tbuckley/cabot-search huggingface dataset:
An analysis of erythropoietin (EPO) and venous thromboembolic events (VTE) in multiple myeloma (MM) patients (pts) treated with anthracycline-based chemotherapy and the immunomodulator agent thalidomide
Authors: R. C. Baz, E. Walker, M. Kelly, M. A. Hussein
Journal: Journal of Clinical Oncology (2007)

8107 Background: The use of EPO has recently been reported to be associated with higher rates of VTE in MM pts receiving lenalidomide or thalidomide and dexamethasone (Knight et al. NEJM 2006). Uncontrolled erythrocytosis, a recognized risk factor for VTE, may complicate therapy with EPO when the hemoglobin is not carefully monitored. Other risk factors such as renal failure in this pt population might contribute to hypercoagulability. We sought to evaluate the contribution of EPO use to the development of VTEs in pts with MM treated with the immunomodulator agent thalidomide in combination with chemotherapy. Methods: We retrospectively reviewed records of 105 pts enrolled on a clinical trial for newly diagnosed or relapsed MM pts with pegylated liposomal doxorubicin, vincristine, dexamethasone and thalidomide (DVd-T). In this study pts pts were aggressively monitored for VTE as previously described (Hussein et al Mayo Clin.Proc. 81 (7):889–895, 2006). Demographic variables, aspirin therapy (on intent to treat basis), EPO therapy, as well as the occurrence of VTEs were extracted. Results: The median age was 63 years and 62 (59%) received EPO in conjunction with their MM therapy. VTE prophylaxis with aspirin (81mg daily) was administered to all but 21 pts. Of the 62 pts receiving EPO, 15 (24%) had a VTE compared to 11 (26%) who did not receive EPO (OR 0.928, 95% CI 0.38 - 2.3). Among the 21 pts who did not receive aspirin as VTE prophylaxis, 11 (52%) experienced a VTE compared to 18% (15/84) in those who did receive aspirin as VTE prophylaxis (OR 5.1, 95% CI 1.8 - 14). In the subgroup of 62 pts that received EPO, 54% (7/13) of pts who did not receive aspirin developed a VTE compared to 16% (8/49) who received aspirin and developed a VTE (OR 6, 95% CI 1.6 - 22.6), which is comparable to the overall study population. Conclusions: These results do not indicate an association between EPO use and VTE in MM pts receiving anthracycline-based chemotherapy with the immunomodulator thalidomide and on intent to treat basis low dose aspirin is effective in reducing the incidence of VTE with this complex regimen. [Table: see text]
Cytosine Arabinoside Chemotherapy Does Not Enrich For Leukemic Stem Cells In Xenotransplantation Model Of Human Acute Myeloid Leukemia
Authors: Fabienne de Toni, Robin L. Perry, Estelle Saland, Mayumi Sugita, Marion David, François Vergez, Eric Delabesse, Véronique De Mas Mansat, Cécile Demur, Jason Iacovoni, Stéphane Manenti, Gwenn Danet-Desnoyers, Christian Recher, Martin Carroll, Jean-Emmanuel Sarry
Journal: Blood (2013)
RTOG 0618: Stereotactic body radiation therapy (SBRT) to treat operable early-stage lung cancer patients.
