Pediatric Neuro-oncology in Small Centers – Quality Control of Network Support: The HIT-GBM Experience

Results

Patients. A total of 310 patients (173 boys and 137 girls) were registered in the HIT-GBM® database between 1995 and 2003 and followed up until 2005. The age at time of diagnosis ranged from 3.3 to 18.0 years (median 9.9 years). The primary tumor locations were the cerebral hemispheres in 84 patients, thalamus and basal ganglia in 38, pons in 134, brain stem outside of the pons in 14, cerebellum in 14, spinal cord in 8 and multiple overlapping areas in 18 patients. The surgical procedure was reported as a complete resection in 49 patients, subtotal resection in 35, partial resection in 58, biopsy only in 99, and no surgery in 69 patients. A total of 123 tumors were classified as grade IV (WHO), 101 as grade III, and 15 as low grade. No histological data were available in 71 patients. Patients with low grade histology and without histological diagnosis had pontine glioma and were enrolled based on radiographic criteria. The median OS time from diagnosis was 1.02 years (95% CI: 0.91-1.12), and the median event-free survival time was 0.54 years (95% confidence interval (CI): 0.48-0.59). Standard risk factor analysis based on tumor biological criteria and the treatment and toxicity results of the various protocols have been published elsewhere (11).

Time intervals, process quality. The imaging delay time was documented in only 129 patients. It ranged from −3 to 1113 days (median: 23 days, a negative value refers to imaging that was performed for a different indication and clinical tumor signs were recognized only thereafter). The median surgery delay was seven days and five patients had a surgical delay of more than 60 days (n=surgical delay time documented: 105 patients). The median treatment delay was 20 days (range: 0-513, n=288). The time delay between initial clinical signs and the initial diagnostic imaging was shorter in the subgroup of patients who developed high-grade glioma as a second malignancy (p=0.004), and no patient with a secondary high-grade glioma had an imaging delay of more than 21 days. Patients who underwent the initial imaging within 21 days more frequently had surgery within seven days than patients who had longer imaging delay times (p<0.0005). The surgery delay time was predictive of surgical outcome, as surgical procedures within seven days were more likely to be complete resections than were surgeries done later (p=0.026 by the Pearson correlation). The longest imaging delay times were found in patients with fibrillary astrocytoma of the pons (four patients, median imaging delay time: 214 days). The times until nonsurgical treatment started were generally longer in the earlier years of study enrollment: early surgery within seven days after imaging was more frequent in the latest protocol (p<0.0005).

Center size and quality of care. Patients were enrolled from 72 hospitals in Germany, Austria, Switzerland, and Slovenia. The number of patients at each hospital varied from one to 17. Nine hospitals registered ten or more patients, while 21 hospitals registered only one patient. Eighty-one patients were registered at centers located in sparsely populated areas, whereas 34 patients were registered at centers located in major cities. All available risk factors were compared according to center size, and only the patients' gender distribution was unequal in medical centers of different sizes (more girls in larger centers, p=0.014). Thus it can be concluded that there was no influence of center size on overall patient outcome. Patients treated in centers that had registered five patients or fewer had a median overall survival time of 1.08 years (95% CI: 0.96-1.21), patients registered in centers that had registered six to 12 patients had a median overall survival time of 1.03 years (95% CI: 0.84-1.23), and patients registered at centers enrolling more than twelve patients had a median overall survival time of 0.96 years (95% CI: 0.71-1.21). This was also true when the total group of patients was divided in subgroups by age, gender, histology or tumor locations, and analyzed separately, or when event-free survival was used as endpoint. There was also no difference in response to treatment or in the indirect parameters when comparing smaller and larger centers, except for one subgroup analysis which showed an apparent shorter surgery delay in centers with less than ten patients registered as compared to larger centers (10.1 days±17 standard deviation versus 21.3±30.7 days, p=0.019).

• Download figure
• Open in new tab
• Download powerpoint

Figure 1.

Effect of imaging delay time on overall survival in patients with DIPGs. Counter intuitively, delay of >21 days was associated with better prognosis. (No delay n=27, censored=2; delay n=24, censored=1, p=0.0048).

Process quality and outcome. In the total patient cohort, there was no statistically significant difference in survival time between patients with an imaging delay of longer than 21 days and those with shorter delays. This was different in the subgroup of patients with diffuse intrinsic pontine glioma (DIPG). In those patients, an imaging delay time of more than 21 days was associated with a longer median overall survival time than a shorter delay (median survival: 1.12±0.17 years versus 0.87±0.06 years, n: 24 versus 27 excluding 81 with insufficient documentations, p=0.0048; Figure 1). Although there was no significant association between surgical delay and patient outcome, there was a trend toward improved survival for patients who underwent surgery within seven days of the initial diagnostic imaging (Figure 2). However, patients for whom the treatment (radiation or chemotherapy) delay was longer than 21 days, had a strong tendency toward prolonged overall survival, compared to patients in whom the treatment delay was less than 21 days (median survival: 1.24±0.13 years versus 0.95±0.07 years, p=0.0525).