Conor Mallucci

Primary postoperative chemotherapy without radiotherapy for intracranial ependymoma in children: the UKCCSG/SIOP prospective study

BACKGROUNDnOver half of childhood intracranial ependymomas occur in children younger than 5 years. As an adjuvant treatment, radiotherapy can be effective, but has the potential to damage the childs developing nervous system at a crucial time-with a resultant reduction in IQ and cognitive impairment, endocrinopathy, and risk of second malignancy. We aimed to assess the role of a primary chemotherapy strategy in avoiding or delaying radiotherapy in children younger than 3 years with intracranial ependymoma.nnnMETHODSnBetween December, 1992, and April, 2003, we enrolled 89 children with ependymoma who were aged 3 years or younger at diagnosis, of whom nine had metastatic disease on pre-operative imaging. After maximal surgical resection, children received alternating blocks of myelosuppressive and non-myelosuppressive chemotherapy every 14 days for an intended duration of 1 year. Radiotherapy was withheld unless local imaging (ie, from the childs treatment centre) showed progressive disease.nnnFINDINGSn50 of the 80 patients with non-metastatic disease progressed, 34 of whom were irradiated for progression. The 5-year cumulative incidence of freedom from radiotherapy for the 80 non-metastatic patients was 42% (95% CI 32-53). With a median follow-up of 6 years (range 1.5-11.3), overall survival for the non-metastatic patients at 3 years was 79.3% (95% CI 68.5-86.8) and at 5 years 63.4% (51.2-73.4). The corresponding values for event-free survival were 47.6% (36.2-58.1) and 41.8% (30.7-52.6). There was no significant difference in event-free or overall survival between complete and incomplete surgical resection, nor did survival differ according to histological grade, age at diagnosis, or site of disease. In 47 of 59 (80%) patients who progressed, relapse resulted from local control only. The median time to progression for the 59 patients who progressed was 1.6 years (range 0.1-10.2 years). The median age at irradiation of the whole group was 3.6 years (range 1.5-11.9). For the 80 non-metastatic patients, the 23 who achieved the highest relative dose intensity of chemotherapy had the highest post-chemotherapy 5-year overall survival of 76% (95% CI 46.6-91.2), compared with 52% (33.3-68.1) for the 32 patients who achieved the lowest relative dose intensity of chemotherapy.nnnINTERPRETATIONnThis protocol avoided or delayed radiotherapy in a substantial proportion of children younger than 3 years without compromising survival. These results suggest, therefore, that primary chemotherapy strategies have an important role in the treatment of very young children with intracranial ependymoma.

Endoscopic Third Ventriculostomy in the Treatment of Childhood Hydrocephalus

OBJECTIVEnTo develop a model to predict the probability of endoscopic third ventriculostomy (ETV) success in the treatment for hydrocephalus on the basis of a childs individual characteristics.nnnSTUDY DESIGNnWe analyzed 618 ETVs performed consecutively on children at 12 international institutions to identify predictors of ETV success at 6 months. A multivariable logistic regression model was developed on 70% of the dataset (training set) and validated on 30% of the dataset (validation set).nnnRESULTSnIn the training set, 305/455 ETVs (67.0%) were successful. The regression model (containing patient age, cause of hydrocephalus, and previous cerebrospinal fluid shunt) demonstrated good fit (Hosmer-Lemeshow, P = .78) and discrimination (C statistic = 0.70). In the validation set, 105/163 ETVs (64.4%) were successful and the model maintained good fit (Hosmer-Lemeshow, P = .45), discrimination (C statistic = 0.68), and calibration (calibration slope = 0.88). A simplified ETV Success Score was devised that closely approximates the predicted probability of ETV success.nnnCONCLUSIONSnChildren most likely to succeed with ETV can now be accurately identified and spared the long-term complications of CSF shunting.

