A single-arm phase II Austrian/German multicenter trial on continuous daily sunitinib in primary glioblastoma at first recurrence (SURGE 01-07)

Background

Due to the redundancy of molecular pathways simultaneously involved in glioblastoma growth and angiogenesis, therapeutic approaches intervening at multiple levels seem particularly appealing.

Methods

This prospective, multicenter, single-arm phase II trial was designed to evaluate the antitumor activity of sunitinib, an oral small-molecule inhibitor of several receptor tyrosine kinases, in patients with first recurrence of primary glioblastoma using a continuous once-daily dosing regimen. Patients received a starting dose of sunitinib 37.5 mg, followed by a maintenance dose between 12.5 mg and 50 mg depending on drug tolerability. The primary endpoint was a 6-month progression-free survival (PFS) rate. Secondary endpoints included median PFS, overall survival (OS), safety/toxicity, quality of life, and translational studies on the expression of sunitinib target molecules.

Results

Forty participants were included in this study, and no objective responses were detected. PFS6 was 12.5%, median PFS 2.2 months, and median OS 9.2 months. Five participants (12.5%) showed prolonged stable disease ≥6 months with a median PFS of 16.0 months (range, 6.4–41.4 mo) and a median OS of 46.9 months (range, 21.2–49.2 mo) for this subgroup. c-KIT expression in vascular endothelial cells (n = 14 participants) was associated with improved PFS. The most common toxicities were fatigue/asthenia, mucositis/dermatitis, dysesthesias, gastrointestinal symptoms, cognitive impairment, leukoctopenia, and thrombocytopenia. Two participants (5%) terminated treatment due to toxicity.

Conclusion

Continuous daily sunitinib showed minimal antiglioblastoma activity and substantial toxicity when given at higher doses. High endothelial c-KIT expression may define a subgroup of patients who will benefit from sunitinib treatment by achieving prolonged PFS.ClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT00535379","term_id":"NCT00535379"}}NCT00535379.     

How many people are able to control a P300-based brain–computer interface (BCI)?

An EEG-based brain–computer system can be used to control external devices such as computers, wheelchairs or Virtual Environments. One of the most important applications is a spelling device to aid severely disabled individuals with communication, for example people disabled by amyotrophic lateral sclerosis (ALS). P300-based BCI systems are optimal for spelling characters with high speed and accuracy, as compared to other BCI paradigms such as motor imagery. In this study, 100 subjects tested a P300-based BCI system to spell a 5-character word with only 5 min of training. EEG data were acquired while the subject looked at a 36-character matrix to spell the word WATER. Two different versions of the P300 speller were used: (i) the row/column speller (RC) that flashes an entire column or row of characters and (ii) a single character speller (SC) that flashes each character individually. The subjects were free to decide which version to test. Nineteen subjects opted to test both versions. The BCI system classifier was trained on the data collected for the word WATER. During the real-time phase of the experiment, the subject spelled the word LUCAS, and was provided with the classifier selection accuracy after each of the five letters. Additionally, subjects filled out a questionnaire about age, sex, education, sleep duration, working duration, cigarette consumption, coffee consumption, and level of disturbance that the flashing characters produced. 72.8% (N = 81) of the subjects were able to spell with 100% accuracy in the RC paradigm and 55.3% (N = 38) of the subjects spelled with 100% accuracy in the SC paradigm. Less than 3% of the subjects did not spell any character correctly. People who slept less than 8 h performed significantly better than other subjects. Sex, education, working duration, and cigarette and coffee consumption were not statistically related to differences in accuracy. The disturbance of the flashing characters was rated with a median score of 1 on a scale from 1 to 5 (1, not disturbing; 5, highly disturbing). This study shows that high spelling accuracy can be achieved with the P300 BCI system using approximately 5 min of training data for a large number of non-disabled subjects, and that the RC paradigm is superior to the SC paradigm. 89% of the 81 RC subjects were able to spell with accuracy 80–100%. A similar study using a motor imagery BCI with 99 subjects showed that only 19% of the subjects were able to achieve accuracy of 80–100%. These large differences in accuracy suggest that with limited amounts of training data the P300-based BCI is superior to the motor imagery BCI. Overall, these results are very encouraging and a similar study should be conducted with subjects who have ALS to determine if their accuracy levels are similar.     

