21.1 Introduction

Primary treatment strategies for vestibular schwannoma (VS) have evolved remarkably since the advent of stereotactic radiosurgery (SRS), which has become a staple of the skull base armamentarium, alongside microsurgery (MS) and close observation. Although it is frequently a first-line treatment for growing small-to-medium-sized VS, one of the most important and well-studied indications for radiotherapy (RT) in general and SRS in particular in the VS paradigm is tumor recurrence or progression. Primary treatment strategies are reviewed in detail in preceding chapters; however, a brief overview of treatment failure, extent of resection, and recurrence/progression provides an important conceptual foundation for our discussion of the indications for secondary SRS in the VS treatment paradigm.

With respect to primary SRS, the goal of therapy is arrest of tumor growth. Therefore, we define treatment failure as serial growth on two or more follow-up magnetic resonance imaging (MRI) studies, which allows for the expected early tumor expansion and pseudoprogression that is frequently witnessed during the first 6 to 18 months after treatment, a phenomenon discussed further in Chapter 25.s. Literatur ^,​ s. Literatur ^,​ s. Literatur ^,​ s. Literatur ^,​ s. Literatur ^,​ s. Literatur ^,​ s. Literatur Our institutional experience parallels most major preceding series: for single-session SRS at a margin dose of 12 to 14 Gy, long-term tumor control is 92 to 95%, with an all-comers risk of facial weakness approaching 1%, and preservation of useful hearing (i.e., AAO-HNS [American Academy of Otolaryngology—Head and Neck Surgery] class A or B) ranging from 60 to 80% at 3 years, with a decline to less than 50% at 5 years and ultimately below 25% at 10 years.s. Literatur ^,​ s. Literatur ^,​ s. Literatur ^,​ s. Literatur

Although the debate regarding SRS versus MS as primary treatment for slow-growing, small-to-medium-sized tumors has been hotly contested, best available evidence (level 2–3) has demonstrated nearly equivalent tumor control and improved cranial nerve outcomes after SRS at 5 years.s. Literatur ^,​ s. Literatur ^,​ s. Literatur ^,​ s. Literatur Correspondingly, in our practice, patients harboring tumors < 3 cm without brainstem compression and with growth rates < 2.5 mm/year are typically presented with the above data regarding the risks, benefits, and outcomes of both SRS and MS, to facilitate shared decision making and an individualized primary treatment plan. Those patients who elect primary SRS and subsequently experience a treatment failure are typically offered salvage MS, although repeat SRS or secondary RT may be considered under special circumstances, discussed in detail below.s. Literatur ^,​ s. Literatur ^,​ s. Literatur

By contrast, for patients undergoing primary MS, achievement of gross total resection (GTR) is the single most important parameter for predicting the likelihood of secondary treatment, which can be defined using either surgeon’s impression or absence of nodular enhancement on postoperative MRI.s. Literatur ^,​ s. Literatur ^,​ s. Literatur ^,​ s. Literatur ^,​ s. Literatur ^,​ s. Literatur ^,​ s. Literatur Some attention has been directed toward separating near-total resection (NTR; defined using variable parameters to signify a minimal residual tumor volume, typically adherent to the facial nerve) from subtotal resection (STR; with definitions ranging from any postoperative residuum, to any remnant > 5% initial tumor volume, among others); however, these terms have been used inconsistently, and rarely demonstrated a statistically significant or clinically meaningful difference in long-term outcomes, particularly compared independently to GTR.s. Literatur Consequently, the most conceptually useful parameters guiding indications for secondary treatment after primary MS are recurrence, defined as new nodular enhancement after clinically and/or radiographically confirmed GTR, and progression, defined as a ≥2-mm increase in size of any documented postoperative tumor residuum. Using these parameters, large preceding analyses, including our own series, have demonstrated that recurrence is rare after GTR, occurring in 0.05 to 9.2%, whereas progression after STR has been reported in up to 44%. s. Literatur ^,​ s. Literatur ^,​ s. Literatur ^,​ s. Literatur ^,​ s. Literatur ^,​ s. Literatur ^,​ s. Literatur ^,​ s. Literatur ^,​ s. Literatur

