tbuckley/cabot-search huggingface dataset:
SIRFLOX: Randomized Phase III Trial Comparing First-Line mFOLFOX6 (Plus or Minus Bevacizumab) Versus mFOLFOX6 (Plus or Minus Bevacizumab) Plus Selective Internal Radiation Therapy in Patients With Metastatic Colorectal Cancer
Authors: Guy A. van Hazel, Volker Heinemann, Navesh K. Sharma, Michael P.N. Findlay, Jens Ricke, Marc Peeters, David Perez, Bridget A. Robinson, Andrew H. Strickland, Tom Ferguson, Javier Rodríguez, Hendrik Kröning, Ido Wolf, Vinod Ganju, Euan Walpole, Eveline Boucher, Thomas Tichler, Einat Shacham-Shmueli, Alex Powell, Paul Eliadis, Richard Isaacs, David Price, Fred Moeslein, Julien Taieb, Geoff Bower, Val Gebski, Mark Van Buskirk, David N. Cade, Kenneth Thurston, Peter Gibbs
Journal: Journal of Clinical Oncology (2016)

SIRFLOX was a randomized, multicenter trial designed to assess the efficacy and safety of adding selective internal radiation therapy (SIRT) using yttrium-90 resin microspheres to standard fluorouracil, leucovorin, and oxaliplatin (FOLFOX)-based chemotherapy in patients with previously untreated metastatic colorectal cancer.Chemotherapy-naïve patients with liver metastases plus or minus limited extrahepatic metastases were randomly assigned to receive either modified FOLFOX (mFOLFOX6; control) or mFOLFOX6 plus SIRT (SIRT) plus or minus bevacizumab. The primary end point was progression-free survival (PFS) at any site as assessed by independent centralized radiology review blinded to study arm.Between October 2006 and April 2013, 530 patients were randomly assigned to treatment (control, 263; SIRT, 267). Median PFS at any site was 10.2 v 10.7 months in control versus SIRT (hazard ratio, 0.93; 95% CI, 0.77 to 1.12; P = .43). Median PFS in the liver by competing risk analysis was 12.6 v 20.5 months in control versus SIRT (hazard ratio, 0.69; 95% CI, 0.55 to 0.90; P = .002). Objective response rates (ORRs) at any site were similar (68.1% v 76.4% in control v SIRT; P = .113). ORR in the liver was improved with the addition of SIRT (68.8% v 78.7% in control v SIRT; P = .042). Grade ≥ 3 adverse events, including recognized SIRT-related effects, were reported in 73.4% and 85.4% of patients in control versus SIRT.The addition of SIRT to FOLFOX-based first-line chemotherapy in patients with liver-dominant or liver-only metastatic colorectal cancer did not improve PFS at any site but significantly delayed disease progression in the liver. The safety profile was as expected and was consistent with previous studies.
A single-center retrospective analysis: The correlation of grade, chromogranin-A, SST2 IHC stains, and OctreoScan imaging in small bowel and pancreatic NETs.
Authors: I. A. Onwere, T. O'Dorisio, M. O'Dorisio, Y. Menda, B. DeYoung
Journal: Journal of Clinical Oncology (2010)

e14585 Background: Previous analyses have demonstrated that neuroendocrine tumor (NET) grade correlates well with OctreoScan positivity, SST2, and Chromogranin-A immunohistochemical (IHC) staining. Historically lower grade tumors were more likely to have a higher amplification of STT2 receptors and OctreoScan positivity. There have however been reports of pancreatic neuroendocrine tumors expressing a high degree of SST2 receptors. We hypothesized that tumor origin Chromogranin-A (ChrgA) and SST2 IHC staining would correlate with OctreoScan positivity and Wick's grade, but were unsure if this would be the case with pancreatic NETs. Methods: We retrospectively analyzed 79 formalin-fixed paraffin-embedded tumor specimens based on tumor histological origin for 1) Wick's tumor grade, 2) SST2 receptor, and 3) ChrgA IHC staining. We sought to primarily analyze NETs of the small bowel and pancreas. CT scan evidence of stage IV disease was corroborated with OctreoScan imaging, but only pancreatic primaries were assessed. OctreoScan imaging was graded as positive or negative. Wick's grading system of: 1 = well differentiated; 2 = moderately differentiated; 3 = poorly differentiated; SST2 and ChrgA IHC stains were performed and graded: 1 +, 2+ or 3+. Results: See Table. Conclusions: Although published reports have demonstrated a higher correlation of OctreoScan positivity with lower grade neuroendocrine tumors, our results demonstrate that pancreatic neuroendocrine tumors were consistently higher grade, OctreoScan positive, and ChrgA and SST2 rich. Small bowel tumors were more likely to be lower grade (Wick's grade 1-2) as consistent with published reports. ChrgA and SST2 IHC staining of 2-3+ appeared to correlate with Wick grade in NETs of the small bowel, but were neither sensitive nor specific in those of pancreatic neuroendocrine origin. Primary tumor (NETs) Wick grade 1 Wick grade 2 Wick grade 3 Small bowel 21/56 26/56 9/56 Pancreatic 3/23 8/23 12/23 Chromogranin-A IHC STAIN Small bowel tumors Pancreatic tumors 1+ 2/56 2/23 2+ 5/56 3/23 3+ 49/56 17/23 Neg 0/56 1/23 SST2 IHC STAIN Small bowel tumors Pancreatic tumors 1+ 23/56 3/23 2+ 16/56 10/23 3+ 14/56 8/23 Neg 3/56 2/23 No significant financial relationships to disclose.
PAP smear in third world countries? Still an option
Authors: F. C. Duarte Munoz, J. Figueroa, A. Andrade, G. Aguilar, C. Ayala, M. Sanchez
Journal: Journal of Clinical Oncology (2005)

