tbuckley/cabot-search huggingface dataset:
Intracerebral presentation of Hodgkin’s disease mimicking meningioma
Authors: N. Apollonsky, G. Karayalcin
Journal: Journal of Clinical Oncology (2007)

12533 A 23-year-old woman presented with headaches, diplopia, nausea and vomiting. CT scan revealed frontal extradural mass consistent with meningioma. After excision of the mass light microscopic evaluation revealed a polymorphous variably cellular neoplasm with a background of normal small lymphocytes, eosinophils, histiocytes with large, atypical, often multinucleated cells. Immunohistochemical studies demonstrated large cell strongly positive for CD 30 and focally positive for CD 15 and negative for EMA and ALK1. The morphology, architectural features, and immunohistochemical findings were consistent with Hodgkin disease, the nodular sclerosing type. Systemic work up revealed stage IV disease. Patient was successfully treated with chemotherapy for Advance Stage HD and involved field RT, involving brain. The patient remains disease free 4 years after completion of treatment. Intracranial involvement (IC) of the Hodgkin disease (HD) is a rare entity. In the majority of cases intracranial involvement has been seen during relapsed and progressive disease. Until now nine cases of initial presentation of the HD as a brain tumor with appropriate morphological and histochemical confirmation were reported. Among those patients six patients had isolated primary IC HD and three patients after further investigation were found to have extracranial involvement. Seven of the nine patients had nodular sclerosing histology, one had mixed cellularity and in one case histology was not reported. All patients following resection of the IC mass received cranial RT. Two patients also received intrathecal chemotherapy. Patients with the extracranial involvement received systemic chemotherapy. All patients responded to the treatment and were disease free on the subsequent follow up 6–48 months after the completion of the therapy. No significant financial relationships to disclose.
Dihydropyrimidine dehydrogenase deficiency (DPD) in GI malignancies: Experience of 4 years
Authors: R. Mehra, L. K. Mattison, L. Ledbetter, H. Ezzeldin, R. B. Diasio, M. W. Saif
Journal: Journal of Clinical Oncology (2006)

2056 Background: 5-Fluorouracil (5-FU) is an integral part of treatment of GI malignancies. While normal DPD enzyme activity is rate limiting in 5-FU catabolism, its deficiency could increase concentrations of bioavailable 5-FU anabolic products leading to 5-FU related toxicity syndrome. With DPD deficiency, 5-FU is discontinued. Data regarding safety of capecitabine (CAP) in this population is scarce. Methods: Patients were tested for DPD deficiency after excessive toxicities from 5-FU and CAP at UAB between 2001 and 2005. DPD activity was evaluated by PBMC radio assay, genotyping of DPYD gene by DHPLC, or 2- 13 C uracil breath test (UraBT). Results: Of 23 patients with GI malignancies (small intestine, gastric, pancreatic, HCC, and colorectal) evaluated, 7 (30%) were DPD deficient. Among these 7 patients, DPD activity ranged from 0.064 - 0.18 nmol/min/mg. Age ranged from 51–75 years, M:F ratio = 1.3:1, and ethnicities included Caucasian (71%), African-American (14%) and South-Asian (14%). Four were treated with 5-FU/LV (2 Roswell; 2 Mayo); 2 CAP (1800mg/m 2 ); and 2 high dose bolus 5-FU (1400mg/m 2 ) + PN401 (tri-acetyluridine). Toxicities included mucositis (71%), diarrhea (43%), nausea (29%), memory loss/altered mental status (43%), cytopenias (43%), hypotension (14%), respiratory distress (14%), acute renal failure (14%), and severe skin rashes (43%). Re-challenge with CAP in 1 patient after the Mayo regimen caused grade 3 HFS only on dorsal surfaces of hands. One patient on PN401 had a grade 3 facial rash as the worst toxicity. Genotypic analysis of the DPYD gene in the second on PN401, who had severe leucopenia, demonstrated a heterozygous mutation (IVS14+1 G&gt;A, DPYP*2A). UraBT in 2 patients revealed 1 to be DPD-deficient (DOB 50 of 112.8; PDR of 49.4%) and borderline normal values (DOB 50 of 130.9; PDR of 52.5%) in a second patient. There were 2 toxicity-related deaths (28%): 1 on CAP and 1 on 5-FU + PN401. Conclusions: DPD deficiency was observed in several ethnicities. Patients with CAP toxicities should also be tested for DPD deficiency. Role of PN401 in rescuing 5-FU toxicity in DPD deficiency is not clear. Screening patients for DPD deficiency prior to administration of 5-FU or CAP, using UraBT, could potentially lower risk of toxicity. Future studies should validate this technique. [Table: see text]
Phase II study of sunitinib as second-line therapy in malignant pleural mesothelioma (MPM)
Authors: A. K. Nowak, M. J. Millward, R. Francis, A. van der Schaaf, A. W. Musk, M. J. Byrne
Journal: Journal of Clinical Oncology (2008)

