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It is controversial if distant recurrence of glioblastoma is more common after temozolomide (TMZ) concurrent with radiotherapy (RT). Optimal therapy for patients with recurrent disease after RT/TMZ is unclear. Our purpose was to evaluate recurrence patterns in glioblastoma and the effect of treatment at recurrence upon survival.
We performed a retrospective review of 67 patients with newly diagnosed glioblastoma treated with RT/TMZ between 2003-2007. Statistical analyses included Kaplan-Meier method for survival, and multivariate Cox proportional hazards model for the effect of salvage treatment on survival.
58 patients (86.6%) recurred locally; 9 patients (13.4%) had a distant non-contiguous focus of new disease. Median survival(MS) was 17 months; median time-to-progression(TTP) 6.8 months. The local and distant groups had comparable prognostic factors. There was no difference in MS(p=0.35) or TTP(p=0.95) by location of recurrence. At relapse, 26 patients(38.8%) received continuous, dose-intense TMZ, 24(35.8%) other therapy(4.5% RT; 20.9% lomustine+/-procarbazine; 4.5% etoposide; 1.5% conventional TMZ; 4.5% TMZ then lomustine), and 17(25.4%) were untreated. Dose-intense TMZ was associated with prolonged MS compared to all other patients(21.5 months vs. 12.4 months, p=0.019, HR=3.86, 95%CI: 1.81-8.22) and similar to MS with other chemotherapy regimens(18.8 months, p=0.40, HR=1.30, 95% CI: 0.65-2.61).
The pattern of recurrence of glioblastoma treated with RT/TMZ was predominantly local. Second-line treatment with continuous dose-intense TMZ may prolong survival in patients with recurrent glioblastoma. Overall survival is similar to other conventional salvage regimens; however TMZ may be better tolerated. This study is limited by its retrospective nature and potential selection bias. Prospective controlled studies are needed.
Pseudoprogression (psPD) is now recognised following radiotherapy with concurrent temozolomide (RT/TMZ) for glioblastoma multiforme (GBM). The aim of this study was to determine the incidence of psPD following RT/TMZ and the effect of psPD on prognosis.
All patients receiving RT/TMZ for newly diagnosed GBM were identified from a prospective database. Clinical and radiographic data were retrospectively reviewed. Early progression was defined as radiological progression (RECIST criteria) during or within eight weeks of completing RT/TMZ. Pseudoprogression was defined as early progression with subsequent disease stabilization, without salvage therapy, for at least six months from completion of RT/TMZ. The primary outcome was overall survival (Kaplan-Meier) and log rank analysis was used to compare groups.
Out of 111 patients analyzed, 104 were evaluable for radiological response. Median age was 58 years and median follow-up 55 weeks. Early progression was confirmed in 26% and within this group 32% had psPD. Median survival for the whole cohort was 56.7 weeks [95% CI (51.0, 71.3)]. Median survival for patients with psPD was significantly higher than for patients with true early progression (124.9 weeks versus 36.0 weeks, p=0.0286).
Approximately one third of patients with early progression were found to have psPD which was associated with a favourable prognosis. Maintenance TMZ should not be abandoned on the basis of seemingly discouraging imaging features identified within the first three months after RT/TMZ.
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