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

Amyotrophic lateral sclerosis and frontotemporal dementia: A behavioural and cognitive continuum

Our objective was to compare the cognitive and behavioural profile of patients with amyotrophic lateral sclerosis (ALS) and behavioural variant frontotemporal dementia (bvFTD), and to explore the continuum between these disorders according to neuropsychological and behavioural performance using novel methods of testing and analysis. Twenty patients with ALS, 20 bvFTD patients and 20 healthy controls completed a neuropsychiatric and neuropsychological assessment including cognitive screening, working memory, inhibitory control, decision making and emotion recognition. The resulting neuropsychological and behavioural data were analysed by Rasch analysis. ALS patients showed a similar profile to bvFTD patients on tests of working memory, inhibitory control and behavioural measures. Nine ALS patients (45%) had cognitive impairment and five (25%) met criteria for bvFTD. Even in a subset of MND patients with no impairment on the ACE-R, subtle impairment of inhibitory control together with moderate to severe apathy, were found. The Rasch analysis confirmed that all patients could be ranked on the same continuum, based on their neuropsychological performance and behaviour. Thus, the cognitive and behavioural profiles of ALS mirror those seen in bvFTD. Impaired inhibitory control and behavioural changes suggest subtle orbitofrontal dysfunction in ALS. The Rasch analysis revealed a clear overlap between bvFTD and ALS

Emotion processing deficits distinguish pure amyotrophic lateral sclerosis from frontotemporal dementia

Amyotrophic lateral sclerosis (ALS) is a multisystem disease that overlaps with frontotemporal dementia (FTD). Although FTD patients exhibit prominent deficits in emotion perception and social cognition, these domains have received relatively little attention in ALS. Moreover, direct comparisons between ALS and FTD on emotion processing tasks remain lacking. Twenty-nine patients with ALS (16 with coexisting FTD (FTD-ALS) and 13 without dementia), 25 behavioural variant FTD patients and 30 healthy controls completed neuropsychological and emotion tasks (Ekman Caricatures and the TASIT). Both ALS and FTD patient groups showed significant deficits on the emotion tasks compared to controls. After dividing ALS patients into those with and without FTD, only the patients with coexisting FTD (FTD-ALS) were impaired. FTD-ALS and FTD patient groups displayed similar levels of impairment, even after controlling for measures of general cognition, and demonstrated similar profiles across different types of emotions. We conclude that patients with FTD-ALS and FTD show similar, significant impairments in emotional processing. By contrast, ALS patients without dementia exhibit preserved emotion processing. Performance on emotion processing tasks may provide a useful clinical tool in identifying those with early FTD-ALS.8 page(s

Cortical atrophy in ALS is critically associated with neuropsychiatric and cognitive changes

Objective: To characterize the patterns of brain atrophy in patients with amyotrophic lateral sclerosis (ALS) with and without cognitive and neuropsychiatric symptoms, in comparison to controls and patients with ALS-frontotemporal dementia (FTD).   Methods: A total of 57 participants (ALS = 22; ALS-FTD = 17; controls = 18) were included, following current ALS and FTD criteria. Patients with ALS were further subclassified into ALS with cognitive and behavioral symptoms (ALS-plus; n = 8) and those without (ALS; n = 14). By definition, ALS-plus did not reach the diagnostic threshold for ALS-FTD. All patients underwent neuropsychological and neuropsychiatric assessments, and underwent a brain MRI. Voxel-based morphometry analysis was conducted to establish patterns of brain atrophy.   Results: Cortical atrophy in ALS was linked to neuropsychiatric and cognitive changes (ALS-plus vs ALS). Patients with ALS-plus had significant atrophy across motor and somatosensory as well as adjacent frontal and parietal areas, even after strict multiple comparison correction. By contrast, patients with ALS showed no significant cortical atrophy, and only brainstem atrophy. Importantly, atrophy in ALS-plus was not as widespread as in ALS-FTD, with ALS-plus atrophy mostly confined to motor and somatosensory areas, while atrophy in ALS-FTD also included substantial frontal and temporal atrophy.   Conclusions: The present findings establish that cortical atrophy in ALS is highly dependent upon neuropsychiatric and cognitive changes. Previous inconsistent findings of cortical atrophy in ALS likely relate to the inclusion of cognitively affected patients and patients with pure motor ALS

