Multifocal Glioblastoma Multiforme Eric Wing Sun Tam The

Multifocal Glioblastoma Multiforme Eric Wing Sun Tam The Chinese University of Hong Kong

The Patient n n n n n E. C. F 71 Presented with ataxia and poor penmanship 1 episode of focal motor seizure of left leg Hemochromatosis, No PMH of Malignancy FH of malignancy 4/5 Iliopsoas and hamstrings Unsteady; wide-based gait MRI showed multiple homogenously brightly enhancing masses CT torso, mammogram negative

Differential Diagnosis n n n CNS Lymphoma Multiple Metastases Multifocal Glioblastoma

Differential Diagnosis n CNS Lymphoma Multiple Metastases n Multifocal Glioblastoma n

Multifocal GBM - Definition n Batzdorf et al. (1963) distinguish between "Multicentric" and "Multifocal" Showalter et al. (2007) suggests that "the clinical utility of this. . . may be scant. " Lim et al. (2007) hypothesize that multifocal GBM is a subtype of GBM arising from Subventricular zone (SVZ) stem cells

Questions 1. 2. Does surgical resection prolong survival in patients with conventional glioblastoma? Does surgical resection prolong survival in patients with multifocal glioblastoma?

Design of these studies n volumetric or non-volumetric ways

Non-Volumetric Studies

Sanai et al. Surgery = Increased Survival Surgery = No Increased Survival

Non-volumetric studies Surgery = Increased Survival

Surgery better than Biopsy - WHO Grade IV, p<0. 05 in multivariate Study Year Shibamoto et al. 1990 Simpson et al. 1993 Jeremic et al. 1994 Ushio et al. 2005 Sample size Survival Benefit 135 645 86 105 4 months 4. 7 months 6. 7 months 12 months

Non-volumetric studies Surgery = No Increased Survival

Volumetric Studies

n Sanai et al. (2008)

Limitations of these studies n Study Design q n Selection bias: q n Keles et al. include only patients with KPS >= 70 Assessment method: q q n RCT impossible The true outer border of the tumor? CT and MRI are used in the same study Post-op treatment: q Up to 1/3 of patients in some studies did not receive Chemo

Questions 1. 2. Does surgical resection prolong survival in patients with conventional glioblastoma? Does surgical resection prolong survival in patients with multifocal glioblastoma?

The Role of Surgery in Multifocal GBM n n No RCT to date Surgery (+/-RT/CT) vs Biopsy (+/-RT/CT) q q Pro-surgery: Salvati et al. (2003) Pro-biopsy: Timothy et al. (2007)

Pro-surgery n Salvati et al. (2003) q Sample size: 25 q Both Grade III and Grade IV included q Survival: n n q Biopsy only: mean 2. 8 months Aggressive surgery: mean 9. 5 months Long term survivor

Pro-surgery

Pro-surgery n Limitations: q small sample size q Both group III and IV are included q no selection criteria for surgery q no multivariate analysis q no p-value or CI provided (probably NS) q confounding factors affecting survival n n those who underwent SB only tend not to receive RT those who underwent surgery tend to receive RT

Pro-biopsy n Showalter et al. q q Retrospective cohort 50 out of 497 patients are multifocal GBM WBRT or 3 D-CRT Multivariate analysis n n n No difference in survival regardless of extent of surgery in (p = 0. 238) GTR prolongs time to progression No difference in survival regardless of WBRT or 3 D-CRT (p = 0. 331)

Pro-conservative treatment n Limitations q q Primary purpose is not to assess the role of surgery in multifocal GBM No description of how to determine GTR or STR

Conclusions n n n Multifocal GBM is likely a more migratory and invasive type of GBM arising from SVZ stem cells Controversy still exists regarding the role of surgery in prolonging survival in conventional GBM Surgery probably prolongs survival, albeit modestly, in conventional GBM based on accumulating evidence Limited data on whether surgery prolongs survival in multifocal GBM Attaining gross (close to) total resection in multifocal GBM is difficult and thus surgery may be of limited value in multifocal GBM

Acknowledgements n Dr. Chen

References n n n Lim et al: Relationship of glioblastoma multiforme to neural stem cell regions predicts invasive and multifocal tumor phenotype. Neuro Oncol. 2007 October; 9(4): 424– 429. Nadar Sanai, et al: Glioma Extent of Resection and its impact on patient outcome. Neurosurgery 62: 753 - 766, 2008 Michel Lacroix, et al: A multivariate analysis of 416 patients with glioblastoma multiforme: prognosis, extent of resection, and survival. J Neurosurg 95: 190– 198, 2001 G. Evren Keles et al: Effect of Extent of Resection on Time to Tumor Progression and Survival in Patients with Glioblastoma Multiforme of the Cerebral Hemisphere. Surg Neurol 1999; 52: 371– 9 Timothy N. Showalter et al: Multifocal Glioblastoma Multiforme: Prognostic Factors and Patterns of Progression. Int. Journal of Radiation Oncology 69: 820 -824, 2007 Salvati et al. Multicentric glioma: our experience in 25 patients and critical review of the literature. Neurosurg Rev. 2003 Oct; 26(4): 275 -9. Epub 2003 Jul 26.