Quality Control of Ionizing Radiation in Radiotherapy

This work includes the results of our research on the measurement of the dose delivered by an external beam in radiotherapy. The use of scintillating fibers in high-energy experiments produced rapid and reliable results and allows new dosimeters to be built and extends their use to measure the dose of an external beam of electrons, photons, and hadrons in radiotherapy.The chapter starts from the description of the radiation used in radiotherapy, presents the new approaches and then the tools used to perform the quality control of therapeutic beams, and finally shows the characteristics and differences compared to the traditional quality controls by using our results on the scintillating fibers used as a dosimeter. Some care should be taken into account during the collection and processing of data, for the treatment of some systematic errors in the method. In this chapter, we describe the procedure to be followed

Radiation therapy during the coronavirus disease 2019 (covid-19) pandemic in Italy: a view of the nation's young oncologists

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Intra- and inter-fraction breath-hold variations and margins for radiotherapy of abdominal targets

Radiotherapy in expiration breath-hold (EBH) has the potential to reduce treatment volumes of abdominal targets compared to an internal target volume concept in free-breathing. The reproducibility of EBH and required safety margins were investigated to quantify this volumetric benefit. Pre- and post-treatment diaphragm position difference and the positioning variability were determined on computed tomography. Systematic and random errors for EBH position reproducibility and positioning variability were calculated, resulting in margins of 7 to 12 mm depending on the prescription isodose and fractionation. A reduced volume was shown for EBH for lesions with superior-inferior breathing motion above 4 to 8 mm

Salvage stereotactic body radiotherapy for isolated lymph node recurrent prostate cancer : single institution series of 94 consecutive patients and 124 lymph nodes

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Salvage Stereotactic Reirradiation for Local Recurrence in the Prostatic Bed After Prostatectomy: A Retrospective Multicenter Study

Background: Management of local recurrence of prostate cancer (PCa) in the prostatic bed after radical prostatectomy (RP) and radiotherapy remains challenging. Objective: To assess the efficacy and safety of salvage stereotactic body radiotherapy (SBRT) reirradiation in this setting and evaluate prognostic factors. Design, setting, and participants: We conducted a large multicenter retrospective series that included 117 patients who were treated with salvage SBRT for local recurrence in the prostatic bed after RP and radiotherapy in 11 centers across three countries. Outcome measurements and statistical analysis: Progression-free survival (PFS; biochemical, clinical, or both) was estimated using the Kaplan-Meier method. Biochemical recurrence was defined as prostate-specific antigen nadir +0.2 ng/ml, confirmed by a second increasing measure. The cumulative incidence of late toxicities was estimated using the Kalbfleisch-Prentice method by considering recurrence or death as a competing event. Results and limitations: The median follow-up was 19.5 mo. The median SBRT dose was 35 Gy. The median PFS was 23.5 mo (95% confidence interval [95% CI], 17.6-33.2). In the multivariable models, the volume of the recurrence and its contact with the urethrovesical anastomosis were significantly associated with PFS (hazard ratio [HR]/10 cm3 = 1.46; 95% CI, 1.08-1.96; p = 0.01 and HR = 3.35; 95% CI, 1.38-8.16; p = 0.008, respectively). The 3-yr cumulative incidence of grade ≥2 late GU or GI toxicity was 18% (95% CI, 10-26). In the multivariable analysis, a recurrence in contact with the urethrovesical anastomosis and D2% of the bladder were significantly associated with late toxicities of any grade (HR = 3.65; 95% CI, 1.61-8.24; p = 0.002 and HR/10 Gy = 1.88; 95% CI, 1.12-3.16; p = 0.02, respectively). Conclusions: Salvage SBRT for local recurrence in the prostate bed may offer encouraging control and acceptable toxicity. Therefore, further prospective studies are warranted. Patient summary: We found that salvage stereotactic body radiotherapy after surgery and radiotherapy allows for encouraging control and acceptable toxicity in locally relapsed prostate cancer

Quality assurance for automatically generated contours with additional deep learning

Objective: Deploying an automatic segmentation model in practice should require rigorous quality assurance (QA) and continuous monitoring of the model’s use and performance, particularly in high-stakes scenarios such as healthcare. Currently, however, tools to assist with QA for such models are not available to AI researchers. In this work, we build a deep learning model that estimates the quality of automatically generated contours. Methods: The model was trained to predict the segmentation quality by outputting an estimate of the Dice similarity coefficient given an image contour pair as input. Our dataset contained 60 axial T2-weighted MRI images of prostates with ground truth segmentations along with 80 automatically generated segmentation masks. The model we used was a 3D version of the EfficientDet architecture with a custom regression head. For validation, we used a fivefold cross-validation. To counteract the limitation of the small dataset, we used an extensive data augmentation scheme capable of producing virtually infinite training samples from a single ground truth label mask. In addition, we compared the results against a baseline model that only uses clinical variables for its predictions. Results: Our model achieved a mean absolute error of 0.020 ± 0.026 (2.2% mean percentage error) in estimating the Dice score, with a rank correlation of 0.42. Furthermore, the model managed to correctly identify incorrect segmentations (defined in terms of acceptable/unacceptable) 99.6% of the time. Conclusion: We believe that the trained model can be used alongside automatic segmentation tools to ensure quality and thus allow intervention to prevent undesired segmentation behavior

