ABSTRACT
AIM: Comparison of the therapeutic effect of treatment of non-muscle invasive bladder carcinoma (NMIBC) after intravesical Interleukin-2 (IL-2) instillations in the presence and absence of a marker tumour. MATERIALS AND METHODS: Two pilot studies were performed in patients with NMIBC. The first study (10 patients) was performed in Krakow (Poland), the second (26 patients) in Vilnius (Lithuania). In Krakow the tumours were treated with incomplete transurethral resection (TUR) leaving a marker tumour of 0.5-1.0-cm followed by IL-2 instillations (3 × 10(6) IU IL-2) on five consecutive days. In Vilnius the tumours were treated with complete TUR, followed by IL-2 instillations (9 × 10(6) IU IL-2) on five consecutive days. RESULTS: During 30 months follow-up, the recurrence-free survival was 5/10 (50%) and 6/26 (23%) after incomplete and complete TUR, respectively. So, the ratio of the recurrence-free survival after incomplete/complete TUR of 50/23=2.2. The median of the recurrence-free survival is >20.5 months and 7 months after incomplete and complete TUR, respectively. So, this ratio was >20.5/7= >2.9. The hazard ratio which combines both the chance of the disease recurrence and its timing for both censored and uncensored cases was 0.53, again confirming the better outcome after incomplete TUR. CONCLUSION: A possible explanation for the better therapeutic effects after incomplete TUR compared with complete TUR is that the marker tumour has tumour-associated antigens (TAA) that could lead to an immune reaction that is stimulated by local application of IL-2. After complete TUR, no TAA are available to initiate and to stimulate an immune reaction; consequently, local IL-2 therapy is less effective after complete TUR. The results of these two pilot studies have led to the recent start of a randomised prospective clinical trial in which therapeutic effects of local IL-2 therapy after complete and incomplete TUR are compared.
Subject(s)
Antineoplastic Agents/therapeutic use , Biomarkers, Tumor/analysis , Interleukin-2/therapeutic use , Neoplasm Recurrence, Local/mortality , Urinary Bladder Neoplasms/mortality , Administration, Intravesical , Adult , Aged , Aged, 80 and over , Combined Modality Therapy , Female , Follow-Up Studies , Humans , Lithuania , Male , Middle Aged , Neoplasm Grading , Neoplasm Recurrence, Local/drug therapy , Neoplasm Recurrence, Local/surgery , Neoplasm Staging , Pilot Projects , Poland , Prognosis , Survival Rate , Urinary Bladder Neoplasms/drug therapy , Urinary Bladder Neoplasms/surgeryABSTRACT
This functional magnetic resonance imaging (fMRI) study systematically investigates whether there is a neurofunctional overlap of nonsymbolic numerical and spatial cognition in (intra)parietal regions in children and adults. The study also explores the association between finger use and (nonsymbolic) number processing across development. Twenty-four healthy individuals (12 children, 12 adults) were asked to make nonsymbolic numerical and spatial (experimental tasks) as well as color discriminations (control task). Using identical stimulus material across the three tasks disentangled nonsymbolic number representations from general attentional mechanisms, visual-spatial processing and response selection requirements. In both age groups, behavioral distance effects were obtained upon processing numerical (but not spatial and/or color) stimuli. Baseline imaging effects revealed age-dependent, partly overlapping activations of nonsymbolic numerical and spatial processing in the right posterior superior parietal lobe (PSPL) in adults only. Interestingly, regions more activated in children relative to adults were centred on bilateral supramarginal gyrus (SMG) and lateral portions of the anterior intraparietal sulcus (IPS), further extending to adjacent right post- and precentral gyrus, the latter of which has been reported to support grasping previously (Simon et al., 2002). Overall, our results are first evidence for an age-dependent neurofunctional link between areas supporting finger use and nonsymbolic number processing and furthermore, might be suggestive of a special role of fingers for the development of number magnitude representations and early arithmetic.
Subject(s)
Brain Mapping , Concept Formation/physiology , Discrimination, Psychological/physiology , Mathematics , Parietal Lobe/physiology , Space Perception/physiology , Adult , Age Factors , Attention/physiology , Child , Child Development/physiology , Color Perception/physiology , Female , Humans , Magnetic Resonance Imaging , Male , Orientation/physiology , Pattern Recognition, Visual/physiology , Photic Stimulation , Reaction Time/physiology , Reference ValuesABSTRACT
The therapeutic effect of intratumoural application of Interleukin-2 (IL-2) was studied in patients with stage III-IV nasopharyngeal carcinoma (NPC) that received radiotherapy. Patients with stage III-IV NPC receiving a standard treatment of 7,000 cGy external beam irradiation have a mean disease-free survival of about 1.5 years. In this paper, we describe ten of these patients who were treated with additional peritumoural and intratumoural injections with 3 x 10(4) U IL-2 on 5 days in weeks 2, 4, and 6 of the 7-weeks' irradiation period. This combined treatment group was compared with a historical group of patients treated with standard irradiation alone. Local IL-2 therapy showed a marked clinical and statistical significant improvement of disease-free survival. After 5 years, 63% of the IL-2 treated patients were disease-free versus 8% of the control patients. These results suggest that the therapeutic results of radiotherapy can be significantly improved by combining it with local IL-2 treatment. To our knowledge, this is the first clinical report showing that local IL-2 therapy is effective against an infiltrative and locally metastasizing tumour in human patients.
