Dramatic Growth of a Vestibular Schwannoma after 16 Years of Postradiosurgery Stability in Association with Exposure to Tyrosine Kinase Inhibitors

Background: Vestibular schwannoma (VS) is a benign nerve sheath tumor, with an incompletely characterized immune microenvironment. Subtotal resection (STR) is the most significant predictor of recurrence after surgical resection; however, many tumor remnants stabilize, and understanding of the major contributing factors to posttreatment behavioral phenotype is poor. Previous research has shown that PD-L1+ tumor-associated macrophages (TAMs) are associated with more aggressive behavior after resection, including higher rates of recurrence, unfavorable facial nerve outcomes, and postoperative complications, highlighting a key opportunity for possible medical intervention using systemic immunomodulation. Notwithstanding, interactions between the tumor and immune compartments in VS are complex, and the potential for unanticipated or idiosyncratic responses to novel biologics is not negligible. We report the first case of a VS that demonstrated an excellent response to stereotactic radiosurgery (SRS) including radiographically proven stability for over 16 years, followed by dramatic expansion of the tumor following treatment with tyrosine kinase inhibitors (TKIs) for an unrelated indication.

Methods: Case report.

Results: A 57-year-old man initially presented with left-side hearing loss and episodic vertigo; a small intracanalicular tumor was identified and the patient elected treatment with SRS. Treatment response was excellent, with >50% reduction in total tumor, loss of central enhancement, and no evidence of progression as of 13 years post-SRS. The patient subsequently developed unrelated metastatic gastrointestinal stromal tumor (GIST), and was initiated on multiple tyrosine kinase inhibitors over a 5-year period, including imatinib, sunitinib, regorafenib, and nilotinib. At 16 years po-SRS, the patient developed subacute left House–Brackmann grade IV facial weakness and severe gait apraxia. Repeat MRI demonstrated dramatic VS expansion from 14 to 25 mm in maximum diameter, with new brain stem compression. At that time, the patient had recently been given a prognosis of less than 1 year by medical oncology; correspondingly, he discontinued all biologics, and declined translabyrinthine resection of the recurrence.

Conclusion: We report the first case of post-SRS VS that was stable for 16 years before initiation of TKIs for an unrelated GIST, which likely resulted in rapid and dramatic tumor progression. The VS immune microenvironment clearly plays an integral role in treatment response and posttreatment behavior; however, the complex interactions between systemic immunomodulatory agents and disease phenotype remain incompletely understood, and the potential for both benefit and harm may be considerable. As immunomodulatory agents become more prevalent in the oncologic armamentarium, further translational study will be required to more precisely define the interactions between VS tumor cells and the immune system, with an eye toward mechanistically deconstructing potential targets for individualized therapies, as well as anticipating possible consequences of unrelated therapies on VS, as was observed in our patient.