Objective To determine the cost effectiveness of intensive follow up compared with conventional follow up in patients with colorectal cancer. Design Incremental cost effectiveness analysis recognising differences in follow up strategies, based on effectiveness data from a meta-analysis of five randomised trials. Setting United Kingdom. Main outcome measures Taking a health service perspective, estimated incremental costs effectiveness ratios for each life year gained for five trials and four trials designed for early detection of extramural recurrences (targeted surveillance). Results Based on five year follow up, the numbers of life years gained by intensive follow up were 0.73 for the five trial model and 0.82 for the four trial model. For the five trials, the adjusted net (extra) cost for each patient was £2479 (€3550; $4288) and for each life year gained was £3402, substantially lower than the current threshold of NHS cost acceptability (£30 000). The corresponding values for the four trial model were £2529 and £3077, suggesting that targeted surveillance is more cost effective. The main predictor of incremental cost effectiveness ratios was surveillance costs rather than treatment costs. Judged against the NHS threshold of cost acceptability, the predicted incremental cost threshold was ninefold and the effectiveness threshold was 3%. Conclusions Based on the available data and current costs, intensive follow up after curative resection for colorectal cancer is economically justified and should be normal practice. There is a continuing need to evaluate the efficacy of specific surveillance tools: this study forms the basis for economic evaluations in such trials.

Purpose/Objective(s): Liver transplant, the gold standard treatment for most Hepatocellular carcinomas (HCC), was till recently not being considered as an option in patients having portal vein tumor thrombus (PVTT). These patients were offered only palliative treatments like Radio frequency ablation (RFA), Trans-arterial chemo-embolization (TACE) and conventional external beam radiation therapy (EBRT). With advent of SBRT, precise targeting and motion management has improved local control, making it possible to offer curative liver transplant post SBRT (Stereotactic Body Radiation therapy) to these cases where transplant was ruled out in the past. Materials/Methods: We present 48 of our cases, initially considered unfit for transplant and referred for SBRT to PVTT alone or with HCC lesion from April 2011 till November 2015. Adequate respiratory motion management with either deep inspiratory breath hold (DIBH) or synchrony respiratory tracking was used in all cases. Post SBRT, cases were assessed at 4, 8 and 12 weeks for transplant feasibility. Plan details and follow up data was analyzed with primary end point as amenability to liver transplant. Results: Intent of treatment was curative in 32 (66.6%) cases with limited disease and palliative in remaining 16 (33.3%) cases. Of all the cases, 38 (79%) had multi centric disease and 34 cases (70.8%) had received alternative multimodality treatment in past, before SBRT. Based on Japan cancer group classification 12.5% (n Z 6), 25% (n Z 12), 22.9% (n Z 11) and 39.5% (n Z 19) cases had Vp1, Vp2, Vp3 and Vp4 type PVTT, respectively. Twenty cases (42%) were treated on robotic radiosurgery and 28 cases (58%) on Linac with DIBH. Most frequent dose fractionation used was 60 Gy (range 25 -60 Gy) in 5 fractions (range 3-20 fr). Treatment was well tolerated with mild nausea and fatigue being the most common side effect with no RTOG grade 3 or more toxicity reported. At the time of analyses, amongst 32 curative cases, 23 (71.9%) were alive while 6 (18.8%) had expired and 3 (9.3%) were lost to follow up. Eleven (34.3% of 32 curative) cases underwent successful transplant, 2-3 months post SBRT while 5 (15.6%) are awaiting response assessment. Remaining 2 (6.2%) cases are living with stable disease and 5 (15.6%) with systemic progression. Amongst 16 palliative cases, 7 (43.75%) were still alive, 4 cases (25%) lost to follow up and 5 (31.25%) had expired. Median survival was 13 months in all 48 cases and 26 months (range 8-46 months) for transplant cases. Conclusion: Presence of PVTT is no longer considered a contraindication to liver transplant. Adequately selected cases can be offered SBRT as single modality or as a part of multimodality regime. With growing data from well-designed future studies, PVTT-SBRT promises to improve outcomes in selected HCC cases by making them amenable to liver transplant. SBRT-PVTT therefore merits attention for its potential as an integral part of multidisciplinary treatment approach towards inoperable HCC, realizing the unmet need of adequate local c...

The aim of this study was to clarify the role of APC and K-ras mutations in non-polypoid colorectal tumorigenesis. DNA from 63 adenomas (31 polypoid, 17 superficial elevated, 15 superficial depressed), 66 submucosally invasive carcinomas (47 polypoid, 19 non-polypoid) and 34 advanced carcinomas were examined for K-ras codon 12 point mutations and APC mutations in the mutation cluster region. K-ras mutation: the frequency in superficial depressed adenomas was lower than that in polypoid adenomas (0% vs 31%: P= 0.018). The frequency in non-polypoid carcinomas was lower than that in polypoid carcinomas (11% vs 56%: P = 0.0008), and was relatively low compared with that in polypoid adenomas (11% vs 31%). APC mutation: the frequency in superficial depressed adenomas was lower than that in polypoid adenomas (7% vs 43%: P = 0.016), and that in polypoid carcinomas was similar to that in non-polypoid carcinomas. Polypoid adenomas, polypoid carcinomas and advanced carcinomas had almost the same frequency. There may be some pathway other than the conventional adenoma-carcinoma sequence in development of non-polypoid carcinomas. The precursors of most non-polypoid carcinomas are considered to be de novo or superficial depressed adenomas. In this non-polypoid pathway, APC mutation seems to be requisite but K-ras mutation not. It is possible that new APC mutations are acquired after the development of superficial depressed adenomas.

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