Okay. Welcome to our WNS APP module on pediatric brain tumors. My name is Elias Rizik. I'm an associate professor at Penn State Hershey Medical Center. Brain tumors are a very common childhood malignancy. About 20% of childhood malignancies end up in the brain tumor category. They are the second most frequent cancer of childhood after leukemias, and they have a wide variety of tumor pathology from half of them being histologically benign to more aggressive, very embryonic stage tumor. They have sometimes difficulty achieving growth total resection and can end up with significant neurological deficits and or mortality with specific subtypes of tumors. We know that over time, the successes of brain tumor management have improved slowly and gradually over time. That is the case not just in pediatric brain tumors, but also overall our treatment and management of brain tumors have slowly and gradually been improving over time with five-year survival rates increasing by about 20% in each age group. The frequency and survival of different brain tumors is based on pathology, of course. You have low-grade tumors like the pylocytic astrocytomas that have a very good five-year survival rate. This is in comparison to a very poor outcome in brainstem gliomas where a significant majority die within the first year of life. The pediatric brain tumors are very different from those in adults. About half of them are low-grade astrocytomas. Another 25% are medial blastomas, and this cancer has been very successful in its management and cure. And also, you are going to see a very wide variety of unusual rare cases of embryonal tumors that have varying survivals and very wide management and protocols in their treatments. Pediatric brain tumors present with generalized non-localizing symptoms sometimes. The child is usually developmentally regressed. They have abnormal gait or regression of their gait. They are fatigued. They don't want to engage. They look sickly sometimes or cacectic. They have anorexia or repeated vomiting of unexplained etiology. Some of the patients have progressive sixth cranial nerve palsies requiring multiple evaluations by the ophthalmologist. And the level of energy and evaluation of the patient typically ranges from being less engaged or listless to more lethargic and then ultimately comatose in patients who have missed diagnosis of their elevated intracranial pressure. Some patients can present with seizures, and they are subsequently found to have underlying brain pathology. And some patients do have localizing signs depending upon the location of the tumor. Localizing signs are appropriate and helpful in the evaluation. Typically, patients with cerebellar masses will have balance problems, ataxia, or nystagmus. Brain stem lesions will typically present with cranial nerve palsies, abnormal eye movements, gait abnormalities. Optic tract masses will have visual field deficits, changes in their acuity, or even changes on eye examination. In cerebral cortex presentations, they can have neurological deficits, motor or sensory, and or seizures is a very usual presentation. And hypothalamic masses typically present with sodium imbalances, DI, diabetes insipidus, visual changes, precocious puberty, or even diencephalic syndrome. You need a team of specialists to help with pediatric brain tumors. It's not enough to have a pediatric neurosurgeon. You really need a family of physicians to care for somebody in a well-rounded, complete fashion. A pediatric oncologist is a major expert person in the treatment of the patient, but also you need multidisciplinary care from rehab, psychology, endocrinology, child life care, and social workers, and even pediatric neurologists to manage patients' seizures or medications. And a group of patient physicians that are able to help with diagnosis and treatment through radiation oncology and pathology. Like we talked about, some patients can present with diencephalic syndrome. They are usually happy, hyper alert, euphoric, but at the same time, they have wasting, and despite adequate intake, they have more of a cacectic body habitus. They have a normal linear growth and have a normal intellect, and visual loss and nystagmus and ocular bobbing can be a presentation in their evaluation. In the fourth ventricle, you will have a differential of medulloblastoma that is usually the most common. This is closely followed by ependymoma and brainstem gliomas, dorsal exophytic brainstem gliomas, and or coronary plexus tumors. The patients who present with cerebellar masses can have gliomas, medulloblastomas, or even hemangioblastomas. In the pineal region, you will encounter germ cell and germ cell line tumors, including germinomas, which is the most common and the most treatment responsive. You will have a variation of immature or mature teratomas, embryonal cell tumors, endodermal sinus tumors, or even choriocastenomas that have different histological findings and or CSF markers. Pineocytomas and pineoblastomas. You can also have retinoblastomas in association with pineoblastomas, gliomas, meningiomas, pineal cysts, and or venous malformation that has to be ruled out before intervening with a surgical intervention. Supracellular masses are common in the pediatric age group, and the two most common are craniofaryngiomas and optic pathway gliomas. But you also can have aneurysms or even autoimmune histiocytic or hematomas and abnormal tissue collection in the supracellular region, rastkase cleft