Breast cancer management pathways during the COVID-19 pandemic: outcomes from the UK ‘Alert Level 4’ phase of the B-MaP-C study

Abstract: Background: The B-MaP-C study aimed to determine alterations to breast cancer (BC) management during the peak transmission period of the UK COVID-19 pandemic and the potential impact of these treatment decisions. Methods: This was a national cohort study of patients with early BC undergoing multidisciplinary team (MDT)-guided treatment recommendations during the pandemic, designated ‘standard’ or ‘COVID-altered’, in the preoperative, operative and post-operative setting. Findings: Of 3776 patients (from 64 UK units) in the study, 2246 (59%) had ‘COVID-altered’ management. ‘Bridging’ endocrine therapy was used (n = 951) where theatre capacity was reduced. There was increasing access to COVID-19 low-risk theatres during the study period (59%). In line with national guidance, immediate breast reconstruction was avoided (n = 299). Where adjuvant chemotherapy was omitted (n = 81), the median benefit was only 3% (IQR 2–9%) using ‘NHS Predict’. There was the rapid adoption of new evidence-based hypofractionated radiotherapy (n = 781, from 46 units). Only 14 patients (1%) tested positive for SARS-CoV-2 during their treatment journey. Conclusions: The majority of ‘COVID-altered’ management decisions were largely in line with pre-COVID evidence-based guidelines, implying that breast cancer survival outcomes are unlikely to be negatively impacted by the pandemic. However, in this study, the potential impact of delays to BC presentation or diagnosis remains unknown

Bridging pre-surgical endocrine therapy for breast cancer during the COVID-19 pandemic: outcomes from the B-MaP-C study

Purpose: The B-MaP-C study investigated changes to breast cancer care that were necessitated by the COVID-19 pandemic. Here we present a follow-up analysis of those patients commenced on bridging endocrine therapy (BrET), whilst they were awaiting surgery due to reprioritisation of resources. Methods: This multicentre, multinational cohort study recruited 6045 patients from the UK, Spain and Portugal during the peak pandemic period (Feb–July 2020). Patients on BrET were followed up to investigate the duration of, and response to, BrET. This included changes in tumour size to reflect downstaging potential, and changes in cellular proliferation (Ki67), as a marker of prognosis. Results: 1094 patients were prescribed BrET, over a median period of 53 days (IQR 32–81 days). The majority of patients (95.6%) had strong ER expression (Allred score 7–8/8). Very few patients required expedited surgery, due to lack of response (1.2%) or due to lack of tolerance/compliance (0.8%). There were small reductions in median tumour size after 3 months’ treatment duration; median of 4 mm [IQR − 20, 4]. In a small subset of patients ( n = 47), a drop in cellular proliferation (Ki67) occurred in 26 patients (55%), from high (Ki67 ≥ 10%) to low (< 10%), with at least one month’s duration of BrET. Discussion: This study describes real-world usage of pre-operative endocrine therapy as necessitated by the pandemic. BrET was found to be tolerable and safe. The data support short-term (≤ 3 months) usage of pre-operative endocrine therapy. Longer-term use should be investigated in future trials

Revisiting the effects of rTMS over the dorsolateral prefrontal cortex on pain: An updated systematic review and meta-analysis

Background: Our previous study synthesized the analgesic effects of repetitive Transcranial Magnetic Stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) trials up to 2019. There has been a significant increase in pain trials in the past few years, along with methodological variabilities such as sample size, stimulation intensity, and rTMS paradigms. Objectives/Methods: This study therefore updated the effects of DLPFC-rTMS on chronic pain and quantified the impact of methodological differences across studies. Results: A total of 36 studies were included. Among them, 26 studies were clinical trials (update = 9, 307/711 patients), and 10 (update = 1, 34/249 participants) were provoked pain studies. The updated meta-analysis does not support an effect on neuropathic pain after including the additional trials (pshort-term = 0.20, pmid-term = 0.50). However, there is medium-to-large analgesic effect in migraine trials extending up to six weeks follow-up (SMDmid-term = −0.80, SMDlong-term = −0.51), that was not previously reported. Methodological differences wthine the studies were considered. DLPFC-rTMS also induces potential improvement in the emotional aspects of pain (SMDshort-term = −0.28). Conclusions: The updated systematic meta-analysis continues to support analgesic effects for chronic pain overall. However, the updated results no longer support DLPFC-rTMS for pain relief in neuropathic pain, and do supports DLPFC-rTMS in the management of migraine. There is also evidence for DLPFC-rTMS to improve emotional aspects of pain

Abstract 337: cAbl Tyrosine Kinase Increases Catalase Activity in the Catalase-Dysregulated Newborn Rabbit Heart

Introduction: Pediatric patients undergoing corrective cardiothoracic surgery numbered in the tens of thousands annually and therefore it is necessary that pre- and post-operative strategies be employed to limit ischemia-reperfusion (IR) injury. We have found differences in the way the newborn (versus the adult) heart responds to IR injury. In the adult, catalase activity increases appropriately with increasing levels of hydrogen peroxide (H2O2), conferring cardioprotection. This effect however does not occur in the newborn. Materials and Methods: Hypoxia studies were carried out using primary cardiomyocytes from adult (&gt;8 weeks) and newborn rats. Ischemia-reperfusion (IR) studies were performed using newborn (4-5 days) rabbits. Isolated rat cardiomyocytes were exposed to 1 hour of hypoxia (95%N2,5%CO2). Immunoprecipitation and western blot analysis were done for phosphorylated and total catalase and c-Abl. In addition, catalase activity was determined spectrophotometrically by measuring the decomposition of H2O2. Newborn rabbit hearts were perfused using Langendorff method with ischemia and reperfusion periods lasting 30 and 60 minutes, respectively. DPH (200µM), a cAbl activator was injected directly into the newborn right ventricle (RV) two minutes before the reperfusion period. Results: Following hypoxia, the ratio of phosphorylated to total catalase and c-Abl in isolated newborn rat myocytes did not increase and were significantly lower (1.92- and 6.21-fold, respectively; p&lt;0.05) than their adult counterparts. Interestingly, when DPH was administered one hour prior to hypoxia, not only was catalase activity significantly increased 6.28-fold (p&lt;0.01) but phosphorylation levels were also altered. Finally, direct injection of DPH into the RV of Langendorff-perfused newborn rabbit hearts caused a significant improvement in percent recovery of developed pressure (from 49.53±5.42% to 125.5±15.5%) after IR, a key indicator of cardiac function. Catalase activity in these same hearts increased 2.92-fold. Conclusion: In the newborn, decreased phosphorylation of catalase by c-Abl potentially mediates IR-induced dysfunction. Activation of c-Abl may be a strategy to prevent ischemic injury associated with surgical procedures. </jats:p