tbuckley/cabot-search huggingface dataset:
Valve Repair Improves the Outcome of Surgery for Chronic Severe Aortic Regurgitation. A Propensity Score Analysis
Authors: Christophe de Meester de Ravenstein, Sophie F. Piérard, Stéphanie Seldrum, Bernhard Gerber, David Vancraeynest, Anne-Catherine Pouleur, Philippe Noirhomme, Agnes Pasquet, Gebrine El Khoury, Jean-Louis Vanoverschelde
Journal: Circulation (2012)

Background. For patients with aortic regurgitation (AR), aortic valve (AV) repair represents as an attractive alternative to AV replacement (R), as it does not expose the patients to the risk of prosthetic valve complications. Although the durability of AV repair has been documented, its superiority to prosthetic AVR has not yet been established. Methods. We examined the outcome of 317 consecutive patients who underwent surgical correction of severe AR between 1995 and 2010, of whom 264 underwent AV repair and 53 AVR. Results. Operative mortality was similar in the AV repair and AVR groups (1% vs 4%, p=0.19). Kaplan Meier survival analysis indicated a significantly better overall 6-year survival after AV repair than after AVR (88% vs 69%, log rank p=0.0002). These differences persisted after age adjustment. Cox's proportional survival analysis demonstrated that the choice of treatment was an independent predictor of post-operative survival. To reduce the effect of selection bias, we matched 49 pairs of patients using a propensity score. For these 98 propensity-score matched patients, overall survival remained significantly better after AV repair than after AVR (83% vs 68%, log rank p=0.037). Finally, the improved survival after AV repair was not offset by an increased reoperation rate as re-operation free survival was similar in the 2 groups (96% vs 98%, log rank p=0.52). Conclusion. AV repair significantly improves postoperative outcomes in patients with AR and whenever feasible, should probably be the preferred mode of surgical correction.
Temozolomide (TMZ) plus thalidomide (THAL) as adjuvant therapy in patients with stage III and stage IV malignant melanoma
Authors: W.-J. Hwu, D. Coit, D. Jaques, K. S. Panageas, L. A. Lamb, C. J. Quinn
Journal: Journal of Clinical Oncology (2004)

7574 Background: TMZ plus THAL is effective and well tolerated in patients (pts) with unresectable stage III and IV melanoma (JCO 2003;21:3351). We investigated this combination as adjuvant therapy in pts with stage III and IV melanoma who were free of disease but at high risk for recurrence. Methods: Pts were rendered clinically disease-free by surgery or radiation before treatment. TMZ was given at 75 mg/m2/day for 6 weeks followed by a 2-week break. Pts<70 years old received THAL 200 mg/day, while those ≥ 70 years old received THAL 100 mg/day with escalation to 200 mg/day. Imaging studies were performed after each 8-week cycle. Treatment continued for 3 cycles unless the tumor recurred earlier. Results: 26 pts were treated; 15 stage III (8 IIIb, 7IIIc) and 11 stage IV (4 M1a, 5M1b, 2M1c); 19 men/7 women; median age 59 (range 28–78). All pts underwent surgical resection except 1 who received RT for a bone metastasis. 21 pts completed 3 cycles. Of the remaining 5, 2 had recurrence after 1 cycle, 2 were removed after 1 cycle for toxicity (bradycardia, pneumonia), and one was diagnosed with stage I renal cancer after 2 cycles. 10 pts (5/15 stage III, 5/11 stage IV) had disease recurrence. 19 pts are currently alive without disease (11 stage III, 8 stage IV), 5 are alive with disease (4 stage III, 1 stage IV), and 2 died of disease, 1 at 14 mos (brain metastasis) and 30 mos (bone metastasis). The median followup among survivors is 23.4 mos (range 6.3, 46.3). Median time to recurrence is 27.4 mos; 1 year (yr) recurrent rate 80.8%, 2 yr 58.5% and 3 yr 46.8. Overall survival at 1 yr is 100%, 2 yr 95.5% and 3 yr 71.3%. Conclusions: TMZ plus THAL was well-tolerated as adjuvant therapy for pts with high-risk stage III and IV melanoma. Efficacy needs evaluation in a larger clinical trial. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Schering-Plough
DO/NDR/02 a novel polymeric nanoparticle paclitaxel: Results of a phase I dose escalation study
Authors: P. P. Bapsy, D. Raghunadharao, A. Majumdar, S. Ganguly, A. Roy, G. Uppal, R. Mukherjee, A. Burman, N. Saha
Journal: Journal of Clinical Oncology (2004)

