tbuckley/cabot-search huggingface dataset:
Obesity in adult lymphoma survivors.
Authors: F. Lynce, M. Pehlivanova, J. P. Catlett, V. Malkovska
Journal: Journal of Clinical Oncology (2010)

e19509 Background: Obesity, defined as a body mass index of ≥ 30, is a late effect of therapy in childhood survivors of acute lymphoblastic leukemia (ALL) but the prevalence of obesity in adult lymphoma survivors is not known. We studied the weight changes and associated risk factors in a population of patients with Hodgkin and non-Hodgkin lymphoma following treatment. Methods: We conducted a retrospective chart review of adult patients with lymphoma treated at our institution between January 2002 and May 2009. Three hundred forty-nine patients were included. Demographic characteristics, lymphoma type and comorbid conditions were recorded for each patient, as well as chemotherapy regimen and clinical condition at each visit. Percentage of weight change from baseline and at each clinic visit at 6, 12 and 18 months was recorded. Possible predictors of weight gain were evaluated at each visit using multiple regression analysis, and the overall effect of these variables on weight gain was assessed with a linear mixed model. Results: The mean follow-up time was 38 months. Sixty-three percent of patients were overweight or obese at baseline and 73.24% at 18 months. For three different time periods, there was a progressive increase in weight from the initial visit with an increase of 1.46% at 6 months, 4.51% at 12 months and 6.38% at 18 months (p<0.0001). There was a statistically significant association between increase in weight and age at diagnosis with weight increase diminishing with increasing age (p<0.0001). Patients who did not receive radiation had a greater increase in weight at all three visits. Radiation status had a marginally significant effect at all time points (p=0.0765). Gender, race, number of regimens, steroids use and disease outcome had no effect on weight gain. Conclusions: Lymphoma patients experience progressive weight gain after therapy. Younger age at diagnosis was an important predictive factor for weight gain. Prospective studies are needed to identify patients who would benefit from early preventive strategies. No significant financial relationships to disclose.
Results of the X-PECT study: A phase III randomized double-blind placebo-controlled study of perifosine plus capecitabine (P-CAP) versus placebo plus capecitabine (CAP) in patients (pts) with refractory metastatic colorectal cancer (mCRC).
Authors: Johanna C. Bendell, Thomas J. Ervin, Neil N. Senzer, Donald A. Richards, Irfan Firdaus, A. Craig Lockhart, Allen Lee Cohn, Mansoor N. Saleh, Lesa R. Gardner, Peter Sportelli, Cathy Eng
Journal: Journal of Clinical Oncology (2012)

LBA3501 The full, final text of this abstract will be available at abstract.asco.org at 12:01 AM (EDT) on Sunday, June 3, 2012, and in the Annual Meeting Proceedings online supplement to the June 20, 2012, issue of Journal of Clinical Oncology. Onsite at the Meeting, this abstract will be printed in the Sunday edition of ASCO Daily News.
Planned interim analysis and its role in cancer clinical trials.
Authors: N L Geller
Journal: Journal of Clinical Oncology (1987)

Although interim analyses in cancer clinical trials are commonplace, clinical trials are usually designed with the implicit assumption that data analysis will occur only after the trial is completed. The design of randomized trials with planned interim analyses, "group sequential trials," is described and examples are given. A method to redesign trials in which unplanned interim analyses have been undertaken is described. Planned interim analysis should be considered whenever a cancer clinical trial is designed.
Association between cerebral ventricular enlargement and suicide attempts in chronic schizophrenia
Authors: A B Levy, N Kurtz, A S Kling
Journal: American Journal of Psychiatry (1984)

The ventricular-brain ratios (VBRs) of 32 chronic schizophrenic men were determined by CAT scan. Ten of the 12 patients with VBRs above 8.4% had made suicide attempts, compared with two of the 20 patients with VBRs below 8.4%.
Phase II study of oxaliplatin, high-dose capecitabine, and sorafenib in patients with advanced pancreatic cancer.
Authors: S. J. Lubner, W. R. Schelman, D. Mulkerin, K. D. Holen, S. Seo, N. K. LoConte
Journal: Journal of Clinical Oncology (2010)

