Purpose/Objective(s): Irradiating glioblastoma preoperative edema (PE) remains controversial. Currently, the European Organisation for Research and Treatment of Cancer (EORTC) adopts a 2-cm volumetric expansion of the gross tumor volume (GTV) to generate the clinical target volume (CTV) in a single phase of 60 Gy in 30 fractions. The Radiation Therapy Oncology Group (RTOG) defines CTV1 as surgical resection cavity plus residual tumor plus surrounding edema with a 2-2.5-cm margin to receive 46 Gy in 23 fractions, followed by cone down boost to the tumor bed with a 2-cm margin as CTV2 to receive an additional 14 Gy in 7 fractions. Glioblastoma progression patterns are diverse, depending on the tumor PE extent and invasion into the synchronous subventricular zone and corpus callosum (sSVZCC). We investigated the associations between tumors' PE extent with invasion into synchronous subventricular zone and corpus callosum (sSVZCC) and treatment outcomes to provide the clinical evidence for radiotherapy decision-making. Purpose/Objective(s): Extensive PE (EPE) was defined as PE extending ≥ 2 cm from the tumor margin and extensive progressive disease (EPD) as tumors spreading ≥ 2 cm from the preoperative tumor margin along PE. The survival and progression patterns were analyzed according to EPE and sSVZCC invasion. Results: In total, 136 patients were followed for a median of 74.9 (range, 47.6-102.1) months. A radiotherapy dosage of 46 Gy for the PE and an additional 8-14 Gy for the tumor bed was administered concurrently with temozolomide. The median overall survival and progression-free survival were 19.7 versus 28.6 months (P = 0.005) and 11.0 versus 17.4 months (P = 0.011) in patients with EPE+ versus EPE-, and were 18.7 versus 25.4 months (P = 0.021) and 10.7 versus 14.6 months (P = 0.020) in those with sSVZCC+ versus sSVZCC-. Using multivariate analyses with the factors of age, Karnofsky performance status, tumor size, and resection extent, EPE remained significant for a poor OS (hazard ratio (HR), 1.98; 95% confidence interval (CI), 1.28-3.05) and both EPE and sSVZCC invasion remained significant for a poor PFS (HRs, 1.84 and 1.56; 95% CIs, 1.23-2.76 and 1.03-2.38, respectively). The EPD rates for tumors categorized as EPE-/sSVZCC-(Group I), EPE-/sSVZCC+ (Group II), EPE+/sSVZCC-(Group III), and EPE+/sSVZCC+ (Group IV) were 2.8%, 7.1%, 37.0%, and 71.9%, respectively. In EPE+/sSVZCC+, tumor migration was associated with the PE along the corpus callosum (77.8%) and subventricular zone (50.0%). Conclusion: EPE with sSVZCC invasion determines the survival and EPD rates. According to the clinical evidence, we proposed the corresponding RT target volume delineations and dose prescriptions to patients of the four groups, including EORTC guideline for Group I and II, RTOG guideline for Group III, and high irradiation dose to both PE and tumor bed for Group IV. Our study supports the need for developing individualized irradiation strategies for glioblastomas according to the imaging biomarkers of EPE and sSVZCC invasion.
Liang, H. K. T., Chen, W. Y., Lai, S. F., Su, M. Y., You, S. L., Chen, L. H., … Tseng, W. Y. I. (2017). The Extent of Edema and Tumor Synchronous Invasion into the Subventricular Zone and Corpus Callosum Classify Outcomes and Radiation Therapy Strategies of Glioblastomas. International Journal of Radiation Oncology*Biology*Physics, 99(2), S187–S188. https://doi.org/10.1016/j.ijrobp.2017.06.467