tbuckley/cabot-search huggingface dataset:
Vitamin D levels and survival in colorectal cancer (CRC).
Authors: K. M. Wesa, G. Jacobs, D. Woo, A. Cronin, N. H. Segal, M. Coleton, L. Saltz, B. R. Cassileth
Journal: Journal of Clinical Oncology (2010)

3615 Background: Higher serum D levels are associated with decreased incidence of CRC. However, the prevalence of vit D deficiency at CRC diagnosis is not documented; most published studies measured vit D levels years prior to CRC diagnosis. We therefore conducted a retrospective study of baseline vit D levels in newly diagnosed stage IV CRC patients(pts) to determine whether serum vit D levels at diagnosis predict survival. Vit D levels of 40-60 ng/mL are considered optimal for bone health, and recent data suggest that levels near 40 ng/mL may increase survival in pts with breast cancer. The optimal level of vit D for CRC pts is not known. Methods: MSKCC maintains an extensive bank of frozen sera. For this study, stored sera from CEA measurements obtained between February 2005 and March 2006 were screened for study inclusion. The first 250 pts with CEA drawn ± 30 days of stage IV CRC diagnosis and for whom survival data were available were included in this analysis. Vit D levels were determined on all samples. Information regarding metastatic sites, chemotherapy received, body mass index and demographic data were obtained from patient charts. Results: Of the 250 pts, 153 had died as of April 2009. On univariate analysis vit D was significantly associated with survival when analyzed as continuous variable (p = 0.036). Patients with vit D deficiency (< 30 ng/mL) had survival outcomes approximately 1.5 times worse than those with normal levels. The median vit D level for all 250 patients was 21.5 ng/mL; 207 patients (83%) were vit D deficient (defined as < 30 ng/mL). Only 7 patients had serum vit D levels > 40 ng/mL. Vit D levels were not significantly associated with age, gender, BMI or race. Conclusions: A majority of patients with newly diagnosed stage IV CRC are vit D deficient at the time of diagnosis. For patients with stage IV CRC, higher vit D levels at diagnosis are associated with better overall survival. Whether aggressive vit D repletion would improve outcome in vit D deficient CRC patients remains unknown. Clinical trials addressing this question are warranted. We are about to initiate such a study. No significant financial relationships to disclose.
EMILIA: A phase III, randomized, multicenter study of trastuzumab-DM1 (T-DM1) compared with lapatinib (L) plus capecitabine (X) in patients with HER2-positive locally advanced or metastatic breast cancer (MBC) and previously treated with a trastuzumab-based regimen.
Authors: S. Verma, V. Dieras, L. Gianni, D. Miles, M. Welslau, M. D. Pegram, J. Baselga, E. Guardino, L. Fang, C. M. Linehan, K. L. Blackwell
Journal: Journal of Clinical Oncology (2011)

TPS116 Background: Despite advances in the treatment of HER2 overexpressed MBC, nearly all patients develop progressive disease and innovative well-tolerated HER2-directed therapies are needed. T-DM1 is a unique antibody-drug conjugate that combines the antitumor activities of trastuzumab with intracellular delivery of the highly potent cytotoxic agent, DM1 (derivative of maytansine). In two phase II studies (TDM4258g; TDM4374g) single-agent T-DM1 3.6 mg/kg IV q3w showed substantial efficacy in patients with HER2-positive MBC who had received prior chemotherapy and ≥1 HER2-directed therapy for MBC (Burris JCO 2010; Krop ESMO 2010) providing strong rationale to assess T-DM1 in the phase III setting. In addition, comparable response rates and improved safety relative to trastuzumab and docetaxel were reported in a randomized phase II study of T-DM1 in first-line MBC (Perez ESMO 2010). Methods: EMILIA (TDM4370g, registry #NCT00829166) is an international, phase III study evaluating the safety and efficacy of T-DM1 compared with L plus X in patients with HER2-positive locally-advanced or MBC following prior trastuzumab-based and taxane-containing therapy. Patients are randomized 1:1 to T-DM1 3.6 mg/kg IV q3w, or L 1250 mg/day (Days 1 to 21) plus X 2000 mg/m2/day (Days 1 to 14) q3w, until disease progression or unmanageable toxicity. Central confirmation of HER2 status (IHC 3+ or FISH-positive) is required for enrollment. The co-primary endpoints are progression-free survival (PFS) by independent review facility and overall survival (OS). The trial has 80% power to detect a hazard ratio (HR) of 0.8 for OS (corresponding to a 4.3 month improvement in median OS) and 90% power to detect an HR of 0.75 for PFS (corresponding to a 2.1 month improvement in median PFS). Secondary endpoints include objective response rate, duration of response, and patient-reported QOL and toxicity outcomes. Enrollment began in February 2009. As of January 31, 2011, 582 of a projected 980 patients were enrolled at 203 sites in 22 countries. Results from this first phase III study of T-DM1 are eagerly awaited.
Intra-arterial chemotherapy using docetaxel and cisplatin + RT with radiomodification in combined treatment of patients with locally advanced SCC of the oral cavity
Authors: D. G. Adilbay, G. B. Adilbayev, D. N. Ahmetov, G. Z. Kydirbaeva
Journal: Journal of Clinical Oncology (2007)