4143 Background: Pancreatic cancer is a highly lethal malignancy, resistant to many cytotoxic chemotherapies. Combinations of capecitabine and oxaliplatin have demonstrated some disease control. A high-dose, 2-day capecitabine schedule with oxaliplatin (2DOC) plus sorafenib yielded 1 partial response (PR) and 2 pts had stable disease (SD) in a phase Ib trial, with minimal grade 3 toxicity at the phase II dose. We report the results of the phase II portion of this trial. Methods: An open label phase Ib/II trial was opened through the UW Carbone Cancer Center. For this phase II study, all patients had biopsy proven pancreatic cancer. Prior chemotherapy was allowed if > 4 wks from enrollment. Patients received sorafenib 200 mg BID with oxaliplatin 85 mg/m2 IV on days 1 and 15, followed by capecitabine 2,250 mg/m2 PO every 8 hours for six doses starting on days 1 and 15 of a 28-day cycle. Disease evaluations were performed every two cycles. The primary objective was the objective response rate by RECIST; secondary objectives were progression-free survival (PFS), overall survival (OS), and safety. Results: 24 patients (11 women, 13 men) were enrolled on the phase II portion of the study. The most common toxicities were fatigue, nausea, neuropathy, anemia, leukopenia, and low platelets; most were grade 1-2. Grade 3 hand-foot syndrome was rare (1 pt). Two pulmonary emboli (grade 4) were the most severe toxicities. 2 PRs were seen (8%), and 13 patients had stable disease (54%). PFS was 5.98 mo, and the median OS endpoint has not yet been reached (6 mo OS 62%). Conclusions: 2DOC+sorafenib produced partial responses in patients with advanced pancreatic cancer, and demonstrated a PFS of nearly 6 mo. Use of 2DOC+sorafenib is associated with few grade 3-4 toxicities. This unique drug combination and schedule may be considered in patients who cannot tolerate other forms of chemotherapy and merits further study. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Abbott Laboratories Bayer, sanofi-aventis
Allogeneic marrow transplantation for refractory Hodgkin's disease.
Authors: G L Phillips, D E Reece, M J Barnett, J M Connors, J W Fay, G P Herzig, R H Herzig, H G Klingemann, J D Shepherd, S N Wolff
Journal: Journal of Clinical Oncology (1989)

Eight patients with refractory Hodgkin's disease received intensive combination chemotherapy conditioning with cyclophosphamide, carmustine (BCNU), and etoposide (VP 16-213), and allogeneic marrow transplants. All patients achieved complete responses. Three patients relapsed; two died of Hodgkin's disease and one of chronic graft-v-host disease (GVHD) and infection. In all, four patients died due to transplant-related toxicity. One patient developed a fatal B-cell lymphoproliferative disorder soon after transplantation, and died without evidence of Hodgkin's disease. One patient is alive and free of progression 29 months after transplantation. These data indicate that allogeneic marrow transplantation may be considered as therapy for selected patients with advanced Hodgkin's disease and, despite substantial toxicity, will occasionally result in long-term responses. Better patient selection would likely improve results.
Serum microRNA signatures identified in a genome-wide profiling predict the mortality of patients with sepsis
Authors: Lixin Xie, Huijuan Wang
Journal: European Respiratory Journal (2011)

