William R. Kennedy, Todd A. DeWees, Sahaja Acharya, Mustafaa Mahmood, Nels C. Knutson, S. Murty Goddu, James A. Kavanaugh, Timothy J. Mitchell, Keith M. Rich, Albert H. Kim, Eric C. Leuthardt, Joshua L. Dowling, Gavin P. Dunn, Michael R. Chicoine, Stephanie M. Perkins, Jiayi Huang, Christina I. Tsien, Clifford G. Robinson, and Christopher D. Abraham
The internal high-dose volume varies widely for a given prescribed dose during stereotactic radiosurgery (SRS) to treat brain metastases (BMs). This may be altered during treatment planning, and the authors have previously shown that this improves local control (LC) for non–small cell lung cancer BMs without increasing toxicity. Here, they seek to identify potentially actionable dosimetric predictors of LC after SRS for melanoma BM.
The records of patients with unresected melanoma BM treated with single-fraction Gamma Knife RS between 2006 and 2017 were reviewed. LC was assessed on a per-lesion basis, defined as stability or a decrease in lesion size. Outcome-oriented approaches were utilized to determine optimal dichotomization for dosimetric variables relative to LC. Univariable and multivariable Cox regression analysis was implemented to evaluate the impact of collected parameters on LC.
Two hundred eighty-seven melanoma BMs in 79 patients were identified. The median age was 56 years (range 31–86 years). The median follow-up was 7.6 months (range 0.5–81.6 months), and the median survival was 9.3 months (range 1.3–81.6 months). Lesions were optimally stratified by volume receiving at least 30 Gy (V30) greater than or equal to versus less than 25%. V30 was ≥ and < 25% in 147 and 140 lesions, respectively. For all patients, 1-year LC was 83% versus 66% for V30 ≥ and < 25%, respectively (p = 0.001). Stratifying by volume, lesions 2 cm or less (n = 215) had 1-year LC of 82% versus 70% (p = 0.013) for V30 ≥ and < 25%, respectively. Lesions > 2 to 3 cm (n = 32) had 1-year LC of 100% versus 43% (p = 0.214) for V30 ≥ and < 25%, respectively. V30 was still predictive of LC even after controlling for the use of immunotherapy and targeted therapy. Radionecrosis occurred in 2.8% of lesions and was not significantly associated with V30.
For a given prescription dose, an increased internal high-dose volume, as indicated by measures such as V30 ≥ 25%, is associated with improved LC but not increased toxicity in single-fraction SRS for melanoma BM. Internal dose escalation is an independent predictor of improved LC even in patients receiving immunotherapy and/or targeted therapy. This represents a dosimetric parameter that is actionable at the time of treatment planning and warrants further evaluation.
Amar S. Shah, Peter T. Sylvester, Alexander T. Yahanda, Ananth K. Vellimana, Gavin P. Dunn, John Evans, Keith M. Rich, Joshua L. Dowling, Eric C. Leuthardt, Ralph G. Dacey, Albert H. Kim, Robert L. Grubb, Gregory J. Zipfel, Mark Oswood, Randy L. Jensen, Garnette R. Sutherland, Daniel P. Cahill, Steven R. Abram, John Honeycutt, Mitesh Shah, Yu Tao, and Michael R. Chicoine
Intraoperative MRI (iMRI) is used in the surgical treatment of glioblastoma, with uncertain effects on outcomes. The authors evaluated the impact of iMRI on extent of resection (EOR) and overall survival (OS) while controlling for other known and suspected predictors.
A multicenter retrospective cohort of 640 adult patients with newly diagnosed supratentorial glioblastoma who underwent resection was evaluated. iMRI was performed in 332/640 cases (51.9%). Reviews of MRI features and tumor volumetric analysis were performed on a subsample of cases (n = 286; 110 non-iMRI, 176 iMRI) from a single institution.
The median age was 60.0 years (mean 58.5 years, range 20.5–86.3 years). The median OS was 17.0 months (95% CI 15.6–18.4 months). Gross-total resection (GTR) was achieved in 403/640 cases (63.0%). Kaplan-Meier analysis of 286 cases with volumetric analysis for EOR (grouped into 100%, 95%–99%, 80%–94%, and 50%–79%) showed longer OS for 100% EOR compared to all other groups (p < 0.01). Additional resection after iMRI was performed in 104/122 cases (85.2%) with initial subtotal resection (STR), leading to a 6.3% mean increase in EOR and a 2.2-cm3 mean decrease in tumor volume. For iMRI cases with volumetric analysis, the GTR rate increased from 54/176 (30.7%) on iMRI to 126/176 (71.5%) postoperatively. The EOR was significantly higher in the iMRI group for intended GTR and STR groups (p = 0.02 and p < 0.01, respectively). Predictors of GTR on multivariate logistic regression included iMRI use and intended GTR. Predictors of shorter OS on multivariate Cox regression included older age, STR, isocitrate dehydrogenase 1 (IDH1) wild type, no O
6-methylguanine DNA methyltransferase (MGMT) methylation, and no Stupp therapy. iMRI was a significant predictor of OS on univariate (HR 0.82, 95% CI 0.69–0.98; p = 0.03) but not multivariate analyses. Use of iMRI was not associated with an increased rate of new permanent neurological deficits.
GTR increased OS for patients with newly diagnosed glioblastoma after adjusting for other prognostic factors. iMRI increased EOR and GTR rate and was a significant predictor of GTR on multivariate analysis; however, iMRI was not an independent predictor of OS. Additional supporting evidence is needed to determine the clinical benefit of iMRI in the management of glioblastoma.