Assessing satisfaction with a nurse-led clinical trials clinic

This article reports the results of a patient satisfaction questionnaire used to evaluate a newly established gastrointestinal cancer clinical trials nurse-led clinic. The service was set up to accommodate the increased clinical trials portfolio at Great Western Hospital, Swindon (Winter et al 2011). While patients were overwhelmingly positive about the clinic and the practitioner providing it, the survey indicated areas for improvement, which include offering the option of seeing a doctor or nurse, changes in allocated clinic times to avoid delays and the need to address patients’ anxiety

Phase II study to evaluate combining gemcitabine with flutamide in advanced pancreatic cancer patients

A phase II study was undertaken to determine the safety of combining flutamide with gemcitabine, with response rate being the primary end point. Twenty-seven patients with histologically proven, previously untreated, unresectable pancreatic adenocarcinoma received gemcitabine, 1 g m−2 intravenously on days 1, 8 and 15 of a 28 day cycle, and flutamide 250 mg given orally three times daily. Treatment was halted if there was unacceptable toxicity, or evidence of disease progression. Toxicity was documented every cycle. Tumour assessment was undertaken after cycles 2 and 4, and thereafter at least every additional four cycles. One hundred and seventeen cycles of treatment were administered, median four cycles per patient (range 1–18). Gemcitabine combined with flutamide was well tolerated, with most toxicities being recorded as grade 1 or 2 and only nine treatment cycles associated with grade 3 toxicity. The most frequent toxicity was myelosuppression. One case of transient jaundice was recorded. The commonest symptomatic toxicity was nausea and vomiting. The response rate was 15% (four partial responses), median survival 6 months and 22% of patients were alive at 1 year. These results suggest antitumour activity of the combination therapy to be equivalent to single agent gemcitabine

Sorafenib for the treatment of advanced hepatocellular cancer – a UK audit

Aims: Sorafenib is the current standard treatment for advanced hepatocellular carcinoma. We carried out a national audit of UK patients treated with sorafenib as standard-of-care and those treated with systemic therapy in first-line trials. Materials and methods: Sorafenib-treated and trial-treated patients were identified via the Cancer Drugs Fund and local databases. Data were collected retrospectively from medical records according to a standard case report form. The primary outcome measure was overall survival, estimated by the Kaplan–Meier method. Results: Data were obtained for 448 sorafenib-treated patients from 15 hospitals. The median age was 68 years (range 17–89) and 75% had performance status ≤ 1. At baseline, 77% were Child-Pugh A and 16.1% Child-Pugh B; 38% were albumin–bilirubin grade 1 (ALBI-1) and 48% ALBI-2; 23% were Barcelona Clinic Liver Classification B (BCLC-B) and 72% BCLC-C. The median time on sorafenib was 3.6 months, with a mean daily dose of 590 mg. The median overall survival for 448 evaluable sorafenib-treated patients was 8.5 months. There were significant differences in overall survival comparing Child-Pugh A versus Child-Pugh B (9.5 versus 4.6 months), ALBI-1 versus ALBI-2 (12.9 versus 5.9 months) and BCLC-B versus BCLC-C (13.0 versus 8.3 months). For trial-treated patients (n = 109), the median overall survival was 8.1 months and this was not significantly different from the sorafenib-treated patients. Conclusion: For Child-Pugh A patients with good performance status, survival outcomes were similar to those reported in global randomised controlled trials. Patients with ALBI grade > 1, Child-Pugh B or poor performance status seem to derive limited benefit from sorafenib treatment

Identifying the deficiencies of current diagnostic criteria for neurofibromatosis 2 using databases of 2777 individuals with molecular testing

