Primary brain tumors represent 2% of all cancers and 2% of annual deaths caused by cancer.

            In children it is the second cause of cancer.

           Brain metastases are more common than primary brain tumors.

          Autopsy shows that 25-30% of patients with systemic cancer have brain metastases.

            In Romania the estimated incidence for 2000 was 9.24 per 100,000 population and mortality of 7.96 per 100,000 inhabitants.

   Risk Factors

 1. Exposure to radiation: meningioma, astrocytoma

2. Immunosupression in transplant patients and AIDS patients: primary brain lymphoma

3. Neurofibromatosis type I: optic glioma, astrocytoma intracranial

4. Neurofibromatosis type II ependymoma and meningioma

5. Sclerotuberosa (Bourneville disease): giant cell astrocytoma

6. Nevic basal horn syndrome (Gorlin): medulloblastoma, meningioma, craniopharyngioma

7. Von Hippel Lindau disease: Retinal hemangioblastoma, cerebellar,of the spinal cord

8. Turcot syndrome: glioblastoma, medulloblastoma and colon tumor

9. Li-Fraumeni syndrome: primary brain tumors

See table no. 53: Histological Classification of brain tumors

 I. Tumors of the neuroepithelial tissue 1. astrocytoma: anaplastic astrocytoma, glioblastoma, astrocytoma pilocitic. 2. oligodendroglioma: anaplastic oligodendroglioma 3. ependymoma: anaplastic ependymoma 4. Joint Oligoastrocytoma 5.Tumorsof the choroid plexus choroid plexus carcinoma 6. Neural tumors 7. Neuroglial tumors 8.Tumori pineal: pinocitom, Pineoblastomas embryonic 9.Embryonary tumors: a) medulloblastoma b) Neuroblastoma c) Ependimoblastoma d) Primitive e) Neuroectodermal tumor (PNET)

II. Cranial nerves and spinal tumors 1. schwannoma 2. neurofibroma 3. malignant schwannoma.

III. Tumors of the meninges 1. meningioma 2. anaplastic meningioma

IV. Primary malignant lymphoma

V germial cell tumors. 1. Germinoma 2. embryonic carcinoma 3. endodermal sinus tumor 4. choriocarcinoma 5. teratoma 6. mixed germ cell tumor

VI. Cysts and lesions like tumors 1. epidermoid cyst 2. Dermoid cysts 3. colloid cysts of the of the third ventricle

VII. Tumors of the pituitary 1. adenoma 2. carcinoma 3. craniopharyngioma

VIII. Metastatic tumors: lung 36%; Breast 14%; hipernefrom 8%; gastro-intestinal 6%; 5% melanoma; 3% of the female genital tract; Thyroid 2%; sarcoma 3%; unknown primary seat 5-20%.

Signs and symptoms: persistent headaches, seizures, intracranial hypertension signs (nausea, vomiting, headache, hemiparesis, cranial nerve palsy 3, papilledema), ataxia, vertigo, nystagmus, hemiparesis, paraparesis. Extension tumor implantation and seeding by LCR Within the central nervous system metastases are uncommon.

Diagnosis: Diagnostic is recommended C.T. skull, cranial MRI.

Lumbar puncture can be performed only after performing CT and M.R.I. in patients who show no evidence of intracranial hypertension. It is indicated only in tumors with a tendency to spread about LCR: medulloblastoma, ependymoma, choroid plexus carcinoma, primary CNS lymphoma. Examine the CRL for glucose, protein, BHCG and AFP.

Systemic evaluation is recommended for patients after diagnosis of brain tumor was demonstrated on CT or MRI to determine the etiology and to exclude metastatic tumors, strokes, infectious processes. The assessment includes: PA and lateral chest x-ray, complete blood count, liver and kidney function tests, electrolytes, calcium, magnesium, glucose, mammography, genital examination, occult bleeding.

Definitive diagnosis is based on histopathological examination set by surgery which is also based and treatment of brain tumors.

The most common histological types of glioma brain tumors are I. Gliomas 55.6% 1.Glioblastom 20% 2. Cerebellar astrocitoma 0.9% 3. Other gliomas 34.8% II. Meningioma 19.5% III. Adenoma 14.4% IV. Neurinoma 6.9% V. medulloblastoma 2.2% VI. Other 1.4%.

Primary brain tumors staging is not applicable because they are locally invasive and do not disseminate to regional lymph nodes or distant. Staging MRI of the spinal cord and CSF assessment it is important to: medulloblastoma, ependymoma, and neuroectodermal tumors because they can disseminate about LCR Histological malignancy is judged by cellularity, pleomorphism, nuclear atypia, mitotic activity, invasiveness, cell differentiation.

