tbuckley/cabot-search huggingface dataset:
Impact of allogeneic hematopoietic stem cell transplant (HSCT) on patients harboring the spliceosome mutation <i>SRSF2</i>.
Authors: Betty Ky Hamilton, Ali Tabarroki, Paul Elson, Edy Hasrouni, Valeria Visconte, Shawnda Tench, Matt E. Kalaycio, Mikkael A. Sekeres, Ronald M. Sobecks, Hien Kim Duong, Brian Thomas Hill, Brian James Bolwell, Edward Alan Copelan, Ramon Velasquez Tiu
Journal: Journal of Clinical Oncology (2013)

7008 Background: Molecular predictors of outcome are increasingly important in determining optimal therapy for myeloid neoplasms. Mutations (mut) in spliceosome genes U2AF1 and SRSF2 predict poor outcome in MDS and related diseases. The purpose of this study was to investigate the role of HCT on the prognostic impact of U2AF1 and SRSF2 in myeloid malignancies. Methods: 123 patients (pts) with MDS (33%), AML (51%), MPN (10%), and MDS/MPN (5%) receiving an allogeneic HCT from 2003-2012 for whom genomic DNA was available from a time when the disease was active, were evaluated for mut in U2AF1 and SRSF2 by direct sequencing. Data were analyzed using competing risks methods (relapse and non-relapse mortality, NRM), proportional hazards (overall survival, OS) and logistic regression models (GVHD). Results: Median time of follow up was 38 months (range 1.5-108). Median age at HCT was 51 yrs (range 18-71). 53 (43%) pts were in remission and 70 (57%) had active disease prior to HCT. 20 (16%) pts had low, 48 (39%) intermediate and 32 (26%) high risk cytogenetics respective to their disease, (per CALGB criteria for AML, IPSS-MF for MPN and IPSS-R for MDS), with missing data on 23 (19%) pts. 89 (72%) had myeloablative transplants, and 34 (28%) received reduced intensity regimens. 54 (44%) had related, 52 (42%) unrelated and 17 (14%) cord blood donors. SRSF2 mut were detected in 13 (11%) pts and U2AF1 in 2 (2%) pts. Due to the low incidence of U2AF1 mut in our cohort, further analysis was focused on SRSF2. There were no significant differences in baseline characteristics between mut and wild-type (wt) pts except SRSF2 mut tended to occur in older AML pts (median age 64 vs 50 yrs, p=0.0004). SRSF2 mut and wt had similar OS (p=0.95), relapse (p=0.28), NRM (p=0.45) and rates of acute (p=0.41) and chronic (p=0.67) GVHD. Results were similar, adjusting for factors such as age, disease type, cytogenetics, comorbidity, transplant type and stem cell source. Conclusions: SRSF2 has previously been associated with dismal outcomes in MDS pts, with 5 yr-OS of &lt;20%. In this cohort of transplanted pts, SRSF2 mut had similar outcomes to wt, suggesting HSCT may compensate for the adverse impact of SRSF2.
Safety and efficacy of TNFerade in unresectable, locally advanced pancreatic cancer (LAPC): Results of the first three cohorts of a dose-escalating study
Authors: N. Senzer, T. Chung, J. R. Hecht, J. Neumuniatis, M. Javle, T. Reid, J. Macko, M. Posner, K. J. Chang, N. Hanna
Journal: Journal of Clinical Oncology (2004)

