tbuckley/cabot-search huggingface dataset:
Phase II study of talabostat and rituximab in fludarabine/rituximab-resistant or refractory patients with CLL
Authors: K. D. Khan, S. O’Brien, K. R. Rai, J. R. Brown, C. Abboud, D. D. Hurd, P. Conkling, Z. Yang, E. J. Haltom, M. J. Uprichard
Journal: Journal of Clinical Oncology (2006)

6598 Background: Talabostat (TAL) is an orally administered small molecule inhibitor of dipeptidyl peptidases such as CD26 and fibroblast activation protein (FAP) in bone marrow, lymph nodes, and stroma of solid tumors, and TAL induces cytokine and chemokines in lymph nodes and spleen. TAL enhances the activity of rituximab (RTX) in a mouse model of lymphoma. This study evaluates the efficacy of TAL + RTX in patients with advanced CLL who failed fludarabine (FLU) and/or RTX. Methods: Single-arm, open-label study of RTX 375mg/m 2 weekly × 4 weeks, and TAL-300mcg BID for 6 days following each RTX infusion for a tx course of 28 days. Additional courses permitted depending on tolerability. Eligibility criteria include ECOG PS 0–2, CD20+ B-CLL, Rai Stage III/IV or Rai I/II with marked lymphadenopathy, no CNS metastases, and primary resistance or PD following FLU and/or RTX. Primary endpoint is response rate per NCI-WG criteria. Secondary endpoints include response duration, PFS, and survival. Results: 40 patients (32 men, 8 women), median age 64.0 (range 42–83) have entered the study. Most (85%) are caucasian, and 78% of patients are Rai Stage IV. Mean serum B2 microglobulin is 6.5mg/L. The median number of prior regimens is 4 (range 1 to 10); 78% of patients received prior RTX and 33% prior alemtuzumab. Partial response (PR) has been reported in 8/36 evaluable patients (22%), 6 of whom had failed RTX; 3 of these patients had also failed alemtuzumab. Response duration currently ranges from 2 to 10 months (median 5.0 months). Most toxicities are Grade 1 or 2, and include nausea, fever (28% each), and edema (25%). Fever with associated Grade 3 or 4 neutropenia is reported in 2 and 1 patient, respectively. Other Grade 3 AEs include dyspnea (n=3), fatigue (n=2), and aspergillus pneumonia and a dermal fungal infection in 1 patient each. Grade 4 AEs are thrombocytopenia, hypoglycemia, and pulmonary embolism in 1 patient each. 4 patients died due to CLL (2 due to PD) or related complications (PE or MRSA pneumonia, 1 each). Conclusions: TAL + RTX shows promising activity in CLL patients with advanced disease who failed FLU and/or RTX. AEs are similar to those seen with RTX, with the exception of edema in 25% of patients. Updated results, including median PFS and survival will be presented at the annual meeting. [Table: see text]
Obesity in Childhood
Authors: J K Lloyd
Journal: Journal of the Royal Society of Medicine (1979)

Obesity is now the most frequent nutritional disorder of childhood in the so‐called developed countries of the world. It is due to an increase in the amount of adipose tissue but, because it is technically difficult to measure the exact amount of adipose tissue, obesity is usually defined in terms of body weight. In general an individual who weighs 20% or more than the weight expected for his height and age can be regarded as being obese. By this criterion the incidence of obesity amongst schoolchildren in Britain is probably at least 3%, although accurate contemporary figures are not available. Studies in the United States of America have suggested that amongst adolescent girls between 10–15% can be expected to be overweight.
Human papilloma virus: Is it a new etiological factor in breast cancer?
Authors: M. Gumus, F. Yumuk, T. Salepci, M. Aliustaoglu, M. Ekenel, G. Basaran, F. Dane, H. Kaya, N. Barisik, N. S. Turhal
Journal: Journal of Clinical Oncology (2004)