cyst, pituitary adenomas, and germ cell tumors. In the cerebrum, the presentation and most likely finding would be an astrocytoma, but you can also have a variety of different pathologies, and those are listed, including PXAs, PNETs, DIGs, gangliogliomas, oligodendrogliomas, glioblastomas, or even low-grade gliomas. Intraventricular masses, the two most common tumors are choroflexus tumors, including papillomas and carcinomas, but you can also have sub-ependymal giant cell tumors included in tuberous sclerosis syndromes, ependymomas, neurocytomas, and or colloid cysts at the foramen of Monroe. The mainstay of treatment is surgery, radiation, and chemotherapy, and a lot of the decisions will hinge on the surgery type and also the amount of surgery outcome with the patient. Like I said, it's important for the diagnosis to help manage the treatment options. The treatment could be varied based on the amount of resection and the results of the pathology. You can have supportive measures to temporize the patient and allow for the management of chemotherapy and radiation to take effect, so patients with obstructive hydrocephalus and ability to undergo endoscopic third ventriculostomy can obviate the hydrocephalus, obtain a tissue biopsy, and treat potential germinomas, for example, with radiation to overcome the hydrocephalus and treat the tumor at the same time. Gross total resections are not always feasible, and judgment is definitely needed. You will end up with major neurological deficits in selected cases of gross total resection if it's involving critical structures or very delicate and sensitive structures. A biopsy could be an option, and a biopsy can help guide the care in certain instances and obviate the need for a more destructive surgery and utilize chemotherapy and or radiation for treatment and or cure. Adjuncts and surgery includes multiple options now, including the microscope, ultrasonic aspirators that are ubiquitous now in operating neurosurgical rooms, intraoperative navigation in areas that are critical, and patients that are appropriate. You can do awake functional resection surgery, especially in delicate areas of the brain for speech and motor power. You can utilize neuroendoscopy for intraventricular masses and also use the laser and interstitial therapy of lesions that are deep-seated and easier to address with laser interstitial therapy. One of the most common tumors that you'll encounter will be medulloblastomas. They usually peak at the age of four to five years of age. These tumors arise in the cerebellum, and they grow rapidly and can spread throughout the spinal cord but rarely go outside the brain. They are usually localized in the posterior fossa, and the risk of these tumors is dependent on several factors. The average risk usually occurs in patients that are more than three years of age. They don't have widespread disease, and this is the most common subgroup. The high risk usually has evidence of spread or incomplete resection or response to treatment, and usually infants less than three years of age have different presentation and tumor response treatment rather than the older age patients. The treatment involves complete surgical resection and craniospinal radiation with boost to the tumor. Chemotherapy has improved significant treatment options in this subcategory of disease, and the patient is usually undergoing chemotherapy, which reduces the long-term effect of higher-dose radiotherapy by itself. You can see event-free survival and survival from study entry from the recent Packard data showing a very good outcome in patients with medulloblastoma undergoing the combined surgery, chemo, and radiation protocol for treatment of medulloblastoma. What's new in medulloblastoma over the past five to 10 years? We started to understand more about the genetics of medulloblastoma, and now we know that there are subgroup genetic anomalies, including the Wnt and sonic hedgehog group that have a higher cure rate compared to the poor outcomes in group D and group C. These help with the management of the patient, and looking at prognosis and outcome. The other major category that we see frequently in the pediatric age group is ependymoma. These are 5 to 14% of childhood tumors, and the median age is 2 to 6 years of age. The patients present with posterior fossa masses, but also can present with supratentorial masses. Spinal ependymomas are a different category by itself, and they can have either intramedullary or amyxopapillary ependymoma in the conus or the coda aquina. This is imaging of a patient with an ependymoma in the posterior fossa, and typically the mainstay of treatment is complete surgical resection with long-term cure rate of 80% in gross total resection compared to 22% with subtotal removal. Improvement in surgical techniques have helped tremendously with the amount of surgical resection, including the microscope, the ultrasonic aspirator, and neuromonitoring intraoperatively to help delineate desiccant areas and stay away from structures that are sensitive and can end up with major neurological deficits. Treatment is conformant radiation to the margins of the tumor, and outcomes are better with patients who have gross total resection, and about 75% three-year progression free survival in patients who undergo gross total resection with conformal radiation in addition to treatment. Low-grade astrocytomas are the most common brain tumor in children, and sometimes it's associated with neurofibromatosis