tbuckley/cabot-search huggingface dataset:
Response to imatinib mesylate (IM) in fibrosarcoma (FS) arising in dermatofibrosarcoma protuberans (DFSP)
Authors: A. Gronchi, S. Stacchiotti, F. Pedeutour, P. Collini, E. Tamborini, C. Morosi, F. Crippa, U. Pastorino, S. Pilotti, P. G. Casali
Journal: Journal of Clinical Oncology (2008)

10593 Background: IM is active in DFSP by targeting PDGFRB that is constitutively activated in this rare low grade malignant tumor as a consequence of the chromosomal translocation t (17;22). Fibrosarcomatous transformation rarely occur in DFSP, with an increased risk for metastasis. IM activity in FS arising from DFSP is less well defined. Methods: From June 2007, 2 patients with metastatic high- grade FS in DFSP (both men, age 45/75, PS 2) were treated with IM 400 mg/day. Both cases have been investigated by FISH analysis for t (17;22) in the DFSP and in the FS component. We also review all patients (pts) surgically treated at our institution from 1997 for localized FS in DFSP. Results: Both pts treated with IM had a RECIST PR, along with PET and subjective major response after 4 weeks of treatment (SUV max decrease >75%), but they both dramatically progressed, after 4 months in one case (A) and after 5 months in the second (B). Pt A underwent macroscopically complete surgery of a mediastinic metastatic lesion after progression, with no evidence of response on the surgical specimen. Pt B died 1 month later for brain metastasis. By FISH analysis the fusion gene was present before treatment with IM in both tumor components, in the same proportion (2–3 fusion gene/nucleus). Biochemical and cytogenetic analyses on patient A metastasis are ongoing. A retrospective analysis was made in 205 pts surgically treated at our institution for localized DFSP: 12 showed a fibrosarcomatous component. Only 2 pts of this series relapsed with distant metastases, to the brain in one case. Both pts died in a few months. Pathology of these 12 patients is under review and FISH analysis is ongoing. Conclusions: FS in DFSP can maintain the t (17;22) translocation and can be sensitive to IM, but the response may be short in time. Of interest, CNS metastases have been observed in this series. The molecular basis of disease progression on IM is under study. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Glaxo, MedImmune, Novartis, Pfizer Oncology, sanofi-aventis Novartis, PharmaMar, Sigma Tau Jansen Cilag, Novartis, Pfizer Oncology, Sigma Tau Novartis, PharmaMar
TLR9-targeted CpG immunostimulatory treatment of metastatic melanoma: A phase II trial with CpG 7909 (ProMune)
Authors: S. N. Wagner, M. Pashenkov, G. Goess, C. Wagner, A. Schneeberger, A. M. Krieg, G. Stingl
Journal: Journal of Clinical Oncology (2004)