1030 Background: Cervical cancer is the most frequent malignancy in 3rd world countries. Early detection programs have not helped to decrease mortality in this countries because they have not been able to cover entire population. This has created the misconception that those programs are not useful in 3rd world countries. This is true due several reasons including lack of knowledge, low income and impossibility to mobilize to places were this test can be performed. The cost for the governments can be high and they do not invest enough resources because cancer is not a priority in our countries. Since 1999 we started a program in a defined area trying to cover the entire population and by using a different approach we believe there is a cost effective way to run nationwide programs. Method: From 1999 to 2004 we started a early detection and prevention program for cervical cancer in a very poor area in Tegucigalpa denominated Campo Cielo that included 23 small neighborhoods, this included a 11,000 houses and more than 60,000 people living. We did targeted the female population in the range of 25 to 59 years old that resulted in 15,731 ladies. This project was sponsored by UICC. The program was based in trained technicians that spent his time at the community and were promoting and educating people in the area in a home by home basis and taking PAP smear in different areas every day (mobile clinics) trying to cover the entire population. The results were sent the same day for processing and they were deliver to the ladies in a personal basis to ensure they receive it. If the result was positive for malignancy a major effort to assure treatment was done. Emphasis was taken in quality control. Results: The initial results were discouraging, only 400 PAP smears the first year mostly due reluctant population. Once the people was educated the number increased up to 11,310 a year covering more than 70% of the population. Initial non adequate smears of 3.68% that dropped to 1,15%. The percentage of first time patients also dropped from 33% to 15%. We found 137 Low grade lesions, 164 High grade lesions and 51 with invasive carcinoma. Conclusion: It is feasible to develop an effective cost effective early detection program for uterine cervix cancer in 3rd world countries using intensive education and mobile clinics for PAP smear. No significant financial relationships to disclose.
Microdomains, Inflammation, and Atherosclerosis
Authors: Mary G. Sorci-Thomas, Michael J. Thomas
Journal: Circulation Research (2016)

Elevated levels of cholesteryl ester (CE)-enriched apoB containing plasma lipoproteins lead to increased foam cell formation, the first step in the development of atherosclerosis. Unregulated uptake of low-density lipoprotein cholesterol by circulating monocytes and other peripheral blood cells takes place through scavenger receptors and over time causes disruption in cellular cholesterol homeostasis. As lipoproteins are taken up, their CE core is hydrolyzed by liposomal lipases to generate free cholesterol (FC). FC can be either re-esterified and stored as CE droplets or shuttled to the plasma membrane for ATP-binding cassette transporter A1-mediated efflux. Because cholesterol is an essential component of all cellular membranes, some FC may be incorporated into microdomains or lipid rafts. These platforms are essential for receptor signaling and transduction, requiring rapid assembly and disassembly. ATP-binding cassette transporter A1 plays a major role in regulating microdomain cholesterol and is most efficient when lipid-poor apolipoprotein AI (apoAI) packages raft cholesterol into soluble particles that are eventually catabolized by the liver. If FC is not effluxed from the cell, it becomes esterified, CE droplets accumulate and microdomain cholesterol content becomes poorly regulated. This dysregulation leads to prolonged activation of immune cell signaling pathways, resulting in receptor oversensitization. The availability of apoAI or other amphipathic α-helix-rich apoproteins relieves the burden of excess microdomain cholesterol in immune cells allowing a reduction in immune cell proliferation and infiltration, thereby stimulating regression of foam cells in the artery. Therefore, cellular balance between FC and CE is essential for proper immune cell function and prevents chronic immune cell overstimulation and proliferation.
Phase I trial involving the pharmacodynamic (PD) study of circulating tumour cells, of CP-751,871 (C), a monoclonal antibody against the insulin-like growth factor 1 receptor (IGF-1R), with docetaxel (D) in patients (p) with advanced cancer
Authors: G. Attard, P. C. Fong, R. Molife, S. Reade, H. Shaw, A. Reid, J. Spicer, J. Hamlin, A. Gualberto, J. S. De Bono
Journal: Journal of Clinical Oncology (2006)

