Survival analysis of HDR brachytherapy versus reoperation versus temozolomide alone: a retrospective cohort analysis of recurrent glioblastoma multiforme

Abstract

ObjectivesTumour recurrence of glioblastoma multiforme (GBM) after initial treatment with surgical resection, radiotherapy and chemotherapy is an inevitable phenomenon. This retrospective cohort study compared the efficacy of interstitial high dose rate brachytherapy (HDR-BRT), re-resection and sole dose dense temozolomide chemotherapy (ddTMZ) in the treatment of recurrent glioblastoma after initial surgery and radiochemotherapy.DesignRetropective cohort study.SettingPrimary level of care with two participating centres. The geographical location was central Germany.ParticipantsFrom January 2005 to December 2010, a total of 111 patients developed recurrent GBM after initial surgery and radiotherapy with concomitant temozolomide. The inclusion criteria were as follows: (1) histology-proven diagnosis of primary GBM (WHO grade 4), (2) primary treatment with resection and radiochemotherapy, and (3) tumour recurrence/progression.InterventionsThis study compared retrospectively the efficacy of interstitial HDR-BRT, re-resection and ddTMZ alone in the treatment of recurrent glioblastoma.Primary and secondary outcome measuresMedian survival, progression free survival and complication rate.ResultsMedian survival after salvage therapy of the recurrence was 37, 30 and 26 weeks, respectively. The HDR-BRT group did significantly better than both the reoperation (p<0.05) and the ddTMZ groups (p<0.05). Moderate to severe complications in the HDR-BRT, reoperation and sole chemotherapy groups occurred in 5/50 (10%), 4/36 (11%) and 9/25 (36%) cases, respectively.ConclusionsCT-guided interstitial HDR-BRT attained higher survival benefits in the management of recurrent glioblastoma after initial surgery and radiotherapy with concurrent temozolomide in comparison with the other treatment modalities. The low risk of complications of the HDR-BRT and the fact that it can be delivered percutaneously in local anaesthesia render it a promissing treatment option for selected patients which should be further evaluated.

Salvage therapy for recurrent glioblastoma multiforme: a multimodal approach combining fluorescence-guided resurgery, interstitial irradiation, and chemotherapy

“…Based on the results of our retrospective study on recurrent glioblastoma, we now combine resurgery and HDR brachytherapy with intensive temozolomide chemotherapy. 2 We used the 1 week on/1 week off temozolomide with a daily dose of 150 mg/m 2 , until documented disease progression or unacceptable toxicity. We chose this more rigorous dose regimen of TMZ according to the publications of Wick et al who reported a 3 months PFS as high as 48% with an overall survival for 12 months of 81%.…”

“…However, a randomized controlled trial might be difficult to conduct given the obvious symptomatic benefits that surgery can provide in many instances and the survival benefits that HDR-BRT has showed in our recent retrospective studies. 2,12 This report compares and contrasts the outcomes and toxicity rates of a multimodal salvage therapy case group to a control group of patients treated with ddTMZ alone. Our CTCAE-based toxicity profile is quite favourably compared to the prior reports and is devoid of any high-grade toxicity, including radiation necrosis, hydrocephalus, intracranial hemorrhage, or meningitis.…”

“…At our institution, retrospective studies of treatment with interstitial highdose temporary brachytherapy using 192 Ir indicated an added survival benefit. 2,12,13 Various chemotherapeutic modalities are employed for recurrent gliomas ranging from a metronomic schedule of temozolomide as dense dose treatment modality to other forms of chemotherapy such as fotemustine, or anti-angiogenic agents such as bevacizumab. 14 In recurrent GBM, temozolomide compared with standard chemotherapy improves time-to-progression and may have benefits on quality of life without increasing adverse events.…”

“…For large tumors with associated edema, mass effect, and clinical symptoms of increased intracranial pressure, tumor debulking followed by brachytherapy may be a treatment option. 2,12,13 Interstitial brachytherapy is the practice of administering therapeutic irradiation by means of a source placed within the tumor being treated. Although focal forms of therapy show promising results in malignant gliomas, yet in several studies, analysing the pattern of recurrence after external beam irradiation, local recurrence within 2 cm of the primary tumor was the most common pattern of failure.…”

Indications and Efficacy of Gamma Knife Stereotactic Radiosurgery for Recurrent Glioblastoma: 2 Decades of Institutional Experience

“…2 Options include repeat surgery, 3–9 chemotherapy (eg, temozolomide, 10–18 irinotecan, 19 or nitrosoureas 20 ), bevacizumab, 21,22 experimental agents, or re-irradiation. 23 Numerous re-irradiation strategies exist, including conventional fractionated external beam radiotherapy (EBRT), 24,25 fractionated stereotactic radiotherapy, 23,26 hypo-fractionated stereotactic radiotherapy, 27 high dose rate (HDR) brachytherapy, 28–30 low dose rate (LDR) brachytherapy, 31–33 or single fraction SRS. Despite numerous options, median survival post-recurrence remains poor at 9–20 months.…”