7513 Background: Malignant melanoma is widely accepted as an immunologically responsive tumor, but large recently reported chemobiotherapy trials have been disappointing and prognosis is poor. The new synthetic oligodeoxynucleotide CpG 7909 activates plasmacytoid dendritic cells (pDC) and B cells through specific interaction with Toll-like receptor 9 (TLR9) and is a strong activator of both innate and specific immunity. CPG 7909 crossreacts with mouse TLR9 and has shown impressive antitumor activity in preclinical tumor models when used as monotherapy. Methods: Patients with confirmed metastatic melanoma (stage IV without CNS metastases) were enrolled into an open-label, multicenter, single arm study. Pts received 6 mg CPG 7909 weekly by SC injection for 24 weeks or until disease progression in an outpatient setting. Disease status was assessed at screening and weeks 8, 16, and 24 according to RECIST. Results: 20 pts (5 female, 15 male, aged between 37 and 74) were enrolled. Two pts achieved a confirmed partial response (PR) and one has maintained this response with continuing therapy for over 13 months. Three pts achieved stable disease (SD). CPG 7909 was well tolerated. Adverse events included transient injection site reactions (erythema, swelling, induration), fever and arthralgias. Hematological and non-hematological toxicities were limited, transient and did not result in any withdrawals. Phenotyping of PBMC revealed activation of pDC under CPG 7909 therapy consistent with the mode of action and pts exhibiting PR or SD could be distinguished from non-R pts by differential dynamics in NK cell-cytotoxicity (1.6-fold increase vs. 1.7-fold decrease in lytic units, p<0.05) during the first 8 weeks of treatment. Conclusions: CPG 7909 exerts anti-tumor activity in pts with metastatic melanoma, can be administered safely and induces a phenotypic signature in PBMC associated with exposure and, possibly, response to therapy. A randomised phase II/III trial has been initiated to compare efficacy and safety of two dose levels of CPG 7909, CPG 7909 in combination with DTIC, and DTIC alone. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Coley Pharmaceutical Group Coley Pharmaceutical Group Coley Pharmaceutical Group Coley Pharmaceutical Group Coley Pharmaceutical Group
Pathological characteristics and clinical outcome in triple-negative breast cancer (BC) patients (PTS): Results from the NORA study
Authors: M. E. Cazzaniga, G. Mustacchi, P. Pronzato, F. Di Costanzo, A. De Matteis, A. Ravaioli, T. Gamucci, M. Brugia, M. Bari, E. Rulli
Journal: Journal of Clinical Oncology (2007)

11014 Background: Different studies have recently focused the attention on the so-called triple-negative pts, defined as ER-/PR- /HER2-. Although triple-negative tumours have been reported to be more aggressive, there are limited long-term data evaluating outcome as a function of this classification. Methods: NORA is an observational study aimed at investigating treatment modalities and clinical outcome of 3515 patients (pts) with early breast cancer (EBC) treated in 77 Oncological Centres in Italy from to 2000 to 2003, whose overall results have been already published. We now compare pathological characteristics and clinical outcome of pts for whom ER and PR andHER2 tests are negative with remaining pts (OTH). Results: 123 (4.1%) of 2968 evaluable pts resulted triple-negative. Out of these 123, 76 pts (61.7% vs 63.2% of OTH) were treated with conservative surgery (CS). Pathological T stage was T1 in55.3% pts (OTH: 59.6%), 47.9% were pN+ (OTH: 45.3%), 63.2 had G3 tumours (OTH: 34.1%). Chemotherapy alone was administered in 89.4% pts, mainly anthracycline-based (54.1%). At a median follow up of 27 months, all triple-negative pts were alive, 11 (8.9%) with relapse. No difference has been observed between two groups both in DFS (HR=0.74; 95%CI: 0.39–1.40; p=0.35) and OS (HR not estimated, p=0.99). Conclusions: Our results suggest that triple-negative pts have pathological characteristics similar to what observed in the other pts, receive CS in the same percentage of the cases, but have a 3-fold increase of undifferentiated tumours. On the contrary to what observed by other Authors, our data show that triple- negative pts do not have worse prognosis. Longer follow up is required to confirm these data. No significant financial relationships to disclose.
Do We Overtreat Patients Undergoing Transurethral Resection of the Prostate?
Authors: R G Notley, F A W Schweitzer
Journal: Journal of the Royal Society of Medicine (1978)

Two hundred unselected patients undergoing transurethral resection of the prostate have been surveyed. The routine use of endotracheal intubation, muscle relaxants, intermittent positive pressure respiration, intravenous fluids and postoperative sedation was avoided whereever possible. The results of this survey are presented and indicate that such measures can be omitted from the management of patients undergoing transurethral resection of the prostate with no significant increase in morbidity or mortality and, indeed, morbidity and mortality may be decreased by their exclusion.
Abstract 12263: Loss of p47phox Subunit of NADPH Oxidase Enhances Susceptibility to Biomechanical Stress: Novel Role Of p47phox in the Regulation of Cortactin and Actin Filaments
Authors: Vaibhav B Patel, Pavel Zhabyeyev, Wang Wang, Subhash K Das, Ratnadeep Basu, Zuocheng Wang, Zamaneh Kassiri, Gavin Y Oudit
Journal: Circulation (2012)