Are gender-associated differences in quality of life in colorectal cancer patients disease-specific?

Purpose  The purpose of this study was to investigate gender-associated differences in quality of life in colorectal cancer patients and compare such differences to the general population. Methods  Colorectal cancer patients attending three oncological centres in Austria were consecutively recruited and assessed with the EORTC QLQ-C30. For the purpose of comparison, a gender- and age-matched healthy control group was drawn from a representative sample of the Austrian general population. Results  About 206 patients (47.1% women; mean age 64.8 years) with colorectal cancer were included and compared with 206 persons from the general population. A two-way analysis of variance showed significant main effects (gender and colorectal cancer vs. healthy) for most EORTC QLQ-C30 scales, but a significant interaction effect was only found for diarrhea. This means that gender-associated differences specific for colorectal cancer patients were only found for diarrhea. Conclusion  The vast majority of studies on gender-associated differences in quality of life compare male and female oncological patients and neglect the issue of the disease-specificity of such differences. Our study revealed that women and men suffering from colorectal cancer scored differently across many aspects of quality of life, but with the exception of diarrhea, these differences were also found in the general population, i.e. they indicated no gender-specific reaction to disease.     

Nucleolar silver staining patterns of lymphocytes in sarcoidosis.

Bronchoalveolar lavage lymphocytes from 15 patients with pulmonary sarcoidosis and 8 healthy controls were investigated for nucleolar silver staining patterns and lymphocyte subpopulations. Patients with sarcoidosis had increased numbers of silver stained dots versus controls (2.20 +/- 0.24 versus 1.78 +/- 0.07; p less than 0.001). The number of silver stained dots showed the strongest positive correlation to helper cells (OKT 4+) (r = 0.781; p less than 0.0001). These results may be interpreted as further evidence of lymphocytic activation, especially of helper cells (OKT 4+) in pulmonary sarcoidosis.     

Carcinoembryonic antigen (CEA) in gastrointestinal and extragastrointestinal tumors and its relationship to tumor-cell differentiation

Carcinomas of gastrointestinal (colon, stomach, pancreas, liver) and of extragastrointestinal (bronchus, breast, tonsil, anus, ovary) origin and normal large-bowel mucosa were studied by indirect immunofluorescence for the presence of the carcinoembryonic antigen (CEA). In addition, an attempt was made to correlate the CEA content of the tumors with the degree of their cellular differentiation. In well-differentiated tumors of the colon, including hypersecretory well-differentiated mucoid carcinomas, CEA was abundant on the luminal tumor cell surface and in the lumina of the glands. In moderately differentiated ones, CEA was present in rather low concentrations on the luminal surface and in secondary glandular structures. In poorly differentiated anaplastic carcinomas, CEA was absent. In non-cancerous colonic mucosa surrounding the tumor, in colonic mucosa distant from the tumor as well as in colonic mucosa taken at autopsy from subjects with non-neoplastic extragastrointestinal diseases, CEA could not be found by indirect immunofluorescence. The CEA content of gastric carcinomas was lower than in colonic tumors, although the distribution was similar. In pancreatic cancers, CEA was present in variable amounts depending upon the differentiation of the individual tumor. In these malignancies, CEA was found not only on the luminal surface and in the lumina, but also in the cytoplasm of isolated tumor cells. CEA was not detected in carcinomas of extragastrointestinal origin by indirect immunofluorescence. The localization of CEA on the surface (probably glycocalyx) of the cell, together with its dependence upon a certain degree of tumor cell differentiation, suggest that CEA is a secretion product rather than a constituent of the tumor cell membrane.     

Pathologisch-anatomische Befunde bei mit E 39 behandelten Fällen von Leukosen und malignen Geschwülsten

Zusammenfassung Es werden morphologische Veränderungen an mit E 39 behandelten Leukosefällen und Geschwülsten verschiedenster Art geschildert. Sie dokumentieren sich in intensiver Verfettung, Vacuolisierung und Nekrose der Tumorelemente mit Bildung oft enormer und bizarr geformter Riesenkerne und Kerndegenerationszeichen. Als Reaktion des Stromas findet sich eine oft hochgradige Fibrose. Nicht alle Tumorarten reagierten in der gleichen Art.Mit 10 Textabbildungen