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Survival Studies with Malignant Glioma
The most accurate way to estimate survival is to classify the patient according to the RTOG classes and then use this table or more simply go here.

Elderly patients, in poor health, who under go a limited resection do very poorly. Anaplastic astrocytoma patients do better than Glioblastoma multiforme patients,  and low grade glioma patients do the best of all (go here and here. Also patients treated with chemotherapy combined with radiation may do better (go here.)

Note  that the grade of the glioma is critical. (see images of the different grades here.) (Grade 1 or 2 are called low grade glioma, grade 3 is anaplastic astrocytoma, and only grade 4 is glioblastoma. (Low grade gliomas are discussed elsewhere, go here.) Grade 3 or anaplastic astrocytoma (AA) are treated similar to grade IV or glioblastoma (GBM) as per NCCN. But the prognosis for a grade III glioma is much better than for grade IV, ( in the original RTOG trial median of 27 months versus median of 8 months.

See survival sections here and here and the studies noted below. Survival for recurrent tumors treated with further surgery here

Also note that there has been more evidence of a survival benefit when chemotherapy (e.g.  temozolomide (Temodar) or thalidomide are added to radiation) see below and in the chemotherapy section (where patients with glioblastoma may have a median survival of 14 - 16 months and a 2 years survival of 26 - 31%.)   A recent trial did not show much benefit from adding cisplatin (go here) another showed real benefit for Avastin plus Camptosar (go here). A recent trial combined radiation with CCNU and Temodar with good results (go here).

Elderly patients have a worse outlook but they may still benefit from radiation and chemotherapy (go here).

Survival analysis following the addition of temozolomide to surgery and radiotherapy in patients with glioblastoma multiforme

Gil-Salu JL . Neurocirugia
2004 Apr;15(2):144-50. Patients were divided into 4 treatment groups: group 1, untreated patients (" no treatment" option was chosen by the family); group 2, patients undergoing surgery only; group 3 (n=24), patients undergoing surgery + standard radiotherapy; group 4 (n=27), patients undergoing surgery + radiotherapy + chemotherapy (temozolomide [TMZ]) (current study group). RESULTS: analysis yielded the following 50% survival cutoffs (weeks): group 1, 16; group 2, 14.29; group 3, 42; group 4, 64.43. see table below
 
Treament for Glioblastoma Multiforme Median Survival
No Surgery 16 weeks
Surgery 14 weeks
Surgery plus Radiation 42 weeks
Surgery plus Radiation plus Temodar 64 weeks


 

Treatment for GBM (J Neurooncol. 2004;67:191 Median Survival
Surgery plus Radiation plus  Thalidomide 63 weeks
Surgery plus Radiation plus Thalidomide plus Temodar 103 weeks

 

Some of the studies that relate to survival are noted below

J Natl Cancer Inst 1993 May 5;85(9):704-10

Recursive partitioning analysis of prognostic factors in three Radiation Therapy Oncology Group malignant glioma trials.

Curran WJ  Fox Chase Cancer Center, Philadelphia, PA 19111.

We used a recursive partitioning technique to analyze survival in 1578 patients entered in three Radiation Therapy Oncology Group malignant glioma trials from 1974 to 1989 that used several radiation therapy (RT) regimens with and without chemotherapy or a radiation sensitizer.  Twenty-six pretreatment characteristics and six treatment-related variables were analyzed. RESULTS: The years). Patients younger than 50 years old were categorized by histology (astrocytomas with anaplastic or atypical foci [AAF] versus glioblastoma multiforme [GBM]) and subsequently by normal or abnormal mental status for AAF patients and by performance status for those with GBM. For patients aged 50 years or older, performance status was the most important variable, with normal or abnormal mental status creating the only significant split in the poorer performance status group. Treatment-related variables produced a subgroup showing significant differences only for better performance status GBM patients over age 50 (by extent of surgery and RT dose). Median survival times were 4.7-58.6 months for the 12 subgroups resulting from this analysis, which ranged in size from 32 to 256 patients.

 

Short course radiotherapy is an appropriate option for most malignant glioma patients.

