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https://www.readbyqxmd.com/read/28636991/non-invasive-detection-of-somatic-mutations-using-next-generation-sequencing-in-primary-central-nervous-system-lymphoma
#1
Maxime Fontanilles, Florent Marguet, Élodie Bohers, Pierre-Julien Viailly, Sydney Dubois, Philippe Bertrand, Vincent Camus, Sylvain Mareschal, Philippe Ruminy, Catherine Maingonnat, Stéphane Lepretre, Elena-Liana Veresezan, Stéphane Derrey, Hervé Tilly, Jean-Michel Picquenot, Annie Laquerrière, Fabrice Jardin
PURPOSE: Primary central nervous system lymphomas (PCNSL) have recurrent genomic alterations. The main objective of our study was to demonstrate that targeted sequencing of circulating cell-free DNA (cfDNA) released by PCNSL at the time of diagnosis could identify somatic mutations by next-generation sequencing (NGS). PATIENTS AND METHODS: PlasmacfDNA and matched tumor DNA (tDNA) from 25 PCNSL patients were sequenced using an Ion Torrent Personal Genome Machine (Life Technologies®)...
June 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28633037/treatment-with-methotrexate-rituximab-and-cytosine-arabinoside-followed-by-autologous-stem-cell-transplantation-in-primary-central-nervous-system-lymphoma-a-single-center-experience
#2
Pinar Ataca Atilla, Erden Atilla, Sinem Civriz Bozdag, Meltem Kurt Yuksel, Selami Kocak Toprak, Pervin Topcuoglu, Taner Demirer, Osman Ilhan, Onder Arslan, Gunhan Gurman, Muhit Ozcan
OBJECTIVE/BACKGROUND: Primary central nervous system lymphoma (PCNSL) is associated with worst prognosis compared with other aggressive non-Hodgkin's lymphomas. However, recent trials have demonstrated that long-term progression-free survival can be achieved by immunochemotherapy. Our goal is to present our experience in aggressive PCNSL in this study. METHODS: We retrospectively evaluated the clinical features and management of 13 PCNSL patients who were diagnosed and treated between 2006 and 2015...
June 15, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/28619981/ibrutinib-unmasks-critical-role-of-bruton-tyrosine-kinase-in-primary-cns-lymphoma
#3
Christian Grommes, Alessandro Pastore, Nicolaos Palaskas, Sarah S Tang, Carl Campos, Derrek Schartz, Paolo Codega, Donna Nichol, Owen Clark, Wan-Ying Hsieh, Daniel Rohle, Marc K Rosenblum, Agnes Viale, Viviane Tabar, Cameron W Brennan, Igor T Gavrilovic, Thomas J Kaley, Craig Nolan, Antonio M P Omuro, Elena Pentsova, Alissa A Thomas, Elina Tsyvkin, Ariela Noy, M Lia Palomba, Paul A Hamlin, Craig Sauter, Craig H Moskowitz, Julia Wolfe, Ahmet Dogan, Minhee Won, Jon Glass, Scott Peak, Enrico C Lallana, Vaios Hatzoglou, Anne S Reiner, Philip Gutin, Jason T Huse, Katherine Panageas, Thomas G Graeber, Nikolaus Schultz, Lisa M DeAngelis, Ingo K Mellinghoff
Bruton tyrosine kinase (BTK) links the B-cell antigen receptor (BCR) and Toll-like receptors with Nuclear factor kappa B (NF-κB). The role of BTK in primary CNS lymphoma (PCNSL) is unknown. We performed a Phase 1 clinical trial with ibrutinib, the first-in-class BTK inhibitor, for patients with relapsed or refractory CNS Lymphoma. Clinical responses to ibrutinib occurred in 10/13 (77%) PCNSL patients, including five complete responses. The only PCNSL with complete ibrutinib resistance harbored a mutation within the coiled-coil domain of Caspase Recruitment Domain Family Member 11, a known ibrutinib resistance mechanism...