2026 Background: DO/NDR/02 is a novel Cremophor free Paclitaxel formulation in which the drug is delivered as nano micelles using a polymeric carrier. A phase I dose escalation study evaluating a three weekly regimen is being conducted to determine the maximum tolerated dose (MTD), safety profile and pharmacokinetic (PK) profiles of this formulation when given to refractory or metastatic solid tumors. Method: DO/NDR/02 was administered as a one-hour infusion without premedications in doses ranging from 135 to 375 mg/m2 for a maximum of six cycles. Serial blood samples were collected for PK analysis during cycles 1 and 2 and Paclitaxel concentrations were determined using a validated HPLC method. Results: Twenty-three patients have been treated at various dose levels up to 375mg/m2. Till date there has been no incidence of hypersensitivity reactions, febrile neutropenia or neuropathies above grade 1. The major non-hematological toxicities were grade 3 infection without neutropenia (n=1) seen at 135 mg/m2 and grade 3 diarrhea (n = 2) at 300 and 375 mg/m2 respectively. The major hematological toxicities have been grade 4 neutropenia (n = 2) at 135 and 375 mg/m2. The MTD has been determined at 375mg/m2. Objective responses (OR) are seen in 6 out of 18 (33.3%) patients evaluated so far. 5 out of 10 (50%) cases of heavily pretreated breast cancer have shown OR. PK analysis has shown a linear correlation between the mean AUC and dose up to 375mg/m2. Conclusions: The initial results of this study reveals that DO/NDR/02 may be safely administered without any premedications, to a higher dose than Cremophor Paclitaxel. It has also shown a linear PK profile and encouraging clinical activity in advanced breast cancers. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Dabur Research Foundation Dabur Research Foundation Dabur Research Foundation Dabur Research Foundation
Abstract 19062: Copeptin-to-BUN Ratio Predicts Outcome in Patients with Advanced Heart Failure: A key to the use of vasopressin antagonists?
Authors: Rudolf Jarai, Serdar Farhan, Michael A Schwarz, Kurt Huber
Journal: Circulation (2012)

Background: The arginine-vasopressin-aldosteron system is activated in patients with chronic heart failure and elevated serum concentrations of vasopressin as well as the c-terminal portion of its prohormone (copeptin) strongly predicts outcome of these patients. Re-absorption of urea by the kidneys is regulated by vasopressin and thereby it also influences blood urea nitrogen (BUN) concentrations. In the present study we investigated, whether the ratio of serum copeptin and BUN (copeptin-to-BUN) could be used to estimate long-term outcome of patients with chronic stable heart failure (CHF). Methods: We measured copeptin, BUN, high-sensitivity troponin T (hs-cTnT), plasma MR-proANP, MR-proADM and Nt-proBNP concentrations in 174 patients with CHF. Patients were followed for all-cause mortality and rehospitalization due to heart failure during a median time of 834days. Results: The ratio of copeptin-to-BUN was significantly higher among patients who died or were re-admitted to the hospital compared to those who remained event-free (0.86 vs. 0.45; p&lt;0.001). In univariate Cox regression analysis, patients with copeptin-to-BUN ratio higher than the median had significantly higher risk of death or hospital re-admission than patients with lower copeptin-to-BUN ratio (HR 2.16 p&lt;0.001; Figure). In multivariate analyses adjusted for several clinical variables and laboratory measures - including Nt-proBNP, MR-proADM, MR-proANP, hs-cTnT - the ratio of copeptin-to-BUN remained a highly significant determinant of long-term outcome (HR 1.645; p=0.023). Conclusion: In addition to well-established modern biomarkers, the copeptin-to-BUN ratio is a significant independent determinant of survival of patients with CHF. Future studies should evaluate whether copeptin-to-BUN ratio could be used to identify patients with advanced heart failure who might benefit from the use of vasopressin antagonists.
Long-term survivors of a systemic and intraventricular chemotherapy with deferred radiotherapy in primary central nervous system lymphoma (PCNSL)
Authors: U. Schlegel, A. Juergens, S. Rogowski, H. Schulz, H. Reichmann, M. Vogt-Schaden, U. Bode, I. G. Schmidt-Wolf, H. Pels
Journal: Journal of Clinical Oncology (2008)