3038 Background: TNFerade is a replication-deficient adenovector containing the TNF-α gene regulated by a radiation-inducible promoter Egr-1. This dose-escalating study evaluated the safety and early efficacy of TNFerade + chemoradiation in patients with locally advanced, unresectable pancreatic cancer (LAPC). Methods: A standard dose-escalating design with three dosing levels was used. Five-week treatment consisted of weekly intratumoral injections of 2 ml TNFerade, continuous infusion 5-FU and 50.4 Gy radiation. TNFerade was administered via either percutaneous transabdominal approach or endoscopic ultrasound. The route of administration was based on site preference. Endpoints: Safety, radiographic tumor response. A standardized imaging protocol with all studies assessed by an independent core lab. Results: 37 patients were enrolled. Baseline characteristics for the 4x109 pu (n=10), 4x1010 pu (n=20), and 4x1011 pu (n=7) groups, respectively: mean tumor size (cm2) = 23, 16, 19; and mean CA19–9 (pg/mL) =5,717, 1,374, 3,462. One dose limiting toxicity (hypotension, grade 3) occurred in a PTA patient at 4x1010 pu, who was subsequently able to resume treatment; all other adverse events potentially related to TNFerade were grade 1–2, and were most commonly fever (27%), fatigue (19%) and rigors (19%). The 4x1011 pu dose was associated with 100% locoregional control of treated tumors, greater survival without progression, and a greater proportion of patients with stable or decreasing CA19–9, as compared to the other doses at 3 months post treatment (table). Four of 6 patients that were surgically explored underwent resection, one was a complete pathologic response. Conclusions: TNFerade combined with chemotherapy shows promise in treatment of LAPC. Increased doses beyond 4 x 1011 may be feasible. Randomized studies are warranted. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration GenVec GenVec GenVec GenVec
Gardasil: A false sense of immunity?
Authors: M. Boen, D. DeLeon, C. L. Bennett, A. T. Samaras, J. M. Mckoy
Journal: Journal of Clinical Oncology (2010)

e13023 Background: Gardasil, a quadrivalent vaccine for human papilloma virus (HPV), is recommended to women aged 9 to 26 to prevent cervical cancer. Over 26 million doses of Gardasil have been administered since its approval by the FDA in June 2006. The vaccine, which protects women from infection by four types of HPV, has been implicated in Guillain-Barre Syndrome (GBS), a rare paralytic disorder. Methods: We conducted a search of the Vaccine Adverse Event Reporting System (VAERS). Our analysis included reports from June 2006 and Aug 2009 of women ages 9 to 26 who had received Gardasil and no other vaccines (concurrent or recent) and presented with either confirmed or suspected GBS. Results: We found 42 incidences of Gardasil-related GBS (reported mainly by medical personnel), including pts receiving Gardasil alone (N=27; age 10-26 yrs; mean 16.67 for the 18 subjects for which age was reported). Of the 27 incidences, 33% were complete reports, with 10 reports after the first dose and 4 reports after the third dose. Initial symptoms averaged 30 days post-Gardasil injection for these 11 cases. GBS was confirmed as final diagnosis in 20 reports, and was highly suspected in 7 reports. Conclusions: A majority of the VAERS data was incomplete: missing pt age, Gardasil dose, or date of GBS onset. Serious adverse events such as GBS require improved efforts at obtaining complete information. Prospective studies are needed to evaluate the link between GBS and Gardasil. Date reported to VAERS (N=none) Age Gardasil dose Onset of symptoms (days) Confirmed diagnosis (Y=yes, S=suspected) 9/7/06 16 1 14 Y 9/14/06 15 1 50 Y 12/3/06 13 N/A 9 Y 4/6/07 N/A N/A N/A Y 5/3/07 18 1 1 Y 5/14/07 13 N/A N/A Y 8/2/07 N/A N/A N/A S 10/12/07 19 1 N/A Y 11/26/07 14 1 1 Y 10/15/07 N/A N/A N/A S 10/15/07 23 N/A N/A Y 1/16/08 18 N/A 15 Y 3/17/08 N/A 1 N/A Y 3/17/08 19 1 150 Y 5/19/08 14 N/A N/A Y 6/19/08 N/A 3 N/A S 6/19/08 N/A 3 N/A S 8/18/08 N/A N/A N/A S 9/17/08 11 N/A N/A S 9/17/08 15 1 75 Y 12/9/08 11 N/A N/A Y 12/22/08 24 3 1 Y 2/10/09 10 1 13 Y 2/18/09 26 1 1 Y 3/16/09 N/A N/A N/A S 4/8/09 N/A N/A N/A Y 4/17/09 21 3 N/A Y No significant financial relationships to disclose.
The impact of physician specialty on quality of melanoma care.
Authors: J. N. Cormier, Y. T. Shih, Y. Xu, I. Pan, R. L. Askew, M. I. Ross, J. E. Gershenwald, J. E. Lee, R. Royal, Y. Xing
Journal: Journal of Clinical Oncology (2010)

