tbuckley/cabot-search huggingface dataset:
Abstract 12422: Evaluation of RV and LV Mass by CMR and Comparison to Recipient Heart Following Heart Transplant; The First-Ever CMR Human Autopsy Study
Authors: Sahadev T Reddy, Nicholas Farber, Mark Doyle, Geetha Rayarao, Diane Thompson, Ronald B Williams, June A Yamrozik, Srinivas Murali, Robert W Biederman
Journal: Circulation (2014)

Introduction: CMR is considered the ‘gold standard’ for noninvasive LV and RV mass quantitation. This concept is predominantly based on GRE sequences yet never validated in humans undermining its credibility. SSFP offers superior image contrast potentially redefining the CMR gold standard for mass. Objective: To establish correlations between SSFP-CMR LV and RV mass vs. pathology mass using Htx pts. Methods: Over 3 years, 68 pts were evaluated including 48 HTx explants obtained immediately from the OR upon HTx. They were prepared (removed PM/AICD and/or LV/RVAD) and scanned ex vivo via SSFP for CMR LV/RV mass (1.5T GE, WI). Via an A utomatic T hresholding program for segmentation with M anual T rimming (ATMT) of extraneous cardiac tissue a 3D LV model was generated. The weight of total heart including papillary and trabeculae for LV and RV was measured via high-fidelity scale. Correlations were between 3D CMR vs. pathology with B-A plots. A separate cohort of 20 non-Htx pts underwent in vivo validation. Results: Of 48 Htx pts, 3 (6%) were excluded due to poor images (peri-surgical destruction) leaving 45 (94%) for analysis. Correlations: 1) Total CMR 3D mass (448±116g) vs. total pathology mass (444±118g; r=0.99, p&lt;.001); 2) 3D CMR-LV mass (297±95g) vs. pathology-LV mass (308±96g; r =0.95, p&lt;.001) 3) 3D CMR-RV mass (152±44g) vs pathology-RV mass (132±41g; r = 0.76, p&lt;.001). The equation y = 1.01x - 6.6b regressed the LV (r = 0.95). Avg bias between CMR and pathology for total, LV and RV mass was +4.4g. For the validation cohort LVEDV r=0.99; LVESV r= 0.99. Conclusions: SSFP-CMR accurately defines total cardiac, LV and RV mass as compared to explanted hearts (despite variable surgical removal of instrumentation). Thus, while GRE was the original ‘gold standard’ for LV mass, SSFP, despite its universal acceptance as the ‘ de facto gold standard is now formally validated in a first-ever human autopsy study. Further, the regression equation now includes , not excludes papillary and trabecular mass.
Phase II trial of liposomal doxorubicinin disseminated endometrial carcinoma: A Gynecologic Oncology Group study
Authors: H. D. Homesley, J. A. Blessing, J. I. Sorosky, G. C. Reid, K. Y. Look
Journal: Journal of Clinical Oncology (2005)

5019 Background: In spite of the proven high activity of doxorubicin as a single agent in chemotherapy of endometrial carcinoma, the Gynecologic Oncology Group (GOG) prudently decided to conduct a phase II clinical trial of liposomal doxorubicin, (from Ortho Biotech Products L.P., Raritan, NJ), in patients with disseminated endometrial carcinoma before replacing doxorubicin with liposomal doxorubicin. Methods: Eligible patients with initial histologic confirmation of endometrial carcinoma presenting with disseminated cancer had not previously received cytotoxic drugs. Also, eligible patients had measurable disease, GOG performance status 0–2, and adequate bone marrow, renal and hepatic function according to standard criteria. Liposomal doxorubicin 40 mg/m2 was given by intravenous injection on an every four week cycle. Patients who remained free from tumor progression or intolerable toxicity received at least one to a maximum of 20 cycles of liposomal doxorubicin. Response by measurable disease change and survival were the endpoints of the trial compared to historical controls especially that of doxorubicin alone. Results: Fifty-six patients were registered, of whom three were determined ineligible (prior malignancy=2, inadequate pathology material=1). One patient never received therapy, leaving 52 evaluable patients. Two patients (3.8%) achieved a complete response, four (7.7%) exhibited a partial response, and 31 (59.7%) had stable disease. The most common adverse effects were constitutional (32/52), anemia (28/52), pain (27/52), dermatologic (25/52) and cardiovascular (12/52). Conclusions: In this trial, liposomal doxorubicin had a response rate of 11.5% in first line treatment of disseminated endometrial carcinoma with tolerable toxicity when given at 40 mg/m2 every four weeks. It is unlikely that liposomal doxorubicin with the associated skin toxicity at this dose would be suitable as a replacement for the much more active doxorubicin for therapy of endometrial carcinoma. No significant financial relationships to disclose.
Monitoring of non-invasive ventilation: Is the strategy used in daily practice enough?
Authors: Marjolaine Georges, Claudio Rabec, Ntumba Kabeya, Danièle NGuyen, Ameline Vagner, Philippe Camus
Journal: European Respiratory Journal (2011)