June 15, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28581466/high-dose-chemotherapy-and-autologous-stem-cell-transplantation-for-primary-central-nervous-system-lymphoma-a-multi-centre-retrospective-analysis-from-the-united-kingdom
#4
S Kassam, E Chernucha, A O'Neill, C Hemmaway, T Cummins, S Montoto, A Lennard, G Adams, K Linton, P McKay, D Davies, C Rowntree, S Easdale, T A Eyre, R Marcus, K Cwynarski, C P Fox
The prognosis of patients with primary central nervous system lymphoma (PCNSL) has improved in recent years. This has partly been achieved by remission induction protocols incorporating high-dose methotrexate (HD-MTX) and rituximab. Given the high rates of relapse, consolidation therapy is usually considered in first response. Whole brain radiotherapy may prolong PFS but appears to confer no long-term survival advantage and is associated with significant neurocognitive dysfunction. Attempts to improve efficacy and reduce neurotoxicity of consolidation therapy have included thiotepa-based high-dose chemotherapy and autologous stem cell transplant (HDC-ASCT)...
June 5, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28577579/patterns-of-relapse-in-primary-central-nervous-system-lymphoma-inferences-regarding-the-role-of-the-neuro-vascular-unit-and-monoclonal-antibodies-in-treating-occult-cns-disease
#5
Prakash Ambady, Rongwei Fu, Joao Prola Netto, Cymon Kersch, Jenny Firkins, Nancy D Doolittle, Edward A Neuwelt
BACKGROUND AND PURPOSE: The radiologic features and patterns of primary central nervous system lymphoma (PCNSL) at initial presentation are well described. High response rates can be achieved with first-line high-dose methotrexate (HD-MTX) based regimens, yet many relapse within 2 years of diagnosis. We describe the pattern of relapse and review the potential mechanisms involved in relapse. METHODS: We identified 78 consecutive patients who attained complete radiographic response (CR) during or after first-line treatment for newly diagnosed PCNSL (CD20+, diffuse large B cell type)...
June 2, 2017: Fluids and Barriers of the CNS
https://www.readbyqxmd.com/read/28559537/high-dose-chemotherapy-with-autologous-haematopoietic-stem-cell-support-for-relapsed-or-refractory-primary-cns-lymphoma-a-prospective-multicentre-trial-by-the-german-cooperative-pcnsl-study-group
#6
B Kasenda, G Ihorst, R Schroers, A Korfel, I Schmidt-Wolf, G Egerer, L von Baumgarten, A Röth, J Bloehdorn, R Möhle, M Binder, U Keller, M Lamprecht, M Pfreundschuh, E Valk, H Fricker, E Schorb, K Fritsch, J Finke, G Illerhaus
To investigate safety and efficacy of high-dose chemotherapy followed by autologous stem cell transplantation (HCT-ASCT) in relapsed/refractory (r/r) primary CNS lymphoma (PCNSL). We conducted a single-arm multicentre study for immunocompetent patients (<66 years) with PCNSL failing high-dose methotrexate (HD-MTX) based chemotherapy. Induction consisted of 2 courses of rituximab (375 mg/m(2)), high-dose cytarabine (2 × 3 g/m(2)) and thiotepa (40 mg/m(2)) with collection of stem cells in between. Conditioning for HCT-ASCT consisted of rituximab 375 mg/m(2), carmustine 400 mg/m(2) and thiotepa (4 × 5 mg/kg)...