Emerging role of microRNAs in breast cancer radiotherapy: DOI: 10.14800/rd.786

Breast cancer represents the leading cause of death in women worldwide. Ionizing radiation is one of the most relevant therapeutic approaches for the treatment of this type of cancer. Unfortunately, either resistance of tumor cells to therapeutic doses of radiation or normal tissue tolerance have proven to limit the effectiveness of radiotherapy. In the last few years, several studies have highlighted an important link between radioresistance, cancer and microRNAs (miRNAs), an emerging class of endogenous non coding RNAs that control gene expression at post-transcriptional/translational level. MiRNAs may influence carcinogenesis at multiple stages and effectively control tumor radiosensitivity as they affect levels of DNA damage repair, cell cycle checkpoint, apoptosis, radio-related signal transduction pathways and tumor microenvironment-related genes. Since radiation- and multidrug resistances are the characteristic properties of numerous type of tumors, there is increasing interest in establishing a clear association between miRNA expression in tumors and chemo- or radio-sensitivity, with regard to predicting or modulating sensitivity. In the present review, we summarize the emerging evidence of miRNA involvement in the radioresponse of breast tumors and discuss their potential as radiosensitizers

Unraveling Mitochondrial Determinants of Tumor Response to Radiation Therapy

Radiotherapy represents a highly targeted and efficient treatment choice in many cancer types, both with curative and palliative intents. Nevertheless, radioresistance, consisting in the adaptive response of the tumor to radiation-induced damage, represents a major clinical problem. A growing body of the literature suggests that mechanisms related to mitochondrial changes and metabolic remodeling might play a major role in radioresistance development. In this work, the main contributors to the acquired cellular radioresistance and their relation with mitochondrial changes in terms of reactive oxygen species, hypoxia, and epigenetic alterations have been discussed. We focused on recent findings pointing to a major role of mitochondria in response to radiotherapy, along with their implication in the mechanisms underlying radioresistance and radiosensitivity, and briefly summarized some of the recently proposed mitochondria-targeting strategies to overcome the radioresistant phenotype in cancer

Upfront Advanced Radiotherapy and New Drugs for NSCLC Patients with Synchronous Brain Metastases: Is the Juice Worth the Squeeze? A Real-World Analysis from Lombardy, Italy

Aim: Healthcare administrative databases represent a valuable source for real-life data analysis. The primary aim of this study is to compare effectiveness and cost profile in non-small-cell lung cancer (NSCLC) patients harboring synchronous brain metastases (BMs) who received non-chemo first-line systemic therapy with or without advanced radiotherapy (aRT). Methods: Diagnostic ICD-9-CM codes were used for identifying all patients with a new diagnosis of lung cancer between 2012 and 2019. Among these, patients who had started a first-line systemic treatment with either TKIs or pembrolizumab, alone or in combination with intensity-modulated or stereotactic RT, were selected. Clinical outcomes investigated included overall survival (OS), progression-free survival (PFS), and time-to-treatment failure (TTF). The cost outcome was defined as the average per capita cumulative healthcare direct costs of the treatment, including all inpatient and outpatient costs. Results: The final cohort included 177 patients, of whom 58 were treated with systemic treatment plus aRT (STRT) and 119 with systemic treatment alone. The addition of aRT to systemic treatment was associated with a significantly better OS (p = 0.020) and PFS (p = 0.041) than systemic therapy alone. The ICER (incremental cost-effectiveness ratio) value indicated an average cost of €3792 for each month of survival after STRT treatment and confirmed clinical effectiveness but higher healthcare costs. Conclusions: This real-world study suggests that upfront aRT for NCLSC patients with synchronous BMs represents a valid treatment strategy, boosting the efficacy of novel and emerging drug classes with sustainable costs for the health service. Translational relevance: The present real-world study reports that the use of upfront advanced radiotherapyaRT and new-generation systemic agents, such as TKIs and pembrolizumab, may have higher oncological control and an improved cost-effectiveness profile than the use of new-generation systemic agents alone in NCLSC patients with synchronous brain metastases. Acquired evidence can also be used to inform policymakers that adding advanced radiotherapy results is a sustainable cost for the health service. Since approximately 50% of patients do not meet RCT inclusion criteria, a significant proportion of them is receiving treatment that is not evidence-informed; therefore, these results warrant further studies to identify the best radiotherapy timing and possible dose escalation approaches to improving treatment efficacy in patient subgroups not typically represented in randomized controlled trials