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https://www.readbyqxmd.com/read/28646771/efficacy-of-alectinib-in-central-nervous-system-metastases-in-crizotinib-resistant-alk-positive-non-small-cell-lung-cancer-comparison-of-recist-1-1-and-rano-hgg-criteria
#1
Leena Gandhi, Sai-Hong Ignatius Ou, Alice T Shaw, Fabrice Barlesi, Anne-Marie C Dingemans, Dong-Wan Kim, D Ross Camidge, Brett G M Hughes, James C-H Yang, Javier de Castro, Lucio Crino, Hervé Léna, Pascal Do, Sophie Golding, Walter Bordogna, Ali Zeaiter, Ahmed Kotb, Shirish Gadgeel
BACKGROUND: Central nervous system (CNS) progression is common in patients with anaplastic lymphoma kinase-positive (ALK+) non-small-cell lung cancer (NSCLC) receiving crizotinib. Next-generation ALK inhibitors have shown activity against CNS metastases, but accurate assessment of response and progression is vital. Data from two phase II studies in crizotinib-refractory ALK+ NSCLC were pooled to examine the CNS efficacy of alectinib, a CNS-active ALK inhibitor, using Response Evaluation Criteria in Solid Tumours (RECIST version 1...
June 21, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28640701/primary-cns-lymphoma
#2
Christian Grommes, Lisa M DeAngelis
Primary CNS lymphoma (PCNSL) is a rare form of extranodal non-Hodgkin lymphoma that is typically confined to the brain, eyes, and cerebrospinal fluid without evidence of systemic spread. The prognosis of patients with PCNSL has improved during the last decades with the introduction of high-dose methotrexate. However, despite recent progress, results after treatment are durable in half of patients, and therapy can be associated with late neurotoxicity. PCNSL is an uncommon tumor, and only four randomized trials and one phase III trial have been completed so far, all in the first-line setting...
June 22, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28639735/neonates-with-cancer-and-causes-of-death-lessons-from-615-cases-in-the-seer-databases
#3
Ahmad S Alfaar, Waleed M Hassan, Mohamed Sabry Bakry, Ibrahim Qaddoumi
Neonatal tumors are rare with no standard treatment approaches to these diseases, and the patients experience poor outcomes. Our aim was to determine the distribution of cancers affecting neonates and compare survival between these cancers and older children. We analyzed SEER data (1973-2007) from patients who were younger than 2 years at diagnosis of malignancy. Special permission was granted to access the detailed (i.e., age in months) data of those patients. The Chi-square Log-rank test was used to compare survival between neonates (aged <1 month) and older children (>1 month to <2 years)...
June 22, 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28627634/dtx3l-is-upregulated-in-glioma-and-is-associated-with-glioma-progression
#4
Peng Xu, Xuelei Tao, Chengjin Zhao, Qingfeng Huang, Hao Chang, Na Ban, Yuanqi Bei, Xiaojie Xia, Chaoyan Shen, Kun Wang, Li Xu, Peizhang Wu, Jianbing Ren, Donglin Wang
Gliomas are the most common primary brain tumors of the central nervous system (CNS). Due to the poor prognosis of glioma patients, it is urgent to develop more effective therapies. Deltex-3-like (DTX3L), also known as B-lymphoma and BAL-associated protein (BBAP), has been reported to play an important role in the progression of many tumors. This study aimed to investigate the clinical significance and biological function of DTX3L in human glioma. Clinically, the protein expression level of DTX3L is increased in glioma tissues compared with that observed in normal brain tissues...
June 13, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28620498/diabetes-insipidus-and-hypopituitarism-in-hiv-an-unexpected-cause
#5
Carlos Tavares Bello, Francisco Sousa Santos, João Sequeira Duarte, Carlos Vasconcelos
Central diabetes insipidus (DI) is a rare clinical entity characterized by low circulating levels of antidiuretic hormone (ADH) presenting with polyuria and volume depletion. Pituitary surgery is the most common cause of central DI in adults. Pituitary and hypothalamic disease, particularly invasive neoplasms, rarely cause DI, being idiopathic cases responsible for the majority of non-surgical cases. HIV patients, especially those with poor virulogical control, are prone to the development of CNS neoplasms, particularly lymphomas...