May 31, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28553124/efficacy-and-safety-of-pemetrexed-on-recurrent-primary-central-nervous-system-lymphomas-in-china-a-prospective-study
#7
Yi Sun, Yong Wang, Shaolong Han, Bo Xing, Hong Li, Yufang Zhu, Shizhen Zhou, Xiuhua Wang, Jun Xu, Rongjie Tao
BACKGROUND: Pemetrexed, a new and novel agent for primary central nervous system lymphomas (PCNSLs), has shown to be efficient as a savage therapy for recurrent PCNSLs. However, more studies are needed. A prospective study was performed on 17 recurrent PCNSL patients with pemetrexed at Shandong Tumor Hospital in China to assess the efficacy and safety of pemetrexed for recurrent PCNSL patients. MATERIALS AND METHODS: The medical records and imaging data on all the cases of recurrent PCNSL patients with pemetrexed in our study were collected during August 2012 and April 2015...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28552327/inhibition-of-b-cell-receptor-signaling-by-ibrutinib-in-primary-cns-lymphoma
#8
Michail S Lionakis, Kieron Dunleavy, Mark Roschewski, Brigitte C Widemann, John A Butman, Roland Schmitz, Yandan Yang, Diane E Cole, Christopher Melani, Christine S Higham, Jigar V Desai, Michele Ceribelli, Lu Chen, Craig J Thomas, Richard F Little, Juan Gea-Banacloche, Sucharita Bhaumik, Maryalice Stetler-Stevenson, Stefania Pittaluga, Elaine S Jaffe, John Heiss, Nicole Lucas, Seth M Steinberg, Louis M Staudt, Wyndham H Wilson
Primary CNS lymphoma (PCNSL) harbors mutations that reinforce B cell receptor (BCR) signaling. Ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, targets BCR signaling and is particularly active in lymphomas with mutations altering the BCR subunit CD79B and MYD88. We performed a proof-of-concept phase Ib study of ibrutinib monotherapy followed by ibrutinib plus chemotherapy (DA-TEDDi-R). In 18 PCNSL patients, 94% showed tumor reductions with ibrutinib alone, including patients having PCNSL with CD79B and/or MYD88 mutations, and 86% of evaluable patients achieved complete remission with DA-TEDDi-R...
June 12, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28552326/ibrutinib-in-pcnsl-the-curious-cases-of-clinical-responses-and-aspergillosis
#9
Christian Grommes, Anas Younes
In this issue of Cancer Cell, Lionakis et al. demonstrate that the combination of temozolomide, etoposide, doxorubicin, dexamethasone, rituximab, and the Bruton tyrosine kinase (BTK) inhibitor ibrutinib induced frequent responses in patients with primary central nervous system lymphoma but was associated with significant toxicity, including pulmonary and cerebral aspergillosis infections.
June 12, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28521029/soluble-taci-and-soluble-bcma-as-biomarkers-in-primary-central-nervous-system-lymphoma
#10
Franziska S Thaler, Sarah A Laurent, Marion Huber, Matthias Mulazzani, Martin Dreyling, Uwe Ködel, Tania Kümpfel, Andreas Straube, Edgar Meinl, Louisa von Baumgarten
Background: B-cell survival is regulated through interactions of B-cell-activating factor (BAFF) and a proliferation-inducing ligand (APRIL) with their receptors transmembrane activator and CAML interactor (TACI) and B-cell maturation antigen (BCMA). We evaluated the diagnostic potential of soluble TACI (sTACI) and soluble BCMA (sBCMA) in cerebrospinal fluid (CSF) and serum as biomarkers in primary CNS lymphoma (PCNSL). Methods: CSF (n=176) and serum samples (n=105) from patients with clinically or radiologically suspected PCNSL as well as from control patients were collected prospectively...
May 17, 2017: Neuro-oncology
https://www.readbyqxmd.com/read/28514747/diagnostic-value-of-using-18f-fdg-pet-and-pet-ct-in-immunocompetent-patients-with-primary-central-nervous-system-lymphoma-a-systematic-review-and-meta-analysis
#11
Yaru Zou, Jianjing Tong, Haiyan Leng, Jingwei Jiang, Meng Pan, Zi Chen
BACKGROUND: 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) and PET/CT have become two of the most powerful tools for malignant lymphoma exploration, but their diagnostic role in primary central nervous system lymphoma (PCNSL) is still disputed. The purpose of our study is to identify the usefulness of 18F-FDG PET and PET/CT for detecting PCNSL. RESULTS: A total of 129 patients, obtained from eight eligible studies, were included for this systematic review and meta-analysis...
