External Beam Radiotherapy in the Management of Low Grade Astrocytoma of the Brain / 대한방사선종양학회지

PURPOSE: This study was designed to evaluate the effectiveness of postoperative radiotherapy for patients with low-grade astrocytomas and to define an optimal radiotherapeutic regimen and prognostic factors. MATERIALS AND METHODS: A total of 69 patients with low-grade astrocytomas underwent surgery and postoperative radiotherapy immediately following surgery at our institution between October 1989 and September 2006. The median patient age was 36 years. Forty-one patients were 40 years or younger and 28 patients were 41 years or older. Fourteen patients underwent a biopsy alone and the remaining 55 patients underwent a subtotal resection. Thirty-nine patients had a Karnofsky performance status of less than 80% and 30 patients had a Karnofsky performance status greater than 80%. Two patients were treated with whole brain irradiation followed by a coned down boost field to the localized area. The remaining 67 patients were treated with a localized field with an appropriate margin. Most of the patients received a dose of 50~55 Gy and majority of the patients were treated with a dose of 54 Gy. RESULTS: The overall 5-year and 7-year survival rates for all of the 69 patients were 49% and 44%, respectively. Corresponding disease free survival rates were 45% and 40%, respectively. Patients who underwent a subtotal resection showed better survival than patients who underwent a biopsy alone. The overall 5-year survival rates for patients who underwent a subtotal resection and patients who underwent a biopsy alone were 57% and 38%, respectively (p<0.05). Forty-one patients who were 40 years or younger showed a better overall 5-year survival rate as compared with 28 patients who were 41 years or older (56% versus 40%, p<0.05). The overall 5-year survival rates for 30 patients with a Karnofsky performance status greater than 80% and 39 patients with a Karnofsky performance status less than 80% were 51% and 47%, respectively. This finding was not statistically significant. Although one patient was not able to complete the treatment because of neurological deterioration, there were no significant treatment related toxicities. CONCLUSION: Postoperative radiotherapy following surgery is a safe and effective treatment for patients with low-grade astrocytomas. The extent of surgery and age were noted as significant prognostic factors in this study. However, further effective treatment might be necessary in the future to improve long-term survival rates.

Treatment Results and Prognostic Variables of Supratentorial Low-grade Astrocytomas which were Treated with Radiation Therapy Following Incomplete Resection in Adults

The natural history of low-grade astrocytomas is variable. Although many patients survive for an extended period of time, other patients have a rapidly progressive course and early death. In order to determine the specific prognostic factors in low-grade astrocytoma(LGA) patients with uniform contemporary technique, data from 41 consecutive supratentorial LGA patients(>or=18 years of age) treated with radiation therapy following incomplete resection between June 1989 and May 1993 at our hospital were analyzed. Variable factors were examined for their association with survival: age at the time of diagnosis, gender, length and type of neurological symptoms, preoperative neurological status, contrast enhancement pattern on CT, and extent of the lesion as defined by CT/MRI. The following characteristics were associated with improved patient survival by univariate analysis(p12 months, and seizure as a presenting symptom at the time of admission. Other factors were not significant in determining the length of survival. Overall acturial survival at 3 and 5 years was 82% and 70%, respectivley. Nine of these 41 patients had tumor recurrences/progressions with a mean time of 20.6 months. Among 9 tumor recurrences/progressions, second surgery was perfomed in 5 patients and 3 of these 5 patients had progressed to high-grade lesions(2 glioblastoma multiformes, 1 anaplastic astrocytoma). Seven patients died from tumor progression/recurrence. Concerning surgical removal, an attempt should be made, whenever possible, for a gross total resection. But, when that is not possible, we think that biopsy or partial debulking without undue risk of significant neurologic compromise followed by radiation therapy can serve as an alternative treatment option in supratentorial LGAs.

Angiogenensis and Overexpression of p53 Gene Produc in Brain Tumor

Angiogenesis depends on the net balance between positive and negative angiogenic factors. Tumor cells are angiogenic resulting from increased production of positive factors and decreased production of negative factors. Among these, vascular endothelial growth factor and glioma- derived angiogenesis inhibiting factor are related to glioblastoma multiforme. The p53 gene is more frequently mutated than any other known oncogene or tumor suppressor gene in human tumors including glioblastoma multiforme. Angiogenesis is reported to be controlled by p53 regulation in recent studies. To examine the effect of p53 overexpression on angiogenesis in glioblastoma multiforme, we performed immunohistochemical staining in 51 cases of glioblastoma multiforme, using monoclonal antibodies to p53 protein and factor VIII. 20 cases of low grade astrocytoma were used as control. p53 overexpression was present in 15(75%) of 20 cases of low grade astrocytoma and the mean vessel count was 37.7+/-9.9 at x200 field and 17.5+/-5.8 at x400 field. p53 overexpression was present in 35(68%) of 51 cases of glioblastoma multiforme and the mean vessel count was 91.9 45.8 at x200 field and 40.7 19.1 at x400 field. Mean vessel count in low grade astrocytoma with p53 overexpression was 39.4 10.2 at x200 field and 18.9 5.7 at x400 field, while in cases without p53 overexpression it was 32.4+/-7.6 at x200 field and 13.2 3.5 at x400 field. Mean vessel count in glioblastoma multiforme with p53 overexpression was 94.5+/-51.8 at x200 field and 42.1+/-16.8 at x400 field, while in cases without p53 overexpression it was 86.1+/-29.5 at x200 field and 37.1+/-16.8 at x400 field. The mean survival time was 12.4 months in the 39 cases of glioblastoma multiforme in which follow-up studies were possible. Significant prognostic factors were age, p53 overexpression and adjuvant therapy. These results show that p53 gene mutation is one of the many contributing factors to angiogenesis in glioblastoma multiforme. In addition, other oncogenes and tumor suppressor genes, as well as growth factors may be involved. Age, p53 overexpression and adjuvant therapy proved to be significant prognostic factors, while microvessel density was not.

