GROSS-TOTAL RESECTION OF MALIGNANT GLIOMAS IN ELDERLY PATIENTS: IMPLICATIONS IN SURVIVAL

Background

• The relative incidence of glioblastoma multiforme (GBM) among individuals older than 70 years of age has risen as a result of an increasing elderly population and an improvement in diagnostic procedures.
• Because elderly patients are usually excluded from treatment trials, there is no consensus on current management of GBM in this population. Options vary from palliative care to aggressive multimodal treatment, often depending on the individual experience of clinicians rather than on scientific evidence.
• Although some researchers have reported a higher incidence of neurological and systemic complications in elderly patients undergoing extensive surgery, others have defended aggressive treatment, including gross total resection, radiotherapy, and chemotherapy.

Objective

To analyze the outcome of elderly patients (>65 years) after surgery and radiochemotherapy, compared to a younger collective (≤65 years).

Title/Citation

Martinez R, Janka M, Soldner F, Behr R. Gross-total resection of malignant gliomas in elderly patients: implications in survival. Zentrabl Neurochir. 2007;68:176-181.

Funding

No financial support was reported.

Trial design

Retrospective

Enrollment

138 consecutive patients with malignant glioma between 1999 and 2004.

Inclusion criteria

138 patients surgically treated; 98 patients with GBM, 25 anaplastic astrocytomas, 15 anaplastic mixed gliomas.

Exclusion criteria

Exclusion criteria were not provided.

Study groups

• Patients with malignant glioma ≤65 years of age.
• Patients with malignant glioma >65 years of age.

End points

• Neurological status (pre- and postoperative).
• Sawaya Functional Grade (SFG)
• Neurological Performance Score (NPS)
• Karnofsky Performance Status (KPS)
• Neurological deficits at presentation.
• Extent of surgical procedure.
• Preoperative medical risk factors.
• Postoperative complications.
• Neurological functional (directly induced neurological impairment).
• Neurological regional (circumscribed to the surgical site without producing neurological deficit).
• Systemic complications (all other non-central nervous system-related deteriorations of condition).
• Survival time.

Statistical analyses

• Kaplan-Meier method for time to relapse and cumulative survival.
• Log-rank test to compare survival curves for different groups.
• Fisher Yates corrected or Mehta-Patel corrected Chi-square tests and Tarone trend test to estimate significance levels for variables.
• Mann-Whitney U-test to determine correlations between qualitative variables.
• Configuration frequency analysis to evaluate qualitative variables between age-based clusters.
• Cox proportional hazard model for multivariate analysis of survival time and therapy modalities.
• Method of Grambsch and Therneau for proportionality.

Baseline characteristics

• 138 patients surgically treated; 98 patients with GBM, 25 anaplastic astrocytomas, 15 anaplastic mixed gliomas.
• 76 patients ≤65 years, 62 patients >65 years.
• 79 patients were male, 59 were female.
• Mean age at diagnosis 58.3 years.
• In both groups, tumors were mostly located in frontal and temporal lobes, followed by parietal and occipital areas.
• Tumors affecting both hemispheres were rarely observed (6.5% and 4.3% for younger and older patients, respectively).
• Higher percentage of patients >65 years had medical risk factors, including hypertension, cardiac pathology, diabetes, pulmonary disease, gastric disease, and urinary disease.
• Regarding neurological signs at diagnosis, psychosyndrome was observed more frequently in older patients, whereas seizures occurred less frequently in younger patients with astrocytoma grade III.
• Postoperative radiotherapy was performed in 89.5% and 91.9% of older and younger patients, respectively.
• Chemotherapy was administered to 45.1% and 52.6% of older and younger patients, respectively.

End points

Patients with Malignant Glioma ≤65 Years of Age:

• Neurological status (pre- and postoperative).
• Younger patients more frequently displayed NPS grade 0 and 1.
• Neurological deficits at presentation.
• Seizures occurred more frequently in younger patients.
• Extent of surgical procedure.
• No differences between groups with respect to type of procedure.
• Gross total resection (vs biopsy or subtotal resection) was associated with longer survival in both groups.
• Preoperative medical risk factors included in baseline characteristics.
• Postoperative complications (neurological and systemic).
• The most common complications were of neurologic origin, affecting 3.9% of patients.
• Regional neurological complications occurred in 5.2% of patients, mostly consisting of cerebrospinal fluid (CSF) leak (3.9%), followed by brain edema (1.3%).
• 1 case of surgery-related death from therapy refractory brain edema.
• Survival time.
• Survival rate at 12 and 24 months was 59.2% and 31.7%, respectively.
• Median survival was 14 months, and 8.5 months when considering only GBMs.
• In subgroups of grade III and IV astrocytoma, younger patients survived significantly longer than older patients.

Patients with Malignant Glioma >65 Years of Age:

• Neurological status (pre- and postoperative).
• Elderly patients had lower KPS, higher SFG, and higher NPS.
• Neurological deficits at presentation.
• Psychosyndrome was observed more frequently in older patients.
• Preoperative medical risk factors included in baseline characteristics.
• Postoperative complications (neurological and systemic).
• The most common complications were of neurologic origin, affecting 4.8% of patients.
• Regional neurological complications occurred in 6.5% of patients, mostly consisting of CSF leak (3.2%), followed by brain edema (3.2%).
• Older patients who had diabetes showed more regional neurological complications (especially CSF leak).
• Several complications occurred significantly more frequently in older vs younger patients: psychosyndrome (19.3% vs 5.3%), aphasia/dysphagia (6.5% vs 2.6%), and cardiac pathology (17.7% vs 1.3%).
• Survival time
• Survival rate at 12 and 24 months was 9.6% and 0%, respectively.
• Median survival was 6 months, and 4 months when considering only GBMs.

Conclusion

Gross total resection of malignant gliomas in elderly patients is associated with a survival benefit without increased morbidity.

Study strengths/ limitations

Strengths:

• The relationship between extent of resection and survival time was examined.
• Results contribute to evidence that gross total resection (vs biopsy or subtotal resection) offers elderly patients a survival advantage.
• Results confirm the well-established relationship between age, KPS, and survival.
• Survival benefit was found to be independent of the neurological status, KPS, and medical risk factors at diagnosis.
• Significance levels in the elderly group were comparable to those observed in the younger group.

 
Limitations

• Given the retrospective nature of the trial, it remains unclear whether surgical intervention offers similar risks and benefits in older vs younger patients with GBM.
• Insufficient information was provided regarding exclusion and inclusion criteria.
• For comparison purposes, historical data on survival of older patients (>65 years of age) who undergo less aggressive treatment for malignant glioma should have been included.
• Researchers conclude that gross total resection of malignant gliomas in elderly patients is not associated with increased morbidity, however, results indicate that several complications occurred significantly more frequently in older vs younger patients.

Implications

• Gross total resection may offer older patients a survival benefit and, therefore, should not be excluded in an elderly population on the basis on age alone.
• A multidisciplinary evaluation of prognostic factors (eg, neurological and neurocognitive status, KPS, tumor-related characteristics) should be considered in order to individualize the therapeutic approach.