Resection and survival in glioblastoma multiforme: an RTOG recursive partitioning analysis of ALA study patients

Abstract

The benefit of cytoreductive surgery for glioblastoma multiforme (GBM) is unclear, and selection bias in past series has been observed. The 5-aminolevulinic acid (ALA) study investigated the influence of fluorescence-guided resections on outcome and generated an extensive database of GBM patients with optimized resections. We evaluated whether the Radiation Therapy Oncology Group recursive partitioning analysis (RTOG-RPA) would predict survival of these patients and whether there was any benefit from extensive resections depending on RPA class. A total of 243 per-protocol patients with newly diagnosed GBM were operated on with or without ALA and treated by radiotherapy. Postoperative MRI was obtained in all patients. Patients were allocated into RTOG-RPA classes III-V based on age, KPS, neurological condition, and mental status (as derived from the NIH Stroke Scale). Median overall survival among RPA classes III, IV, and V was 17.8, 14.7, and 10.7 months, respectively, with 2-year survival rates of 26%, 12%, and 7% (p = 0.0007). Stratified for degree of resection, survival of patients with complete resections was clearly longer in RPA classes IV and V (17.7 months vs. 12.9 months, p = 0.0015, and 13.7 months vs. 10.4 months, p = 0.0398; 2-year rates: 21.0% vs. 4.4% and 11.1% vs. 2.6%, respectively), but was not in the small subgroup of RPA class III patients (19.3 vs. 16.3 months, p = 0.14). Survival of patients from the ALA study is correctly predicted by the RTOG-RPA classes. Differences in survival depending on resection status, especially in RPA classes IV and V, support a causal influence of resection on survival.

Fig. 1.

Kaplan-Meier estimates of overall survival of 5-aminolevulinic acid (ALA) study patients according to Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) classes. Abbreviation: CI, confidence interval; O, observed events; N, total number of patients.

Fig. 2.

Kaplan-Meier estimates of overall survival of 5-aminolevulinic acid (ALA) study patients according to Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) class IV, stratified by resection. Abbreviations: O, observed events; N, total number of patients; CR, complete resection; IR, incomplete resection; CI, confidence interval.

Fig. 3.

Kaplan-Meier estimates of overall survival of 5-aminolevulinic acid (ALA) study patients according to Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) class V, stratified by resection. Abbreviations: O, observed events; N, total number of patients; CR, complete resection; IR, incomplete resection; CI, confidence interval.

Fig. 4.

Kaplan-Meier estimates of overall survival of 5-aminolevulinic acid (ALA) study patients according to Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) class III, stratified by resection. Abbreviations: O, observed events; N, total number of patients; CR, complete resection; IR, incomplete resection; CI, confidence interval.