tbuckley/cabot-search huggingface dataset:
Abstract 16059: T Wave Inversion, QRS Duration and QRS/T-Angle as Electrocardiographic Predictors of the Risk for Sudden Cardiac Death
Authors: Jari A Laukkanen, Hassan Khan, Sudhir Kurl
Journal: Circulation (2013)

Aims: To investigate the prognostic utility of isolated T wave inversion (TWI), QRS duration and QRS/T angle on resting ECG as predictors for sudden cardiac death (SCD) and all-cause mortality. Met...
Duration of sleep and risk of colorectal adenoma.
Authors: L. Li, C. L. Thompson, N. A. Berger, S. Redline, S. R. Patel, E. Larkin
Journal: Journal of Clinical Oncology (2010)

e14023 Background: Very few studies have investigated the associations of duration and quality of sleep with risk of colorectal neoplasia. Methods: In an ongoing screening colonoscopy-based study of colorectal adenomas, the Pittsburg Sleep Quality Index (PSQI) was administered to 1,240 study participants prior to their screening colonoscopy. Three hundred and thirty eight (27.3%) of the participants were diagnosed with incident colorectal adenomas. Results: Although there was no appreciable difference in the overall sleep quality as measured by the PSQI score between cases and adenoma-free controls (5.32 vs. 5.11; p = 0.37), we found a statistically significant association of colorectal adenoma with the PSQI component 3, which corresponds to sleep duration (p = 0.018). Cases were more likely to average less than 6 hours of sleep per night (28.9% vs. 22.1% in controls, univariate p = 0.013). In multivariate regression analysis adjusted for age, gender, race, smoking, income, family history of colorectal cancer, and waist-hip ratio, individuals averaging less than 6 hours per night had an almost 50% increase in risk of colorectal adenomas (OR = 1.47, CI:1.05-2.06, p for trend = 0.023) as compared with individuals sleeping less at least 7 hours per night. Cases were also more likely to report of being diagnosed with sleep apnea (9.8% vs. 6.5%, p = 0.045) and more likely to have worked alternate shifts (54.0% vs. 46.1%, p = 0.013), although these differences were not significant in multivariate models. Conclusions: Our results suggest quality of sleep, sleep duration in particular as a novel risk factor for colorectal neoplasia. No significant financial relationships to disclose.
Quinine Poisoning
Authors: Elizabeth Hillman, E. R. Harpur
Journal: New England Journal of Medicine (1961)

THE recent occurrence of 2 cases of acute quinine intoxication, 1 of which was fatal, has prompted us to look into the current concepts of the mode of action of the drug and methods of treatment of the poisoned patient.1 , 2 Case ReportTwo male children, 3 and 5 years of age, were taken to the hospital by police car from their home in suburban Montreal. The mother stated that she had found the children pale and nauseated in the bedroom shortly after 11 a.m. Nearby was an open box of pills, of which only 3 remained. A more fortunate 2-year-old . . .
Prognostic value of serum CD44, ICAM-1 and VCAM-1 levels in patients with indolent non-Hodgkin’s lymphomas
Authors: N. Shah, F. Cabanillas, L. Feng, B. McIntyre, P. McLaughlin, M. A. Rodriguez, J. E. Romaguera, A. Younes, F. B. Hagemeister, L. Kwak, L. E. Fayad
Journal: Journal of Clinical Oncology (2008)

