Pretreatment factors predict overall survival for patients with low-grade glioma: a recursive partitioning analysis.

Bauman G,  Int J Radiat Oncol Biol Phys. 1999 Nov 1;45(4):923-9.

Department of Oncology, University of Western Ontario, and London Regional Cancer Centre, Canada. glenn_bauman@lrcc.on.ca

PURPOSE: Three databases were pooled and analyzed to determine which groupings of prognostic factors best predicted overall survival for patients with low-grade gliomas treated with surgery and immediate or delayed radiotherapy. METHODS AND MATERIALS: Databases of patients with low-grade gliomas compiled at the London Regional Cancer Centre (LRCC), the Norwegian Radium Hospital (NRH), and the University of California, San Francisco (UCSF) were merged. Inclusion criteria for the pooled analysis included: age > or =18 years and histologically confirmed low-grade (World Health Organization Grade II) supratentorial fibrillary astrocytoma, oligodendroglioma or mixed oligoastrocytoma. Factors analyzed for prognostic significance included: age at diagnosis, gender, seizures at presentation, presence of enhancement on computed tomography (CT) or magnetic resonance imaging (MRI), Karnofsky Performance Status (KPS) at diagnosis, histology, extent of surgical resection, timing of radiotherapy, and treating institution. Univariate and multivariate analysis of overall survival for these factors was performed. Recursive partitioning was performed to generate prognostic groups using these factors. RESULTS: From the combined databases, 401 patients were eligible for analysis. Median survival for the entire group was 95 months/7.9 years. On univariate analysis age 18-40, presence of seizures at presentation, KPS > or =70, treating institution, and absence of contrast enhancement were associated with improved overall survival. On multivariate analysis, these factors remained independent predictors of improved overall survival. Recursive partitioning analysis yielded four prognostic groups with statistically different median survivals (MS): Group I (n = 41: KPS <70, age >40) MS 12 months; Group II (n = 34: KPS > or =70, age >40, enhancement present) MS 46 months; Group III (n = 138: KPS <70, age 18-40 or KPS > or =70 age >40, no enhancement) MS 87 months; Group IV (n = 188: KPS > or =70, age 18-40) MS 128 months. CONCLUSION: Clusters of pretreatment prognostic factors described subgroups of low-grade glioma patients with divergent overall survivals. Consideration of these prognostic subgroups may be important when considering timing of interventions for these patients and in the stratification of patients for clinical trials.

Radiotherapy in low-grade gliomas: pros.

Kortmann RD.  Semin Oncol. 2003 Dec;30(6 Suppl 19):29-33.

Department of Radiotherapy, Hoppe-Seyler-Str 3, D-72076 Tuebingen, Germany.

Although surgery is generally accepted as an important initial treatment in patients with low-grade gliomas, the role of postoperative radiotherapy (RT) is the subject of ongoing controversy. What is the most appropriate timing of RT? Is it best to deliver RT immediately after surgery or to watch and wait until disease progression? Numerous retrospective studies have shown that immediate postoperative RT provides a survival benefit. A recently published prospective study conducted by the European Organisation for Research and Treatment of Cancer has also shown that immediate postoperative RT significantly improved 5-year progression-free survival, but overall survival was not improved. Given the uncertainty about the overall survival benefit of immediate RT and the potential for radiation-induced toxicity, it is important to consider prognostic factors when selecting patients. Subgroups of patients with poor prognostic factors are more likely to benefit from immediate postoperative RT. Available data indicate that a carefully balanced therapeutic approach is needed to optimize treatment outcomes in patients with low-grade gliomas. Patients with more aggressive disease and a high risk of malignant transformation will likely benefit from immediate RT, whereas patients with low-risk disease, particularly oligodendrogliomas, can reasonably be observed. However, one cannot exclude the possibility that delaying RT may result in a worse long-term clinical outcome.

Radiotherapy in low-grade gliomas: Cons.

Mirimanoff RO, Stupp R.  Semin Oncol. 2003 Dec;30(6 Suppl 19):34-8.