8063 Background: There is no standard second-line therapy for progressive MPM following first line chemotherapy. Sunitinib is a multi-targeted tyrosine kinase inhibitor of VEGFR, PDGFR, c-Kit and Flt-3. VEGFR and PDGFR are potential targets in MPM. We examined the safety and efficacy of sunitinib as second line treatment in MPM. Methods: Eligible patients had progressive MPM during or after first-line chemotherapy with platinum and antimetabolite, ECOG PS 0–1, adequate organ function, measurable disease, and gave informed consent. Treatment: sunitinib 50 mg/day x28d q6 weeks. Primary endpoint was objective response defined by either a). Modified RECIST Criteria (MRC) on CT scan or b) metabolic response on FDG-PET in patients without prior talc pleuradesis (Francis et al, J Nuc Med (48) 1449–58; 2007). Imaging was performed at baseline and after cycles 1, 2, and every 2 cycles thereafter. Simon's 2 stage design required 2 responses in 23 patients (stage I) to give α = 0.05, β = 0.1 assuming a true RR of 20% to be of interest. Stage I is reported here. Results: From May 2006 to October 2007 23 patients were accrued: 22 radiologically assessable for response. Demographics: M/F (18:5); median age 65 (range 49–81); histology epithelial/sarcomatoid/mixed/unknown (11:0:2:10). ECOG PS 0/1 (4:19). Prior platinum/pemetrexed 57%, prior platinum gemcitabine 43%. Best MRC response: CR 0; PR 3 (15%); SD 11 (55%); PD 6 (30%). Metabolic response on PET: 3 of 10 assessable (30%), 1 also with MRC response. Total protocol-defined response 5/22 (23%, 95% CI 5%-40%). Median follow up is 9.5 months (range 1.2–18.5 months). Median OS was 5.9 months (95% CI 2.4–9.4). Median TTP was 3.5 months (95% CI 2.8–4.2). Total cycles given is 51. Adverse events (% of all cycles): Grade 4, thrombocytopenia 1%; Grade 3, fatigue 17%, anorexia 3%, diarrhea 3%. 5/23 required dose reduction. There was one possible treatment-related death from pulmonary infiltrates and respiratory failure. Three patients developed increasing pleural effusions or ascites without other radiologic evidence of PD. Treatment was otherwise well tolerated. Conclusions: Sunitinib has activity in previously treated MPM. Stage II will continue to accrue to 51 patients. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Pfizer Oncology
Treatment of preleukemic syndromes with continuous intravenous infusion of low-dose cytosine arabinoside.
Authors: J D Griffin, D Spriggs, J S Wisch, D W Kufe
Journal: Journal of Clinical Oncology (1985)