3023 Background: C is the first specific, fully human, monoclonal antibody to target IGF-1R in clinical trials. It potently inhibits IGF-1R signaling, enhancing D antitumour activity. This trial investigated the safety, feasibility, dose limiting toxicity (DLT), PK and antitumor activity of D administered with C every 3 weeks. PD studies evaluated circulating tumor cell (CTC) IGF-1R expression and CTC counts pre- and post-treatment. Methods: The C doses tested were 0.1, 0.4, 0.8, 1.5, 3.0, 6.0 and 10 mg/kg in sequential cohorts of 3–6 p. D was fixed at 75mg/m 2 . P achieving disease control continued on C alone if experiencing D toxicity. Results: 21 p (20 male) have received 100 courses of C with D. 7 p received 8 or more courses of the combination. A further 21 courses of C alone have been administered. No toxicity has been attributed to C to date with the observed toxicities being attributable to D. Grade 3/4 toxicities were neutropenia (16/21 p) and neutropenic fever in 2/21 p. Grade 3 diarrhea was reported in 3 p, but this was easily controlled with antidiarrheals. Transient grade 1 hyperglycaemia was noted largely on day 1, following steroid premedication (14 p), but no significant C related hyperglycemia has been observed. An MTD has not been reached. Serial echocardiograms demonstrated no cardiac toxicity. Of 18 castration resistant prostate cancer (CRPC) p treated, 4 have had a confirmed PR, with 2 unconfirmed PR and 2 having disease stabilization for &gt; 6 months (median number of courses: 10; range: 3–12). 5 p have maintained SD with C alone for 2–7 courses. CTC were detected in 16 of 18 p (CTC numbers ranged from 1 to 202 in 7.5ml of blood). IGF-1R expression was detected in 12 p. CTC IGF-1R was undetectable following treatment with C at doses above 3 mg/kg. Conclusions: This combination is safe and feasible with no toxicity attributed to C and encouraging antitumor activity in CRPC. [Table: see text]
Tropical Pulmonary Eosinophilia
Authors: E A Ottesen, T B Nutman
Journal: Annual Review of Medicine (1992)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
The Intensive Care Global Study on Severe Acute Respiratory Infection (IC-GLOSSARI): a multicenter, multinational, 14-day inception cohort study
Authors: Yasser Sakr, Ricard Ferrer, Konrad Reinhart, Richard Beale, Andrew Rhodes, Rui Moreno, Jean Francois Timsit, Laurent Brochard, B. Taylor Thompson, Ederlon Rezende, Jean Daniel Chiche
Journal: Intensive Care Medicine (2016)
Antitumor activity of MDV3100 in a phase I/II study of castration-resistant prostate cancer (CRPC)
Authors: H. I. Scher, T. M. Beer, C. S. Higano, M. Taplin, E. Efstathiou, A. Anand, D. Hung, M. Hirmand, M. Fleisher
Journal: Journal of Clinical Oncology (2009)

