Capecitabine (oral 5-fluorouracil pro-drug) treatment for colorectal carcinoma causing ischaemic chest pain

We present a case of cardiac ischaemia associated with capecitabine chemotherapy. An elderly female receiving capecitabine chemotherapy developed acute onset severe anterior chest pain associated with ischaemic changes on ECG. The pain and ECG changes failed to respond to thrombolysis and she proceeded to coronary angiogram and stenting of a thrombosed right coronary vessel. She inadvertently recommenced her capecitabine with a further episode of chest pain. On cessation of capecitabine she had no further episodes of chest pain

Towards detection of early response in neoadjuvant chemotherapy of breast cancer using Bayesian intravoxel incoherent motion

IntroductionThe early identification of good responders to neoadjuvant chemotherapy (NACT) holds a significant potential in the optimal treatment of breast cancer. A recent Bayesian approach has been postulated to improve the accuracy of the intravoxel incoherent motion (IVIM) model for clinical translation. This study examined the prediction and early sensitivity of Bayesian IVIM to NACT response.Materials and methodsSeventeen female patients with breast cancer were scanned at baseline and 16 patients were scanned after Cycle 1. Tissue diffusion and perfusion from Bayesian IVIM were calculated at baseline with percentage change at Cycle 1 computed with reference to baseline. Cellular proliferative activity marker Ki-67 was obtained semi-quantitatively with percentage change at excision computed with reference to core biopsy.ResultsThe perfusion fraction showed a significant difference (p = 0.042) in percentage change between responder groups at Cycle 1, with a decrease in good responders [−7.98% (−19.47–1.73), n = 7] and an increase in poor responders [10.04% (5.09–28.93), n = 9]. There was a significant correlation between percentage change in perfusion fraction and percentage change in Ki-67 (p = 0.042). Tissue diffusion and pseudodiffusion showed no significant difference in percentage change between groups at Cycle 1, nor was there a significant correlation against percentage change in Ki-67. Perfusion fraction, tissue diffusion, and pseudodiffusion showed no significant difference between groups at baseline, nor was there a significant correlation against Ki-67 from core biopsy.ConclusionThe alteration in tumour perfusion fraction from the Bayesian IVIM model, in association with cellular proliferation, showed early sensitivity to good responders in NACT.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT03501394, identifier NCT03501394

Analysis of the Clinical Advancements for BRCA-Related Malignancies Highlights the Lack of Treatment Evidence for BRCA-Positive Male Breast Cancer

Funding: This research was funded by The University of Aberdeen Development Trust, Breast Cancer UK and NHS Grampian Breast Cancer Endowment Fund. S.C. is in receipt of an Elphinstone Scholarship.Peer reviewedPublisher PD

Proposed Anti-Seizure Medication Combinations With Rufinamide in the Treatment of Lennox-Gastaut Syndrome: Narrative Review and Expert Opinion

Lennox-Gastaut syndrome (LGS) is a severe, chronic, complex form of early childhood-onset epilepsy characterized by multiple seizure types, generalized slow (≤2.5 Hz) spike-and-wave activity and other electroencephalography abnormalities, and cognitive impairment. A key treatment goal is early seizure control, and several anti-seizure medications (ASMs) are available. Due to the low success rate in achieving seizure control with monotherapy and an absence of efficacy data supporting any particular combination of ASMs for treating LGS, a rational approach to selection of appropriate polytherapy should be applied to maximize benefit to patients. Such rational polytherapy involves consideration of factors including safety (including boxed warnings), potential drug-drug interactions, and complementary mechanisms of action. Based on the authors\u27 clinical experience, rufinamide offers a well-considered first adjunctive therapy for LGS, particularly in combination with clobazam and other newer agents for LGS, and may be particularly useful for reducing the frequency of tonic-atonic seizures associated with LGS

Structural variants at the BRCA1/2 loci are a common source of homologous repair deficiency in high grade serous ovarian carcinoma

PURPOSE: The abundance and effects of structural variation at BRCA1/2 in tumours are not well understood. In particular, the impact of these events on homologous recombination repair deficiency (HRD) has yet to be demonstrated. EXPERIMENTAL DESIGN: Exploiting a large collection of whole genome sequencing data from high grade serous ovarian carcinoma (N=205) together with matched RNA-seq for the majority of tumours (N=150), we have comprehensively characterised mutation and expression at BRCA1/2. RESULTS: In addition to the known spectrum of short somatic mutations (SSMs), we discover that multi-megabase structural variants (SVs) are a frequent, unappreciated source of BRCA1/2 disruption in these tumours, and we find a genome wide enrichment for large deletions at the BRCA1/2 loci across the cohort. These SVs independently affect a substantial proportion of patients (16%) in addition to those affected by SSMs (24%), conferring homologous recombination repair deficiency (HRD) and impacting patient survival. We also detail compound deficiencies involving SSMs and SVs at both loci, demonstrating that the strongest risk of HRD emerges from combined SVs at both BRCA1 and BRCA2 in the absence of SSMs. Further, these SVs are abundant and disruptive in other cancer types. CONCLUSIONS: These results extend our understanding of the mutational landscape underlying HRD, increase the number of patients predicted to benefit from therapies exploiting HRD, and suggest there is currently untapped potential in SV detection for patient stratification