8563 Background: This study aimed to investigate associations between physician specialty and nonadherence to National Comprehensive Cancer Network (NCCN) stage-specific treatment guidelines in a population-based cohort of elderly melanoma patients. Methods: Patients with stage I-III melanoma were identified from the SEER-Medicare database (age ≥ 65, 2004- 2005). Stage-specific multivariate analyses were performed to assess physician specialty and nonadherence to NCCN guidelines while adjusting for demographics, socioeconomic status, comorbidity, and histology. Results: A total of 3,287 patients were identified with stage IA (47%), stage IB (26%), stage II (21%), and stage III (6%) melanoma. Initial melanoma diagnosis was made by dermatologists (DERM: 56%), general surgeons (SURG: 18%), primary care physicians (PCP: 10%), plastic surgeons (PLS: 8%), surgical oncologists (SURGONC: 2%), and other specialties (6%). Definitive treatment was subsequently rendered by SURG (32%), DERM (28%), PLS (10%), SURGONC (5%), other surgical specialties (OSS: 4%), PCP (3%), and unknown provider types (18%). Of the 13% of patients receiving suboptimal/nonadherent treatment, 91% were stage IB or II largely due to the omission of sentinel lymph node mapping. In patients with stage IB and II melanoma, multivariate analyses revealed that provider of definitive treatment, patient age, marital status, geographic area, and histology were significant predictors of nonadherence. The likelihood of receiving nonadherent treatment varied according to the specialty of the provider: DERM (odds ratio [OR] = 17.1, 95% confidence interval [CI]: 8.4-34.7), PCP (OR = 3.5 [1.5-8.5]), SURG (OR = 1.3 [0.7-2.5]), PLS (OR = 2.2 [1.1-4.6]), and OSS (OR = 2.5 [1.1-5.5]) when compared to SURGONC. Conclusions: For elderly patients with stage IB and II melanoma, provider specialty is a significant predictor of guideline based treatment. Melanoma patients treated by SURG and SURGONC are more likely to receive treatment according to NCCN guidelines. The benefits of sentinel lymph node mapping should be promoted among all health care specialties related to melanoma care. No significant financial relationships to disclose.
The usefulness of serum tumor markers in monitoring of response to systemic chemotherapy in patients with gastric cancer: Ca 72-4 and CEA.
Authors: B. Han, D. Y. Zang, H. J. Kim, H. Y. Kim
Journal: Journal of Clinical Oncology (2011)

e14580 Background: Evaluation of response after chemotherapy in patients with gastric carcinoma is sometimes difficult. The authors investigated whether changes in the serum levels of two tumor markers – CA 72-4 and CEA can be used to predict the clinical outcome after chemotherapy. Methods: Eighty patients with advanced or recurrent gastric carcinoma were treated with DOS (docetaxel + oxaliplatin + TS-1) or DS (docetaxel + TS-1). The serum levels of CEA and CA 72-4 were measured prior to and after chemotherapy. Responders were defined as those in whom abnormal serum levels of tumor markers decreased to at least 50% of the pretreatment levels. We assessed treatment responses by the computed tomography and serum tumor marker levels, and compared the survival rates of two assessment modalities. Results: The response assessed by serum CA 72-4 level was significantly related with the response by imaging study, but that by serum CEA level was not. On CT assessment the median durations of survival for 28 responders and 38 non-responders were 706.3 days and 332.5 days, respectively. And on serum CA 72-4 assessment, they were 435.9 days in 28 responders and 276.8 days in 13 non-responders with statistically significant difference, but there was no significant difference of survival on serum CEA assessment . Conclusions: The serial measurement of the serum CA 72-4 level may be a useful tool of monitoring response and predicting the prognosis after chemotherapy for patients with gastric cancer of increased pretreatment level.
Differences in auditory timing between human and nonhuman primates
Authors: Henkjan Honing, Hugo Merchant
Journal: Behavioral and Brain Sciences (2014)

