Generation and validation of a prognostic score to predict outcome after re-irradiation of recurrent glioma.
ABSTRACT Re-irradiation using high-precision radiation techniques has been established within the clinical routine for patients with recurrent gliomas. In the present work, we developed a practical prognostic score to predict survival outcome after re-irradiation. Patients and methods. Fractionated stereotactic radiotherapy (FSRT) was applied in 233 patients. Primary histology included glioblastoma (n = 89; 38%), WHO Grade III gliomas (n = 52; 22%) and low-grade glioma (n = 92; 40%). FSRT was applied with a median dose of 36 Gy in 2 Gy single fractions. We evaluated survival after re-irradiation as well as progression-free survival after re-irradiation; prognostic factors analyzed included age, tumor volume at re-irradiation, histology, time between initial radiotherapy and re-irradiation, age and Karnofsky Performance Score. Results. Median survival after FSRT was 8 months for glioblastoma, 20 months for anaplastic gliomas, and 24 months for recurrent low-grade patients. The strongest prognostic factors significantly impacting survival after re-irradiation were histology (p < 0.0001) and age (< 50 vs. ≥ 50, p < 0.0001) at diagnosis and the time between initial radiotherapy and re-irradiation ≤ 12 vs. > 12 months (p < 0.0001). We generated a four-class prognostic score to distinguish patients with excellent (0 points), good (1 point), moderate (2 points) and poor (3-4 points) survival after re-irradiation. The difference in outcome was highly significant (p < 0.0001). Conclusion. We generated a practical prognostic score index based on three clinically relevant factors to predict the benefit of patients from re-irradiation. This score index can be helpful in patient counseling, and for the design of further clinical trials. However, individual treatment decisions may include other patient-related factors not directly influencing outcome.
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ABSTRACT: To determine aggregate outcomes and prognostic covariates in patients with recurrent glioma enrolled onto phase II chemotherapy trials. Patients from eight consecutive phase II trials included 225 with recurrent glioblastoma multiforme (GBM) and 150 with recurrent anaplastic astrocytoma (AA). Their median age was 45 years (range, 15 to 82 years) and their median Karnofsky performance score was 80 (range, 60 to 100). Prognostic covariates were analyzed with respect to tumor response, progression-free survival (PFS), and overall survival (OS) by multivariate logistic and Cox proportional hazards regression analyses. Overall, 34 (9%) had complete or partial response, whereas 80 (21%) were alive and progression-free at 6 months (APF6). The median PFS was 10 weeks and median OS was 30 weeks. Histology was a robust prognostic factor across all outcomes. GBM patients had significantly poorer outcomes than AA patients. The APF6 proportion was 15% for GBM and 31% for AA, whereas the median PFS was 9 weeks for GBM and 13 weeks for AA. Results were also significantly poorer for patients with more than two prior surgeries or chemotherapy regimens. Histology is a dominant factor in determining outcome in patients with recurrent glioma enrolled onto phase II trials. Future trials should be designed with separate histology strata.Journal of Clinical Oncology 09/1999; 17(8):2572-8. · 18.04 Impact Factor
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ABSTRACT: Reirradiation is a treatment option for recurrent high-grade glioma with proven but limited effectiveness. Therapies directed against vascular endothelial growth factor have been shown to exert certain efficacy in combination with chemotherapy and have been safely tested in combination with radiotherapy in a small cohort of patients. To study the feasibility of reirradiation combined with bevacizumab treatment, the toxicity and treatment outcomes of this approach were analyzed retrospectively. After previous treatment with standard radiotherapy (with or without temozolomide) patients with recurrent malignant glioma received bevacizumab (10 mg/kg intravenous) on Day 1 and Day 15 during radiotherapy. Maintenance therapy was selected based on individual considerations, and mainly bevacizumab-containing regimens were chosen. Patients received 36 Gy in 18 fractions. The data of the medical charts of the 30 patients were analyzed retrospectively. All were irradiated in a single institution and received either bevacizumab (n = 20), no additional substance (n = 7), or temozolomide (n = 3). Reirradiation was tolerated well, regardless of the added drug. In 1 patient treated with bevacizumab, a wound dehiscence occurred. Overall survival was significantly better in patients receiving bevacizumab (p = 0.03, log-rank test). In a multivariate proportional hazards Cox model, bevacizumab, Karnovsky performance status, and World Health Organization grade at relapse turned out to be the most important predictors for overall survival. Reirradiation with bevacizumab is a feasible and effective treatment for patients with recurrent high-grade gliomas. A randomized trial is warranted to finally answer the question whether bevacizumab adds substantial benefit to a radiotherapeutic retreatment setting.International journal of radiation oncology, biology, physics 10/2010; 82(1):67-76. · 4.59 Impact Factor
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ABSTRACT: Recurrent malignant gliomas have a very poor prognosis. This trial aimed to evaluate the benefits of reirradiation in case of recurrent glioblastoma multiforme (GBM) using hypofractionated stereotactic radiotherapy (hFSRT) after primary high-dose percutaneous irradiation. Between 1998 and 2008, 53 patients with recurrent GBM were treated by hFSRT based on CT and MR imaging. At the time of recurrence, a median total dose of 30 Gy (20-60 Gy) was delivered in median fractions of 3 Gy/day (2-5Gy). The reirradiation was well tolerated (no acute or late toxicity > grade 2), despite the relatively large median tumor volume (35.01 ml). Karnofsky Performance Score was the strongest predictor for survival after reirradiation (p = 0.0159). Tumor volume (p = 0.4690), patient age (p = 0.4301), second operation (p = 0.6930), and chemotherapy (p = 0.1466) at the time of reirradiation did not affect survival. After hFSRT, the median survival was 9 months, and the 1-year progression-free survival (PFS) amounted to 22%.The median overall survival from initial diagnosis was 27 months. 1-year survival from first diagnosis was 83%, 2-year survival 45%. The median time to progression from the end of initial irradiation to recurrence was 12 months. 1-year PFS before reirradiation was 40%. hFSRT as a secondary treatment of recurrent GBM is a feasible and effective treatment option. Only minor side effects were observed with prolonged life expectancy of 9 months.Strahlentherapie und Onkologie 04/2009; 185(4):235-40. · 4.16 Impact Factor