Generation and Validation of a Prognostic Score to Predict Outcome after Re-irradiation of Recurrent Glioma

University Hospital of Heidelberg, Department of Radiation Oncology , Heidelberg , Germany.
Acta oncologica (Stockholm, Sweden) (Impact Factor: 3). 06/2012; 52(1). DOI: 10.3109/0284186X.2012.692882
Source: PubMed


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.

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).

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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Available from: Thomas Welzel, Apr 27, 2015
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    • "For all patients, PRS was measured from the first day of re-irradiation until death or last follow-up and progression-free survival until progressive disease or death (otherwise censored). The Heidelberg score was determined as described elsewhere [7]. A two-tailed p-value ≤ 0.05 was considered significant. "
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    ABSTRACT: Purpose Re-irradiation has been shown to be a valid option with proven efficacy for recurrent high-grade glioma patients. Overall, up to now it is unclear which patients might be optimal candidates for a second course of irradiation. A recently reported prognostic score developed by Combs et al. may guide treatment decisions and thus, our mono-institutional cohort served as validation set to test its relevance for clinical practice. Patients and methods The prognostic score is built upon histology, age (< 50 vs. ≥ 50 years) and the time between initial radiotherapy and re-irradiation (≤ 12 vs. > 12 months). This score was initially introduced to distinguish patients with excellent (0 points), good (1 point), moderate (2 points) and poor (3–4 points) post-recurrence survival (PRS) after re-irradiation. Median prescribed radiation dose during re-treatment of recurrent malignant glioma was 36 Gy in 2 Gy single fractions. A substantial part of the patients was additionally treated with bevacizumab (10 mg/kg intravenously at d1 and d15 during re-irradiation). Results 88 patients (initially 61 WHO IV, 20 WHO III, 7 WHO II) re-irradiated in a single institution were retrospectively analyzed. Median follow-up was 30 months and median PRS of the entire patient cohort 7 months. Seventy-one patients (80.7%) received bevacizumab. PRS was significantly increased in patients receiving bevacizumab (8 vs. 6 months, p = 0.027, log-rank test). KPS, age, MGMT methylation status, sex, WHO grade and the Heidelberg score showed no statistically significant influence on neither PR-PFS nor PRS. Conclusion In our cohort which was mainly treated with bevacizumab the usefulness of the Heidelberg score could not be confirmed probably due to treatment heterogeneity; it can be speculated that larger multicentric data collections are needed to derive a more reliable score.
    Full-text · Article · Jun 2014 · Radiation Oncology
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    • "The tumour and treatment volumes were identified as prognosis factor for the post-SRS survival in the bivariate analyses but not in the multivariate analyses. Kong et al. [13] and Combs et al. [28] obtained the similar results, although the latter treated patients with fractionated stereotactic radiotherapy instead of SRS. According to our statistical analyses, higher KPS score was statistically significant correlated with post-SRS survival . "
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    ABSTRACT: Purpose: To analyse the survival after salvage radiosurgery and to identify prognostic factors. Methods: We retrospectively reviewed 87 consecutive patients, with recurrent high-grade glioma, that underwent stereotactic radiosurgery between 1997 and 2010. We evaluated the survival after initial diagnosis and after reirradiation. The prognostic factors were analysed by bivariate and multivariate Cox regression model. Results: The median age was 48 years old. The primary histology included anaplastic astrocytoma (47%) and glioblastoma (53%). A margin dose of 18 Gy was administered in the majority of cases (74%). The median survival after initial diagnosis was 21 months (39 months for anaplastic astrocytoma and 18.5 months for glioblastoma) and after reirradiation it was 10 months (17 months for anaplastic astrocytoma and 7.5 months for glioblastoma). In the bivariate analyses, the prognostic factors significantly associated with survival after reirradiation were age, tumour and treatment volume at recurrence, recursive partitioning analyses classification, Karnofsky performance score, histology, and margin to the planning target volume. Only the last four showed significant association in the multivariate analyses. Conclusion: stereotactic radiosurgery is a safe and may be an effective treatment option for selected patients diagnosed with recurrent high-grade glioma. The identified prognostic factors could help individualise the treatment.
    Full-text · Article · May 2014 · BioMed Research International
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    • "Thus, it makes sense that several major centers are involved in the generation and validation of a scoring system to predict the benefit of reirradiation in high-grade gliomas. Combs et al. encouraged us kindly to validate the recently presented Heidelberg prognostic score [3] with our independent cohort. However, the subclassification of our patients into the four scoring groups did not demonstrate a convincing correlation with overall survival after reirradiation in visual validation and in log rank test (Figure 4). "
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    ABSTRACT: Purposes: First, to evaluate outcome, the benefit of concurrent chemotherapy and prognostic factors in a cohort of sixty-four high-grade glioma patients who underwent a second course of radiation therapy at progression. Second, to validate a new prognostic score for overall survival after reirradiation of progressive gliomas with an independent patient cohort.Patients and methods: All patients underwent fractionated reirradiation with a median physical dose of 36 Gy. Median planned target volume was 110.4 ml. Thirty-six patients received concurrent chemotherapy consisting in 24/36 cases (67%) of carboplatin and etoposide and in 12/36 cases (33%) of temozolomide. We used the Kaplan Meier method, log rank test and proportional hazards regression analysis for statistical assessment. Median overall survival from the start of reirradiation was 7.7 +/- 0.7 months. Overall survival rates at 6 and 12 months were 60 +/- 6% and 24 +/- 6%, respectively. Despite relatively large target volumes we did not observe any major acute toxicity. Concurrent chemotherapy did not appear to improve outcome. In contrast, female gender, young age, WHO grade III histology, favorable Karnofsky performance score and complete resection of the tumor prior to reirradiation were identified as positive prognostic factors for overall survival. We finally validated a recent suggestion for a prognostic score with our independent but small patient cohort. Our preliminary findings suggest that its ability to discriminate between different prognostic groups is limited. Outcome of our patients was comparable to previous studies. Even in case of large target volumes reirradiation seems to be feasible without observing major toxicity. The benefit of concurrent chemotherapy is still elusive. A reassessment of the prognostic score, tested in this study, using a larger patient cohort is needed.
    Full-text · Article · Jul 2013 · Radiation Oncology
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