Background: Non-invasive ventilation (NIV) is recognized as an effective treatment in respiratory failure. However, empirically determined NIV settings may not achieve optimal ventilatory support. As a result, NIV should be systematically monitored. Current strategy used for this monitoring includes clinical assessment, arterial blood gases (ABG) and oximetry. Ideally, complete polysomnography should be done but actually this practice is infrequent. Simple tools such as capnography (TcPCO2) or built-in ventilator software (VPAP-Reslink™, ResMed, Australia) provide reliable information but their role should be defined.

Objectives: To determine effectiveness of current strategy versus different simplified tools in assessing NIV effectiveness.

Methods: Efficacy of NIV was assessed in 95 patients. They underwent oximetry, TcPCO2, Reslink and ABG during spontaneous ventilation. Subjective comfort of NIV was evaluated by questionnaire.

Results: While the usual approach including oximetry and ABG considered 42 patients as correctly ventilated, only 10 patients (11%) are effectively treated as questionnaire, ABG, oxymetry, TcPCO2 and Reslink were normal. Therefore, current strategy gave a wrong estimate of NIV quality in 34% of patients. Adding Reslink to this strategy recognized 20 patients as inadequately ventilated whereas adding TcPCO2 allowed to identify 8 patients.

An alternative non-invasive strategy combining Reslink and TcPCO2 identified 21 patients with good NIV performance. Among them, 8 (9%) had pathological ABG and were badly classified.

Conclusion: The usual strategy overestimates quality of NIV. Combining Reslink and TcPCO2 allows detecting NIV failure in 75% of patients without ABG.
Weekly paclitaxel (wP) as single agent or in combination with weekly topotecan (wT) or carboplatin (C) in patients with resistant ovarian cancer (ROC): The phase II CARTAXHY randomized trial from GINECO
Authors: L. Gladieff, A. Lortholary, R. Largillier, B. Weber, J. Alexandre, X. Durando, B. Slama, J. Dauba, D. Paraiso, E. Pujade-Lauraine
Journal: Journal of Clinical Oncology (2009)

5557 Background: For ROC patients (pts) with early progression during or after (&lt; 6 months) platinum and 3 weekly P, use of single non-platinum agent including wP is standard (Kristensen G, et al. J Clin Oncol 26: 2008 abstr 5508). Few randomized trials have explored combination therapy in this setting. Methods: Pts with ROC after a first or second line including a platinum and a taxane were randomized to receive wP (80 mg/m 2 /week) alone or in combination with wT (3mg/m 2 /week) or C (AUC 5 every 4 weeks). The primary end-point was the comparison of progression-free survival (PFS) between single non-platinum agent and combination therapy (wP+wT or wP+C). Secondary objectives included safety, QoL, response rate (RR) and overall survival. Results: From April 2004 to August 2008, 165 pts were accrued (wP 57, wP+wT 57, wP+C 51). Median number of cycles and P dose-intensity (mg/m 2 /week) was 4.6 and 70, 4.2 and 63 in monotherapy and combination therapy arms respectively. Non-hematological toxicity was not different between the arms, except an excess of hypersensitivity reactions in the wP+C arm. Grade 3–4 neutropenia (48 vs 13% of pts), and anemia (24 vs 6%) were more frequent in combination therapy than in single agent arm and similar with wT or C combination. Febrile neutropenia was experienced by 5 pts treated with combination therapy. Discontinuation from drug treatment was more frequent with combination therapy (24% of pts) than with monotherapy (4%), mainly due to hematotoxicity. RR was 34, 38 and 39% for wP, wP+wT and wP+C respectively. Median PFS of pts treated with single agent (112 days) was not significantly different from those treated with combination therapy (149 days) (p = 0,62) and was similar in wP+wT (152 days) or wP+C (146 days) arms. Treatment with single non-platinum agent or combination therapy was not found an independent parameter when added to a Cox model including prognostic variables. Conclusions: Combination therapy (CT) in platinum resistant ovarian cancer was found more toxic than weekly paclitaxel and the PFS advantage from CT was not statistically significant. No significant financial relationships to disclose.
A web based survey of healthcare provider and patient interests in the creation of future Internet based cancer information programs
Authors: J. M. Metz, J. Draznin-Maltzman, M. Hampshire
Journal: Journal of Clinical Oncology (2004)

