Randomized clinical trial on 7-days-a-week postoperative radiotherapy for high-risk squamous cell head and neck cancer

PURPOSE: To evaluate the normal tissue reactions and loco-regional control rates (LRC) in patients treated with 7-days-a-week postoperative continuous irradiation (p-CAIR) compared to conventionally fractionated 5-days-a-week postoperative radiotherapy (CF). MATERIALS/METHODS: Between 2001 and 2004, 279 patients with high-risk squamous cell cancer of the larynx (158 pts.) or cancer of the oral cavity/oropharynx (121 pts.) were enrolled. They were stratified according to the primary cancer site (larynx vs. others) and the treating center and randomized to receive 63 Gy in fractions of 1.8 Gy given 5-days-a-week (140 pts: CF) or 7-days-a-week (139 pts: p-CAIR). RESULTS: The acute and late toxicity was considered acceptable, although the proportion of patients with confluent mucositis was higher in p-CAIR compared to CF (60.0 vs. 33.3%). The actuarial 3-year LRC were 64 vs. 70% for CF and p-CAIR, respectively, p=0.32. A statistically significant improvement in 3-year LRC in p-CAIR arm appeared in a subset of the patients with cancer of the oropharynx/oral cavity (74% p-CAIR vs. 53% CF, p=0.02). By contrast, there was no improvement in LRC in a subset of the patients with cancer of the larynx (p=0.46). CONCLUSION: An improvement in LRC attributable to acceleration of postoperative radiotherapy appeared restricted to the patients with cancer of the oropharynx/oral cavity. In patients with cancer of the larynx acceleration of postoperative radiotherapy did not have any beneficial effect.     

Usefulness of whole blood aggregometry and its comparison with thromboxane generation assay in monitoring acetylsalicylic acid effectiveness--a multiparametric study in rats.

BACKGROUND: There is a need for consensus concerning universal methodological criteria for detection of suboptimal response to acetylsalicylic acid (ASA) therapy. Therefore, animal models to test for ASA effectiveness remain of interest. Our objective was to verify the usefulness of multiparametric whole-blood impedance aggregometry and thromboxane A(2) generation, which are the most popular techniques used for monitoring of ASA treatment effectiveness. METHODS: Using multiparametric analysis of whole-blood impedance aggregometry, we examined which parameters of platelet aggregation or disaggregation allow for the best discrimination between ASA-treated (4 or 40 mg/kg for 60 days) and non-treated male rats. The effectiveness of ASA-mediated inhibition of platelet cyclooxygenase-1 was verified by determination of plasma thromboxane B(2) and urine 11-dehydro-thromboxane B(2), accepted as reference assays for monitoring of ASA-mediated platelet cyclooxygenase-1 inhibition. RESULTS: Two of the platelet agonists used, collagen (1 mg/L) and arachidonic acid (0.5 mmol/L), allowed discrimination of control and ASA-treated animals, whereas adenosine diphosphate (5 micromol/L) was not effective. It is noteworthy that only ASA-mediated changes in duration of the rising phase for platelet aggregation and the area under the curve for collagen-induced aggregation allowed significant discrimination between low and high ASA dose and remained correlated with the reference parameter, plasma thromboxane B(2). CONCLUSIONS: Analysis of aggregation curves, routinely based only on the amplitude and rate of platelet aggregation, may not be enough discriminative to distinguish between varying ASA doses and treatment schedules.     

Carcinoembryonic antigen,squamous cell carcinoma antigen,CYFRA 21-1, and neuron-specific enolase in squamous cell lung cancer patients

BACKGROUND: Carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC-Ag), and CYFRA 21-1 are the most useful markers for non-small cell lung cancer (NSCLC), but neuron-specific enolase (NSE) is a tumor maker of choice for SCLC. The determination of NSE in NSCLC could allow selection of patients with neuroendocrine features. NSCLC patients whose tumors have neuroendocrine properties may be more responsive to chemotherapy; however, these tumors have been reported to be more aggressive. Tumor markers are not suitable for diagnosis; their principal applications are in monitoring of therapy and prognosis. METHODS: Tumor markers were measured in 200 untreated patients with squamous cell lung cancer (SQC) and a reference group (n = 220; 124 healthy persons and 96 patients with nonmalignant lung disease). CEA and SCC-Ag were measured by microparticle enzyme immunoassays on Abbott AxSYM and IMx analyzers. CYFRA 21-1 and NSE were measured by electrochemiluminescence immunoassays on the Roche Elecsys 2010. RESULTS: CEA, SCC-Ag, CYFRA 21-1, and NSE were increased above the cutoffs in 26%, 32%, 67%, and 28% of tested patients, respectively. The area under the ROC curve for CYFRA 21-1 was higher than those for CEA, SCC-Ag, and NSE (SQC vs controls). CYFRA 21-1 and CEA were significantly higher in advanced SQC than in early stages of disease (P <0.0001 and P <0.0004, respectively). In multivariate analysis of survival, CYFRA 21-1 was an independent but nonspecific prognostic factor in the operable group of SQC patients, whereas NSE was an independent prognostic factor in the advanced stages of disease. CONCLUSION: CYFRA 21-1 is an independent prognostic factor in earlier stages and NSE in the advanced stages of SQC.