tbuckley/cabot-search huggingface dataset:
Renal safety of zoledronic acid administration beyond 24 months in breast cancer patients with bone metastases
Authors: M. K. Altundag, M. Dincer, H. Harputluoglu, S. Aksoy, Y. Ozisik, N. Guler, G. Tekuzman
Journal: Journal of Clinical Oncology (2007)

19669 Background: Zoledronic acid (ZA) delays the onset or reduces the incidence of skeletal complications in breast cancer patients with bone metastases. However there are few data on the long-term renal safety of ZA. Methods: We retrospectively evaluated 43 breast cancer patients with bone metastases who received ZA more than 24 months. The following parameters measured prior to first ZA use and after the last dose of ZA administration were compared: serum creatinine (SCr), blood urea nitrogen (BUN), alkaline phosphatase (ALP), calcium (Ca), and phosphorous (P). Results: Forty-three breast cancer patients with documented bone metastases were evaluated. Median age at the start of treatment was 53 years (range, 37 to 77). Median overall duration of ZA administration was 36 months (25 to 62). There were no statistically significant differences in the pre- and post-treatment levels of SCr, BUN, Ca and P. However, ALP levels after long-term ZA administration were decreased significantly (P &lt;0.05). Conclusion: More than 24 months of ZA administration did not adversely affect the renal function. ZA can be used safely in breast cancer patients with bone metastases beyond 2 years. [Table: see text] No significant financial relationships to disclose.
Prognostic Significance of CD20 Expression in Adult B-Cell Precursor Acute Lymphoblastic Leukemia.
Authors: Sébastien Maury, Françoise Huguet, Arnaud Pigneux, Emmanuel Raffoux, Xavier Thomas, Kheira Beldjord, Eric Delabesse, Patrice Chevallier, Agnès Buzyn, André Delannoy, Yves Chalandon, Jean-Paul Vernant, Philippe Rousselot, Marina Lafage-Pochitaloff, Agnès Chassevent, Véronique Lheritier, Elizabeth Macintyre, Norbert Ifrah, Herve Dombret, Marie-Christine Béné
Journal: Blood (2007)
Autologous Hematopoietic Cell Transplantation in Patients with High Risk Multiple Myeloma: Post- Transplant Responses Do Not Translate to Longer Survival
Authors: Manish Sharma, Parmeswaran Hari, Jennifer Le-Rademacher, Amrita Krishnan, Yago Nieto, Cristina Gasparetto, Jiaxing Huang, Emma C. Scott, Anita D'Souza
Journal: Blood (2015)
Association Between Duration of Resuscitation and Favorable Outcome After Out-of-Hospital Cardiac Arrest
Authors: Joshua C. Reynolds, Brian E. Grunau, Jon C. Rittenberger, Kelly N. Sawyer, Michael C. Kurz, Clifton W. Callaway
Journal: Circulation (2016)

Little evidence guides the appropriate duration of resuscitation in out-of-hospital cardiac arrest, and case features justifying longer or shorter durations are ill defined. We estimated the impact of resuscitation duration on the probability of favorable functional outcome in out-of-hospital cardiac arrest using a large, multicenter cohort.This was a secondary analysis of a North American, single-blind, multicenter, cluster-randomized, clinical trial (ROC-PRIMED [Resuscitation Outcomes Consortium Prehospital Resuscitation Using an Impedance Valve and Early Versus Delayed]) of consecutive adults with nontraumatic, emergency medical services-treated out-of-hospital cardiac arrest. Primary exposure was duration of resuscitation in minutes (onset of professional resuscitation to return of spontaneous circulation [ROSC] or termination of resuscitation). Primary outcome was survival to hospital discharge with favorable outcome (modified Rankin scale [mRS] score of 0-3). Subjects were additionally classified as survival with unfavorable outcome (mRS score of 4-5), ROSC without survival (mRS score of 6), or without ROSC. Subject accrual was plotted as a function of resuscitation duration, and the dynamic probability of favorable outcome at discharge was estimated for the whole cohort and subgroups. Adjusted logistic regression models tested the association between resuscitation duration and survival with favorable outcome.The primary cohort included 11 368 subjects (median