8589 Background: Indolent lymphomas are the most common non-Hodgkin’s lymphomas (NHL). The cell adhesion molecules CD44, ICAM-1 and VCAM-1 present on lymphoma cells regulate cell-matrix interactions and lymphocyte migration. Elevated serum levels of CD44, ICAM-1 and VCAM-1 have been linked to poor prognosis in high grade lymphomas but their utility in low grade lymphomas remains undefined. Methods: To determine the clinical significance of CD44, ICAM-1 and VCAM-1 levels in patients with indolent NHL, we evaluated outcomes of 100 patients with newly diagnosed indolent NHL in relation to their CD44, VCAM-1 and ICAM-1 levels at presentation. All 3 markers were measured using commercially available ELISA kits. Median values of markers obtained from preliminary data analysis (CD44: 540 ng/ml, ICAM-1: 300 ng/ml VCAM-1: 1120 ng/ml) were used as cutpoints for analysis. Kaplan-Meier curves and the log-rank test were used to compare the difference in survival between the serum marker high and low groups. Multivariate analysis was done with Cox proportional hazard models. Tests were two-sided; p-values less than 0.05 were considered statistically significant. Results: Of 93 evaluable patients followed for a median of 15.2 years, 62% relapsed and 47% died. On univariate analysis elevated CD44, ICAM-1 and VCAM-1 were significantly associated with worse overall survival (OS) and relapse free survival (RFS). The predictive value of CD44, ICAM-1 and VCAM-1 for overall survival persisted even when only stage IV patients were analyzed (p<0.05). However, none of the serum markers were independent predictors of OS or RFS in a multivariate analysis that included the Follicular Lymphoma International Prognostic Index (FLIPI) score. Conclusions: Serum levels of the cell-adhesion molecules CD44, ICAM-1, and VCAM-1 are accurate predictors of outcome in patients with indolent NHL. The prognostic value is maintained within the sub-population of Stage IV patients. Unlike the FLIPI, which is limited to initial presentation, cell adhesion molecules may hold promise as serum biomarkers of response to therapy or progression of disease. No significant financial relationships to disclose.
Phase II study of sequential non-cross-resistant chemotherapy using weekly 24-hour infusion of cisplatin, high-dose 5-fluorouracil and leucovorin (P-HDFL) followed by weekly docetaxel and irinotecan (DI) for recurrent or metastatic gastric cancer: an interim analysis
Authors: K. Yeh, C. Hsu, Y. Lu, C. Hsu, S. Kuo, C. Huang, Y. Shen, C. Hsiao, C. Yang, A. Cheng
Journal: Journal of Clinical Oncology (2006)

14063 Weekly 24-hour infusion of high-dose 5-FU and leucovorin (HDFL)-based regimens are highly effective for advanced gastric cancer (AGC). Although the response rate has been improved, the overall survival (OS) was not significantly prolonged. To prolong the OS, we designed a sequential chemotherapy strategy incorporating non-cross-resistant docetaxel and irinotecan (DI). All patients had patho/cytologically confirmed recurrent/metastatic chemonaive AGC, at least 1 measurable lesion, a fasting serum triglyceride level &gt; 70 mg/dl, adequate hepatic, renal, and marrow functions. Induction regimen was P-HDFL (cisplatin 35 mg/m 2 , i.v. 24-hr, D1, 8; 5-FU 2600 mg/m 2 and leucovorin 300 mg/m 2 , i.v. 24-hr, D1, 8, 15; every 4 wks), and consolidation regimen was weekly DI (docetaxel 30–35 mg/m 2 /wk, i.v. 30-min, then irinotecan 60–70 mg/m 2 /wk, i.v. 30-min, D1, 8, 15; every 4 wks). Patients with inferior conditions (prior Gr4 neutropenia or Gr3/4 infection, poor marrow reserve with delayed hemogram recovery, poor nutritional status or ileus) started with dose-modified DI (D: 30, I: 60 mg/m 2 /wk). For CR patients by P-HDFL, 3 cycles of DI were given; and for PR or SD patients, DI was continued till 2 cycles after CR, disease progression, or unacceptable toxicities. Between Jun. 2000 and Dec. 2005, 23 patients were enrolled (M:11, F:12) with a median age of 52 (37–68). Total 114 cycles (median: 6, range: 2–8) of P-HDFL were given. Overall RR was 60.9% (38–80%, 95% C.I.) with 3 CRs and 11 PRs. Gr3/4 toxicities: neutropenia (14%), infection (4.4%), thrombocytopenia (1.6%), diarrhea (5%), and vomiting (7%). Gr1/2 hand-foot syndrome was noted in 11% of cycles. Patients with CR, PR, and SD were treated with weekly DI regimen. Total 59 cycles (median: 4, range: 1–10) of weekly DI were given. Gr3/4 toxicities: neutropenia (30.5%), infection (13%), thrombocytopenia (2%), and diarrhea (17%). Median OS of the whole intent-to-treat group is 18 months (3 to 62+), and median OS of 14 responders of P-HDFL is 20 months (7 to 62+). This sequential non-cross-resistant strategy is very effective for prolongation of OS in advanced AGC. No significant financial relationships to disclose.
Sunitinib malate in advanced hepatocellular carcinoma: Results of a phase II study.
Authors: C. Barone, M. Basso, A. Cassano, V. Rufini, E. D'Argento, L. Riccardi, G. Schinzari, M. Pompili, A. Grieco
Journal: Journal of Clinical Oncology (2010)