The Role of Radiotherapy in the Management of Supratentorial Low Grade Astrocytoma / 대한치료방사선과학회지

PURPOSE: To evaluate the role of radiotherapy in the management of incompletely resected supratentorial low grade astrocytoma with the analysis of the survival, the pattern of failure, and the prognostic variables affecting survival. MATERIAL AND METHODS: Between January 1990 and December 1995, fifty- one patients with supratentorial low grade astrocytoma received radiotherapy after subtotal resection(16 patients) or stereotactic biopsy(35 patients) at Asan Medical Center. External radiotherapy was done by conventional fractionation with the total dose of 4820cGy to 6000cGy(median 5580cGy) and partial brain volume. The follow-up was done from 6 to 79 months(median 48 months). RESULTS: Overall actuarial survival rate at 2 and 5 years were 83.4% and 54.8%, respectively. Progression free survival at 2 and 5 years were 67.4% and 48.7%, respectively. The significant prognostic factors affecting overall survival rate were the performance status, T stage, histologic subtype, radiation field and radiation response. The major pattern of failure was local failure, such as progressive disease and primary site recurrence in 23 patients (45.1%). Progression free survivors excluding 2 patients were physically and intellectually intact without major neurologic deficit. CONCLUSION: Although the follow-up period of this study was relatively short, overall actuarial and progression free survival rate were encouraging. Patients with good performance status, lower T stage, pilocytic subtype, patients treated with small radiation field and radiation responder showed better survival. As the local failure was the major pattern of failure, the various efforts to decrease the local failure is necessary.

Survival and Prognostic Factors of Supratentorial Hemispheric Low-grade Fibrillary Astrocytomas

The natural history of supratentorial hemispheric low-grade fibrillary astrocytomas is extremely variable. Although many patients wurvive for an extended period of time, other patients show a rapidly progressive course and early death. In an effort to clarify the natural history and prognostic factors, we conducted a retrospective study. Of 49 patients treated at Yonsei University Hospital between January 1980 and December 1991 for histologically confirmed low-grade fibrillary astrocytomas of cerebral hemisphere, 46 patients were followed for more than 30 months. Pilocytic and gemistocytic astrocytomas were excluded, as were tumors originating in the basal ganglia, thalamus, hypothalamus, optic path-ways, and posterior fossa. Mixed gliomas were also excluded. Survival rates were estimated by the method of Kaplan-Meir. The prognostic factors were analyzed by log-rank test and Cox stepweise multiple regression test for multivariates. The 46 patients consisted of 31 males and 14 females who ranged in age from 6 to 64 years(median 32.9 years). The median symptom duration before diagnosis was 10 months(1-120 months). Frontal lobe was the most common site of involvement and 70% of patients presented with seizure Ten(21.7%) cases were surface(gyral) type and 36 were located mainly in the deep white matter. Gross total removal was performed in 11 patients(24%), and 29 patients(63%) received postoperative irradiation. Overal actuarial survival rates at 5, 10 years ere 59%, 54%, respectively. Five-year progression-free survival was 52.7%. Of 16 patients with recurrence or progression of tumor with a median time to recurrence of 29 months, 6 undersent additional resection ot tumor. A dedifferentiation toward astrocytoma Grade 3 or 4 occurred in 2 of 6 patients(33.3%). The median time from recurrence ot death was 8 months. Younger age(8 months), normal preoperative mental status, a history of preoperative seizure, the presence of cyst, well-defined tumor margin, and no extension into the corpus callusum or contralateal hemisphere were associated with a better prognosis on univariate analysis. Among 7 good prognostic factors, the significance of preoperative mental status and sharpeness of the tumor border were confirmed by multivariate stepweise regression test.

Radiotherapy for the Low-grade Astrocytomas / 대한치료방사선과학회지

PURPOSE: To evaluate the efficacy of radiotherapy for the low-grade astrocytomas and confirm the variables influencing treatment results. MATERIALS AND METHODS: Forty-six patients with low-grade astrocytoma received radiotherapy after surgical removal (36 patients) or biopsy (10 patients) from 1979 to 1990. Twenty patients had grade I histology and 26 had grade II. External radiotherapy was done by conventional schedule with the total dose of 45 to 60 Gy (median; 54 Gy). The median follow-up period was 5 years. RESULTS: The 2-year and 5-year survival rates were 80% and 72%, respectively and the 2-year and 5-year progression-free survival was 75% and 63%, respectively. The survival was influenced significantly by the histologic grade, the gistologic type, and performance status. Major complication was not found. CONCLUSION: In spite of good survival, the local failure was still the major problem. Age and the extent of surgery as well as three favorable factors should be considered in the future treatments.