age, 69 years [interquartile range, 56-81 years]; 7121 men [62.6%]). Of these, 4023 (35.4%) achieved ROSC, 1232 (10.8%) survived to hospital discharge, and 905 (8.0%) had an mRS score of 0 to 3 at discharge. Distribution of cardiopulmonary resuscitation duration differed by outcome (P<0.00001). For cardiopulmonary resuscitation duration up to 37.0 minutes (95% confidence interval, 34.9-40.9 minutes), 99% with an eventual mRS score of 0 to 3 at discharge achieved ROSC. The dynamic probability of an mRS score of 0 to 3 at discharge declined over elapsed resuscitation duration, but subjects with initial shockable cardiac rhythm, witnessed cardiac arrest, and bystander cardiopulmonary resuscitation were more likely to survive with favorable outcome after prolonged efforts (30-40 minutes). After adjustment for prehospital (odds ratio, 0.93; 95% confidence interval, 0.92-0.95) and inpatient (odds ratio, 0.97; 95% confidence interval, 0.95-0.99) covariates, resuscitation duration was associated with survival to discharge with an mRS score of 0 to 3.Shorter resuscitation duration was associated with likelihood of favorable outcome at hospital discharge. Subjects with favorable case features were more likely to survive prolonged resuscitation up to 47 minutes.URL: http://clinicaltrials.gov. Unique identifier: NCT00394706.
Predictors of satisfaction with decision in patients with advanced cancer.
Authors: Felicitas Hitz, Dirk Klingbiel, Karin Ribi, Qiyu Li, Thomas Cerny, Dieter Koeberle
Journal: Journal of Clinical Oncology (2012)

9045 Background: Treatment decisions in palliative cancer care depend on various patient-, treatment, and disease-related factors. This study investigated patients’ satisfaction with decision and decision-making preferences in a Swiss oncology network and evaluated factors that predict satisfaction with decision (SWD). Methods: Patients receiving a new line of palliative cancer treatment completed a multi-dimensional questionnaire 4-6 weeks after treatment decision. Patient-reports comprised socio-demographic information, satisfaction with decision (primary endpoint), subjective treatment goal, preferences for decision-making, health, locus of control, and several quality of life (QoL) domains. Information on diagnosis, line of therapy, metastases, prognosis, performance status and duration of consultation were provided by the attending physician. Predictors of SWD (range: 0=worst; 30=best) were evaluated by uni- and multivariate (primary analysis, 80% power, 5% significance level) regression models. We consider ≥24 points as high SWD. Results: 445 out of 480 patients treated in 8 hospitals and 2 private practices completed all questions regarding the primary endpoint. 44% of patients preferred shared-, 42% physician-centered decision making. Median duration of consultation was 30 minutes (range 10-200 minutes). Overall, 326 (73%) patients reported high SWD. In univariate analyses various factors (e.g. global and physical QoL, performance status, treatment goal, locus of control, prognosis and duration of consultation) were significant predictors of SWD. The only significant predictor in the multivariate analysis was duration of consultation, which was positively associated with SWD (p=0.01). Conclusions: SWD is generally high in patients with advanced cancer treated in an oncology network in Switzerland. Our results indicate that duration of consultation is a very important factor among many others in predicting SWD. In busy clinical practice, taking your time with patients may be a simple measure to enhance patients’ SWD.
Four Years of Follow-Up of 1027 Patients with Late Chronic Phase (L-CP), Accelerated Phase (AP), or Blast Crisis (BC) Chronic Myeloid Leukemia (CML) Treated with Imatinib in Three Large Phase II Trials.
Authors: Richard T. Silver, Moshe Talpaz, Charles L. Sawyers, Brian J. Druker, Andreas Hochhaus, Charles A. Schiffer, Francois Guilhot, John M. Goldman, B. Douglas Smith, Manisha Mone, Tillmann Kranhnke, Hagop M. Kantarjian
Journal: Blood (2004)
Detail Characterization of 22q11 Deletion and Mir-650 Role in CLL Patients.