In spite of the clear tumor control advantage associated with GTR, aggressive resection also increases the probability of unfavorable cranial nerve outcomes. Correspondingly, a variety of strategies have been advocated in an attempt to find equipoise between these competing goals, including NTR followed by observation, STR followed by either close observation or upfront SRS, and planned debulking followed by upfront SRS.s. Literatur ^,​ s. Literatur ^,​ s. Literatur ^,​ s. Literatur ^,​ s. Literatur Although several studies have compared these treatment approaches, results have been equivocal overall, and in our own experience, among patients selected for primary MS, excellent tumor control and facial nerve outcomes have been consistently achieved by pursuing GTR, as the paramount goal of surgery, and accepting aggressive STR in markedly adherent tumors.s. Literatur ^,​ s. Literatur ^,​ s. Literatur

In summary, secondary SRS is most frequently employed in the treatment of tumor progression after primary MS resulting in STR, or less frequently tumor recurrence after GTR, as well as uncommon circumstances where repeating a course of radiation is preferable to secondary MS. Although pertinent data are scattered, retrospective, and based on small patient numbers, each of these cohorts has been studied, and our chief aim herein is to describe and synthesize the key findings and their clinically significant implications.

21.2 Secondary SRS after MS

Disease recurrence/progression after primary MS is by far the most common indication for secondary SRS, as well as the best studied (Table 21‑1 ). Although increasingly large proportions of the VS population are either observed or treated with primary SRS, MS remains the most common primary treatment modality overall, particularly in younger patients, individuals desiring to avoid radiation, large tumors, or tumors producing symptomatic mass effect, via either brainstem compression/edema or hydrocephalus.s. Literatur ^,​ s. Literatur ^,​ s. Literatur ^,​ s. Literatur ^,​ s. Literatur ^,​ s. Literatur Consequently, the more widespread acceptance of SRS as a secondary modality has both historical roots (e.g., during the technology’s developmental phase, patients requiring salvage therapy were considered a lower-risk/higher-reward cohort) and clinical motivations (e.g., patients requiring urgent surgery for indications described above have previously tipped the primary treatment balance toward MS, as have surgeon preferences to avoid MS after SRS; discussed below).s. Literatur ^,​ s. Literatur ^,​ s. Literatur ^,​ s. Literatur Interestingly, this balance has reversed somewhat as the fraction of incidentally diagnosed or minimally symptomatic tumors has increased alongside improved access to MRI.s. Literatur ^,​ s. Literatur ^,​ s. Literatur

As a secondary modality for treatment of recurrence/progression after primary MS, SRS has demonstrated compelling tumor control results, with an overall median growth arrest rate of 94% (range, 75–100%) at a median follow-up of 69 months after secondary treatment (range, 36–156; Table 21‑1 ). Follow-up imaging after secondary SRS demonstrated frank reduction in tumor size in 36 to 80% of cases, typically observed within 12 months of treatment.s. Literatur ^,​ s. Literatur ^,​ s. Literatur ^,​ s. Literatur Time-to-secondary-treatment was a median 37 months after primary MS (range, 0–329 months), with an increase of treatment interval from 37 to 57 months for patients who recurred after NTR/STR, as compared to those who recurred after GTR, respectively.s. Literatur Durable tumor control after secondary SRS was not significantly different between patients being treated for progression and those being treated for recurrence.s. Literatur ^,​ s. Literatur ^,​ s. Literatur ^,​ s. Literatur ^,​ s. Literatur

Median tumor margin dose was 12 Gy at secondary SRS (range, 9–20 Gy), while median tumor volume was 3.3 cm³ (range, 0.03–36.1 cm³), attributable to the considerable fraction of tumors that were initially too large for primary SRS (e.g., >2.5 or 3 cm maximum diameter) that underwent STR at primary MS and subsequently progressed. Overall, these results are favorable when compared to repeat MS, the details of which are reviewed in Chapter 43, rendering SRS as the preferred secondary modality after primary MS for most cases of recurrent/progressive VS.