Authors: Robert D. Timmerman, Rebecca Paulus, Harvey I. Pass, Elizabeth Gore, Martin J. Edelman, James M. Galvin, Hak Choy, William Straube, Lucien Alexander Nedzi, Ronald McGarry, Cliff Grant Robinson, Peter B. Schiff, Jeffrey D. Bradley
Journal: Journal of Clinical Oncology (2013)

7523 Background: The Radiation Therapy Oncology Group (RTOG) protocol 0618 was a phase II trial utilizing SBRT to treat early stage non-small cell lung cancer in operable patients (pts). Methods: All pts were deemed operable by a thoracic surgeon utilizing specific criteria. Pts with biopsy proven peripheral T1-T3, N0, M0 tumors were eligible. The prescription dose was 18 Gy X 3 fractions delivered in 1½-2 weeks. The primary endpoint was 2-year primary tumor control (PTC, avoidance of in-field (INF) and marginal failure (MF)) with overall and progression free survival (OS, PFS), adverse events (AE), local (LF), regional (RF), and distant failure (DF) as secondary endpoints. Early surgical salvage was directed as part of protocol design in the event of LF after SBRT. Results: The study opened December 2007 and closed May 2010 after accruing a total of 33 pts. Of 26 evaluable pts, 23 had T1, and 3 had T2 tumors. Median age was 72 years. Median FEV 1 , DLCO at enrollment were 72%, 68% predicted, respectively. 4 pts (16%) had SBRT related grade 3 AEs while 0 had grade 4-5 AEs. Median follow-up was 25 months. 2 pts have been scored with INF (11.7 and 12.4 months post SBRT) and 1 with MF (32.5 months post SBRT) giving an estimated 2-year primary tumor failure rate of 7.7% (95% CI: 0.0%, 18.1%). 2-year estimates of LF (primary tumor plus involved lobe failure), RF, and DF are 19.2% (95% CI: 3.7%, 34.7%), 11.7% (95% CI: 0.0%, 24.5%), and 15.4% (95% CI: 1.2%, 29.6%), respectively. Only one patient was eligible for attempted surgical salvage and underwent lobectomy 1.2 years post SBRT complicated by a grade 4 cardiac arrhythmia. 2-year estimates of PFS and OS are 65.4% (95% CI: 44.0%, 80.3%) and 84.4% (95% CI: 63.7%, 93.9%), respectively. Conclusions: SBRT given appears to be associated with a high rate of PTC, moderate treatment related morbidity, and infrequent need for surgical salvage in operable early stage lung cancer pts with peripheral lesions. These results support ongoing enrollment into the ACOSOG Z4099-RTOG 1021 trial comparing SBRT to sublobar resection in high risk operable pts. The project was supported by RTOG grant U10 CA21661, CCOP grant U10 CA37422, and ATC U24 CA81647 from the National Cancer Institute. Clinical trial information: NCT00551369.
Pre-operative chemotherapy with epirubicin, cisplatin and 5FU/capecitabine in patients with operable oesophageal cancer
Authors: E. Boleti, D. Sharland, D. Weeden, I. Bailey, A. Bateman, T. Geldart, S. Crabb, E. Copson, A. Darby, T. Iveson
Journal: Journal of Clinical Oncology (2006)

14011 Background: The MRC OE02 study demonstrated pre-operative chemotherapy in patients with potentially operable oesophageal cancer improved survival. Pre-operative chemotherapy has been widely adopted in the UK. At our institution for the past 5 years patients with operable oesophageal cancer have routinely been given pre-operative chemotherapy with 3 cycles of Epirubicin, Cisplatin and Protracted Venous Infusion (PVI) 5FU (ECF). Recently, PVI 5FU has been replaced by Capecitabine (ECX). Methods: From March 2000 to October 2005, patients with operable oesophageal carcinoma have received 3 cycles of ECF or ECX (Epirubicin 50mg/m 2 , Cisplatin 60mg/m 2 , and PVI 5FU 200mg/m 2 per day or Capecitabine 625mg/m 2 po bd for 21 days). Disease response was assessed by CT scan and surgery was performed 4–6 weeks after completion of chemotherapy. Results: 59 patients received neo-adjuvant chemotherapy (48 received ECF, 11 ECX). Median age was 64. Fifty-three patients (89.8%) completed the planned 3 cycles of chemotherapy. WHO grade 3 or 4 toxicity occurred in 7 patients (11.8%): 6 haematological with 1 toxic death among them (1.7%) and 1 mucositis. Forty-four of 49 patients (89.7%) with dysphagia reported improvement of their symptoms as a result of chemotherapy. Fifty-two patients (88.1%) proceeded to surgery of which 47 (90.3%) underwent complete tumour resection, 4 patients (7.7%) were found to have inoperable/metastatic disease and 1 patient had incomplete excision (1.9%). Median follow-up was 26.8 months with overall median survival of 36.2 months and a 2-year survival of 63.2%. Thirty-four (57.6%) patients remain alive to date of which, 30 are disease-free and 4 are alive with recurrent disease. Conclusions: These encouraging results demonstrate that 3 cycles of preoperative ECF/ECX chemotherapy in patients with operable oesophageal cancer allow surgery to be safely performed in the vast majority of patients and our 2-year survival compare favourably with previously reported series. These results suggest that 3 cycles of pre-operative treatment with ECF/ECX chemotherapy may improve survival in this group of patients and is worthy of further research. No significant financial relationships to disclose.
