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The study purpose was to assess the predictive value of 2-[fluorine-18]fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET)/computerized tomography (CT) metabolic response after a single course of chemotherapy in patients with metastatic colorectal cancer (mCRC).FDG-PET/CT scans were carried out at baseline and on day 14 in 41 patients with unresectable mCRC treated with a biweekly regimen of chemotherapy. Metabolic nonresponse was defined by15% decrease in FDG uptake in the dominant proportion of the patient's lesions or if a lesion was found metabolically progressive. The PET-based response was correlated with radiological response (primary end point) and patient's outcome (secondary end points).RECIST response rate in metabolically responding patients was 43% (10 of 23) compared with 0% (0 of 17) in nonresponding patients (P=0.002). The metabolic assessment's predictive performance for RECIST response was sensitivity 100% [95% confidence interval (CI) 69% to 100%], specificity 57% (95% CI 37% to 75%), positive predictive value 43% (95% CI 23% to 66%), and negative predictive value 100% (95% CI 80% to 100%). Comparing metabolically responding versus nonresponding patients, the hazard ratio (HR) was 0.28 (95% CI 0.10-0.76) for overall survival and 0.57 (95% CI 0.27-1.21) for progression-free survival.The metabolic response measured by FDG-PET/CT after a single course of chemotherapy in mCRC is able to identify patients who will not benefit from the treatment.

Advanced distal neoplasia found at sigmoidoscopy could be the marker for more proximal lesions.In the setting of a screening clinic, subjects underwent flexible sigmoidoscopy. If no significant lesion was found, sigmoidoscopy was planned after 5 years. If an advanced neoplasia was found, colonoscopy was performed just after the first sigmoidoscopy and at 1, 3 and 5 years. If a non-advanced neoplasia was found, sigmoidoscopy was performed at 1, 3 and 5 years and followed by colonoscopy if advanced lesion was found.At first screening 1704/1912 (88%) subjects had a negative sigmoidoscopy, 104 (5.4%) had an advanced neoplasia, 96 (6%) had a non-advanced neoplasia and eight (0.4%) had invasive colorectal cancer (CRC). At follow-up examinations at 1, 3 and 5 years, among 170 subjects with advanced and non-advanced neoplasia, one developed invasive CRC and 47 (31.6%), advanced neoplasia. At 5 years, among 718 first negative sigmoidoscopies, 572 (80%) were confirmed negative and 97 (14%) had advanced neoplasia. Colorectal cancer status at 5 years could be checked for interval cancers in 97% of subjects and no CRC was diagnosed in subjects who did not attend sigmoidoscopy at 5 years. Comparison of the incidence of invasive CRC to the data of registries of the Netherlands and Luxembourg suggested that the incidence of CRC was decreased by 36%-46%. Seven of the nine CRCs were Duke's A and the two others were Duke's B and C.Screening with sigmoidoscopy followed by colonoscopy in case of positive sigmoidoscopy leads to substantial decreases in the incidence of CRC. Most CRCs found are at an early, curable stage of their development.

Aim: Triweekly DCF is a standard treatment in aGC, but is, however, associated with a bleak 30% febrile neutropenia (FN) incidence requiring prophylactic administration of granulocyte-colony stimulating factor (G-CSF). The DoGE study aims to define efficient but less toxic alternate DCF combinations. Methods: Chemonaive patients (pts) with aGC, age ≥ 18, PS ≤1 and normal organ function were randomized in a multicentric phase II trial (EudraCT 2008-000551-10) between a weekly (D 40 mg/m2,C 35 mg/m2, folinic Acid (FA) 400 mg/m2, F 1800 mg/m2 24 h infusion on days 1 and 8 every 3 weeks (wks), arm 1) and a biweekly regimen (D 50 mg/m2, C 50 mg/m2, FA 400 mg/m2, F 2000 mg/m2 48 h infusion every 2 wks, arm 2). G-CSF was allowed only as secondary prevention. The tumors were assessed every 6 wks. A Briant & Day two -teps design with toxicity and rate of non-progressive disease as primary endpoints was used. Insufficient efficacy was defined as 6 wks-disease control rate (DCR) 25% FN (b = 10% and a = 10% for activity, 15% for toxicity). Results: Between Oct 2008 and Oct 2013, 106 pts were recruited in 15 centers: 76 males (71.7%), PS 0/1: 60 (57%)/46 (43%), median age 62(33-85). Early study closure due to slow accrual led to a reduced 80% power. Among the 103 pts who received the study medications (52 arm 1 and 51 arm 2), 77% and 86% experienced grade III-IV toxic reactions, mainly neutropenia (21%,95% CI 12-34 in arm 1 vs 59%, 95% CI 45-71 in arm 2), and similar fatigue (27% vs 25%), anorexia (19% vs 18%) and diarrhea (15% vs 12%) in both arms. The 6 wks-DCR was 83%, 95% CI 71-91 in arm 1 and 79%, 95% CI 67-88 in arm 2. The pts' outcomes are reported hereunder. Regimen Grade III-IV toxicities * FN at 6 wks * Toxic deaths * mOS¶ mPFS¶ Weekly (arm1) 77 (64-86) 9.6 (4-21) 9 (4-20) 8.2 (6.0-14.5) 5.1 (3.2-6.5) Biweekly (arm2) 86 (74-93) 6 (2-16) 4 (1-13) 11.9 (7.4-15.9) 5.2 (3.0-6.9) * in % (95% CI); ¶ in months (95% CI) Conclusions: Weekly and biweekly DCF meet the study's safety requirements with less than 10% FN rate without G-CSF support. Both regimens have adequate efficacy according to the study design, consistent with the literature findings on the triweekly regimen, and represent valuable alternatives for further clinical development. Disclosure: All authors have declared no conflicts of interest.