e14557 Background: In 2007, sorafenib (SOR) was shown effective in improving overall survival (OS) when compared to best supportive care in patients with hepatocellular carcinoma (HCC) and a good liver function (Child A). Sunitinib is another multi-kinase inhibitor that is active against VEGF-R, PDGF-R and c-KIT. We designed a phase II study, according with a two-step Simon's model, to assess safety and efficacy of sunitinib in HCC patients. Methods: Eligibility criteria were: unresectable or metastatic HCC; no prior chemotherapy. PS (ECOG) 0-1; measurable disease according to RECIST criteria. Child C patients were excluded. Schedule: 50 mg each day, four weeks on, two weeks off. CT scan: every two cycles. PET-TC scan: at baseline and after the first cycle. Primary end-point was response rate according to RECIST criteria. Results: Thirty-three patients enrolled. ChildA/ChildB = 21/12 (64%/36%). Seventy-five cycles were administered. Grade 3 adverse effects included fatigue (26.6% of cycles), piastrinopenia (17.3%), neutropenia (13.3%), encephalopathy (8%), gastrointestinal bleeding (5.3%), nausea/vomiting (5%), diarrhea (4.1%), stomatitis (2.6%). Seven pts (21%) required dose reductions because of toxicity. Six pts (18%) died within 60 days since enrollment. Five of them belonged to Child B group and died because of liver failure. The Child A patient had a bone metastasis to the clivus, that was the probable cause of death but autopsy was not performed. Objective response rate was 10%. Thirteen patients (43.3%) experienced a disease stabilization and 14 (46.6%) progressed. All responders and seven patients (53%) among those with stable disease had a significant metabolic response at PET-TC and they experienced a prolonged time to progression with a significant clinical benefit. Conclusions: The dose of 50 mg is probably high in HCC patients with liver cirrhosis and it is not tolerable for Child B patients. However, sunitinib is able to induce a low but definite response rate and a high percentage of disease stabilization; PET-scan may select good responders. No significant financial relationships to disclose.
Proteomic biomarkers in colorectal cancer
Authors: S. J. Clarke, L. Jankova, C. Chan, L. Horvath, X. Song, Y. Kwun, P. Chapuis, L. Bokey, M. Baker, G. Robertson, M. Molloy
Journal: Journal of Clinical Oncology (2008)

