Longer time to testosterone recovery impacts favorably on outcomes for prostate cancer following androgen deprivation and radiotherapy.

PURPOSE: To evaluate the impact of sustained hypogonadism after androgen deprivation therapy (ADT) associated with radiotherapy in prostate cancer (PCa) patients with biochemical relapse-free survival (bRFS). METHODS: A retrospective cohort analysis of 213 consecutive PCa patients referred for radiotherapy plus ADT was carried out. Follow-up times including time to testosterone recovery (TTR) and bRFS were calculated from the end of ADT. Univariate and multivariate Cox regression analyses predicting bRFS were used. The optimal cutoffs for TTR and duration of ADT were determined using the maximally selected rank statistics (MSRS). RESULTS: After a median follow-up of 104 months, 18 patients relapsed among those who had recovered testosterone levels and 9 among those who did not. Median ADT duration was 36 months. The optimal cutoff for TTR was determined using MSRS. TTR >48 months was significantly associated with better bRFS (logrank, p < 0.0027). Five-year bRFS was 100% for >48 months vs. 85% for <48 months. TTR was the only significant variable for bRFS in multivariate Cox analysis. CONCLUSION: Our data show an association between longer TTR and bRFS values among PCa patients treated with ADT.

LDR brachytherapy offers superior tumor control to single-fraction HDR prostate brachytherapy: A prospective study.

PURPOSE: To compare the clinical outcomes of single-fraction high-dose-rate (HDR) brachytherapy and single-fraction low-dose-rate (LDR) brachytherapy as the sole treatment for primary prostate cancer. MATERIAL AND METHODS: A quasi-randomized study that allocated, from March 2008 to February 2012, 129 low and intermediate risk prostate cancer patients to one single-fraction HDR of 19 Gy (61 patients) or to a 145 Gy 125 I LDR permanent implant (68 patients. Biochemical relapse-free survival (bRFS) and overall survival (OS) were compared using the Kaplan-Meier method and Cox regression analysis. RESULTS: After a median follow-up of 72 months in the HDR group, 26 patients relapsed, and after a median follow-up of 84 months in the LDR group, 7 patients relapsed (p < 0.0001). The 5-year bRFS was significantly better for the LDR group than for the HDR group (93.7% and 61.1%, respectively) (p < 0.0001). The 5-year OS also was significantly better in the LDR group (95.5% vs. 89.9%) (p = 0.0436). CONCLUSIONS: Permanent LDR prostate implant brachytherapy offers better clinical outcomes than single-fraction HDR for prostate cancer.

Postoperative endometrial carcinoma treated with external beam irradiation plus vaginal-cuff brachytherapy. Is there a dose relationship with G2 vaginal complications?

AIM: To analyse the possible relationship between the EQD2(α/ß=3Gy) at 2 cm3 of the vagina and late toxicity in vaginal-cuff-brachytherapy (VBT) after external-beam-irradiation (EBRT) for postoperative endometrial carcinoma (EC). MATERIALS AND METHODS: From 2014 to 2016, 62 postoperative EC patients were treated with EBRT + VBT. The median EBRT dose was 45 Gy (44 Gy-50.4 Gy). VBT involved a single 7 Gy dose. Toxicity was prospectively evaluated using the RTOG score for the rectum and bladder and the objective LENT-SOMA criteria for the vagina. EQD2(α/ß = 3Gy) at 2 cm3 of the most exposed part of the vagina was calculated by the sum of the EBRT + VBT dose. Statistics: Boxplot, Student's t and Chi-square tests and ROC curves. RESULTS: Mean follow-up: 39.2 months (15-68). Late toxicity: bladder:0 patient; rectum:2 patients-G1; Vagina: 26 patients-17G1, 9G2; median EQD2(α/ß=3Gy) at 2 cm3 in G0-G1 patients was 70.4 Gy(SD2.36), being 72.5 Gy(SD2.94) for G2p. The boxplot suggested a cut-point identifying the absence of G2: 100 % of G2p received >68 Gy, ROC curves showed an area under the curve of 0.72 (sensitivity of 1 and specificity of 0.15). CONCLUSIONS: Doses >68 Gy EQD2(α/ß=3Gy) at 2 cm3 to the most exposed area of the vagina were associated with late G2 vaginal toxicity in postoperative EC patients treated with EBRT + VBT suggesting a very good dose limit to eliminate the risk of G2 late toxicity. The specificity obtained indicates the need for prospective analyses.

