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Metastasis outside the cerebrospinal axis

From Laurent J. Classification system for primitive neuroectodermal tumors (medulloblastoma) of the posterior fossa. Cancer 1985;56:1807, with permission.

From Laurent J. Classification system for primitive neuroectodermal tumors (medulloblastoma) of the posterior fossa. Cancer 1985;56:1807, with permission.

Table 17-7. Medulloblastoma Risk Categories

Risk Category

Average

High

Extent of disease

Volume of residual tumor*

Histology

Age at diagnosis

Negative CSF cytology Normal MRI of spine <1.5 cm2

Undifferentiated >3 years

Positive CSF cytology

Positive MRI of spine with Gd-DTPA

Large-cell anaplastic <3 years

* On a 2-dimensional measurement.

survival improves for patients who have had a radical resection of their tumor. Occasionally a child presents with life-threatening raised intracranial pressure due to obstruction of the fourth ventricle. In these cases, preoperative endoscopic third ven-triculostomy or shunting should be performed to reduce the intraoperative mortality of definitive tumor resection in the presence of increased ICP.

Radiation Therapy

Radiation therapy plays a critical role in treatment. Medulloblastomas are one of the most radiosensitive primary CNS tumors of childhood. The standard dose of radiotherapy is 5400-5580 cGy to the area of the primary tumor, with 2340 cGy given to the neuroaxis for localized disease, 3600 cGy for disseminated disease. Use of IMRT to spare the cochlea is important in decreasing therapy-induced hearing loss.

Radiation therapy to children under 3 years of age with medulloblastoma is controversial. Chemotherapy should be utilized so that radiation can either be omitted or postponed in this young age group (see pages 528-529).

Chemotherapy

The relatively rapid rate of growth and high mitotic index of medulloblastoma result in this tumor's responsiveness to a number of chemotherapeutic agents:

1. Adjuvant chemotherapy improves the disease-free survival for medulloblas-toma patients who have high-risk disease (Table 17-7). Accordingly, adjuvant chemotherapy is clearly recommended in combination with craniospinal radiation. The current Children's Oncology Group (COG) trial tests the utility of car-boplatin with vincristine as a radiosensitizer, followed by vincristine and cyclophosphamide with or without cisplatin. Preliminary results using aggressive multiagent chemotherapy for 4 months, followed by autologous stem cell rescue with carboplatin, thiotepa, and etoposide (Table 17-8), are encouraging. The use of second-look surgery when appropriate is being investigated.

2. Patients with average-risk disease (Table 17-7) have a greater than 60% 5-year disease-free survival with surgery and radiotherapy. A recent study utilizing craniospinal irradiation following surgery and adjuvant CCNU, vincristine, and cisplatin (Table 17-4) chemotherapy has demonstrated an 89% PFS rate in nondisseminated posterior fossa medulloblastoma with a decreased cran-iospinal irradiation dose. Trials are now under way to compare various chemotherapy regimens in an attempt to decrease local recurrences and to attempt to further decrease radiation therapy dosages.

Prognosis

Survival for patients with average-risk medulloblastoma treated with adjuvant radiation and chemotherapy is 89% at 5 years. In high-risk patients using craniospinal radiation with chemotherapy, 45-50% of patients are disease free at 5 years. When

Table 17-8. Conditioning Regimen for Autologous Stem Cell Transplantation

Carboplatin

500 mg/m2/day IVa

Days -8 to -6

Thiotepa

300 mg/m2/day IV

Days -5 to -3

Etoposide

250 mg/m2/day IV

Days -5 to -3

Rest

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