15033 Background: Colorectal cancer (CRC) is a leading cause of cancer death in the Western world. Identification of improved diagnostic, prognostic and predictive biomarkers could significantly improve outcomes for CRC patients. This study aimed to discover and validate potential CRC tissue biomarkers with diagnostic and prognostic value using quantitative mass spectrometry based techniques and immunohistochemistry (IHC). Methods: Comparative iTRAQ (isobaric Tags for Relative and Absolute Quantitation) labelling followed by multidimensional liquid chromatography and tandem mass spectrometry was used to quantify protein levels of fresh CRC specimens and matched adjacent normal tissue from 16 patients with Australian Clinico-pathological stage A-D, and 2 sub-groups with MLH1 -ve or +ve tumours. Differential expressions of 10 candidate biomarkers were validated by IHC on paraffin-embedded colon tumour specimens from the same patients. Presence and localisation of protein staining was confirmed by a histopathologist (CC). Results: This is the first large- scale study to utilize iTRAQ technology to examine CRC tissues. Approximately 2,000 proteins were identified, 75% of them with relative quantification between the tumour and adjacent normal tissue. As a result of manual analysis, differentially expressed proteins observed across most of the samples were chosen as potential biomarkers. We identified several proteins that were consistently up-regulated including S100 family proteins, alpha-defensin 3, maspin and lactate dehydrogenase amongst others, and several consistently down-regulated including liver fatty acid binding protein, selenium binding protein, galectins 3 & 4 and carbonic anhydrase, in most tumour tissues independent of staging. These represent potential tissue-based diagnostic biomarkers. Numerous other proteins, HLA-DRA, STAT1, galectin 10 and some stromal proteins, showed highly variable expression, suggesting their potential as prognostic biomarkers. Variability in protein expression levels did not correlate with disease stage or phenotype. In the majority of cases, IHC was consistent with the expression levels measured by iTRAQ. Hierarchical clustering analysis of iTRAQ results and tissue microarray analysis of candidate biomarkers in 200 stage C patients with known outcomes are underway. No significant financial relationships to disclose.
The impact treatment has on cardiovascular risks factors for breast cancer survivors.
Authors: John R. Keyserlingk, David H. Jones, Melisa Nestore, Alain Steve Comtois, Sara Henophy, Julie Cousin, Helen Hu
Journal: Journal of Clinical Oncology (2013)

106 Background: The Integrative Health and Wellness center at VM Medical was established to monitor the body composition, activity level and vital signs of both the regular patients and the cancer survivors during their annual mammography screening. To determine if body composition and basic cardiovascular function of cancer survivors may vary depending on the type of adjuvant therapy dispensed. Methods: Kinesiologists performed base line measurements on 4,414 patient at The VM Medical Breast Center. Measurements were obtained on 3,674 non-oncology female patients and 740 cancer survivors. The data included BMI, resting heart rate, blood pressure, total body fat, lean muscle and waist circumference. The cancer survivors were stratified into 8 different groups (G1-G8) according to the type of surgery they underwent and compared to the regular patients(R). A one way ANOVA was performed with Dunnet post hoc analysis, significance was set at p &lt; 0.05. The two largest groups were; women who underwent surgery, chemotherapy, radiotherapy and hormone therapy (G5) 243 patients, as part of their treatment and women who underwent surgery, radiotherapy and hormone therapy (G6) 207 patients, as part of their treatment. The other 290 patients were separated into the other 6 treatment groups. Results: Significant differences were seen between the cancer survivors in all groups and the regular patients with p= 0.00 in 7 key variables. BMI(F=4.30) µ= 26.08 (R) vs µ= 27.10 (G6), resting heart rate (F= 6.24) µ= 73.04 bts/min (R) vs µ= 76.45 bts/min (G5), diastolic blood pressure (F= 4.65) µ= 74.18 mmHg (R) vs µ= 77.00 mmHg (G5), systolic blood pressure (F= 8.75) µ= 123.04 mmHg (R) vs µ= 130.14 mmHg (G6), lean muscle (F= 3.48) µ= 10.09 kgs (R) vs µ= 9.74 kgs (G6), total body fat (F=9.02) µ= 34.45% (R) vs µ= 37.49% (G6) and waist circumference (F= 4.44) µ= 84.91 cm (R) vs µ= 87.68 cm (G5). Conclusions: It would appear that different treatment protocols are associated with an increase in negative body composition and blood pressure measurements in cancer survivors. This information is important for the medical team to consider when directing the cancer survivors on healthy lifestyle choices post treatment.
Results of a phase III randomized, double-blind, placebo-controlled, multicenter trial (CORRECT) of regorafenib plus best supportive care (BSC) versus placebo plus BSC in patients (pts) with metastatic colorectal cancer (mCRC) who have progressed after standard therapies.
Authors: Axel Grothey, Alberto F. Sobrero, Salvatore Siena, Alfredo Falcone, Marc Ychou, Heinz-Josef Lenz, Takayuki Yoshino, Frank Cihon, Andrea Wagner, Eric Van Cutsem
Journal: Journal of Clinical Oncology (2012)