Patients' view of the differences in topical creams for radiation dermatitis prevention. A pilot study of cosmetic properties.

AIM: To investigate the feasibility of including patients' reports on the cosmetic properties of topical formulations for acute radiation dermatitis (ARD). BACKGROUND: No topical agent tested for acute radiation dermatitis (ARD) has proven to be better than any other, all achieving similar objective outcomes. No clear guidelines have therefore been established in clinics. Because the vehicle for such creams has shown to be an important factor in patient adherence to treatments in other dermatological diseases, patients' opinions are evaluated. MATERIAL AND METHODS: Seventy breast cancer patients referred for postoperative radiotherapy after conservative surgery were enrolled. Patients were assigned to use one of the 7 topical agents that are most-commonly used in the prevention of ARD. Patients' reports were assessed using continuous visual analogue scales (VAS), objective signs and symptoms produced by ARD, and were rated using the RTOG and RISRAS scales. RESULTS: The creams tested differed in their cosmetic properties significantly (p = 0.044). The performance of the agent, their absorption and any residue left over were also significantly different (p = 0.022, 0.014 and 0.02, respectively). CONCLUSIONS: Topical agents for preventive ARD are reported by patients to show different cosmetic properties. Cosmetic properties are important when choosing topical agents for ARD prevention. Recommending those with better cosmetic profiles would improve patient adherence to treatments.

Radiomics of CT Features May Be Nonreproducible and Redundant: Influence of CT Acquisition Parameters.

Purpose To identify the reproducible and nonredundant radiomics features (RFs) for computed tomography (CT). Materials and Methods Two phantoms were used to test RF reproducibility by using test-retest analysis, by changing the CT acquisition parameters (hereafter, intra-CT analysis), and by comparing five different scanners with the same CT parameters (hereafter, inter-CT analysis). Reproducible RFs were selected by using the concordance correlation coefficient (as a measure of the agreement between variables) and the coefficient of variation (defined as the ratio of the standard deviation to the mean). Redundant features were grouped by using hierarchical cluster analysis. Results A total of 177 RFs including intensity, shape, and texture features were evaluated. The test-retest analysis showed that 91% (161 of 177) of the RFs were reproducible according to concordance correlation coefficient. Reproducibility of intra-CT RFs, based on coefficient of variation, ranged from 89.3% (151 of 177) to 43.1% (76 of 177) where the pitch factor and the reconstruction kernel were modified, respectively. Reproducibility of inter-CT RFs, based on coefficient of variation, also showed large material differences, from 85.3% (151 of 177; wood) to only 15.8% (28 of 177; polyurethane). Ten clusters were identified after the hierarchical cluster analysis and one RF per cluster was chosen as representative. Conclusion Many RFs were redundant and nonreproducible. If all the CT parameters are fixed except field of view, tube voltage, and milliamperage, then the information provided by the analyzed RFs can be summarized in only 10 RFs (each representing a cluster) because of redundancy.

Radiation Oncology Teaching Programmes as Part of the Undergraduate Degree in Medicine in Spanish Universities: the Need for an Update of the Contents and Structure.