Phase II, two-arm, double-blind, multicenter, randomized study of the combination of oral WX-671 plus capecitabine versus capecitabine in first-line HER2-negative metastatic breast cancer (MBC).
Authors: L. J. Goldstein, S. M. Stemmer, B. Schmalfeldt, N. Gottschalk, F. Cardoso, H. Dushkin, C. Mala, N. Uebler, P. Bevan, N. Harbeck
Journal: Journal of Clinical Oncology (2010)

TPS131 Background: uPA and its inhibitor PAI-1 play a key role in tumor invasion, metastasis, and tumor growth. High levels of uPA/PAI-1 in breast tumors have been demonstrated to be significant prognostic factors of disease-free (DFS) and overall survival (OS) as well as predictors of benefit from adjuvant chemotherapy. WX-UK1 is an active site competitive inhibitor of uPA with an inhibition constant in the submicromolar range. WX-671, the hydrobenzamidino derivative of WX-UK1, is an oral prodrug of WX-UK1. In preclinical tumor models, parentally administered WX-UK1 and orally administered WX-671 reduced the growth rate of implanted tumors, inhibited invasion, and reduced metastases. A phase I study of capecitabine plus WX-UK1 in advanced solid tumors showed that WX-UK1 added no additional toxicity to capecitabine, the MTD was not reached, there were no drug-drug interactions, and adequate WX-UK1 concentrations were achieved. In this study, heavily pretreated MBC patients (pts) were on average treated with 5 cycles until disease progression, some up to 16 cycles with 3 partial responses. This current proof of concept study is designed to substantiate the antimetastatic properties of WX-671 in early MBC. Methods: Female pts age ≥18, with HER2-negative MBC appropriate for first-line mono-chemotherapy with capecitabine, with adequate performance status, organ function, bone marrow reserve without brain metastases are eligible. Pts will be randomized in a double-blind fashion to receive WX-671 (200 mg orally daily for 21 days) plus capecitabine (1,000 mg/m2 orally twice daily for 14 days) vs. capecitabine (1,000 mg/m2 orally twice daily for 14 days) in 3 week treatment cycles until progressive disease or unacceptable toxicity. The primary endpoint is the efficacy of the combination of WX-671 plus capecitabine compared to monotherapy as assessed by comparison of progression free survival. The secondary objectives are OS, objective response rates, safety and tolerability, and to assess the pharmacokinetics of WX-671 and capecitabine when combined. So far, of the 114 patients planned for accrual, 65 pts have been enrolled. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration WILEX Roche, WILEX WILEX Roche
ERCC2 polymorphism Asp711Asp is associated with risk of young-onset pancreatic cancer
Authors: R. R. McWilliams, J. Cunningham, W. Bamlet, K. Rabe, L. Tordsen, C. Olswold, M. de Andrade, G. Petersen
Journal: Journal of Clinical Oncology (2005)

9688 Background:DNA repair has become an area of intense research in the study of human malignancies. Though germline mutations in DNA repair genes such as Fanconi anemia genes and BRCA2 have been studied in pancreatic cancer, common polymorphisms of the more than 100 other DNA repair genes have not been well studied. Methods:Since 2000, we have conducted a Mayo Clinic-based case-control study consisting of ultra-rapidly recruited patients with the diagnosis of pancreatic adenocarcinoma. Controls were selected from a pool of healthy patients receiving screening colonoscopies. In all, 481 cases of pancreatic cancer (all ages) were compared with 623 controls. Germline DNA was collected from blood samples, and analyzed by Pyrosequencing of known polymorphisms of three DNA repair genes, ERCC1 A118 (rs3177700), ERCC2 A711(rs1052555), and OGG S326C (rs 1052133). Frequencies were compared using the Cochran Armitage Trend Test (one-sided Pr > Z). Young-onset