LBA385 Background: Regorafenib (BAY 73-4506) is an oral multikinase inhibitor of a broad range of angiogenic, oncogenic, and stromal kinases. The phase III CORRECT trial was conducted to evaluate efficacy and safety of regorafenib in pts with mCRC who had progressed after all approved standard therapies. Methods: Enrollment criteria included documented mCRC and progression during or ≤3 months after last standard therapy. Pts were randomized 2:1 to receive regorafenib (160 mg od po, 3 weeks on/1 week off) plus BSC, or placebo (PL) plus BSC. Pts continued on treatment until progression, death, or unacceptable toxicity. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR), safety, and quality of life. Results: From May 2010 to March 2011, 760 pts were randomized (regorafenib: 505; PL: 255). Baseline characteristics were balanced between two arms. Preliminary results are available from a pre-planned formal interim analysis. The estimated hazard ratio (HR) for OS was 0.773 (95% CI: 0.635, 0.941; 1-sided p=0.0051). Median OS was 6.4 mos (95% CI: 5.9, 7.3) for regorafenib and 5.0 mos (95% CI: 4.4, 5.8) for PL. The estimated HR for PFS was 0.493 (95% CI: 0.418, 0.581; 1-sided p &lt; 0.000001). Median PFS was 1.9 mos (95% CI: 1.88, 2.17) for regorafenib and 1.7 mos (95% CI: 1.68, 1.74) for PL. ORR was 1.6% for regorafenib and 0.4% for PL. DCR was 44% for regorafenib and 15% for PL (p &lt; 0.000001). Since the prespecified OS efficacy boundary was crossed (nominal α: 0.0093), the Data Monitoring Committee recommended to unblind the study and pts on PL were allowed to cross over to regorafenib. The most frequent grade 3+ AEs in the regorafenib arm were hand-foot skin reaction (17%), fatigue (15%), diarrhea (8%), hyperbilirubinemia (8%), and hypertension (7%). Updated results will be presented. Conclusions: Statistically significant benefit in OS and PFS was observed for regorafenib over PL in pts with mCRC who have failed all approved standard therapies. No new or unexpected safety signal was found.
Development of a minimal residual disease ovarian cancer model in immunocompetent mice
Authors: J. Y. Shin, J. Baker, A. Beilhack, T. A. Longacre, R. Nishimura, R. S. Negrin, J. K. Chan
Journal: Journal of Clinical Oncology (2008)