8557 Background: To evaluate survival, quality of life and neurotoxic sequelae in long-term survivors with primary central nervous system lymphoma (PCNSL) after systemic and intraventricular chemotherapy with deferred radiotherapy. Patients and Methods: From 09/1995 to 12/2001, 65 patients with PCNSL (median age 62 years) were enrolled in a pilot/phase II study evaluating chemotherapy without radiotherapy; thirty patietns were younger than 60 years. A high-dose methotrexate (MTX) (cycles 1,2,4,5) and cytarabine (ara-C) (cycles 3,6) based systemic therapy (including dexamethasone, vinca-alkaloids, ifosfamide and cyclophosphamide) was combined with intraventricular MTX, prednisolone and ara-C. All living patients were contacted, a neurological examination, comprehensive neuropsychological testing, Quality of Life (QoL) - Assessment (EORTC QLQ-C30 (Version 3.0) und EORTC QLQ-BN20) and imaging were performed. Results: Twenty-one of 65 patients (32 %) are alive. Of these, 17 patients were younger than 60 years at diagnosis, resulting in long-termsurvival rate of 17 of 30 patients (57 %). Median follow up is 99.5 months (range, 70 to 147 months) in surviving patients. Seventeen/21 patients completed all investigations, in three patients test results are pending, one is lost to follow up. One patient is currently undergoing therapy for tumor relapse; one other patient developed a second malignoma (liposarcoma). In three patients, a pure extraneural relapse was diagnosed after nine, 31 and 40 months and showed complete remission to high-dose chemotherapy in all. There was no evidence of late onset neurotoxity nor compromise of therapy- or tumor-related QoL measures in any of the examined patients. Conclusions: Primary polychemotherapy based on high- dose MTX and ara-C is highly efficient in PCNSL. More than half of patients < 60 years can obviously be cured with this regimen without suffering from long term neurotoxic sequelae. No significant financial relationships to disclose.
Mediator release during combined radio chemotherapy in rectal carcinoma
Authors: C. Matuschek, E. Bölke, S. Gripp, W. Budach, D. Hermsen, M. Peiper
Journal: Journal of Clinical Oncology (2009)

3043 Background: Bacterial translocation is a well-documented phenomenon after polytrauma and major abdominal surgery. Today neoadjuvant chemoradiotherapy is the gold standard for uT3, N+ rectal cancer. The aim of this study was to evaluate if a gut barrier dysfunction occurred during radiotherapy and elective rectal surgery. Methods: We investigated in 45 patients (25 male, 20 female) with uT3N+ rectal carcinoma and neoadjuvante long-term radio chemotherapy with 5-FU and pelvis irridation up to 50.4 Gy on admission and weekly during radiotherapy and after surgery IL-6, LPS-binding protein, IL-8, TNF-α and procalcitonin. Results: There were no clinical complications in all patients. During radiochemotherapy we could not detect a significant increase of the acute phase response. IL-6 plasma levels showed maximal values 6 h after surgery (270 pg/ml) und CRP had its maximal values 48 h (185 mg/l). IL-8, TNF-α, LPS-BP, and procalcitonin were not elevated during an uncomplicated postoperative course. Conclusions: During an uncomplicated course of radio chemotherapy we could not detect elevated mediator releases. During surgery we could find a significant mediator liberation, which correlated with the amount of the operative trauma. No significant financial relationships to disclose.
Fulvestrant in advanced breast cancer following following failure of tamoxifen and a third generation aromatase inhibitor
Authors: J. Wang, S. Jain, W. Heller, D. Mackie, V. Watson, M. Dweck, R. C. Coombes, C. Palmieri
Journal: Journal of Clinical Oncology (2007)