16543 Background: Our previous studies of using intra-arterial induction chemotherapy in locally advanced SCCHN have showed a low level of toxicities, we haven't experienced any III grade toxicity, there was only 18,8% of grade I and II leucopenia. So this method allows intensify chemoradiotherapy. The addition of radiomodificant agent to standard RT increases its response rate. In our study we have used radiomodification with Arglabin, which showed a good results in different studies performed in Kazakhstan and Russia. To elevate the effect of intra-arterial induction chemotherapy + RT we have studied intensified preoperative chemoradiotherapy. Methods: 15 patients with previously untreated oral cancer (T 3–4 N 0–2 M 0 ) received chemoradiotherapy by followed scheme: 1st day intra-arterial chemotherapy by catheterization of the feeding arteries of tumor through the superficial temporal artery: docetaxel - 80 mg/m 2 , cysplatin - 100 mg/m 2 , from 2 nd to 21 st day RT with intra-arterial radiomodification arglabin-70 mg/m 2 (28 Gy by 4 Gy - 3 times week), 22 nd day second course of intra-arterial chemotherapy and after RT (total dose- 60 Gy by 2 Gy 5 times week), depending on the results surgical treatment in necessary volumes. Results: The clinical effects were CR in 12 (80.0%) patients, PR in 3 (20,0%) patients. The following main toxicities of chemoradiotherapy were observed: only 1 case of grade III neutropenia, Non-hemathologic toxicity: 13% grade III mucosal events, alopecia 66,7%. All results have been confirmed by cytomorphology. All patients have being followed up. Conclusions: Using intra-arterial path of delivery allows intensify chemoradiotherapy. And adding radiomodification increases the results of combined treatment. Therefore this method needs further investigations. No significant financial relationships to disclose.
Ki-67 is a Luminal B marker that identifies a high-risk subgroup in hormone receptor positive and node negative breast cancer
Authors: M. Cheang, D. Voduc, S. Leung, D. Turbin, P. S. Bernard, M. Ellis, E. Mardis, C. M. Perou, T. O. Nielsen
Journal: Journal of Clinical Oncology (2007)

10521 Background: Gene expression profiling studies have revealed prognostically significant intrinsic breast cancer subtypes, designated Luminal A, Luminal B, Basal and Her2. Expression of ER and associated genes characterizes the luminal breast cancers. The Lum B subgroup is associated with poor outcome, but we lack immunohistochemical (IHC) markers to distinguish Lum A and Lum B subgroups. MKI67 is one gene known to be highly expressed in Lum B tumors, encoding the Ki-67 protein, a robust marker of cell proliferation. In this study, we perform IHC analysis of Ki-67 in a large breast cancer tissue microarray. Methods: Our patient cohort consists of 2222 consecutive cases of invasive breast cancer referred to the BC Cancer Agency from 1986 to 1992. Archival paraffin tissue blocks were used to construct a tissue microarray that was then stained for Ki-67 using a commercially available mouse monoclonal antibody. Ki-67 staining was scored quantitatively by automated image analysis and a tumor was positive if the percent positive nuclei was &gt;30%’ Results: Of the 2,222 patients, there are 1,437 Luminal tumors as defined by IHC (ER or PR positive). As Her2 positive status is an established marker of poor prognosis, we excluded these tumors from our analysis. Of the remaining tumors, 9% were Ki-67 positive when using a ki-67 cut off of 30% positive nuclei. In survival analysis of patients ER/PR positive and Her2 negative, we found that Ki-67 identifies a population with poor prognosis (10-yr BCSS 60% vs. 80%). In a multivariate Cox regression we found that Ki-67 is independently prognostic. We repeated Cox regression analysis including only node negative patients and again found that Ki-67 is an independent predictor of poor outcome. Conclusions: Ki-67 has prognostic significance on multivariate survival analysis. Hormone receptor positive and node negative status is typically associated with a favorable outcome for breast cancer. However, Ki-67 is able to identify a small, but clinically significant subgroup with a particularly poor outcome. Defining the Luminal B subtype as (ER or PR) positive and (HER2 or Ki-67) positive, results in a subgroup that contains 18% of hormone receptor positive breast cancers with 10-yr BCSS of 61%. No significant financial relationships to disclose.
Abstract 10861: Serum Levels of VEGF-C, but not VEGF-A, are Inversely Correlated with Systolic Dysfunction
Authors: Mitsuru Ishii, Hiromichi Wada, Masaharu Akao, Shuichi Ura, Nobutoyo Masunaga, Takashi Unoki, Mitsuru Abe, Yasuyo Nakashima, Mikihiko Kanasaki, Genta Osakada, Noriko S Asahara, Akira Shimatsu, Koji Hasegawa
Journal: Circulation (2012)