16590 Background: To develop an immunocompetent mouse ovarian cancer model in immunocompetent mice. Methods: Clonal cell lines of mouse ovarian surface epithelial cells (MOSEC) were transfected with firefly luciferase. After FACS analysis, luciferase stably-transfected MOSEC were injected intraperitoneally into C57/BL6 mice using various titrations of MOSEC. Tumors were visualized using a bioluminescence imaging system and measured using hematoxylin and eosin staining. Survival analyses were calculated using Kaplan-Meier analysis. Results: In vitro bioluminescence of MOSEC gfp-luc cells were visualized with as low as 976 cells. Mice injected intraperitoneally with 0.1, 1.0, and 5.0 × 106 MOSEC gfp-luc demonstrated increasing levels of bioluminescence with corresponding median survivals of 95, 112, and 124 days, respectively (p<0.001). Immunocompetent C57/BL6 mice that underwent sublethal radiation had increased tumor burden and rapid tumor progression compared to those without radiation. At early-stage disease, microscopic tumor implants were visualized and resected using bioluminescence imaging. On ex vivo resection, tumors were found to have microscopic disease during surgical dissection. On ex vivo imaging, these tumors which were located on the ovary, liver, and small bowel mesentery, had average measurements of 50–100 microns. Tumor implantation, growth, and metastases closely resembled that of human ovarian cancer with hemorrhagic ascites, omental caking, intestinal obstruction, and large pelvic tumors. Conclusions: This immunocompetent mouse model of ovarian cancer with minimal residual disease state closely resembles that of human ovarian cancer. Using this sygeneic cancer model, we are now able to study the effects of biologic therapy in an immunocompetent system. No significant financial relationships to disclose.
Lenalidomide, bortezomib, pegylated liposomal doxorubicin hydrochloride, and dexamethasone in newly diagnosed multiple myeloma: Initial results of phase I/II MMRC trial
Authors: A. J. Jakubowiak, C. C. Hofmeister, E. L. Campagnaro, T. M. Zimmerman, R. L. Schlossman, S. Lonial, D. E. Reece, M. S. Kaminski, K. C. Anderson, P. G. Richardson
Journal: Journal of Clinical Oncology (2009)

8517 Background: Three-drug combinations with lenalidomide (Revlimid, Rev) and bortezomib (Velcade, Vel) are highly active in previously untreated multiple myeloma (MM). Among the most active are RVD (Revlimid, Velcade, Dexamethasone) and VDD (Velcade, Doxil, Dexamethasone) with ≥ PR rate of 100% and 93%, and a CR/nCR rate of 44% and 40%, respectively. Pre-clinical evaluations suggest that adding pegylated liposomal doxorubicin hydrochloride (Doxil, Dox) to RVD (RVDD) may have higher activity. This phase I/II study was designed to determine the maximum tolerated dose (MTD) of RVDD, assess safety and evaluate efficacy of this 4-drug regimen in newly diagnosed MM. Methods: Four dose levels are being evaluated: Rev 15–25 mg (days 1–14), Vel 1.3 mg/m 2 (days 1, 4, 8, 11), dexamethasone (Dex) 20/10 mg (cycles 1–4/5–8; days of and after Vel), Dox 20 and 30 mg/m 2 (day 4), with dose assignment for patients (pts) according to the TITE-CRM algorithm. Eight 21-day cycles are planned with 38 pts to be treated at the MTD in phase II. Pts who achieve ≥ PR can proceed to autologus stem cell transplant (ASCT) after ≥ 4 cycles, while all others receive 21-day maintenance cycles with Rev (days 1–14), Vel (day 1 and 8), and Dex (days of and after Vel) at the doses tolerated by the end of initial treatment. Results: The study has enrolled 23 pts to date. Four pts received level 1 (Rev/Dox 15/20), 11 pts level 2 (Rev/Dox 20/20, and 8 pts level 3 (Rev/Dox 25/20). Nineteen pts are evaluable for toxicity after completion of a median of 4 cycles (range 1–8). Two pts developed DLT at dose level 2, consisting of grade (G) 3 asymptomatic neutropenia and G3 elevation of transaminase. The MTD has not been reached. Overall, toxicities have been manageable with no additional G3 hematologic events. There have been 4 additional G3 non-hematologic events including one case each of pneumonia, DVT, fatigue, and hypotension. After a median of 12 (range 3–24) weeks of treatment, preliminary response rates by modified EBMT/UC in 19 evaluable pts are: 95% ≥ PR, 47% ≥ VGPR, 26% CR/nCR. Conclusions: RVDD is well tolerated in newly diagnosed MM and appears highly active with an overall response (≥ PR) of 95%. Accrual is ongoing, with updated toxicity and efficacy data to be presented at the meeting. [Table: see text]