Background-Wallstents (Schneider Stent, Inc., USA) used for the palliation of malignant biliary strictures, although associated with prolonged patency, can occlude. There is no consensus regarding the optimal management of Wallstent occlusion. Aims-To evaluate the eYcacy of different endoscopic methods for managing biliary Wallstent occlusion. Methods-A multicentre retrospective study of patients managed for a biliary Wallstent occlusion. Results-Data were available for 38 patients with 44 Wallstent occlusions, all of which had initial endoscopic management. Twenty four patients had died and 14 were alive after a median follow up of 231 (30-1095) days following Wallstent occlusion. Occlusions were managed by insertion of another Wallstent in 19, insertion of a plastic stent in 20, and mechanical cleaning in five. Endoscopic management was successful in 43 (98%). Following management of the occlusion, bilirubin decreased from 6.0 (0.5-34.3) to 2.1 (0.2-27.7) mg/100 ml (p<0.05). No complications occurred. The median duration of second stent patency was 75 days (95% confidence interval 43 to 107) after insertion of another Wallstent, 90 days (71 to 109) after insertion of a plastic stent, and 34 days (30 to 38) after mechanical cleaning (NS). The respective median survivals were 70 days (22-118), 98 days (54-142), and 34 days (30-380) (NS). Incremental cost eVective analysis showed that plastic stent insertion is the most cost eVective option. Conclusion-Although all three methods are equally eVective in managing an occluded Wallstent, the most cost eVective method appears to be plastic stent insertion.

No abstract

BackgroundVEGF-targeted therapy has become the mainstay of treatment for majority of mRCC patients. For most patients, benefit is short-lived and therefore treatment remains palliative in intent. HD IL2 is an effective immunotherapy treatment capable of durable remission in some patients but its unselected use has been difficult due to its modest response rate and considerable adverse effects. Using set pathology criteria as a selection tool in clinical practice, we have been able to show improved outcomes in our previous report. Here, we present an updated and extended report of this treatment and seek to explore any pathological, clinical and treatment variables likely to predict better outcomes.MethodsThis is an extension of a previously reported clinical audit, which includes mRCC cases treated with HD IL2 between 2003 and 2013. Since 2006, tumour specimens of potential candidates were routinely reviewed prospectively and stratified into Favourable or Other categories based on constitution of histological growth pattern, namely alveolar or solid versus papillary and/or sarcomatoid architecture; clear cell versus granular cell cytoplasmic morphology. HD IL2 was preferentially offered to patients with Favourable pathology. Outcome evaluation includes response rates, survival, and treatment tolerance. Multivariate analysis was performed to explore potential prognostic and predictive factors.ResultsAmong prospectively selected patients with Favourable pathology (n = 106), overall response rate was 48.1 % (51/106) with CR rate of 21.6 % (23/106). Median OS was 58.1 months. Factors associated with significantly better response and/or survival includes favourable pathology pattern, higher cycle 1 tolerance and lower number of metastatic organ sites (<3). CAIX (Carbonic anhydrase 9) has prognostic value but is not predictive of response. Toxicities were those expected of IL2 but were manageable on general medical wards, with no treatment-related death. Importantly most complete responses were durable with 76 % (23/30) cases remained relapse-free (median 39 months follow up) and 2 of the seven who relapsed had had long-term disease free survival after resection of oligometastatic relapse.ConclusionsOur experience shows that HD IL2 remains an effective and safe treatment in well-selected cases of mRCC. The result in this single-institution patient series confirms similar outcomes to our previously reported retrospective series. Given the prospect of long-term remission, fit patients with Favourable histology and low disease burden should be considered for HD IL2 in an experienced centre. Better understanding has been gained from this in-depth analysis especially the examination of possible response predictors and strategies that can improve treatment outcome.Electronic supplementary materialThe online version of this article (doi:10.1186/s40425-016-0174-5) contains supplementary material, which is available to authorized users.

TPS9587 Background: Circulating tumor DNA (ctDNA; the tumour derived fraction of circulating free DNA in the blood) has been shown to be a biomarker of tumor burden/progression in many cancers. We recently accurately monitored treatment response and resistance in stage IV melanoma by ctDNA analysis in serial peripheral blood samples. Pre-clinical data has previously revealed that BRAF inhibition provokes a micro-environment with increased T cell infiltration, improved T cell recognition of melanoma associated antigens and reduced production of immunosuppressive cytokines that could enhance immune responses. We aimed to test the hypothesis that ctDNA could be implemented as a personalised, real-time liquid biopsy to identify when tumours are responding to targeted therapy in order optimise a switch to immunotherapy. Methods: We validated the ctDNA assays for BRAF mutation calling as a primary trial endpoint. We designed a phase II multicenter, parallel arm study across 6 UK sites, to assess primary objectives of i). Whether a ctDNA result can be turned around within 7 days and actioned in a clinically relevant timeframe ii). to assess whether a decrease in ctDNA levels of mutant BRAF by ≥80% from baseline on targeted therapy is an appropriate ‘cut off’ to instruct switching to immunotherapy. Secondary endpoints include Overall Response Rate (ORR) to immunotherapy, radiological/clinical and ctDNA determined progression free survival (PFS) on each treatment. Forty patients are planned based on inclusion criteria of stage IV or stage III unresectable cutaneous BRAF mutant melanoma, baseline ctDNA BRAF variant allele frequency (VAF) ≥1.5%, ECOG 0/1/2, no symptomatic brain metastases, no prior adjuvant nivolumab plus ipilimumab (N+I). Prior adjuvant dabrafinib + trametinib (D+T) is allowed as long as recurrence is >6 months from completion. Patients are randomised 1:1 to either standard Arm A; investigator choice of either D+T (150mg BD +2mg OD respectively) or N+I (1 mg/kg N +3 mg/kg I q3 wkly, then N 480mg q4 wkly) first line, then switch on progression to the other treatment. In the experimental Arm B; all patients start on D+T and have BRAF ctDNA monitored q2 wkly for 4 wks then q4 wkly. When ≥80% decrease vs. baseline in ctDNA BRAF VAF occurs, patients switch to N+I. If patients subsequently progress on N+I, they will resume D+T. The study is open with 9 patients enrolled at time of submission. Clinical trial information: NCT03808441.

A frequent dilemma faced in the inflammatory bowel disease (IBD) clinic is how to best treat a patient with a previous cancer diagnosis. The changing demographics of our patient population will make this quandary more common. Previous guidance has emphasised the importance of lengthy postcancer drug holidays and cautious use of IBD therapies. However, accumulating evidence suggests this approach may be unnecessarily conservative. This review considers recent evidence on the safety of IBD drugs, cancer and recurrent cancer risk in patients with IBD and provides a framework for shared decision making involving patient, gastroenterologist and oncologist.