Purpose:  Serum miRNAs are present and stable, reproducible, and consistent among individuals in the serum and plasma of humans and other animals. And they can be fingerprints of different diseases. We used genome-wide serum miRNA expression profiling analysis to investigate the role of serum miRNA in predicting prognosis of sepsis.   Patients and methods:  According to the 28-days mortality, Solexa sequencing followed by individual quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) assays was used to test the difference in levels of serum miRNAs between survivors and nonsurvivors. There were 9survivors and 9 nonsurvivors matched by age, sex, and stage for the early detection. The detected serum miRNAs then were validated in 92 sepsis patients (39 survivors and 53 nonsurvivors) and 24 healthy controls.   Results:  Twelve serum miRNAs were found to be altered more than two-fold by Solexa sequencing between survival and nonsurvival group, qRT-PCR was preformed in 6 miRNAs (miR-206, miR-378, miR-223, miR-15b, miR-15a and miR-16) according to the previous studies. MiR-223 ( p =0.002 p =0.008 )  and miR-16  (p =0.009   Conclusion:  MiR-223,miR-15b and miR-16 from the serum may serve as a noninvasive predictor of the mortilty of sepsis patients.
Incorporation of the plasma cell labeling index into the international staging system of multiple myeloma: Impact on prognostic value
Authors: P. Kapoor, C. Snozek, C. L. Colby, D. R. Larson, J. A. Katzmann, T. E. Witzig, S. V. Rajkumar, P. R. Greipp
Journal: Journal of Clinical Oncology (2008)

8591 Background: Its easy clinical applicability and validation in different populations has led to widespread adoption of the International Staging System (ISS) for multiple myeloma (MM). We assessed the prognostic value of adding the plasma cell labeling index (LI), a measure of MM cell proliferation, to the ISS in a cohort of patients with extensive follow up. Methods: ISS stage was assigned and validated in 467 newly-diagnosed MM patients seen between May 1986 and December 1998. DNA S-phase measurement (LI) of bone marrow plasma cells was performed by a rapid, fluorescent microscope slide-based method using BU-1 antibody. A cutoff of 1% was used to group patients into low LI or high LI categories within each stage. Survival was defined as time from start of treatment to death or last follow-up. Survival estimates were created using the Kaplan-Meier method; the effect of LI was evaluated using Cox proportional hazards models, both univariate and multivariate analyses adjusted for other prognostic factors such as age and free light chain ratio. Results: Overall survival was significantly inferior in patients with LI ≥1% compared to those with LI <1% (hazard ratio 1.43; CI 1.16, 1.76). When analyzed in the context of the ISS, LI contributed significantly to estimating prognosis for patients in stages 1 and 2, but not stage 3 (Table). Conclusions: Addition of LI to the ISS enhanced the prognostic impact of low (ISS 1) and intermediate (ISS 2) stages in 328 patients, but did not provide any additional prognostic value to 139 high stage (ISS 3) patients. As MM patient management strategies require adequate risk profiling prior to therapy, these results suggest that use of LI at a cutoff of 1%, in addition to ISS staging, would provide more accurate risk-stratification and prognosis. Survival Analysis Factor N Median Survival (months) Univariate Multivariate * HR (95%CI) p-value HR (95%CI) p-value ISS 1 120 45 LI < 1 87 50 1.0 (reference) 1.0 (reference) LI ≥ 1 33 29 1.9 (1.2, 2.9) 0.01 1.8 (1.1, 2.9) 0.01 ISS 2 208 34 LI < 1 141 39 1.0 (reference) 1.0 (reference) LI ≥ 1 67 26 1.6 (1,2, 2.2) <0.01 1.7 (1.2, 2.3) <0.01 ISS 3 139 18 LI < 1 82 24 1.0 (reference) 1.0 (reference) LI ≥ 1 57 18 1.2 (0.8, 1.7) 0.42 1.1 (0.7, 1.6) 0.63 * Adjusted for age (>65 vs. ≤ 65) and free light chain ratio (<1/32 or > 32 vs. 1/32–32) No significant financial relationships to disclose.
Efficacy and safety of trastuzumab plus vinorelbine as second-line treatment for women with HER2-positive metastatic breast cancer beyond disease progression
Authors: T. Bachelot, L. Mauriac, C. Delcambre, P. Maillart, C. Veyret, M. Mouret-Reynier, I. Van Praagh, P. Chollet
Journal: Journal of Clinical Oncology (2007)