Preleukemic syndromes compose a group of acquired bone marrow disorders characterized by dysplastic maturation of hematopoietic cells and peripheral blood cytopenias. These syndromes have been generally considered untreatable. We administered low doses of cytosine arabinoside by continuous infusion for 14 to 21 days (20 mg/m2/d) to 16 patients with preleukemia in various stages of evolution to acute leukemia. Steady state plasma cytosine arabinoside levels ranged from 41.8 to 64.2 nmol/L. Eleven patients demonstrated marked improvement in hematopoiesis and loss of transfusion requirements for periods ranging from two to 27 + months. All but one responding patient developed recurrent pancytopenia, but additional responses to low-dose cytosine arabinoside were achieved in five of five retreated patients. Median overall survival time is 12 months for the 11 responding cases, and nine months for nonresponders. The major toxicity of low-dose cytosine arabinoside is myelosuppression, and most patients required platelet transfusion support and administration of antibiotics. Chromosome analyses demonstrated evolution to a new clone of hematopoietic cells in three patients, and persistence of the same abnormal clone in another patient. These results suggest that low-dose cytosine arabinoside therapy may result in improved hematopoiesis by promoting maturation or by selecting new stem cell clones. Low-dose cytosine arabinoside therapy thus deserves further evaluation both as a single agent and in combination with other agents in the treatment of myelodysplastic syndromes.
Gene-expression profiling to demonstrate select neutrophils from breast cancer patients versus healthy women as cytotoxic against breast cancer cells via novel chemokine-mediated mechanisms.
Authors: Elizabeth Anne Comen, Paulina Wojnarowicz, Venkatraman E. Seshan, Brian Blum, Riddhi Shah, Courtney Coker, Larry Norton, Robert Benezra
Journal: Journal of Clinical Oncology (2014)

11086 Background: We have previously shown that neutrophils, entrained by a primary breast tumor, inhibit metastatic seeding and are cytotoxic to cancer cells in mouse models (Granot et al., 2010). We further demonstrated that neutrophils from human breast cancer patients are cytotoxic to breast cancer cells, and show a significantly higher cytotoxicity than neutrophils from cancer-free controls. We identified the cytokines IL1a, MCP-1, and TNF as being associated with neutrophil cytotoxicity and showed that these cytokines stimulate neutrophil cytotoxicity against breast cancer cells in cell culture assays. To further investigate neutrophil cytotoxicity, we preformed RNA-seq analyses on neutrophils from breast cancer patients and cancer-free controls. Methods: We purified neutrophils from 50 newly diagnosed pre-operative breast cancer patients and 25 cancer-free controls. Neutrophil cytotoxicity against MDA-MB-231 breast cancer cells was assessed in these samples by previously described methods. (Granot et al., 2010). RNA-seq was performed on 61 of these samples (36 breast cancer patients and 25 controls) using the Illumina HiSeq2500 platform. Comparative analyses were performed to identify genes differentially expressed between patients and controls and between samples showing high and low cytotoxicity. Results: Preliminary comparative analyses of the RNA-seq derived gene expression profiles identified 138 genes to be differentially expressed between patients and controls. Confirming our previous observations, IL1 family members and TNF were overexpressed in patient samples in comparison to cancer-free controls. Comparative analyses also identified 43 genes differentially expressed between patient samples with high cytotoxicity and those with low cytotoxicity. Conclusions: Our results have identified unique gene expression profiles associated with neutrophil cytotoxicity against breast cancer cells. We are currently evaluating the mechanism of action of neutrophil cytotoxicity as well as the prognostic and therapeutic roles of cytotoxic neutrophils in breast cancer patients.
A phase II trial of perifosine as second line therapy for advanced pancreatic cancer. A study of the Princess Margaret Hospital [PMH] Phase II Consortium
Authors: D. Hedley, M. J. Moore, H. Hirte, L. Siu, M. Vincent, D. Jonker, H. Mwang, J. Nagai, J. Dancey
Journal: Journal of Clinical Oncology (2005)