and have a different genetic variation compared to non- and F-related gliomas. It is a chronic condition at times, and based on its localization, you can manage this disease appropriately with chemotherapy and keep it under control more than 70% of the time. Treatment selection is based on the logical function, localization of tumor, and the finding on biopsy and or tumor resection when indicated. Some tumors can be watched for a prolonged period of time without any significant growth, and a lot of the tumors can respond adequately to chemotherapy and stay under control for a prolonged period of time, like I explained. Many low-grade tumors can be easily surgically resected, especially in the cerebellar hemisphere or hemispheric tumors, but surgical adjuncts allow for surgical resection, including microscopic resection, awake craniotomies, and functional resections, and also neuromonitoring intraoperatively, especially working around the brainstem location. In patients who have unacceptable neurological deficits with different locations that are critical in the brain, a subtotal resection and or pathology biopsy could be the treatment in that group, and you can utilize chemotherapy, focus radiation, or even gamma knife radiation for residual disease. The two options of surgery could end up with appropriate results. You can see in this patient, a surgical route was used to decompress and resect in a subtotal fashion this large tumor of the brainstem. On the other hand, you can also utilize chemotherapy to resect a similar tumor and obtain adequate results with chemotherapy alone following needle biopsy, and it's all tailored based on the tumor location, tumor pathology, the amount of neurological deficit at the time of presentation, the adequate selection of treatment options, and a discussion with a multidisciplinary team, and including your neurosurgical colleagues to try to offer the best care for the patient. Infant brain tumors is a balancing act, cure versus sequelae of treatments. Obviously, you're using high-dose chemotherapy and or high-dose radiation on a child that has full survival if they did not have a specific condition. So, we have to deal not just with the acts of surgery and the consequences of the tumor, but also the consequences of the treatments provided. So, this is a case I placed of a 16-month-old who has been having problems with respiratory difficulty, vomiting, and at 16 months of age, presented with irritability and vomiting. GI workup was performed, and the patient was diagnosed with reflux. The patient at 16 months of age was evaluated by the pediatrician again and was noted to have bulging fontanelle. MRI at the time showed intracranial hydrocephalus and a very large intraventricular mass. The patient underwent a near-total resection and ended up having a choroid plexus carcinoma. Post-op MRI showed a residual mass, and following five cycles of intensive chemotherapy, there was a gross total resection of the tumor. This patient is now 12 years old from his presentation without recurrence, neurologically intact except for hearing loss, but normal IQ. So, even in the best of hands and best of outcomes, secondary to the treatments provided with intensive chemotherapy, the child lost their hearings, and they have to deal with this for the rest of their lives, even in the setting of a complete cure from a brain tumor. Another group of brain tumors that you're going to face or see in the pediatric office is the intrinsic pontine gliomas, which are about 10% of all brain tumors. The patients who have DIPGs, diffuse intrinsic pontine gliomas, will have a median survival of 9 to 12 months, and patient survival is dependent on the genetic anomalies seen in histone acetylation of the tumor itself. So, in some circumstances, when appropriate, a biopsy can help tailor prognosis and outcome in these patients. There is a transient response to radiotherapy, and sometimes steroids will help in the acute phase, but there is no real therapy or long-term cure from this disease at the moment. We continue to study this disease and have multiple groups and faculties really engaging and trying to find out treatment options and prognosis and targeted therapies in this age group or treatment or this tumor group. This is a typical DIPG MRI scan, and you see an enlargement and diffuse enlargement in the brainstem. This tumor is engulfing the basilar artery here, and you'll see infiltrative changes in the brainstem itself, with sometimes acute hydrocephalus developing from obstruction of the posterior fossil draining pathways. In summary, surgery is a vital part of tumors and can provide cure for many tumors. We can debulk biopsy or complete or undergo a complete tumor resection. It also helps provide critical diagnosis to tailor treatments and genetic tailored options. It can direct future therapies and treatments, and also, every patient should be approached in a careful, multidisciplinary fashion to try to reduce the risks of surgery, chemo, and or radiation therapies. We want to consider watchful follow-up in the clinic after treatment resections, and judicious treatment options should be considered based on age group, type of tumor, and surgical results or outcomes. Thank you very much for joining us for this webinar, and hopefully, we'll see you on the next one.

pediatric brain tumors

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brain tumor management

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