Kleinberg L, Int J Radiat Oncol Biol Phys 1997 Apr 1;38(1):31-6

Division of Radiation Oncology, The Johns Hopkins Oncology Center, Baltimore, MD 21287-8922, USA. kleinla@wpmail.onc.jhu.edu

The study group includes 219 patients treated during 1975-1993 with 51 Gy in 17 fractions. Patients were retrospectively assigned to six prognostic groups previously identified in a recursive partitioning analysis of the RTOG. The prognostic groups are based on age, histology, performance status, mental status, neurologic function, resection extent, length of symptoms, and RT dose. RESULTS: The six RTOG prognostic groupings were significantly predictive of outcome for patients treated with this shortened regimen (log-rank, p < 0.001). The median survival for our patients by RTOG groups 1-6 were 68, 57, 22, 13, 8, and 5 months, respectively. Two-year survival results were 64, 67, 45, 8, 3, and 3%. The median and two-year survival results for each prognostic grouping were similar to the results achieved by aggressive treatment on RTOG malignant glioma trials for selected patients. Treatment toxicity was uncommon. CONCLUSION: This shortened regimen is an appropriate treatment option for most malignant glioma patients (RTOG groups 4-6), resulting in similar survival as standard regimens with reduced patient effort and cost. Although acute side effects are acceptable and the risk of brain necrosis is low, we do not recommend this treatment to the minority of patients who have a substantial long term survival probability (RTOG groups 1-3) because long term neurocognitive assessment is lacking.

Cancer 1983 Sep 15;52(6):997-1007

Comparison of postoperative radiotherapy and combined postoperative radiotherapy and chemotherapy in the multidisciplinary management of malignant gliomas. A joint Radiation Therapy Oncology Group and Eastern Cooperative Oncology Group study.

Chang.The four options were: (1) control radiation; 6000 rad/6-7 weeks to whole brain; (2) a higher radiation dose; Control dose plus a booster dose of 1000 rad/1-2 weeks to the tumor; (3) control radiation dose plus BCNU (80 mg/m2/day IV X 3 and repeat BCNU every 8 weeks); (4) Control radiation dose plus combination methyl-CCNU (125 mg/m2/day orally X 1 and repeat methyl-CCNU every 8 weeks), and DTIC (150 mg/m2/day IV X 5 and repeat DTIC every 4 weeks). Patients who were younger than age 40 years had an 18-month survival of 64%, patients who were age 40-60 years had an 18-month survival of 20%, and patients who were older than age 60 had an 18-month survival of 8%. Patients with anaplastic astrocytoma had a median survival of 27 months as compared to 8 months for patients with glioblastoma. In further evaluation of any beneficial effect of chemotherapy, it was identified that only among the 40-60-year-old groups, BCNU treated patients appeared to have significantly increased survival than patients in the control groups. Similarly, methyl-CCNU + DTIC was suggestively better than the control.. The higher radiation dose, 7000 rad/8-9 weeks appeared to give no significantly better survival over the control dose option.

Int J Radiat Oncol Biol Phys 1998 Dec 1;42(5):981-7

Outcome in elderly patients undergoing definitive surgery and radiation therapy for supratentorial glioblastoma multiforme at a tertiary care institution.

Mohan DS, Suh JH, Phan JL, Kupelian PA, Cohen BH, Barnett GH

Department of Radiation Oncology, Cleveland Clinic Foundation, OH 44195, USA.

