K. Čustović (1) M. Omerhodzic (1) K. Dizdarevic (1) N. Iblizovic (1) A. Hasanagic (1) Z. Merhemic (2)

(1) Department of Neurosurgery, KCUS
(2) Institute of Radiology, KCUS, Sarajevo, BiH

This paper was presented on 3rd Congress of the Croatian Neurolosurgical Society with international participation, Zagreb, Croatia, 6.-8. june 2002

Ovaj rad je usmeno prezentiran na 3. Kongresu hrvatskoga Neurohirurškog društva sa međunarodnim učećem, održanom u Zagrebu, R Hrvatska, od 6. do 8. juna 2002. godine

ABSTRACT

76 with recurrent intracranial astrocytoma grade 3 and 4 were reoperated in our clinic during the years 1996 - 2000. The median age of the patients was 41 years. 72% patients had astrocytoma grade 3 and 28% had astrocytoma grade 4. In 58 out of 76 cases surgically resection was grossly total, in others was subtotaly. Preoperative neurological status was the most significant determinant of survival after reoperation in patients with astrocytoma gradus 3. However, in patients with astrocytoma gradus 4, preoperative neurosurgical status was not significantly related to duration of survival. Correlation of the radiological, operative and pathological finding has led to a useful list of prognostic criteria for high grade astrocytomas. In our experience, reoperation should be performed whenever it seems to be possible and should be followed by a complete course of radiotherapy. Radical surgery is the first step in treatment, followed by irradiation and chemotherapy. The importance of detailed histological diagnosis is stressed because of different biological behaviour with regard to conventional and optimal therapy.
Key words: High grade astrocytoma, glioblastoma multiforme, surgery, long term survivor

Background

The role of surgery to obtain a tissue diagnosis and to decompress mass effect in high grade supratentorial glioma - astrocytoma in adult is a straightforward issue, whereas oncological significance of aggressive tumor resection has been more difficult to access.
In this study we examine a number of major series published over the last 15 years to evaluate the effect of surgery on survival in adult patients with high grade supratentorial astrocytomas. The disagreement about nomenclature and classification persists. The Kernohan system subdivides astrocytic neoplasms in to astrocytoma grades I-IV, whereas other classification utilize three division such as astrocytoma, anaplastic or malignant astrocytoma and glioblasoma multiform (GBM). Confusion is created especially for the lesions designed only as astrocytoma grades III.
The overall prognosis for patients with recurrent supratentorial high-grade astroglial tumors is poor and patients mostly died during first year. Radical surgical resection followed by adjuvant radiation and chemotherapy increased survival length. (50% survive more than 12 months)

Material and methods:

76 patients with recurrent astrocytoma gr. III and IV were operated in neurosurgical Department from January 1996 to December 2000. Median age of the patients was 41 years. Gender rate man: women were 2,5:1. Most frequent localization was frontal and temporal lobes. The patients were presented with signs and symptoms of increased intracranial pressure, new onset of drug resistant seizures, progression of neurological symptoms and changes in mentation

Patients operated on for recurrent astrocytoma during 1996-2000.

72% patients had astrocytoma gr. III and 28% had astrocytoma gr. IV.

In 38 out of 76 cases surgicaly resection was grossly total, 32 cases was subtotal. Stereotactic biopsy was performed in 6 cases in tumors located in basal ganglia an eloquent area.

Extensity of resection is defined:

• Biopsy (including stereotactic biopsy) = < 10% resection of tumor. Performed in older patients with poorer clinical state and/or deep seated tumors.
• "Subtotal resection " = 10%-90% resection
• "Gross total or near-total resection " = >90% resection of tumor. Performed in younger patient in good clinical grade and by lobar location of the tumor.

Time interval between first operation and reoperation was 2 month to 2 years. Operative mortality during 1 week was in 6 cases (8%). After reoperation our patients were followed-up a period running from 2 to 6 month and during this period completed a new course of radiotherapy.

Results:

Outcome results in patients operated on for recurrent supratentorial astrocytomas during 1996-2000.

Postoperative complications were:

• Postoperative intracerebral haematomas at previous surgical site in 4 cases
• Cerebral edema (therapeutically resistant) in 6 cases
• Acute hydrocephalus in 3 cases

Discussion:

Patients with malignant gliomas had poor prognosis despite of vigorous multimodality treatment. Advanced age is associated with a less favorable response to radiation therapy for GBM.
Older patients may have different genetic tumor abnormalities, which may or may not code for radiosensitivity. It seems also that older patients present with larger tumors. The brain atrophy allows a larger mass to develop without new simptoms. The molecular and biological factors clearly are responsible for this age-related phenomenon.
There is a strong correlation between the extent of necrosis measured on MRI and survival of GBM patients and more complete tumor resections can result in improved survival. (Hammoud MA et all. 1996; Lacroix M. et all. 2001)
Some neurosurgeon will nevertheless have treated GBM patients with a surprisingly long survival (Chandler K.L. et all.) GBM with a predominance of bizarre, multinucleated giant cells ("giant cell glioblastoma") may have somewhat better prognosis.

Generally the reasons for extraordinarily long survival in patients with GBM may be:

• Incorrect diagnosis
• An extremely long "tumor doubling time" cause by:
  • e.g. extensive intrinsic cell death (papooses)
  • single cell necrosis or
  • more extensive necrosis of tumor tissue adding space for a continuous cell proliferation (Western K. et all. 1994)

When a complete resection (as much tumor as possible) was made, longer survival and better quality of life can be achieved. ( Ammirati; Ciric; Frankel; Weir; Laws etc.).

Other authors suggest only biopsy for diagnosis verification to be performed. Punt J. et all.)

In our department we performed maximum radical operation followed by radiation therapy. That doesn't mean complete excision of the tumor. There are limiting factors mentioned above, such as: deep brain localization, eloquent area, and poor patient condition.
After radical operation selected patients underwent radiation therapy. Selection criteria were younger age, better neurological condition, and more extensive surgical resection.
Radical operation and radiation therapy in selected cases predicted better survival. Older patients with recurrent glioma had poorer clinical responses. We hypothesized that older patients with GBM might have more radioresistant tumors.

Enlarging, enchasing masses in early postoperative imaging is sign of active progression of the tumor. In differential diagnosis radiation necrosis is present.

Conclusions:

According to our experience most important factors determining outcome and length of survival are:

1. Radical tumor resection whenever possible
2. Tumor location in nondominant, noneloquent brain areas that permit radical resection
3. Younger age
4. Better general and neurological status
5. Longer post operative symptom free period
6. Aggressive multimodality treatment including radiation imuno and chemotherapy

These were also our selection criteria for reoperation for recurent high grade astrocytomas. In our experience reoperation should be performed whenever it seems to be possible and should be followed by a complete course of radiotherapy.

Authors adress:
Kemal Čustović. MD PhD
Professor of neurosurgery
Univerzitety Hospital Sarajevo
Dpt. of Neurosurgery,
Bolnička 25, 71000 Sarajevo
Bosnia and Herzegovina