The relevance of radiation oncology (RO) teaching in the Faculty of Medicine Degree Plan is justified by the high number of cancer patients who will require it at some point in their evolution of radiotherapy (RT). About 40 % of the population who will suffer cancer will be cured by RT alone or other related treatment modalities. Therefore, cancer education and RT teaching needs to have an in depth impact in the undergraduate medicine programmes. This education component is highly variable, not only among countries but also within each country, in terms of content (theory and practical training), number of credits and departmental affiliation of the teachers. Our aim is to take a snapshot of the situation of the teaching of RO in undergraduate university education in Spain. We have analysed 40 Spanish universities about specific aspects related to the teaching of RT. Information was obtained by mail or telephone contact throughout 2015. We have analysed the elements involved in teaching performance. In universities with various instructional units, we have taken the average of them. Among the Universities consulted in Spain, during the period of the medical degree, the average time allocated to RT lectures is 12 h (range, 0-36), the mean time allocated to seminars is 4 h (range, 0-22), and the mean time assigned to practices is 11 h (range, 0-38). The subject is mainly taught by a radiation oncologist and 80 % of Spanish universities have at least one radiation oncologist on staff. Undergraduate radiation oncology teaching in Spain shows structural heterogeneity. The Spanish Society of Radiation Oncology (SEOR) University Forum has identified new opportunities and elaborated a proposal to improve undergraduate education in oncology.

Do Patients Feel Well Informed in a Radiation Oncology Service?

Information received by cancer patients has gained importance in recent decades. The aim of this study was to evaluate the perception of information received by oncological patients in a radiotherapy department and to measure the importance of the other information sources. A cross-sectional study was conducted, evaluating patients who received radiotherapy. All the patients were asked two questionnaires: the EORTC QLQ-INFO26 module evaluating their satisfaction with received information, and a questionnaire analyzing other sources of information search. One hundred patients between 27 and 84 years were enrolled. Breast cancer (26 %) was the commonest cancer. Patients felt better informed about the medical tests and secondly about the performed treatment. The younger patients were those who were more satisfied with the information received and patients with no formal education felt less satisfied, with statistically significant differences. Patients did not seek external information; at the most, they asked relatives and other people with cancer. Patients were satisfied with the received information, although a high percentage would like more information. In general, patients did not search for external information sources. Age and educational level seem to influence in the satisfaction with the received information.

Effect of rectal enemas on rectal dosimetric parameters during high-dose-rate vaginal cuff brachytherapy: A prospective trial.

PURPOSE: To evaluate the effects of rectal enemas on rectal doses during postoperative high-dose-rate (HDR) vaginal cuff brachytherapy (VCB). PATIENTS AND METHODS: This prospective trial included 59 patients. Two rectal cleansing enemas were self-administered before the second fraction, and fraction 1 was considered the basal status. Dose-volume histogram (DVH) values were generated for the rectum and correlated with rectal volume variation. Statistical analyses used paired and unpaired t-tests. RESULTS: Despite a significant 15 % reduction in mean rectal volume (44.07 vs. 52.15 cc, p = 0.0018), 35.6 % of patients had larger rectums after rectal enemas. No significant rectal enema-related DVH differences were observed compared to the basal data. Although not statistically significant, rectal cleansing-associated increases in mean rectal DVH values were observed: D0.1 cc: 6.6 vs. 7.21 Gy; D1 cc: 5.35 vs. 5.52 Gy; D2 cc: 4.67 vs. 4.72 Gy, before and after rectal cleaning, respectively (where Dx cc is the dose to the most exposed x cm(3)). No differences were observed in DVH parameters according to rectal volume increase or decrease after the enema. Patients whose rectal volume increased also had significantly larger DVH parameters, except for D5 %, D25 %, and D50 %. In contrast, in patients whose rectal volume decreased, significance was only seen for D25 % and D50 % (Dx % dose covering x % of the volume). In the latter patients, nonsignificant reductions in D2 cc, D5 cc and V5 Gy (volume receiving at least 5 Gy) were observed. CONCLUSION: The current rectal enemas protocol was ineffective in significantly modifying rectal DVH parameters for HDR-VCB.

Radiotherapy for Graves' disease. The possible role of low-dose radiotherapy.

