Pseudoprogression (PsP) is a treatment-related phenomenon which hinders response interpretation. Its prevalence and clinical impact have not been evaluated in children/adolescents. We assessed the characteristics, risk factors and prognosis of PsP in children/adolescents and young-adults diagnosed with non-brainstem high grade gliomas (HGG) and diffuse intrinsic pontine gliomas (DIPG). Patients aged 1-21 years diagnosed with HGG or DIPG between 1995 and 2012 who had completed radiotherapy were eligible. PsP was assessed according to study-specific criteria and correlated with first-line treatment, molecular biomarkers and survival. Ninety-one patients (47 HGG, 44 DIPG) were evaluable. Median age: 10 years (range, 2-20). Eleven episodes of PsP were observed in 10 patients (4 HGG, 6 DIPG). Rates of PsP: 8.5 % (HGG); 13.6 % (DIPG). Two episodes of PsP were based on clinical findings alone; nine episodes had concurrent radiological changes: increased size of lesions (n = 5), new focal enhancement (n = 4). Temozolomide, MGMT methylation or H3F3A mutations were not found to be associated with increased occurrence of PsP. For HGG, 1-year progression-free survival (PFS) was 41.9 % no-PsP versus 100 % PsP (p = 0.041); differences in 1-year overall survival (OS) were not significant. For DIPG, differences in 1-year PFS and OS were not statistically significant. Hazard ratio (95 %CI) of PsP for OS was 0.551 (0.168-1.803; p = 0.325) in HGG; and 0.308 (0.107-0.882; p = 0.028) in DIPG. PsP occurred in both pediatric HGG and DIPG patients at a comparable rate to adult HGG. PsP was associated with improved 1-yr PFS in HGG patients. PsP had a protective effect upon OS in DIPG patients.
The results of this study define reference ranges of two common measures of acetabular morphology and confirm statistically significant differences between men and women.
Cancer is the leading cause of death in children older than 1 year of age and new drugs are necessary to improve outcomes. Imaging is crucial to the drug development process and assessment of therapeutic response. In adults, tumours are often assessed with CT using size criteria. Unfortunately, techniques established in adults are not necessarily applicable in children due to differing pathophysiology, ability to cooperate and increased susceptibility to ionising radiation. MRI, in particular quantitative MRI, has to date not been fully utilised in children with extracranial neoplasms. The specific challenges of imaging in children, the potential for functional imaging techniques to inform upon and their inclusion in clinical trials are discussed.
Objective: Surgery for the varicose short saphenous vein (SSV) remains unsatisfactory. Specific problems include locating the saphenopopliteal junction (SPJ) and whether the trunk should be stripped. Recurrence rates are high. The objective was to review the morphology of varicose SSV and to address these aspects. Methods: Retrospective study of consecutive patients scheduled for SSV surgery based on initial continuous wave Doppler assessment. Detailed analysis of preoperative duplex ultrasound examinations with quantified reflux. Results: A total of 56 limbs (unilateral) were studied, male to female ratio was 18:38 and mean age was 51 years. SPJ: severe reflux in 47, mean diameter 8.1 mm (all above the skin crease [mean 2.7 cm]). Reflux was 'focal', being confined to the peri-junctional area with normal sized and competent distal short saphenous trunks in 29. In the remainder, incompetence was 'complete' with dilatation and reflux of the entire system. In only one limb did varicosities arise distally from a proximally competent system. Long saphenous vein ( LSV): coexistent reflux in 17, with communications with the SSV in 11. Deep reflux: at least one segment of deep reflux was found in 24 limbs. In this small study, no significant association with other morphology was found apart from 'complete' SSV reflux. Conclusion: The SPJ is usually severely incompetent, enlarged and sited above the skin crease. The morphology of the varicose SSV exhibits important differences from the LSV. In over half, incompetence is 'focal', confined to the peri-junctional vein and the distal trunk is competent suggesting a case for selective trunk stripping. Varicosities arising from a distally incompetent short saphenous trunk are uncommon.
Introduction. RECIST guidelines constitute the reference for radiological response assessment in most paediatric trials of anticancer agents. However, these criteria have not been validated in children. We evaluated the outcomes and patterns of progression of children/adolescents enrolled in phase I trials in two paediatric drug development units. Methods. Patients aged ࣘ21 assessed with RECIST (v1.0 or v1.1) were eligible. Clinico-radiological data were analysed using Mann-Whitney U and log-rank tests to correlate response categories and sum of longest diameters (SLD) with time-toevent variables and overall survival (OS). Results. Sixty-one patients (71 enrolments) were evaluated; median age: 12.7 years (range, 3.1-20.9). Overall, 7% achieved complete/partial response (n = 5) and 31% disease stabilisation (n = 22). Median (95% CI) OS (in months) was 29.1 (27.6-30.6) with complete/partial response, 8.9 (2.0-15.8) with stable disease and 2.8 (2.3-3.3) with disease progression (P < 0.001); 32.6% patients with measurable disease presented exclusive progression of existing non-target lesions and/or new lesions. The change in SLD at best response showed a linear correlation with duration of response (r = −0.605; P = 0.004) and time on trial (r = −0.61; P = 0.003), but the change in SLD at progression did not correlate with time to progression (r = −0.219; P = 0.206). Conclusions. Response assessment according to RECIST correlated with OS in children/adolescents treated on phase I trials. The reduction in SLD at best response correlated with more prolonged responses. Tumour size did not constitute an optimal method to assess disease progression in one third of patients with measurable disease. Further refinement of current response assessment guidelines will enable the development of paediatric-specific radiological criteria.
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