Endoscopic treatment of suprasellar and third ventricle-related arachnoid cysts

Abstract.Objective: To evaluate the role of neuroendoscopy in the treatment of rare suprasellar and other third ventricle-related arachnoid cysts. Methods: A review of supratentorial midline arachnoid cysts treated by endoscopic fenestration. Results: Ten cases were identified. The median age of these ten patients was 7.5xa0years. In three a cysto- or ventriculoperitoneal shunt had previously been inserted. Six cysts were located in the suprasellar/prepontine area, one was a combined suprasellar/middle fossa cyst, and three were complex cysts arising mainly in the quadrigeminal cistern and extending into the third ventricle. Successful endoscopic fenestration to both the ventricular system and the basal cisterns (bipolar fenestration) was achieved in all cases. In seven cases a cystoventriculostomy and cystocisternostomy was performed, while in three a cystoventriculostomy was combined with a third ventriculostomy, achieving additional communication to the subarachnoid space. The previously inserted shunts were removed at the end of the procedure. The median follow-up period was 17 (range 1–30)xa0months. The clinical outcome was excellent in all cases, despite only marginal reduction in the cyst size and persistence of ventriculomegaly in some cases. No further treatment to the cyst was required during the period of follow-up. Conclusion: Third ventricle-related arachnoid cysts can be satisfactorily and safely treated by endoscopy. This approach leaves the patient shunt independent.

Endoscopic Third Ventriculostomy Vs Cerebrospinal Fluid Shunt in the Treatment of Hydrocephalus in Children: A Propensity Score-Adjusted Analysis

BACKGROUNDEndoscopic third ventriculostomy (ETV) has preferentially been offered to patients with more favorable prognostic features compared with shunt. OBJECTIVETo use advanced statistical methods to adjust for treatment selection bias to determine whether ETV survival is superior to shunt survival once the bias of patient-related prognostic factors is removed. METHODSAn international cohort of children (≤ 19 years of age) with newly diagnosed hydrocephalus treated with ETV (n = 489) or shunt (n = 720) was analyzed. We used propensity score adjustment techniques to account for 2 important patient prognostic factors: age and cause of hydrocephalus. Cox regression survival analysis was performed to compare time-to-treatment failure in an unadjusted model and 3 propensity score—adjusted models, each of which would adjust for the imbalance in prognostic factors. RESULTSIn the unadjusted Cox model, the ETV failure rate was lower than the shunt failure rate from the immediate postoperative phase and became even more favorable with longer duration from surgery. Once patient prognostic factors were corrected for in the 3 adjusted models, however, the early failure rate for ETV was higher than that for shunt. It was only after about 3 months after surgery did the ETV failure rate become lower than the shunt failure rate. CONCLUSIONSThe relative risk of ETV failure is initially higher than that for shunt, but after about 3 months, the relative risk becomes progressively lower for ETV. Therefore, after the early high-risk period of ETV failure, a patient could experience a long-term treatment survival advantage compared with shunt. It might take several years, however, to realize this benefit.

Endoscopic treatment of middle fossa arachnoid cysts: a series of 40 patients treated endoscopically in two centres

PurposeMiddle fossa arachnoid cysts (MFAC) are a relatively common, benign pathology that pose a therapeutic challenge for both symptomatic and asymptomatic patients. The optimal surgical strategy and indication to treat are still debated by neurosurgeons. We reviewed our experience and results in a group of patients treated with endoscopic fenestration with the aim to assess indications to treat and clinical and neuroradiological results.MethodsThe data on 40 patients operated with endoscopic fenestration for MFAC in two centres, “Anna Meyer” Children’s Hospital, Florence, Italy, and Royal Liverpool Children’s Hospital “Alder Hey”, Liverpool, UK, between 2001 and 2007 were retrospectively reviewed with prospective follow-up. We analysed clinical and neuroradiological presentation, indications to treat, surgical technique, complications, and clinical and neuroradiological follow-up.ResultsThere were 30 males and ten females: mean age, 7.8xa0years; mean follow-up, 21xa0months. The neuronavigation system was used in 12 patients in the English cohort. Thirty-seven patients (92.5%) had a satisfactory clinical outcome. The cyst was reduced in size or completely disappeared in 29 patients (72.5%). There was no death or significant morbidity associated with the procedure. Four patients required further surgical treatment. Four patients experienced a post-traumatic intracystic bleeding after surgery.ConclusionCompared to microsurgical fenestration and cyst shunting, our experience with endoscopic fenestration was as effective and safe but less invasive. Each case must be assessed with its individual characteristics to define the optimal surgical strategy. Successful treatment may not reduce the risk of post-traumatic head injury haemorrhage.

