Pediatric Supratentorial PNET

PEDIATRIC CNS TUMORS
Sheilaine Mabanta, MD

Amended 12/06 by STY

SUPRATENTORIAL TUMORS

• They include
• low-grade astrocytomas (23%),
• malignant gliomas (6%),
• craniopharyngioma (6%),
• PNET (4%),
• pineal tumors (4%),
• ependymoma (4%) and
• oligodendroglioma (2%).

• Tumors according to region:
• suprasellar (glial tumor of optic chiasm, hypothalamic area, craniopharyngioma, and germ cell tumors),
• central deep seated (germ cell, glioma and PNET), and
• peripheral (gliomas, ependymoma and PNET).

• Only time one would not consider biopsy is if optic pathway tumor or pineal tumor with elevated AFP or BHCG.
• NF1 includes 6 or > café au lait spots and/or peripheral neurofibromas. AD with 17q defect. Can be associated with gliomas in 15-20%.

Presentation

Seizures, Lateral neurological signs, Increased intracranial pressures, Hormonal problems, Visual defects, Pineal tumors (Parinaud\’s syndrome), H/N and N/V.

LOW GRADE ASTROCYTOMAS

• ⅓-½ of all pediatric CNS tumors
• Cerebellar are most common (15-25%)

• Pathology:
• Astrocytoma NOS: fibrillary, gemistocytic (degenerate to high grade) and protoplasmic – little enhancement with contrast.
• JPA (juvenile pilocytic astrocytoma): well circumscribed, T1-enhancing, tumor
• Pleomorphic xanthrocytoma
• Subependymal giant cell astrocytoma: lie along ventricles, very indolent, almost no recurrences after surgery.
• Gliomatosis cerebri: diffuse infiltrating low-grade lesions, non-enhancing, recurrence within one year despite therapy.
• Burger grading 1) JPA 2) NOS 3) anaplastic astrocytoma 4) GBM.
• Glial fibrillary acidic protein (GFAP) positive on pathology stains.

• Treatment:

• Surgery: If complete resection is possible, DFS is about 90%. If the lesion is in the diencephalon then only 40% resectable.

• Radiation: RT may be given after subtotal resection and improves PFS but does not effect OS.
• Leibel showed a 10-yr survival advantage with RT+ incomplete resection 35% v. 11% with incomplete resection alone.
• Shaw **showed benefit for adults in OS at 10 years 39% versus 19% for >53Gy.
• Mayo clinic** showed 87% PFS.
• Pollack (UCSF) showed an 80% RFS at 10 years after S + RT.
• Volume: 1-2 cm margin beyond the tumor on T1 images.
• Treat gemistocytic as a malignant glioma with 2-3cm margin and higher dose (@ UF).
• Dose: Traditional doses are 54Gy/30 fractions at 1.8Gy/fraction.

• Chemotherapy: may be used to delay radiation; carboplatin and vincristine shows 3-yr PFS of 77% (Packer 1997).

• Observation: It may be plausible to just observe tumor especially JPA in a central area with very close follow-up for very young patients <3-5 years old, especially with NF or tectal tumors with hydrocephalus relieved by CSF diversion alone.
• May give post-op RT if unresectable/subtotal resection and symptomatic and/or growing.

OPTIC PATHWAY TUMORS

• Tumors involve the chiasm or the nerve.
• 25%-40% are associated with NF1.
• Typically low grade astrocytomas and gangliogliomas.
• Treatment:
• Surgery: No role for surgery, except to biopsy globular lesions of hypothalamus that could be germ-cell tumors or aggressive gliomas.
• Observation: **If unsymptomatic, then avoid radiation; however, 70% progress within 6 years of diagnosis.
• Radiation:** Treat when tumor progression (exam or scans) or for significant visual deficit. With RT, RFS at 10 years is 70-80% if chiasm tumor. 25-35% have visual improvement. 10-20% have visual deficit after RT. Problems with RT include second malignancies and Moyamoya syndrome with vessel constriction. Doses are 50-54Gy at 1.8cgy with XRT and 45Gy for children less than 3 years old.
• Chemotherapy: Packer gave Dactinomycin (or Carboplatin/vincristine) for tumor reduction in 25% to delay RT.
• Results: 70-90% survival at 10 years.

OLIGODENDRIOGLIOMA

• Mostly in the cerebral hemisphere.
• Total resection is the treatment of choice with 10-year survival at 60%.
• Subtotal resection + RT has been shown to be better than subtotal alone by **Shaw **(62% versus 25% at 5 years).
• If low grade then treat to 54Gy/30 fractions but if an anaplastic oligodendroglioma then treat like GBM.

GANGLIGLIOMAS

• Benign rare tumors with neuronal and glial components.
• They are typically resected with usually no role for RT.

MALIGNANT GLIOMAS

• Include the anaplastic astrocytomas and GBM
• \~6% of brain tumors in children
• Enhancing lesions with edema and central necrosis.
• LM spread is present in 15-20%.
• Treatment:
• Surgery: Complete resection (image-confirmed) is helpful with OS at 3-yrs \~60% but difficult to achieve (\~25% of the time).
• Radiation therapy: Wide local fields to doses of 55-60Gy (at UF use 60/40 with reduction at 45/30). No need to hyperfractionated. Volume includes lesion seen on T2 images and place a 2-3cm margin for 95% line around the target volume which includes the tumor + edema on T2.
• Chemotherapy:__ __Sposto CCNU, vincristine and prednisone (PCV) + RT versus RT alone (45% versus 17% at 5 years) but questionable with benefit seen only for patients with GBM.
• Results: Median survival is 1.5-2 years. 3-yr OS is about up to 60% for total resection, but only 15-20% with RT  surgery.