1. Gliomas are made of astrocytoma, oligodendroglioma, and ependymoma and represents 60% of all brain tumors. Based on histology (nuclear atypia, endothelial cell proliferation, mitosis, necrosis)  astrocytomas stage in 4 WHO grades: low grade Glioma: 1. Level I: pilocitic astrocytoma (benign tumor) 2. Level II: low grade astrocytoma high grade Glioma : 3. Grade III anaplastic astrocytoma 4. Grade IV Multiform glioblastoma: the most common primary brain tumor, accounting for over 50% of all gliomas.

2. Ependymomas 2% of all brain tumors but are common in children under 3 years, giving birth to the posterior fossa. They are usually low grade tumors, but often recur. 3.

3. Medulloblastomas represents 2.2% of all primary brain tumors but is the 2nd frequency in children (the first being cerebellar astrocytoma). Medulloblastoma and neuroectodermal tumors (PNET) cell tumors are small and stained positive for S-100. If present in the posterior fossa are called meduloblastoame and always are high grade tumors. If they are in the supratentorial compartment they are called PNET tumors. Primitive neuroectodermal tumors (PNET) are high grade aggressive tumors.

4. Acoustic neuroma (acoustic schwannoma) is 6% of brain tumors. They are benign tumors that arise from the acoustic nerve.

5. Meningiomas represent 19.5% of brain tumors. Arachnoid cells arise from the meninges. They are staged into 4 grades, 80% of which are benign (1.2 degree).

6. Pituitary adenomas represent 10% of brain tumors and arise from the anterior and posterior pituitary gland. Two thirds are nonsecretante and the rest produce prolactin or growth hormone.


It aims Supportive therapy treatment of cerebral edema, intracranial hypertension and prevent seizures.

Cerebral edema, cerebral edema treatment is an important factor in the increased intracranial pressure. Peritumoral edema is particularly high in rapidly growing brain tumors and metastatic tumors.

Glucocorticoids decrease in tumor blood-brain barrier permeability, reduces edema formation rate and cytostatic effect. The therapeutic response occurs within 24 hours.

Dexamethasone at a dose of 4 mg i.v. 6 h administers throughout the treatment with gradual dose reduction thereafter.

Methylprednisolone administered an initial dose of 120 mg, then 20 mg to 6 h. In all patients it is associated IV cimetidine to prevent the risk of digestive bleeding.

Osmotic diuretics. Mannitol is administered osmotic diuretic effect, with rapid effect. It is administered at a dose of 0.25 to 1 g / kg 6-12 h. Two thirds of diuresis must be replaced. Furosemide dose of 10-20 mg every 6-12 hours by drying the peritumoral edema decreases.

Anticonvulsilvants: in patients with brain tumors and seizures brain herniation risk. Use of phenytoin at a dose of 5 mg / kg / day (300 mg / day) po in one outlet. Phenobarbital at a dose of 1-5 mg / kg / day, 100-200 mg / day Carbamazepine 7-15mg / kg / day divided in 2-3 doses (600 mg / day)

Cerebral herniation treated by decreasing intracranial pressure: · lifting · hyperventilating patient seated at a pressure of 50 mm Hg PCO2 · Mannitol 1 g / kg iv (50-100g) · dexamethasone 20 mg to 6 h.i.v.

Therapeutic Modalities: Surgery is the base of the diagnosis and treatment of primary brain tumors. The goals of surgery are: diagnosis, excision or reducing tumor volume and mass effect, cure the disease. Complete surgical excision is the most important prognostic factor. The histological classification of the tumor proper planning is important for determining prognosis and subsequent therapy.

External beam radiation therapy given after surgery has become the standard treatment for patients with malignant gliomas. a) Carry out the entire skull irradiation at a dose of 5500 cGy cGy- 6000. Higher doses of 6000 cGy produce brain damage. Doses used should be between 50-57 Gy in 30-35 fractions of 180-200 cGy daily fractioning. Larger fractioned doses or total doses of 6000 cGy produce necrosis. For the spinal cord is considered safe dose of 4500 cGy total in 22 fractions in 5 weeks myelopathy risk is less than 0.2%. b) Another way of irradiation of the whole skull consists of irradiation with a dose of 4300 cGy addition to tumor volume of 1700 cGy. No differences in survival between the 2 methods. c) Irradiation associated with the radiosensitizer (mizonidazole or iododeoxyuridine). The overall rate of response is similar, with or without radiosensitising. d) temporary brachytherapy by implanting iodine 125 sources associated with external radiation. Studies suggest but do not prove that the survival is longer as that obtained only by external radiotherapy. e) radiosurgery with linear accelerator is beneficial in patients with primary and metastatic small tumors, meningioma and acoustic neuroma. It has a clear role in the treatment of metastatic brain tumors.

