cell lung cancer with different schemes of conformal radiotherapy in the dynamics of treatment

Background. Overcoming radioresistance is an important problem in radiation oncology. Therefore, the development of new approaches to modeling the radiosensitivity of tumors in cancer patients becomes relevant and important. Cyclooxygenase-2 (COX-2) inhibitors are new agents for radiomodification in various radiation therapy schemes, the use of which slows down angiogenesis by suppressing the activity of the COX-2 enzyme.&#x0D; Purpose. To determine the content of indicators of radioresistance: vascular endothelial growth factor (VEGF), COX-2, prostaglandin E-2 (PGE-2) in the blood serum of patients with non-small cell lung cancer (NSCLC) and changes in their levels with different schemes of radiation therapy (RT).&#x0D; Materials and methods. 36 patients with NSCLC were examined and treated, who were divided into four groups: RT (the first group – 16 patients), RT with the COX-2 inhibitor – ranselex (the second group – 9 patients), RT with ranselex and cisplatin (the third group – 5 patients ) and RT with cisplatin (fourth group – 6 patients). The patients received a course of radiation treatment using a Clinac 600C linear accelerator. The classical fractionation mode was used, the total focal doses were 60–66 Gy. Cisplatin was prescribed at 30 mg/m2 per week up to a total dose (SD) of 200 mg, the COX-2 inhibitor Rancelex® at a dose of 100 mg per day (active substance – celecoxib). The levels of VEGF, COX-2, and PGE-2 in the blood serum of patients with NSCLC were determined by enzyme-linked immunosorbent assay (ELISA) before and after treatment.&#x0D; Results. The level of the angiogenesis marker VEGF after treatment in the group with RT decreases by 1.46 times, in the group with the combined action of RT and ranselex – 2.4 times, in the group with the combined action of PT, ranselex and cisplatin – by 3.7 times, and in the group with the combined effect of RT and cisplatin, it decreases by 1.1 times. The greatest decrease in the level of VEGF is observed with RT in combination with ranselex and cisplatin, which indicates a more effective enhancement of the antiangiogenic effect.&#x0D; Conclusions. It has been proven that with various schemes of RT using the COX-2 inhibitor – ranselex and cisplatin in patients with NSCLC, there is a decrease in the radioresistance markers PGE-2 and COX-2, the angiogenesis marker – VEGF, which indicates that the effect of radiomodification on the angiogenesis process is most pronounced in the combined actions of RT and both radio modifiers. The use of COX-2 inhibitors as radiosensitizers in combination with RT provides a new opportunity to increase tumor radiosensitivity.

Good clinical practice and the use of hypofractionation radiation schedules as weapons to reduce the risk of COVID-19 infections in radiation oncology unit: A mono-institutional experience.

After coronavirus disease outbreak emerged in 2019, radiotherapy departments had to adapt quickly their health system and establish new organizations and priorities. The purpose of this work is to report our experience in dealing with COVID-19 emergency, how we have reorganized our clinical activity, changed our priorities, and stressed the use of hypofractionation in the treatment of oncological diseases. The patients' circuit of first medical examinations and follow-up was reorganized; a more extensive use of hypofractionated schedules was applied; a daily triage of the patients and staff, use of personal protective equipment, hand washing, environment sanitization, social distancing and limitations for the patients' caregivers in the department, unless absolutely essential, were performed; patients with suspected or confirmed COVID-19 were treated at the end of the day. In addition, the total number of radiotherapy treatment courses, patients and sessions, in the period from February 15 to April 30, 2020, comparing the same time period in 2018 were retrospectively investigated. In particular, changes in hypofractionated schedules adopted for the treatment of breast and prostate cancer and palliative bone metastasis were analyzed. Between February 15, and April 30, 2020, an increased number of treatments was carried out: Patients treated were overall 299 compared to 284 of the same period of 2018. Stressing the use of hypofractionation, 2036 RT sessions were performed, with a mean number of fractions per course of 6.8, compared to 3566 and 12.6, respectively, in 2018. For breast cancer, the schedule in 18 fractions has been abandoned and treatment course of 13 fractions has been introduced; a 27% reduction in the use of 40.5 Gy in 15 fractions, (67 treatments in 2018-49 in 2020) was reported. An increase of 13% of stereotactic body radiation therapy for prostate cancer was showed. The use of the 20 Gy in 4 or 5 sessions for the treatment of symptomatic bone metastasis decreased of 17.5% in favor of 8 Gy-single fraction. Three patients results COVID-19 positive swab: 1 during, 2 after treatment. Only one staff member developed an asymptomatic infection. The careful application of triage, anti-contagion and protective measures, a more extensive use of hypofractionation allowed us to maintain an effective and continuous RT service with no delayed/deferred treatment as evidenced by the very low number of patients developing COVID-19 infection during or in the short period after radiotherapy. Our experience has shown how the reorganization of the ward priority, the identification of risk factors with the relative containment measures can guarantee the care of oncological patients, who are potentially at greater risk of contracting the infection.