Department of Radiation Oncology, University Hospital (CHUV), Rue du Bugnon 46, CH-1011, Lausanne, Switzerland.

Although postoperative radiotherapy (RT) is widely used in patients with low-grade gliomas (LGGs), its clinical benefit remains unproven. Because LGGs include diseases with many different histologies, cytogenetic patterns, and natural histories, evaluating the effect of any treatment for LGGs is difficult. Analysis of prognostic subgroups has shown median survival rates ranging from 1 to 10 years. The clinical benefit of postoperative RT in LGGs in retrospective studies is confounded by the heterogeneity of LGGs and treatment-related variables. These studies report conflicting results, most likely because of differences in patient populations. The only prospective, randomized trial comparing postoperative RT with observation failed to show a survival benefit but showed a modest, although statistically significant, improvement in time to progression. Given that two thirds of patients in the observation group received RT at progression, the absence of a survival benefit suggests that RT is active in LGGs, but that delayed RT may provide the same survival advantage as postoperative RT. Moreover, high-dose or whole-brain RT can cause cognitive deficits. Our opinion is that postoperative RT should not be administered routinely to patients with LGGs. If RT is deemed necessary, such as in progressive or inoperable disease causing neurologic symptoms, a total dose of </=50 Gy with a fractional dose of </=1.8 to 2 Gy should be administered using modern, highly conformal techniques. Ideally, RT should be used only within the context of clinical research protocols.

Immediate postoperative radiotherapy or "watch and wait" in the management of adult low-grade glioma?

Kortmann RD, Strahlenther Onkol. 2004 Jul;180(7):408-18.

Department of Radiooncology, University of Tuebingen, Germany, Rolf-Dieter.Kortmann@medizin.uni-leipzig.de

BACKGROUND: The EORTC Trial 22845 on the role of immediate postoperative radiotherapy in patients with supratentorial lowgrade glioma revealed an advantage of immediate postoperative radiotherapy for progression-free survival, but not for overall survival. It is still an open question in which clinical setting immediate radiotherapy should be considered and whether chemotherapy may become a useful alternative. MATERIAL AND METHODS: Reports in the literature spanning 60 years of radiation therapy were reviewed with respect to timing of radiotherapy, prognostic factors, dose prescriptions, modern treatment techniques, and late effects. Data on chemotherapy were also reviewed. Based on these data, the role of immediate postoperative radiotherapy or chemotherapy in adult low-grade glioma is presented. RESULTS: Radiotherapy is able to control symptoms in up to 80% of cases. Malignant transformation occurs in 36-86% of cases upon progressive disease. Long-term median survival crucially depends on prognostic factors and ranges between 12 months and 10 years. Radiotherapy does not cause neurocognitive deficits, provided that modern treatment techniques and moderate dose prescriptions are used. Recent series with small patient numbers indicate that chemotherapy using PCV or temozolomide may prolong median survival and induces response rates of 50% in oligodendroglial tumors. CONCLUSION: The arguments for immediate postoperative irradiation include: low-grade gliomas respond to radiotherapy; the tumors often display an aggressive pathobiological behavior; patients with high risk profile may benefit from immediate radiotherapy in terms of progression-free and overall survival; modern focal radiotherapy is far less toxic than feared; radiotherapy might be more effective at diagnosis than at progression. Chemotherapy might be an alternative in immediate postoperative treatment. Its role, however, is unclear. The forthcoming prospective trial of the EORTC will address this issue in a randomized setting.

Progress in long-term survival in adult patients with supratentorial low-grade gliomas: a population-based study of 993 patients in whom tumors were diagnosed between 1970 and 1993.

Johannesen TB, J Neurosurg. 2003 Nov;99(5):854-62.

