Royal Surrey County Hospital

About: Royal Surrey County Hospital is a healthcare organization based out in Guildford, United Kingdom. It is known for research contribution in the topics: Cancer & Population. The organization has 2222 authors who have published 3064 publications receiving 86753 citations.

Efficacy of neoadjuvant bevacizumab added to docetaxel followed by fluorouracil, epirubicin, and cyclophosphamide, for women with HER2-negative early breast cancer (ARTemis): an open-label, randomised, phase 3 trial

Abstract: Summary Background The ARTemis trial was developed to assess the efficacy and safety of adding bevacizumab to standard neoadjuvant chemotherapy in HER2-negative early breast cancer. Methods In this randomised, open-label, phase 3 trial, we enrolled women (≥18 years) with newly diagnosed HER2-negative early invasive breast cancer (radiological tumour size >20 mm, with or without axillary involvement), at 66 centres in the UK. Patients were randomly assigned via a central computerised minimisation procedure to three cycles of docetaxel (100 mg/m 2 once every 21 days) followed by three cycles of fluorouracil (500 mg/m 2 ), epirubicin (100 mg/m 2 ), and cyclophosphamide (500 mg/m 2 ) once every 21 days (D-FEC), without or with four cycles of bevacizumab (15 mg/kg) (Bev+D-FEC). The primary endpoint was pathological complete response, defined as the absence of invasive disease in the breast and axillary lymph nodes, analysed by intention to treat. The trial has completed and follow-up is ongoing. This trial is registered with EudraCT (2008-002322-11), ISRCTN (68502941), and ClinicalTrials.gov (NCT01093235). Findings Between May 7, 2009, and Jan 9, 2013, we randomly allocated 800 participants to D-FEC (n=401) and Bev+D-FEC (n=399). 781 patients were available for the primary endpoint analysis. Significantly more patients in the bevacizumab group achieved a pathological complete response compared with those treated with chemotherapy alone: 87 (22%, 95% CI 18–27) of 388 patients in the Bev+D-FEC group compared with 66 (17%, 13–21) of 393 patients in the D-FEC group (p=0·03). Grade 3 and 4 toxicities were reported at expected levels in both groups, although more patients had grade 4 neutropenia in the Bev+D-FEC group than in the D-FEC group (85 [22%] vs 68 [17%]). Interpretation Addition of four cycles of bevacizumab to D-FEC in HER2-negative early breast cancer significantly improved pathological complete response. However, whether the improvement in pathological complete response will lead to improved disease-free and overall survival outcomes is unknown and will be reported after longer follow-up. Meta-analysis of available neoadjuvant trials is likely to be the only way to define subgroups of early breast cancer that would have clinically significant long-term benefit from bevacizumab treatment. Funding Cancer Research UK, Roche, Sanofi-Aventis.

A 10-year study of outcome following hepatic resection for colorectal liver metastases - The effect of evaluation in a multidisciplinary team setting.

Abstract: Aims Colorectal carcinoma is the second most common cause of cancer death in the western world and nearly 50% of patients develop liver metastases. Many cancers are managed via a multidisciplinary team process. This study compares the long term outcome of patients with metastatic colorectal cancer referred via a multidisciplinary team including a liver surgeon (MDT) with those referred directly to a specialist hepatobiliary unit. Patients and method This is a prospective study of 331 consecutive referrals made to a specialist hepatobiliary unit over ten years out of which 108 patients were referred via a colorectal MDT which included a liver surgeon and 223 were directly referred via colorectal MDTs without a liver surgeon. Pre-operative assessment and management were standardised and short and long term data were recorded. Results Patients referred via the MDT had 1-, 3- and 5-year survival rates of 89.6%, 67.5% and 49.9% respectively and 1-, 3- and 5-year disease-free survival of 65.4%, 31% and 27.2% respectively. Patients referred directly had 1-, 3- and 5-year survival rates of 90.3%, 54.1% and 43.3% respectively and 1-, 3- and 5-year disease-free survival rates of 70.3%, 37.6% and 27.9% respectively. The difference in overall survival was significant (P = 0.0001), although the difference in disease-free survival was not (P = 0.21). Conclusion Assessing, managing and referring patients with metastatic colorectal cancer via a multidisciplinary team including a liver surgeon is associated with improved overall survival.

High dose methylprednisolone can induce remissions in CLL patients with p53 abnormalities.

Abstract: Abnormalities of the p53 gene are known to confer detrimental effects in chronic lymphocytic leukaemia (CLL) and are associated with short survival. We have used high dose methylprednisolone (HDMP) to treat 25 patients with advanced refractory CLL of whom 45% had p53 abnormalities shown by one or more methods: flow cytometry, fluorescent in situ hybridisation and direct DNA sequencing. Fifteen were resistant to fludarabine and 16 were non-responders to their most recent therapy. Methylprednisolone had a cytotoxic effect on lymphocytes from 95% of cases assessed by an ex vivo apoptotic drug sensitivity index (DSI). HDMP was given alone or in combination with other drugs: vincristine, CCNU, Ara-C, doxorubicin, mitoxantrone and chlorambucil, according to the results of DSI. Three patients were treated twice and each treatment was analysed separately. The overall response rate was 77% with a median duration of 12 months (range 7 –23+). Responders included 5/10 with abnormal p53, of which two achieved nodular PR. Patients with p53 abnormalities fared worse than those with normal p53. There were no differences in response according to whether HDMP was used alone or in combination. Nine of the 22 evaluable patients (3 NR and 6 PR) have died from progressive disease or transformation. Main toxicity was infection in 7/25 patients. Event free and overall survival were significantly better in responders vs non-responders (P>0.0001 and P=0.04 respectively). Patients with a DSI of 100% to steroids had a better overall and event free survival, but this was not statistically significant. This study demonstrates that HDMP alone or in combination with other agents is a useful treatment strategy in refractory CLL including patients with p53 abnormalities.

Care of dying adults in the last days of life .

Abstract: Care of people in their last days of life should be based on compassion, respect and, wherever possible, on research evidence. Previously the Liverpool Care Pathway attempted to facilitate this but it was withdrawn after an independent government report found that its uncritical implementation could lead to poor care. This Concise Guideline overviews NICE Clinical Guideline (NG31), which addresses: recognising dying; communication and shared decision making; maintaining hydration; and pharmacological symptom control, including anticipatory prescribing. Doctors may need to change their attitudes to care of dying people and those important to them. Specific areas where practices will need to reflect the individualised approach to care are highlighted. Limitations of the guideline are discussed. Potential barriers to implementation include need for further training and 24/7 availability of specialist support to front-line clinicians.