Phase II study of irinotecan in combination with temozolomide (TEMIRI) in children with recurrent or refractory medulloblastoma: a joint ITCC and SIOPE brain tumor study

BackgroundThis multicenter phase II study investigated temozolomide + irinotecan (TEMIRI) treatment in children with relapsed or refractory medulloblastoma.MethodsPatients received temozolomide 100–125 mg/m2/day (days 1–5) and irinotecan 10 mg/m2/day (days 1–5 and 8–12) every 3 weeks. The primary endpoint was tumor response within the first 4 cycles confirmed ≥4 weeks and assessed by an external response review committee (ERRC). In a 2-stage Optimum Simon design, ≥6 responses in the first 15 evaluable patients were required within the first 4 cycles for continued enrollment; a total of 19 responses from the first 46 evaluable patients was considered successful.ResultsSixty-six patients were treated. Seven responses were recorded during stage 1 and 15 in the first 46 ERRC evaluated patients (2 complete responses and 13 partial responses). The objective response rate during the first 4 cycles was 32.6% (95% confidence interval [CI], 19.5%–48.0%). Median duration of response was 27.0 weeks (7.7–44.1 wk). In 63 patients evaluated by local investigators, the objective response rate was 33.3% (95% CI, 22.0%–46.3%), and 68.3% (95% CI, 55.3%–79.4%) experienced clinical benefit. Median survival was 16.7 months (95% CI, 13.3–19.8). The most common grade 3 treatment-related nonhematologic adverse event was diarrhea (7.6%). Grade 3/4 treatment-related hematologic adverse events included neutropenia (16.7%), thrombocytopenia (12.1%), anemia (9.1%), and lymphopenia (9%).ConclusionsThe planned study primary endpoint was not met. However, its tolerability makes TEMIRI a suitable candidate chemotherapy backbone for molecularly targeted agents in future trials in this setting

Clinical value of SPECT/CT for evaluation of patients with painful knees after total knee arthroplasty- a new dimension of diagnostics?

<p>Abstract</p> <p>Background</p> <p>The purpose of our study was to evaluate the clinical value of hybrid SPECT/CT for the assessment of patients with painful total knee arthroplasty (TKA).</p> <p>Methods</p> <p>Twenty-three painful knees in patients following primary TKA were assessed using Tc-99m-HDP-SPECT/CT. Rotational, sagittal and coronal position of the TKA was assessed on 3D-CT reconstructions. The level of the SPECT-tracer uptake (0-10) and its anatomical distribution was mapped using a validated localization scheme. Univariate analysis (Wilcoxon-Mann-Whitney, Spearmean`s-rho test, p < 0.05) was performed to identify any correlations between component position, tracer uptake and diagnosis.</p> <p>Results</p> <p>SPECT/CT imaging changed the suspected diagnosis and the proposed treatment in 19/23 (83%) knees. Progression of patellofemoral OA (n = 11), loosening of the tibial (n = 3) and loosening of the femoral component (n = 2) were identified as the leading causes of pain after TKA.</p> <p>Patients with externally rotated tibial trays showed higher tracer uptake in the medial patellar facet (p = 0.049) and in the femur (p = 0.051). Patients with knee pain due to patellofemoral OA showed significantly higher tracer uptake in the patella than others (p < 0.001).</p> <p>Conclusions</p> <p>SPECT/CT was very helpful in establishing the diagnosis and guiding subsequent management in patients with painful knees after TKA, particularly in patients with patellofemoral problems and malpositioned or loose TKA.</p

Long Time to Diagnosis of Medulloblastoma in Children Is Not Associated with Decreased Survival or with Worse Neurological Outcome

International audienceBACKGROUND: The long time to diagnosis of medulloblastoma, one of the most frequent brain tumors in children, is the source of painful remorse and sometimes lawsuits. We analyzed its consequences for tumor stage, survival, and sequelae. PATIENTS AND METHODS: This retrospective population-based cohort study included all cases of pediatric medulloblastoma from a region of France between 1990 and 2005. We collected the demographic, clinical, and tumor data and analyzed the relations between the interval from symptom onset until diagnosis, initial disease stage, survival, and neuropsychological and neurological outcome. RESULTS: The median interval from symptom onset until diagnosis for the 166 cases was 65 days (interquartile range 31-121, range 3-457). A long interval (defined as longer than the median) was associated with a lower frequency of metastasis in the univariate and multivariate analyses and with a larger tumor volume, desmoplastic histology, and longer survival in the univariate analysis, but not after adjustment for confounding factors. The time to diagnosis was significantly associated with IQ score among survivors. No significant relation was found between the time to diagnosis and neurological disability. In the 62 patients with metastases, a long prediagnosis interval was associated with a higher T stage, infiltration of the fourth ventricle floor, and incomplete surgical resection; it nonetheless did not influence survival significantly in this subgroup. CONCLUSIONS: We found complex and often inverse relations between time to diagnosis of medulloblastoma in children and initial severity factors, survival, and neuropsychological and neurological outcome. This interval appears due more to the nature of the tumor and its progression than to parental or medical factors. These conclusions should be taken into account in the information provided to parents and in expert assessments produced for malpractice claims