While the science of medicine tries to understand the rules and hidden laws behind diseases and their management, the art of medicine aims to treat individual patients by matching clinical observations and existing knowledge. The ambiguity between the art and the science of medicine has never been so obvious than in our attempts to tailor cancer treatment to individual patients: the growing evidence of tumor heterogeneity makes understanding a patient's disease increasingly complex, especially when one considers the inadequacy of current assessment tools, which is becoming more apparent each day. In the setting of advanced colorectal cancer (aCRC), three main clinical situations coexist: metastasis that is immediately resectable with curative intent, borderline resectable disease and definitively non-resectable disease. Despite broad parameters within which to treat disease, clinicians lack tools that can rapidly and reliably point out treatment inefficiency in order to allow a therapeutic strategy to be quickly stopped or adapted. The usual endpoints of prospective randomized trials, which form the basis of the science of medicine, are seldom usable at the bedside to exercise the art of medicine. Death (overall survival) and progression (progression-free survival) both occur too long after the beginning of a treatment, and quality of life is much too subjective. The RECIST-based response rate is more readily available and relatively well standardized, but careful analysis reveals a definite but only small correlation with survival outcome in the aCRC setting. Several alternates for tumor response assessment have been studied: plasma tumor markers, circulating tumor cells, and functional imaging, notably the FDG-PET scan. However, few data from well-structured studies are available, and they are sometimes discordant. Among these alternatives, metabolic imaging by FDG-PET appears to be the most promising, bearing the highest and the most reproducible negative predictive value. This means that it could become useful both in the daily clinic and to develop new concepts for clinical trials. The aim of this review is to present the available evidence, point out areas of weakness, and consider how current findings might shape the future development of both FDG-PET techniques and study designs. Disclosure The author has declared no conflicts of interest.

Objectives Early metabolic response measured by the change of FDG maximum Standardized Uptake Value (SUVmax) on PET-CT after 1 cycle of chemotherapy in patients with metastatic colorectal cancer (mCRC) can predict negative objective response and is correlated to Overall Survival (OS) (Hendlisz et al. 2011). The aim of this work is to assess the correlation between the change in FDG-PET whole body metabolic tumoral load parameters and the RECIST response, progression free survival (PFS), OS. Methods FDG-PET/CT scans were performed at baseline and on Day 14, in 41 patients with unresectable mCRC undergoing a biweekly chemotherapy regimen. Patients were followed-up for up to 28 months. The change in Functional Tumor Volume (FTV) and Total Lesion Glycolysis (TLG) (TLG = FTV x SUVmean) of all the lesions was calculated using a fixed threshold segmentation algorithm (threshold for segmentation = SUV mean of 30 mm sphere in the right lobe of the liver plus 3 standard deviations) corrected to lean body mass (Wahl et al 2009). Predictive and prognostic value was tested through correlation with RECIST response (using independent dedicated CT), PFS and OS. A cutoff value for TLG responding patients was set at 40% or more decrease in the baseline value. Results 39 patients were evaluable for analysis. The median OS was 20 months (95% CI, 10 to 28), the change in whole body FTV and TLG were significantly related to RECIST response (p-value: 0.015 and 0.0038), to PFS (P-value: 0.009, 0.018) and to OS (p-value: 0.002, 0.0027). Patients with > 40% decrease in TLG have better PFS: median 12 months compared to median 3 months in the rest of the patients [log rank test p-value 0.004; HR 0.31 (95% CI, 0.14 to 0.72)], and a better median OS 27 months compared to 11 months [log rank test p-value 0.05; HR 0.38 (95% CI, 0.14 to 1.04)]. Conclusions Changes in the metabolic tumoral load parameters after one cycle of standard chemotherapy for mCRC are predictors of RECIST response, progression free and overall survival. Disclosure All authors have declared no conflicts of interest.

Background Several phases I and II trials including mCRC and metastatic breast cancer patients have suggested an interesting clinical activity in solid tumors with a SOR-CAP combination. SoMore's aim is to assess its potential benefit in chemorefractory mCRC and the predictive value of early metabolic response (MR) on survival. Methods SoMore (EUDRACT 2010-023695-91) is a multicentric phase II in PS 0-1 chemorefractory mCRC pts. Two co-primary objectives were defined 1) to demonstrate that overall survival (OS) at 6 months is > 30% (67 pts needed to have 90% power to detect a true rate of 50% at 1-sided level 2.5%); 2) to compare OS between early PET responders and non responders (62 deaths required before analysis -on pts assessable for MR- to detect a true HR 2.5 liver uptake; size > 15 mm). Results Between February and October 2011, 92 eligible pts were recruited in 6 centers: 50 male pts (54%), ECOG PS 0/1 : 51 (55%)/41 (45%), median age of 61 years. A median of 5 treatment cycles were given (0-18 + , treatment ongoing in 11 pts). No toxic death was observed. Grade III-IV toxic reactions were reported in 53% of the pts, mainly fatigue (17%), hand-foot skin reaction (13%), diarrhea (13%). 3/81 pts stopped their treatment due to toxicity. OS rate at 6 months was 65/92 (71%, 95% CI : 61%-79%), significantly higher than 50% (p Conclusions SoMore largely met one of its primary objectives with an observed 71% OS at 6 months for this heavily pretreated mCRC population with manageable toxicity. Data about PET assessment according to mOS and PFS will likely be mature at the time of the meeting and presented if available. Disclosure All authors have declared no conflicts of interest.