Abstract The gradual audiomotor evolution hypothesis is proposed as an alternative interpretation to the auditory timing mechanisms discussed in Ackermann et al.'s article. This hypothesis accommodates the fact that the performance of nonhuman primates is comparable to humans in single-interval tasks (such as interval reproduction, categorization, and interception), but shows differences in multiple-interval tasks (such as entrainment, synchronization, and continuation).
Sequential therapy with carboplatin (C) followed by paclitaxel (P) as first-line chemotherapy in 105 patients with advanced ovarian cancer (AOC): Results of a multicenter phase II study of the Northeastern German Society of Gynecological Oncology
Authors: G. Oskay-Oezcelik, A. Mustea, H. Sommer, E. Keil, M. Höckel, J. Pfisterer, O. Camara, H. J. Hindenburg, W. Lichetenegger, J. Sehouli
Journal: Journal of Clinical Oncology (2007)

5533 Background: For the adjuvant setting of AOC after primary radical surgery the combination of paclitaxel and platinum in a three weeks schedule has emerged as the current standard. Exposition duration of the drug is important for cell death. In animal model additional anti-angionetic effects of low dose paclitaxel infusion was observed. A sequential schedule of these agents can potentially yield in an improved therapeutic index. Methods: In this multicenter-phase II trial after primary radical surgery 4 cycles of Carboplatin at a dose of AUC 5 (d1/q21d) followed by 12 cycles weekly paclitaxel at a dose of 80mg/m 2 (d1/q7d) was applied. All patients with haemoglobin levels &lt; 12mg/dl get primary erythropoietin. No primary use of other growth factors were allowed. Eligibility criteria were: AOC (FIGO IIb-IV), ECOG performance status 0–2, normal organ functions. Results: Between 07/2003 and 05/2005, 105 patients from 27 institutions were enrolled. The median age was 60 years (23–80). FIGO-stages were: II: 11.4%, III: 67.6%, IV: 14.2%. 1,441 cycles were analyzed and in median 16 courses were applied (range 0–16). The incidence of non-hematological toxicities was very low. 25 % of all patients experienced alopecia (grade 1–2). Neurotoxicity and nausea/vomiting (grade III-IV) occurred in no patients. Grade 3–4 hematological toxicity (% of all pts) included: thrombocytopenia (16 %), anemia (3%), leucopenia (22%), neutropenic fever (0%). 96% received erythropoietin. Thromboembolic events (5%) were not increased in patients who received erythropoietin. After a median follow-up interval of 10 months (range: 1–27 months) 20 patients died, the median overall survival is already not reached. The progression free survival is 19 months (range:10–23 months). Conclusions: These results suggest that this sequential regimen using weekly paclitaxel represents an efficacious and well-tolerated regimen. A randomized study comparing this new schedule with the conventional 3-week protocol is warranted. (Supported by Bristol Myers Squibb Germany and Ortho Biotech Germany) No significant financial relationships to disclose.
A phase II multicenter study on the histone deacetylase (HDAC) inhibitor MS-275, comparing two dosage schedules in metastatic melanoma
Authors: A. Hauschild, U. Trefzer, C. Garbe, K. Kaehler, S. Ugurel, F. Kiecker, T. Eigentler, H. Krissel, D. Schadendorf
Journal: Journal of Clinical Oncology (2006)