Norwegian Cancer Registry, Institute of Population-Based Cancer Research, Oslo, Norway. tomj@trollnet.no

OBJECT: The goal of this study was to document and compare long-term survival during the periods 1970 through 1981 and 1982 through 1993 in all adult patients in Norway with histologically verified supratentorial low-grade gliomas (LGGs). METHODS: Nine hundred ninety-three patients 15 to 69 years of age were found to have a primary supratentorial diffuse astrocytoma, oligodendroglioma, oligoastrocytoma, or pilocytic astrocytoma. Survival time was analyzed in all patients and, in a subset of 451 patients, the influence of new imaging methods on the time from symptom onset to imaging diagnosis was estimated. Overall median survival was 6.4 years (95% confidence interval [CI] 5.7-7.1 years). Survival times for patients in whom a diagnosis was made between 1970 and 1981 (397 patients) and between 1982 and 1993 (596 patients) were 4.1 years (95% CI 3.3-4.9 years) and 9.2 years (95% CI 7.9-10.6 years), respectively (p < 0.0001). Survival also improved in the later period within each histological subgroup. In patients in whom a biopsy was performed the median length of survival was 6.4 years (95% CI 3.1-9.7 years); in patients treated with subtotal tumor resection it was 6.8 years (95% CI 5.8-7.7 years); and in those treated with gross-total tumor resection it was 7.6 years (95% CI 5.5-9.7 years), a nonsignificant difference (p = 0.59). A considerable age-dependent variation in overall survival was demonstrated. The availability of computerized tomography (CT) scanning and/or magnetic resonance (MR) imaging as a diagnostic tool reduced the median period of symptoms prior to diagnosis by 6 months. CONCLUSIONS: Long-term overall survival significantly improved, but age-related differences in prognosis persisted. The increased sensitivity of the diagnostic method due to the availability of CT scanning and/or MR imaging may partly, but not entirely, account for the observed magnitude of improvement in overall survival. Thus local tumor treatment improved during the study period.

Supratentorial low-grade glioma: results and prognostic factors following postoperative radiotherapy.

Grabenbauer GG, Strahlenther Onkol. 2000 Jun;176(6):259-64.

Department of Radiation Oncology, University Hospitals of Erlangen-Nurnberg, Germany. gerd.grabenbauer@strahlen.imed.uni-erlangen.de

BACKGROUND AND PURPOSE: To assess treatment outcome and prognostic factors following postoperative external radiotherapy in 77 patients with low-grade glioma. PATIENTS AND METHODS: Between 1977 and 1996, 45 patients with astrocytoma, 14 with oligodendroglioma and 18 with mixed glioma received postoperative radiotherapy with a median total dose of 52 Gy (range, 45 to 61 Gy). Sixty-seven patients were treated immediately following surgery, 10 patients with tumor progression. The influence of various factors including histology, gender, age, seizures, duration of symptoms (< or = 6 weeks vs > 6 weeks), CT pattern (enhancement vs no enhancement), type of surgery, total radiotherapy dose and timing of radiotherapy on relapse-free survival and overall survival was investigated. RESULTS: The median overall survival time was 81 months, the 5- and 10-year survival rates were 54% and 31%, respectively. The median time to progression was 56 months, while the 5- and 10-year progression-free survival rates were 45% and 24%. Univariate analyses identified the total radiotherapy dose (p = 0.01), duration of symptoms (p = 0.05), the presence of seizures (p = 0.04), and the CT pattern following intravenous contrast (p = 0.005) as significant prognostic factors for overall survival. Progression-free survival rates were influenced by the total dose (p = 0.04), the duration of symptoms (p = 0.01) and CT pattern (p = 0.006). On multivariate analysis, only the CT pattern (enhancement vs no enhancement) remained as independent prognostic factors for both progression-free survival and overall survival. CONCLUSIONS: A minimum total dose of 52 Gy is recommended for the postoperative radiotherapy in low-grade glioma. Tumors with CT enhancement seem to need further intensification of treatment.

Ann Acad Med Singapore 1996 May;25(3):392-6

Supratentorial low-grade glioma: is there a role for radiation therapy?

Trautmann TG, Shaw EG

Department of Radiation Oncology, Bowman Gray School of Medicine, Winston-Salem, North Carolina 27157-1030, USA.