Background: The classical phagocyte NADPH oxidase (gp91phox or Nox2) is expressed in cardiomyocytes, fibroblasts and vasculature. Nox2 activation requires membrane translocation of the p47phox subu...
SWOG 0338: A phase II trial of imatinib mesylate in combination with capecitabine in metastatic breast cancer
Authors: H. K. Chew, W. E. Barlow, K. S. Albain, D. Lew, G. T. Budd, G. Allen, J. Gralow, R. Livingston
Journal: Journal of Clinical Oncology (2006)

10529 Background: Imatinib mesylate targets c-kit and platelet derived growth factor receptor (PDGFR) tyrosine kinases, and both are variably expressed in breast cancer. Inhibition of PDGFR by imatinib mesylate may decrease tumor interstitial pressure and improve delivery of chemotherapy. Based on preclinical synergy, SWOG conducted a phase II trial in metastatic breast cancer. Methods: Patients were eligible if they had adenocarcinoma of the breast that had progressed on at least 1 but ≤ 2 prior chemotherapy regimens for metastatic disease. No prior 5-FU or capecitabine for metastatic disease was allowed. Patients had to be &gt; 18 years with a Zubrod performance status ≤ 2 and have adequate organ function. Patients with brain metastases were ineligible. Patients received imatinib mesylate 400 mg orally daily and capecitabine 1000 mg/m 2 orally twice daily on days 1–14 of a 21-day cycle. If tolerated, the imatinib mesylate was increased to 600 mg daily in subsequent cycles. This was a 2-stage design with 25 patients with measurable disease accrued in the first stage. A total of 70 patients was planned, including those with nonmeasurable disease, if accrual proceeded to the second stage. The primary endpoint was to determine the confirmed response rate (RR) to the combination therapy. Secondary endpoints were to estimate the 6-month progression free survival, to determine the toxicities, and to explore c-kit and PDGFR in this population. Results: 27 patients were accrued; 6 were ineligible. 19 patients received therapy and were evaluable for toxicity. The median age was 59 years (36–78). Four responses were seen: 1 complete, 1 confirmed partial, and 2 unconfirmed partial (RR 21%). The 6-month progression free survival was 16%. There were no grade 4 toxicities. The most common grade 3 toxicities, seen in 7 patients, were diarrhea, fatigue, and hand-foot syndrome. As 2 of the 4 responses were unconfirmed, accrual did not proceed to the second stage. Conclusions: The combination of imatinib mesylate and capecitabine was well tolerated in patients with metastatic breast cancer, but the RR was not better than was seen in a prior study of single agent capecitabine. Correlative studies to explore c-kit, PDGFR, and estrogen receptor expression and response are in progress. No significant financial relationships to disclose.
Demographic factors on the incidence of KRAS mutation in colorectal cancers.
Authors: R. Abboud, R. Pai, J. Picus, L. E. Hall-Daniels, R. Suresh, A. Wang-Gillam, S. Sorscher, B. R. Tan
Journal: Journal of Clinical Oncology (2010)