2017: Endocrinology, Diabetes & Metabolism Case Reports
https://www.readbyqxmd.com/read/28619981/ibrutinib-unmasks-critical-role-of-bruton-tyrosine-kinase-in-primary-cns-lymphoma
#6
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/28612664/primary-central-nervous-system-t-cell-lymphoma-with-aberrant-expression-of-cd20-and-cd79a-a-diagnostic-pitfall
#7
Neha Gupta, Mansoor Nasim, Silvia G Spitzer, Xinmin Zhang
Primary central nervous system T-cell lymphoma (PCNSTCL) is rare, accounting for 2% of CNS lymphomas. We report the first case of PCNSTCL with aberrant expression of CD20 and CD79a in an 81-year-old man with a left periventricular brain mass. A biopsy revealed dense lymphoid infiltrate consisting of medium-sized cells in a background of gliosis and many histiocytes. The lymphoid cells were positive for CD2, CD3, CD7, CD8, T-cell intracellular antigen-1, granzyme B, CD20, and CD79a and negative for CD4, CD5, PAX-5, OCT-2, BOB-1, human herpes virus-8, and Epstein-Barr virus-encoded small RNAs...
June 1, 2017: International Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28611025/how-i-treat-patients-with-aggressive-lymphoma-at-high-risk-of-cns-relapse
#8
Collin K Chin, Chan Yoon Cheah
Central nervous system (CNS) relapses are an uncommon yet devastating complication of non-Hodgkin lymphomas. The identification of patients at high risk of secondary CNS relapse is therefore paramount. Retrospective data indicate prophylactic CNS-directed therapies may reduce the risk of CNS involvement; however, no consensus exists about dose, timing or route of therapy. In addition, prophylaxis is not without risk of treatment-related complications and morbidity. Here we present a series of case vignettes highlighting our approach to common dilemmas encountered in routine clinical practice...
June 13, 2017: Blood
https://www.readbyqxmd.com/read/28596436/checkpoint-inhibition-in-cns-lymphoma
#9
Beth Christian
No abstract text is available yet for this article.
June 8, 2017: Blood
https://www.readbyqxmd.com/read/28593796/the-standard-international-prognostic-index-for-predicting-the-risk-of-cns-involvement-in-dlbcl-without-specific-prophylaxis
#10
Naoto Tomita, Masahiro Yokoyama, Wataru Yamamoto, Reina Watanabe, Yutaka Shimazu, Yasufumi Masaki, Saburo Tsunoda, Chizuko Hashimoto, Kayoko Murayama, Takahiro Yano, Rumiko Okamoto, Ako Kikuchi, Kazuo Tamura, Kazuya Sato, Kazutaka Sunami, Hirohiko Shibayama, Rishu Takimoto, Rika Ohshima, Hiromichi Takahashi, Yukiyoshi Moriuchi, Tomohiro Kinoshita, Masahide Yamamoto, Ayumi Numata, Hideaki Nakajima, Ikuo Miura, Kengo Takeuchi
Central nervous system (CNS) involvement is a serious complication in patients with diffuse large B-cell lymphoma (DLBCL) and evaluating CNS risk is an important issue. Using the standard international prognostic index (IPI) and CNS-IPI, a recently proposed model including IPI risk factors and adrenal/kidney involvement, we assessed CNS risk in 1220 untreated DLBCL patients who received R-CHOP without prophylaxis. According to the standard IPI, the cumulative incidences of CNS involvement at 2 years were 1...
June 8, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28588795/cancer-survival-in-qidong-between-1972-and-2011-a-population-based-analysis
#11
Jian-Guo Chen, Jian Zhu, Yong-Hui Zhang, Yi-Xin Zhang, Deng-Fu Yao, Yong-Sheng Chen, Jian-Hua Lu, Lu-Lu Ding, Hai-Zhen Chen, Chao-Yong Zhu, Li-Ping Yang, Yuan-Rong Zhu, Fu-Lin Qiang
Population-based cancer survival is an improved index for evaluating the overall efficiency of cancer health services in a given region. The current study analysed the observed survival and relative survival of leading cancer sites from a population-based cancer registry between 1972 and 2011 in Qidong, China. A total of 92,780 incident cases with cancer were registered and followed-up for survival status. The main sites of the cancer types, based on the rank order of incidence, were the liver, stomach, lung, colon and rectum, oesophagus, breast, pancreas, leukaemia, brain and central nervous system (B and CNS), bladder, blood [non-Hodgkin's lymphoma (NHL)] and cervix...
June 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28586279/alectinib-versus-crizotinib-in-untreated-alk-positive-non-small-cell-lung-cancer
#12
Solange Peters, D Ross Camidge, Alice T Shaw, Shirish Gadgeel, Jin S Ahn, Dong-Wan Kim, Sai-Hong I Ou, Maurice Pérol, Rafal Dziadziuszko, Rafael Rosell, Ali Zeaiter, Emmanuel Mitry, Sophie Golding, Bogdana Balas, Johannes Noe, Peter N Morcos, Tony Mok
Background Alectinib, a highly selective inhibitor of anaplastic lymphoma kinase (ALK), has shown systemic and central nervous system (CNS) efficacy in the treatment of ALK-positive non-small-cell lung cancer (NSCLC). We investigated alectinib as compared with crizotinib in patients with previously untreated, advanced ALK-positive NSCLC, including those with asymptomatic CNS disease. Methods In a randomized, open-label, phase 3 trial, we randomly assigned 303 patients with previously untreated, advanced ALK-positive NSCLC to receive either alectinib (600 mg twice daily) or crizotinib (250 mg twice daily)...