The supratentorial low-grade gliomas are a heterogeneous group of central nervous system tumours. Knowledge of their biology, primarily based on histologic subtype and patient age, is helpful in determining prognosis and guiding therapeutic recommendations. The pilocytic tumours usually occur in younger patients and carry a favourable prognosis. Recurrence following gross total excision is rare, and approximately 80% of patients undergoing subtotal removal with or without postoperative radiation therapy (RT) will survive 10 years or longer. In contrast, non-pilocytic, supratentorial low-grade tumours (including the diffuse fibrillary, protoplasmic and gemistocytic subtypes), as well as mixed oligoastrocytomas and oligodendrogliomas are infrequently cured, even with gross total excision. Survival benefit with postoperative RT has been suggested by several retrospective studies. When RT is prescribed, localized treatment fields are suggested for total doses of 4500 to 6500 cGy. Ongoing prospective, randomized studies hopefully will clarify the role of RT in these neoplasms, as well as the optimal dose.

J Neurosurg 1989 Jun;70(6):853-61

Radiation therapy in the management of low-grade supratentorial astrocytomas.

Shaw EG, Daumas-Duport C, Scheithauer BW, Gilbertson DT, O'Fallon JR, Earle JD, Laws ER Jr, Okazaki H

Division of Radiation Oncology, Mayo Clinic, Rochester, Minnesota.

The records of 167 patients with grade 1 or 2 supratentorial pilocytic astrocytomas (41 patients), ordinary astrocytomas (91 patients), or mixed oligoastrocytomas (35 patients) diagnosed between 1960 and 1982 are retrospectively reviewed. The extent of surgical tumor removal was gross total or radical subtotal in 33 patients (20%) and subtotal or biopsy only in the remaining 134 patients (80%). Postoperative radiation therapy was given to 139 (83%) of the 167 patients, with a median dose of 5000 cGy (range 600 to 6500 cGy). Multivariate analysis revealed that a pilocytic histology was the most significant prognostic variable associated with a good survival. The 5- and 10-year survival rates were, respectively, 85% and 79% for the 41 patients with pilocytic astrocytomas compared to 51% and 23% for the 126 patients with ordinary astrocytomas or mixed oligoastrocytomas. Postoperative irradiation did not appear to be associated with improved survival times in the patients with pilocytic astrocytomas; however, in the 126 patients with ordinary astrocytomas or mixed oligoastrocytomas, those who received "high-dose" radiation (greater than or equal to 5300 cGy) had significantly better survival times than those who received "low-dose" radiation (less than 5300 cGy) or surgery alone. The 5- and 10-year survival rates were, respectively, 68% and 39% for the 35 patients receiving high-dose radiation, 47% and 21% for the 67 receiving low-dose radiation, and 32% and 11% for the 19 treated with surgery alone. The survival rate was poor for the 23 patients with ordinary astrocytomas and oligoastrocytomas who underwent gross total or radical subtotal tumor removal (14 of whom were also irradiated): 52% at 5 years and 21% at 10 years, with 19 of 23 patients developing tumor progression and dying 1 to 12 years postoperatively. In contrast, all 10 patients with pilocytic astrocytomas who had gross total or radical subtotal tumor removal alone were long-term survivors, with follow-up periods of about 4 to 25 years.

Cancer 1993 Jul 1;72(1):190-5

Supratentorial low-grade astrocytoma. Correlation of computed tomography findings with effect of radiation therapy and prognostic variables.

Shibamoto Y, Kitakabu Y, Takahashi M, Yamashita J, Oda Y, Kikuchi H, Abe M

Department of Radiology, Faculty of Medicine, Kyoto University, Japan.