e14040 Background: KRAS mutation status in colorectal cancers (CRCs) is predictive of response to anti-epidermal growth factor receptor therapies, such as cetuximab and panitumimab. Our objective was to determine the demographic factors on KRAS mutation status among patients with CRC seen at Washington University in St. Louis. Our secondary objective was to examine survival of patients stratified by age, race, disease location, and mutation status. Methods: A retrospective review of 271 patients on the CRC registry at Washington University was done between 1/17/07 and 12/18/09. All patients had KRAS mutational analysis. Patients with mutations to codons 12 or 13 were considered mutated. Others were considered wild-type. Age, sex, race, and location of primary tumor were examined for correlation with the rate of KRAS mutations. Survival was measured from the date of metastatic disease diagnosis to the date of death. Results: Patient cohort: Median age 58 (24–94), 20% AAs, 54% males. The overall rate of KRAS mutations was 43.5%. We found no significant association between KRAS mutation status and age or sex. The KRAS mutation rate among AAs (47%) was relatively higher than among Caucasians (43%). The KRAS mutation rate in colon cancers (46%) was higher than that in rectal cancers (37%). Median and overall survival statistics are preliminary; 76% of patients are still alive. However, overall survival is higher for wild type patients in all groups. Conclusions: In this single-institution retrospective study, KRAS mutation rates appear to be higher among AA patients and patients with colon, rather than rectal, primaries. Colorectal cancer patients with KRAS mutation have less therapeutic options than those with wild-type tumors. Thus, the difference in KRAS mutation rates among AA and Caucasians may, in part, elucidate factors contributing to worse outcomes among AA patients with colorectal cancers. Similarly, the higher rate of KRAS mutation in colon versus rectal tumors may contribute to worse prognoses. Mutated Nonmutated Median survival (days) Total (n) Age >= 50 43% 57% 614 203 < 50 44% 56% 577.5 68 Sex Male 43% 57% 565 145 Female 44% 56% 625.5 126 Race AA 47% 53% 573 55 Caucasian 43% 57% 617.5 210 Location Rectal 37% 63% 626 84 Colon 46% 54% 599 187 No significant financial relationships to disclose.
ErbB/Her dimerization in breast and lung cancer
Authors: S. Pidaparthi
Journal: Journal of Clinical Oncology (2005)

643 Background: Transmembrane receptor tyrosine kinases play an important role in the pathogenesis of many types of cancer. The EGFR family includes erbB1 (EGFR or Her1), erbB2 (Her2 or neu), erbB3 (Her3), and erbB4 (Her4). It is well established that ligands like EGF and HRG bind to the extracellular region of the EGFR monomers and promote receptor dimerization. Receptor dimerization leads to increased tyrosine kinase activity resulting in uncontrolled cell proliferation and inhibition of apoptosis. We have developed a method for the determination of Her dimerization patterns in cancer using eTag™ multiplexed assays. Materials and Method: We have analyzed a total of 73 snap-frozen human breast tissues and 37 lung tissues comprising of both tumor and normal samples. Using the proximity-based multiplexed eTag assays, we determined the dimerization profiles in these tissues. Results: ErbB/Her dimerization was detected only in tumor tissues but not in normal breast tissues, whether matched with the same donor or not. Out of the 31 breast tumor samples analyzed, Her1/2 dimers were detected in 20 tumor samples. Her-2/3 dimers were detected in 29 out of 43 tumor samples. We also found that all tumor samples had higher Her-2 levels compared to normal breast samples. In addition, we detected Her-2/2 homodimers in 27 out of 43 tumor samples. In lung tissues, seven out of 27 tumors had Her1/1 dimers while four out of 27 tumors had Her1/2 dimers, indicating that the predominant dimerization types in lung are Her1/1 and Her1/2. Our quantitative dimerization assays showed that the total receptor expression levels and dimerization profiles were different in different tumor samples both in lung and breast samples. Conclusion: eTag technology can offer a valuable prognostic and quantitative tool for stratifying cancer patients for targeted therapy. In addition, eTag technology can help in assessing the activation state of the receptor during the course of patient treatment. No significant financial relationships to disclose.
Safety and efficacy of modified dose-attenuated FOLFIRINOX chemotherapy in patients over 65 years with advanced pancreatic adenocarcinoma.
Authors: Matheus Bongers Alessandretti, Erika Pereira Brandao, Carina Meira Abrahão, Aline Rocha Lino, Rodnei Macambira Junior, Marcos André Costa, Marcelo Rocha Cruz
Journal: Journal of Clinical Oncology (2013)