cases (<60 yrs.) were analyzed as a subgroup. Results:The AA and AG genotypes of the ERCC2 Asp711Asp variant were more frequently noted in the young onset cases compared with either all controls (p=0.023) or young (<60) controls (p=0.015). No difference was seen in the other two loci investigated. Conclusions:Preliminary data shows that genotypes containing the A allele of the DNA repair gene ERCC2 may increase risk for young-onset pancreatic cancer. Further confirmation in follow-up studies is needed. Author Disclosure Genotype Frequencies for All Cases and Controls and those under 60 years of Age Gene (Locus) Genotype All Cases (n=481) All Controls (n=623) Cases < age 60 (n=136) Controls < age 60 (n=191) ERCC2 (Asp711Asp) A/A 67 (14%) 69 (11%) 21 (15%) 31 (11%) ERCC2 (Asp711Asp) A/G 203 (42%) 260 (43%) 64 (47%) 120 (41%) ERCC2 (Asp711Asp) G/G 211 (44%) 282 (46%) 51 (38%) 140 (48%) OGG1 (Ser326Cys) C/C 23 (5%) 42 (7%) 5 (4%) 16 (5%) OGG1 (Ser326Cys) C/G 181 (38%) 224 (37%) 52 (38%) 103 (35%) OGG1 (Ser326Cys) G/G 277 (58%) 345 (56%) 79 (58%) 173 (59%) ERCC1 (Asn118Asn) C/C 75 (16%) 85 (14%) 25 (18%) 42 (14%) ERCC1 (Asn118Asn) C/T 205 (43%) 282 (46%) 60 (44%) 129 (44%) ERCC1 (Asn118Asn) T/T 200 (42%) 245 (40%) 51 (38%) 121(41%) No significant financial relationships to disclose.
Combined modality therapy with carboplatin, irinotecan and radiation therapy followed by consolidation docetaxel for patients with stage III NSCLC
Authors: L. E. Raez, E. Roman, L. Negret, C. Takita, C. Lobo, P. Kummar, G. Lopes, N. Farfan, M. Karr, C. Rocha-Lima
Journal: Journal of Clinical Oncology (2006)

17088 Background: Irinotecan (I) has an active role and potential as a radiosensitizing agent in patients with NSCLC. SWOG 9504 established the concept of “consolidation” chemotherapy with 3 cycles of docetaxel (D) after chemo/radiation (CRXT). We evaluated the efficacy and safety of administering weekly doses of carboplatin/irinotecan (CI) concomitantly with radiation therapy followed by D chemotherapy for patients (pts) with stages IIIA/B NSCLC. Methods: We have enrolled 23 pts, treatment included: C: (AUC = 2) and I: 30 mg/m 2 , weekly concomitant with radiation therapy, and D: 75 mg/m 2 every 3 weeks for 3 times after CRXT was finished. The daily administered dose of radiation was 1.8 Gy, 5 days a week for 5 weeks, 25 fractions, (45 Gy) to the primary tumor and mediastinum (primary planning target volume: PPTV. After 45 Gy, the primary tumor and involved nodal metastasis (secondary planning target volume: SPTV) was boosted at 2 Gy per day to 18 Gy in 9 fractions. The total dose given was 63 Gy in 35 fractions over seven weeks. Evaluation of response has been done with RECIST criteria. Results: Median age is 55 years (range: 42–78), 18 (78%) of the pts are female, 17 (74%) are white, 13 (57%) are Hispanic, and 14 (65%) had an ECOG 1. Most common histologies are poorly differentiated and squamous cell carcinomas: 14 pts (61%), and half of the pts are stage IIIB. 111 weeks of CI and 39 cycles of D have been administered and we have documented 22 grade 3/4 adverse events (AE) among them: 4 pts pneumonia (17%), 3 pts radiation pneumonitis (13%), 2 pts: dehydration o neutropenia o dyspnea (9%) and 1 pt with diarrhea, nausea and vomiting (4.5%). No grade 4 neutropenia, esophagitis or diarrhea was reported. 12 severe AE were reported including: 2 pts with pneumonia (9%), 2 pts with dehydration (9%), and 2 pts with radiation pneumonitis (9%) requiring hospitalization. The rest of SAE were unrelated to therapy. Data for response is available in 18 pts. A partial response was seen in 10 pts (56%), and stable disease in 6 pts (33%). 2 pts are ineligible for response. Median survival (and PFS) has not been reached and it will be presented in the meeting. Conclusions: CI administered with radiation therapy and followed by D is safe and efficacious in the treatment of stage III NSCLC. [Table: see text]