Authors: Marek Mraz, Karla Malinova, Sarka Pavlova, Boris Tichy, Katerina Stano Kozubik, Jitka Malcikova, Marek Borsky, Jan Verner, Michael Doubek, Yvona Brychtova, Martin Trbusek, Jiri Mayer, Sarka Pospisilova
Journal: Blood (2009)
Clinical outcome of adult brainstem glioma treated with concurrent chemoradiotherapy: An institutional experience.
Authors: Haresh Kunhiparambath, Subhash Gupta, Supriya Mallick, Manikandan Annamalai, Dayanand Sharma, Pramod Kumar Julka, Goura Kisor Rath
Journal: Journal of Clinical Oncology (2015)

2064 Background: Brainstem glioma (BSG) is an aggressive tumor of adulthood. Treatment outcomes remain dismal and role of concurrent chemoradiotherapy (CTRT) is not established in these patients .We intended to study the clinical characteristics along with outcome of adult BSG patients treated with CTRT. Methods: We retrospectively evaluated 29 patients, age more than 18 years, with BSG treated at our department in the period Jan 2007 to December 2012. Demographic and disease characteristics in this patient cohort were recorded, and their progression free survival (PFS) was analyzed with respect to sex, grade, use of CTRT and adjuvant chemotherapy. Results: Median age at presentation was 35 years (range 22-66 years), with a male: female ratio of 2:1.18 patients presented with gait ataxia and 16 presented with cranial nerve palsies.18 patients were diagnosed radiologically as low grade. None of the patient underwent surgery. Radiotherapy dose was 56-60 Gray over 5.5 -6 weeks at 1.8-2 gray/fraction. All patients completed their radiotherapy. 11 patients received concurrent Temozolomide (75 mg/m2), 10 patients received adjuvant Temozolomide (150-200 mg/m2 D1-5 q4 weeks for 3-6 cycles) and 6 patient received both concurrent and adjuvant Temozolomide. Median follow up duration was 9.77 months (range 0.3-54.82 months). At last follow up, 27 patients had progressive disease. Median PFS for the entire group was 64.19 months. PFS was significantly poorer in the patients who received concurrent Temozolomide than those who did not (Median PFS 64.19 vs. NR months; p = .016) on Univariate analysis. Sex, grade, and adjuvant chemotherapy did not statistically alter treatment outcomes. Conclusions: Outcome of adult BSG is better in our cohort compared to reported results. CTRT with Temozolomide has detrimental effect on survival and its use should be discouraged. Radiotherapy alone with standard fractionation remains the treatment of choice in inoperable adult BSG.
Preliminary International Validation of the Quality of Life in Myelodysplasia Scale (QUALMS)
Authors: Gregory A. Abel, Fabio Efficace, Rena Buckstein, Sara Tinsley, Joseph G. Jurcic, Yolanda Martins, David P. Steensma, Corey D Watts, Azra Raza, Alan F. List, Robert J. Klaassen
Journal: Blood (2014)
Influencing the Tumor Microenvironment: A Phase II Study of Copper Depletion Using Tetrathiomolybdate in Patients with Breast Cancer at High Risk for Recurrence and in Preclinical Models of Lung Metastases
Authors: Nancy Chan, Amy Willis, Naomi Kornhauser, Maureen M. Ward, Sharrell B. Lee, Eleni Nackos, Bo Ri Seo, Ellen Chuang, Tessa Cigler, Anne Moore, Diana Donovan, Marta Vallee Cobham, Veronica Fitzpatrick, Sarah Schneider, Alysia Wiener, Jessica Guillaume-Abraham, Elnaz Aljom, Richard Zelkowitz, J. David Warren, Maureen E. Lane, Claudia Fischbach, Vivek Mittal, Linda Vahdat
Journal: Clinical Cancer Research (2016)