1094 Background: There is increasing evidence that women with HER2-positive metastatic breast cancer (MBC) benefit from continued trastuzumab (H) therapy beyond disease progression (PD). In a Phase II multicentre 2-step trial we evaluated women for their response to second-line treatment with H + vinorelbine (N) following PD after receiving first-line H + taxane for HER2-positive MBC. Methods: Women aged =18 years with HER2-positive MBC received H (8 mg/kg loading dose followed by 6 mg/kg q3w or 4 mg/kg loading dose followed by 2 mg/kg qw) + N (30 mg/m 2 days 1 and 8 q3w) until PD. The primary end point was overall response rate (ORR); secondary end points included time to progression, time to treatment failure, overall survival and safety. Data from a planned interim analysis are presented. Results: Seventeen out of a planned 50 patients (pts) were enrolled between June 2003 and October 2006, with a mean age of 54 years (range 42–70). Nine pts had hormone receptor-positive disease at baseline and 17 pts had HER2-positive disease (16 pts IHC 3+; 1 pt IHC 2+ and CISH+). Pts had previously received H in combination with paclitaxel (9 pts) or docetaxel (8 pts) as first-line therapy for MBC. Pts received a median of 6 treatment cycles with H + N (range 2–14), with 2 pts receiving H q3w and 15 pts receiving H qw. ORR was 29%, with 2 pts showing a complete response, 3 pts experiencing a partial response and 4 pts achieving stable disease lasting 6 months. Eight pts experienced PD. Re-treatment with H + N was well tolerated beyond PD, with grade 3/4 haematological toxicities being the most common serious adverse events, leading to a delay and dose reduction of N. No relevant cardiac toxicities were reported, with only 2 grade 1 cardiac events. All pts withdrew, 14 due to PD. Conclusions: This interim analysis indicates that treatment with Herceptin plus chemotherapy beyond PD is active (ORR 29%) and well tolerated, and provides further evidence that re-treatment with H is a promising therapeutic option. Pt accrual is ongoing and updated results will be presented. No significant financial relationships to disclose.
Combined deletion of Xrcc4 and Trp53 in mouse germinal center B cells leads to novel B cell lymphomas with clonal heterogeneity
Authors: Zhangguo Chen, Mihret T. Elos, Sawanee S. Viboolsittiseri, Katherine Gowan, Sonia M. Leach, Michael Rice, Maxwell D. Eder, Kenneth Jones, Jing H. Wang
Journal: Journal of Hematology & Oncology (2016)

Activated B lymphocytes harbor programmed DNA double-strand breaks (DSBs) initiated by activation-induced deaminase (AID) and repaired by non-homologous end-joining (NHEJ). While it has been proposed that these DSBs during secondary antibody gene diversification are the primary source of chromosomal translocations in germinal center (GC)-derived B cell lymphomas, this point has not been directly addressed due to the lack of proper mouse models. In the current study, we establish a unique mouse model by specifically deleting a NHEJ gene, Xrcc4, and a cell cycle checkpoint gene, Trp53, in GC B cells, which results in the spontaneous development of B cell lymphomas that possess features of GC B cells. We show that these NHEJ deficient lymphomas harbor translocations frequently targeting immunoglobulin (Ig) loci. Furthermore, we found that Ig translocations were associated with distinct mechanisms, probably caused by AID- or RAG-induced DSBs. Intriguingly, the AID-associated Ig loci translocations target either c-myc or Pvt-1 locus whereas the partners of RAG-associated Ig translocations scattered randomly in the genome. Lastly, these NHEJ deficient lymphomas harbor complicated genomes including segmental translocations and exhibit a high level of ongoing DNA damage and clonal heterogeneity. We propose that combined NHEJ and p53 defects may serve as an underlying mechanism for a high level of genomic complexity and clonal heterogeneity in cancers.
Molecular drivers of the non-T cell-inflamed tumor microenvironment in urothelial bladder cancer.
Authors: Randy F. Sweis, Stefani Spranger, Thomas Gajewski
Journal: Journal of Clinical Oncology (2015)