June 6, 2017: New England Journal of Medicine
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
#13
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/28577295/response-assessment-with-the-cxcr4-directed-positron-emission-tomography-tracer-68-ga-pentixafor-in-a-patient-with-extranodal-marginal-zone-lymphoma-of-the-orbital-cavities
#14
Peter Herhaus, Stefan Habringer, Tibor Vag, Katja Steiger, Julia Slotta-Huspenina, Carlos Gerngroß, Benedikt Wiestler, Hans-Jürgen Wester, Markus Schwaiger, Ulrich Keller
CXCR4 belongs to the family of chemokine receptors. Together with its sole known ligand CXCL12 (SDF-1alpha), it has a pivotal role during organogenesis and for homing of hematopoietic stem cells. CXCR4 is overexpressed in various malignancies, and this is often associated with poor prognosis. Therefore, molecular imaging of CXCR4 bears a great potential for diagnostics and selecting patients for CXCR4-directed therapies. The CXCR4-directed positron emission tomography (PET) tracer [(68)Ga]Pentixafor has been shown to visualize CXCR4 expression in various malignancies in vivo...
December 2017: EJNMMI Research
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
#15
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/28558176/primary-vitreoretinal-lymphoma-a-review
#16
Iguaracyra Araujo, Sarah E Coupland
Primary vitreoretinal lymphoma (PVRL) is the most common intraocular lymphoma occurring in the eye. It is a high-grade typically B-cell malignancy, arising in the retina, and is often associated with central nervous system (CNS) disease and thereby a poor prognosis. It needs to be distinguished from choroidal low-grade B-cell lymphomas, which do not disseminate to the brain and have a good prognosis. Because of the rarity of PVRL, information is lacking regarding its true incidence, its geographical or ethnic variation, and underlying risk factors apart from immunosuppression associated with human immunodeficiency virus (HIV) and Epstein Barr virus...
May 2017: Asia-Pacific Journal of Ophthalmology
https://www.readbyqxmd.com/read/28556945/leukemia-lymphoma-related-factor-lrf-exhibits-stage-and-context-dependent-transcriptional-controls-in-the-oligodendrocyte-lineage-and-modulates-remyelination
#17
Nathan L Davidson, Fengshan Yu, Naruchorn Kijpaisalratana, Tuan Q Le, Laurel A Beer, Kryslaine L Radomski, Regina C Armstrong
Leukemia/lymphoma-related factor (LRF), a zinc-finger transcription factor encoded by Zbtb7a, is a protooncogene that regulates differentiation in diverse cell lineages, and in the CNS, its function is relatively unexplored. This study is the first to examine the role of LRF in CNS pathology. We first examined LRF expression in a murine viral model of spinal cord demyelination with clinically relevant lesion characteristics. LRF was rarely expressed in oligodendrocyte progenitors (OP) yet, was detected in nuclei of the majority of oligodendrocytes in healthy adult CNS and during remyelination...
May 30, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28554659/naloxegol-an-opioid-antagonist-with-reduced-cns-penetration-mode-of-action-and-human-relevance-for-rat-testicular-tumours
#18
Håkan Andersson, Terri Mitchard, Nakpangi Johnson, Eike Floettmann
Naloxegol is an opioid antagonist which has been developed for the treatment of patients with opioid induced constipation. In the nonclinical safety program naloxegol was shown to have a very benign toxicity profile. In the rat, but not the mouse, 2-year carcinogenicity study a change in tumour pattern with an increase in testicular Leydig cell tumours (LCT) was observed after dosing at high (supra-pharmacological) concentrations. To establish the basis of the increase in LCT and to assess its potential relevance to humans, studies to exclude and potentially identify mode-of-action (MoA) were performed...
May 26, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28552327/inhibition-of-b-cell-receptor-signaling-by-ibrutinib-in-primary-cns-lymphoma
#19
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/28543967/central-nervous-system-involvement-of-primary-cutaneous-diffuse-large-b-cell-lymphoma-leg-type-13-cases
#20
LETTER
E Gardette, A Maraval, F Brunet-Possenti, G Quereux, H Beltraminelli, I Templier, J Hodel, E Scherman, E Durot, M Bagot, A Pham-Ledard, F Grange, M Beylot-Barry, S Ingen-Housz-Oro
No abstract text is available yet for this article.
May 23, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
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