Pseudoprogression and pseudoresponse in the management of high-grade glioma : optimal decision timing according to the response assessment of the neuro-oncology working group

Abstract

Objective: We evaluated pseudoprogression (PsPD) following radiation therapy combined with concurrent temozolomide (TMZ), and we assessed pseudoresponse following anti-angiogenic therapy for patients with recurrent disease using the Response Assessment of the Neuro-Oncology Working Group.

Methods: Patients who were pathologically confirmed as having high-grade glioma received radiotherapy with concurrent TMZ followed by adjuvant TMZ. Bevacizumab (Avastin) with CPT-11 were used as a salvage option for cases of radiologic progression. Magnetic resonance imaging (MRI) was routinely performed 1 month after concurrent radiochemotherapy (CRT) and every 3 months thereafter. For cases treated with the bevacizumab-containing regimen for progressive disease, MRI was performed every 2 months.

Results: Of 55 patients, 21 (38%) showed radiologic progression within 4 weeks after CRT. Of these patients, 16 (29%) showed progression at second post-CRT MRI (etPD) and five (9%) showed improvement (PsPD). Seven of thirty-four initially non-progressed patients showed progression at the second post-CRT MRI (ltPD). No difference in survival was observed between the etPD and ltPD groups (p=0.595). Five (50%) of ten patients showed a radiological response after salvage bevacizumab therapy. Four of those patients exhibited rapid progression immediately after discontinuation of the drug (drug holiday).

Conclusion: Twelve weeks following treatment could be the optimal timing to determine PsPD or true progression. MRI with gadolinium enhancement alone is not sufficient to characterize tumor response or growth. Clinical correlation with adequate follow-up duration and histopathologic validation may be helpful in discriminating PsPD from true progression.

Keywords: Concurrent radiochemotherapy; High-grade glioma; Pseudoprogression; Pseudoresponse.

Fig. 1

Kaplan-Meier curve showing overall survival of the etPD and ltPD groups. etPD : early true progression, ltPD : late true progression.

Fig. 2

Kaplan-Meier curve showing overall survival of the MGMT methylation and unmethylation groups (available data, p=0.178). MGMT : O-6 methylguanine-DNA methyltransferase.

Fig. 3

Gadolinium-enhanced MRI of a patient with pseudoresponse (patient 4 of Table 3). The patient had enhancing lesion at posterior resection margin located at left basal ganglia and insula [A, 2 weeks before bevacizumab (BVZ)]. The lesion had nearly disappeared after the administration of BVZ (B). A month after discontinuation of BVZ, rapid progression with edema was seen in MRI (C). The lesion was confirmed as a true progression in subsequent surgical resection.