Is there an indication for ETV in young infants in aetiologies other than isolated aqueduct stenosis

ObjectivesThe objective was to determine whether endoscopic third ventriculostomy (ETV) has a role in the management of obstructive hydrocephalus in aetiologies other than idiopathic aqueduct stenosis (AS) in infants.Materials and methodsIn addition to reviewing the literature, we performed a retrospective analysis of our endoscopy database, which was established in 1998, and analysed the outcome results of all cases of ETV in those under 1xa0year of age which were performed between 1998 and 2003. We included cases of idiopathic AS in the outcome analysis as a benchmark of successful outcome. Successful outcome was assessed by resolution of the presenting clinical features and shunt freedom.ResultsAetiologies that were identified included, in addition to idiopathic AS, suprasellar arachnoid cysts, AS in association with post-haemorrhagic hydrocephalus (PHH), post-infectious hydrocephalus (PIH), tumour-related hydrocephalus and a heterogenous group including Dandy–Walker malformation and other developmental anomalies. Suprasellar arachnoid cysts had a 100% outcome success. Idiopathic AS had a 50% outcome success and the successful outcome of PHH cases was poor at 18%. A statistical analysis revealed no effect of age at the time of ETV on the outcome in the aetiological groups.ConclusionsThe definitive initial neurosurgical management of suprasellar arachnoid cysts causing significant hydrocephalus is ETV, whereas that for PHH and PIH is probably that of a ventriculo-peritoneal shunt placement. We speculate that there may be a sub-group of AS cases, termed pure or idiopathic AS, which have a higher rate of successful outcome that may be durable from a younger age. The role of repeat ETV is controversial.

Surgery for hydrocephalus in sub-Saharan Africa versus developed nations: a risk-adjusted comparison of outcome

PurposeSurgery for children in developing nations is challenging. Endoscopic third ventriculostomy (ETV) is an important surgical treatment for childhood hydrocephalus and has been performed in developing nations, but with lower success rates than in developed nations. It is not known if the lower success rate is due to inherent differences in prognostic factors.MethodsWe analyzed a large cohort of children (≤20xa0years old) treated with ETV in developed nations (618 patients from Canada, Israel, United Kingdom) and developing nations of sub-Saharan Africa (979 patients treated in Uganda). Risk-adjusted survival analysis was performed.ResultsThe risk of an intra-operative ETV failure (an aborted procedure) was significantly higher in Uganda regardless of risk adjustment (hazard ratio (HR), 95% confidence interval (CI), 11.00 (6.01 to 19.84) Pu2009<u20090.001). After adjustment for patient prognostic factors and technical variation in the procedure (the use of choroid plexus cauterization), there was no difference in the risk of failure for completed ETVs (HR, 95% CI, 1.04 (0.83 to 1.29), Pu2009=u20090.74).ConclusionsThree factors account for all significant differences in ETV failure between Uganda and developed nations: patient prognostic factors, technical variation in the procedure, and intra-operatively aborted cases. Once adjusted for these, the response to completed ETVs of children in Uganda is no different than that of children in developed nations.

Prenatal diagnosis of suprasellar arachnoid cyst and postnatal endoscopic treatment

Abstract. Arachnoid cysts are benign developmental anomalies that occur in the cerebrospinal axis in relation to the arachnoid membrane. An antenatal ultrasound scan first raises the suspicion of arachnoid cysts, but misdiagnoses have been reported. Confirmatory antenatal magnetic resonance imaging (MRI) is very useful to delineate anatomical detail and help in correct diagnosis. This helps proper counselling and treatment planning. Controversy also surrounds the surgical management, in terms of both the indications and the procedures employed. We report the successful endoscopic treatment, in a neonate, of an arachnoid cyst diagnosed by antenatal ultrasound and MRI. In this case accurate diagnosis and detailed assessment led to objective counselling and helped to optimise neonatal management.