Chemotherapy plays an increasing role in the treatment of brain tumors. Drugs used in the treatment of central nervous system tumors must have the following properties may: the ability to pass the blood brain barrier, high solubility in lipids, small capacity to induce peritumoral edema or diffuse cerebral. Most of cytostatic agents with antitumor activity on the central nervous system readily cross the blood brain barrier: BCNU, CCNU, Procarbazine, temozolomide. Agencies that do not have readily crosses the barrier hematoencelafică limited antitumor activity of the central nervous system: Bleomycin, Adriblastină, Cisplatin, Mithramycin and Vincristine. There BCNU relationship between sensitivity and number of chromosomes in the tumor cells. Gliomas by more than 60% cells are sensitive to BCNU hiperdiploide, while almost diploid chromosome number of cells are resistant to BCNU. Overexpression of the MDR-1 gene encoding the P-glycoprotein (acting as a pump energy dependent efflux of the drug), is present in 1/3 of the tumors studied. Some gliomas that have resistance to vincristine, Adriamycin and Etoposide show the overexpression of MDR1 gene.

Monochemotherapy. The most active drugs are: 1). BCNU – 200 mg / m2 / day i.v. (Maximum cumulative dose 1500mg / m2) at 8 weeks 2). CCNU – 110 mg / m2 / day i.v. 6-8 weeks 1 day 3). ACNU- 100mg / m2 / day IV on day 1- repeat  every 6-8 weeks –4). Procarbazine – 150mg / m2 / day x 30 days with a break of 30 days 5). Temozolomide – 150-200mg / m2 / day on days 1-5 repeated after 28 days. It is recommended in patients previously treated.

The multi-agent chemotherapy regimen used is polichemotherapy PCV (in gliomas and meduloblastomas).

I. low grade glioma 1). Pilocitic juvenile astrocytoma is located in the cerebellum. The preferred treatment is surgery. If macrospic tumor is removed survival at 10 years is greater than 10 years. 2). Low grade astrocytoma is usually located in the optical paths, cerebellum and brainstem. Surgery is the recommended treatment depends on tumor location. For unresectable tumors radiotherapy is recommended in doses of 55-59 Gy with a median survival of 4-5 years. 30% of patients with low grade astrocytoma show tumor progression in high-grade tumors.

B.Gliomas include high-grade anaplastic astrocytoma (grade III) and multiform glioblastomas (grade IV). represents 50% of gliomas. Surgical biopsy establishes the diagnosis. Whenever possible extensive resection of the tumor is performed depending on its neuroanatomical location. Tumor resection treats symptoms, prolonged survival, radiotherapy and chemotherapy allows. Postoperative radiotherapy is the most important therapeutic way. The total dose of 60 Gy is used. Chemotherapy definite therapeutic value, although limited. Use BCNU, CCNU and PCV scheme.

– Table no. 54 Polichemotherapy schemes

1. standard PCV:

CCNU 110 mg / m2 / day p.o. Day 1

Procarbazine 60 mg / m2 / day p.o. 8-21 days

                                    Vincristine 1.4 mg / m2 / day i.v. (Maximum 2 mg) days 8:29

            Repeat 6-8 weeks -6 cycles

            It is used in astrocytoma, oligodendroglioma.

            ————————————————– ——————————————

            2. intensified PCV

                                    CCNU 130mg / m2 p.o. Day 1

                                    Procarbazine 75 mg / m2 / day p.o. 8-21 days

                                    Vincristine 1.4 mg / m2 i.v. days 1:29

                                    (No limit of dose), repeat 6-8 weeks

            ————————————————– ——————————————

            3. 8 in 1 meduloblastomas used in children

                                    Methylprednisolone 300 mg / m2 iv 6 hours on day 1 – h 0, 6 and 12

                                    Vincristine 1.5mg / m2 (max 2mg) Day 1 – h 0

                                    Lomustine 75 mg / m2 p.o. Day 1 – h 0

                                    Procarbazine 75 mg / m2 p.o. Day 1 – h 1

                                    Hydroxyurea 1500 mg / m2 p.o. Day 1 – h 2

                                    Cisplatin 60 mg / m2 day 1 – h 3-9

 Cytarabine 300 mg / m2 i.v. x 15 minutes during the day 1 – h 9

                                    Cyclophosphamide 300 mg / m2 i.v. x 15 minutes during the day 1 – h 12

                                    Repeat 2-4 weeks

            ————————————————– ——————————————

            4. ECB (recommended in medulloblastoma, glioma high grade)

                                    BCNU 150mg / m2 on 1.i.v.