BACKGROUND. In supratentorial low-grade astrocytoma, radiation therapy effects and prognostic factors, especially with respect to computed tomography (CT) findings, are not yet well established. A retrospective analysis of 119 patients with this disease (histologically confirmed ordinary astrocytoma) therefore was conducted. METHODS. Between 1965 and 1989, 101 patients received postoperative radiation therapy, whereas 18 patients received surgery alone. Radiation was directed to the tumor plus a 1- to 3-cm margin in almost all cases; the dose range was 41 to 66 Gy (mean, 57 Gy). CT scan was performed before treatment on 74 patients. Postoperative survival rates were compared by both univariate and multivariate analyses. RESULTS. The 5- and 10-year survival rates for the irradiated group were 60% and 41%, respectively, which were significantly better than those for the surgery-alone group (37% and 11%, P = 0.048). Among various potential prognostic factors for the irradiated patients, only a lower age was associated with a better prognosis. Sex, tumor site (deep-seated or not), extent of surgery, radiation dose and field, and adjuvant chemotherapy did not influence the prognosis significantly. Among various CT findings, a clear tumor margin, a maximum tumor area less than 25 cm2, presence of a cyst, and lack of mass effect were associated with a better prognosis on univariate analysis (P = 0.02-0.12), but contrast enhancement was not related to prognosis. On multivariate analysis, however, mass effect was the only significant factor. CONCLUSIONS. Radiation therapy appears definitely to be effective in improving the prognosis for low-grade astrocytoma. Younger age, and the absence of mass effect determined by CT, were associated significantly with a better prognosis.

Bull Cancer Radiother 1995;82(4):388-95

Radiation therapy with or without surgery in the management of low-grade brain astrocytomas. A retrospective study of 120 patients.

Touboul E, Schlienger M, Buffat L, Balosso J, Minne JF, Schwartz LH, Pene F, Masri-Zada T, Lot G, Devaux B

Services de cancerologie-radiotherapie A et B, hopital Tenon, Paris, France.

From 1977 to 1988, 120 consecutive patients with a diagnosis of low-grade astrocytoma were referred to our department for radiotherapy. Fourty-one patients (group 1) underwent surgery and post operative external radiation therapy (2 gross total resections and 39 subtotal resections). Sixty-nine patients underwent exclusive external radiotherapy (group 2). In ten patients, the irradiation was delivered by stereotactic implantation of iridium-192 wires into the tumor with or without external irradiation (group 3). Ten had pilocytic astrocytomas (mean age, 24 years) and twenty had microcystic astrocytomas (mean age, 35.4 years). The 5- and 10-year survival rates were 55.6% and 44.4%, respectively and 55% and 48%. Ninety astrocytomas were classified as "ordinary" astrocytoma (mean age, 36.8 years). The 5- and 10-year overall survival rates were 51% and 20.5%, respectively. The same probabilities at 5 and 10 years were 65% and 37% respectively, for group 1, 38.8% and 12.7% for group 2 and, 78.8 and 22.5% for group 3. In multivariate analysis, two prognostic factors had a significant impact on overall survival: IK score (IK < 90 vs IK > or = 90, p = 0.0001), surgical resection (surgical resection and post operative radiotherapy vs radiation therapy alone, p = 0.012). However, the patients who underwent surgical resection were those in the best condition, having tumors that were easily accessible and less invasive.

Int J Radiat Oncol Biol Phys 1989 Mar;16(3):663-8

Postoperative radiotherapy of supratentorial low-grade gliomas.

Shaw EG, Scheithauer BW, Gilbertson DT, Nichols DA, Laws ER, Earle JD, Daumas-Duport C, O'Fallon JR, Dinapoli RP

Division of Radiation Oncology, Mayo Clinic, Rochester, MN 55905.

Forty-nine patients with supratentorial low-grade gliomas underwent surgery (biopsy or subtotal resection) and postoperative radiotherapy at the Mayo Clinic between 1976 and 1983. The median, 5-, and 10-year overall survivals for the total group were 6.5 years, 62%, and 14%, respectively. Nine prognostic variables were examined for their possible association with survival, including age, sex, site, size, CT enhancement, histologic type, extent of resection, radiation volume, and radiation dose. Of these variables, only histologic type was significantly associated with survival. The estimated 5-year survival was 100% for the 5 patients with pilocytic astrocytomas, 83% for the 20 patients with oligodendrogliomas or mixed oligo-astrocytomas, and 40% in the 24 patients with ordinary astrocytomas (log rank p = 0.001). Other possible prognostic variables, such as radiation volume or total dose, showed no association with survival. Twenty-seven patients had a documented treatment failure. For the 20 patients in whom the pattern of failure could be determined, all failed within their radiation portals. Eleven patients had additional tissue obtained following suspected disease recurrence. Tumor was found in ten of these patients, and radionecrosis in one.

