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Lucie Lafay-Cousin, Ute Bartels, Charles Raybaud, Abhaya V. Kulkarni, Sharon Guger, Annie Huang and Eric Bouffet

✓Intracystic bleomycin therapy has been proposed as a treatment for predominantly cystic craniopharyngioma. The risks of using this therapy, however, have not been clearly identified. The authors report on three children treated with intracystic bleomycin who developed initially mild symptoms during their course of therapy. They describe the neuroimaging findings from computed tomography (CT) scans and magnetic resonance (MR) images and the medical management of these three cases.

Two patients in whom craniopharyngioma was recently diagnosed and one patient with recurrent craniopharyngioma were treated with a course of 3 mg of intracystic bleomycin three times a week for 5 weeks, followed by once every week for 10 weeks. All patients had a negative reservoir permeability test prior to beginning intracystic bleomycin therapy. Patients were asymptomatic or had mild symptoms at the time of neuroimaging.

Magnetic resonance images revealed extensive vasogenic edema surrounding the cyst in all three patients, consistent with signs of bleomycin leakage. The edema occurred near the time of the 12th injection in two patients, and at the end of treatment in the remaining patient. Subsequently, two patients developed further symptoms suggestive of hypothalamic injury. These two patients received corticosteroids, leading to a rapid and sustained clinical improvement. Follow-up serial MR images showed a progressive regression of the surrounding edema.

Neuroimaging documentation of bleomycin toxicity has been described mainly in adults experiencing severe toxicity. There was no correlation between clinical symptoms and the extent of edema in these three patients. An MR image provides a higher resolution than CT scans for evaluating the adjacent cerebral structures and is very sensitive in detecting early abnormalities, even in asymptomatic patients. Bleomycin therapy requires close clinical monitoring. Imaging evaluation should be performed using MR imaging during treatment to ensure the safety of the therapy. In the authors' experience, the toxicity to bleomycin was transient. Management of the toxicity using high-dose steroid administration appears to contribute to controlling the bleomycin-induced inflammatory process.

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Lucie Lafay-Cousin, Gillian Lindzon, Michael D. Taylor, Walter Hader, Cynthia Hawkins, Robert Nordal, Normand Laperriere, Suzanne Laughlin, Eric Bouffet and Ute Bartels


Primary CNS sarcomas are very rare pediatric tumors with no defined standard of care.


This study was a retrospective review of children diagnosed with a primary CNS sarcoma and treated at 2 Canadian tertiary care centers between 1995 and 2012. This report focuses on patients with cerebral hemispheric tumor location due to their specific clinical presentation.


Fourteen patients with nonmetastatic primary CNS sarcoma were identified; in 9 patients, tumors were located in the cerebral hemisphere and 7 of these patients presented with intratumoral hemorrhage. One infant who died of progressive disease postoperatively before receiving any adjuvant therapy was not included in this study. The final cohort therefore included 8 patients (4 males). Median patient age at diagnosis was 11.8 years (range 5.8–17 years). All tumors were located in the right hemisphere. Duration of symptoms prior to diagnosis was very short with a median of 2 days (range 3–7 days), except for 1 patient. Three (37.5%) patients had an underlying diagnosis of neurofibromatosis Type 1 (NF1). Gross-total resection was achieved in 5 patients. The dose of focal radiation therapy (RT) ranged between 54 Gy and 60 Gy. Concomitant etoposide was administered during RT. ICE (ifosfamide, carboplatin, etoposide) chemotherapy was administered prior to and after RT for a total of 6–8 cycles. Seven of the 8 patients were alive at a median time of 4.9 years (range 1.9–17.9 years) after treatment.


In this retrospective series, patients with primary CNS sarcomas located in the cerebral hemisphere most commonly presented with symptomatic acute intratumoral hemorrhage. Patients with NF1 were overrepresented. The combination of adjuvant ICE chemotherapy and focal RT provided encouraging outcomes.

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Lucie Lafay-Cousin, Donald J. Mabbott, William Halliday, Michael D. Taylor, Uri Tabori, Ian D. Kamaly-Asl, Abhaya V. Kulkarni, Ute Bartels, Mark Greenberg and Eric Bouffet


Choroid plexus carcinomas (CPCs) are rare pediatric tumors with a generally poor prognosis. Although the role of surgery is well recognized, the role of adjuvant chemotherapy and radiation therapy remains unclear. In this paper, the authors' goal was to assess the role of second-look surgery and neoadjuvant ifosfamide, carboplatin, etoposide (ICE) chemotherapy in the management of CPC and to study neurocognitive outcome.


