Duration and Timing of Transient Tumor Enlargement after Gamma Knife Radiosurgery for Vestibular Schwannomas

Objective Differentiating pseudoprogression from true tumor growth is a difficult clinical problem in the management of vestibular schwannomas after radiosurgery. Controversy exists regarding how much tolerance a clinician should have for tumor enlargement following treatment, before recommending salvage therapy. In this study, we sought to describe the distribution of tumor volume behaviors after radiosurgery, identify factors associated with transient growth, and identify an ideal timeframe for differentiating true growth from pseudoprogression.

Methods A retrospective study including all sporadic vestibular schwannomas treated with gamma knife radiosurgery between 2002 and 2014 at the University of California, San Francisco Medical Center, was performed. Volumetric tumor analysis was performed on all available MR T1 postcontrast imaging. Tumor behavior after treatment was classified as “stable/reduced,” “transient growth,” or “persistent growth” based on the volumetric curves. For tumors classified as having “transient growth,” the time to onset of tumor enlargement, time of peak enlargement, maximal percent volume increase, and time to complete resolution of enlargement were calculated. The distributions of these attributes were then analyzed and cumulative probability plots were made. Univariate statistics were performed to identify demographic, clinical, radiographic, and volume curve attributes that were significantly associated with duration of transient tumor growth.

Results A total of 114 patients underwent gamma knife SRS and were included in this study; 44 (39%) remained stable or decreased in volume, 48 (42%) demonstrated transient growth, and 22 (19%) had persistent growth at last follow-up. Volumetric curves are shown in Fig. 1. Median tumor volumes were 0.8 ± 1.9 cm³, 0.6 ± 0.9 cm³, and 1.2 ± 2.5 cm³ (p = 0.01) respectively, and median follow-up was 4.2 ± 2.6 years, 4.8 ± 2.8 years, and 2.7 ± 1.5 years (p = 0.004) respectively (Table 1). For transiently growing tumors, the median time to onset of growth was 1 ± 0.9 years (90% occurring by 2.5 years), median time to peak tumor enlargement was 1 ± 1 year (90% occurring by 3.5 years), median peak percent volume change was 0.5 ± 0.4% (90% of cases with < 115% volume increase at peak), and the median time to resolution of transient enlargement was 2.4 ± 2.1 years (90% of cases resolved by 6.9 years; Fig. 2). Time to onset of enlargement, time to peak enlargement, and peak percent volume change were all significantly correlated with the duration of pseudoprogression (Fig. 3).

Conclusion In this series, 42% of patients experienced transient tumor enlargement (pseudoprogression) after radiosurgical treatment of their vestibular schwannoma. Factors significantly differentiating pseudoprogression from persistent growth were tumor volume and follow-up duration. While the median time to resolution of pseudoprogression was 2.4 years, the resolution rate did not reach 90% until 6.9 years. These results suggest that longer follow-up and observation (4–6 years) after radiosurgical treatment may be indicated before opting for salvage intervention.

Fig. 1

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Fig. 3 (A086)