ABSTRACT
Background: Pediatric low-grade glioma [PLGG] is often a chronic progressive disease requiring multiple treatments, i.e. surgery, chemotherapy and irradiation. The multi-state model [MSM] allows an extended analysis of disease-states, that patients may undergo, incorporating competing risks over the course of time. Purpose: We studied disease-state-probabilities of the German SIOP-LGG 2004 cohort from the initial state "diagnosis" to the final state "death". Transient "disease-states" incorporated successive surgical and non-surgical treatments. We evaluated clinical risk factors for highly progressive disease requiring multiple interventions and death. Results: We identified 22 states within 1587 patients (median follow-up 6.3 years). For robust statistical calculation, we reduced the model to 7 states and eventually to three levels of disease-progressiveness: non, low and highly progressive. Five years after diagnosis state-probabilities were: 0.11 no therapy, 0.49 one and 0.11 two or more surgeries only, 0.19 one and 0.06 two or more non-surgical interventions with or without prior surgery. At this time point higher probability for highly progressive disease was found in infants (0.30), supratentorial-midline location (0.17) and diffuse astrocytoma WHO-grade II (0.12). Neurofibromatosis type-1 patients were most likely not to be treated (0.36) or to have received only non-surgical therapy (0.45). Two years after diagnosis 3-year predictions for highly progressive disease and death increased with the number of interventions patients underwent in the first 2 years after diagnosis. Conclusion: In this first MSM analysis we delineated a refined description of PLGG disease course over time, identifying three levels of progressiveness. Growth behavior in the first two years predicted future progressiveness and death.
ABSTRACT
BACKGROUND: Up to 43% of survivors of pediatric acute lymphoblastic leukemia (ALL) may exhibit fine-motor problems. Information on manual dexterity in this cohort is still limited. OBJECTIVES: We tested survivors of childhood ALL treated with chemotherapy-only for fine-motor function in terms of drawing and handwriting abilities using a Digitizing Tablet (DT) with three tasks for drawing and handwriting of varying complexity, for ataxia using the International Cooperative Ataxia Rating Scale (ICARS), and for tremor and hand-eye coordination using the Nine Hole Steadiness Tester (NHST). RESULTS: We examined a cohort of non-irradiated survivors (n = 31) after a median time of 3.5 years after end of therapy. In all tasks of the DT the cohort demonstrated significant (p < 0.05) impairment of speed, automation, and variability in at least two tasks and significantly more pressure. Impaired speed (SPV) inversely correlated with lag time since end of therapy. Dexterity performance of six survivors (19%) lay below the 5th percentile. No survivor exhibited ataxia, tremor, or impaired hand-steadiness. CONCLUSION: Despite the absence of gross ataxia, tremor, and impaired hand-eye coordination, we nevertheless detected significant fine-motor impairment in a relevant number of survivors of childhood ALL. Prospective studies are needed to reveal the pathophysiological underpinnings and genetic risk factors for development of such deficits due to ALL and its treatment.