Use of angiopoietin-1 expression in squamous cell carcinoma of the head and neck to predict disease-free survival.
Authors: M. Dhiwakar, J. P. Malone, P. A. Kay, K. T. Robbins, S. Ran
Journal: Journal of Clinical Oncology (2010)

5542 Background: Angiopoietin (Ang)-1 and -2 are secreted glycoproteins that are thought to promote blood vessel stabilization and destabilization respectively in various tumors. However, their roles in angiogenesis and metastasis in squamous cell carcinoma of the head and neck (SCCHN) are currently unknown. Objective: To determine Ang-1 and -2 expression profiles and their correlation with disease outcomes in SCCHN. Methods: Tumors from 65 patients with previously untreated SCCHN were stained using antibodies against Ang-1 and Ang-2. Matched peritumoral mucosa was available for 20 patients. Mucosa from 12 patients without SCCHN served as the control group. Intensity of staining was scored semiquantitatively and correlated with clinico-pathological parameters and outcomes. Results: Ang-1 was significantly overexpressed in SCCHN and matched peritumoral mucosa as compared with normal mucosa (both p<0.001). Although overexpression of Ang-1 did not correlate with tumor variables, it did independently predict improved disease-free survival (p=0.044 by Cox proportional hazards model). Ang-2 expression was low in most specimen and did not correlate with any parameter examined in this study. Conclusions: Expression of Ang-1 in SCCHN is associated with improved disease-free survival. The likely mechanism is Ang-1 induced stabilization of blood vasculature and possible suppression of metastasis. Ang-1 may serve as an important prognostic tool and needs to be confirmed by further studies. No significant financial relationships to disclose.
Suicidal behaviors in adult psychiatric outpatients, I: Description and prevalence
Authors: G M Asnis, T A Friedman, W C Sanderson, M L Kaplan, H M van Praag, J M Harkavy-Friedman
Journal: American Journal of Psychiatry (1993)

Because the findings of previous studies of suicidal behaviors in psychiatric outpatients may not necessarily generalize to outpatients with a wide spectrum of psychiatric diagnoses, the authors evaluated the prevalence of suicidal behaviors in a large general psychiatric outpatient clinic whose patients represented a full spectrum of psychiatric illness.A total of 651 patients participated in the study between 1987 and 1989. These patients had sought treatment at the outpatient psychiatry department of a private nonprofit hospital. Before being interviewed for treatment, all patients were given a comprehensive self-rating survey packet that included the Harkavy Asnis Suicide Survey and the Hopkins Symptom Checklist-90. The Harkavy Asnis Suicide Survey is a self-report questionnaire that assesses demographic variables, current and past history of suicidal behaviors of the patient as well as family members and peers, and a detailed description of each previous attempt.Fifty-five percent of the patients had a history of suicidal ideation, and 25% reported at least one previous suicide attempt. Approximately half of the suicide attempters reported multiple attempts. The predominant methods of attempt were overdose (53%), jumping (17%), and wrist cutting (17%). Suicidal behavior was prevalent in most diagnostic groups. The rates of suicidal ideation among patients with mood disorders (major depression, dysthymia, and bipolar disorder), adjustment disorders, and alcohol/substance abuse were significantly greater than that of the patients with generalized anxiety disorder.The authors conclude that suicidal behavior is prevalent among patients who seek treatment in a general outpatient department.