Purpose We have evaluated deficiencies in existing diagnostic criteria for neurofibromatosis 2 (NF2). Methods Two large databases of individuals fulfilling NF2 criteria (n = 1361) and those tested for NF2 variants with criteria short of diagnosis (n = 1416) were interrogated. We assessed the proportions meeting each diagnostic criterion with constitutional or mosaic NF2 variants and the positive predictive value (PPV) with regard to definite diagnosis. Results There was no evidence for usefulness of old criteria “glioma“ or “neurofibroma.” “Ependymoma” had 100% PPV and high levels of confirmed NF2 diagnosis (67.7%). Those with bilateral vestibular schwannoma (VS) alone aged ≥60 years had the lowest confirmation rate (6.6%) and reduced PPV (80%). Siblings as a first-degree relative, without an affected parent, had 0% PPV. All three individuals with unilateral VS and an affected sibling were proven not to have NF2. The biggest overlap was with LZTR1-associated schwannomatosis. In this category, seven individuals with unilateral VS plus ≥2 nondermal schwannomas reduced PPV to 67%. Conclusions The present study confirms important deficiencies in NF2 diagnostic criteria. The term “glioma” should be dropped and replaced by “ependymoma.” Similarly “neurofibroma” should be removed. Dropping “sibling” from first-degree relatives should be considered and testing of LZTR1 should be recommended for unilateral VS

Effects of a period of high temperature during grain filling on the grain growth characteristics and malting quality of three Australian malting barleys

Short periods of high temperatures (up to 35°C) during mid grain filling appear to reduce yield and quality in barley. Plants of 3 malting barley varieties, Schooner, Arapiles, and Sloop (a new South Australian malting variety), were grown under constant environment conditions from germination to maturity and exposed to 5 days of high temperatures (up to 35°C) during mid grain filling. Schooner and Sloop showed similar patterns of accumulation of dry matter under control conditions (21°C/16°C, day/night temperature) and in response to high temperatures. In all varieties, the reduction in starch accumulation represented the most significant detrimental effect of high temperature and made the greatest contribution to the reduction in final grain weight. The reduction in absolute grain nitrogen (N) in heat-treated Arapiles grains represents a potentially important response under high temperature conditions. In this study, water loss did not have a decisive role in the termination of grain filling. Continued accumulation of endosperm dry matter at low moisture levels suggested that water distribution and/or components of water potential may be more important than overall water content in the cessation of grain filling. Final grain composition depended not only on the amount of endosperm storage component present in the grain but also on the contribution of the non-endosperm components (including the embryo and husk) to final grain dry weight. In some cases, changes in the contribution made by the non-endosperm components of the grain to final grain weight masked important high temperature effects on key endosperm storage components. Hot water extract (HWE) values were similar within treatments and ranged from 73% to 78%. High temperature exposure reduced HWE for all varieties. Malt b-glucan was lower in heat-treated grains than in control grains. Despite relatively high malt protein levels in all varieties, higher free amino N levels in heat-treated grains indicated a higher protein modification than in control grains.M. A. B. Wallwork, S. J. Logue, L. C. MacLeod and C. F. Jenne

Metabolic response at repeat PET/CT predicts pathological response to neoadjuvant chemotherapy in oesophageal cancer.

OBJECTIVES: Reports have suggested that a reduction in tumour 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET) examination during or after neoadjuvant chemotherapy may predict pathological response in oesophageal cancer. Our aim was to determine whether metabolic response predicts pathological response to a standardised neoadjuvant chemotherapy regimen within a prospective clinical trial. METHODS: Consecutive patients staged with potentially curable oesophageal cancer who underwent treatment within a non-randomised clinical trial were included. A standardised chemotherapy regimen (two cycles of oxaliplatin and 5-fluorouracil) was used. PET/CT was performed before chemotherapy and repeated 24-28 days after the start of cycle 2. RESULTS: Forty-eight subjects were included: mean age 65 years; 37 male. Using the median percentage reduction in SUV(max) (42%) to define metabolic response, pathological response was seen in 71% of metabolic responders (17/24) compared with 33% of non-responders (8/24; P = 0.009, sensitivity 68%, specificity 70%). Pathological response was seen in 81% of subjects with a complete metabolic response (13/16) compared with 38% of those with a less than complete response (12/32; P = 0.0042, sensitivity 52%, specificity 87%). There was no significant histology-based effect. CONCLUSIONS: There was a significant association between metabolic response and pathological response; however, accuracy in predicting pathological response was relatively low