1073 Background: Endocrine therapy is a key modality in the management of estrogen receptor positive metastatic breast cancer. Fulvestrant (ICI 182,780) is an estrogen receptor downregulator. It has previously been shown to be as effective as anastrozole in patients who had previously progressed on tamoxifen. Methods: A retrospective study was carried out of metastatic breast cancer patients treated at Charing Cross Hospital between 2002–2005 who had received fulvestrant following treatment failure with tamoxifen and a third generation aromatase inhibitor. All patients were postmenopausal and received fulvestrant 250mg IM every 28 days. Measurable disease was assessed by response evaluation criteria in solid tumors (RECIST). Results: A total of 45 patients were identified with a median age of 60 (range 36 to 90). The ER status was known in 95% (n=43) of patients and was positive in all cases, it was unknown in 2% (n=2). At the time of commencing fulvestrant, 96% (n=43) had metastatic disease and 4% (n=2) locally advanced disease. All patients had received at least 2 lines of prior endocrine therapy (including adjuvant therapy), at time of starting fulvestrant the median number of prior regimens was 3 (range 3–5). Fulvestrant was administered for a median of 4 months (range 1 to 20 months), with 4 patients currently still receiving therapy as of 1 November 2006. Of the 45 patients, 2.2% (n=1) achieved a partial response, while 31% (n=14) achieved stable disease for at least 6 months. Thus, 33.3% (n=15) obtained clinical benefit (defined as PR or SD for at least 6 months). The response rates based on line of therapy will be presented. Of the 45 patients, 41 were evaluable for survival data. The median survival of the remaining patients from the start of fulvestrant therapy was 9 months (range 1 to 48 months). Of the 44 patients, 14% (n=6) remain alive. The treatment was well tolerated and toxicity data will be presented. Conclusions: Fulvestrant is well tolerated and is efficacious as treatment for advanced breast cancer that has failed tamoxifen and a third generation aromatase inhibitors. No significant financial relationships to disclose.
Safety of Prophylactic Use of Darbepoetin Alfa in Patients with Diffuse Large B-Cell Lymphoma (DLBCL) Treated with R-CHOP 14 or R-CHOP21: Preliminary Results of the LNH03-6B Randomized GELA Study.
Authors: R. Delarue, N. Mounier, C. Haioun, B. Coiffier, C. Gisselbrecht, H. Ghesquieres, P. Lederlin, M. Blanc, C. Recher, O. Hermine, F. Reyes, H. Tilly, A. Bosly
Journal: Blood (2006)
Chemokine receptor CXCR4 mRNA expression may be a marker of the presence of compromised lymph nodes in oral cavity squamous cell carcinoma
Authors: C. M. Campofiorito, F. R. R. Mangone, F. S. Pasini, S. Maistro, I. M. L. Snitcovsky, F. Walder, C. Lehn, M. B. Carvalho, M. M. Brentani, M. H. H. Federico
Journal: Journal of Clinical Oncology (2005)