Background:  Vascular endothelial growth factor-A (VEGF-A) plays a pivotal role in cardiac angiogenesis and is required for preventing the transition from compensatory left ventricular hypertrophy (LVH) to heart failure (HF). Vascular endothelial growth factor-C (VEGF-C), a homologue of the VEGF family, plays a key role in lymphangiogenesis. However, the relationship between VEGF-C and HF is unknown.   Methods and Results:  We carried out a cross-sectional study involving 401 outpatients whose New York Heart Association functional classes were stable for at least 3 months. We performed echocardiography and calculated the left ventricular ejection fraction (LVEF) and left ventricular mass index (LVMI). Serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), VEGF-A, and VEGF-C were determined employing specific enzyme-linked immunosorbent assays. Patients were divided into three groups: those with systolic dysfunction (HF+; LVEF   116 in males, >104g/m 2  in females), and those without LVH or systolic dysfunction (Control). There were no significant differences in the body mass index and prevalence of a male gender and dyslipidemia among the three groups. Age was greater and hypertension, diabetes, and chronic kidney disease were more prevalent in HF+ than Control. Levels of NT-pro BNP were significantly higher in HF+ than Control and LVH+. Conversely, those of VEGF-C were significantly lower in HF+ than Control ( P  = 0.005) and LVH+ ( P  = 0.027), whereas those of VEGF-A were similar among the three groups. Multivariate logistic regression analyses, including age, a male gender, hypertension, diabetes, dyslipidemia, current smoking, obesity, chronic kindey disease, NT-proBNP, and either of VEGF-C or VEGF-A, revealed that diabetes (odds ratio [95% CI]: 9.7 [1.97-47.9],  P  = 0.0005), obesity (13.0 [2.7-63.5],  P  = 0.029), NT-proBNP (5.9 [2.8-12.4],  P   P  = 0.029), but not VEGF-A, were independently associated with systolic dysfunction.   Conclusions:  Low serum levels of VEGF-C, but not VEGF-A, were independently associated with systolic dysfunction. VEGF-C signaling might be involved in the pathophysiology of HF in humans.
Preclinical evaluation of the HSP-90 inhibitor 17AAG in Hodgkin’s and non-Hodgkin’s lymphomas: Induction of apoptosis and potentiation of chemotherapy cytotoxicity
Authors: G. V. Georgakis, Y. Li, A. Younes
Journal: Journal of Clinical Oncology (2005)