9635 Background: Viruses are known to be associated with human malignancies, e.g.,; Epstein-Barr virus, human papilloma virus (HPV) and human T-cell leukemia virus type I. HPV DNA has been found in uterine cervix, anogenital, oral cavity and esophagus tumors. HPV also has been shown to immortalize the breast epithelial cells and increase their proliferation in vitro. We conducted a prospective study to define the role of HPV in breast cancer. Materials and Methods: The malignant and normal breast tissue samples of 30 consecutive breast cancer patients were obtained postoperatively within the 1st hour of operation. All tissue samples were proven to be invasive ductal/lobular carcinoma histopathologically. DNA extracted from all tissues was amplified with the polymerase chain reaction using HPV consensus primer (MY11; 5'GCMCAGGGWCATAAYAATGG-3'; MY9; 5'CGTCCMARRGGAWACTGATC-3') and HPV type specific primers. HPV 11, 16, 18, 33 subtypes were searched in HPV-DNA positive samples. Results: The median age was 53 (range 30–75). Twenty-five samples (83.3%) of tumoral breast tissue expressed HPV-DNA, 13 normal breast tissue samples (43.3%) were positive as well. But there was a significant difference in HPV-DNA positivity between normal and tumoral breast tissue samples (p= 0.003; Fisher's exact test). HPV 18 was detected in 20 of the HPV-DNA positive tumoral tissue (80%) and in 9 of the HPV-DNA positive normal tissue (69.2%) (p=0.689). HPV-33 also was detected in 24 (96 %) of the HPV-DNA positive tumoral tissue and in 12 (92.3 %) of the HPV-DNA positive normal tissue samples (p= 1.000). The distribution of HPV types 18 and 33 between the normal tissue and tumoral tissue was not significantly different. HPV-11 and 16 were not found in any of the HPV-DNA positive samples. Conclusion: HPV DNA was significantly associated with breast tumor tissue compared to normal breast tissue. Our study could not define the specific HPV subtype involved in breast cancer etiology due to the small number of samples and the possible presence of other HPV subtypes which are not analyzed in the present study. Additional studies looking at other HPV subtypes are needed to clarify the etiological role of the HPV in breast cancer. No significant financial relationships to disclose.
Evaluation of early response to primary systemic chemotherapy in breast cancer patients by <sup>18</sup>FDG PET: Preliminary findings from the Arianna Project 01
Authors: C. Zamagni, S. Fanti, A. Bernardi, F. Sperandi, S. Quercia, D. Santini, A. Musto, P. Castellucci, M. Taffurelli, A. Martoni
Journal: Journal of Clinical Oncology (2006)

10722 Background: Pathological complete remission after primary systemic chemotherapy (PSC) for early breast cancer (BC) correlates with a better prognosis in terms of survival. The Arianna Project 01 was designed to study the relationship between clinical, hystological, biological, gene-expression profile characteristics and response to PSC in BC pts. Methods: Pts treated with 6 cycles of adriamycin 60 mg/m 2 and paclitaxel 200 mg/m 2 were evaluated at baseline and before each cycle by physical exam, 18 FDG-PET, circulating tumor cells and bio-markers (serum EGFR, VEGF, UPA, plasma PAI-I and the circulating portion of HER2/neu receptor). At baseline and every other cycle mammography, ultrasound and breast MRI were also done. This preliminary report is focused on the correlation between PET monitoring and pathological response. Changes in tumoral 18 FDG uptake, expressed as Standardized Uptake Value (SUV), were compared with the hystopathological response assessed according to Miller-Payne scale, which estimates the Tumour Regression Grade (TRG). Results: Up to now 12 pts (T &gt; 2 cm) have been enrolled in the study and 9 completed PSC and were submitted to surgery. Baseline PET was abnormal in all pts (SUVmax range: 3.9–17.1). No cases of complete pathological remission have been observed so far. In 2 pts the TRG was grade 4 ( &gt; 90% reduction of tumor cells), TRG was grade 3 (30 to 90% reduction) in 3 cases, grade 2 (minor loss of tumor cells) in 4 cases. After the 1st, the 2nd and the 3rd cycle of PSC the SUV decrease (Δ SUV) in primary tumors was ≥ 50%, ≥ 75% and ≥ 85% only in the two pts that at the end of PSC obtained a TRG grade 4 (see table ). Conclusions: Our preliminary results suggest that an early prediction of pathological response by PET is possible and the optimal timing to perform PET during PSC could be after 2 or 3 cycles. The study is still ongoing and the relationship between evaluation performed by PET and by mammography, ultrasound and breast MRI will be presented at the ASCO meeting. [Table: see text] No significant financial relationships to disclose.
Can the Prognosis of Cardiac Resynchronization Therapy Be Predicted by Gated SPECT?
Authors: Shengmei Qin, Hongcheng Shi, Yangang Su, Shuguang Chen, Wenzhi Pan, Junbo Ge
Journal: Clinical Nuclear Medicine (2015)