Immunomodulatory effects of low-dose radiotherapy (LD-RT) have been used for the treatment of several benign diseases, including arthrodegenerative and inflammatory pathologies. Graves' disease is an autoimmune disease and radiotherapy (RT) is a therapeutic option for ocular complications. The dose recommended in the clinical practice is 20 Gy (2 Gy/day). We hypothesized that lower doses (<10 Gy total dose, <1 Gy/day) could results in higher efficacy if we achieved anti-inflammatory and immunomodulatory effects of LD-RT. We review current evidence on the effects of RT in the treatment of Graves' disease and the possible use of LD-RT treatment strategy.

Decentralisation of radiation therapy. Is it possible and beneficial to patients? Experience of the first 5 years of a satellite radiotherapy unit in the province of Tarragona, Spain.

BACKGROUND: The concept of satellite radiotherapy originates in countries whose populations are largely dispersed in order to treat homogenously the population by a unique fixed team. AIM: This report describes the creation and management of a satellite radiotherapy unit in Spain (RUTE-Radiotherapy Unit, Terres de l'Ebre). It is managed by the Radiation Oncology Department at Hospital Universitari Sant Joan de Reus. We report the benefit gained in the comfort of patients and the economic benefit gained by reducing the expense of transport for the health care system. MATERIALS AND METHODS: RUTE is equipped with a linear accelerator. A team of 10 physicians, specialised in different oncology pathologies, travel to RUTE on a rotational basis from the main Radiation Oncology Department. Simulation and planning of treatment is managed at the Radiation Oncology Department in Reus. Patients from RUTE only have to visit the centre in Reus once throughout the treatment process. RESULTS: Since August 2008, 1500 patients have completed treatment in the satellite unit. The implementation of RUTE has greatly improved the comfort of patients and along with that, there have been important savings in transport costs to the regional health care system. CONCLUSIONS: Despite the high technological requirements of our speciality, decentralising radiotherapy is feasible. We can guarantee the highest standards of treatment with no differences from attending the main centre. It implies a clear benefit for the comfort of the patients and an economic benefit by decreasing transport costs.

The effect of lymphadenectomy and radiotherapy on recurrence and survival in endometrial carcinoma. Experience in a population reference centre.

AIM: To evaluate the effect of lymphadenectomy and/or radiotherapy on recurrence and survival patterns in endometrial carcinoma (EC) in a radiotherapy reference centre population. MATERIAL AND METHODS: A retrospective population-based review was conducted on 261 patients with stages I-III EC. Univariate and multivariate analyses were carried out. Both recurrence and survival were analysed according to patient age, FIGO stage, tumour size, myometrial invasion, tumour grade, lymphadenectomy, external beam irradiation (EBI), and brachytherapy (BT). RESULTS: Median age: 64.8 years. Median follow-up: 151 months. The following treatments were administered: surgery, 97.32%; lymph-node dissection, 54.4%; radiotherapy, 162 patients (62%) (EBI and BT: 64.1%, BT alone: 30.2%, EBI alone: 5.6%). Twenty-six patients (9.96%) suffered loco-regional recurrence, whilst 27 (10.34%) suffered distant failure. The 5-year overall survival (OS) for all stages was 80.1%. The 5-year disease free survival (DFS) was 92.1% for all patients. The 10-year DFS was 89.9%. The independent significant prognostic factors for a good outcome identified through the multivariate analysis were: age <75 years (p = 0.001); tumour size ≤2 cm (p = 0.003); myometrial invasion ≤50% (p = 0.011); lymphadenectomy (p = 0.02); EBI (p = 0.001); and BT (p = 0.031). Toxicity occurred in 114 of the 162 patients who received radiotherapy (70.5%). The toxicity was mainly acute, and late in only 28.3% (n = 45) of cases. The majority experienced G1-2 toxicity, and only 3% of patients experienced G3 late toxicity (5/162). CONCLUSIONS: Our results suggest that age <75 years, tumour size ≤2 cm, myometrial invasion ≤50%, lymphadenectomy, EBI, and BT, are predictors of a good outcome in EC.

Do breast cups improve breast cancer dosimetry? A comparative study for patients with large or pendulous breasts.