6570 Background: Heat shock protein (HSP)-90 is an intracellular protein that chaperons several client oncoproteins important for the neoplastic process, making it a promising molecular target for cancer therapy. HSP-90 maintains the conformation, stability, and function of several critical client oncoproteins involved in regulating cell survival, proliferation, and apoptosis. 17-AAG, a small molecule analog of geldanamycin, binds specifically and inhibits HSP-90 function causing degradation of its client oncoproteins that are involved in cell signaling, survival, and proliferation. 17-AAG has demonstrated anti proliferative activity against several solid tumor and leukemia cells in preclinical models. However, the activity of 17-AAG in non-Hodgkin’s lymphoma (NHL) and Hodgkin’s lymphoma (HL) is not known. Methods: The activity of 17-AAG was determined in 9 lymphoma cell lines (Hodgkin Lymphoma, Anaplastic Large Cell Lymphoma, Mantle Cell Lymphoma). Cell viability was determined by the MTS assay, and apoptosis by Annexin-V binding. Molecular changes were determined by western blot. Results: HSP90 was abunndently expressed in all lymphoma cell lines. 17-AAG induced cell death in all cell lines in a time and dose dependent manner. The antiproliferative activity was due to cell cycle arrest in the G0/G1 phase, or in the G2/M phase which was followed by apoptosis. Apoptosis was triggered by activating the intrinsic caspase pathway (by cleaving caspase 9 and PARP), and was partially reversed by the administration of the pan-caspase inhibitor Z-VAD-FMK. Furthermore, 17-AAG decreased the cellular contents of the antiapoptotic proteins (cFLIP, XIAP, Bcl-2), as well as survival and proliferation signaling molecules (AKT, ERK1/2). Moreover, 17-AAG showed synergistic effect when combined with doxorubicin chemotherapy, the proteasome inhibitor bortezomib and the anti-TRAIL death receptors R1 and R2 monoclonal antibodies (HGS-ETR1 and HGS-ETR2). Conclusions: Based on these favorable activities of 17-AAG, we are conducting a phase-II study of 17-AAG in patients with relapsed HL and NHL. No significant financial relationships to disclose.
Anemia Associated With Feline Leukemia Virus Infection in Cats 2
Authors: Lindsay Mackey, William Jarrett, Oswald Jarrett, Helen Laird
Journal: JNCI Journal of the National Cancer Institute (1975)

The types of anemia associated with natural and experimental feline leukemia virus (FeLV) infection in cats were investigated. In one experiment, 10 kittens were inoculated neonatally with Jarrett FeLV-1, an isolate of subgroup A; 6 developed anemia a few weeks later. This anemia was characterized by macrocytosis, normoblastosis, increased erythropoiesis in the bone marrow, and extramedullary hematopoiesis in the spleen. Anemia was transient and nonfatal and occurred before the onset of lympoid malignancy. The same type of anemia was also seen in 9 of 24 kittens inoculated with Jarrett FeLV-9 of subgroups A and B. A different form of anemai occurred in another experiment in which 10 kittens were inoculated with FeLV-C of subgroup C only. All 10 kittens developed a profound aplastic or erythroblastopenic anemia in which the bone marrow became depleted of erythroid tissue; all kittens died within 16 weeks, most as a direct result of anemia. In an experiment in which kittens were inoculated with FeLV-B of subgroup B only, no kitten showed anemia. Cats with naturally acquired, nonleukemic lymphosarcoma were also studied. Of 33 lymphosarcomas in which myelophthisis was excluded as a cause, 54% of the affected cats had anemia, the features of which were consistent with hemolytic origin. When virus could be grown from these lymphosarcomas, it was of subgroup A alone or a combination of A and B. With one exception, anemic cats had low or negative titers to feline oncornavirus-associated cell membrane antigens. Until more isolates have been tested, it is not known if the various hematologic changes reflected differences in the pathogenic effects of the subgroups of the virus or of types of strains within them.
Thirty-Day Postoperative Mortality Risk Estimates and 1-Year Survival in Veterans Health Administration Surgery Patients
Authors: Tracy Smith, Xinli Li, William Nylander, William Gunnar
Journal: JAMA Surgery (2016)

