Multiparameter Phase I trials: a tool for model-based development of targeted agent combinations--example of EVESOR trial.

Optimal development of targeted drug combinations is one of the future challenges to be addressed. Computerization and mathematical models able to describe biological phenomena and to simulate the effects of changes in experimental conditions may help find solutions to this issue. We propose the concept of 'multiparameter trials', where biological, radiological and clinical data required for modeling purpose are collected and illustrated by the ongoing academic EVESOR trial. The objective of the model-based work would be the determination of the optimized doses and dosing schedules of everolimus and sorafenib, offering the maximization of the predicted modeled benefit/toxicity ratio in patients with solid tumors. It may embody the 'proof of concept' of model-based drug development of anticancer agent combinations.

Long-term follow-up analysis of 100 patients with splenic marginal zone lymphoma treated with splenectomy as first-line treatment.

Splenectomy is considered as one of the first-line treatments for symptomatic patients with splenic marginal zone lymphoma (SMZL). Between 1997 and 2012, 100 hepatitis C virus-negative patients with SMZL were treated by splenectomy as first-line treatment. At 6 months, all patients but three recovered from all cytopenias. The median lymphocyte count at 6 months and 1 year was 11.51 × 10(9)/L and 6.9 × 10(9)/L, respectively. Median progression-free survival (PFS) was 8.25 years. The 5-year and 10-year overall survival (OS) rates were 84% and 67%, respectively. Histological transformation occurred in 11% of patients, and was the only parameter significantly associated with a shorter time to progression (p = 0.0001). Significant prognostic factors for OS were age (p = 0.0356) and histological transformation (p = 0.0312). In this large retrospective cohort, we confirmed that splenectomy as first-line treatment in patients with SMZL corrected cytopenias and lymphocytosis within the first year and was associated with a good PFS.

Nodal marginal zone B-cell lymphoma: a diagnostic and therapeutic dilemma.

In the last lymphoma classifications, three types of marginal zone lymphoma (MZL) were delineated: extranodal mucosa-associated lymphatic tissue (MALT) lymphoma, splenic MZL, and nodal MZL (NMZL). While MALT lymphoma is already well characterized and has been extensively studied, the pathogenesis of the other two types, especially that of NMZL, remains incompletely understood. The tumor is rather uncommon, although it shares morphologic and immunophenotypic similarities with the other MZLs. Few series have been published, and the description is quite heterogeneous, reflecting the lack of consensus criteria for its diagnosis; the ability to develop such criteria is impeded by the absence of specific immunological or molecular abnormalities. The disease develops from peripheral (mostly cervical) and abdominal lymph nodes, with or without bone marrow and blood involvement. How to differentiate NMZL from lymphoplasmacytic lymphoma remains a key point of debate. NMZL also represents a therapeutic dilemma, given the absence of published large or prospective series. The 5-year overall survival as well as the failure-free survival of patients appear to be lower than those of patients with extranodal MZL.The aim of this review is twofold: to summarize descriptions of the clinical presentation provided in published series in order to help clinicians recognize and treat patients, and to discuss diagnostic difficulties faced by hematopathologists when dealing with these lesions and others in the differential diagnosis that must be distinguished from one another.

Outcome in relation to treatment modalities in 48 patients with localized gastric MALT lymphoma: a retrospective study of patients treated during 1976-2001.

The aim of this study was to retrospectively analyze survival and tumor response data in patients with localized gastric MALT lymphoma treated by different treatment modalities other than anti-Helicobacter pylori treatment (diagnosis made before 1993, or after failure of antibiotics + anti-acid), including surgery, chemotherapy or combined treatment. Here we studied a series of 48 patients with stage IE or IIE disease treated during the past 11 years. These patients received different treatments: chemotherapy was proposed to 19 (40%) patients; gastric surgery to 21 (43%) patients, consisting of partial gastrectomy of 7 patients and total gastrectomy in 14 patients; combined treatment to 8 (17%) patients, consisting of surgery + chemotherapy in 7 patients and surgery + chemotherapy + radiotherapy in 1 patient. At diagnosis, 85% of the patients had good PS and no B symptoms. Complete response after treatment was reached in 45 (94%) patients (chemotherapy: 84% of the patients; surgery alone: 95%; combined treatment: 100%). Progression was observed in 16 (33%) patients. No statistical difference in the survival was found among the different therapeutic modalities: 5-year overall survival year FFP survival was 81% for chemotherapy, 86% for surgery alone and 95% for combined treatment. Prognostic factors for survival were age, performance status and hemoglobin level at diagnosis. Considering the natural bias of a retrospective analysis, surgery or chemotherapy was associated with a similar outcome in patients with MALT lymphoma after antibiotics failure.