The ROAM/EORTC-1308 trial: Radiation versus Observation following surgical resection of Atypical Meningioma: study protocol for a randomised controlled trial.

BackgroundAtypical meningiomas are an intermediate grade brain tumour with a recurrence rate of 39–58xa0%. It is not known whether early adjuvant radiotherapy reduces the risk of tumour recurrence and whether the potential side-effects are justified. An alternative management strategy is to perform active monitoring with magnetic resonance imaging (MRI) and to treat at recurrence. There are no randomised controlled trials comparing these two approaches.Methods/DesignA total of 190 patients will be recruited from neurosurgical/neuro-oncology centres across the United Kingdom, Ireland and mainland Europe. Adult patients undergoing gross total resection of intracranial atypical meningioma are eligible. Patients with multiple meningioma, optic nerve sheath meningioma, previous intracranial tumour, previous cranial radiotherapy and neurofibromatosis will be excluded. Informed consent will be obtained from patients. This is a two-stage trial (both stages will run in parallel):Stage 1 (qualitative study) is designed to maximise patient and clinician acceptability, thereby optimising recruitment and retention. Patients wishing to continue will proceed to randomisation.Stage 2 (randomisation) patients will be randomised to receive either early adjuvant radiotherapy for 6xa0weeks (60xa0Gy in 30 fractions) or active monitoring.The primary outcome measure is time to MRI evidence of tumour recurrence (progression-free survival (PFS)). Secondary outcome measures include assessing the toxicity of the radiotherapy, the quality of life, neurocognitive function, time to second line treatment, time to death (overall survival (OS)) and incremental cost per quality-adjusted life year (QALY) gained.DiscussionROAM/EORTC-1308 is the first multi-centre randomised controlled trial designed to determine whether early adjuvant radiotherapy reduces the risk of tumour recurrence following complete surgical resection of atypical meningioma. The results of this study will be used to inform current neurosurgery and neuro-oncology practice worldwide.Trial registrationISRCTN71502099 on 19 May 2014.

The British antibiotic and silver-impregnated catheters for ventriculoperitoneal shunts multi-centre randomised controlled trial (the BASICS trial): study protocol

BackgroundInsertion of a ventriculoperitoneal shunt (VPS) for the treatment of hydrocephalus is one of the most common neurosurgical procedures in the UK, but failures caused by infection occur in approximately 8% of primary cases. VPS infection is associated with considerable morbidity and mortality and its management results in substantial cost to the health service. Antibiotic-impregnated (rifampicin and clindamycin) and silver-impregnated VPS have been developed to reduce infection rates. Whilst there is some evidence showing that such devices may lead to a reduction in VPS infection, there are no randomised controlled trials (RCTs) to support their routine use.Methods/designOverall, 1,200 patients will be recruited from 17 regional neurosurgical units in the UK and Ireland. Patients of any age undergoing insertion of their first VPS are eligible. Patients with previous indwelling VPS, active and on-going cerebrospinal fluid (CSF) or peritoneal infection, multiloculated hydrocephalus requiring multiple VPS or neuroendoscopy, and ventriculoatrial or ventriculopleural shunt planned will be excluded. Patients will be randomised 1:1:1 to either standard silicone (comparator), antibiotic-impregnated, or silver-impregnated VPS. The primary outcome measure is time to VPS infection. Secondary outcome measures include time to VPS failure of any cause, reason for VPS failure (infection, mechanical failure, or patient failure), types of bacterial VPS infection (organism type and antibiotic resistance), and incremental cost per VPS failure averted.DiscussionThe British antibiotic and silver-impregnated catheters for ventriculoperitoneal shunts multi-centre randomised controlled trial (the BASICS trial) is the first multi-centre RCT designed to determine whether antibiotic or silver-impregnated VPS reduce early shunt infection compared to standard silicone VPS. The results of this study will be used to inform current neurosurgical practice and may potentially benefit patients undergoing shunt surgery in the future.Trial registrationInternational Standard Randomised Controlled Trial Number:ISRCTN49474281.