Assessment of the Proliferation Marker Ki67 By Eus-fna in Pancreatic Endocrine Tumours. a Comparative Analysis With Histology of the Surgical Specimen
Authors: Violaine Bernard, Birgit Weynand, A. Jouret, Catherine Hubert, Jean-François Gigot, Pierre Henri Deprez, Ivan Borbath
Journal: Annals of Oncology (2010)
Efficacy and safety of cooling helmets (CH) for the prevention of chemotherapy-induced alopecia (CIA): A prospective study of 911 patients (pts)
Authors: D. Spaeth, E. Luporsi, B. Weber, S. Guiu, D. Braun, M. Rios, P. Evon, S. Ruck
Journal: Journal of Clinical Oncology (2008)

9564 Background: CIA, one of the most feared side effects of chemotherapy (CT), could be prevented by CH, but there are concerns that an inappropriate tumor cell protection could raise the risk of scalp, skull or even brain metastasis (Cephalic events (CE)). Methods: Pts were included prospectively in 2 parallel cohorts: cohort A pts agreeing to wear CH (Elasto-Gel, Akromed INC, or Penguin, MSC Ltd) in a precisely defined protocol; CH could be given up at any time of the study; cohort B pts not agreeing to wear CH. The principal objective was efficacy (% of pts not needing a whig or headband), secondary objectives: tolerance, safety, quality of life (QoL), predictive factors (PF) of CH efficacy. Inclusion criteria: CT regimen with adriamycin, epirubicine, docetaxel, cyclophosphamide < 750 mg/sqm, topotecan, irinotecan, written informed consent. Exclusion: hematologic malignancies, previous skull or brain radiotherapy, known cephalic soft tissue skull or brain metastasis, CT regimens with etoposide, paclitaxel, ifosfamide, cyclophosphamide > 750 mg/sqm. Whig requirement, self-questionnaires on CH tolerance, CIA grade and straight discomfort, Qol questionnaires (QLQ C30 + body image module) were recorded at study entry, at each CT cycle and 1 month after last cycle; CE events were prospectively recorded during a minimum 2 years follow-up (FU). Results: From 2002 to 2006, 911 pts were included in 8 centers, 770 in cohort A, 141 in cohort B. Median age was 54, sex-ratio male 3,8% / women 96,2%; breast cancer 93%; CT regimens: anthracyclins (A) < 75mg/m2 or/and taxotere (T) < 75mg/m2)(at) 456 (50%); A > 75mg/m2 or T > 75mg/m2 (AT) 426 (46,8%), topoII inhibitor (T2) 29 (3,2%). With a median FU of 36 months the CE rate was 4,3 % in cohort A and 2,9 % in cohort B, (p = 0.43). The success rate (no whig or headband) was 46,3 % in cohort A and 31,2 % in cohort B (p = 0.0017). Efficacy was better for at (48,5 %) and T2 (89,7 %) regimens than for TA (28,4 %) (p<0,0001 and p<0,0001). Conclusions: CH is an efficient tool for the prevention of CIA and is safe without excess of CE. It should be offered to pts wanting to try to avoid CIA in selected CT regimens (at and T2 chiefly) and after a thorough search of exclusion criteria. Data on Qol, tolerance, and PF will be reported at the meeting. No significant financial relationships to disclose.