Cancer 1990 Jul 1;66(1):6-14

Low-grade cerebral astrocytomas. Survival and quality of life after radiation therapy.

North CA, North RB, Epstein JA, Piantadosi S, Wharam MD

Department of Radiation Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205.

Of 77 patients with supratentorial Grades I and II astrocytoma diagnosed from January 1975 to December 1984, 66 were treated with postoperative radiation therapy. The patients received a tumor dose of 5000 to 5500 cGy in 180 cGy fractions, five fractions per week, over 5.5 to 6 weeks. Overall actuarial survival at 2, 5, and 10 years was 71%, 55%, and 43%, respectively. Progression-free survival at 2, 5, and 10 years was 69%, 50%, and 39%, respectively. Survival for patients receiving postoperative radiation therapy in the range of 4500 to 5900 cGy was 78% and 66% at 2 and 5 years, respectively. Quality of life was determined at two points in time: 1 to 2 years postoperatively, and at last follow-up (2-12 years postoperatively). The occurrence of mental retardation was specifically addressed in long-term survivors, and was observed in 50% of children. Overall, however, 80% of short-term survivors and 67% of long-term survivors were intellectually and physically intact, without major neurologic deficit. Specific prognostic factors were assessed by multivariate analysis. Improved survival was observed with young patients, females, normal preoperative mental status, surgical resection (versus biopsy alone), involvement of only one lobe with tumor, and a history of preoperative seizures. A weighted prognostic factor score derived from these observations permits a clinically useful assessment of risk for individual patients.

Neurosurgery 1992 Oct;31(4):636-42; discussion 642

Treatment and survival of low-grade astrocytoma in adults--1977-1988.

McCormack BM, Miller DC, Budzilovich GN, Voorhees GJ, Ransohoff J

Department of Neurosurgery, New York University Medical Center, New York.

A retrospective review of the records of the Division of Neuropathology at the New York University Medical Center between 1977 and 1988 revealed 53 cases of adult supratentorial astrocytomas. Fifty were fibrillary, and three were gemistocytic. Two additional patients had pilocytic tumors and were not included in the study. The majority of patients had either a subtotal (64%) or gross total resection (19%). Biopsy (17%) was performed for deep-seated lesions and for those lesions confined to eloquent cortex. Forty-eight patients (91%) received postoperative radiation therapy. The median survival was 7 1/4 years with a 5-year survival of 64%. Multivariate regression analysis demonstrated that the most important prognosticators for improved survival were young age, absence of contrast enhancement of the original tumor on computed tomography (CT) and the performance status of the patient. Patients with hemispheric tumors died from dedifferentiation into an anaplastic astrocytoma or a glioblastoma multiforme, with a median time to recurrence of 4.5 years from the original surgery. Survival from the time of recurrence was 12 months. Subsequent operations confirmed progression towards malignancy in six of seven (86%) recurrent tumors. CT contrast enhancement of the original tumor was associated with a 6.8-fold increase in risk for later recurrence. Patients with thalamic tumors (six patients) had a poor prognosis with a median survival of less than 2 years. A review of their CT scans suggest that four died of progressive low-grade disease; however, confirmatory autopsy data were available for only one patient. This study supports others that have shown improved survival for adult patients with astrocytomas treated in the CT era.

Radiother Oncol 1993 May;27(2):112-6

Radiotherapy for supratentorial low-grade gliomas: results and prognostic factors with special focus on tumour volume parameters.

Miralbell R, Balart J, Matias-Guiu X, Molet J, Ariza A, Craven-Bartle J

Department of Radiation Oncology, Hospital de Sant Pau, Universitat Autonoma de Barcelona, Spain.