PURPOSE: Treating patients with large or pendulous breasts is challenging. Although brassiere cups are currently in use, no study has yet been carried out to assess their dosimetric impact. The aim of the present study was to evaluate the possible dosimetric advantages of the use of breast cups on patients with large or pendulous breasts. MATERIALS AND METHODS: Two CT studies were carried out on 12 breast cancer patients with large or pendulous breasts, with one study involving the use of breast cups. Radiation plans were developed in accordance with each of the CT studies. The following were compared: planning target volume (PTV), volume irradiated by the 95% isodose, conformity index, homogeneity index, mean lung dose, and mean heart dose was also compared for left breast treatment. The plan involving the use of cups was found to be the best option, leading to all patients being treated with cups. The resulting acute toxicity and cosmesis were also recorded. Both scenarios involved the use of film dosimetry to evaluate the skin doses. RESULTS: The use of breast cups resulted in a significant reduction of the PTV volume (from 1640 cm3 to 1283 cm3), of the irradiated volume (from 2154 cm3 to 1477 cm3) and of the conformity index (from 1383 to 1213). Despite slight improvements in the homogeneity index (from 0.12 to 0.10), statistical significance was not attained. The use of breast cups also led to significant dose reductions in V20 for lung (from 13.7% to 1.7%) and V5 for heart (from 9.8% to 2.7%). No differences in acute toxicity or cosmesis were observed compared to patients treated without cups. CONCLUSIONS: Our results show that the use of brassiere cups during breast radiation therapy leads to improvements in the main dosimetric factors analyzed. Furthermore, modifications to standard irradiation protocols are not required. In summary, we consider the technique of using breast cups with radiation therapy highly appropriate when treating breast cancer patients with large or pendulous breasts.

METhodological RadiomICs Score (METRICS): a quality scoring tool for radiomics research endorsed by EuSoMII.

PURPOSE: To propose a new quality scoring tool, METhodological RadiomICs Score (METRICS), to assess and improve research quality of radiomics studies. METHODS: We conducted an online modified Delphi study with a group of international experts. It was performed in three consecutive stages: Stage#1, item preparation; Stage#2, panel discussion among EuSoMII Auditing Group members to identify the items to be voted; and Stage#3, four rounds of the modified Delphi exercise by panelists to determine the items eligible for the METRICS and their weights. The consensus threshold was 75%. Based on the median ranks derived from expert panel opinion and their rank-sum based conversion to importance scores, the category and item weights were calculated. RESULT: In total, 59 panelists from 19 countries participated in selection and ranking of the items and categories. Final METRICS tool included 30 items within 9 categories. According to their weights, the categories were in descending order of importance: study design, imaging data, image processing and feature extraction, metrics and comparison, testing, feature processing, preparation for modeling, segmentation, and open science. A web application and a repository were developed to streamline the calculation of the METRICS score and to collect feedback from the radiomics community. CONCLUSION: In this work, we developed a scoring tool for assessing the methodological quality of the radiomics research, with a large international panel and a modified Delphi protocol. With its conditional format to cover methodological variations, it provides a well-constructed framework for the key methodological concepts to assess the quality of radiomic research papers. CRITICAL RELEVANCE STATEMENT: A quality assessment tool, METhodological RadiomICs Score (METRICS), is made available by a large group of international domain experts, with transparent methodology, aiming at evaluating and improving research quality in radiomics and machine learning. KEY POINTS: • A methodological scoring tool, METRICS, was developed for assessing the quality of radiomics research, with a large international expert panel and a modified Delphi protocol. • The proposed scoring tool presents expert opinion-based importance weights of categories and items with a transparent methodology for the first time. • METRICS accounts for varying use cases, from handcrafted radiomics to entirely deep learning-based pipelines. • A web application has been developed to help with the calculation of the METRICS score ( https://metricsscore.github.io/metrics/METRICS.html ) and a repository created to collect feedback from the radiomics community ( https://github.com/metricsscore/metrics ).

Are 7.5 Gy×2 fractions more efficient than 6 Gy×3 in exclusive postoperative endometrial cancer brachytherapy? A clinical and dosimetrical analysis.

