Evidence-based guidelines for hypofractionated radiation in breast cancer: conclusions of the Catalan expert working group

Breast cancer; Hypofractionation; RadiotherapyCàncer de mama; Hipofraccionament; RadioteràpiaCáncer de mama; Hipofraccionamiento; RadioterapiaIntroduction Daily, moderate hypofractionation has become standard treatment for breast cancer following breast-conserving surgery, although substantial variation exists in its use. This paper describes the generation of consensus-based recommendations for the utilisation of this therapy at the healthcare system level and compares these to American Society for Radiation Oncology (ASTRO) guidelines. Materials and methods Consensus-based guidelines were developed in three steps, including a systematic literature review and involvement of radiation oncologists specialising in breast cancer in Catalonia: (a) creation of a working group and evidence review; (b) consideration of the levels of evidence and agreement on the formulation of survey questions; and (c) performance of survey and development of consensus-based recommendations. Results were compared to the ASTRO recommendations. Results Consensus was above 80% for 10 of the 14 survey items. Experts supported hypofractionated radiotherapy for all breast cancer patients aged 40 years or more; with invasive carcinoma and breast-conserving surgery; without radiation of lymph nodes; and regardless of the tumour size, histological grade, molecular subtype, breast size, laterality, other treatment characteristics, or need for a boost. Over half favoured its use in all situations, even where available scientific evidence is insufficient. The resulting recommendations and the quality of the evidence are comparable to those from ASTRO, despite some differences in the degree of consensus. Conclusion Specialists agree that hypofractionation is the standard treatment for breast cancer following breast-conserving surgery, but some specific areas require a higher level of evidence before unequivocally extending indications.Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature

GSEA of mouse and human mitochondriomes reveals fatty acid oxidation in astrocytes

The prevalent view in neuroenergetics is that glucose is the main brain fuel, with neurons being mostly oxidative and astrocytes glycolytic. Evidence supporting that astrocyte mitochondria are functional has been overlooked. Here we sought to determine what is unique about astrocyte mitochondria by performing unbiased statistical comparisons of the mitochondriome in astrocytes and neurons. Using MitoCarta, a compendium of mitochondrial proteins, together with transcriptomes of mouse neurons and astrocytes, we generated cell-specific databases of nuclear genes encoding for mitochondrion proteins, ranked according to relative expression. Standard and in-house Gene Set Enrichment Analyses (GSEA) of five mouse transcriptomes revealed that genes encoding for enzymes involved in fatty acid oxidation (FAO) and amino acid catabolism are consistently more expressed in astrocytes than in neurons. FAO and oxidative-metabolism-related genes are also up-regulated in human cortical astrocytesversus the whole cortex, and in adult astrocytes versus fetal astrocytes. We thus present the first evidence of FAO in human astrocytes. Further, as shown in vitro, FAO coexists with glycolysis in astrocytes and is inhibited by glutamate. Altogether, these analyses provide arguments against the glucose-centered view of energy metabolism in astrocytes and reveal mitochondria as specialized organelles in these cells

CREB Regulates Distinct Adaptive Transcriptional Programs in Astrocytes and Neurons

The cyclic AMP response element binding protein (CREB) is a primary hub of a activity-driven genetic programs in neurons controlling plasticity, neurogenesis and survival. By contrast, the gene networks coordinated by CREB in astrocytes are Unknown despite the fact that the astrocytic CREB is a also activity-driven and neuroprotective. Herein we identified the transcriptional programs regulated by CREB in astrocytes as compared to neurons using, as study materials, transcriptome databases of astrocyte exposed to weII-known activators of CREB-dependent transcription as well as publidy available transcriptomes of neuronal cultures. Functional CREB signatures were extracted from the transcriptomes using Gene Ontology, adult-brain gene lists generated by Translating Ribosome Affinity Purification (TRAP) and CREB-target gene repositories. We found minimal overlap between CREB signatures in astrocytes and neurons. In astrocytes, the top triad of functions regulated by CREB consists of'Gene expression', 'Mitochondria', and 'Signa Iling', while in neurons it is 'Neurotransmission', 'Signalling' and 'Gene expression', the latter being represented by different genes from those in astrocytes. The newly gene rated data bases Will provide a tool to explore novel means whereby CREB impinges on brain functions requiring adaptive, long-lasting changes by coordinating transcriptionaI cascades in astrocytes

