Timothy J Brown

Association of the Extent of Resection With Survival in Glioblastoma: A Systematic Review and Meta-analysis

Importance Glioblastoma multiforme (GBM) remains almost invariably fatal despite optimal surgical and medical therapy. The association between the extent of tumor resection (EOR) and outcome remains undefined, notwithstanding many relevant studies. Objective To determine whether greater EOR is associated with improved 1- and 2-year overall survival and 6-month and 1-year progression-free survival in patients with GBM. Data Sources Pubmed, CINAHL, and Web of Science (January 1, 1966, to December 1, 2015) were systematically reviewed with librarian guidance. Additional articles were included after consultation with experts and evaluation of bibliographies. Articles were collected from January 15 to December 1, 2015. Study Selection Studies of adult patients with newly diagnosed supratentorial GBM comparing various EOR and presenting objective overall or progression-free survival data were included. Pediatric studies were excluded. Data Extraction and Synthesis Data were extracted from the text of articles or the Kaplan-Meier curves independently by investigators who were blinded to each others results. Data were analyzed to assess mortality after gross total resection (GTR), subtotal resection (STR), and biopsy. The body of evidence was evaluated according to Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria and PRISMA guidelines. Main Outcome and Measures Relative risk (RR) for mortality at 1 and 2 years and progression at 6 months and 1 year. Results The search produced 37 studies suitable for inclusion (41 117 unique patients). The meta-analysis revealed decreased mortality for GTR compared with STR at 1 year (RR, 0.62; 95% CI, 0.56-0.69; P < .001; number needed to treat [NNT], 9) and 2 years (RR, 0.84; 95% CI, 0.79-0.89; P < .001; NNT, 17). The 1-year risk for mortality for STR compared with biopsy was reduced significantly (RR, 0.85; 95% CI, 0.80-0.91; P < .001). The risk for mortality was similarly decreased for any resection compared with biopsy at 1 year (RR, 0.77; 95% CI, 0.71-0.84; P < .001; NNT, 21) and 2 years (RR, 0.94; 95% CI, 0.89-1.00; P = .04; NNT, 593). The likelihood of disease progression was decreased with GTR compared with STR at 6 months (RR, 0.72; 95% CI, 0.48-1.09; P = .12; NNT, 14) and 1 year (RR, 0.66; 95% CI, 0.43-0.99; P < .001; NNT, 26). The quality of the body of evidence by the GRADE criteria was moderate to low. Conclusion and Relevance This analysis represents the largest systematic review and only quantitative systematic review to date performed on this subject. Compared with STR, GTR substantially improves overall and progression-free survival, but the quality of the supporting evidence is moderate to low.

Ex vivo drug response profiling detects recurrent sensitivity patterns in drug-resistant acute lymphoblastic leukemia

Drug sensitivity and resistance testing on diagnostic leukemia samples should provide important functional information to guide actionable target and biomarker discovery. We provide proof of concept data by profiling 60 drugs on 68 acute lymphoblastic leukemia (ALL) samples mostly from resistant disease in cocultures of bone marrow stromal cells. Patient-derived xenografts retained the original pattern of mutations found in the matched patient material. Stromal coculture did not prevent leukemia cell cycle activity, but a specific sensitivity profile to cell cycle-related drugs identified samples with higher cell proliferation both in vitro and in vivo as leukemia xenografts. In patients with refractory relapses, individual patterns of marked drug resistance and exceptional responses to new agents of immediate clinical relevance were detected. The BCL2-inhibitor venetoclax was highly active below 10 nM in B-cell precursor ALL (BCP-ALL) subsets, including MLL-AF4 and TCF3-HLF ALL, and in some T-cell ALLs (T-ALLs), predicting in vivo activity as a single agent and in combination with dexamethasone and vincristine. Unexpected sensitivity to dasatinib with half maximal inhibitory concentration values below 20 nM was detected in 2 independent T-ALL cohorts, which correlated with similar cytotoxic activity of the SRC inhibitor KX2-391 and inhibition of SRC phosphorylation. A patient with refractory T-ALL was treated with dasatinib on the basis of drug profiling information and achieved a 5-month remission. Thus, drug profiling captures disease-relevant features and unexpected sensitivity to relevant drugs, which warrants further exploration of this functional assay in the context of clinical trials to develop drug repurposing strategies for patients with urgent medical needs.

2E-3 Asset Tracking on the International Space Station Using Global SAW Tag RFID Technology

Final preparations are underway to test global SAW tag (GST) RFID technology for tracking assets aboard the International Space Station (ISS). This will be the first test of RFID technology on ISS. It is planned for early 2008 by the Expedition 16 crew. It will evaluate the ability of SAW RFID to track consumable items while packed in standard crew bags. The GST system was selected based on its signal penetration ability and its anti-collision capabilities that allow reliable detection of tags even when placed on, behind, and between items with high liquid and metal content in randomly packed crew bags. Substantial savings of highly-valuable crew time is projected with corresponding improvements in ISS crew productivity.

Pasireotide for the treatment of refractory hypoglycaemia from malignant insulinoma

Dear Editor, Insulinomas are rare, usually solitary benign tumours. The presence of metastases defines malignant insulinomas.1 Medical therapy primarily treats symptomatic hypoglycaemia, alleviates symptoms and improves the quality of life in affected individuals. While diazoxide is used as firstline therapy, the incomplete response rate and complications associated with diazoxide provide a role for somatostatin analogues in difficulttotreat hypoglycaemia.

Cutaneous adnexal adenocarcinoma with exquisite sensitivity to trastuzumab: Trastuzumab sensitivity in cutaneous adnexal adenocarcinoma

Cutaneous adnexal adenocarcinoma is a rare cancer that is occasionally human epidermal growth factor receptor‐2 (HER‐2)‐positive, and demonstrates variable response to HER‐2 inhibitors.

Novel Application of Extracorporeal Photopheresis as Treatment of Graft-versus-Host Disease Following Liver Transplantation

A 48-year-old man with hepatitis C virus (HCV) cirrhosis complicated by hepatocellular carcinoma underwent liver transplantation. His course was complicated by fever, diarrhea, abdominal pain, and pancytopenia. He developed a diffuse erythematous rash, which progressed to erythroderma. Biopsies of the colon and skin were consistent with acute graft-versus-host disease. Donor-derived lymphocytes were present in the peripheral blood. The patient was treated with corticosteroids and cyclosporine; however, he had minimal response to intensive immunosuppressive therapy. Extracorporeal photopheresis was initiated as a salvage therapy. He had a dramatic response, and his rash, diarrhea, and pancytopenia resolved. He is maintained on minimal immunosuppression 24 months later.

Large saddle embolus during cancer therapy

A 67-year-old non-smoking man with stage IV (T2N2cM0) p16-positive squamous cell carcinoma of the tongue, undergoing curative-intent hypofractionated radiation as part of a clinical trial, uneventfully received his fourth dose of weekly cisplatin 30 mg/m2. Later, he developed sudden onset of diaphoresis and experienced a near-syncope while waiting in his car outside the University Hospital. He spontaneously recovered and decided to drive home. On arriving home, he collapsed inside his doorway. …