We selected elderly patients (> or = 70 years) who had primary treatment for glioblastoma multiforme at our tertiary care institution from 1977 through 1996. The study group (n = 102) included 58 patients treated with definitive radiation, 19 treated with palliative radiation, and 25 who received no radiation. To compare our results with published findings, we grouped our patients according to the applicable prognostic categories developed by the Radiation Therapy Oncology Group (RTOG): RTOG group IV (n = 6), V (n = 70), and VI (n = 26). Patients were retrospectively assigned to prognostic group IV, V, or VI based on age, performance status, extent of surgery, mental status, neurologic function, and radiation dose. Treatment included surgical resection and radiation (n = 49), biopsy alone (n = 25), and biopsy followed by radiation (n = 28). Patients were also stratified according to whether they were optimally treated (gross total or subtotal resection with postoperative definitive radiation) or suboptimally treated (biopsy, biopsy + radiation, surgery alone, or surgery + palliative radiation). Patients were considered to have a favorable prognosis (n = 39) if they were optimally treated and had a Karnofsky Performance Status (KPS) score of at least 70. RESULTS: The median survival for patients according to RTOG groups IV, V, and VI was 9.2, 6.6, and 3.1 months, respectively (log-rank, p < 0.0004). The median overall survival was 5.3 months. The definitive radiation group (n = 58) had a median survival of 7.3 months compared to 4.5 months in the palliative radiation group (n = 19) and 1.2 months in the biopsy-alone group (p < 0.0001). Optimally treated patients had a median survival of 7.4 months compared to 2.4 months in those suboptimally treated (p < 0.0001). The favorable prognosis group had an 8.4-month median survival compared to 2.4 months in the unfavorable group (p < 0.0001). On multivariate analysis, the KPS, RTOG group, favorable/unfavorable prognosis, and optimal treatment/suboptimal treatment were significant predictors of survival. CONCLUSION: Elderly patients with good performance status (> or = 70 KPS) when treated aggressively with maximal resection and definitive radiation had longer survival than those treated with palliative radiation and biopsy. Aggressive treatment in such patients should be considered.

Int J Radiat Oncol Biol Phys 1993 May 20;26(2):239-44

Influence of location and extent of surgical resection on survival of patients with glioblastoma multiforme: results of three consecutive Radiation Therapy Oncology Group (RTOG) clinical trials.

Simpson JR, Horton J, Scott C, Curran WJ, Rubin P, Fischbach J, Isaacson S, Rotman M, Asbell SO, Nelson JS, et al

Washington University.

Six hundred forty-five patients with a diagnosis of glioblastoma multiforme on central pathological review were analyzed for survival with respect to known prognostic factors, that is, age and Karnofsky Performance Status, as well as extent of surgery, site, and size. Surgical treatment consisted of biopsy only in 17%, partial resection in 64%, and total resection in 19%. Tumors were located in frontal lobe in 43%, temporal lobe in 28%, and parietal lobe in 25%. Maximum tumor diameter as determined on computed tomography or magnetic resonance imaging scans was less than 5 cm for 38%, between 5-10 cm for 56% and greater than 10 cm for 6% of patients. The extent of surgical therapy was the same for tumors greater than 5 or greater than 10 cm, whereas total resection was more often performed for tumors less than 5 cm. The extent of surgery did not appear to vary with age or site. RESULTS: Patients undergoing total resection had a median survival of 11.3 months compared to 6.6 months for patients with a biopsy only. A significant difference in median survival was also found for partial resection versus biopsy only treatment (10.4 vs. 6.6 months). There was no difference in survival for the different tumor sizes. Patients with frontal lobe tumors survived longer than those with temporal or parietal lobe lesions (11.4 months, 9.1 months, and 9.6 months, respectively) (p = 0.01). A Cox multivariate model confirmed a significant correlation of age, Karnofsky Performance Status, extent of surgery, and primary site with survival. The best survival rates occurred in patients who had at least three of the following features: < 40 years of age, high Karnofsky Performance Status, frontal tumors, and total resection (17 months median). CONCLUSION: We conclude that biopsy only yields inferior survival to more extensive surgery for patients with glioblastoma multiforme treated with surgery and radiation therapy.

Int J Radiat Oncol Biol Phys 1998 Dec 1;42(5):977-80

Efficacy of radiotherapy for malignant gliomas in elderly patients.

Villa S, Vinolas N, Verger E, Yaya R, Martinez A, Gil M, Moreno V, Caral L, Graus F

Service of Radiation Oncology, Institut Catala d'Oncologia, L'Hospitalet, University of Barcelona, Spain.

