Upfront VIP-reinforced-ABVD (VIP-rABVD) is not superior to CHOP/21 in newly diagnosed peripheral T cell lymphoma. Results of the randomized phase III trial GOELAMS-LTP95.

Peripheral T-Cell lymphomas (PTCL) are relatively rare diseases but appear to be highly aggressive and display worse remission and survival rates than B-cell lymphomas. Despite unsatisfactory results with the cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) regimen, it remains the reference front-line therapy in these diseases, but has not been challenged in phase III trials. The Groupe Ouest Est d'Etude des Leucémies et Autres Maladies du Sang (GOELAMS) devised an alternative therapeutic schedule including etoposide, ifosfamide, cisplatin alternating with doxorubicin, bleomycin, vinblastine, dacarbazine (VIP-reinforced-ABVD; VIP-rABVD) and compared it to CHOP/21 as front-line treatment in non-cutaneous PTCL. All newly diagnosed patients were eligible. The primary objective was to improve the 2-year event-free survival (EFS) rate. Secondary objectives were to compare the response rate, overall survival, and toxicities as well as identify prognostic factors. Eighty-eight patients were identified between 1996 and 2002. Both arms were well balanced for patients' characteristics in terms of histological and clinical presentation. No significant difference was observed between the two arms in terms of 2-year EFS. Anaplastic large cell lymphoma type and Ann Arbor stage I-II were identified as two independent favourable prognostic factors influencing survival. VIP-rABVD was not superior to CHOP/21 in terms of EFS as first-line treatment of PTCL, confirming that CHOP/21 remains the reference regimen in these lymphomas.

Detection of urinary cell-free miR-210 as a potential tool of liquid biopsy for clear cell renal cell carcinoma.

BACKGROUND: Recent findings show that cell-free miRNAs are stable in biological fluid. Urine provides an alternative to blood serum or plasma as a potential source of tumor biomarkers. MiR-210 is proven to be overexpressed in patients with a clear cell renal cell carcinoma (ccRCC). The purpose of this pilot study was to examine the urinary cell-free miR-210 as a potential tool of liquid biopsy for ccRCC. METHODS: Overall, 75 patients with a ccRCC and 45 control subjects without a cancer were included in this study. Urine samples were centrifuged twice and the cell-free urine supernanants were stored in -80°C until use. A total of 350µl cell-free urine was used for the extraction of total RNA. The expression levels of these miRNAs were performed by using quantitative RT-PCR. RESULTS: The level of urinary cell-free miR-210 was significantly higher in patients with ccRCC than in control subjects (P<0.001). The urinary cell-free miR-210 yielded the areas under the receiver operating characteristics curve of 0.76 in discriminating the patients with ccRCC from the control subjects with a sensitivity of 57.8% and a specificity of 80.0%. Moreover, the expression level of urinary cell-free miRNA-210 was significantly decreased in the patients a week after surgery (P<0.001). CONCLUSION: Urinary cell-free miR-210 may be used as a potential tool of liquid biopsy for ccRCC diagnosis. Further studies are needed to confirm our results.

Impact of Expert Pathologic Review of Lymphoma Diagnosis: Study of Patients From the French Lymphopath Network.

Purpose To prospectively assess the clinical impact of expert review of lymphoma diagnosis in France. Materials and Methods From January 2010 to December 2013, 42,145 samples from patients with newly diagnosed or suspected lymphomas were reviewed, according to the 2008 WHO classification, in real time by experts through the Lymphopath Network. Changes in diagnosis between referral and expert review were classified as major or minor according to their potential impact on patient care. Results The 42,145 reviewed samples comprised 36,920 newly diagnosed mature lymphomas, 321 precursor lymphoid neoplasms, 314 myeloid disorders, and 200 nonhematopoietic neoplasms, with 4,390 benign lesions. There were 4,352 cutaneous and 32,568 noncutaneous lymphomas. The most common mature noncutaneous lymphomas were diffuse large B-cell lymphomas (32.4%), follicular lymphomas (15.3%), classic Hodgkin lymphomas (13%), peripheral T-cell lymphomas (6.3%) of which angioimmunoblastic T-cell lymphomas (2.3%) were the most frequent, and mucosa-associated lymphoid tissue lymphomas (5.8%). A diagnostic change between referral and expert review occurred in 19.7% of patients, with an estimated impact on patient care for 17.4% of patients. This rate was significantly higher for patients sent with a provisional diagnosis seeking expert second opinion (37.8%) than for patients sent with a formal diagnosis (3.7%). The most frequent discrepancies were misclassifications in lymphoma subtype (41.3%), with 12.3% being misclassifications among small B-cell lymphoma entities. Fewer than 2% of changes were between benign and malignant lymphoid conditions. Minor changes (2.3%) mostly consisted of follicular lymphoma misgrading and diffuse large B-cell lymphoma subtype misclassification. Conclusion To our knowledge, this study provides the largest ever description of the distribution of lymphoma entities in a western country and highlights how expert review significantly contributes to a precise lymphoma diagnosis and optimal clinical management in a proportion of patients.