4511 Background: A T cell-inflamed tumor microenvironment is linked to response to immunotherapies and survival in malignancies including urothelial bladder cancer (UBC). We recently identified tumor-intrinsic β-catenin activation in melanoma as causally related to T cell exclusion. However, molecular mechanisms that prevent T cell infiltration in other cancers are incompletely defined. Using gene expression profiling and exome sequencing, we pursued targetable pathways associated with absence of T cells in UBC. Methods: RNA sequencing and exome somatic mutation data from 267 UBC samples in the cancer genome atlas were downloaded. Unsupervised hierarchical clustering was performed on 16,197 filtered genes. A 725-gene cluster contained 12 genes from a previously described T cell signature and was used to segregate samples. Differential gene expression was detected using ANOVA with a false discovery rate q < 0.01 and fold change > 2.0. Enriched pathways were identified by Ingenuity Pathways Analysis. Somatic variants were converted to VCF format and analyzed according to immune phenotype. Results: Expression of CD8A was positively correlated with inhibitory molecules PDL1, IDO1, FOXP3, TIM3, and LAG3 (all p < 0.0001). Based on a signature of T cell inflammation, 36% of bladder tumors showed a T cell-inflamed phenotype, 33% were non-inflamed, and the remainder intermediate. The non-inflamed group contained 730 over-expressed genes. Pathway analysis revealed the most significantly activated regulators were Wnt/β-catenin and peroxisome proliferator-activated receptor gamma (PPARG) (both p = 0.003). Exome mutation analysis revealed no difference in mutation number per patient for each group (p = 0.80). Genes mutated in two or more samples included 891 occurring only in non-inflamed tumors. FGFR3 was the most common mutation exclusive to non-inflamed tumors (p < 0.0001). Expression of WNT7B, PPARG, and FGFR3 were inversely correlated with CD8A (all p < 0.0001). Conclusions: Bladder tumors are characterized by T cell-inflamed and non-inflamed phenotypes. Mutational burden does not vary between these subsets. Activation of β-catenin, PPARG, and FGFR pathways are strongly correlated with T cell exclusion in UBC.
Skin Lesions in Malignancy
Authors: P. Steve, C. Thieblemont, C. Dumontet, F. Bouafia, P. Arnaud, O. Hequet, Daniel Espinouse, G. Salles, B. Coiffer
Journal: Journal of Clinical Oncology (2001)

Article Tools DIAGNOSIS IN ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2001.19.7.2100 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11283146 Skin Lesions in Malignancy Case 3. Yellow Nail Syndrome in Non-Hodgkin's Lymphoma P. StevexP. SteveSearch for articles by this author , C. ThieblemontxC. ThieblemontSearch for articles by this author , C. DumontetxC. DumontetSearch for articles by this author , F. BouafiaxF. BouafiaSearch for articles by this author , P. ArnaudxP. ArnaudSearch for articles by this author , O. HequetxO. HequetSearch for articles by this author , Daniel EspinousexDaniel EspinouseSearch for articles by this author , G. SallesxG. SallesSearch for articles by this author , B. CoifferxB. CoifferSearch for articles by this author Show More Centre Hospitalier Lyon Sud, Pierre-Benite, France, Copyright © 2001 American Society of Clinical Oncology https://doi.org/10.1200/JCO.2001.19.7.2100 First Page Full Text PDF Figures and Tables © 2001 by American Society of Clinical Oncology
Asthma phenotypes and IgE responses
Authors: Antoine Froidure, Jonathan Mouthuy, Stephen R. Durham, Pascal Chanez, Yves Sibille, Charles Pilette
Journal: European Respiratory Journal (2015)

