Combined salvage therapies for recurrent glioblastoma multiforme: evaluation of an interdisciplinary treatment algorithm.

Glioblastoma multiforme patients presenting with recurrence following multimodality therapy have limited palliative treatment options when the major modalities of therapy including surgery, radiochemotherapy and adjuvant chemotherapy have been exhausted. The authors introduce a clinical and radiological indication-solving algorithm and provide outcome rates of a glioblastoma recurrence cohort. Sixty six consecutive adult patients with recurrent glioblastoma who underwent a combined scheme of salvage treatments consisting of reoperation, high dose rate (HDR) brachytherapy and chemotherapy were included in this prospective study and were compared to a historical control group of 24 recurrent glioblastoma patients who have been treated with intensive temozolomide chemotherapy as the only treatment modality. Median follow-up was 32 months (range 28-36 months). Median survival was 9 months for the entire cohort after salvage treatment and can be translated into a 3-month improvement in survival compared to the control group of patients with glioblastoma recurrence treated with temozolomide alone (P = 0.043). Toxicity and adverse events of reoperation, HDR brachytherapy combined with chemotherapy were quite favourable compared to intensive temomozolomide chemotherapy as the only treatment. Our experience suggests that a combined salvage treatment plan appears to be both feasible and effective and can be considered in selected patients affected by recurrent high grade gliomas. The authors' clinical and radiological indication-solving algorithm may assist in providing the best possible salvage treatment for this difficult population.

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

OBJECTIVES: Several studies have revealed that different salvage treatments in glioblastoma multiforme patients presenting a recurrence have limited palliative treatment options. The aim of this study was to evaluate the utility and limitations of multimodal salvage treatments in recurrent glioblastoma multiforme patients combining 5-aminolevulinic acid (5-ALA) fluorescence-guided resurgery, interstitial irradiation, and dense dose temozolomide chemotherapy (ddTMZ). METHODS: Seventeen consecutive patients with recurrent globlastoma multiforme underwent a combined scheme of salvage treatments including fluorescence-guided reoperation, high dose rate (HDR) brachytherapy, and ddTMZ chemotherapy and were included in this prospective study. This multimodal treatment group was compared with a 1∶1 matched historical control group of 17 patients who have been treated with intensive temozolomide chemotherapy as the only treatment modality. All patients were previously treated with surgery of the primary pathology, concomitant, and adjuvant radiochemotherapy with temozolomide. RESULTS: Median follow-up was 32 months (range: 28-36 months). Median survival was 9 months for the entire cohort after salvage treatment and can be translated into a 3-month improvement in survival compared to the control group of patients with glioblastoma recurrence treated with temozolomide alone (P  =  0·043). Complications rates of multimodal salvage treatment were comparable with the temozolomide control group. DISCUSSION: Our experience suggests that a combined salvage treatment plan have the advantages of all three methods and, thus, provide additional survival benefit and can be considered in selected patients affected by recurrent high grade gliomas. Nonetheless, more cases and additional studies are necessary to further prove the advantages of this multimodal treatment.

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

OBJECTIVES: Tumour 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. DESIGN: Retropective cohort study. SETTING: Primary level of care with two participating centres. The geographical location was central Germany. PARTICIPANTS: From 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. INTERVENTIONS: This study compared retrospectively the efficacy of interstitial HDR-BRT, re-resection and ddTMZ alone in the treatment of recurrent glioblastoma. PRIMARY AND SECONDARY OUTCOME MEASURES: Median survival, progression free survival and complication rate. RESULTS: Median 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. CONCLUSIONS: CT-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.

CT-guided interstitial HDR brachytherapy for recurrent glioblastoma multiforme. Long-term results.

BACKGROUND AND PURPOSE: Recurrences of glioblastoma multiforme (GBM) within previously irradiated volumes pose a serious therapeutic challenge. This retrospective study evaluates the long-term tumor control of recurrent GBM treated with interstitial high-dose-rate brachytherapy (HDR-BRT). PATIENTS AND METHODS: Between 1995 and 2003, 84 patients were treated for recurrent cerebral GBM located within previously irradiated volumes. All patients had received adjuvant external radiotherapy following primary surgery, with a focal dose up to 60 Gy. The median recurrent tumor volume was 51 cm(3) (3-207 cm(3)), and the HDR-BRT consisted of an afterloading (192)Ir implant which delivered a median dose of 40 Gy (30-50 Gy). Catheter implantation was implemented using interactive computed tomography (CT) guidance under local anesthesia and sedoanalgesia. RESULTS: After a median follow-up of 61 months, 5/84 patients (6%) were alive. The median post-BRT survival was 37 weeks, and the median overall survival 78 weeks. Moderate to severe complications occurred in 5/84 cases (6%). CONCLUSION: For patients with recurrences of GBM within previously irradiated volumes, CT-guided interstitial HDR-BRT is a feasible treatment option that can play an important role in providing palliation.