The use of an interstitial boost in the conservative treatment of breast cancer: how to perform it routinely in a radiotherapy department

Purpose: to demonstrate the utility of a boost with interstitial brachytherapy (BT) in breast-conserving therapy (BCT) by doing a thorough review of the literature and describing in detail our technique for delivering this boost. Material and methods: our department has been delivering the boost with interstitial BT since 1989, in most cases with rigid needles and a theoretical dosimetry. In the early years, we used low-dose-rate (LDR) with iridium-192 wires. The dose administered was 15 Gy if there were no risk factors for local relapse or 20-25 Gy in the presence of risk factors. The risk factors considered were the presence of a close margin (less than 10 mm) and an extensive intraductal component (more than 25%). After 2002, we switched to high-dose-rate (HDR); using the linear quadratic model we changed the low dose to 3 fractions of 4.5 Gy in the case of no risk factors for local relapse or to 3 fractions of 5 Gy in the presence of risk factors. Results: in 79 consecutive boost patients treated in our department between 2010 and 2011, with a median follow-up of 46 months, the local control rate was 97.47%. With respect to cosmesis, fibrosis occurred in 17 cases (21.5%) and hyperpigmentation in 26 cases (32.9%). Our hospital's results are comparable in terms of local control and cosmesis to those of other authors. Conclusions: this educational article describes our department's boost technique with rigid needles and comments briefly on our results using this technique in a group of consecutively treated patients in our department. A review of the literature and the published results on local control and cosmesis is also described

Assessment of non-adherence to external radiotherapy treatment in cancer patients in Catalonia,Spain

Purpose or Objective: Non-adherence to external radiotherapy is an aspect of treatment which has not been fully explored. The objective of this study is to analyse the relevance of this problem and its impact on 1-year surviva

Improving quality of care and clinical outcomes for rectal cancer through clinical audits in a multicentre cancer care organisation

Introduction: Colorectal cancer treatment requires a complex, multidisciplinary approach. Because of the potential variability, monitoring through clinical audits is advisable. This study assesses the effects of a quality improvement action plan in patients with locally advanced rectal cancer and treated with radiotherapy. Methods: Comparative, multicentre study in two cohorts of 120 patients each, selected randomly from patients diagnosed with rectal cancer who had initiated radiotherapy with a curative intent. Based on the results from a baseline clinical audit in 2013, a quality improvement action plan was designed and implemented; a second audit in 2017 evaluated its impact. Results: Standardised information was present on 77.5% of the magnetic resonance imaging (MRI) staging reports. Treatment strategies were similar in all three study centres. Of the patients whose treatment was interrupted, just 9.7% received a compensation dose. There was an increase in MRI re-staging from 32.5 to 61.5%, and a significant decrease in unreported circumferential resection margins following neoadjuvant therapy (ypCRM), from 34.5 to 5.6% (p < 0.001). Conclusions: The comparison between two clinical audits showed improvements in neoadjuvant radiotherapy in rectal cancer patients. Some indicators reveal areas in need of additional efforts, for example to reduce the overall treatment time

Impact of non-adherence to radiotherapy on 1-year survival in cancer patients in Catalonia, Spain

This study aims to assess the effects of non-adherence to external beam radiation therapy in cancer patients receiving treatment with a curative. This retrospective cohort study collected health records data for all cancer patients treated with external beam radiotherapy with curative intent in 2016 in Catalonia, Spain. Adherence was defined as having received at least 90% of the total dose prescribed. A logistic regression model was used to assess factors related to non-adherence, and its association with one-year survival was evaluated using Cox regression. The final sample included 8721 patients (mean age 63.6 years): breast cancer was the most common tumour site (38.1%), followed by prostate and colon/rectum. Treatment interruptions prolonged the total duration of therapy in 70.7% of the patients, and 1.0% were non-adherent. Non-adherence was associated with advanced age, female gender, and some localization of primary tumour (head and neck, urinary bladder, and haematological cancers). The risk of death in non-adherent patients was higher than in adherent patients (hazard ratio [HR] 1.63, 95% confidence interval 0.97-2.74), after adjusting for the potential confounding effect of age, gender, tumour site and comorbidity. Non-adherence to radiotherapy, as measured by the received dose, is very low in our setting, and it may have an impact on one-year survival