Bone marrow-derived progenitor cells, including VEGFR2+ endothelial progenitor cells (EPCs) and copper-dependent pathways, model the tumor microenvironment. We hypothesized that copper depletion using tetrathiomolybdate would reduce EPCs in high risk for patients with breast cancer who have relapsed. We investigated the effect of tetrathiomolybdate on the tumor microenvironment in preclinical models.Patients with stage II triple-negative breast cancer (TNBC), stage III and stage IV without any evidence of disease (NED), received oral tetrathiomolybdate to maintain ceruloplasmin (Cp) between 8 and 17 mg/dL for 2 years or until relapse. Endpoints were effect on EPCs and other biomarkers, safety, event-free (EFS), and overall survival (OS). For laboratory studies, MDA-LM2-luciferase cells were implanted into CB17-SCID mice and treated with tetrathiomolybdate or water. Tumor progression was quantified by bioluminescence imaging (BLI), copper depletion status by Cp oxidase levels, lysyl oxidase (LOX) activity by ELISA, and collagen deposition.Seventy-five patients enrolled; 51 patients completed 2 years (1,396 cycles). Most common grade 3/4 toxicity was neutropenia (3.7%). Lower Cp levels correlated with reduced EPCs (P = 0.002) and LOXL-2 (P < 0.001). Two-year EFS for patients with stage II-III and stage IV NED was 91% and 67%, respectively. For patients with TNBC, EFS was 90% (adjuvant patients) and 69% (stage IV NED patients) at a median follow-up of 6.3 years, respectively. In preclinical models, tetrathiomolybdate decreased metastases to lungs (P = 0.04), LOX activity (P = 0.03), and collagen crosslinking (P = 0.012).Tetrathiomolybdate is safe, well tolerated, and affects copper-dependent components of the tumor microenvironment. Biomarker-driven clinical trials in high risk for patients with recurrent breast cancer are warranted. Clin Cancer Res; 23(3); 666-76. ©2016 AACR.
FDA analysis of the characteristics and relevance of serious adverse events that are Grade 1 or 2 in severity.
Authors: M. Naomi Horiba, Sandra J. Casak, Steven J. Lemery, Patricia Keegan, Richard Pazdur, Amy E. McKee
Journal: Journal of Clinical Oncology (2016)

2538 Background: In New Drug Approval (NDA) applications, sponsors must provide an integrated summary of the safety of the drug product, including serious adverse events (SAEs), defined as adverse events (AE) resulting in death, life-threatening AEs, inpatient hospitalization or prolongation of hospitalization, persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. The National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) grades the severity of AEs from 1 (mild) to 5 (death). This analysis attempts to quantify and characterize Grade 1-2 toxicities reported as SAEs. Methods: We reviewed SAEs from registrational trials submitted in nine NDAs for new molecular entities approved by FDA in 2014. Results: A total of 28,467 AEs were reported in 1,699 patients, of which 2,073 (7.3%; range 3.2- 10.9) were reported as SAEs. Of these 2,073 SAEs, 528 (25.5%; range 15.5-37.5) were Grade 1-2. Of 1,489 hospitalizations reported as SAEs, 93 (7.6%) reported no Grade 3-5 toxicities. Forty-four (8.3%) Grade 1 or 2 SAEs were not listed in the CTCAE dictionary, including dosing errors, catheter placement, and hospitalization for observation. A total of 65 (12.3%) Grade 1-2 SAEs were reported concomitantly with Grade 3-5 SAEs (e.g., Grade 2 fever with Grade 4 pneumonia). Of all Grade 1-2 SAEs, 24 (4.5%) were related to medication errors not resulting in toxicity; 57 (10.8%) were infections; 51 (9.6%) were neurologic complications; 44 (8.3%) were pyrexia; 28 (5.3%) were metabolic disturbances and 16 (3%) were abnormal laboratory findings; 12 (2.2%) were related to device/catheter complications. Fourteen SAEs were erroneously reported as Grade 1-2; i.e., CTCAE only defined the events as Grade 3 to 5 in severity (e.g., septic shock). Conclusions: A significant amount of time is spent by applicants, investigators, cooperative groups, and FDA conducting analyses of both SAEs and AEs by CTCAE grade. In most cases, this is a duplication of efforts. Most reported Grade 1-2 events were, by definition, non-severe. Minor changes in the CTCAE definition and/or SAE definition could serve to streamline clinical trial processes.