The discovery of IgE represented a major breakthrough in allergy and asthma research, whereas the clinical interest given to IgE in asthma has been blurred until the arrival of anti-IgE biotherapy. Novel facets of the complex link between IgE and asthma have been highlighted by the effect of this treatment and by basic research. In parallel, asthma phenotyping recently evolved to the concept of endotypes, relying on identified/suspected pathobiological mechanisms to phenotype patients, but has not yet clearly positioned IgE among biomarkers of asthma. In this review, we first summarise recent knowledge about the regulation of IgE production and its main receptor, FcεRI. In addition to allergens acting as classical IgE inducers, viral infections as well as air pollution may trigger the IgE pathway, notably resetting the threshold of IgE sensitivity by regulating FcεRI expression. We then analyse the place of IgE in different asthma endo/phenotypes and discuss the potential interest of IgE among biomarkers in asthma.
Olaparib plus paclitaxel plus carboplatin (P/C) followed by olaparib maintenance treatment in patients (pts) with platinum-sensitive recurrent serous ovarian cancer (PSR SOC): A randomized, open-label phase II study.
Authors: Amit M. Oza, David Cibula, Ana Oaknin, Christopher John Poole, Ron H.J. Mathijssen, Gabe S. Sonke, Nicoletta Colombo, Jirí Špacek, Peter Vuylsteke, Hal W. Hirte, Sven Mahner, Marie Plante, Barbara Schmalfeldt, Helen Mackay, Jacqui Rowbottom, Ilian Tchakov, Michael Friedlander
Journal: Journal of Clinical Oncology (2012)

5001 Background: The oral PARP inhibitor olaparib has shown antitumor activity in pts with SOC. Our multicenter study compared the efficacy of (Arm A) olaparib capsules plus P/C for 6 cycles then maintenance olaparib monotherapy vs (Arm B) P/C alone for 6 cycles and no further therapy in pts with PSR SOC (NCT01081951). Methods: Pts received 6 x 21-day(d) cycles of olaparib (200 mg bid, d1–10/21) + P (175 mg/m 2 iv, d1) + C (AUC4 iv, d1), then olaparib monotherapy as maintenance (400 mg bid, continuous) (Arm A), or 6 x 21d cycles of P (175 mg/m 2 iv, d1) + C (AUC6 iv, d1) then no further therapy (Arm B), until progression. Randomization (1:1) was stratified by number of platinum treatments and platinum-free interval. Primary endpoint: progression-free survival (PFS) by central review (RECIST 1.1). Secondary endpoints: overall survival (OS), objective response rate (ORR), safety. Archival tissue was collected where available for analysis of biomarker correlation. Results: Of 162 pts randomized (n=81 per arm), 156 received treatment (Arm A, n=81; Arm B, n=75) and 121 began the maintenance/no further therapy phase (Arm A, n=66; Arm B, n=55). Olaparib + P/C (AUC4) followed by maintenance olaparib showed a significant improvement in PFS vs P/C (AUC6) alone (HR = 0.51, 95% CI 0.34, 0.77; P=0.0012; median = 12.2 vs 9.6 months). OS data are immature (total events: 14%). ORR was similar for Arm A and Arm B (64 vs 58%). Most common AEs during the combination phase were alopecia (74 vs 59%), nausea (69 vs 57%) and fatigue (64 vs 57%) for Arm A vs Arm B, respectively. Pts with grade ≥3 AEs (65 vs 57%), serious AEs (SAEs: 15 vs 21%) and AEs leading to treatment discontinuation (19 vs 16%) were similar for Arm A vs Arm B. Most common AEs during maintenance/no further therapy were nausea (50 vs 6%) and vomiting (29 vs 7%). 29 vs 16% of pts had grade ≥3 AEs, 9 vs 7% had SAEs and 8% vs N/A discontinued due to AEs in the olaparib vs no treatment arms, respectively. There were no fatal AEs. Conclusions: In pts with PSR SOC, olaparib plus P/C (AUC4) followed by olaparib 400 mg bid monotherapy maintenance treatment resulted in a significant improvement in PFS vs P/C (AUC6) alone.