5011 Background: MDV3100 is a novel AR antagonist selected for activity in prostate cancer model systems with overexpressed AR. In contrast to bicalutamide, MDV3100 blocks nuclear translocation of AR and DNA binding, and has no known agonist activity when AR is overexpressed. Antitumor activity of MDV3100 in a Phase I/II trial was assessed by prostate-specific antigen (PSA), soft tissue and osseous disease, circulating tumor cells (CTC), and time on treatment. Methods: Patients (pts) with progressive CRPC were enrolled in sequential cohorts of 3–6 pts at 30, 60, 150, 240, 360, 480 and 600 mg/day. Once the safety of a dose was established, enrollment was expanded at doses &gt;60 mg/day to include 12 chemotherapy-naïve (naïve) and 12 post-chemotherapy pts per cohort. Results: 140 pts were enrolled. 114 pts at 30–360 mg/day have been followed for &gt;12 weeks. PSA declines (&gt;50% from baseline) were observed at week 12 in 57% (37/65) of naïve and 45% (22/49) of post-chemo pts. Data suggest a dose-response trend particularly in post-chemo pts where PSA responses were 32% at 60 and 150 mg/day and 58% at 240 and 360 mg/day. At 12 weeks, radiographic control (no progression) was observed in 35/47 pts (74%) with evaluable soft tissue lesions per PCWG2 guidelines and 50/81 pts (62%) with bone lesions. CTC counts on 101 of 114 pts showed 92% (56/61) with favorable (&lt;5) counts pretreatment maintained favorable posttreatment counts, while 53% (21/40) converted from unfavorable to favorable posttreatment. For post-chemo pts, favorable retention was 100% (17/17) and unfavorable to favorable conversion at 240 and 360 mg/day was 60% (6/10). 87 pts at 30–240 mg/day have been followed for &gt;24 weeks; 35 (40%) received treatment &gt;24 weeks. At 600 mg/day, 2 of 3 pts had dose limiting toxicity (rash; seizure). Dose reductions due to fatigue were noted at 480 and 360 mg/day. Conclusions: MDV3100 is a promising candidate for the treatment of prostate cancer assessed by PSA, imaging, CTC, and time on treatment. The data suggest a dose-response trend and consistency across endpoints. Pt follow-up is continuing. The efficacy comparable to that at higher doses and the better adverse event profile, led to the selection of 240 mg/day as the recommended dose for a phase III trial in CRPC. [Table: see text]
Transmission of BCG-Associated Tumor Resistance From Maternal to Newborn Guinea Pigs 2
Authors: Percy Minden, Jonni Sandridge, Mark A. Wainberg, J. Kenneth McClatchy
Journal: JNCI Journal of the National Cancer Institute (1976)

Resistance to line-10 hepatocarcinoma was studied in the newborn offspring of inbred strain-2 Sewall Wright guinea pigs that had recovered from this tumor after prior administration of subcellular components of Mycobacterium bovis strain BCG. These mothers gave birth to 15 offspring, 53% of which resisted repeated challenges with this tumor. Offspring of mothers who had been given only BCG components were similarly tested. Complete protection was observed in 23.5% of 17 babies and attenuation of disease in many others. All control offspring from normal, untreated mothers succumbed to this tumor. Resistance was associated with delayed cutaneous hypersensitivity reactions to tumor and mycobacterial antigens.
Correlation between preoperative endometrial sampling diagnosis of FIGO grade 1 endometrial adenocarcinoma and final hysterectomy pathology
Authors: S. Kehoe, N. R. Abu-Rustum, L. Gattoc, C. Rabbitt, R. A. Soslow, R. R. Barakat, M. M. Leitao
Journal: Journal of Clinical Oncology (2008)

5586 Background: To evaluate the ability of a preoperative diagnosis of FIGO grade 1 endometrial adenocarcinoma and intraoperative depth of myoinvasion (DOI) to predict low- (LR) and high-risk (HR) final uterine pathology. Methods: We reviewed 1423 consecutive cases with endometrial cancer treated at our institution from 1/1/93 to 5/31/06 to identify cases with a preoperative endometrial biopsy demonstrating FIGO grade 1 endometrial adenocarcinoma. All cases were reviewed at our institution and had surgical therapy at our institution. We excluded equivocal preoperative biopsies and serous or clear cell histology. Final uterine pathologic findings were grouped into low- and high- risk based on the risk of nodal metastasis reported in GOG 32. HR uterine pathology was defined as FIGO grade 2 or 3 with inner and middle third myoinvasion, any grade with outer third myoinvasion, or serous/clear cell histology regardless of degree of myoinvasion. Chi-square and Fisher-exact test were used as appropriate. Results: We identified 490 cases. The median age was 60 years (range 29–90 years). FIGO grade was upgraded in 71 (14.7%) of 482 cases (66 (13.7%) grade 2 and 5 (1%) grade 2–3 and 3) in which final pathologic grade was assessable. Serous or clear cell histology was diagnosed in 6 (1.2%) additional cases. HR final uterine pathology was seen in 86 (18.5%) cases. Frozen section assessment of DOI was performed in 270 (55%) cases. Frozen section assessment of DOI was associated with HR pathology (p<0.001). HR pathology was present in 3 (3.6%) of 84 cases with either no tumor or myoinvasion identified on frozen section. HR pathology was identified in 27 (18%) out of 197 cases with myoinvasion <50% on frozen section and in 15 (65%) of 22 cases with ≥50% myoinvasion. Lymph node metastasis was identified in 9 (4.4%) of 205 patients that had nodal evaluation. Conclusions: Preoperative FIGO grade 1 diagnosis correlates with final grade diagnosis in 85% of cases. The rate of HR uterine pathology based on preoperative grade 1 alone is 18.5%. Frozen section, although not entirely accurate, may help further stratify for the risk of final HR uterine pathology. The rate of HR pathology is 4% if no invasion is identified on frozen section and 18% if 50% myoinvasion is identified. No significant financial relationships to disclose.
A randomized phase 3 trial of gemcitabine with or without carboplatin in performance status 2 (PS2) patients (pts) with advanced (stage IIIB with pleural effusion or stage IV) non-small cell lung cancer (NSCLC)
Authors: C. K. Obasaju, P. Conkling, D. Richards, J. Fitzgibbons, J. Arceneau, K. A. Boehm, L. Asmar, J. Cunneen, G. Peng, C. Reynolds
Journal: Journal of Clinical Oncology (2007)

