We reviewed with interest the article entitled as “The impact of surgery on the survival
of patients with recurrent glioblastoma” in this issue of AJNS. This case–control
study evaluates the impact of surgery on the survival of the patients with recurrent
glioblastoma over a 5-year period. One hundred and fifty-seven cases of recurrent
glioblastoma are enrolled, and the baseline characteristics and survival of the patients
who had at least one new tumor resection followed by chemotherapy (reoperation group,
n = 59) are compared with those who received only medical treatment for recurrence
(no-reoperation group, n = 98). The study concludes that repeated surgery for those
patients with recurrent glioblastoma who have a good functional status (the WHO performance
status of 0 or 1 and KPS score > 70) helps achieve prolonged survival with an acceptable
complication rate given the overall poor prognosis of glioblastoma multiforme (GBM).
The treatment of recurrent glioblastoma is one of the most challenging issues in neuro-oncology
practice. Patients with recurrent GBM usually face a rapid decline in performance
status, quality of life, neurocognitive adverse effects from previous treatments,
and median overall survival <1 year.[[1]] Several studies have confirmed a role for performance status, age, focal versus
multifocal disease, smaller preoperative tumor size, and favorable tumor location
with a greater likelihood of complete and safe resection as predictors of improved
survival.[[2]],[[3]],[[4]]
Although re-radiation, repeated resection, antivascular endothelial growth factor
(VEGF) agents, and chemotherapy are still the most common used therapies for treating
recurrent glioblastoma, the clinical benefit from these treatments is still not well
established and is limited due to retrospective study designs and lack of randomization.[[5]]
There is a growing body of evidence suggesting that a personalized therapeutic approach
for the stratification of glioblastoma patients to novel treatment regimens is necessary
to improve survival rates for glioblastoma patients. Indeed, genetic profiling of
glioblastoma samples has revealed aberrant expression of several potential therapeutic
targets including a number of receptor tyrosine kinases (EphA3, EGFR, VEGF, platelet-derived
growth factor receptors, and MET),[[6]],[[7]] however, there has been variable and limited success rates for clinical application
of inhibitors of these targets as anticancer therapy have been reported. This elucidates
that a better understanding of the basic biology of GBM is required so that additional
targets can be identified. The heterogeneity in glioblastoma is both intertumoral
and intratumoral, with each tumor presenting a complex heterogeneous setting of cell
biology. The resistance of GBM to current aggressive chemoradiotherapy can be attributed
to the tumor's extensive cellular heterogeneity and the presence of multiple subclonal
populations that invariably either respond to or escape therapy, regenerating treatment-refractory
recurrent tumor. Current models for the study of GBM fail to directly address the
problem of GBM recurrence and continue to focus efforts on understanding primary,
treatment-naive tumor biology. New models of GBM must address both spatial and temporal
intratumoral heterogenicity. A detailed understanding of the evolutionary dynamics
of tumor progression will provide insight into the associated molecular genetic mechanisms
underlying GBM recurrence.
Despite the promising outlook for personalized therapeutic approaches to treating
GBM patients, identification of therapeutics that can cross the BBB, while maintaining
therapeutic concentrations, still remains a challenge. Furthermore, although targeted
therapies show limited efficacy as single agents, the combination of several targeted
therapies may be of benefit to GBM patients. Thus, further studies are required both
to identify new therapeutic targets and to design novel therapeutic strategies for
the treatment of glioblastoma.
The identification of pathways governing therapy resistance in clonal subpopulations
will allow clinicians to offer patients therapeutics that selectively target the specific
subclonal populations that drive GBM recurrence in each individual patient, leading
to improved prognosis and outcomes.[[8]]
Last but not least, an interdisciplinary dedicated team, including neuro-oncology,
radiology, radiation oncology, and neurosurgery, is needed to manage the patients
who suffer from glioblastoma recurrence, a multifaceted problem that needs multidisciplinary
management. We would encourage constituting institutional dedicated teams within referral
centers for a deep understanding and handling of recurrent glioblastoma.