Semantic deficits in amyotrophic lateral sclerosis

Objective: To investigate, and establish neuroanatomical correlates of, semantic deficits in amyotrophic lateral sclerosis (ALS) and amyotrophic lateral sclerosis-frontotemporal dementia (ALS-FTD), compared to semantic dementia (SD) and controls. Methods: Semantic deficits were evaluated using a naming and semantic knowledge composite score, comprising of verbal and non-verbal neuropsychological measures of single-word processing (confrontational naming, comprehension, and semantic association) from the Sydney Language Battery (SYDBAT) and Addenbrooke’s Cognitive Examination - Revised (ACE-R). Voxel-based morphometry (VBM) analysis was conducted using the region of interest approach. Results: In total, 84 participants were recruited from a multidisciplinary research clinic in Sydney. Participants included 17 patients with ALS, 19 patients with ALS-FTD, 22 patients with SD and 26 age- and education- matched healthy controls. Significant semantic deficits were observed in ALS and ALS-FTD compared to controls. The severity of semantic deficits varied across the clinical phenotypes; ALS patients were less impaired than ALS-FTD patients, who in turn were not as impaired as SD patients. Anterior temporal lobe atrophy significantly correlated with semantic deficits. Conclusion: Semantic impairment is a feature of ALS and ALS-FTD, and reflects the severity of temporal lobe pathology

Neutrophil-lymphocyte and platelet-lymphocyte ratio as predictors of disease specific survival after resection of adrenocortical carcinoma

Background: The systemic inflammatory response may be associated with tumor progression. We sought to analyze the impact of neutrophillymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) on recurrence-free survival (RFS) and disease-specific survival (DSS) among patients who underwent surgery for adrenocortical carcinoma (ACC). Methods: Patients undergoing surgery for ACC were identified from a multi-center database. Cut-off values of 5 and 190 were defined as elevated NLR and PLR, respectively, and long-term outcome was assessed. Results: Among 84 patients with ACC, 29 (34.%) had NLR>5 while 32 (40.5%) had PLR>190. NLR and PLR were associated with larger tumors (NLR>5: 5 cm, 0% vs. >5 cm, 39.7%; PLR>190: 5cm, 0% vs. >5 cm, 45.7%), as well as need to resect of other organs (NLR>5: other organ resected 48.8% vs. not resected 20.9%; PLR>190: other organ resected 25.0% vs. not resected 56.4%)(all P<0.05). Five-year RFS was associated with an elevated NLR (NLR5, 14.2% vs. NLR>5, 10.5%) and PLR (PLR190: 19.4% vs. PLR>190: 5.2%) (both P<0.05). On multivariate survival analyses, PLR remained a predictor of RFS (HR 1.72), while NLR was associated with both DSS (HR 2.21) and RFS (HR 1.99) (both P<0.05). Conclusions: Immune markers such as NLR and PLR may be useful to stratify patients with regards to prognosis following surgery for ACC

Neutrophil-lymphocyte and platelet-lymphocyte ratio as predictors of disease specific survival after resection of adrenocortical carcinoma.

BackgroundThe systemic inflammatory response may be associated with tumor progression. We sought to analyze the impact of neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) on recurrence-free survival (RFS) and disease-specific survival (DSS) among patients who underwent surgery for adrenocortical carcinoma (ACC).MethodsPatients undergoing surgery for ACC were identified from a multi-center database. Cut-off values of 5 and 190 were defined as elevated NLR and PLR, respectively, and long-term outcome was assessed.ResultsAmong 84 patients with ACC, 29 (34.%) had NLR > 5 while 32 (40.5%) had PLR > 190. NLR and PLR were associated with larger tumors (NLR > 5: ≤ 5 cm, 0% vs. >5 cm, 39.7%; PLR > 190: ≤ 5cm, 0% vs. >5 cm, 45.7%), as well as need to resect of other organs (NLR > 5: other organ resected 48.8% vs. not resected 20.9%; PLR > 190: other organ resected 25.0% vs. not resected 56.4%)(all P < 0.05). Five-year RFS was associated with an elevated NLR (NLR ≤ 5, 14.2% vs. NLR> 5, 10.5%) and PLR (PLR ≤ 190: 19.4% vs. PLR > 190: 5.2%) (both P < 0.05). On multivariate survival analyses, PLR remained a predictor of RFS (HR 1.72), while NLR was associated with both DSS (HR 2.21) and RFS (HR 1.99) (both P < 0.05).ConclusionsImmune markers such as NLR and PLR may be useful to stratify patients with regards to prognosis following surgery for ACC