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Sutton, United Kingdom

Calton E.A.,St Georges, University of London | Le Doare K.,St Georges, University of London | Appleby G.,St Georges, University of London | Chisholm J.C.,Children and Young Peoples Unit | And 9 more authors.
Pediatric Blood and Cancer

Background: Cancer is the second most common cause of childhood deaths in the United Kingdom and infection contributes to a quarter of all cancer-related deaths. This study aimed to estimate the risk, aetiology and outcome of bloodstream bacterial and fungal infections in children with cancer within a geographically defined region in South-West London over a 3-year period. Methods: Web-based questionnaires were completed using case records of children with positive blood cultures admitted to five London hospitals during 2009-2011. Results: A total of 112 children with a median age of 5.4 (IQR 3.6-11.2) years had 266 significant blood cultures during 149 infection episodes. Haematological malignancy affected 68 patients (60.7%) and solid tumours 44 (39.3%). The overall bloodstream infection rate was 1.5 episodes per 1,000 days-at-risk (95% CI, 1.2-1.8) and was similar for those with haematological malignancies and solid tumours. Most episodes were attributed to central venous catheter infection (120/149, 80.5%). Coagulase-negative staphylococci were isolated in almost half the bloodstream infections (127/266; 47.7%), while Gram-negative organisms accounted for a further quarter (64/266; 24.1%). Fungal isolates from blood were uncommon (8/112 children, 7.1%) but significantly associated with neutropenia (18/149 [12.1%] vs. 1/114 [0.9%], P=0.0004). Six children (5.4%) died, including three (2.7%; 95% CI, 0.6-7.6%) whose deaths were infection-related. Conclusions: This study provides an updated risk estimate for bloodstream infections in children with cancer and adds to the framework for developing evidence-based guidance for management of suspected infections in this highly vulnerable group. Pediatr Blood Cancer 2014;61:1239-1245. © 2014 Wiley Periodicals, Inc. Source

Thway K.,Sarcoma Unit | Chisholm J.,Children and Young Peoples Unit | Hayes A.,Sarcoma Unit | Swansbury J.,Clinical Cytogenetics | Fisher C.,Sarcoma Unit
Human Pathology

We describe a case of superficial low-grade fibromyxoid sarcoma (LGFMS) in a 12-year-old boy, confirmed by the detection of FUS-CREB3L2 fusion transcripts by reverse-transcription polymerase chain reaction and FUS rearrangement with fluorescence in situ hybridization, which had morphological features similar to ossifying fibromyxoid tumor (OFMT), including an almost complete rim of mature, metaplastic bone. LGFMS and OFMT can appear morphologically similar, with bland ovoid cells within a fibrous to myxoid matrix. Both can occur superficially; and whereas MUC4 immunoreactivity is characteristic of LGFMS, this can also be seen in some OFMTs. As the morphological spectrum of LGFMS is wide, we highlight the potential for diagnostic confusion with OFMT, which is clinically pertinent as most OFMTs behave in a benign manner whereas LGFMS is a malignant neoplasm with a propensity for local recurrence and a significant metastatic rate. © 2015 Elsevier Inc. Source

Gatz S.A.,Children and Young Peoples Unit | Thway K.,The Royal Marsden NHS Foundation Trust | Mandeville H.,The Royal Marsden NHS Foundation Trust | Kerawala C.,Head and Neck Unit | And 2 more authors.
Pediatric Blood and Cancer

Ameloblastic fibro-odontosarcoma (AFOS) is an extremely rare malignant odontogenic tumor. Complete surgical excision is the treatment of choice. Deaths due to disease recurrence and/or progression are documented. Here, we report the case of a 15-year-old female with multiple recurrent AFOS. She responded to chemotherapy with ifosfamide and doxorubicin consolidated by stereotactic reirradiation using cyberknife and remained in complete remission 14 months from the end of reirradiation therapy. Chemotherapy with ifosfamide and doxorubicin should be considered in advanced cases of AFOS. © 2015 Wiley Periodicals, Inc. Source

Carceller F.,Children and Young Peoples Unit | Carceller F.,The Institute of Cancer Research | Bautista F.J.,Clinical Trials Unit | Fowkes L.A.,The Royal Marsden NHS Foundation Trust | And 12 more authors.
Pediatric Blood and Cancer

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-to-event 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. © 2016 Wiley Periodicals, Inc. Source

Moreno L.,Children and Young Peoples Unit | Moreno L.,Paediatric Drug Development Unit | Moreno L.,Clinical Research Programme | Marshall L.V.,Children and Young Peoples Unit | And 3 more authors.
British Medical Bulletin

IntroductionNeuroblastoma is one of the commonest and deadliest forms of childhood cancer and major initiatives are ongoing to improve the outcome of these patients.Sources of dataData for this review were obtained from PubMed and abstracts from the American Society of Clinical Oncology and Advances in Neuroblastoma Research.Areas of agreementCollaborative clinical trials have led to major improvements in treatment outcomes for low and intermediate risk neuroblastoma, and international initiatives such as the International Neuroblastoma Risk Group have produced a very refined risk stratification incorporating clinical and biological risk factors.Areas of controversyDespite many efforts, the outcome for high-risk neuroblastoma is still poor and the only new strategy incorporated into frontline treatment is anti-GD2 immunotherapy. It is unclear how new drugs targeting specific molecular aberrations will be incorporated.Growing pointsGenomic characterization and drug development have undergone major advances in the last 5 years leading to a much deeper understanding of tumour biology as well as active biomarker-driven preclinical and clinical research on new molecules that will hopefully progress faster and more efficiently into frontline combination treatment strategies.Areas timely for developing researchSignificant effort remains to be done in integrating the different new strategies, combining new molecularly targeted agents to maximize therapeutic benefit and incorporate immunotherapy together with targeted therapies. © The Author 2013. Source

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