8044 Background: The acetylation of histones is a key component of gene regulation, which plays an important role in tumor initiation and progression. MS-275, an inhibitor of the benzamide series, is a synthetic orally available inhibitor of HDACs which showed anti-tumor activity in 3 phase 1 trials. Methods: A phase II, multicenter, randomized, parallel-group study of oral MS-275 evaluated the efficacy and toxicity in patients with non-resectable metastatic melanoma. Patients should have received at least one, but not more than two previous systemic therapies (chemo- and/or immunotherapy) for stage IV melanoma. Patients were stratified to receive either 3 mg MS-275 biweekly (days 1+15 of a 4-week cycle) or 7 mg MS-275 weekly (days 1+8+15 of a 4-week cycle) until disease progression or unacceptable toxicity. Study endpoints were the assessment of tumor response and toxicity. Results: A total of 28 patients have been randomized equally to the two dosing groups. Patients were classified as belonging to AJCC stage IVa (n=0), IVb (n=9; 32%), and IVc (n=19; 68%). In general, MS-275 was very well tolerated. No treatment-related SAEs have been observed. Most frequently reported side effects were nausea (CTC Grade 1+2, 32%) hypophosphatemia (CTC Grade 1–3, 29%), and diarrhea (CTC Grade 1+2, 18%). Stable diseases lasting from 8 wks to more than 48 wks have been observed in 4 pts (29%) in the 3 mg and 3 pts (21%) in the 7 mg dose group. Stabilizations occurred in these metastatic localizations: skin, peripheral and visceral lymph nodes, lung and bone, respectively. However, objective tumor responses were not observed. Conclusions: The results suggest that MS-275 is well tolerated and shows long-lasting tumor stabilizations in patients with pre-treated metastatic melanoma. The failure of objective tumor responses in the single-agent treatment with MS-275 warrants further evaluation also in combinational settings. [Table: see text]
Cutaneous manifestations of Erdheim-Chester disease (ECD): Clinical, pathological, and molecular features in a monocentric series of 40 patients
Authors: François Chasset, Stéphane Barete, Frédéric Charlotte, Fleur Cohen-Aubart, Laurent Arnaud, François Le Pelletier, Jean-François Emile, Camille Francès, Zahir Amoura, Julien Haroche
Journal: Journal of the American Academy of Dermatology (2016)
Large B-cell transformation in nodular lymphocyte-predominant Hodgkin lymphoma: 40-year experience from a single institution
Authors: Saad Sirop Kenderian, Thomas M. Habermann, William R. Macon, Kay M. Ristow, Stephen M. Ansell, Joseph P. Colgan, Patrick B. Johnston, David J. Inwards, Svetomir N. Markovic, Ivana N. Micallef, Carrie A. Thompson, Luis F. Porrata, James A. Martenson, Thomas E. Witzig, Grzegorz S. Nowakowski
Journal: Blood (2016)
Influence of Dietary Fat on the Growth of Mammary Ducts in BALB/c Mice&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: M J Miyamoto-Tiaven, L A Hillyard, S Abraham
Journal: JNCI Journal of the National Cancer Institute (1981)

Essential fatty acid (EFA)-deficient diets, when fed to weanling BALB/c mice, retarded the rate of mammary ductal growth. Ductal growth was also markedly retarded in pups fed only EFA-deficient foods from birth (milk from mothers fed EFA-deficient diets for the first 3 wk until weaning, then an EFA-deficient diet for an additional 5 wk). The ability of dissociated mammary epithelial cells to form outgrowths was reduced, and the growth rate of those outgrowths that did form was retarded when such cells were injected into gland-free mammary fat pads in syngeneic hosts fed EFA-deficient diets. Indomethacin, an inhibitor of prostaglandin synthesis, when added at a level of 0.003% to a 15% corn oil-containing diet, resulted in the retardation of ductal growth to about the same extent as did a 15% hydrogenated cottonseed oil-containing diet; however, unlike that associated with EFA-deficient diets, the retardation associated with indomethacin was temporary. EFA appears to be required for normal ductal growth in BALB/c mice, and prostaglandins may be involved in the growth-regulating process.
Abstract P248: Oxidized Phospholipids and Risk of Peripheral Arterial Disease in Men
Authors: Monica L Bertoia, Jennifer K Pai, Sotirios Tsimikas, Michel M Joosten, Murray A Mittleman, Eric B Rimm, Kenneth J Mukamal
Journal: Circulation (2012)

