Baseline carcinoembryonic antigen (CEA) serum levels predict bevacizumab-based treatment response in metastatic colorectal cancer.

Carcinoembryonic antigen (CEA) affects tumorigenesis by enhancing tumor cell survival and by inducing tumor angiogenesis. This study aimed to evaluate baseline CEA serum levels to predict bevacizumab-based therapy effect and survival in patients with metastatic colorectal cancer (mCRC). Two hundred and ninety eight mCRC patients receiving chemotherapy plus either bevacizumab or cetuximab were analyzed in a retrospective study. Disease control (DC), progression-free survival (PFS), and overall survival were assessed and related to pretreatment CEA serum levels. Patients with baseline CEA serum levels below the statistical median of 26.8 ng/mL (group I) were compared with patients with higher CEA levels (group II). The cetuximab-based treatment cohort was analyzed for specificity assessment of CEA to predict the anti-vascular endothelial growth factor effect in mCRC. Baseline CEA serum levels inversely correlated with therapeutic response in patients receiving bevacizumab-based treatment (disease control rate, 84% vs 60%), inversely correlated with median PFS leading to a median PFS benefit of 2.1 months for patients in group I when compared with group II, as well as inversely correlated with median overall survival (37.5 months vs 21.4 months). In an independent cohort of 129 patients treated with cetuximab-based therapy, no association of therapeutic response or PFS with CEA serum levels was found. As expected, baseline CEA levels were prognostic for mCRC. These data give first evidence that baseline serum CEA levels might constitute an important predictor for the efficacy of first-line bevacizumab-based therapy in patients with mCRC.

Sorafenib in advanced, heavily pretreated patients with soft tissue sarcomas.

Therapeutic options for patients with advanced pretreated soft tissue sarcomas are limited. However, in this setting, sorafenib has shown promising results. We reviewed the data of 33 patients with soft tissue sarcoma treated with sorafenib within a named patient program in Austria. Twelve physicians from eight different hospitals provided records for the analysis of data. Among the 33 patients, the predominant histological subtype of sarcoma was leiomyosarcoma (n=18, 55%). Other subtypes were represented by only one or two cases. Fifteen patients presented with metastases at the time of diagnosis. Another 17 patients developed metastases later in the course of the disease (data on one patient are missing). Most of the 33 patients had undergone resection of the primary (n=29, 88%) and half of the patients had received radiotherapy (n=17, 52%). Chemotherapy for metastatic disease had been administered to 30 patients (91%). The majority had received two or more regimens of chemotherapy (n=25, 76%) before sorafenib treatment. The use of sorafenib resulted in a median time to treatment failure of 92 days in patients with leiomyosarcoma and 45 days in patients with other histological subtypes. One-third of the patients derived benefits from treatment: four patients were documented with partial response and six with stabilized disease. In terms of treatment-related toxicity, skin problems of various degrees and gastrointestinal disturbances were frequently reported. In this retrospective analysis of heavily pretreated patients with advanced soft tissue sarcomas, sorafenib was associated with some antitumor activity and an acceptable toxicity profile.

A randomized clinical trial of continuous flow nitrous oxide and nalbuphine infusion for sedation of patients during radiofrequency atrial flutter ablation.

BACKGROUND: In patients with common atrial flutter (CAF), radiofrequency ablation (RFA) causes discomfort. Patients undergoing RFA often feel pain which is difficult to control as the mechanisms are unclear. HYPOTHESIS: Inhaled nitrous oxide (N2O) is a potent sedative-analgesic-anxiolytic agent that may relieve anxiety and discomfort during CAF ablation. METHODS AND RESULTS: In a prospective randomized study, the effect of Inhaled N2O was compared with that of intravenous sedation with Nalbuphine during CAF ablation in 76 patients (64 +/- 13 years, 56 men). We used a 24 pole mapping catheter around the tricuspid annulus and a 8-mm tip ablation catheter for each patient. Forty-two patients (group 1) underwent radiofrequency (RF) application to the cavotricuspid isthmus 5 minutes after the beginning of inhalation of a (50% N2O/50% O2) mixture. Thirty-four patients (group 2), underwent the first RF application 15 minutes after the end of an infusion of Nalbuphine (20 mg delivered over 15 minutes). Ablation-related anxiety and discomfort were assessed using a visual analog scale (VAS) ranging from 0 to 100 mm, with 0 correlating to the statement "no pain at all" and 100 with "the worst possible pain." The VAS score was determined at the end of each application. The number of RF applications (group 1; 10 +/- 8 vs group 2; 11 +/- 6, P = NS) and procedure duration (group 1; 75 +/- 53 minutes vs group 2; 72 +/- 45 minutes, P = NS), were similar for the two groups. N(2)O sedation compared with nalbuphine infusion reduced VAS for anxiety (10 mm +/- 8 vs 58 mm +/- 22, P < 0.05) and for discomfort (18 mm +/- 9 vs 45 mm +/- 34, P < 0.01), respectively. Although there was more frequent vomiting in group 1; 7 of 42 (17%) than in group 2; 3 of 34 (9%), P < 0.05, patients were less likely to have hypotension during the procedure 1 of 42 (2.5%) versus 4 of 34 (12%), P < 0.05, respectively. CONCLUSION: Inhalation of a (50% N2O/50% O2) mixture during RF ablation for atrial flutter is a safe and efficient way to reduce anxiety and discomfort caused by RF applications.

Simple and efficient identification of conduction gaps in post-ablation recurring atrial flutters.

AIMS: Cavo-tricuspid isthmus (CTI) radiofrequency (RF) ablation is a curative therapy for common atrial flutter (AFl), but is associated with a recurrence rate of 5-26%. Although complete bidirectional conduction block is usually achieved, the recurrence of AF is due to recovered conducting isthmus tissue through which activation wavefronts pass. We evaluated a simple and efficient electrophysiological strategy, which pinpoints the ablation target. METHODS AND RESULTS: Twenty-five patients (19 men), mean age 61 +/- 6, with recurrent AFl required a repeat ablation, 250 +/- 160 days after a successful RF CTI procedure. Transverse CTI conduction was monitored during AFl or coronary sinus (CS) pacing by a 24-pole mapping catheter positioned in the right atrium (RA), with the distal poles in the CS, proximal poles on the lateral RA, and intermediate poles on the CTI. A slow conduction area traversing the CTI (velocity, 37 +/- 22 vs. 98 +/- 26 cm/s on either side, P < 0.05) and a lower potential amplitude than at both sides (0.2 +/- 0.15 vs. 0.5 +/- 0.5 mV, P < 0.05), defined by a bayonet-shaped depolarization sequence, were considered to represent the incomplete line of block (InLOB). An ablation catheter was progressively dragged up to this InLOB, from the tricuspid annulus to the inferior vena cava, analysing the widely separated double potentials (DPs) until these coalesced. In nine patients (35%), the target conduction gap was a coalesced fractionated atrial potential within the InLOB (duration, 77 +/- 12 ms), and in 16 patients (65%), a narrow DP toward the healthy margins of this InLOB (duration, 28 +/- 15 ms). Adopting this strategy yields 100% successful re-ablation of recurring AFl leading to bidirectional block, with a mean 2.7 +/- 1.4 RF applications. CONCLUSION: Transverse CTI mapping precisely locates the InLOB and helps find conduction gaps along the CTI in re-ablation procedures for common AFl.