Population-Based Study of Pseudoprogression after Chemoradiotherapy in GBM

Abstract

Patients with glioblastoma (GBM), the most common primary brain tumor in adults, have a median survival of about one year. In 2005, Stupp et al 1 published the results of a randomized controlled clinical trial in GBM demonstrating a significant survival benefit by adding temozolomide (TMZ) to radiation. In this study, patients with newly diagnosed GBM were treated with low dose temozolomide daily during radiation therapy (termed "concurrent treatment") followed by six monthly cycles of TMZ administered five days out of every 28 ABSTRACT: Introduction: Chemoradiotherapy followed by monthly temozolomide (TMZ) is the standard of care for patients with glioblastoma multiforme (GBM). Case reports have identified GBM patients who experienced transient radiological deterioration after concurrent chemoradiotherapy which stabilized or resolved after additional cycles of adjuvant TMZ, a phenomenon known as radiographic pseudoprogression. Little is known about the natural history of radiographic pseudoprogression. Methods: We retrospectively evaluated the incidence of radiographic pseudoprogression in a population-based cohort of GBM patients and determined its relationship with outcome and MGMT promoter methylation status. Results: Out of 43 evaluable patients, 25 (58%) exhibited radiographic progression on the first MRI after concurrent treatment. Twenty of these went on to receive adjuvant TMZ, and subsequent investigation demonstrated radiographic pseudoprogression in 10 cases (50%). Median survival (MS) was better in patients with pseudoprogression (MS 14.5 months) compared to those with true radiologic progression (MS 9.1 months, p=0.025). The MS of patients with pseudoprogression was similar to those who stabilized/responded during concurrent treatment (p=0.31). Neither the extent of the initial resection nor dexamethasone dosing was associated with pseudoprogression. Conclusions: These data suggest that physicians should continue adjuvant TMZ in GBM patients when early MRI scans show evidence of progression following concurrent chemoradiotherapy, as up to 50% of these patients will experience radiologic stability or improvement in subsequent treatment cycles. RÉSUMÉ: Étude de population sur la pseudoprogression après la chimioradiothérapie dans le glioblastome multiforme. Introduction : Le traitement standard du glioblastome multiforme (GBM) est la chimioradiothérapie suivie de l'administration mensuelle de témozolomide (TMZ). Certains cas de patients atteints de GBM, qui ont présenté une détérioration radiologique transitoire après la chimioradiothérapie qui s'est stabilisée ou s'est résorbée après des cycles additionnels de TMZ, un phénomène connu sous le nom de pseudoprogression radiologique, ont été rapportés. Méthodes : Nous avons évalué rétrospectivement l'incidence de la pseudoprogression radiologique chez une cohorte de patients atteints de GBM tirée de la population et nous avons déterminé sa relation avec le résultat du traitement et avec l'état de méthylation du promoteur MGMT. Résultats : Vingt-cinq des...

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