Functional Features of the Pancreas during Chronic Pancreatitis
Authors: B.F. Shevchenko, A.M. Babiy, O.М. Tatarchuk, V.A. Makarchuk, V.E. Kudryavtseva
Journal: GASTROENTEROLOGY (2016)

Aim of study: to identify functional status of pancreas in patients with chronic pancreatitis depending on the stage of fibrotic transformation and activity of parenchymal inflammation. Materials and methods. The preoperative laboratory results and the data of morphological study performed on biopsies obtained during surgery in 88 patients with complications of chronic pancreatitis (CP) were compared. According to morphological study of pancreatic biopsies, the early pancreatic parenchymal fibrosis (I–II degree) has been diagnosed in 31 cases (35.2 %), late fibrosis (III–IV degree) — in 57 (64.8 %) cases. Results. Active parenchymal inflammation at early and late stages of pancreatic fibrosis are associated with changes in pancreatic secretion and intracellular activation of pancreatic enzymes, leading to autodigestion and release of these enzymes from acinar cells into the blood, which has been confirmed by an increase of trypsin and amylase activity in blood compared with inactive inflammation. At late stages of fibrosis reduction of fecal elastase‑1 (161.7 ± 4.8) mg/g was observed in 73.9 % of patients. Reverse correlation has been found between fibrotic transformation of pancreatic parenchyma and the level of fecal elastase‑1 (r = –0.46; p = 0.05), i.e. progressing fibrotic transformation of pancreas leads to reduced exocrine function. Correlation analysis showed that the progression of fibrotic transformation violates carbohydrate metabolism — a direct correlation with glycosylated hemoglobin (r = 0.496; p = 0.05), namely, the endocrine secretion deficiency. Novelty in science. The pancreas functioning was studied depending on the inflammation activity and stage of fibrosis transformation of its parenchyma at chronic pancreatitis. The active inflammation of the pancreas was found to be accompanied by significant activation of pancreatic enzymes (significant increase in blood amylase and trypsin activity), which causes the progression of fibrotic transformation of pancreas in CP. Conclusions. Progression of fibrotic transformation of the pancreatic parenchyma in CP leads to deterioration of the exocrine pancreatic function, as defined by a decrease in the level of fecal elastase‑1 in case of late fibrosis of the pancreas and to the deterioration of endocrine pancreatic function, as manifested by impaired fasting glucose metabolism both at early and late stages of fibrosis, the development of pancreatogenic type II diabetes at the early stages of pancreatic fibrotic transformation, insulin resistance and type I diabetes at later stages of pancreatic fibrotic transformation.
Clinical-pathologic characteristics and outcomes of true interval compared to screen-detected breast cancer among participants in a Canadian breast screening program: A nested case-control study
Authors: D. Rayson, J. I. Payne, M. Abdolell, P. J. Barnes, A. Burns, R. MacIntosh, T. Foley, T. Younis, J. Caines
Journal: Journal of Clinical Oncology (2009)

6528 Background: It has been hypothesized that, compared to screen-detected breast cancer (Scr), true interval breast cancers (Int) are associated with adverse prognostic factors and outcomes. Data has remained controversial due to failure to control for age at diagnosis and screening interval as well as lack of information regarding adjuvant therapies and inclusion of other categories of interval cancers (e.g., missed or noncompliant). Methods: A case-control study nested among participants of the population-based Nova Scotia Breast Screening Program diagnosed with invasive disease between the ages 40–69 in the period 1991–2006 was performed. Ints were validated by blinded review of the pre-diagnostic screening mammogram by 3 mammographers, 2 or 3 of whom had to agree that it was negative for inclusion as a true Int. Scrs were matched to Ints on a 2:1 basis by 5 year age group at diagnosis and screening interval (40–49 yo, annual; 50–69 yo + family history, annual; 50–69 yo - family history, biennial). Results: 243 true Ints were observed and matched to 485 Scrs. The Table presents (i) univariate analysis of selected pathology variables for the entire cohort of Ints vs Scrs (ii) multivariate analysis of these selected variables. In addition to standard adjuvant hormonal, radiation and trastuzumab therapies, 62.4% of Ints received standard adjuvant chemotherapy (adjC) vs. 30.6% of Scrs. 5 year disease-free (DFS) and overall (OS) survival rates for Int vs Scr were 82.6% vs 92.3% and 87.2% vs 93.3% respectively. Cox proportional hazards modeling for (i) DFS shows HR=1.96 (p=0.0024) for Int vs Scr, dropping to HR=1.57 (p=0.0556) after adjusting for adjC received and (ii) OS shows HR=1.99 (p=0.0028) for Int vs Scr, dropping to 1.61 (p=0.0487) after adjusting for adjC received. Conclusions: True Ints present with more adverse prognostic factors compared to Scrs. Despite more use of adjC, outcomes are significantly poorer. [Table: see text] No significant financial relationships to disclose.