We examined 85 consecutive elderly patients with a histological diagnosis of MG. Age ranged from 65 to 81 years (median 70 years). Glioblastoma multiforme (GBM) was diagnosed in 64 patients (75.3%). Surgical treatment included needle biopsy in 32 patients (37.6%). Median postoperative Karnofsky Performance Status (KPS) was 60 (range: 30-100). Median survival time for all patients was 18.1 weeks. In multivariate analysis, RT was the only independent prognostic variable for survival (HR: 9.1 [95% CI: 4.5-18.7]). Forty-two patients did not start RT mostly due to low KPS (<50). The median survival of the 43 patients who started RT was 45 weeks. In these patients, Cox multivariate analysis indicated that age was independently associated with prolonged survival (HR: 2.85 [95% CI 1.31-6.19]). Median survival of patients age 70 years and younger was 55 weeks compared with 34 weeks for patients older than 70 years. CONCLUSIONS: The overall survival for elderly patients with MG is poor. RT seems to improve survival in patients up to 70 years, but in older patients treated with RT the survival is significantly shorter.

Cancer 1999 Nov 15;86(10):2117-23

The role of tumor resection in the treatment of glioblastoma multiforme in adults.

Kreth FW, Berlis A, Spiropoulou V, Faist M, Scheremet R, Rossner R, Volk B, Ostertag CB

Abteilung Neurochirurgie, Klinikum Grosshadern, Universitat Munchen, Germany.

BACKGROUND: The therapeutic impact of tumor resection is poorly defined. Therefore the current study was conducted. METHODS: A retrospective, 2-institutional study was conducted (1991-1994) to compare the treatment results of stereotactic biopsy plus radiation therapy (99 patients; tumor dose: 60 gray [Gy]) with those of surgical resection plus radiation therapy (126 patients; tumor dose: 60 Gy). Patients were categorized in the Radiation Therapy Oncology Group (RTOG) Classes IV (46 patients), V (157 patients), and VI (22 patients). The resection group and the biopsy group did not differ in terms of age, pretreatment Karnofsky performance status KPS), gender, duration of symptoms, presenting symptoms, tumor location, tumor size, and the frequency of midline shift. Patients in the biopsy group more often were found to have left-sided tumors (P < 0.001). Transient perioperative morbidity and mortality rates were 1% and 1%, respectively, in the biopsy group and 5% and 1.6%, respectively, in the resection group (P > 0.05). The median survival time was 37 weeks for the resection group and 33 weeks for the biopsy group. The difference was not statistically significant (P = 0.09). The most favorable pretreatment prognostic factor was patient age < 60 years (P < 0.01). Tumor resection was highly effective in patients with midline shift (P < 0.01). In patients without midline shift radiation therapy alone was found to be as effective as tumor resection plus radiation therapy (P = 0.5). Patients with midline shift were more likely to have a worse KPS during the course of primary radiation therapy (P < 0.05). CONCLUSIONS: For RTOG Classes IV-VI patients with moderate mass effect of the tumor, radiation therapy alone is a rational treatment strategy. Tumor resection should be performed in patients with pretreatment midline shift whenever possible.

J Neurooncol 1999 Aug;44(1):85-90

Short-course radiotherapy in elderly and frail patients with glioblastoma multiforme. A phase II study.

Jeremic B, Shibamoto Y, Grujicic D, Milicic B, Stojanovic M, Nikolic N, Dagovic A, Aleksandrovic J

Department of Oncology, University Hospital, Kragujevac, Yugoslavia. bjeremic@med.uni-tuebingen.de