6124 Background: Although many web resources have been created for patients and healthcare providers, data regarding users desires for program content and ability to utilize broadband features are lacking. Methods: Between 5/03 and 10/03, 448 responders completed this internally validated survey placed on OncoLink, the Internet resource at the University of Pennyslvania. OncoLink maintains diverse multi-level content for both cancer patients and healthcare providers. It currently delivers 1–2 million pages to over 385,000 unique IP addresses monthly. Of the survey responders, 63% were 35–64 yrs, 314 (70%) were female, and 334 (75%) were from the US. The study included 121 (27%) healthcare providers and 327 (73%) patients/family/friends. The survey specifically asked users to rate the development priority of 18 different programs for cancer information on the web and rate the most important feature provided by websites. Results: Internet based cancer information was accessed at work and home by 50%, and at home only by 46%. Broadband access was available to 52%. The latest cancer news (44%) and latest cancer treatments (27%) were highest rated features when ranked by the single most important feature on cancer websites. When a variety of features were considered and ranked by priority, the highest scores were for new oncology product information (62%), ask the experts features (54%), interviews with oncology leaders (53%), journal scans (51%), and oncology conference reporting (46%). There were high priority scores from both groups for the development of broadband features such as video webcasting (41%). Healthcare providers were more likely to desire material related to conference reporting (59% vs 33%, p<0.001); patients were more likely to desire survivor stories (48% vs 35%, p<0.001), but no other significant differences were found. Conclusions: Patients and healthcare providers desire similar content development for cancer related information. Resources should be allocated by cancer information services for the development of broadband content. No significant financial relationships to disclose.
A phase I/II study of capecitabine (X), irinotecan (I) and oxaliplatin (O) as first-line therapy in patients (pts) with advanced or metastatic colorectal cancer (MCRC)
Authors: J. A. Maroun, D. Jonker, R. Goel, C. Cripps, D. Lister, G. Chiritescu
Journal: Journal of Clinical Oncology (2006)