PURPOSE: To compare two vaginal brachytherapy (VBT) schedules in postoperative endometrial carcinoma (PEC) patients considering vaginal-cuff relapses (VCR), late toxicities, dosimetry analysis and vaginal dilator use. MATERIAL AND METHODS: 110 PEC patients were treated with exclusive high-dose-rate VBT using two schedules. Group-1:44-patients received 6 Gy×3fractions (September-2011-April-2014); Group-2:66-patients were treated with 7.5 Gy×2fractions with a dose limit of equivalent total doses in 2-Gy fr (EQD2(α/ß=3)) of 68 Gy in the most exposed 2 cm3 of clinical target volume (CTV) (July-2015-November-2021). The dose was prescribed at 5 mm from the applicator surface. Were evaluated the overall radiation dose delivered to 90% of the CTV (D90), the CTV receiving 100% of the prescription dose (V100) and the EQD2(α/ß=3) received in the most exposed 2 cm3 to dose in CTV. Late toxicity was prospectively assessed using RTOG scores for bladder and rectum and objective LENT-SOMA criteria for late vaginal toxicity (LVT). STATISTICS: Descriptive analysis, Chi-square, Student's t-tests and Kaplan and Meier method. RESULTS: The median follow-up was 60 months (15.9-60). There were no VCR or late toxicities in bladder or rectum. LVT ≥ G1 appeared in 26/44 (59.1%) in Group-1 and 25/66 (37.9%) in Group-2. The mean EQD2(α/ß=3) received by the most exposed 2 cm3 of CTV was 63.7 Gy ± 10.0 in Group-1 and 60.5 Gy ± 3.8 in Group-2 (p = 0.063). There were no differences in adherence to vaginal dilator use ≥9 months, overall D90 and V100. CONCLUSION: Considering the lack of vaginal relapses and similar LVT over time, 7.5 Gy×2fractions seem more efficient in terms of patient comfort, workload, and cost. This is the first study using dosimetry parameters to compare effectivity of schedules. Larger series are needed to confirm the present results.

P38 MAPK and Radiotherapy: Foes or Friends?

Over the last 30 years, the study of the cellular response to ionizing radiation (IR) has increased exponentially. Among the various signaling pathways affected by IR, p38 MAPK has been shown to be activated both in vitro and in vivo, with involvement in key processes triggered by IR-mediated genotoxic insult, such as the cell cycle, apoptosis or senescence. However, we do not yet have a definitive clue about the role of p38 MAPK in terms of radioresistance/sensitivity and its potential use to improve current radiotherapy. In this review, we summarize the current knowledge on this family of MAPKs in response to IR as well as in different aspects related to radiotherapy, such as their role in the control of REDOX, fibrosis, and in the radiosensitizing effect of several compounds.

Self-Renewal Inhibition in Breast Cancer Stem Cells: Moonlight Role of PEDF in Breast Cancer.

Breast cancer is the leading cause of death among females in developed countries. Although the implementation of screening tests and the development of new therapies have increased the probability of remission, relapse rates remain high. Numerous studies have indicated the connection between cancer-initiating cells and slow cellular cycle cells, identified by their capacity to retain long labeling (LT+). In this study, we perform new assays showing how stem cell self-renewal modulating proteins, such as PEDF, can modify the properties, percentage of biomarker-expressing cells, and carcinogenicity of cancer stem cells. The PEDF signaling pathway could be a useful tool for controlling cancer stem cells' self-renewal and therefore control patient relapse, as PEDF enhances resistance in breast cancer patient cells' in vitro culture. We have designed a peptide consisting of the C-terminal part of this protein, which acts by blocking endogenous PEDF in cell culture assays. We demonstrate that it is possible to interfere with the self-renewal capacity of cancer stem cells, induce anoikis in vivo, and reduce resistance against docetaxel treatment in cancer patient cells in in vitro culture. We have also demonstrated that this modified PEDF protein produces a significant decrease in the percentage of expressed cancer stem cell markers.