e15176 Background: Few data regard efficacy and safety of FOLFIRINOX (oxaliplatin 85 mg/m 2 , irinotecan 180 mg/m 2 , fluorouracil bolus of 400 mg/m 2 and continuous infusion of 2400 mg/m 2 over 46 hours and leucovorin 400 mg/m 2 ) in patients over 65 years with advanced pancreatic adenocarcinoma. Methods: After Ethical Committee approval, consecutive patients age over 65 with biopsy proven pancreatic adenocarcinoma that received at least one cycle of modified dose-attenuated FOLFIRINOX (no bolus FU and reduced dose of at least one agent since first cycle) were selected (São José Hospital database) for a retrospective review for safety, response, and survival. Results: Nineteen consecutive patients were selected from our database. Patients characteristics included 12 (63,1%) males, 7 (36,9 %) females, median age 72,7 (range 66-79). Tumor location was 11 (57,8 %) head of the pancreas, 6 (31,57 %) body and 2 (11 %) in other sites. Grade 3/4 toxicities were reported in 10 patients (52,6 %): nausea/vomiting 1 (5,2 %), diarrhea 1 (5,2 %), fatigue 3 (15,7%), neutropenia 4 (21 %), thrombocytopenia 1 (5,2%) and febrile neutropenia 3 (15,6 %). Elevations in AST and ALT above the upper limit of normality were identified in 5 (26,31%). No deaths reported due to toxicity. Prophylactic granulocyte colony stimulator factor (G-CSF) was given to 14 (73 %). Seventeen patients completed at least four cycles; disease control was obtained in 15 (83, 3 %) with 1 complete response, 5 partial response and 9 stable diseases. Median reductions in doses in the first cycle of chemotherapy by drugs were: oxaliplatin 23,3 % (10%-30%), irinotecan 24,6 % (0%-60%), fluorouracil 20,6% (0%-40%). Median reductions in doses in the fourth cycle of chemotherapy by drugs were: oxaliplatin 20,8 % (0%-42%), irinotecan 24,9 % (0%-75%), fluorouracil 17,6% (0%-40%).With a median follow up of 4.5 months, median overall or progression free survival is not reached. Conclusions: Modified dose-attenuated FOLFIRINOX is a therapeutic option to elderly with advanced pancreatic adenocarcinoma. Although grade 3 and 4 toxicities were reported, they were manageable. Modified attenuated-dose of FOLFIRINOX needs further investigated.
Phase II study of radiotherapy plus concurrent irinotecan (CPT-11) and infusional 5-fluorouracil (5FU) in the treatment of T3-T4 locally advanced inoperable rectal cancer
Authors: E. L. Levine, S. Gollins, S. Susnerwala, B. Haylock, M. Saunders, S. Myint, A. Biswas
Journal: Journal of Clinical Oncology (2004)