13540 Background: Triplets of I, O and infusional 5-FU/Leucovorin (LV) are associated with high response rates and long survival in first-line MCRC [Falcone et al. JCO 2002;20:4006–14]. The oral fluoropyrimidine X has proved higher response rates and improved safety vs. 5-FU/LV in MCRC. Methods: This ongoing dose-escalation study aims to establish dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and recommended phase II doses (RPIID) of I and O in combination with X as first-line therapy for MCRC and to assess the efficacy and safety of this XIO combination. Starting doses were: I (180mg/m 2 i.v. on day 1), O (85mg/m 2 i.v. on day 1), and X (850mg/m 2 bid orally on days 2–15). Dose escalations are based on toxicity observed at the previous dose level (DL), until DLT, MTD and RPIID are documented, at which time a phase II component begins. Results: We enrolled 18 pts (13 men, 5 women), median age 61 (range 44–74) at 4 DLs. ECOG PS was 0 or 1 in 17 pts, and 2 in 1 pt. Pts received a median of 7 cycles (range 1–15) of XIO. All pts are evaluable for toxicity and 14 for response. The most common adverse events were: neutropenia (83% all grades (G) with 4 G3, 4 G4), diarrhea (67%, 4 G3, one of which was a DLT). Nausea (78%) and vomiting (56%) were mild and controlled with anti-emetics. Fatigue occurred in 50% pts, with 1 G3. The DLT was febrile neutropenia (3 pts at DLs 1, 3, &amp; 4 respectively). One pt at DL4 developed severe neutropenia and sepsis during cycle 3, had aspiration pneumonia and died in hospital from respiratory and cardiac complications. MTD has not yet been reached. Responses were observed at all DLs: 11 partial responses with 2 still unconfirmed (79%, 95% CI 54–100), and 2 stable disease (14%). Progression-free survival and overall survival have not been reached. Conclusions: XIO is well tolerated and demonstrated significant efficacy as first-line treatment in MCRC. Severe neutropenia was significant but was of short duration and manageable. It is likely to be the main DLT. MTD has not yet been identified but is expected in the next few pts. A phase II study to confirm the efficacy and safety of the XIO combination will follow. Supported by Roche, Sanofi Aventis, and Pfizer Canada Inc. [Table: see text]
Association between prothrombin rate, alpha-fetoprotein changes and survival of patients with advanced hepatocellular carcinoma (HCC)
Authors: A. Mauguen, S. Michiels, F. Bonnetain, J. Barbare, O. Bouché, M. Doffoel, L. Bedenne, X. Paoletti
Journal: Journal of Clinical Oncology (2008)

15507 Background: Pro-Thrombin rate (TP) and alpha-fetoprotein (AFP) are commonly associated with overall survival (OS) of patients with HCC. Only their baseline measures are included in prognostic classifications such as the CLIP. The aim of this work was to evaluate the prognostic value of changes in AFP and TP over time on OS. Methods: Using data from 2 randomized trials conducted by the Fédération Francophone de Cancers Digestifs (FFCD) comparing tamoxifen to supportive care or chemoembolisation + tamoxifen to tamoxifen, we studied 3 measures of change in AFP and TP: their (i) value at time t, (ii) difference between value at time t and t-1 and (iii) relative increase as compared to their baseline values. The c-index was used to assess predictive accuracy of the Cox models with time-dependent covariates. External validation was performed on a third trial comparing octreotid- versus placebo of the FFCD. Results: Median OS of the 547 patients included in the first 2 trials was 5.3 months. The median number of TP and AFP measurements by patient was 3. Relative decrease of TP as compared to its baseline value, and log (AFP) at time t were the most strongly associated with OS. A multivariate model combining the latter two factors and CLIP provided a HR=1.19 per 10% decrease for TP, p<10-4 and HR=1.15 per unit increase for log(AFP), p<10-4. The c-index increased from 0.70 (CLIP alone) to 0.75. External validation on the 271 patients of the third trial confirmed the increase in c-index from 0.58 to 0.66. Conclusions: Evolution of TP and AFP over time is significantly associated with survival of patients with advanced HCC. More frequent follow-up visits need to be scheduled in future trials. No significant financial relationships to disclose.
A phase I study of nifurtimox in patients with relapsed/refractory neuroblastoma
Authors: G. Saulnier Sholler, W. Ferguson, B. Laurent, G. Johnson, B. Heath, P. Bingham, A. Taka, B. Kamen, A. Homans
Journal: Journal of Clinical Oncology (2008)