Immunohistochemical study of VEGF, angiopoietin 2 and their receptors in the neovascularization following microinjection of C6 glioma cells into rat brain.

BACKGROUND: Recent papers suggest that two angiogenic factors (angiopoietin 2 and vascular endothelial growth factor) cooperate in tumoral angiogenesis to support the growing tumor. The purpose of the present work was to demonstrate the existence of such cooperation in a longitudinal study of a brain tumor model during tumor growth by means of immunohistochemistry. MATERIALS AND METHODS: The study was performed on 31 rats bearing C6 glioma. At different stages of tumor growth, the histological aspects were described and sections were immunostained for VEGF, Ang-2 and their receptors VEGFR-1, VEGFR-2 and Tie-2. Immunostaining was semi-quantitatively analyzed and the localization of immunostained cells was reported. RESULTS: Ang-2 and Tie-2 were detected in the endothelial cells of vessels surrounded by tumor cells, occuring early in our study, with immunostaining taking place from day 4 to day 24. Immunostaining with VEGF (on tumoral cells) and VEGFR-2 (on endothelial cells) was present after 8 days of tumor growth. A clear increase of vessel density can be observed at the periphery of the tumors after 16 days of tumor growth. At that time, areas of necrosis were present in the tumor with concomitant VEGF and Ang-2 expression. CONCLUSION: The present study demonstrated cooperation between the early effect of Ang-2 and the secondary effect of VEGF to elaborate new vessels in a longitudinal study of experimental brain tumors. This study is favorable to the new model of tumor angiogenesis, with successive vessel cooption, regression and growth mediated by angiopoietins and VEGF.

Mitotic index, microvascular proliferation, and necrosis define 3 groups of 1p/19q codeleted anaplastic oligodendrogliomas associated with different genomic alterations.

BACKGROUND: The aim of this study was to correlate histological features and molecular characteristics in anaplastic oligodendrogliomas (AOs). METHODS: The histological characteristics of 203 AO patients, enrolled in the French national network POLA, were analyzed. The genomic profiles of 191 cases were studied using genomic arrays. IDH mutational status was assessed by immunohistochemistry and direct sequencing. RESULTS: 1p/19q codeletion was present in 79% of cases and was associated with alpha-internexin expression (P < 10(-4)), IDH1/2 mutation (P < 10(-4)), chromosome 4 loss (P < 10(-3)), and better overall survival (P < 10(-4)). Based on mitotic index, microvascular proliferation (MVP), and necrosis, 3 groups of 1p/19q codeleted AOs were identified: (group 1) AO with more than 5 mitoses per 10-HPF, no MVP, and no necrosis; (group 2) AO with MVP and no necrosis; and (group 3) AO with MVP and necrosis. Compared with group 1, groups 2 and 3 AOs had a higher mean Ki-67 proliferation index and a higher rate of 9p and 9q losses. Compared with group 2, group 3 AOs had a higher number of chromosomal alterations including chromosome 4 loss. In the subgroup of 157 1p/19q codeleted AOs, chromosomal instability was associated with shorter progression-free survival (P = .024) and shorter overall survival (P = .023). CONCLUSIONS: The present study shows that oligodendrogliomas with classic histological features remain a molecularly heterogeneous entity and should be stratified according to 1p/19q status because of its major prognostic relevance. Moreover, 1p/19q codeleted AOs are also heterogeneous. Interestingly, mitotic index, MVP, and necrosis help to classify them into 3 groups associated with distinct genomic alterations.

Perfusion-sensitive MRI of pilocytic astrocytomas: initial results.

PURPOSE: To present the imaging and perfusion data obtained in nine patients with pilocytic astrocytomas (PA) and to discuss the original functional issues of this technique. METHOD: Nine patients with pathologically proven PA underwent conventional and perfusion MR imaging. Various areas of relative cerebral blood volume (rCBV) within the tumors were obtained. The maximum rCBV ratios were identified and considered as representative of the tumor. The results were compared with the pathological findings. RESULTS: In all patients, rCBV was <1.5 (mean 1) and the signal intensity curve overshot the baseline. CONCLUSION: PA tend to have low rCBV values and a first-pass curve that crosses the baseline. These characteristics may be explained by the histological profile of the tumoral vascularity and are of relevance in the identification of these rare tumors.