7533 Background: The optimal treatment of patients with advanced NSCLC and PS2 has not been resolved. A retrospective analysis of 99 pts with PS2 in CALGB 9730 (Lilenbaum, JCO 2005) demonstrated improved survival associated with combination carboplatin- paclitaxel versus paclitaxel alone (median overall survival=4.7 vs. 2.4 mos., p=.019). Gemcitabine-carboplatin (GC) is an active doublet in advanced NSCLC and is at least as active as paclitaxel-carboplatin (PC) in PS2 pts (ECOG 1599, Tester ASCO 2004). A prospective validation of the activity of GC is needed, which is addressed by comparing GC versus gemcitabine (G) alone in this setting. Methods: 161 chemonaïve pts with advanced NSCLC and PS2 were randomly assigned to G 1250 mg/m 2 alone on Days 1,8 or GC (G 1000mg/m 2 Days 1,8 followed by C AUC 5 on Day 1). Cycles were repeated every 21 days for 6 cycles or until disease progression or intolerable toxicity. Primary endpoint was median survival. Conclusions: GC resulted in an improved response rate among NSCLC pts with PS2 over G alone. As expected, G3–4 toxicities were greater with GC. Overall survival data will be reported at the time of the meeting. [Table: see text] [Table: see text]
Final results of a prospective multicenter study on the prevalence and genotype/phenotype correlation of the dihydropyrimidine dehydrogenase (DPD) gene exon-14 skipping mutation in patients treated with 5-fluorouracil (5-FU) chemotherapy
Authors: M. Raida, A. Friedrich, H. Borris, D. Niederwieser, D. Behnke, K. O. Kliche, K. Ruffert, A. Schalhorn, W. Schwabe, P. Hausler
Journal: Journal of Clinical Oncology (2006)

3076 Background: DPD represents the initial and rate-limiting enzyme in the catabolism of 5-FU. Deficiency of DPD has been linked to toxic side effects of 5-FU. The most common mutation of the DPD gene resulting in severe DPD deficiency is a G to A mutation in the GT 5’-splice recognition site of intron 14 (exon 14 skipping mutation). The corresponding mRNA lacks exon 14 and the enzymatic activity of the translated DPD protein is virtually absent. In a clinical setting heterozygous and homozygous carriers are being observed. Methods: We developed an RT-PCR based assay suitable for routine identification of the exon 14 skipping mutation. From February 2001 to October 2004 we performed an open, uncontrolled, prospective multicenter study to evaluate the prevalence and genotype/phenotype correlation of the exon 14 skipping mutation in patients treated with 5-FU chemotherapy. 1455 patients from 70 clinical centers in Germany were included in the study. Results: We identified 15 heterozygous carriers confirming a prevalence of 1% in the Caucasian population. For the analysis of 5-FU related toxicity WHO grades were ranked with a toxicity index revealing a significant higher toxicity in heterozygous compared to wildtype patients (p&lt;0.0001). 50% of the heterozygote patients subsequently were treated with reduced doses of 5-FU. Nonetheless the positive predictive value of the screening test was still 50% indicating a strong correlation between genotype and phenotype. To identify patients in risk of severe 5-FU related toxicity we performed 5-FU pharmacokinetics in 12 heterozygous patients and 8 wildtype patients. All heterozygous patients showed a pathological 5-FU half-life with broad variations after intravenous bolus application of 450 mg/m 2 5-FU while 75% of the wildtype controls had physiological results. Conclusions: We conclude that routine testing for the exon 14 skipping mutation and additional 5-FU pharmacokinetics for heterozygous patients prior to 5-FU treatment is an important step towards individually tailored therapy in cancer patients. [Table: see text]