Pilot Study for the Assessment of the Best Radiomic Features for Bosniak Cyst Classification Using Phantom and Radiologist Inter-Observer Selection.

Since the Bosniak cysts classification is highly reader-dependent, automated tools based on radiomics could help in the diagnosis of the lesion. This study is an initial step in the search for radiomic features that may be good classifiers of benign-malignant Bosniak cysts in machine learning models. A CCR phantom was used through five CT scanners. Registration was performed with ARIA software, while Quibim Precision was used for feature extraction. R software was used for the statistical analysis. Robust radiomic features based on repeatability and reproducibility criteria were chosen. Excellent correlation criteria between different radiologists during lesion segmentation were imposed. With the selected features, their classification ability in benignity-malignity terms was assessed. From the phantom study, 25.3% of the features were robust. For the study of inter-observer correlation (ICC) in the segmentation of cystic masses, 82 subjects were prospectively selected, finding 48.4% of the features as excellent regarding concordance. Comparing both datasets, 12 features were established as repeatable, reproducible, and useful for the classification of Bosniak cysts and could serve as initial candidates for the elaboration of a classification model. With those features, the Linear Discriminant Analysis model classified the Bosniak cysts in terms of benignity or malignancy with 88.2% accuracy.

Gradient Boosting Machine Identified Predictive Variables for Breast Cancer Patients Pre- and Post-Radiotherapy: Preliminary Results of an 8-Year Follow-Up Study.

Radiotherapy (RT) is part of the standard treatment of breast cancer (BC) because of its effects on relapse reduction and survival. However, response to treatment is highly variable, and some patients may develop disease progression (DP), a second primary cancer, or may succumb to the disease. Antioxidant systems and inflammatory processes are associated with the onset and development of BC and play a role in resistance to treatment. Here, we report our investigation into the clinical evolution of BC patients, and the impact of RT on the circulating levels of the antioxidant enzyme paraoxonase-1 (PON1), cytokines, and other standard biochemical and hematological variables. Gradient Boosting Machine (GBM) algorithm was used to identify predictive variables. This was a retrospective study in 237 patients with BC. Blood samples were obtained pre- and post-RT, with samples of healthy women used as control subjects. Results showed that 24 patients had DP eight years post-RT, and eight patients developed a second primary tumor. The algorithm identified interleukin-4 and total lymphocyte counts as the most relevant indices discriminating between BC patients and control subjects, while neutrophils, total leukocytes, eosinophils, very low-density lipoprotein cholesterol, and PON1 activity were potential predictors of fatal outcome.

Effect of Low-Dose Radiotherapy on the Circulating Levels of Paraoxonase-1-Related Variables and Markers of Inflammation in Patients with COVID-19 Pneumonia.

The aim of our study was to investigate the changes produced by low-dose radiotherapy (LDRT) in the circulating levels of the antioxidant enzyme paraoxonase-1 (PON1) and inflammatory markers in patients with COVID-19 pneumonia treated with LDRT and their interactions with clinical and radiological changes. Data were collected from the IPACOVID prospective clinical trial (NCT04380818). The study included 30 patients treated with a whole-lung dose of 0.5 Gy. Clinical follow-up, as well as PON1-related variables, cytokines, and radiological parameters were analyzed before LDRT, at 24 h, and 1 week after treatment. Twenty-five patients (83.3%) survived 1 week after LDRT. Respiratory function and radiological images improved in survivors. Twenty-four hours after LDRT, PON1 concentration significantly decreased, while transforming growth factor beta 1 (TGF-ß1) increased with respect to baseline. One week after LDRT, patients had increased PON1 activities and lower PON1 and TGF-ß1 concentrations compared with 24 h after LDRT, PON1 specific activity increased, lactate dehydrogenase (LDH), and C-reactive protein (CRP) decreased, and CD4+ and CD8+ cells increased after one week. Our results highlight the benefit of LDRT in patients with COVID-19 pneumonia and it might be mediated, at least in part, by an increase in serum PON1 activity at one week and an increase in TGF-ß1 concentrations at 24 h.