EMBRYONIC TUMORS/

• Supratentorial PNETS, supratentorial neuroblastomas, ependymoblastomas, pineoblastomas, and medulloepitheliomas.
• Posterior fossa PNET is the medulloblastoma.
• Can be solid or cystic at diagnosis.
• Treatment: Surgery is possible in only 25% of the cases. Post-operative RT is always indicated.
• RT: CSI to 36Gy (180cGy/fx x 20), boost primary (T2 + 2cm) to 50.4Gy (180cGy x 8 = 1440), reduce and boost T1+1.5cm to 55.8Gy (180 x 3 = 540) then consider stereotactic boost to 69.6Gy at UF.
• 5-year survival is \~60%.

PINEAL TUMORS/ INTRACRANIAL GERM CELL TUMORS

• Include germ cell tumors (germinomas, malignant germ cell tumors, teratomas), pineal parenchymal tumors (pineoblastomas = PNET, or pineocytomas = benign mature pineal cell tumor), and gliomas (astrocytomas or ependymomas).
• Associations: pineal germ celladolescent boys, teratomas young kids, malignant histologiesolder kids
• Origin: pineal 55%; ant 3^rd ventricle 35%; multicentricity can be seen
• Germ cell Tumors:
• Rare in US but 9% in taiwan, Japan
• Most common tumor of pinal region (65%)
• Germinomas (65%,) ; do not make AFP, may make low levels of ß-hCG
• Malignant germ cell tumors( 20-25%):
• Endodermal sinus tumor ( elevated AFP);
• choriocarcinomas (high ß-hCG),
• teratomas: 20% - benign, immature, and malignant (malignant may have elevated AFP),
• Presentation:
• Paurinaud\’s syndrome: diminished upward gaze, diminished convergence, and limited constriction to light but retained pupillary response to accommodation.
• ICP due to compression of Sylvian aqueduct
• The classic triad is DI, precocious puberty and visual defectssuprasellar GCT
• Treatment:
• Stereotactic Biopsy – necessary unless CSF or tumor markers +. No confirmed increase risk of dissemination. May need VP shunt.
• If significant increase of Tumor marker (any increase AFP or BHCG of > 100=dx of malign GCT
• Historically give RT 20 to 25Gy if decrease in size then dx of germinoma
• Chemo:
• Intracranial GCT are chemosensitive: cyclophosphamide, carboplatin, CDDP, VP16,; Response 100%
• Sev series: cyclophos + response adjusted RT (24 to 36Gy)
• Chemo alone result in 50% recurrence; less if Bhcg I above 50
• Surgery:
• No advantage to GTR for germinomas
• Can do resection after chemo for choriocarcinoma, aggressive germ cell histiotypes
• Radiation is the main mode of treatment ; Also chemo+ limited vol RT
• Germinoma: 5-yr DFS = 80-90% with CSI.
• Current Controversy: RT vol (tumor vs, 3^rd ventricle vs full ventricle vs cranial vs CSI); Dose ( 40 vs 50Gy)
• 10% risk of subarachnoid dissem in pineal; 43% in biopsied suprasellar germinomas
• Series reporting >90% disease control rate have used low dose CSI but spinal failure 0 to15% in series without RT to spinal axis.; Tumor bed alone very high failure
• For adolescent children and younger, may not need to do CSI: Ventricular system (intra-cranial) to 30Gy (20 fx of 150 cGy/fx) then boost tumor to 49.5 Gy / 33fx.
• No seeding/CSF-: CSI to 21Gy in 14fx at 1.5Gy/fx, boost ventricular system 9Gy in 6 fx (30Gy total), then FSRT boost of 19.5 Gy (150cGy x 13 fx) to tumor for total = 4950 cGy/33 fx.
• Seeding/CSF+: CSI to 24Gy, boost ventricular system to 36Gy, then FSRT to 4950 cGy/33 fx.
• After chemo CR24 to 30Gy; PR30 to 36Gy; Less than PR45Gy
• Non-germinomas: 5-yr DFS = 0-33% for bad, as good as 40-60% with chemo/RT.
• Bad: treat with cisplatin (better than carboplatin) then CSI to 30-36Gy/20-24 fx then boost tumor to 4950 cGy and then 5550 cGy/37 fx.
• Good (mature teratoma): 55.8 / 31 fx at 180 cGy/fx with reduction at 50.4 cGy.
• Pineocytoma: treat to 54/30 fractions with XRT or SRS.
• Pinealblastomas: PNET treatment with CSI to 36Gy (180cGy/fx x 20), boost primary (T2 + 2cm) to 50.4Gy (180cGy x 8 = 1440), reduce and boost T1+1.5cm to 55.8Gy (180 x 3 = 540) then consider stereotactic boost to 69.6Gy at UF.

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