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Background:Peptide receptor radionuclide therapy (PRRT) is an established treatment for patients with metastatic neuroendocrine tumours (NETs), although which factors are associated with an improved overall survival (OS) remains unclear. The primary aim of this study is to determine to what extent a radiological response to 90Y-DOTATOC/90Y-DOTATATE PRRT is associated with an improved OS. The association of biochemical and clinical response to OS were assessed as secondary outcome measures.Methods:A retrospective analysis was conducted on 57 patients: radiological response was classified using RECIST criteria, biochemical response was classified using WHO criteria and clinical response was assessed subjectively. Responses were recorded as positive response (PR), stable disease (SD) or progressive disease (PD), and survival analysed.Results:Radiological response was achieved in 71.5% (24.5% PR, 47% SD) and was associated with a greater OS (51 and 56 months, respectively), compared with PD (18 months). A biochemical or clinical response post PRRT were not associated with a statistically significant improvement in OS. However, when combined with radiological response a survival benefit was observed according to the number of outcomes (radiological, biochemical, clinical), in which a response was observed. Mild haematological toxicity was common, renal toxicity was rare.Conclusion:In patients with progressive metastatic NETs receiving 90Y-DOTATOC/90Y-DOTATATE PRRT, a radiological response with either a PR or a SD post therapy confers a significant OS benefit. [ABSTRACT FROM AUTHOR]

Background: The Notch pathway is frequently activated in cancer. Pathway inhibition by γ-secretase inhibitors has been shown to be effective in pre-clinical models of pancreatic cancer, in combination with gemcitabine., Methods: A multi-centre, non-randomised Bayesian adaptive design study of MK-0752, administered per os weekly, in combination with gemcitabine administered intravenously on days 1, 8 and 15 (28 day cycle) at 800 or 1000 mg m -2 , was performed to determine the safety of combination treatment and the recommended phase 2 dose (RP2D). Secondary and tertiary objectives included tumour response, plasma and tumour MK-0752 concentration, and inhibition of the Notch pathway in hair follicles and tumour., Results: Overall, 44 eligible patients (performance status 0 or 1 with adequate organ function) received gemcitabine and MK-0752 as first or second line treatment for pancreatic cancer. RP2Ds of MK-0752 and gemcitabine as single agents could be combined safely. The Bayesian algorithm allowed further dose escalation, but pharmacokinetic analysis showed no increase in MK-0752 AUC (area under the curve) beyond 1800 mg once weekly. Tumour response evaluation was available in 19 patients; 13 achieved stable disease and 1 patient achieved a confirmed partial response., Conclusions: Gemcitabine and a γ-secretase inhibitor (MK-0752) can be combined at their full, single-agent RP2Ds.

Background: Transarterial chemo-embolisation (TACE) is recommended for patients with BCLC intermediate stage hepatocellular carcinoma (stage B), particularly in patients with good underlying liver function and minimal symptoms. The hepatoma arterial embolisation prognostic (HAP) score combines measures of liver function and tumour-related factors to offer a simple prognostic scoring system. The Albumin-Bilirubin (ALBI) grade permits assessment of the impact of liver function on survival. We aimed to investigate these two models and vascular invasion (VI)., Methods: In an international cohort of 3030 patients undergoing TACE, we examined the impact of liver function as assessed by the ALBI score, the HAP score and VI on survival., Results: Classification according to ALBI grade resulted in non-overlapping survival curves in the overall data set and all regional cohorts. The HAP score was also validated. Tumour number, aetiology and VI were identified as additional independent prognostic risk factors not currently included in the HAP score. Survival was particularly poor for patients with VI., Conclusions: The ALBI grade categorised patients receiving TACE into three clear prognostic groups, thereby emphasising the importance of underlying liver function in the outcome of TACE. The HAP score has been validated internationally and the serious adverse impact of VI is clearly shown.

Background: Diabetes mellitus is frequently observed in pancreatic cancer patients and is both a risk factor and an early manifestation of the disease., Methods: We analysed the prognostic impact of diabetes on the outcome of pancreatic cancer following resection and adjuvant chemotherapy using individual patient data from three European Study Group for Pancreatic Cancer randomised controlled trials. Analyses were carried out to assess the association between clinical characteristics and the presence of preoperative diabetes, as well as the effect of diabetic status on overall survival., Results: In total, 1105 patients were included in the analysis, of whom 257 (23%) had confirmed diabetes and 848 (77%) did not. Median (95% confidence interval (CI)) unadjusted overall survival in non-diabetic patients was 22.3 (20.8-24.1) months compared with 18.8 (16.9-22.1) months for diabetic patients (P=0.24). Diabetic patients were older, had increased weight and more co-morbidities. Following adjustment, multivariable analysis demonstrated that diabetic patients had an increased risk of death (hazard ratio: 1.19 (95% CI 1.01, 1.40), P=0.034). Maximum tumour size of diabetic patients was larger at randomisation (33.6 vs 29.7 mm, P=0.026)., Conclusions: Diabetes mellitus was associated with increased tumour size and reduced survival following pancreatic cancer resection and adjuvant chemotherapy.

Background: The ABC-02 (Advanced Biliary Tract Cancer) study established cisplatin and gemcitabine (CisGem) as the standard first-line chemotherapy for patients with locally advanced or metastatic biliary tract cancer (BTC). We examine quality of life (QoL), describe the long-term survivors and provide a long-term outcome., Methods: A total of 410 BTC patients were randomised to receive either CisGem or gemcitabine alone (Gem); 324 patients consented to complete EORTC QLQ-C30 and EORTC QLQ-PAN26 QoL questionnaires; 268 (83%) patients returned at least one QoL questionnaire (134 in each arm). Long-term survivors were defined as those surviving over 2 years and we performed a final analysis of the primary outcome; overall survival (OS)., Results: Most QoL scales showed a trend favouring the combined CisGem arm, including functional and symptomatic scales, although the differences were not statistically significant. Forty-five (11%)) patients survived at least 2 years (34 received CisGem and 11 Gem) and 21 (5%) 3 years or more (14 received CisGem and 7 Gem). After a median follow-up of 9.2 months and 398 deaths, the median OS was 11.7 months for CisGem and 8.1 months for Gem (hazard ratio (HR)=0.65, 95% CI: 0.53-0.79, P<0.001)., Conclusions: The survival advantage of CisGem compared to Gem was not associated with an improvement or deterioration of QoL. Long-term survivors were more likely to have received CisGem and the long-term OS is identical to that previously described.