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1.
Pancreas ; 50(4): 579-586, 2021 04 01.
Article in English | MEDLINE | ID: mdl-33939672

ABSTRACT

OBJECTIVES: The total psoas area index (TPI) is an emerging alternative to the total skeletal muscle area index as a prognostic factor but has never been evaluated in metastatic pancreatic cancer (mPC). METHODS: Areas were manually recorded, as previously described. Sex-specific cutoffs were identified by optimum stratification of TPI using log-rank χ2 statistic associated with mortality to define sarcopenic psoas. Progression-free survival (PFS) and overall survival (OS) were the primary objectives. Two period groups were used as internal validation. RESULTS: During the period study, 79 patients were treated for mPC. The TPI was correlated with PFS (hazards ratio, 0.81; P = 0.02) and OS (hazards ratio, 0.7; P < 0.001). Optimum thresholds defining sarcopenic psoas were less than 5.73 cm2/m2 in men and less than 4.37 cm2/m2 in women. Patients with sarcopenic psoas (62.0%) had shorter median PFS (2.9 months) compared with the others (6.6 months, adjusted P log-rank = 0.01), independently to the intensity of chemotherapy, weight loss, and performance status greater than 1. Similarly, OS was independently shorter in patients with sarcopenic psoas (7.6 months) versus the others (22.2 months, adjusted P < 0.001). These results were confirmed in the 2 period groups. CONCLUSIONS: A low TPI is a stronger independent prognostic factor in mPC.


Subject(s)
Liver Neoplasms/secondary , Pancreas/pathology , Pancreatic Neoplasms/pathology , Psoas Muscles/pathology , Sarcopenia/diagnosis , Aged , C-Reactive Protein/metabolism , CA-19-9 Antigen/metabolism , Female , Humans , Kaplan-Meier Estimate , Liver Neoplasms/metabolism , Male , Middle Aged , Multivariate Analysis , Pancreas/drug effects , Pancreas/metabolism , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/metabolism , Prognosis , Sarcopenia/diagnostic imaging , Tomography, X-Ray Computed/methods
2.
Clin Gastroenterol Hepatol ; 15(11): 1750-1757.e3, 2017 Nov.
Article in English | MEDLINE | ID: mdl-27890854

ABSTRACT

BACKGROUND & AIMS: We investigated whether serum trough levels of vedolizumab, a humanized monoclonal antibody against integrin α4ß7, during the induction phase of treatment can determine whether patients will need additional doses (optimization of therapy) within the first 6 months. METHODS: We conducted an observational study of 47 consecutive patients with Crohn's disease (CD; n = 31) or ulcerative colitis (UC; n = 16) who had not responded to 2 previous treatment regimens with antagonists of tumor necrosis factor and were starting therapy with vedolizumab at 2 hospitals in France, from June 2014 through April 2016. All patients were given a 300-mg infusion of vedolizumab at the start of the study, Week 2, Week 6, and then every 8 weeks; patients were also given corticosteroids during the first 4-6 weeks. Patients not in remission at Week 6 were given additional doses of vedolizumab at Week 10 and then every 4 weeks (extended therapy or optimization). Remission at Week 6 of treatment was defined as CD activity score below 150 points for patients with CD and a partial Mayo Clinic score of <3 points, without concomitant corticosteroids, for patients with UC. Blood samples were collected each week and serum levels of vedolizumab and antibodies against vedolizumab were measured using an enzyme-linked immunosorbent assay. Median trough levels of vedolizumab and interquartile ranges were compared using the nonparametric Mann-Whitney test. The primary objective was to determine whether trough levels of vedolizumab measured during the first 6 weeks of induction therapy associated with the need for extended treatment within the first 6 months. RESULTS: Based on response to therapy at Week 6, extended treatment was required for 30 of the 47 patients (23 patients with CD and 7 patients with UC). At Week 2, trough levels of vedolizumab for patients selected for extended treatment were 23.0 µg/mL (interquartile range, 14.0-37.0 µg/mL), compared with 42.5 µg/mL in patients who did not receive extended treatment (interquartile range, 33.5-50.7; P = .15). At Week 6, trough levels of vedolizumab <18.5 µg/mL were associated with need for extended therapy (100% positive predictive value, 46.2%; negative predictive value; area under the receiver operating characteristic curve, 0.72) within the first 6 months. Among patients who required extended treatment at Week 10, all of those with trough levels of vedolizumab <19.0 µg/mL at Week 6 had achieved clinical remission 4 weeks later (secondary responders). CONCLUSIONS: In a prospective study of patients with CD or UC receiving induction therapy with vedolizumab, low trough levels of vedolizumab at Week 6 (<19.0 µg/mL) are associated with need for additional doses (given at Week 10 and then every 4 weeks). All patients receiving these additional doses achieved a clinical response 4 weeks later.


Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/pharmacokinetics , Gastrointestinal Agents/administration & dosage , Gastrointestinal Agents/pharmacokinetics , Inflammatory Bowel Diseases/drug therapy , Serum/chemistry , Adult , Female , France , Humans , Induction Chemotherapy , Male , Middle Aged , Prospective Studies , Time Factors
3.
Rev Prat ; 65(6): 793-7, 2015 Jun.
Article in French | MEDLINE | ID: mdl-26298902

ABSTRACT

Prognosis of metastatic colorectal cancer has dramatically improved during these two last decades, through a better understanding of therapeutic goals and the development of news drugs such as biologics. The character resectable, potentially resectable or not resectable of colorectal cancer liver metastasis should be considered at baseline because it determines the systemic chemotherapy which will be conducted. Considering resectable metastasis, 6 courses of FOLFOX (5 fluoro-uracil + oxaliplatin) will be administered before and after surgery in the goal of "cleaning" the body from the potential micrometastasis. In potentially resectable liver metastasis, the objective of the chemotherapy will be to get a tumor shrinkage, enabling microscopically complete resection while leaving enough functional hepatic parenchyma. In case of unresectable metastasis, obtaining a tumor response with an intensive induction chemotherapy is the guarantee of a good disease control, and authorizes to light treatment during a maintenance period, or a therapeutic break in selected patients, without altering the prognosis.


Subject(s)
Colorectal Neoplasms/pathology , Liver Neoplasms/secondary , Liver Neoplasms/therapy , Chemotherapy, Adjuvant , Colorectal Neoplasms/therapy , Humans
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