4166 Background: Perifosine is a synthetic, substituted heterocyclic alkylphospholipid, structurally related to miltefosine, with a unique spectrum of activity across the NCI 60 cell line screen. Phase I testing identified a recommended phase 2 dose (RP2D) of 150 mg/dy on a 21/28 day schedule with anorexia, fatigue, dehydration, nausea/vomiting as the predominant toxicities. Methods: Patients had advanced pancreatic adenocarcinoma and were allowed to have one prior systemic therapy. Perifosine [50mg tablets] was given on a 28 day cycle: Cycle 1 -loading dose 1050 mg over 2 days followed by 150mg daily on days 3–21; Cycle 2 and greater -day 1 dose of 300mg followed by 150mg days 2–21. A 2 stage design was employed with continuation to stage 2 only if 4/15 survive 6 months from study entry. In parallel with stage 1 of the clinical study, Panc-1 and MiaPaCa-2 xenografts were treated with perifosine at the MTD of 200mg/kg on Day 1 followed by 20mg/kg daily by oral gavage. Animals were sacrificed at 0, 24, 48, and 96hr, and tumor tissue analyzed by immunohistochemistry for effects on p21, p27, and cleaved caspase 3, and by immunohistochemistry and western blot for pAkt, pERK, pSAPK/JNK, pp38MAPkinase. If the clinical study proceeded to stage 2, then biopsies to identify effects on identified drug targets in vivo would be undertaken. Results: 19 patients were entered on study and received a total of 36 cycles of therapy. The response was stable disease in 2 [duration 3 & 8 months], progressive disease in 15 and 2 were inevaluable. The median survival time was 3.1 months, the median time to progression was 1.6 months and 5 survived 6 months or greater. The most frequent adverse events were fatigue, anorexia and abdominal pain. In the xenograft studies no significant alterations were detected in any of the biomarkers over the 96 hour experiments. Conclusions: Although 5/17 patients were alive at 6 months, the high rate of early progression and the short median time to progression indicate that single agent perifosine on this schedule is not sufficiently active to warrant study continuation. No significant financial relationships to disclose.
Clinical benefit and survival endpoints from a phase III trial comparing decitabine (DAC) vs supportive care (SC) in patients with advanced myelodysplastic syndromes (MDS)
Authors: H. I. Saba, C. S. Rosenfeld, J.-P. Issa, J. M. Bennett, C. Decastro, J. Dipersio, H. Kantarjian
Journal: Journal of Clinical Oncology (2005)

6543 Background: MDS is a blood disorder characterized by dysplasias of hematopoetic cells resulting in cytopenias and progression to acute myelogenous leukemia (AML). There is only one approved therapy for MDS. Decitabine (Dacogen) is a cytosine analog that reverses aberrant DNA methylation leading to re-expression of silenced tumor suppressor genes. Results of adjudicated data (responses independently judged by a blinded reviewer) are presented for the first time. Methods: We report a phase III, randomized, open-label trial of DAC vs SC in MDS patients (pts) with International Prognostic Scoring System (IPSS) Intermediate (Int)-1 (31%), Int-2 (44%), and high-risk disease (26%). Secondary MDS (14%)/previously treated (27%) pts were included. Co-primary endpoints were response rate (CR + PR) and Time to AML or Death (TTAML/D). Results: 170 pts received either DAC (n = 89) (3-hr infusion; 15 mg/m2/hr q 8 hrs for 3 days q 6 wks) plus SC or SC alone (n = 81). Both groups were comparable for baseline characteristics. Response rate according to International Working Group (IWG) MDS criteria following a blinded, centralized bone marrow review, was 17% for DAC (9%, CR; 8%, PR) vs 0% for SC (p <0.001). Responses occurred in all IPSS groups. Responses were durable, lasting a median of 9 months. DAC responders vs all nonresponders had a median of 491 vs 274 AML-free days until death, a median of 657 vs 384 days of survival, and remained or became RBC/platelet transfusion independent during response. 7 of 15 pts (47%) with CR or PR had a major cytogenetic response and 1 a minor cytogenetic response. Median TTAML/D in all pts was 340 days for DAC vs 219 days for SC (p = 0.043 Wilcoxon, 0.160 Log-rank). Using a Cox proportional hazards model, the probability of progression to AML or death was 1.72-fold greater for SC than DAC (p = 0.017). Quality-of-life evaluations showed DAC to be superior for global health status, physical functioning, fatigue, and dyspnea. As expected, the primary toxicity was myelosuppression, with the major Grade 3–4 toxicity being febrile neutropenia. Conclusion: DAC is a promising therapy for MDS, with predictable toxicity. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Celgene, MGI, SuperGen Amgen, Anormed, MGI, SuperGen Anormed, Food and Drug Administration, National Cancer Institute, National Institutes of Health, SuperGen, Xcyte
Recommendations for Screening for Depression in Adults
Authors: Michael E. Thase
Journal: JAMA (2016)

