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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.
To analyze our experience with a second radiosurgical treatment for brain arteriovenous malformations (BAVMs) after an unsuccessful first radiosurgical treatment.
Between 1993 and 2000, 242 patients were treated by the Toronto Sunnybrook Regional Cancer Center using a LINAC system. Fifteen of these patients required a second radiosurgical intervention due to the failure of the first procedure. Data was collected on baseline patient characteristics, BAVM features, radiosurgery treatment plan and outcomes. Brain arteriovenous malformation obliteration was determined by follow-up MRI and angiography and the obliteration prediction index (OPI) calculated according to a previously established formula.
The median interval between the first and second treatment was 46 months (range 39-109). The median follow-up after the second procedure was 39 months (range 26 to 72). The mean BAVM volume before the first treatment was 8.9cm3 (range 0.3-21) and before the second treatment was 3.6cm3 (range 0.2-11.6). The mean marginal dose during the first treatment was 18Gy (range 12-25) and during the second treatment was 16Gy (range 12-20). After the second treatment, nine patients had obliteration of their BAVM confirmed by angiography and one patient had obliteration confirmed by MRI, resulting in an obliteration rate of 66.6%, which is very comparable to that predicted by the OPI (65%). After the second treatment two patients had a radiation-induced complication (13.3%).
Retreatment of BAVM using a second radiosurgery procedure is a safe and effective option that offers the same rate of success as the initial radiosurgery and an acceptable risk of radiation-induced complication.
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