9622 Background: Chemokine receptors have recently been shown to be involved in metastasis and in this work, we aimed to investigate which receptors CXCR1–5, CCR7 and CX3CR1 may correlate with the spread of Head and Neck Squamous cell cancer to regional lymph nodes. Methods: Chemokine receptor expression were analyzed in 61 fragments of primary tumor (T) and normal tumor adjacent mucosa (M) of 61 patients (pts) with operable HNSCC, by using the Ribonuclease Protection Assay (Riboquant RPA system, Pharmingen. These data, as expressed by densitometry relative to L32 internal control, and of 17 grossly compromised lymph nodes (LN) were correlated with clinical-pathological parameters by using t-paired test. Results: Primary tumors (T) as compared to normal tumor adjacent mucosa (N), (n=61), displayed a higher CXCR1 mRNA expression as expressed by densitometry relative to L32 internal control (Tumor: 0.010 ± 0.020 vs 0.004 ± 0.007: Normal, p=0.039) and a tendency to a higher CXCR3 (T: 0.007 ± 0.012 vs 0.004 ± 0.008:N, p=0.084) and CXCR4 (T: 0.198 ± 0,170 vs 0.156 ± 0.224: N, p=0.088). When oral primary site was individualized, we observed a significant increase in the CXCR4 mRNA expression in primary tumors as compared to normal tissue (T: 0.177 ± 0,117 vs 0.093 ± 0.088:N, p=0.004, n=18). In addition, we did not find diferences between pN0 (n=22) vs pN+ (n=30) primary tumors in the whole group, even though oral subgroup presented higher higher CXCR4 mRNA densitometric values in pN+ pts (0,224 ± 0,119, n=11) as compared to pN0 tumors (0,112 ± 0.081, n=8, p = 0,026, t-test paired). When available compromised lymph nodes (L) were studied, we have found higher CXR4, CXR5, CCR7 and CX3CR1 as compared to matched primary tumors: CXCR4 (L:0.400 ± 0,226 vs 0.182 ± 0.124:T, p=0.001, n=17), CXCR5 (L:0.040 ± 0,038 vs 0.004 ± 0.008:T, p=0.001, n=17), CCR7 (L:0.066 ± 0,067 vs 0.006 ± 0.011:T, p=0.002, n=17), and CX3CR1 (L:0.037 ± 0,036 vs 0.006 ± 0.009:T, p=0.002, n=17). No other differences were found. Conclusions: Among the chemokine receptors here studied, CXCR4 seems to play a role in lymph node spread of HNSCC, at least in oral cavity carcinoma. Further studies are warranted in this area to confirm these results. No significant financial relationships to disclose.
Long-term evaluation of ifosfamide-related nephrotoxicity in children: The French experience
Authors: O. Fawaz, A. Rey, P. Niaudet, D. Orbach, C. Bergeron, J. Gentet, N. Corradini, M. Munzer, H. Rubie, O. Oberlin
Journal: Journal of Clinical Oncology (2007)

9551 Background: Ifosfamide-induced nephrotoxicity is a significant issue in patients treated for tumours during childhood. This study aimed at documenting incidence of late renal toxicity of ifosfamide and its risk factors. Methods: 183 patients have been investigated. 100 were male. Median age at treatment was 9.3 years (0.4–18 years). Median dose of ifosfamide was 54 g/m 2 (18–77 g/m 2 ). No patients received cisplatin and/or carboplatinum. Diagnoses included rhabdomyosarcoma (77), other soft tissue sarcoma (39), Ewing (39), and osteosarcoma (28). Investigations were performed at a median interval of 10.3 years (5–20.7) after the end of the treatment, at a median age of 21.6 years (7.1–44.2). No patient had electrolyte or vitamine supplementation. Glomerular and tubular functions were graded according to the Skinner's system. Results: After 5 year minimal follow-up 55% had normal tubular and 79% had normal glomerular functions. Natraemia, kalaemia, serum HCO3 and calcaemia were normal in all patients. Hypomagnesaemia was observed in 4, hypophosphaetemia in 8 %. The tubular threshold for phosphate was reduced in 44% of the patients (grade 2 or 3 in 15%, grade 3 in 1 pt). Significant glycosuria (&gt; 0.5 g/24h) was detected in 5 % of the patients but it was clearly abnormal only in 5 patients. 34% of the patients had beta2 microglobulinuria, however, proteinuria was observed in only 12%. Cumulative dose of ifosfamide, older age at treatment and follow-up since treatment were predictor for tubulopathy in univariate and multivariate analyse. The glomerular filtration rate was normal in 79% of the patients. 21% had a grade 1 toxicity and 1 patient a grade 2. Univariate analysis did not find any prognostic factor for glomerular toxicity apart from the association with tubular toxicity. Conclusions: Since ifosfamide-induced renal toxicity can be severe, long term evaluation is important and this risk should be balanced carefully against efficacy. No significant financial relationships to disclose.
Diagnostic and prognostic use of FDG-PET scans in Waldenstrom's macroglobulinemia
Authors: B. Harris, X. Leleu, R. Leduc, D. Yarar, A. Sam, M. Rourke, S. Chuma, A. Roccaro, I. Ghobrial
Journal: Journal of Clinical Oncology (2009)

