Presenter(s)
Raj Singh, MD - The Ohio State University Wexner Medical Center, Columbus, OH
R. Singh1, A. Koempel2, H. K. Perlow3, S. Rauh4, T. Kutuk1, R. Kotecha5, W. C. Chen6, D. Raleigh6, K. M. Frechette7, E. J. Lehrer8, S. Magill9, L. Burgess10, A. Sahgal10, M. Deng4, J. Debus4, L. König4, and J. D. Palmer1; 1Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, 2Department of Radiation Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, 3Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, OH, 4Department of Radiation Oncology, University Hospital Heidelberg, Heidelberg, Germany, 5Department of Radiation Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, FL, 6Department of Radiation Oncology, University of California, San Francisco, San Francisco, CA, 7Department of Radiation Oncology, Mayo Clinic Rochester, Rochester, MN, 8Department of Radiation Oncology, Mayo Clinic, Rochester, MN, 9Department of Neurological Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, 10Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, ON, Canada
Purpose/Objective(s): Published retrospective and prospective analyses evaluating the potential utility of dose-escalated post-operative radiation therapy (DE-RT) for high risk meningiomas have been limited to single institution experiences. We aimed to pool outcomes for high risk meningiomas across multiple institutions to compare local control (LC) rates with DE-RT vs. standard dose post-operative radiation therapy (SD-RT). Materials/Methods: A total of 7 institutions participated in this individual patient level meta-analysis on outcomes following SD-RT or DE-RT for high risk meningiomas (one prospective experience on mixed photon and carbon boost DE-RT and 6 retrospective cohorts with information on either DE-RT, SD-RT, or both). High risk meningiomas were defined as per RTOG 0539 (i.e., recurrent WHO Grade 2 meningiomas, new WHO Grade 2 meningiomas after a subtotal resection (STR), or a new or recurrent WHO Grade 3 meningioma after any extent of resection). We defined DE-RT via BED10 and a dose of 80.5 Gy BED10 or greater (correlating to 66 Gy/33 fractions) or having received carbon ion boost. LC was defined as achieving stable disease, partial response, or complete response from the end of RT to time of last follow-up or date of recurrent disease at the irradiated site. We examined LC and compared SD-RT vs. DE-RT via Kaplan-Meier analysis and log-rank t-tests followed by a Cox proportional hazards multivariate analysis. Results: The individual patient level meta-analysis included 220 patients with high risk meningioma (74 received DE-RT and 146 received SD-RT). One-hundred and ninety-four (88.1%) were WHO Grade 2 and the remaining cases were WHO Grade 3. Extent of resection prior to RT was Simpson Grade 4/STR in the majority of cases (143/220; 65%) with Simpson Grade 1-3/gross total resection (GTR) in 70 cases (31.8%) and the remaining 5 cases being biopsy only. Of the included cases, 116/220 cases (52.7%) were recurrent meningiomas. The median BED10 for the DE-RT and SD-RT arms were 84 Gy (range: 82.92-93.8 Gy) and 72 Gy (range: 51.2-79.2 Gy, respectively). DE-RT was associated with higher rates of LC at 3- (90.1% vs. 63.0%) and 5-years (77.8% vs. 45.8%) (p = 0.0006). On Cox MVA, after controlling for extent of resection (i.e., GTR vs. STR/biopsy) and disease status (newly diagnosed vs. recurrent), patients who received DE-RT had superior LC (hazard ratio (HR) = 0.46 (95% CI: 0.30-0.70); p<0.0010). We also noted improved LC among patients following GTR (HR = 0.56 (95% CI: 0.33-0.95); p=0.30) and those with newly diagnosed vs. recurrent meningiomas (HR = 0.49 (95% CI: 0.30-0.79); p=0.004). Conclusion: In the largest series to date on this topic, our analysis suggests that DE-RT results in clinically superior long-term LC outcomes for patients with high risk meningiomas over SD-RT. Large prospective randomized trials are needed to prospectively validate these findings.