Effects of Imatinib Mesylate and Interferon-alpha Combined with Granulocyte Colony-Stimulating Factor on Chronic Myelogenous Leukemia Cells In Vitro.
Authors: Shuichi Ota, Manabu Musashi, Keiichi Kondo, Nobuyasu Toyoshima, Tomomi Toubai, Noriaki Iwao, Junji Tanaka, Masahiro Asaka, Masahiro Imamura
Journal: Blood (2004)
Effect of brain metastases on survival and systemic treatment of EGFR/ALK-driven non-small cell lung cancer (NSCLC).
Authors: Mark Doherty, Grzegorz Korpanty, Pascale Tomasini, Moein Alizadeh, Kevin Jao, Catherine Labbe, Celine Mascaux, Petra Martin, Suzanne Kamel-Reid, Melania Pintilie, Geoffrey Liu, Penelope Ann Bradbury, Ronald Feld, Natasha B. Leighl, Caroline Chung, Frances A. Shepherd
Journal: Journal of Clinical Oncology (2016)

e20527 Background: Survival with EGFR/ALK+ve NSCLC can be prolonged with tyrosine kinase inhibitors (TKIs), but brain metastases (mets) are common. TKIs may control brain mets poorly, and radiation may have neurocognitive toxicity. Deteriorating performance status (PS) due to brain mets may affect the number of lines of treatment. We aimed to evaluate the impact of brain mets on lines of systemic therapy and overall survival (OS). Methods: This retrospective analysis included patients with EGFR/ALK+ve NSCLC treated at Princess Margaret Cancer Centre from 1998-2015. 2 groups were analyzed: those with brain mets at diagnosis of stage IV disease or on 1st line therapy, and those without brain mets. OS was calculated from date of metastatic disease using Kaplan-Meier method, and differences between groups were tested with the log-rank test. Results: 291 patients were included: 141 with and 150 without brain mets. Summary results are shown in the Table. 106/141 had brain mets at diagnosis of stage IV NSCLC. There were more patients with relapsed early stage NSCLC in the no brain mets group (29% vs 19%), and more smokers in the brain mets group (18% vs 7%). 1st treatment for brain mets included WBRT (84), SRS (32) and TKI alone (24). 1st line systemic therapy was TKI in 83% of brain mets group and 61% of no brain mets group. Median OS was longer in the no brain mets group: 4 vs 2.1 years, HR 1.55, p=0.013. There was no observed difference in number of treatment lines: median 1 in both groups, p=0.53. Conclusions: Patients with brain mets from EGFR/ALK+ve NSCLC have inferior OS, despite TKIs and similar exposure to systemic therapy. Further focus on this group is necessary to improve outcomes. No Brain mets N=150 Brain mets N=141 P Age Median (Range) 61.9(27.6- 82.9) 59.8(29.2- 86.3) 0.35 Female 98(65%) 96(68%) 0.71 Smoking History No 139(93%) 115(82%) 0.005 Yes 11(7%) 26(18%) Ethnicity Asian 72(48%) 63(45%) 0.85 Caucasian 55(37%) 56(40%) Other 23(15%) 22(15%) ECOG PS 0-1 141(94%) 133(94%) 0.72 2-3 9(6%) 8(6%) Stage IV at First Dx 106(71%) 114(81%) 0.056 Mutation ALK 21(14%) 14(10%) 0.37 EGFR 129(86%) 127(90%) Lines of treatment Median(range) 1(0-9) 1(0-4) 0.53 Median Survival Years 4.0 2.1 0.011 HR 1.55 (95%CI 1.1-2.2)