Transient Volume Changes After Radio Surgical Management of Vestibular Schwannomas (VS)

Radiosurgery (SRS) and Hypofractionated Stereotactic Radiotherapy (HFSRT). These therapies may be used for upfront management or for salvage treatment as an individualized approach. Herein, we address transient volume changes after radio surgical management of VS in light of the literature. Abstract After Radio Surgical Management of Vestibular Schwannomas (VS). evidence suggests that a considerable proportion of patients receiving radiosurgery for VS may suffer from transient swelling with potential to translate into a temporary clinical deterioration which underscores importance of its consideration as a distinct entity. There is need for further studies addressing transient swelling after VS radiosurgery and related clinical implications. Herein, we address transient volume changes after radio surgical management of VS in light of the literature.


Introduction
Vestibular schwannoma (VS), also referred to as acoustic neuroma or acoustic neurinoma comprises a benign intracranial tumor of the internal auricular canal or the cerebellopontine angle which arises from the Schwann cells of the vestibulocochlear nerve, with an increasing incidence thanks to advances in neuroimaging and aging of the population [1]. These benign tumors typically follow an indolent disease course with a slow growth rate, however, Vestibular schwannoma (VS), also referred to as acoustic neuroma or acoustic neurinoma comprises a benign intracranial tumor of the internal auricular canal or the cerebellopontine angle which arises from the Schwann cells of the vestibulocochlear nerve. Observation with periodical imaging may be a viable option in selected patients given the typically slow growth rate of VS and availability of advanced neuroimaging techniques allowing for precise monitorization of the growth behavior. Nevertheless, management may be warranted for progressive symptomatic presentation or growing tumors with potential to cause severe consequences. Main modalities for VS management include surgery and radiation therapy (RT) with relatively newer adoption of Stereotactic Radiosurgery (SRS) and Hypofractionated Stereotactic Radiotherapy (HFSRT). In the context of VS radiosurgery, while earlier studies reported lower rates of transient swelling, recent evidence suggests that a considerable proportion of patients receiving radiosurgery for VS may suffer from transient swelling with potential to translate into a temporary clinical deterioration which underscores importance of its consideration as a distinct entity. There is need for further studies addressing transient swelling after VS radiosurgery and related clinical implications. Herein, we address transient volume changes after radio surgical management of VS in light of the literature.  Avoiding management of large VS lesions with upfront radiosurgery may be a judicious approach given the considerable rates of transient swelling and the risk of exacerbating the consequences of already present mass effect due to large tumor volume. In a study by Oyama et al. assessing early changes in volume of acoustic neurinomas after radiosurgery, lesion volumes had a tendency for growing slightly at 6 months following radiosurgery and then to shrink to approximately identical volumes at 9 months [65]. Nagano et al. prospectively evaluated volumetric changes in VS after SRS [66]. A total of 100 consecutive patients with unilateral VS were included and mean observation period was 65 months [66]. Lesion volumes increased by 23% at 3 months, and 27% at 6 months, then shrinking to initial size over a mean period of 1 year [66]. Maximum volumetric increase was less than 10% in 26 patients, in the range of 10% to 30% in 23 patients, in the range of 30% to 50% in 22 patients, in the range of 50% to 100% in 16 patients, and more than 100% in 13 patients which was found to be in association with cranial nerve dysfunction [66].

Keywords
Meijer et al. defined the term "transient swelling" as a tumor volume shrinkage to a volume smaller than the pretreatment volume preceded by a tumor volume enlargement [67]. They identified 45 patients receiving radiosurgery with a mean follow up duration of 50 months [67]. At the last follow up neuroimaging with MRI, calculated volumes were smaller in 37 (82.2%) out of the 45 assessed patients [67]. Out of these 37 lesions, 11 lesions (29.7%) demonstrated transient swelling prior to shrinkage [67]. The authors emphasized the importance of optimal scheduling of follow up MRI for avoiding unnecessary interventions [67]. In the study by Aoyama et al. assessing symptomatic outcomes with regard to tumor expansion following fractionated stereotactic RT of VS, postirradiation tumor expansion was observed in 21% of patients which was associated with an elevated risk of serviceable hearing loss,worsening of facial and trigeminal nerve functionality [68].In the study by Hathout et al., rate of transient volume increase with a median time to tumor enlargement of 5.5 months in VS lesions was 25% following RT which was found to be in association with elevated rates of facial and trigeminal neuropathies [69].
In the study by Hayhurst and Zadeh assessing tumor pseudoprogression after radiosurgery for VS, rate of pseudoprogression was found to be 23% with the onset of enlargement at 6 months and regression typically by 2 years, without an association between transient tumor growth and clinical worsening [70]. In this context, the authors suggested that pseudoprogression should be expected and not considered as treatment failure [70].
In the study by Mohammed et al. evaluating pseudoprogression of VS lesions following fractionated stereotactic RT, neuroimaging with MRI revealed pseudoprogression in one third of patients occurring within 3 years of the postirradiation period before regression [71]. The authors emphasized the importance of repeated imaging and vigilant clinical follow up to exclude pseudoprogression so as to avoid unnecessary therapeutic interventions [71].In a study by Mindermann and Schlegel addressing discrimination between tumor growth and transient expansion of VS after radiosurgery, the authors suggested that time could serve as a good parameter to distinguish between tumor growth from transient expansion of VS after radiosurgery [72].
The authors reported that transient expansion of VS frequently occurs at 6 to 18 months after radiosurgery whereas tumor growth seems to develop approximately at 3-4 years [72]. In a comprehensive analysis of MRI volumetric changes following HFSRT for benign intracranial neoplasms, Fega et al. reported that transient volume expansion was a frequent finding after HFSRT of VS which was in association with temporary adverse effects [73]. The authors reported an overall 15% discordance rate regarding the neuroradiologist interpretation and volumetric MRI measurements, which underscores importance of incorporating volumetric measurements as part of detailed assessments to aid in decision making [73]. In a study by Yardımcı [75]. The authors emphasized that the proposed predictive model could allow for individualized treatment selection for VS to improve overall therapeutic outcomes [75].

Conclusion and Future Perspectives
There have been unprecedented breakthroughs in the discipline of radiation oncology in the millennium era leading to significant

Conflicts of Interest
There are no conflicts of interest and no acknowledgements.