Albert L. Siu, MD, MSPH; and the US Preventive Services Task Force (USPSTF); Kirsten Bibbins-Domingo, PhD, MD, MAS; David C. Grossman, MD, MPH; Linda Ciofu Baumann, PhD, RN, APRN; Karina W. Davidson, PhD, MASc; Mark Ebell, MD, MS; Francisco A. R. García, MD, MPH; Matthew Gillman, MD, SM; Jessica Herzstein, MD, MPH; Alex R. Kemper, MD, MPH, MS; Alex H. Krist, MD, MPH; Ann E. Kurth, PhD, RN, MSN, MPH; Douglas K. Owens, MD, MS; William R. Phillips, MD, MPH; Maureen G. Phipps, MD, MPH; Michael P. Pignone, MD, MPH
Translational Bioinformatics: Past, Present, and Future
Authors: Jessica D. Tenenbaum
Journal: Genomics Proteomics & Bioinformatics (2016)

Abstract Though a relatively young discipline, translational bioinformatics (TBI) has become a key component of biomedical research in the era of precision medicine. Development of high-throughput technologies and electronic health records has caused a paradigm shift in both healthcare and biomedical research. Novel tools and methods are required to convert increasingly voluminous datasets into information and actionable knowledge. This review provides a definition and contextualization of the term TBI, describes the discipline’s brief history and past accomplishments, as well as current foci, and concludes with predictions of future directions in the field.
Age and the treatment of breast cancer.
Authors: R D Rubens
Journal: Journal of Clinical Oncology (1993)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1993.11.1.3 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 8418239 Age and the treatment of breast cancer. R D RubensxR D RubensSearch for articles by this author https://doi.org/10.1200/JCO.1993.11.1.3 PDF "Age and the treatment of breast cancer.." Journal of Clinical Oncology, 11(1), pp. 3–4© 1993 by American Society of Clinical Oncology
Viscerally Disseminated Herpes Zoster Presenting Abdominal Pain, Siadh, and Skin Rash in a Follicular Lymphoma Patient
Authors: Hitomi Sumiyoshi, Yukio Kobayashi, Shinichi Makita, Mai Tatsuno, Hideaki Kitahara, Suguru Fukuhara, Wataru Munakata, Tatsuya Suzuki, Dai Maruyama, Kensei Tobinai
Journal: Annals of Oncology (2014)
RP101 improves the efficacy of gemcitabine in treating pancreatic carcinoma
Authors: M. Haenel, D. Quietzsch, V. Heinemann, S. Boeck, R. M. Schmid, A. Liebert, R. Fahrig
Journal: Journal of Clinical Oncology (2006)