2561 Background: Nifurtimox is a nitroheterocyclic compound that has been shown to exert its cytotoxic effect specifically by generating free radicals. The objectives of this study were to test the safety and pharmacokinetic profile of nifurtimox in children with relapsed/refractory neuroblastoma when given alone and in combination with cyclophosphamide and topotecan. Methods: Eligibility criteria included patients <21 years old with relapsed neuroblastoma and measurable disease. Nifurtimox dosing began at 20mg/kg/day orally (3 patients/cohort) and escalated by 10mg/kg/day per cohort until 2/6 patients in a cohort experienced dose limiting toxicities (DLT). Patients received nifurtimox for 21 days (cycle 1), followed by 3 cycles in combination with cyclophosphamide and topotecan. Pharmacokinetic analysis was done on Day 1 and 4 of cycle 1 (nifurtimox alone) and of cycle 2 (nifurtimox with cyclophosphamide and topotecan). DLT was defined as any CTC grade 4 toxicity, grade 3 neurotoxicity, or grade 2 toxicity that persisted for >7 days requiring treatment interruption >7 days. Results: Three patients were enrolled at 20mg/kg/day, 6 patients at 30mg/kg/day and 5 patients at 40mg/kg/day. Toxicities ≥grade 2 included stomach pain (n=1), anorexia (n=6), neuropathy (n=6) and grade 2 seizure (n=5). DLT’s occurred at 40mg/kg/day and included one grade 3 pulmonary hemorrhage and one grade 3 motor neuropathy. The recommended phase II dose is 30mg/kg/day. Pharmacokinetic (PK) analysis show peak serum levels at 3 hours. Although this is a phase I trial, fourteen patients were evaluable for efficacy following nifurtimox treatment alone; 10 displayed stable disease and 4 progressive disease. Of the eleven patients were evaluable for efficacy after 3 cycles with nifurtimox, cyclophosphamide and topotecan, 4 showed a partial response and 7 had stable disease. Conclusions: Nifurtimox can safely be administered orally alone and in combination with cyclophosphamide and topotecan. The results show that nifurtimox has potential as an anti-cancer agent in this resistant/refractory population and warrants further evaluation. Clinical and PK data will be presented. No significant financial relationships to disclose.
포스터 전시 : 간경변증 환자에서 복수와 정맥류의 상관 관계
Authors: 김희만, 전재윤, 윤영준, 안상훈, 박영수, 백용한, 이관식, 한광협, 문영명
Journal: Clinical and Molecular Hepatology (2003)

배경/목적: 간경변증 환자에서 식도 또는 위 정맥류의 진단을 위해 상부위장관 내시경 검사를 시행한다. 이은 출혈의 과거력이 없었던 정맥류의 일차 예방을 위한 베타 차단제의 사용을 가능하게 해주고, 급성 상부위장관 출혈 시 출혈부위를 예측하여 치료의 계획 수립에 도움을 준다. 그러나 식도 또는 위 정맥류가 처음 발견되었을 때 추적 검사의 필요성, 시기, 횟수 등에 관련된 구체적인 원칙은 아직까지 없는 실정이다. 복수는 간경변증의 합병증으로 신체검사나 비침습적인 복부 초음파 검사로 쉽게 진단 할 수 있기 때문에 연자들은 이와같은 복수 진단의 용이함을 이용하여 상부위장관 내시경을 시행하지 않고도 위 또는 식도정맥류의 유무 및 중등도를 예측할 수 있을지를 알아보기 위해 복수를 동반한 간경변증 환자에서 전향적 연구를 시행하였다. 대상과 방법: 1999년부터 2002년까지 병원에 내원한 환자 중 복부 초음파 검사와 상부 위장관 내시경을 같은 시기에 실시한 총 23명의 간경변증 환자들을 대상으로 하였다. 복수의 중등도는 복부 초음파를 통해 small, moderate, large 세 군으로 분류하였고, 위 또는 식도 정맥류는 상부 위장관 내시경을 통해 형태, 색조, 위치에 따라 분류하였다. 이와 같은 정맥류의 분류는 1991년 일본 문맥압 항진증 연구회의 식도 위 정맥류 내시경 소견을 따랐다. 결과: 대상 환자 나이의 중앙값은 53 (39-70)세였으며 성별은 남녀가 각각 15명, 8명이었다. 간경변증의 원인으로 B형 간염이 13명(56.5%), 알코올성 간경변증이 9명(39.1%), 원발성 담즙성 간경변증이 1명(4.3%)이었다. 대상 환자의 간경변증 이환기간은 24 ?5.2개월이었고 복수의 양은 small 군, moderate 군, large 군이 각각 4명(20%), 7명(35%), 9명(45%)이었다. 내시경 소견에서 식도 정맥류는 18명, 위 정맥류는 6명, 식도와 위정맥류가 동시에 있는 경우는 6명이며, 5명은 복수가 있더라도 정맥류가 없었다. 형태에 따른 분류로 볼 때 F0, F1, F2, F3 가 각각 5명, 5명, 12명, 1명이었다. 위치에 따라 하부, 중부, 상부식도가 각각 4명, 11명, 3명이었다. 복부 초음파로 측정한 비장의 크기는 식도정맥류의 형태에 따른 네 군으로 분류하였을 때, 순서대로 평균 11.7 cm, 13.6 cm, 14.4 cm, 15 cm로 비례하는 경향은 보였으나 통계학적 차이는 없었다. 또한, 네 군으로 분류하였을 때 백혈구, 혈소판, 총단백, 알부민 등 혈청학적 검사에서 유의한 차이는 없었으며, 복수의 백혈구, 알부민, 전해질 등과 24시간 소변의 나트륨 농도에서 통계학적으로 유의한 차이는 없었다. 식도정맥류의 형태, 정도 및 위치와 복수의 정도는 통계학적으로 유의한 상관관계를 보이지 않았다. 결론: 초음파 검사를 통해 알 수 있는 복수의 정도는 식도 정맥류의 존재나 중등도를 예측할 수 없었으나 비장의 크기와는 비례하는 경향을 보여 좀 더 많은 환자를 대상으로한 계속적인 연구가 진행중이다.
Civil War Hospital
Authors: D. J. Canale
Journal: JAMA (2005)

