Peritumoral edema status of glioblastoma identifies patients reaching long-term disease control with specific progression patterns after tumor resection and high-dose proton boost.

BACKGROUND: Glioblastoma peritumoral edema (PE) extent is associated with survival and progression pattern after tumor resection and radiotherapy (RT). To increase tumor control, proton beam was adopted to give high-dose boost (> 90 Gy). However, the correlation between PE extent and prognosis of glioblastoma after postoperative high-dose proton boost (HDPB) therapy stays unknown. We intend to utilize the PE status to classify the survival and progression patterns. METHODS: Patients receiving HDPB (96.6 GyE) were retrospectively evaluated. Limited peritumoral edema (LPE) was defined as PE extent < 3 cm with a ratio of PE extent to tumor maximum diameter of < 0.75. Extended progressive disease (EPD) was defined as progression of tumors extending > 1 cm from the tumor bed edge. RESULTS: After long-term follow-up (median 88.7, range 63.6-113.8 months) for surviving patients with (n = 13) and without (n = 32) LPE, the median overall survival (OS) and progression-free survival (PFS) were 77.2 vs. 16.7 months (p = 0.004) and 13.6 vs. 8.6 months (p = 0.02), respectively. In multivariate analyses combined with factors of performance, age, tumor maximum diameter, and tumor resection extent, LPE remained a significant factor for favorable OS and PFS. The rates of 5-year complete response, EPD, and distant metastasis with and without LPE were 38.5% vs. 3.2% (p = 0.005), 7.7% vs. 40.6% (p = 0.04), and 0% vs. 34.4% (p = 0.02), respectively. CONCLUSIONS: The LPE status effectively identified patients with relative long-term control and specific progression patterns after postoperative HDPB for glioblastoma.

Intratumoral injection of thermogelling and sustained-release carboplatin-loaded hydrogel simplifies the administration and remains the synergistic effect with radiotherapy for mice gliomas.

BACKGROUND: Carboplatin, an antineoplastic agent, binds DNA and enhances radiotherapy (RT) effects. Carboplatin-loaded hydrogel (oxidized hyaluronic acid/adipic acid dihydrazide) enables the sustained drug release and facilitates the synergistic effect with RT. PURPOSE: We investigated the effectiveness and convenience of hydrogel carboplatin combined with RT for mice glioma. MATERIALS AND METHODS: Mouse glioma cells (ALTS1C1) were subcutaneously implanted in the right thigh of C57BL/6 mice on Day 0. The mice were categorized by treatments: sham, hydrogel, hydrogel carboplatin, aqueous carboplatin, RT, hydrogel carboplatin/RT, and aqueous carboplatin/RT. Hydrogel carboplatin (300 µg single dose on Day 7) or aqueous carboplatin (100 µg daily dose on Days 7, 8, and 9) was administered via intratumoral injection. RT was delivered a daily dose of 10 Gy on Days 8 and 9. RESULTS: For mice administered hydrogel carboplatin/RT versus those administered aqueous carboplatin/RT, the 24-day tumor growth control rate and 104-day recurrence-free survival rate were 100% and 50% versus 100% and 66.7% (p = 0.648), respectively. However, mice receiving other treatments showed tumor progression by Day 24 and died within 40 days of tumor cell implantation. CONCLUSIONS: Hydrogel carboplatin simplified intratumoral drug delivery and remained the synergistic effects with RT, which is potential for clinical applications.

The extent of edema and tumor synchronous invasion into the subventricular zone and corpus callosum classify outcomes and radiotherapy strategies of glioblastomas.

BACKGROUND AND PURPOSE: Irradiating glioblastoma preoperative edema (PE) remains controversial. 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. MATERIAL AND METHODS: Extensive PE (EPE) was defined as PE extending ≥2 cm from the tumor edge and extensive progressive disease (EPD) as tumors spreading ≥2 cm from the preoperative tumor edge 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. 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-. The EPD rates for tumors with EPE-/sSVZCC-, EPE-/sSVZCC+, EPE+/sSVZCC-, and EPE+/sSVZCC+ were 2.8%, 7.1%, 37.0%, and 71.9%, respectively. In EPE+/sSVZCC+, tumor migration was associated with the PE extending along the corpus callosum (77.8%) and subventricular zone (50.0%). CONCLUSIONS: Our results support the need for developing individualized irradiation strategies for glioblastomas according to EPE and sSVZCC.