Parametric response map as an imaging biomarker to distinguish progression from pseudoprogression in high-grade glioma - PubMed (original) (raw)

Parametric response map as an imaging biomarker to distinguish progression from pseudoprogression in high-grade glioma

Christina Tsien et al. J Clin Oncol. 2010.

Abstract

Purpose: To assess whether a new method of quantifying therapy-associated hemodynamic alterations may help to distinguish pseudoprogression from true progression in patients with high-grade glioma.

Patients and methods: Patients with high-grade glioma received concurrent chemoradiotherapy. Relative cerebral blood volume (rCBV) and blood flow (rCBF) maps were acquired before chemoradiotherapy and at week 3 during treatment on a prospective institutional review board-approved study. Pseudoprogression was defined as imaging changes 1 to 3 months after chemoradiotherapy that mimic tumor progression but stabilized or improved without change in treatment or for which resection revealed radiation effects only. Clinical and conventional magnetic resonance (MR) parameters, including average percent change of rCBV and CBF, were evaluated as potential predictors of pseudoprogression. Parametric response map (PRM), an innovative, voxel-by-voxel method of image analysis, was also performed.

Results: Median radiation dose was 72 Gy (range, 60 to 78 Gy). Of 27 patients, stable disease/partial response was noted in 13 patients and apparent progression was noted in 14 patients. Adjuvant temozolomide was continued in all patients. Pseudoprogression occurred in six patients. Based on PRM analysis, a significantly reduced blood volume (PRM(rCBV)) at week 3 was noted in patients with progressive disease as compared with those with pseudoprogression (P < .01). In contrast, change in average percent rCBV or rCBF, MR tumor volume changes, age, extent of resection, and Radiation Therapy Oncology Group recursive partitioning analysis classification did not distinguish progression from pseudoprogression.

Conclusion: PRM(rCBV) at week 3 during chemoradiotherapy is a potential early imaging biomarker of response that may be helpful in distinguishing pseudoprogression from true progression in patients with high-grade glioma.

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Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.

Fig 1.

Representative patient with glioblastoma multiforme treated with concurrent temozolomide and radiation. T1 postgadolinium magnetic resonance imaging at (A) baseline and (B) 3 months after treatment showed a significant increase in contrast-enhancing lesion. At resection, pathology was notable for (C) fibrinoid radiation necrosis involving blood vessel wall and (D) predominantly gliotic brain parenchyma with no viable neoplasm, consistent with pseudoprogression.

Fig 2.

Fig 2.

Percent change of relative cerebral blood volume (rCBV) and blood flow (rCBF) 3 weeks after treatment initiation compared with pretreatment values is shown for the entire group (N = 27). Data are presented as mean ± SEM. Statistical significance was assessed at P < .0083 using an analysis of variance and Bonferonni posthoc test for multiple comparisons. SD, stable disease; PD, progressive disease; PP, pseudoprogression.

Fig 3.

Fig 3.

A significant difference in fractional tumor volume with decrease in relative cerebral blood volume (parametric response map [PRM]rCBV−) and relative cerebral blood flow (PRMrCBF−) week 3 chemoradiation versus baseline was noted in patients with pseudoprogression (PP) and progressive disease (PD). There was also a significant difference in PRMrCBV− between patients with stable disease (SD) and PD. Statistical significance was assessed at P < .0083.

Fig 4.

Fig 4.

Gadolinium-enhanced images (column 1), relative cerebral blood volume (rCBV) maps with color scale (column 2), and rCBV histograms (column 3) are shown in a patient with pseudoprogression (A, B) and progression (C, D) at baseline and at week 3 of chemoradiation. Additional reduction in mean rCBV was observed in the patient with progressive disease after therapy.

Fig 5.

Fig 5.

Parametric response map of relative cerebral blood volume (PRMrCBV) color-coded overlay of a patient with (A) pseudoprogression and (C) progressive disease. Voxels were designated red with significant increase in rCBV: blue for a significant decrease in rCBV, and green if they remained statistically unchanged. Corresponding quantitative scatter plot analysis showing the distribution of rCBV at baseline compared with week 3 chemoradiation is shown respectively (B, D).

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