From 1973 to 1990, 67 patients with a diagnosis of low-grade glioma were treated in our hospital. Overall survival was analysed as well as the influence of patient, tumour- and treatment-related factors with special focus on tumour volume parameters. Our study group included 49 patients treated by surgery and post-operative radiotherapy (RT) (40 patients) or post-biopsy irradiation alone (9 patients). Total or almost total resection was performed in 16 patients; partial excision was done in 24.  RT was delivered to involved regions: either the residual tumour volume or the tumour bed. The median RT dose was 56 Gy (45-60, range). The 60- and 90-month overall survival (Kaplan-Meier) was 79% and 67%, respectively. Female sex, > 70% Karnofsky (Kf) score, oligodendroglioma and < 71 cm3 (approximately 5 cm diameter sphere) tumour residuals before RT were associated with better overall survival rates (p < 0.05, log-rank). However, a Cox proportional hazards model showed that only the histological subtype and Kf significantly determined the patients' outcome: 60-month overall survival of 100%, 62%, 83% and 64% for oligodendrogliomas, mixed oligo-astrocytomas and grade-I and grade-II astrocytomas, respectively.

J Clin Oncol 1997 Apr;15(4):1294-301

Supratentorial low-grade glioma in adults: an analysis of prognostic factors and timing of radiation.

Leighton C, Fisher B, Bauman G, Depiero S, Stitt L, MacDonald D, Cairncross G

Department of Oncology, University of Western Ontario, London, Canada.

Median survival for the entire group (N = 167; mean age 40.6 years) was 10.5 years with 5- and 10-year survival rates of 72% and 50%, respectively. Median progression-free survival was 4.9 years with 5- and 10-year progression-free rates of 50% and 12%, respectively. Overall and progression-free survivals were longer for patients with an oligodendroglioma or mixed glioma than with astrocytoma (median 13 v 7.5 years, P = .003; progression-free 5.6 v 4.4 years, p = .054). Age at diagnosis < or = 40 years, seizures at presentation, minimal residual tumor after surgery, Karnofsky performance status > or = 70, and oligodendroglioma or mixed glioma pathology were associated with significantly longer median survival on univariate and multivariate analyses. Patients with low-grade glioma diagnosed by modern imaging can be expected to live a long time; timing of radiotherapy may be a less important determinant of survival than nontreatment variables and residual tumor bulk.

Cancer 1994 Apr 1;73(7):1937-45

Low grade supratentorial astrocytomas. Management and prognostic factors.

Janny P, Cure H, Mohr M, Heldt N, Kwiatkowski F, Lemaire JJ, Plagne R, Rozan R

Department of Neurosurgery, Hopital Fontmaure, Chalmalieres, France.

The 49 patients with ordinary astrocytomas who survived surgery (mean age, 37 years) had a median survival time of 64 months and 5- and 10-year survival rates of 54.6% and 34.1%, respectively. Patients with Grade 1 or 2 tumors had a median survival time of 108.6 months, compared with 39.4 months for patients with Grade 3 tumors. Gross total and subtotal resections were significantly associated with longer survival time only in patients with Grade 1 and 2 tumors: in this group, the 5- and 10-year survival rates were 87.5% and 68.2%, respectively, when tumor was completely resected, instead of 57% and 31.2% in patients with incomplete or no surgical resection. There was a trend suggesting that antimitotic drugs and X-ray therapy could benefit patients with Grade 3 tumors.

Cancer 1975 Jun;35(6):1551-7

The role of radiation therapy in the treatment of astrocytomas.

Leibel SA, Sheline GE, Wara WM, Boldrey EB, Nielsen SL

One hundred forty-seven patients with astrocytoma were treated between 1942 and 1967.There were 25 postoperative deaths. The 14 patients in whom the tumor was thought tohave been completely removed were not irradiated and all survived 5 years or longer. Seventy-one of the 108 patients with imcompletely excised lesions received radiation therapy. The 5-year survival rate for those with imcomplete resection alone was 19%, compared to 46% when irradiation was given. Based on observations up to 20 years, after incomplete removal postoperative irradiation significally prolonged useful life and may have lead to permanent control in some. There was no evidence of radiation damage. Most of these tumors were fibrillary astrocytomas, and the results apply particularly to this histologic type. Only 1 of 11 patients with gemistocytic astrocytoma survivied 5 years. The survival rate for Grade i tumors was appreciably greater than for Grade iilesions; in both grades, it was improved by irradiation.

