By Evan Noch, MD, PhD
Assistant Professor, Department of Neurology, Weill Cornell Medicine
SYNOPSIS: Vestibular schwannoma is the most common tumor of the cerebellopontine angle. There is controversy regarding the management of these benign tumors with up-front radiosurgery vs. observation, especially for those that are small- to medium-sized with minimal symptoms. Recent evidence suggests that up-front radiosurgery may reduce tumor volume at four-year follow-up.
SOURCE: Dhayalan D, Tveiten OV, Finnkirk M, et al. Upfront radiosurgery vs a wait-and-scan approach for small- or medium-sized vestibular schwannoma: The V-REX randomized clinical trial. JAMA 2023;330:421-431.
Vestibular schwannomas are benign tumors of the cerebellopontine angle and are responsible for 8% of all intracranial tumors. Their most common presenting symptoms are hearing loss, tinnitus, dizziness, and imbalance, but larger tumors can exhibit brainstem compression or involve neighboring cranial nerves that may affect facial strength and sensation. Management of these tumors involves either observation, surgery, or radiation, which often is tailored to the patient’s tumor size, anatomical relationships, and the patient’s values and preferences. The latter are especially important because of the risk of side effects from microsurgery and radiation, including permanent ipsilateral hearing loss or deafness, facial weakness, and dizziness.
In this study, the authors decided to test the effects of a watch-and-wait approach vs. up-front radiosurgery for vestibular schwannomas that were < 2 cm in maximal diameter. These small- and medium-sized tumors were selected because of a greater amount of uncertainty in their management, as opposed to tumors > 2 cm in diameter that typically benefit from up-front surgery or radiosurgery. The study was conducted at the Norwegian National Unit for Vestibular Schwannoma at Haukeland University Hospital in Norway, with enrollment running from Oct. 28, 2014, to Oct. 3, 2017.
The authors included patients with a newly diagnosed unilateral vestibular schwannoma < 2 cm in maximal diameter and excluded those with neurofibromatosis type 2 in the patient or first-degree relative and those with severe comorbidities. Eligible patients then were randomized in a 1:1 fashion to a watch-and-wait approach or up-front stereotactic radiosurgery with 12 Gy in a single fraction. A total of 142 patients were assessed for eligibility and 100 were randomized, with 50 patients in each group. Forty-eight patients in the up-front radiosurgery group and 50 patients in the watch-and-wait group were included in the primary analysis.
The groups were fairly well-balanced in terms of age, demographics, tumor characteristics, baseline audiometry, facial strength, unsteadiness, vestibular function, and quality of life as regarding tumor-related symptoms. However, the mean tumor volume was 765 mm3 in the radiosurgery group and 514 mm3 in the watch-and-wait group. The most frequent symptoms at presentation were hearing loss (89%) and tinnitus (81%).
The authors found that three patients in the radiosurgery group needed additional treatment because of tumor growth, whereas 21 patients in the watch-and-wait group received radiosurgery and one received microsurgery because of tumor growth. Notably, 28 patients (56%) in the watch-and-wait group did not exhibit tumor growth in the four years of observation and received no treatment during the study period. The ratio of tumor volume at four years compared to baseline was significantly lower in the radiosurgery group as compared to the watch-and-wait group (geometric mean 0.87 compared to 1.51, respectively). The ratio of geometric means in the watch-and-wait group as compared to the radiosurgery group was 1.73 (95% confidence interval, 1.24-2.44; P = 0.002), indicating greater growth of tumors in the watch-and-wait group as compared to the radiosurgery group.
Secondary outcomes were fairly similar in both groups, with the notable exception that facial sensation decreased to a greater extent in the radiosurgery group. Hearing acuity and word recognition declined to the same amount, and caloric asymmetry increased to the same amount, in both groups. Quality of life was unchanged in both groups after four years of follow-up. There were no deaths or radiation-associated complications, including radiation necrosis, malignant transformation, or hydrocephalus, in either group. Four percent of patients in the radiosurgery group and 2% of patients in the watch-and-wait group required salvage radiosurgery. Although the authors found no significant difference in tumor size at one year of follow-up, patients in the radiosurgery group exhibited better tumor volume reduction at each subsequent time point as compared to those in the watch-and-wait group (absolute tumor volume of 333 mm3 in the radiosurgery group vs. 533 mm3 in the watch-and-wait group).
In summary, comparing the effects of a watch-and-wait approach vs. up-front radiosurgery for newly diagnosed vestibular schwannoma, this randomized clinical trial demonstrated a benefit of up-front radiosurgery on tumor size at four years of follow-up. The only secondary outcome out of 26 that was worse in the radiosurgery group was facial sensation. Notably, hearing loss declined in both groups to the same extent.
COMMENTARY
This randomized clinical trial found that tumor size was decreased at four years of follow-up in patients with newly diagnosed vestibular schwannoma who underwent up-front radiosurgery as compared to a watch-and-wait approach. This approach also may benefit patients in whom long-term follow-up is more difficult. The major downside of this up-front radiosurgery approach is a greater reduction in ipsilateral facial sensation. It is interesting to note, however, that more than half of patients who undergo a watch-and-wait approach exhibit no tumor growth at four years, arguing that some patients may benefit from a minimalist approach after initial diagnosis, especially for small, minimally symptomatic lesions.