Purpose The aim of this study was to evaluate the role of gated myocardial perfusion SPECT (GMPS) phase parameters (phase SD and histogram bandwidth) in predicting the short-term response to cardiac resynchronization therapy (CRT) as left ventricle (LV) remodeling and the long-term effect as all-cause mortality or cardiac transplantation and hospitalization for heart failure. Patients and Methods This prospective observational study included 63 consecutive patients undergoing CRT from May 2008 to April 2014. Before CRT, patients underwent evaluation of New York Heart Association functional class, standard 12-lead ECG, 99mTc-MIBI GMPS, and 2-dimensional echocardiography. The patients were grouped according to complete left bundle-branch block (CLBBB). Follow-up was done every 6 months after pacemaker implantation. The short-term end point was reverse LV remodeling in 6 to 12 months follow-up, and the long-term primary end point was all-cause mortality or cardiac transplantation. The secondary end point was hospitalization for heart failure. Results Reverse LV remodeling showed in 60.9% (39/63) patients (74.5% CLBBB [35/47] vs 25.0% non-CLBBB [4/16], P < 0.001). Phase SD less than 55 degrees, CLBBB, and left atrium diameter were independent predictive factors for reverse LV remodeling. At a median follow-up of 39.76 months, there were 17 deaths and 2 transplantations (17.0% CLBBB vs 68.8% non-CLBBB, P < 0.001). Seventeen patients required hospitalization more than once for heart failure, and 2 underwent heart transplantation (14.9% CLBBB vs 62.5% non-CLBBB, P < 0.001). Multivariate logistic regression showed that only CLBBB was an independent predictive factor for both end points. Conclusions The GMPS parameters were not independent predictive factors for all-cause mortality or cardiac transplantation and hospitalization for heart failure.
Chemotherapy for diffuse large-cell lymphoma--rapidly responding patients have more durable remissions.
Authors: J O Armitage, D D Weisenburger, M Hutchins, D F Moravec, M Dowling, S Sorensen, J Mailliard, J Okerbloom, P S Johnson, D Howe
Journal: Journal of Clinical Oncology (1986)

Fifty-one patients with diffuse large-cell lymphoma (DLCL) were treated with a six-drug combination chemotherapy regimen including cyclophosphamide, doxorubicin, procarbazine, bleomycin, vincristine, and prednisone. The patients were restaged after three cycles of therapy, and restaging was repeated at 2-month intervals in patients who had persistent disease. Responding patients received two cycles of therapy after documentation of complete remission (CR). With all patients considered evaluable, 73% of the patients achieved a CR. Twenty-six of the 37 CRs (70%) achieved remission in the first three treatment cycles. The durability of remission in the rapidly responding patients was significantly better than for patients who required five cycles to achieve CR (80% v 40% at 2 years, P = .02) despite the latter patients having received two more cycles of therapy. Rapidly responding patients with DLCL do not require prolonged therapy and have a better prognosis than patients achieving a CR more slowly.
Overall survival using local excision techniques with and without radiation compared with APR for stage I rectal cancer: A SEER based analysis
Authors: A. H. Wortham, D. Schreiber, J. Rineer, E. Katsoulakis, R. Sroufe, E. Marienberg, E. Nwokedi, P. Han, K. Choi, M. Rotman
Journal: Journal of Clinical Oncology (2009)

