Update on new treatments and developments in childhood brain tumors 1/22/10

Department of Pediatric Dentistry
Resident’s Name: Murphy Program: Lutheran Medical Center - Providence
Article title: Update on new treatments and developments in childhood brain tumors
Author(s): Partap, Sonia, Paul Graham Fisher.
Journal: Current Opinions on Pediatrics
Year. Volume (number). Page #’s: 2007. 19. 670-674
Major topic: Various type of brain cancers in children, their symptoms, and treatments.
Minor topic(s): New ideologies for treatment
Main Purpose: To review brain tumors occurring in children, discuss their current treatment options, and analyze new options.
Overview of method of research: n/a
Findings: Primary central nervous system tumors are the second most common cancer in children with 3,400 new cases each year(hematological malignancies are the first). This article discusses three types of brain tumors, their symptoms, prognosis, treatment options, survival rates, and newest research findings.

Medulloblastoma
Medulloblastoma’s account for 40% of pediatric posterior fossa CNS tumors. They arise in the cerebellum, especially in the vermis. It is theorized that they are derived from external granule cells. Incidence is around 5 years old, but can occur in older children. The tumor presents as a large mass effect in the posterior fossa. Children often have symptoms such as nausea/vomiting, headache, and papilledema. These all are from increased intracranial pressure congruent with ataxia. The severity of the tumor is broken down into either average risk or high risk, depending on if there are metastases or not.

Treatment Options for MB
Surgical Removal
This is the first step, with the goal being removing the intracranial pressure and as much as the disease as possible, depending on the level of risk. Total removal of the tumor shows the best survival rates(DUH). Complications areising from removal of the tumor include cerebellar mutism, which is also known as posterios fossa syndrome. Children that develop this usually do so 1-2 days post op and have rapid onset of emotional lability, mutism, and high pitched crying. This resolves on it’s own, however long term issues with speech and cognitive deficits remain.

Radiation and Chemo
While craniospinal radiation(CSRT) is imperative for the treatment of MB, it is associated with neurocognitive effects and endocrinopathies. For years, any pt. W/ MB was treated w/ 36Gy to the craniospinal axis, and 18-24Gy to the posterior fossa. Recently, children with average risk MB have been treated with 23.4Gy to the CSA, and a boost to the posterior fossa. 36Gy remains the standard of care for high-risk children. When used in conjunction w/ CSRT, chemo improves overall survival rate than just chemo alone. The treatment regiment usually includes either cyclophosophamide, vincristine, cisplatin, or lomustine. Less toxicity has been seen w/ lomustine as opposed to cyclophosphamide. Survival rates with this treatment are around 81%(w/ 23.4 Gy). Long term monitoring for hearing, fertility, endocrinopathies, and secondary malignancies are needed, especially when comparing pt’s who receive high amounts of cyclo and less cisplatin and vincristine.

Future Directions
Advances in molecular biology broaden our understanding of correlations between MB subtypes, their features, and their relation to outcomes with respect to how they were treated. For example, a newly found histological subtype, ERBB2 carries a worse prognosis, which can help to dictate proper treatment. As our knowledge of MB precursor cells expands w/ the use of mouse models, new interventions may materialize to help inhibit the progression of MB before it begins.

Ependymoma
EM is the third most common CNS tumor in children. 50% of the kids with this are younger than five. EM often arises from the remnants of the ependymal lining located in the ventricular system of the posterior fossa. EM can cause hydrocephaly and symptoms of intracranial pressure. Pt’s usually present w/ seizures and motor/sensory complaints. EM carries a high risk of recurrence and metastasis.

Treatment Options for EM
Surgical Removal
Total surgical resection is an important prognostic factor for EM. However, only half of children with EM are long term survivors.

Radiation/Chemo
Radiation is standard when the tumor has communicated with the ventricular system, despite it’s detrimental effects on the developing brain. Chemo is ineffective. Sad stuff.

Future Directions
Scientists are attempting to identify a potential biological and therapeutic marker as a prognosticator for EM. Human telomere reverse transcriptase(hTERT), which aids in uncontrolled cell growth, was found in 87 tumors. Tumors tht were hTERT neg had a 5 year survival rate of 84%, while hTERT pos. was 41%.
Advances in stem cell research show promise in trying to find new treatments for EM.

Brainstem Glioma
(All of these are unbelievably bad, but this guy is depressingly terrible)BG represents 8-10% of all pediatric CNS tumors. Prognosis is dismal. Usual age of onset is 7, and median survival time ranges form 9-11 MONTHS. Only 20% last beyond 1 year. Children present with weakness, hemiparesis, ataxia, and difficult with lateral gaze. MRI’s are usually used in the diagnosis, showing obscuration of the pons, and engulfment of the basilar artery.

Treatment Options.
Surgery/Radiation/Chemo
Due to their location and extent in the pons, resection is not possible. The standard of treatment for BG is high levels of radiation. 54Gy is given in 30 daily fractions of 1.8Gy over 6 weeks. This improves survival and also reduces or temporarily stabilizes tumor size, giving the child a better quality of life. SO far, increasing radiation rates, using chemo, and combined therapies show no improvement in survival rate. They tried to use cyclosporine A to breach the blood brain barrier to provide intracerebral chemo, however this study was suspended because it was making kids seize and severly altering their mental status.

Future Directions
So far, progress has been slow. There has been promising data with tipifarnib in adults. More research is needed…obviously.

Brain Tumors as Secondary Malignancies
As the treatment for most pedicatric cancers improve, more people are living longer. The cure rate for ALL, the most common childhood cancer is 80%. The risk for secondary malignancies rises steadily 30 years after the initial treatment, at a % of 10.85%. The long term affects of radiation is also of great importance. Screening of pituitary function in teenager pt.s treated with CNS radiation is paramount due to the lack of adequate hormone levels that place the child at risk for physical and cognitive disabilities. Children treated w/ radiation have increased risk of brain tumors, stroke(6.4% in leukemia surviors and 29% in brain tumor survivors), and CVA’s. The 5 year survival rate is 70%. Clinicians need to shift their focus to include the complete assessment of the treatment, not just irradicating the disease.
Key points/Summary:
Brain tumors are still largely a mystery for clinicians. While surgery, chemo, and radiation work(to some extent) the long term affects can kill a pt. Just as easily as the original tumor.

Assessment of Article: Good article. Very informative. Although I’m definitely depressed after reading it.