April 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28508176/the-prognostic-role-of-cd68-and-foxp3-expression-in-patients-with-primary-central-nervous-system-lymphoma
#12
Hyunsoo Cho, Se Hoon Kim, Soo-Jeong Kim, Jong Hee Chang, Woo Ick Yang, Chang-Ok Suh, June-Won Cheong, Yu Ri Kim, Jung Yeon Lee, Ji Eun Jang, Yundeok Kim, Yoo Hong Min, Jin Seok Kim
The prognostic role of CD68 and FoxP3 in primary central nervous system lymphoma (PCNSL) has not been evaluated. Thus, we examined the prognostic significance of CD68 and FoxP3 expression in tumor samples of 76 newly diagnosed immunocompetent PCNSL patients. All patients were treated initially with high-dose methotrexate (HD-MTX)-based chemotherapy, and 16 (21.1%) patients received upfront autologous stem cell transplantation (ASCT) consolidation. High expression of CD68 (>55 cells/high-power field) or FoxP3 (>15 cells/high-power field) was observed in 10 patients, respectively...
July 2017: Annals of Hematology
https://www.readbyqxmd.com/read/28507804/hla-dependent-immune-escape-mechanisms-in-b-cell-lymphomas-implications-for-immune-checkpoint-inhibitor-therapy
#13
Marcel Nijland, Rianne N Veenstra, Lydia Visser, Chuanhui Xu, Kushi Kushekhar, Gustaaf W van Imhoff, Philip M Kluin, Anke van den Berg, Arjan Diepstra
Antigen presentation by tumor cells in the context of Human Leukocyte Antigen (HLA) is generally considered to be a prerequisite for effective immune checkpoint inhibitor therapy. We evaluated cell surface HLA class I, HLA class II and cytoplasmic HLA-DM staining by immunohistochemistry (IHC) in 389 classical Hodgkin lymphomas (cHL), 22 nodular lymphocyte predominant Hodgkin lymphomas (NLPHL), 137 diffuse large B-cell lymphomas (DLBCL), 39 primary central nervous system lymphomas (PCNSL) and 19 testicular lymphomas...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28489744/diagnostic-accuracy-of-spect-pet-and-mrs-for-primary-central-nervous-system-lymphoma-in-hiv-patients-a-systematic-review-and-meta-analysis
#14
REVIEW
Mo Yang, James Sun, Harrison X Bai, Yongguang Tao, Xiangqi Tang, Lisa J States, Zishu Zhang, Jianhua Zhou, Michael D Farwell, Paul Zhang, Bo Xiao, Li Yang
BACKGROUND: We performed a systematic review and meta-analysis to assess the roles of SPECT, PET, and MRS in distinguishing primary central nervous system lymphoma (PCNSL) from other focal brain lesions (FBLs) in human immunodeficiency virus (HIV)-infected patients. METHODS: PubMed, Scopus, and Medline were systematically searched for eligible studies from 1980 to 2016. Two authors extracted characteristics of patients and their lesions using predefined criteria...
May 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28476199/primary-central-nervous-system-lymphoma-as-a-neurosurgical-problem
#15
REVIEW
Dariusz Szczepanek, Ewa Wąsik-Szczepanek, Filip Stoma, Bożena Sokołowska, Tomasz Trojanowski
Primary central nervous system lymphoma (PCNSL) comprises around 3-5% of primary central nervous system (CNS) tumours and around 1% of all non-Hodgkin lymphoma (NHL). Diffuse large B-cell lymphoma (DLBCL) is the most common histological type. High effectiveness of chemo- and radiotherapy for PCNSL regrettably does not eliminate significant risks of recurrence for CNS tumours. That results in higher interest in other treatment options, including surgical procedures. PCNSL remains in the scope of interest for many specialists and neurosurgeons seem to play a more important role...
April 19, 2017: Neurologia i Neurochirurgia Polska
https://www.readbyqxmd.com/read/28467782/methotrexate-cytarabine-dexamethasone-combination-chemotherapy-with-or-without-rituximab-in-patients-with-primary-central-nervous-system-lymphoma
#16
Xuefei Sun, Jing Liu, Yaming Wang, Xueyan Bai, Yuedan Chen, Jun Qian, Hong Zhu, Fusheng Liu, Xiaoguang Qiu, Shengjun Sun, Nan Ji, Yuanbo Liu
PURPOSE: High-dose methotrexate based chemotherapy is the standard treatment for patients with newly diagnosed primary central nervous system lymphoma (PCNSL). The role of rituximab is controversial because of its large size, which limits its penetration of the blood-brain barrier. In this study, we investigated the efficacy and tolerability of adding rituximab to methotrexate-cytarabine-dexamethasone combination therapy (RMAD regimen). RESULTS: The patients treated with RMAD had a complete remission rate of 66...