The authors performed an institutional retrospective review of patients in whom CPC was diagnosed between 1985 and 2006 at the Hospital for Sick Children in Toronto. Fourteen patients (7 boys and 7 girls) were included. The median age at diagnosis was 18.6 months (range 1.1–65.3 months). Four patients had evidence of metastatic disease at diagnosis. Two of the 14 patients underwent gross-total resection during initial surgery; 12 of the patients received neoadjuvant chemotherapy, 10 of whom underwent second surgery. In total, of 12 patients who received chemotherapy with a curative intent, 11 underwent a greater than 95% resection. Neoadjuvant ICE chemotherapy was given prior to second surgery (median 4 cycles, range 2–5 cycles) and was continued after second resection for a median total of 7 cycles (range 4–16 cycles).


No tumor progression was observed during chemotherapy prior to second surgery. Five patients subsequently experienced tumor progression/relapse. At a median follow-up of 6.9 years (range 1.9–18.5 years), 8 patients are alive. None of the survivors received radiation therapy. However, 6 of 8 display significant neurocognitive and/or sensorial deficit.


In this experience, second surgery following neoadjuvant ICE chemotherapy led to a high rate of complete or near-complete resection. Chemotherapy appears to facilitate second-look surgery, in particular through a reduction of intraoperative blood loss. Despite radiation avoidance, the majority of survivors experienced significant neurocognitive impairment.

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Christian Schneider, Ian Kamaly-Asl, Vijay Ramaswamy, Lucie Lafay-Cousin, Abhaya V. Kulkarni, James T. Rutka, Marc Remke, Daniel Coluccia, Uri Tabori, Cynthia Hawkins, Eric Bouffet and Michael D. Taylor


Choroid plexus carcinomas (CPCs) are rare brain tumors originating from the ventricular choroid plexus. They account for 2%–4% of all pediatric brain tumors and are most frequently seen in very young children. This pediatric proclivity, in combination with a marked vascularity, renders an aggressive resection a difficult and often dangerous endeavor. Blood losses of several total blood volumes in small children are not uncommon, sometimes forcing the neurosurgeon to abort the procedure, often leaving residual tumor. Great extent of tumor resection is an accepted beneficial factor for overall survival. Therefore, a second resection usually follows the administration of adjuvant chemotherapy. Second-look surgery appears to be associated with markedly decreased blood loss. Histological examination of specimens obtained at a second intervention shows decreased vascularity and fibrotic changes in tumor tissue. At the Hospital for Sick Children in Toronto, this empirical finding led to the strategy of neoadjuvant chemotherapy to minimize blood loss and maximize cytoreduction. The authors undertook this study to assess the potentially beneficial effect of neoadjuvant chemotherapy on blood loss during surgery for CPCs.


In this retrospective cohort review, the demographic, clinical, and treatment parameters of 22 consecutive patients diagnosed with CPC are presented. All underwent surgical treatment at the Hospital for Sick Children from 1982 to 2013. Special attention was given to the impact of neoadjuvant chemotherapy on extent of resection and intraoperative blood loss. Extent of resection was calculated based on perioperative neuroimaging, and amount of blood loss was estimated based on transfusion parameters and perioperative changes in hematocrit.


Ten patients did not receive neoadjuvant chemotherapy, and 12 were treated with 2–5 cycles of ICE (ifosfamide, carboplatin, etoposide) chemotherapy in a neoadjuvant fashion. The 22 patients included in the study underwent a total of 37 tumor resection surgeries. In all of the cases in which neoadjuvant chemotherapy was used, at least a near-total resection (> 95% of tumor volume) was achieved. Patients who underwent gross-total resection had prolonged overall survival. Of the 37 resections, 18 were performed after chemotherapy. Mean blood loss in the neoadjuvant chemotherapy group was 22% of total estimated blood volume as opposed to 96% in patients without preoperative chemotherapy.


In children with CPC, the administration of neoadjuvant chemotherapy decreases intraoperative blood loss and increases extent of resection with a significant positive effect on overall survival.