                                    Carboplatin 200 mg / m2 i.v. 1-2 days

                                    Etoposide 100 mg / m2 i.v. Days 1-3

                                    Repeat 3 weeks

5. CCE (recommended in medulloblastoma, high grade glioma).

CCNU 100 mg / m2 p.o. Day 1

                                    Cisplatin 20 mg / m2 / day i.v. days 1-5

                                    Etoposide 100 mg / m2 / day on days 1-5

                                    Was repeated at 6 weeks x 3 sequences.

            ————————————————– ——————————————

            6. brain lymphoma

Methotrexate 1g / m2 iv 1and 8 days (plus folinic acid)

                                    MTX – 12mg intrathecal 1,4,8,11,15,18 days

                                    Dexamethasone 16 mg po Day 1-15

                                    Cytarabine 3g / m2 iv 3 h infusion days 1,2,22,23

Radiotherapy 4-9 weeks.

For anaplastic astrocytoma median survival is 12 months and 2 years survival is 30-40%.

Average survival for glioblastomas is 10-12 months and 2 years survival is 10%.

II. Oligodendrogliomas. Most are low grade tumors, but may appear similar glioblastoma anaplastic forms.

            Treatment consists of surgical resection whenever possible. It is recommended postoperative radiotherapy in doses of 50-55 Gy is effective.

           Oligodendrogliomas anaplastic (grade III and IV) brain tumors are the most sensitive to chemotherapy response rate of 50-60%.

            Use PCV scheme.

  III. Ependimomas are common in children under 3 years old and originate in the posterior fossa around ventricle 4. Treatment consists of surgical resection and postoperative radiotherapy. Survival at 5 to 10 years is 60% and 40% respectively.

IV. Brainstem gliomas occur mainly in children. The diagnosis in some cases be determined clinically other stereotaxic biopsies. Most tumors are unresectable.

Radiation therapy is based.

Palliative chemotherapy is recommended in patients with tumor recurrence, but did not demonstrate value as adjuvant treatment. Median survival is less than 1 year and 2 years survival rate is 10-20%.

V. Medulloblastomas are located either in the cerebellum or the brain stem. They occur in children under 15 years. Tumor seeded L.C.R. which is documented by MRI exam and spinal CSF.

Treatment consists of surgical resection of as much of the tumor.

Craniospinal irradiation is done with a total dose of 54 Gy and 36 Gy to the posterior fossa in 20 fractions spinal shaft with a 5 year survival of 50-60%.

Radiotherapy is not used until the age of 3 years. Adjuvant chemotherapy is used in patients less than 3 years that radiotherapy can partially resected tumors in. Use combination with Cisplatin, Carboplatin, Etoposide, CCNU.

VI. Meningioma. In 80% of cases are benign tumors (low grade). They are located on the convexity of the brain, the skull base and posterior fossa.

When possible, the main treatment is repeated surgical treatment in case of relapse.

Radiation incompletely resected tumors is recommended in high grade tumors and recurrent tumors.

After partial resection and radiotherapy, survival at 10 years is 80%.

  VII. Acoustic schwannomas are benign tumors that arise from acoustic nerve. Treatment is surgical resection with or without associated radiotherapy.

VIII. Primary central nervous system lymphomas occurring in immunosuppressed patients, usually with type B cells can present as a solid tumor mass or multiple tumor masses. Sowing L.C.R. invasion occurs frequently vitreous of the eye.

The tumor is sensitive to chemotherapy and radiation therapy. Treatment consists of 6 cycles of chemotherapy associated with intrathecal methotrexate and irradiation of the whole skull with a total dose of 45-50 Gy.

Treatment CHOP chemotherapy regimens is not the conventional type brain lymphomas. Schemes used include high-dose methotrexate associated with Citosar, intrathecal chemotherapy and cranial radiotherapy. Whole brain irradiation causes in 25% leukoencephalopathy.

IX. Pituitary Adenomas

            In adenomas secrete prolactin with bromocriptine administered medication that decreases prolactinemia and destroy tumor mass. In STH secreting adenomasanalogs with long action of somatostatin are recommended.

If drug therapy is ineffective surgical resection and radiotherapy is used.

  X. Craniopharyngioma represents 5-10% of tumors in children.

Treatment consists of surgical resection associated with radiotherapy.

Survival at 10 years for completely resected patients is 90%.


Unfavorable prognostic factors:

            1. histological grade G3 and G4.

            2. patient age> 40 years

            3. 3, 4 ECOG performance status

Tracking patients

         In astrocytomas g. I and II neurological exam is done by 3 months in the first 2 years, 6 months next 3 years and annually over the next 5 years. It is recommended CT (MRI) brain at 3,6,12 months then annually or depending on the symptoms.

         In meduloblastomas is recommended: MRI (CT) spinal possibly lumbar puncture at 3, 6, 12 months. Subsequently, MRI (CT) spinal is recommended at 6 months during the first 2 years. Bone scan is recommended depending on the symptoms.