3612 Background: Previously, we reported a Phase I study of radiotherapy with concurrent CPT-11 and 5FU for the treatment of locally advanced inoperable rectal cancer (Proc ASCO 2003, abst 1384). In combination with pelvic radiotherapy of 45 Gy in 25 daily fractions over five weeks, this established a recommended dose for CPT-11 of 60 mg/m2 given once per week, during weeks 1, 2, 3 and 4 as a 60 minute infusion, together with continuous infusional 5FU at 200 mg/m2 per day via a central line throughout radiotherapy, including weekends. This dose level was expanded to a cohort of thirty one patients for the present phase II assessment. Methods: All patients were initially staged using MRI. Patients with T3 (with threatened mesorectal edge on MRI scan) or T4 rectal cancer, were treated with the above regime. Surgery was performed 6 - 8 weeks following the completion of chemoradiation. Results: All patients completed chemoradiation as planned. There was only one grade 3 toxicity reported (diarrhoea) and the patient completed treatment successfully. Thirty-one patients entered, of whom twenty-nine (93%) underwent resection. Two patients were deemed inoperable because of unresectable pelvic disease. Sixteen patients (55%) had an anterior resection and thirteen patients (45%) had an abdomino-perineal resection. Twenty-six patients (87%) had complete excision of the tumour (Ro resection). Six patients (21%) had a complete response to chemoradiation (pCR). Four patients in addition (14%) had microfoci only of tumour remaining (near-pCR). Conclusions: Radiotherapy with concurrent CPT-11 and 5FU is a well tolerated treatment for locally advanced inoperable rectal cancer leading to a high probability of complete resection of the cancer. This treatment regime is currently being studied (in the NWCOG-2 trial), in a similar cohort of rectal cancer patients, but substituting Capecitabine for 5FU. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Aventis UK
Usefulness of the proximal isovelocity surface area method for quantification of the severity of aortic regurgitation in patients with eccentric regurgitant jets: Comparison with cardiac magnetic resonance
Authors: Anne-Catherine Pouleur, Agnes Pasquet, Bernhard Gerber, Jean-Louis Vanoverschelde, Jean-Benoît Le Polain De Waroux
Journal: Circulation (2006)

Background. In pts with aortic regurgitation (AR), Doppler-echocardiographic assessment of the proximal isovelocity surface area (PISA) permits quantification of AR severity. Since this assessment ...
Critical Care Medicine Manual.
Journal: Annals of Internal Medicine (1980)

REVIEWStreatment of brain edema and raised intracranial pres- sure with particular reference to normal pressure hy- drocephalus are especially useful since they provide practical diagnostic criteria and ideas concerning therapy.The latest in the pathogenesis and treatment of migraine and a workable scheme of aphasia and apraxia are covered in a very succinct and lucid manner.Finally the chapter "Clinical Application of Computerized Axial Tomography (CT Scanning)" attempts to provide a broad outline of certain well-defined, common, neuro- logical problems.However, as the author suggests, the chapter is somewhat superficial and incomplete and is therefore less useful than is the remainder of the book.
Mild anemia is associated with greater symptom burden (SB) and reduced quality of life (QoL) in cancer patients
Authors: L. Schwartzberg, A. C. Houts, B. V. Fortner
Journal: Journal of Clinical Oncology (2005)

8123 Background: Standard treatment guidelines for AC are not implemented until Hgb concentration falls below 10 g/dL. However, adverse effects of anemia may occurr at higher Hb thresholds. The objective of this study was to compare SB and QoL in pts with mild anemia and pts with normal Hb levels as measured by the Cancer Care Monitor (CCM). Methods: Retrospective study of 3416 pts from a large community oncology database grouped by gender and Hb excluding patients receiving ctx < 30 days or growth factor < 60 days to control for acute effects of ctx. Each pt provided one Hb and same day self-reported scores on the CCM, a validated measure of SB, functioning, and QoL. CCM items are rated for severity on a 0–10 scale. We defined mild anemia by Hb concentrations in the range of 12.0–14.0 g/dL for men, and 10.0–12.0 g/dL for women. Effect sizes of CCM were calculated using Cohen’s exact d relative to normal Hb values for men and women (Hb > 14 and > 12 g/dL, respectively). We compared effect sizes with published SF-36 minimal clinically important differences (MCID). Bryant Paulson comparisons were used to test significance of trends across age-adjusted means within each CCM. Results: We observed greater SB, lower functioning, and decreased QoL in both men and women with mild CRA (p for trend < 0.05). When applying standards for MCID from SF-36 (0.09 < Cohen s d < 0.28), effect sizes obtained for patients with mild anemia suggest that these effects were clinically significant (0.11 < Cohen s d < 0.61). Adjusted means and differences in CCM for patients with mild anemia and without anemia are shown below. Conclusions: Mild anemia was associated with clinically significant impairments in QoL in the cancer pt. Failure to treat AC may result in unnecessary SB and noteworthy decrements in patients’ QoL. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Amgen Amgen