Survival, Prognostic Factors, and Therapeutic Efficacy in Low-Grade Glioma: A Retrospective Study in 379 Patients 

By Knut Lote, J Clin Oncol 1997; 15:3129-3140. 

Purpose: We report survival, prognostic factors, and treatment efficacy in low-grade glioma. 

Patients and Methods: A total of 379 patients with histologic intracranial low-grade glioma received postoperative radiotherapy (n = 361) and intraarterial carmustine (BCNU) chemotherapy (n = 153). Overall survival and prognostic factors were evaluated with the SPSS statistical program (SPSS Inc, Chicago, IL). 

Results: Median survival (all patients) was 100 months (95% confidence interval [CI], 87 to 113); in age group 0 to 19 years (n = 41), 226 months; in age group 20 to 49 years (n = 263), 106 months; in age group 50 to 59 years (n = 49), 76 months; and for older patients (n = 26), 39 months. Projected survival at 10 and 15 years was 42% and 29%, respectively. Patient age, World Health Organization (WHO) performance status, tumor computed tomography (CT) contrast enhancement, mental changes, or initial corticosteroid dependency were significant independent prognostic factors (P < .05), while histologic subgroup, focal deficits, presence of seizures, prediagnostic symptom duration, tumor category, and tumor stage were not. Patients aged 20 to 49 years with no independent negative prognostic factors (n = 132) had a median survival time of 139 months versus 41 months in patients with two or more factors (n = 33). Patients who presented with symptoms of expansion (n = 97) survived longer when resected (P < .03); otherwise no survival benefit was associated with initial tumor resection compared with biopsy. Intraarterial chemotherapy and radiation doses more than 55 Gy were not associated with prolonged survival. Among 66 reoperated patients, 45% progressed to high-grade histology within 25 months. 

Conclusion: Prognosis in low-grade glioma following postoperative radiotherapy seems largely determined by the inherent biology of the glioma and patient age at diagnosis.

Int J Radiat Oncol Biol Phys 1994 Oct 15;30(3):567-573

The role of postoperative irradiation in the treatment of oligodendroglioma.

Gannett DE, Wisbeck WM, Silbergeld DL, Berger MS

PURPOSE: Controversy regarding the role of adjuvant radiation therapy for the treatment of oligodendroglioma continues to exist. To better define the utility of postoperative irradiation for this tumor, the experience at the University of Washington was retrospectively examined. METHODS AND MATERIALS: The histologic samples of 63 patients given the diagnosis of oligodendroglioma were reviewed by a panel of neuropathologists and 41 were classified as pure oligodendroglioma. The two treatment groups included 14 patients treated with surgery only and 27 who received surgery and postoperative radiation and were analyzed using univariate and multivariate analysis with respect to prognostic factors, freedom from relapse, and survival. RESULTS: Univariate statistical analysis of 14 clinical variables showed that a poorer prognosis was associated in patients with high cell density (p = .008), necrosis (p = .017), hemiparesis (p = .026), and papilledema (p = .091), while patients presenting with seizures had a better prognosis (p = .0096). Multivariate analysis showed necrosis (p = .001) and hemiparesis (p = .02) to be associated with decreased survival. Multivariate and univariate analysis of the treatment groups found them to be homogenous with respect to prognostic factors. Survival times were significantly longer in the group treated with postoperative irradiation (median survival time 84 vs. 47 months, p = .032). The 5 and 10 year survival rates were 83% and 46%, respectively, for the irradiated patients compared with 51% and 36% for those treated with surgery alone. Freedom from tumor recurrence times were also longer in irradiated patients (median relapse free time 79 vs. 42 months, p = .01). CONCLUSION: Based on the results of this study, we recommend continuing the practice of treating oligodendroglioma with postresection irradiation until a prospective multicenter clinical trial is conducted to thoroughly evaluate the role of postoperative irradiation in the treatment of this tumor.