Subclinical Left Ventricular Dysfunction Detected by Speckle-Tracking Echocardiography in Breast Cancer Patients Treated With Radiation Therapy:A Six-Month Follow-Up Analysis (MEDIRAD EARLY‐HEART study)

Copyright © 2022 Locquet, Spoor, Crijns, van der Harst, Eraso, Guedea, Fiuza, Santos, Combs, Borm, Mousseaux, Gencer, Frija, Cardis, Langendijk and Jacob. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Background: In the case of breast cancer (BC), radiotherapy (RT) helps reduce locoregional recurrence and BC-related deaths but can lead to cardiotoxicity, resulting in an increased risk of long-term major cardiovascular events. It is therefore of primary importance to early detect subclinical left ventricular (LV) dysfunction in BC patients after RT and to determine the dose-response relationships between cardiac doses and these events. Methods: Within the frame of the MEDIRAD European project (2017-2022), the prospective multicenter EARLY-HEART study (ClinicalTrials.gov Identifier: NCT03297346) included chemotherapy naïve BC women aged 40-75 years and treated with lumpectomy and adjuvant RT. Myocardial strain analysis was provided using speckle-tracking echocardiography performed at baseline and 6 months following RT. A global longitudinal strain (GLS) reduction >15% between baseline and follow-up was defined as a GLS-based subclinical LV dysfunction. Individual patient dose distributions were obtained using multi-atlas-based auto-segmentation of the heart. Dose-volume parameters were studied for the whole heart (WH) and left ventricle (LV). Results: The sample included 186 BC women (57.5 ± 7.9 years, 64% left-sided BC). GLS-based subclinical LV dysfunction was observed in 22 patients (14.4%). These patients had significantly higher cardiac exposure regarding WH and LV doses compared to patients without LV dysfunction (for mean WH dose: 2.66 ± 1.75 Gy versus 1.64 ± 0.96 Gy, p = 0.01). A significantly increased risk of subclinical LV dysfunction was observed with the increase in the dose received to the WH [ORs from 1.13 (V5) to 1.74 (Dmean); p <0.01] and to the LV [ORs from 1.10 (V5) to 1.46 (Dmean); p <0.01]. Based on ROC analysis, the LV-V5 parameter may be the best predictor of the short-term onset of subclinical LV dysfunction. Conclusion: These results highlighted that all cardiac doses were strongly associated with the occurrence of subclinical LV dysfunction arising 6 months after BC RT. Whether measurements of GLS at baseline and 6 months after RT combined with cardiac doses can early predict efficiently subclinical events occurring 24 months after RT remains to be investigated.The European Community’s Horizon 2020 Programme supported the EARLY-HEART study conducted in the frame of the MEDIRAD - Implications of Medical Low Dose Radiation Exposure - project spanning from 2017 to 2021 granted by the Euratom Research and Training Programme 2014-2014 under agreement No. 755523.info:eu-repo/semantics/publishedVersio

Impact of non-adherence to radiotherapy on 1-year survival in cancer patients in Catalonia, Spain

Background: This study aims to assess the effects of non-adherence to external beam radiation therapy in cancer patients receiving treatment with a curative. Methods: This retrospective cohort study collected health records data for all cancer patients treated with external beam radiotherapy with curative intent in 2016 in Catalonia, Spain. Adherence was defined as having received at least 90% of the total dose prescribed. A logistic regression model was used to assess factors related to non-adherence, and its association with one-year survival was evaluated using Cox regression. Results: The final sample included 8721 patients (mean age 63.6 years): breast cancer was the most common tumour site (38.1%), followed by prostate and colon/rectum. Treatment interruptions prolonged the total duration of therapy in 70.7% of the patients, and 1.0% were non-adherent. Non-adherence was associated with advanced age, female gender, and some localization of primary tumour (head and neck, urinary bladder, and haematological cancers). The risk of death in non-adherent patients was higher than in adherent patients (hazard ratio [HR] 1.63, 95% confidence interval 0.97-2.74), after adjusting for the potential confounding effect of age, gender, tumour site and comorbidity. Conclusion: Non-adherence to radiotherapy, as measured by the received dose, is very low in our setting, and it may have an impact on one-year survival