PURPOSE: To evaluate efficacy of short-course radiotherapy (RT) in elderly (> or = 60 years) and frail [Karnofsky performance status (KPS) 50-70] patients with glioblastoma multiforme (GBM).RT alone was administered with tumor dose of 45 Gy in 15 daily fractions in 15 treatment days in 3 weeks to a target volume described as tumor visible on CT scan and a 2-cm margin. RESULTS: Forty-four patients were evaluable for this analysis. There were 15 (34%) CR and 11 (25%) PR, making the overall response rate of 60%. Median duration of response was 9 months (range, 2-36 months). Improvement in pretreatment performance status was observed in 20/44 (45%) patients, 5 of which improved their KPS for 20%. Median survival time is 9 months, and 1-4 year survival rates are 39%, 6.8%, 4.5%, and 0, respectively, while median time to tumor progression is 8 months, and 1-4 year progression-free survival rates are 30%, 4.5%, 4.5%, and 0, respectively. Females did significantly better than males, patients with KPS 60-70 did significantly better than those with KPS 50, patients having tumors 4-5 cm did significantly better than those with tumors 6-8 cm as well as did those with more radical surgery when compared to those with biopsy only. On multivariate analysis, only tumor size and extent of surgery were found to independently influence survival. Acute toxicity was generally assessed as mild. One of the 12 (8%) autopsied patients had RT-induced brain necrosis. CONCLUSION: This shortened RT appears to be an effective tool in palliation of elderly and frail patients with GBM. Further studies with more patients are needed before testing it against more aggressive treatment approaches in this patient population.

Neurosurgery 1994 Jan;34(1):62-6; discussion 66-7

The limited value of cytoreductive surgery in elderly patients with malignant gliomas.

Kelly PJ, Hunt C

Department of Neurosurgery, Mayo Clinic, Rochester, Minnesota.

In this retrospective, consecutive series of 128 elderly patients (over 65 years of age) with histologically proven Grade 4 astrocytomas, 88 patients underwent stereotactic biopsy and 40 patients underwent stereotactic volumetric resection of the mass lesion defined by contrast enhancement on computed tomography. There were no significant differences in age (average age in the biopsy group, 71.6 yr; resection group, 70.15 yr) or Karnofsky Performance Scores (biopsy group, 84.33; resection group, 83.88) between the two groups. Four of the biopsy patients and one of the resection patients died within 30 days of surgery. The overall mean survival was 126 days; 108 days (15.4 wk) in the patients who had biopsies and 189 days (27 wk) in the patients who had resections. Radiation therapy was completed in 62 of the patients who had biopsies (mean survival, 118 d or 16.9 wk) and 34 of the patients undergoing resection (mean survival, 210 d or 30 wk) (log rank P = 0.0215; Smirnov P = 0.006). Although some prolongation of survival is noted after resection (more than after a biopsy) in selected patients over 65 years of age, that benefit is modest.

Am J Clin Oncol 1991 Oct;14(5):365-70

Long-term survival in treated anaplastic astrocytomas. A report of combined RTOG/ECOG studies.

Fischbach AJ, Martz KL, Nelson JS, Griffin TW, Chang CH, Horton J, Nelson DF

Department of Radiation Therapy, LDS Hospital, Salt Lake City, Utah 84143.

This report evaluates the long-term survival of patients with histologically confirmed anaplastic astrocytoma on several combined RTOG (Radiation Therapy Oncology Group) studies. Median survival for patients treated with RT only is 3.0 years. Median survival for patients treated with RT + Chemo is 2.3 years, and for patients treated with RT + Chemo/Miso is 1.2 years. Five-year survival rates are 35% for patients treated with RT only, 29% for patients treated with RT + Chemo, and 24% for patients treated with RT + Chemo/Miso. Age and performance status have been identified in previous studies as important prognostic variables and are confirmed in this analysis. Patients treated with misonidazole had a significantly worse prognosis after adjustment for differences in prognostic factors. Addition of chemotherapy did not improve survival except in less favorable prognostic categories. In general, more aggressive treatment regimens are associated with decreased survival compared to conventional postoperative irradiation.

J Clin Oncol 1997 Sep;15(9):3129-40

Survival, prognostic factors, and therapeutic efficacy in low-grade glioma: a retrospective study in 379 patients.

Lote K, Egeland T, Hager B, Stenwig B, Skullerud K, Berg-Johnsen J, Storm-Mathisen I, Hirschberg H

Department of Oncology, Norwegian Radium Hospital, Oslo, Norway.

A total of 379 patients with histologic intracranial low-grade glioma received post-operative radiotherapy (n = 361) and intraarterial carmustine (BCNU) chemotherapy (n = 153). Median survival (all patients) was 100 months (95% confidence interval [CI], B7 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.