e19518 Background: Waldenstrom's macroglobulinemia (WM) is a rare lymphoplasmacytic lymphoma. More sensitive tools of tumor burden and prognosis are needed in these patients (pts). The use of FDG-PET has not been previously studied in WM but has proved an effective diagnostic and prognostic tool effective in low-grade lymphomas. Therefore the objective of this study was to determine whether FDG-PET was an effective tool in evaluating pts with WM. Methods: We included all pts enrolled on a prospective phase II clinical trial of bortezomib and rituximab for pts with upfront or relapsed/refractory (RR) WM. All pts were CD20 positive with histologically confirmed disease and underwent staging evaluation by FDG-PET in combination with CT scan before and after therapy. Patients received 6 cycles of bortezomib IV weekly at 1.6mg/m2 on days 1, 8, 15q28 and rituximab at 375 mg/m2 on days 1, 8, 15 and 22 in cycles 1 and 4. Correlation was made with the international prognostic scoring system for WM and monoclonal protein response rate. Results: 53 pts were included, of which 35 were RR and 18 pts were upfront. Median age was 63 years (range 42–81), 64% were male. Before therapy, 34 pts (64.2%) had positive FDG-PET findings with a median IgM of 2825, Beta 2 microglobulin of 3.6, and Age of 61. 36 pts showed a minor response or greater with a correlation to negative PETs after therapy. Conclusions: Over 60% of WM pts demonstrated FDG-avid disease when using FDG-PET scans, with the majority showing negative disease after therapy. This correlates with the 67.9% response rate. Positive PET images were inversely correlated to IgM level and directly related to elevated Beta-2 microglobulin and age. Significantly PET positive individuals may demonstrate a poorer prognosis. FDG-PET scans may prove an effective tool in the diagnosis and prognosis in WM. [Table: see text]
Description of palliative medicine in guidelines for digestive system cancer medical care.
Authors: S. Shikata, T. Sato, K. Miyazaki, A. Okumura, N. Takagaki, T. Nakayama, H. Minato, T. Matsuda
Journal: Journal of Clinical Oncology (2010)

e19628 Background: To analyze information on palliative medicine contained in clinical guidelines (GL) for digestive system cancer around the world. Methods: Comprehensive GLs for digestive system cancer (esophagus, stomach, colon, liver, biliary tract and pancreas) drafted and publicly available around the world were studied, and those limited to prevention, screening, chemotherapy, and surveillance were excluded. Publicly available information from databases such as PubMed and NGC (National Guideline Clearinghouse) and from specialized organizations was systematically collected and supplemented with manual searches. This information was utilized to create a database for bibliographical information, quality score of GLs using the AGREE (Appraisal of Guidelines for Research & Evaluation) checklist, GL drafting committee composition, and descriptions on palliative medicine. Contents were analyzed by disease and relationships between them and the GL drafting committee composition were examined. Results: Among 1,420 potentially relevant articles, 73 GLs drafted in 14 countries in 1996 or later were retrieved and made available for analysis. While eight GLs contained a separate chapter on palliative medicine, 30 GLs had no description of palliative medicine. When the GL drafting committee comprised only physicians, descriptions of palliative care were sparse. However, when the drafting committee included patients, nurses and palliative medicine experts, the GL contained a separate chapter on palliative medicine. We identified no disease-dependent trends in description length, but differences were observed by the drafting country (i.e., long descriptions in GLs drafted in Great Britain, but sparse in GLs drafted in the U.S.). Conclusions: The composition of digestive system cancer GL drafting committee may be related to the diversity of GL content. No significant financial relationships to disclose.