Background: Peripheral arterial disease (PAD) is highly prevalent, found in 25% of adults ≥70 years, but its risk factors are less well studied than coronary and carotid atherosclerosis. Proinflammatory oxidized phospholipids (OxPL) are a novel cardiovascular risk factor produced by oxidative stress and are preferentially bound and transported by lipoprotein (a) [Lp(a)] in plasma. Previous studies have shown an association between OxPL on apolipoprotein B-100 (OxPL/apoB) and carotid and femoral atherosclerosis. However, no previous studies have specifically examined the prospective association between OxPL/apoB and risk of PAD in a population-based cohort. Methods: We conducted a nested case-control study among men free of cardiovascular disease within the Health Professionals Follow-up Study (1994–2008) including 143 men with PAD and 429 controls matched on age, month of blood draw, and smoking. OxPL/apoB and Lp(a) were measured in stored baseline plasma. We identified cases of clinically significant PAD based on at least one of the following: (1) amputation, bypass, or other revascularization procedure for occlusive arterial disease, (2) angiogram/ultrasound confirming at least 50% stenosis of at least one artery with congruent symptoms in the ipsilateral limb, (3) ankle-brachial index &lt; 0.9, or (4) physician's diagnosis. We used conditional logistic regression to estimate odds ratios (OR) for PAD according to level of OxPL/apoB. Results: The OR for PAD was 1.24 (95% CI 1.05–1.46) for each 1-standard deviation (SD) increase in OxPL/apoB after adjusting for matching factors. Additional adjustment for family history of MI, triglycerides, HDL-C, LDL-C, C-reactive protein, hemoglobin A1c, pack-years of smoking, physical activity, hypertension, diabetes, hypercholesterolemia, body-mass index, and aspirin use did not change this estimate: 1.24 (95% CI 1.00–1.54). OxPL/apoB was not correlated with any conventional risk factors: Spearman correlation coefficients ranged from 0.0 to 0.13. We observed no interaction with age or LDL-C. Similarly, the OR for PAD was 1.25 (95% CI 0.95–1.63) for each 1- SD increase in ln[Lp(a)] after adjusting for all of the above covariates. Conclusion: OxPL/apoB is positively associated with risk of PAD in men with no appreciable attenuation after adjustment for conventional risk factors.
Application of the Cotswolds Criteria for the assessment of disease response in patients treated for Hodgkin's disease.
Authors: D L Cooper, E Salloum
Journal: Journal of Clinical Oncology (1995)

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.1995.13.5.1283 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 7738635 Application of the Cotswolds Criteria for the assessment of disease response in patients treated for Hodgkin's disease. D L CooperxD L CooperSearch for articles by this author , E SalloumxE SalloumSearch for articles by this author https://doi.org/10.1200/JCO.1995.13.5.1283 PDF "Application of the Cotswolds Criteria for the assessment of disease response in patients treated for Hodgkin's disease.." Journal of Clinical Oncology, 13(5), pp. 1283–1284© 1995 by American Society of Clinical Oncology
22q11.2 deletion syndrome
Authors: Donna M. McDonald-McGinn, Kathleen E. Sullivan, Bruno Marino, Nicole Philip, Ann Swillen, Jacob A. S. Vorstman, Elaine H. Zackai, Beverly S. Emanuel, Joris R. Vermeesch, Bernice E. Morrow, Peter J. Scambler, Anne S. Bassett
Journal: Nature Reviews Disease Primers (2015)