14075 Background: (E)-5-(2-bromovinyl)-2’-deoxyuridine (BVDU, RP101), was initially tested in a phase 1 pilot study in pancreatic cancer. Patients (n=13) received gemcitabine (1000 mg/m 2 ), cisplatin (50 mg/m 2 ) and RP101 (500 mg/day). The median survival was 447 days and the TTP was 280 days. Ten of the 13 pts lived longer than one year, 4 nearly two years. Based on these promising results a phase 2 study was initiated to explore varying doses of RP101 used with a fixed dose of GEM. Methods: Pts with advanced pancreatic adenocarcinoma were eligible for treatment in this single arm study. 22 pts (16 stage IV and 5 stage III) received GEM 1000 mg/m 2 on days 1, 8 and 15 of a 28-day schedule. RP101 treatment, at doses of 500, 625, 750, 875 or 1000 mg/day, was on the same day and for three days after chemotherapy. The mean age was 60 years and 73% of pts were males. Results: The results are based on interim data from an ongoing study and patients at the 2 highest dose groups are still being treated. All RP101 dose groups were combined for analyses, which included all enrolled pts. The data on the 6-month survival status show that 41% are alive; 23% dead; and 36% followed less than 6 months. The median survival (95% CI) is 7.1 months (5.9, not calculated) and 14/22 pts (64%) are still alive. The 6 month survival rate (95% CI) is 0.69 (0.52, 0.85). This compares very favorably with a large recent randomized trial in which pts who received GEM alone had a median survival (95%CI) of 5.9 months (5.1–6.7). PFS and TTP continue to be assessed in this ongoing trial. There appears to be a dose dependent increase in peak GEM levels as a function of the dose of RP101. To date, adverse events are consistent with those observed with GEM or the underlying disease. Conclusion: RP101 may improve treatment of advanced pancreatic cancer when used with gemcitabine. Updated data on survival, PFS, and safety will be presented based on available data. [Table: see text]
구연 : 아이리스 ; B형 간염 바이러스에 중복 감염된 만성 C형 간염 환자들의 임상적 특징 및 페그인터페론 알파2a 와 리바비린 병합 투여요법의 치료 성적 (초)
Authors: 김유진, 김주현, 김연수, 임형준, 박영민, 김보현, 김영석, 정숙향, 이진우, 최종원, 박상훈, 박충기
Journal: Clinical and Molecular Hepatology (2010)
Treatment outcomes with first and second line chemotherapy in advanced and metastatic pancreatic cancer patients
Authors: A. Mancuso, P. Saletti, S. Sacchetta, E. Romagnani, F. Cavalli, C. N. Sternberg
Journal: Journal of Clinical Oncology (2006)

14107 Background: Recent advances in the treatment of pancreatic cancer might influence the management of locally advanced and metastatic disease, nonetheless prognosis remains dismal (1-year survival rates: 24%). The impact on survival of palliative second-line therapy is hotly debated. Methods: We retrospectively reviewed the clinical records of 103 pancreatic cancer patients admitted to San Camillo/Forlanini Hospital (Rome, Italy) and the Oncology Institute of Southern Switzerland during the period June, 1997 to August, 2005 [60 males, 43 females, median age 65 years (range 43–80); median ECOG performance status (PS): 1]. All patients received Gemcitabine as single agent (90%) or in combination with Oxaliplatin (10%) as upfront therapy. A total of 12 fluoropyrimidine-based salvage regimens were administered to 46 patients in the second line setting. Best supportive care was selected in 57 patients after failing first line therapy. Results: Of 103 evaluable patients, first line chemotherapy produced overall tumor growth control of partial response (PR) and stable disease(SD) by RECIST criteria of 52.4% with a median progression free survival (PFS) of 4.6 months. Multivariate analysis revealed that the most important prognostic factor for PFS was the patient’s PS, as patients with PS of 1–2 at diagnosis had significantly worse results than patients with PS = 0 (First line PFS: 110 days vs 193 days, p&lt;0.05). Baseline CA19–9 and number of metastatic sites were not independent prognostic factors for better first-line PFS. PR was observed in 8/46 patients (17.3%) who received second line chemotherapy, SD in 10 (21.7%), and 28 patients progressed (61%). Median overall second line PFS was 3.2 months. Patients who had responded to first-line Gemcitabine were more likely to respond or attain stable disease with second-line treatment, with a PFS of 5.6 vs 2.85 months (p&lt;0.05). The overall survival for all evaluable patients was 8.4 months. 1-year survival was 52% for patients treated with second line therapy. Conclusions: These results are consistent with historical studies and suggest that fluoropyrimidine-based salvage regimens have marginal but definite activity and should be considered in patients who have responded to first line chemotherapy with an optimal PS. No significant financial relationships to disclose.