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Activation of the PI3K/Akt pathway in neuroblastoma
Authors: H. Sartelet, M. Castain, M. Fabre, J. Bosq, A. Rougemont, S. Michiels, G. Vassal
Journal: Journal of Clinical Oncology (2007)

9523 Background: Neuroblastoma is a pediatric malignant neurorectodermal tumor with still a poor survival in children over 1 year of age. In cancer, the PI3K/Akt pathway contributes to tumor aggressiveness (proliferation, metastasis). It is a major target for novel anti- cancer therapies. The objective was to study the activation of the PI3K/Akt pathway in NB. Methods: 101 patients (median age 2.5 years, range: 0–13) with a resected neuroblastoma (16 stage I; 7, II; 22, III; 48, IV and 8, IVS) were included. Tissue microarrays were constructed containing 101 primary tumors, 39 paired metastases and 56 paired normal tissues. Immunohistochemical staining was performed on sections using antibodies against PI3K, Akt and phosphoAkt (S-473). The expression of membrane receptors (EGFR, HER-2, VEGFR1, VEGFR2, PDGFRa, PDGFRβ, IGF1Rβ, TrkB), proteins directly interfering with AKT (PTEN, mTOR) and downstream proteins (phospho-p70S6 kinase, 4eBP1) was studied. The intensity was evaluated by a semi-quantitative score based on the percentage of positive cells. The Wilcoxon signed rank test was applied for the comparison of paired data and adjusted for multiple testing using the False Discovery Rate criterion. Spearman correlation values (rho) were used to compare the expression between genes in the primary tumors. Results: 60% of the tumors expressed PI3K, 80% AKT and 73% pAKT. In addition, phospho-p70S6 kinase and 4eBP1p were expressed in 95% and 85%. All these proteins had a higher expression in tumors as compared with paired normal tissues (fdr-adjusted p&lt;0.001). Akt and pAkt showed a tendency for higher expression in metastases as compared to paired primary tumors (raw p&lt;0.05 for both, but fdr-p=0.11 and fdr-p=0.17 respectively). While EGFR, IGF1Rβ, TrkB, PDGFRa and PDGFRβ were significantly more expressed in primary tumors as compared to normal tissues (fdr-p&lt;0.05), only IGF1Rβ seemed more expressed in metastases (fdr-p=0.09). A significant positive correlation was found between pAkt and the following: VEGFR1, VEGFR2 and IGF1Rβ (rho&gt;0.34, p&lt;0.001), phospho-p70S6 kinase and mTOR(rho&gt;0.26, p&lt;0.01). Conclusions: The PI3K/Akt pathway is activated in neuroblastoma and could be an attractive target for novel therapies. In addition, the data suggested that VEGFR and IGF1R are preferentially committed to this pathway activation. No significant financial relationships to disclose.