Semantic imaging features predict disease progression and survival in glioblastoma multiforme patients.

BACKGROUND: For glioblastoma (GBM), multiple prognostic factors have been identified. Semantic imaging features were shown to be predictive for survival prediction. No similar data have been generated for the prediction of progression. The aim of this study was to assess the predictive value of the semantic visually accessable REMBRANDT [repository for molecular brain neoplasia data] images (VASARI) imaging feature set for progression and survival, and the creation of joint prognostic models in combination with clinical and pathological information. METHODS: 189 patients were retrospectively analyzed. Age, Karnofsky performance status, gender, and MGMT promoter methylation and IDH mutation status were assessed. VASARI features were determined on pre- and postoperative MRIs. Predictive potential was assessed with univariate analyses and Kaplan-Meier survival curves. Following variable selection and resampling, multivariate Cox regression models were created. Predictive performance was tested on patient test sets and compared between groups. The frequency of selection for single variables and variable pairs was determined. RESULTS: For progression free survival (PFS) and overall survival (OS), univariate significant associations were shown for 9 and 10 VASARI features, respectively. Multivariate models yielded concordance indices significantly different from random for the clinical, imaging, combined, and combined + MGMT models of 0.657, 0.636, 0.694, and 0.716 for OS, and 0.602, 0.604, 0.633, and 0.643 for PFS. "Multilocality," "deep white-matter invasion," "satellites," and "ependymal invasion" were over proportionally selected for multivariate model generation, underlining their importance. CONCLUSIONS: We demonstrated a predictive value of several qualitative imaging features for progression and survival. The performance of prognostic models was increased by combining clinical, pathological, and imaging features.

Validation of an established prognostic score after re-irradiation of recurrent glioma.

BACKGROUND: Re-irradiation (Re-RT) is offered widely in clinical routine, and has been established as a key element in the treatment of recurrent gliomas. At our center, generally re-resection is performed widely by an experienced neurosurgical team. Thus, Re-RT mostly offered to patients with macroscopic residuals or irresectable lesions, is applied later compared to other centers. Therefore, we sought to validate the Combs Prognostic Score developed in 2012 using our independent patient cohort. PATIENTS AND METHODS: We included 199 patients treated from 2002 until April 2016 for recurrent glioma at the Department of Radiation Oncology at the Klinikum Rechts der Isar, Munich. Different concepts of Re-RT were applied. RESULTS: Median follow-up after Re-RT was 2.5 months. Median overall survival (OS) after Re-RT was 7.9 months for WHO IV gliomas, 11.3 months for WHO III gliomas, and 13.6 months for low-grade gliomas (WHO I/II). Univariate analyses confirmed the prognostic factors primary histology (p = 0.001), age (p = 0.002), and time between primary radiotherapy and Re-RT (p < 0.001). We also tested Karnofsky Performance Score (KPS), gender, and neurological symptoms before Re-RT as well as planning target volume and found only KPS also significant at p < 0.001. Comparing the prognostic score groups, the outcome was highly statistically significant at p < 0.001. CONCLUSION: In our analysis, we validated the Combs Prognostic Score. Validation in this independent large patient cohort confirms the significance of the score for glioma recurrences. Thus, the role of the Combs Prognostic Score might be an essential component of future clinical decision making and patient stratification.

Moving Second Courses of Radiotherapy Forward: Early Re-Irradiation After Surgical Resection for Recurrent Gliomas Improves Efficacy With Excellent Tolerability.

BACKGROUND: Generally, re-irradiation (Re-RT) is offered to patients with glioma recurrences with macroscopic lesions. Results are discussed controversially, and some centers postulate limited benefit of Re-RT. Re-RT is generally offered to tumors up to 4 cm in diameter. Re-resection is also discussed controversially; however, recent studies have shown significant benefit. OBJECTIVE: To combine proactive re-resection and early Re-RT in patients with recurrent glioma. METHODS: We included 108 patients treated between 2002 and 2016 for recurrent glioma. All patients underwent surgical resection for recurrence; Re-RT was applied with a median dose of 37.5 Gy (range 25 Gy-57Gy/equivalent dose in 2Gy fractions [EQD2]) with high-precision techniques. All patients were followed prospectively in an interdisciplinary follow-up program. RESULTS: Median follow-up after Re-RT was 7 mo. Median survival after surgery and Re-RT was 12 mo (range 1-102 mo). Complete resection had a significant impact on the outcome (P = .03). The strongest predictors of outcome were MGMT-promotor methylation and Karnofsky Performance Score and time interval between primary and second RT. CONCLUSION: Proactive resection of tumor recurrences combined with early Re-RT conveys into promising outcome in recurrent glioma. Complete resection and early Re-RT lead to improved survival. Thus, moving Re-RT to an earlier timepoint during the treatment of recurrent glioma, eg after complete macroscopic removal of the tumor, may be crucial for treatment optimization. Using advanced RT techniques, side effects are low. Currently, this concept is evaluated in the GLIOCAVE/NOA 17 trial.

Modification and optimization of an established prognostic score after re-irradiation of recurrent glioma.

INTRODUCTION: For about 30 years, researchers developed prognostic scores and searched for prognostic factors to predict outcomes for cancer patients. The "Combs Prognostic Score" for re-irradiation in recurrent glioma was recently validated and results showed that the score is a significant (p < .001) and reliable predictor for patients undergoing re-irradiation (re-RT). We sought to enhance the score and generated a novel scoring approach, taking into account the information on resection of recurrent tumors, KPS, and tumor volume. PATIENTS AND METHODS: The prognostic score was generated based on 209 patients treated between 2002 and 2016 for recurrent glioma at the department of radiation oncology at the Klinikum rechts der Isar, Munich. To further enhance the previously validated Combs Prognostic Score, which uses the prognostic factors primary histology, time between primary RT and re-RT, and age, we added KPS, tumor volume (PTV) and re-resection into the scoring scheme. RESULTS: The median follow-up time was 3.5 months. 67.5% were WHO IV gliomas with a median OS after re-RT of 7.9 months, 17.7% were WHO III gliomas with an OS of 11.3 months and 14.8% were WHO I/II gliomas with an OS of 14.7 months. Multivariate analyses confirmed the prognostic factors KPS (p < .001) and showed a tendency to significance for tumor volume (p = .067) and re-resection (p = .064). The new prognostic score demonstrated a high significance (p < .001). CONCLUSION: The "New Combs Prognostics Score" is a significant and useful tool to predict the overall effect of re-RT in patients with recurrence gliomas. This modified score offers an even better way to classify patients in clinical routine and prospective clinical trials investigating re-irradiation.