4032 Background: The standard of care for Stage I rectal cancer is radical resection. Increasingly, local therapies have been used to decrease morbidity and preserve sphincter control. Due to increased risk of local recurrence with less radical surgery, patients often receive adjuvant radiation. This analysis compares the outcomes of sphincter sparing treatment with radical surgery in Stage I rectal cancer. Methods: Using the Surveillance, Epidemiology and End-Results (SEER) registry, we performed a query of patients with Stage T1–2N0 (T=4 cm or less) rectal adenocarcinoma between 1988 and 2003 who were treated with either local excision alone (LE), local excision followed by radiotherapy (LE+RT) or abdominoperineal resection (APR). APR was selected as comparison group to select for a similar cohort of patients with distal tumors that would be eligible for LE. Kaplan-Meier analysis was performed to compare overall survival for patients receiving radical surgery versus local therapy. Subgroup survival analysis was performed by T-stage (T1 vs T2). Results: 2,144 patients were identified: 744 were treated with LE alone, 197 underwent LE+RT, and 1203 underwent APR. Patients undergoing LE ± RT had a median survival (MS) of 131 vs 121 months in the APR group (p=0.574). When comparing LE vs LE+RT, there was no difference in MS for the whole cohort (134 vs 108 months, p=0.39). However, on subgroup analysis there was a significant survival benefit in favor of LE+RT for T2N0 only (104 vs 74 months, p=0.048). For T1N0, the MS for LE+RT was 161 vs 147 months for LE (p=0.621). Comparing with APR, patients undergoing LE+RT had a MS of 108 vs 121 months in the APR group (p=0.684). For T1N0, the MS for LE+RT was 161 vs 153 months for APR (p=0.62). For T2N0 patients, the MS for LE+RT was 104 vs 114 months for APR (p=0.726). Conclusions: According to this analysis, there was no statistical difference in survival for patients with Stage I rectal carcinoma undergoing APR versus LE+RT. Selected patients with T1N0 may undergo local excision alone. However, patients with T2N0 disease should undergo adjuvant radiation after local excision. The risks and benefits of these treatment strategies should be weighed and treatment should be individualized. No significant financial relationships to disclose.
Lung function, forced expiratory volume in 1 s decline and COPD hospitalisations over 44 years of follow-up
Authors: Suneela Zaigham, Per Wollmer, Gunnar Engström
Journal: European Respiratory Journal (2015)

The use of baseline lung function in the prediction of chronic obstructive pulmonary disease (COPD) hospitalisations, all-cause mortality and lung function decline was assessed in the population-based “Men Born in 1914” cohort. Spirometry was assessed at age 55 years in 689 subjects, of whom 392 had spirometry reassessed at age 68 years. The cohort was divided into three groups using fixed ratio (FR) and lower limit of normal (LLN) criterion: forced expiratory volume in 1 s (FEV 1 )/vital capacity (VC) ≥70%, FEV 1 /VC &lt;70% but ≥LLN (FR + LLN − ), and FEV 1 /VC &lt;70% and &lt;LLN (FR + LLN + ). Over 44 years of follow-up, 88 men were hospitalised due to COPD and 686 died. Hazard ratios (95% CI) for incident COPD hospitalisation were 4.15 (2.24–7.69) for FR + LLN − and 7.88 (4.82–12.87) for FR + LLN + (reference FEV 1 /VC ≥70%). Hazard ratios for death were 1.30 (0.98–1.72) for FR + LLN − and 1.58 (1.25–2.00) for FR + LLN + . The adjusted FEV 1 decline between 55 and 68 years of age was higher for FR + LLN − and FR + LLN + relative to the reference. Of those with FR + LLN − at 55 years, 53% had progressed to the FR + LLN + group at 68 years. Airflow obstruction at age 55 years is a powerful risk factor for future COPD hospitalisations. The FR + LLN − group should be carefully evaluated in clinical practice in relation to future risks and potential benefit from early intervention. This is reinforced by the increased FEV 1 decline in this group.
Medical costs associated with imatinib (IM) non-compliance in chronic myeloid leukemia (CML) patients (pts)
Authors: E. Q. Wu, W. Feng, S. Johnson, N. Beaulieu, P. Cremieux, J. Cortes
Journal: Journal of Clinical Oncology (2007)

17514 Background: Not adhering to treatment (tx) may lead to suboptimal outcomes. This study examined associations between medical costs and IM compliance in CML pts. Methods: CML pts under age 65 were identified with ICD-9 diagnosis code (205.1X) using MarketScan Commercial Claims data between 1/1/02–12/31/05. Pts were required to be continuously enrolled in the 4 months prior to (baseline) and the 6 months following (study period) IM initiation. CML severity was categorized into 3 groups by diagnosis of CML and related comorbidities. Compliance was defined by medication possession ratio (MPR=total days of IM supply in the study period divided by 180), and stratified into 3 groups (low: &lt;65%, medium: 65–95%, high: 95–100%). Tx interruption was defined as tx gap of 30 or more consecutive days in the study period. Costs for inpatient (IP), ER, outpatient (OP) services and OP drugs during the study period were adjusted to 2005 dollars. Costs, the number of IP admissions and hospital days were compared across different levels of tx compliance using Wilcoxon tests. A generalized linear model (GLM) was also used to compare costs controlling for age, sex, CML severity, Charlson comorbidity index, year of IM start, etc. Results: The study sample consisted of 404 pts. Compared to the high MPR group, pts in the low MPR group incurred 1.6 times the average total health care costs (p &lt;.001), 5.9 times the IP costs (p&lt;.001), 2.6 times the OP costs (p=.722), 2.1 times the non-IM drug costs (p&lt;.001), and 0.39 times the IM drug costs (p&lt;.001). Compared to the high MPR pts, low MPR pts had on average 3.8 times the IP admissions (p&lt;.001), and 7.3 times the IP days (p&lt;.001). Comparing costs of pts interrupting tx versus those who did not showed similar trends. GLM regression showed that 6-month total health care costs per patient in the low MPR group were 1.4 times (p&lt;.01) those of the high MPR group. Pts who had tx interruption had 1.3 times the total health care costs (p&lt;.01) compared to those who did not. Conclusions: This study shows that better IM compliance was associated with significantly lower health care costs in CML pts, especially for IP costs. Further analyses will be conducted to confirm whether lower compliance leads to more hospitalizations. No significant financial relationships to disclose.
Bone morphogenic proteins are novel suppressors of breast cancer metastasis
Authors: Bedrich Eckhardt, Belinda Parker, Normand Pouliot, Wei-Zu Lai, Robin Anderson
Journal: Cancer Research (2007)

AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA

2177 

The majority of deaths due to breast cancer result from the formation of metastases that arise in distant organs such as lymph nodes, lung, liver and bone. These secondary tumors result in organ failure, spinal cord compression, bone pain and fractures. To date, there is no effective cure and current treatments aim to suppress symptoms arising from metastatic disease. To enhance our current understanding of metastasis, we have utilised a preclinical mouse model to investigate the genetic determinants of breast cancer metastasis. We array profiled several tumor lines from this model and correlated gene expression with their ability to metastasize in vivo . Gene ontology analysis revealed that highly metastatic tumors expressed a greater percentage of  communication genes, an ontology populated with cell signaling and extracellular matrix (ECM). genes. Bone morphogenic protein-4 (BMP4), a cytokine involved in tissue patterning and morphogenesis, was found to have reduced expression in highly metastatic tumors and was further characterised for its potential role as a metastasis suppressor.

Overexpression of BMP4 in highly metastatic 4T1.2 tumors dramatically enhanced the overall survival of mice bearing these tumors. Increased survival was attributed to decreased tumor cell escape from the primary site and a significant reduction in detectable secondary tumors. Similar results were obtained in mice bearing 4T1.2 tumors overexpressing BMP7 or both BMP4 and BMP7. To test the therapeutic potential of BMPs, we administered recombinant BMP4 (rBMP4) protein to tumor cells in vitro and in vivo . Canonical signaling pathways were activated in tumor cells in response to rBMP4 in vitro and administration of rBMP4 significantly extended the overall survival of mice with 4T1.2 tumors. Taken together, these results implicate a novel role for BMPs as suppressors of breast cancer metastasis.
Effects of home oximetry on chronic obstructive pulmonary disease exacerbations
Authors: Mei Ying Chew, T.K. Lim, Pauline Chong, Min Tang, Charmaine Lim
Journal: European Respiratory Journal (2011)

Background:  A large proportion of patients with chronic obstructive pulmonary disease (COPD) require hospitalized care, often at a very high frequency.   Aims:  We hypothesize that home monitoring with pulse oximetry (SpO2) would enable patients to detect exacerbations and start action plans earlier so as to reduce hospitalizations, and also to improve symptom control and quality of life (QOL) by encouraging safer home exercise.   Methods:  We enrolled COPD patients from a university hospital. They were provided with SpO2 for 6 months and were educated on their use to augment action plans for exacerbations. Home exercise was measured with pedometers. The primary outcomes were hospitalization days, emergency department (ED) attendances and intensive care unit (ICU) days. We also measured QOL and 6 minute walk.   Results:  We enrolled 26 patients with mean (SD) age 73 (9) years and mean FEV1 (SD) 47 (17)% pred. There were 84 (6) hospital days vs 50 (2) hospital days (p=0.16) at 6 months. There were 7 (1) ICU days at baseline vs none (p=0.12) at 6 months. The mean SGRQ score was 32 (16) vs 27 (14) at 6 months (p=0.003). The 6 minute walk test (207 (56) vs 212 (67) at 6 months) and pedometer steps (4007 (2706) steps vs 4421 (2969) steps) were also not significantly better. There was 1 death.   Conclusions:  In a comprehensive care setting, self-monitoring of SpO2 in patients with severe COPD may have little effect on hospitalizations and quality of life.