No abstract

Purpose Metastatic breast cancer (mBC) patients with DPYD genetic variants linked to loss of dihydropyrimidine dehydrogenase (DPD) activity are at risk of severe capecitabine-associated toxicities. However, prospective DPYD genotyping has not yet been implemented in routine clinical practice. Following a previous internal review in which two patients underwent lengthy hospitalisations whilst receiving capecitabine, and were subsequently found to be DPD deficient, we initiated routine DPYD genotyping prior to starting capecitabine. This study evaluates the clinical application of routine DPYD screening at a large cancer centre in London. Methods We reviewed medical records for consecutive patients with mBC who underwent DPYD genotyping before commencing capecitabine between December 2014 and December 2017. Patients were tested for four DPYD variants associated with reduced DPD activity. Results Sixty-six patients underwent DPYD testing. Five (8.4%) patients were found to carry DPYD genetic polymorphisms associated with reduced DPD activity; of these, two received dose-reduced capecitabine. Of the 61 patients with DPYD wild-type, 14 (23%) experienced grade 3 toxicities which involved palmar–plantar erythrodysesthesia (65%), and gastrointestinal toxicities (35%); no patient was hospitalised due to toxicity. Conclusions Prospective DPYD genotyping can be successfully implemented in routine clinical practice and can reduce the risk of severe fluoropyrimidine toxicities.

An 84-year-old man presented with a 2-month history of intermittent stridor and worsening difficulty in breathing. Chest X-ray and flexible nasendoscopy were unremarkable but following further deterioration a CT scan revealed an obstructing lesion in the distal trachea. Bronchoscopy revealed an infiltrative tumour arising 3 cm above the carina causing 90% obstruction. The mass was biopsied and surgically debrided to leave a patent airway. Histological analysis revealed a diagnosis of adenoid cystic carcinoma. Transthoracic surgical resection was unsuccessful and the patient continues to be effectively managed with periodic bronchoscopic debulking and radiotherapy. This case highlights the diagnostic and therapeutic dilemmas posed by distal tracheal lesions and the need for specialist input for effective management.

Aim There is significant international variation in the use of neoadjuvant radiation prior to total mesorectal excision. The MERCURY group advocate selective neoadjuvant chemoradiotherapy (CRT). We have performed a retrospective, single‐centre study of patients treated with CRT, where only the circumferential resection margin is threatened, with the aim of identifying whether a more selective approach to CRT provides acceptable local relapse rates (LRRs). Method All consecutive patients who underwent radical surgery for rectal adenocarcinoma over a 5‐year period (2007–2012) in the Oxford University Trust were considered. Electronic hospital systems were reviewed to obtain patient and tumour demographics, treatment and follow‐up information. All patients were classified into risk categories according to National Institute for Health and Care Excellence guidance. Data were analysed using Microsoft Excel and R. Results Two hundred and seventy‐two patients were identified: 123, 89 and 60 in the high‐, intermediate‐ and low‐risk categories, respectively. Seventy‐nine per cent of those in the high‐risk group, 6% in the intermediate and 5% in the low‐risk group underwent CRT. The overall 5‐year LRR and distant recurrence rate (DRR) were 5.2% and 17.8%, respectively. The 5‐year LRR for those who went straight to surgery was 2.0% and for those who had neoadjuvant CRT it was 7.4%. The DRR for these two groups was 8.5% and 18.9%, respectively. Conclusion Our series demonstrates that the use of CRT only in margin‐threatening tumours, results in an exceptionally low LRR for those without margin‐threatening disease. In routine clinical care, this strategy can minimize the significant morbidity of multimodal treatment and allow earlier introduction of systemic therapy to minimize distant recurrence.