April 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28466877/haematological-cancer-nivolumab-is-effective-in-pcnsl-and-ptl
#17
Peter Sidaway
No abstract text is available yet for this article.
June 2017: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/28436974/high-dose-thiotepa-based-chemotherapy-with-autologous-stem-cell-support-in-elderly-patients-with-primary-central-nervous-system-lymphoma-a-european-retrospective-study
#18
E Schorb, C P Fox, K Fritsch, L Isbell, A Neubauer, A Tzalavras, R Witherall, S Choquet, O Kuittinen, D De-Silva, K Cwynarski, C Houillier, K Hoang-Xuan, V Touitou, N Cassoux, J-P Marolleau, J Tamburini, R Houot, V Delwail, G Illerhaus, C Soussain, B Kasenda
In this retrospective multicentre study, we investigated the outcomes of elderly primary central nervous system lymphoma (PCNSL) patients (⩾65 years) who underwent high-dose chemotherapy followed by autologous stem cell transplantation (HDT-ASCT) at 11 centres between 2003 and 2016. End points included remission, progression-free survival (PFS), overall survival (OS) and treatment-related mortality. We identified 52 patients (median age 68.5 years, median Karnofsky Performance Status before HDT-ASCT 80%) who all underwent thiotepa-based HDT-ASCT...
April 24, 2017: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/28434043/early-whole-brain-radiotherapy-in-primary-cns-lymphoma-negative-impact-on-quality-of-life-in-the-randomized-g-pcnsl-sg1-trial
#19
Ulrich Herrlinger, Niklas Schäfer, Rolf Fimmers, Frank Griesinger, Michael Rauch, Heinz Kirchen, Patrick Roth, Martin Glas, Michael Bamberg, Peter Martus, Eckhard Thiel, Agnieszka Korfel, Michael Weller
PURPOSE: In the randomized G-PCNSL-SG-1 trial, the addition of whole brain radiotherapy (45 Gy) to high-dose methotrexate (HD-MTX)-based chemotherapy (early WBRT arm) did not prolong overall survival (OS) as compared to HD-MTX-based chemotherapy alone (no early WBRT arm) in primary CNS lymphoma (PCNSL) patients. To determine whether WBRT might lead to quality of life (QoL)-relevant late neurotoxicity, this trial prospectively monitored QoL. METHODS: QoL measurements were performed using the EORTC-QLQ-C30 and BN20 questionnaires and combined with repeated Mini Mental State Examinations (MMSE)...
April 22, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28432587/rituximab-methotrexate-procarbazine-vincristine-and-intensified-cytarabine-consolidation-for-primary-central-nervous-system-lymphoma-pcnsl-in-the-elderly-a-loc-network-study
#20
Caroline Houillier, Hervé Ghesquières, Cécile Chabrot, Carole Soussain, Guido Ahle, Sylvain Choquet, Emmanuelle Nicolas-Virelizier, Jacques-Olivier Bay, Jacques Vargaftig, Claude Gaultier, Valérie Touitou, Nadine Martin-Duverneuil, Nathalie Cassoux, Magali Le Garff-Tavernier, Myrto Costopoulos, Pierre Faurie, Khê Hoang-Xuan
Primary CNS lymphoma (PCNSL) is chemosensitive to high-dose methotrexate-based chemotherapy. However, responses in the elderly are short-lasting and outcome is poor. Given that radiotherapy and intensive chemotherapy expose elderly to severe toxicities, alternative consolidation approaches need to be evaluated. In this multicenter study, we retrospectively analyzed consecutive patients with newly-diagnosed PCNSL, aged >60, treated with a (R)-MPV-AAA regimen. The regimen consisted of three 28-day cycles of methotrexate (3...
April 21, 2017: Journal of Neuro-oncology
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