For more than 2 decades, the Veterans Health Administration (VHA) has relied on risk-adjusted, postoperative, 30-day mortality data as a measure of surgical quality of care. Recently, the use of 30-day mortality data has been criticized based on a theory that health care professionals manage patient care to meet the metric and that other outcome metrics are available.To determine whether postoperative mortality data identify a delay in care to meet a 30-day mortality metric and to evaluate whether 30-day mortality risk score groups stratify survival patterns up to 365 days after surgery in surgical procedures assessed by the Veterans Affairs Surgical Quality Improvement Program (VASQIP).Patients undergoing VASQIP-assessed surgical procedures within the VHA from October 1, 2011, to September 30, 2013, were evaluated. Data on 365-day survival follow-up of 212 733 surgical cases using VHA Vital Status and admission records were obtained with 10 947 mortality events. Data analysis was conducted from September 3, 2014, to November 9, 2015.Survival up to 365 days after surgery for the overall cohort divided into 10 equal groups (deciles).There were 10 947 mortality events identified in a cohort of 212 733 surgical patients. The mean probability of death was 1.03% (95% CI, 1.01%-1.04%). Risk estimate groups in the 212 733 surgical cases analyzed showed significantly different postoperative survival, with consistency beyond the time frame for which they were developed. The lowest risk decile had the highest 365-day survival probability (99.74%; 95% CI, 99.66%-99.80%); the highest risk decile had the lowest 365-day survival probability (72.04%; 95% CI, 71.43%-72.64%). The 9 lowest risk deciles had linear survival curves from 0 to 365 postoperative days, with the highest risk decile having early survival risk and becoming more linear after the first 180 days. Survival curves between 25 and 35 days were consistent for all risk deciles and showed no evidence that mortality rates were affected in the immediate period beyond day 30. The setting of mortality varied by postoperative day ranges, with index hospitalization events declining and deaths outside of the hospital increasing up to 365 days.Deciles of 30-day mortality estimates are associated with significantly different survival outcomes at 365 days even after removing patients who died within the first 30 postoperative days. No evidence of delays in patient care and treatment to meet a 30-day metric were identified. These findings reinforce the usefulness of 30-day mortality risk stratification as a surrogate for long-term outcomes.
Minimal residual disease in acute lymphoblastic leukemia detected by immune selection and gene rearrangement analysis.
Authors: M Bregni, S Siena, A Neri, R Bassan, T Barbui, D Delia, G Bonadonna, R Dalla Favera, A M Gianni
Journal: Journal of Clinical Oncology (1989)

We have developed an assay for the detection of malignant residual cells in the bone marrow from patients with B- or T-lineage acute lymphoblastic leukemia (ALL) in clinical remission. This assay involves an immune selection step followed by immunoglobulin or T-cell receptor gene rearrangement analysis and allows the detection of one contaminating tumor cell out of 1,000 normal bone marrow cells. We have examined the bone marrow of 11 patients with adult ALL in remission over a 24-month period. Five patients relapsed in the bone marrow and one in the CNS. The assay allowed the detection of minimal residual disease in four of five patients that subsequently relapsed in the bone marrow, 1.5 to 9 months before the relapse became morphologically and clinically manifest. Residual disease was not found in the bone marrow from patients in continuous remission and from the single patient who relapsed in the CNS. We conclude that the ability of the assay described here to detect minimal residual disease with high specificity can provide information for further understanding of the biology of ALL and hopefully for the clinical management of patients with this disease.
Patterns of disease in localized extranodal lymphomas.
Authors: M K Gospodarowicz, S B Sutcliffe, T C Brown, T Chua, R S Bush
Journal: Journal of Clinical Oncology (1987)

The site of origin of lymphoid tissue is an important determinant of lymphocyte migration patterns. The association of gastrointestinal (GI) and Waldeyer's ring lymphoma and the unique lymphocyte migration pattern of gut-associated lymphoid tissue (GALT) have been previously described. To establish whether predictive clinical patterns of disease occur in localized Non-Hodgkin's lymphoma, survival and relapse patterns for 496 patients with stage I and II non-Hodgkin's lymphoma (NHL) treated with loco-regional irradiation (XRT) alone were examined. We identified 139 patients with GALT lymphoma (defined as arising from primitive gut and including Waldeyers' ring, thyroid, and GI lymphomas) and 87 patients with extranodal non-gut-associated lymphoma (ENL). Survival and relapse data were assessed in multifactorial analysis to correct for previously identified other prognostic variables. GALT lymphomas (GALT-L) have a survival advantage compared with other ENL (P = .017) independent of stage and histology. A difference in distant relapse (DR) rate between GALT-L and other ENL (P = .0002) was also identified. The presentation site of localized extranodal NHL is predictive of clinical behavior and is an independent determinant of outcome. This may be an expression of lymphocytic origin and determinants of migration patterns.
Uncommon Sites of Presentation of Hematologic Malignancies
Authors: Abhinav Chandra, David Eilender
Journal: Journal of Clinical Oncology (1999)

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.1999.17.5.1640 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 10334554 Uncommon Sites of Presentation of Hematologic Malignancies Abhinav ChandraxAbhinav ChandraSearch for articles by this author , David EilenderxDavid EilenderSearch for articles by this author Show More Barbara Ann Karmanos Cancer Institute/Wayne State University, Grosse Pointe, MI https://doi.org/10.1200/JCO.1999.17.5.1640 First Page Full Text PDF Figures and Tables © 1999 by American Society of Clinical Oncology