Central Nervous System

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MO_8_2676 - Concurrent Immunotherapy Usage and Asymmetric Growth May Distinguish True Progression from Treatment Effect in Growing Brain Metastases after Stereotactic Radiosurgery

Monday, October 22
10:45 AM - 12:15 PM
Location: Innovation Hub, Exhibit Hall 3

Concurrent Immunotherapy Usage and Asymmetric Growth May Distinguish True Progression from Treatment Effect in Growing Brain Metastases after Stereotactic Radiosurgery
L. C. Peng1, L. Chen1, P. Han1, B. R. Baker1, C. Shen1, C. Gui1, K. Sheikh1, H. Ames2, T. Kirschbaum1, F. Silvestri1, J. Son1, A. Robinson1, E. Huang1, J. Grimm1, K. J. Redmond1, M. Lim1, J. Lee1, and L. R. Kleinberg1; 1Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 2Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD

Purpose/Objective(s): Some brain metastases (BM) treated with Stereotactic Radiosurgery (SRS) will later develop symptomatic growth. Imaging alone, however, is largely unable to distinguish true progression (TP) from treatment effect in these cases. We hypothesized that a set of clinical and imaging features would be significantly associated with TP in growing BM after SRS. Such features could be useful for guiding patient management.

Materials/Methods: Patients treated with SRS for BM who then underwent resection for suspected progression at a single institution were retrospectively reviewed. A set of patients with spontaneous radiographic regression of growth without further treatment were also included. Lesions were contoured at baseline and at progression to determine lesion volumes and any shift in the center of mass. Clinical and imaging features were tested on univariate logistic regression for associations with TP on pathology. Important features (p < 0.2) on univariate analysis were then entered into multivariate logistic regression to find significant predictors of TP.

Results: Eighty-four cases of BM across 68 patients met inclusion criteria including 5 cases diagnosed by radiographic regression alone. Median dose was 18 (range: 14-25) Gy in 1 (1-5) fraction. Median time from SRS to maximum growth was 252 (21-1351) days. In 8 cases, patients received immunotherapy (IT) within 2 weeks of SRS (concurrent SRS/IT) and in 14 cases IT was received non-concurrently. Exactly 50% (42/84) of cases had pure TP on pathology. Poor predictors (p > 0.2) on univariate analysis included treatment machine type, primary histology, original lesion volume, non-concurrent IT/SRS, neutrophil/lymphocyte counts at progression, and time to progression. Table 1 shows results of the multivariate logistic regression model incorporating the remaining features. Table 1:
Odds Ratio for TP (95% CI) p-value
Age > 57 years old 2.12 (0.74, 6.51) 0.17
Infratentorial location 2.78 (0.82, 10.6) 0.11
Prior whole brain radiation 0.28 (0.06, 1.09) 0.08
Prescription Isodose line >69% 1.76 (0.64, 5.00) 0.28
BED10 >34 Gy 0.36 (0.04, 2.17) 0.28
Distance between centers of original lesion and subsequent progression >13 mm 6.58 (1.24, 62.7) 0.05
Concurrent immunotherapy with SRS 0.09 (0.007-0.68) 0.04
Lesion volume at progression >28 cm3 5.10 (0.89, 45.9) 0.09

Conclusion: Asymmetric growth away from the center of the original lesion predicted for TP in this cohort, possibly reflecting cases with surviving tumor cells beyond the centrally ablative region. On the other hand, concurrent IT/SRS predicted for treatment effect while non-concurrent IT use was not predictive of any outcome. This adds further support for the importance of timing with SRS and IT. Validation in larger independent datasets is warranted.

Author Disclosure: L.C. Peng: Employee; Johns Hopkins University School of Medicine. L. Chen: None. P. Han: None. B.R. Baker: None. K. Sheikh: None. T. Kirschbaum: None. F. Silvestri: None. A. Robinson: None. E. Huang: None. J. Grimm: Employee; Academic Urology. Research Grant; Novocure, Accuray. Honoraria; Accuray. Travel Expenses; Accuray. Patent/License Fees/Copyright; DiversiLabs, LLC. K.J. Redmond: Research Grant; Elekta AB, Accuray. Honoraria; AstraZeneca, Accuray. Travel Expenses; Elekta AB, Accuray. M. Lim: Consultant; BMS. Research Grant; Immunocellular, Agenus. Consultant; Stryker. Speaker's Bureau; Stryker. Advisory Board; Baxter, Boston Biomedical, Oncorus, Agenus, Merck. J. Lee: Research Grant; Canon Inc. L.R. Kleinberg: Research Grant; Novocure, Accuray. Honoraria; Accuray. Advisory Board; Novocure.

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