Tarek Boussaha

Efficacy of Adjuvant Chemotherapy in Colon Cancer With Microsatellite Instability: A Large Multicenter AGEO Study

BACKGROUND Deficient mismatch repair (dMMR) colon cancer (CC) is reportedly resistant to 5-fluorouracil (5FU) adjuvant chemotherapy while preliminary data suggest chemosensitivity to oxaliplatin. We assessed the efficacy of fluoropyrimidine with and without oxaliplatin in a large cohort of dMMR CC patients. METHODS This retrospective multicenter study included all consecutive patients who underwent curative surgical resection for stage II or III dMMR CC between 2000 and 2011. Prognostic factors were analyzed using Cox models, and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated. All statistical tests were two-sided. RESULTS A total of 433 dMMR CC patients were included (56.8% stage II, 43.2% stage III). Mean follow-up was 47.0 months. The patients received surgery alone (n = 263) or surgery plus adjuvant chemotherapy consisting of fluoropyrimidine with (n = 119) or without (n = 51) oxaliplatin. Adjuvant chemotherapy was administered to 16.7% of stage II and 69.0% of stage III CC patients. As compared with surgery alone, adjuvant oxaliplatin-based chemotherapy improved disease-free survival (DFS) in multivariable analysis (HR = 0.35, 95% CI = 0.19 to 0.65, P < .001), contrary to adjuvant fluoropyrimidine alone (HR = 0.73, 95% CI = 0.36 to 1.49, P = .38). In the subgroup analysis, the DFS benefit of oxaliplatin-based chemotherapy was statistically significant in multivariable analysis only in stage III (HR = 0.41, 95% CI = 0.19 to 0.87, P = .02). CONCLUSION This study supports the use of adjuvant chemotherapy with fluoropyrimidine plus oxaliplatin in stage III dMMR CC.

Second‐line chemotherapy for advanced biliary tract cancer after failure of the gemcitabine‐platinum combination: A large multicenter study by the Association des Gastro‐Entérologues Oncologues

Few data are available on second‐line chemotherapy (CT2) for advanced biliary tract cancer (ABTC). The aim of this multicenter study was to describe the CT2 regimens used, the response rates, and the outcomes of patients treated with various CT2 regimens.

Predictors of disease-free survival in colorectal cancer with microsatellite instability: An AGEO multicentre study

BACKGROUND A microsatellite instability (MSI) phenotype is found in about 12% of colorectal cancers (CRCs) and is associated with a low recurrence rate after curative surgery. Several studies have identified clinical and pathological factors predictive of recurrence in resected CRC, but not in the MSI subgroup. PATIENTS AND METHODS This multicentre retrospective study included patients with stage I, II or III MSI CRCs. Disease-free survival (DFS) was calculated with the Kaplan-Meier method. Factors associated with DFS were identified in univariate and multivariate Cox analyses. RESULTS We studied 521 patients with MSI CRC. Respectively 11%, 51% and 38% of patients were at stage I, II and III. Mean age was 68.7years and 36% of the patients received adjuvant chemotherapy. Median follow-up was 32.8months. The disease recurrence rates were 6% and 21% in stage II and III patients, respectively. The 3-year DFS rate was 77%. In univariate analysis, age, bowel obstruction, lymph node invasion, stage T4, vascular emboli, lymphatic invasion and perinervous invasion were associated with poorer DFS (P<0.05). Three relevant independent predictors of poor DFS were identified in multivariate analysis, namely bowel obstruction (HR=2.46; 95%CI 1.31-4.62, P=0.005), vascular emboli (HR=2.79; 95%CI 1.74-4.47, P<0.001) and stage T4 (HR=2.16; 95%CI 1.31-3.56, P=0.002). CONCLUSIONS Bowel obstruction, vascular emboli and stage T4 are independently associated with MSI CRC recurrence, suggesting that screening for vascular emboli in routine clinical practice may assist with adjuvant chemotherapy decision-making.

Neoadjuvant sorafenib combined with gemcitabine plus oxaliplatin in advanced hepatocellular carcinoma

This paper reports the first case of a patient with hepatocellular carcinoma with lymph node metastasis treated by sorafenib combined with gemcitabine plus oxaliplatin, with a partial response and normalization of α fetoprotein, which allowed curative surgery. The potential synergy between these three drugs needs to be confirmed, and is currently being investigated in a randomized phase II trial.

Digestive neuroendocrine tumors (DNET): The era of targeted therapies

Neuroendocrine tumors (NETs) are a heterogeneous group of malignancies. Therapeutic options depend on location of the primitive tumor, its expandability, its hormonal symptoms and its differentiation. Though relatively rare, with an increasing incidence and a high prevalence digestive neuroendocrine tumors (DNETs) are ranked just behind colorectal cancer as the most common digestive cancers in developed countries. Three main therapeutic axes have been individualized in the field of well-differentiated DNETs (corresponding to grades 1 and 2 of new WHO classification 2010), firstly, antitumor activity of somatostatin analogs, particularly in slowly progressive metastatic DNETs with limited hepatic invasion, secondly, targeting angiogenesis in these hypervascular tumors and thirdly targeting the mTOR pathway involved in DNETs carcinogenesis. As a consequence of two major randomized phase III trials in 2011, sunitinib and everolimus have been considered as new therapeutic options for well-differentiated, advanced and progressive pancreatic NETs. For everolimus, another phase III study, although non-significant with the chosen criteria, showed effectiveness notably against small intestine NETs. These targeted therapies are new therapeutic weapons in management of well-differentiated DNETs, but its exact role in care strategy, in comparison with other treatments (somatostatin analogs, chemo-embolization, chemotherapy...) deserves to be precise in the future.

Morbidity and mortality after colorectal cancer surgery in patients with cirrhosis: A critical review of the literature.

608 Background: Cirrhotic patients with localized colorectal cancer are potential candidates for tumor resection. The aim of this review was to evaluate the morbi-mortality after colorectal surgery. Methods: Comprehensive search was conducted using PUBMED, EMBASE, and the COCHRANE Library. Prospective and retrospective studies were selected. The study population included cirrhotic patients who underwent colorectal resection for non-metastatic colorectal cancer and patients with benign and other malignant disease. The postoperative morbi-mortality and independent risk factors were analysed. Results: Eight studies were identified. Among these, four studies compared the risk of colorectal surgery in patients with and without liver cirrhosis. The number of patients varied from 41 to 6,120. The severity of cirrhosis in most of the studies was classified with the Child-Pugh score. Class B and C were observed in 20% to 60% of the patients. Sepsis represented the main postoperative complication and occurred in 48...

Métastase pancréatique métachrone d'un adénocarcinome rectal : à propos d'un cas

Les métastases pancréatiques d’origine colorectale sont très rares. Nous rapportons dans cette observation le cas d’une patiente âgée de 73 ans, ayant un adénocarcinome rectal avec des métastases hépatiques et pulmonaires traité chirurgicalement, et qui présente, 46 mois après la fin de la chimiothérapie palliative, une métastase pancréatique métachrone de l’adénocarcinome rectal. Il s’agissait d’une lésion pancréatique localement avancée, et la patiente a eu une chimiothérapie par FOLFIRI et Bevacizumab ayant permis d’obtenir une stabilisation tumorale avec une survie de 18 mois par rapport au diagnostic de la métastase pancréatique.