44.1 Introduction

Surgeons regularly treating patients with vestibular schwannoma (VS) are familiar with cases where radiosurgery fails. Typically, persistent growth is noted on routine magnetic resonance imaging (MRI) examinations after radiosurgery, and the patient may present with increasing symptoms. Although the success rate of radiosurgery is high, it is not 100%—so with more than 80,000 cases of VS treated by Gamma Knife radiosurgery (GKRS), there are many cases in which surgery may be necessary with time.s. Literatur The number of published cases on patients treated with microsurgery following radiation therapy is, however, low. This chapter aims at discussing what time point salvage surgery should be considered for patients who have undergone radiosurgery and what surgical challenges one may encounter, and finally it summarizes the present literature.

44.2 Volume Changes in Vestibular Schwannoma following Radiation

If a VS expands following radiation, the volume increase is usually succeeded by stagnation or regression later on. In 2008, Pollock reported on tumor volume changes in 208 VS patients who had undergone GKRS.s. Literatur He found initial tumor enlargement in 31 (14%) of these, but only 2 cases underwent salvage surgery. In the remaining, expansion was followed by regression in 16, and cessation of growth in 8. In 2008, Nagano and coworkers reported that transient expansion was much more frequent, occurring in up to 75% of cases; a finding later confirmed by others.s. Literatur ^,​ s. Literatur It is now generally accepted that a volume increase following GKRS is a normal phenomenon for a period of up to 2 years and if well tolerated by the patient, it does not indicate the need for additional treatment. Further discussion regarding “pseudoprogression” following radiosurgery is detailed in Chapter 25.

44.3 Radiation-Induced Tissue Changes

Tissue fibrosis and damage to normal cells are consequences of radiotherapy.s. Literatur It is generally acknowledged that whole brain irradiation affects cognition.s. Literatur Cell death from radiation is caused by double-strand DNA damage leading to loss of mitotic activity. Most of the literature on radiation changes in nerve tissue deals with cell death, edema, and gliosis following fractionated therapy. However, typical doses delivered outside the target by stereotactic radiosurgery (SRS) are much lower and the body of literature on histopathological effects in normal tissue caused by a single SRS treatment is limited. As a rule of thumb, necrosis is seen in spot doses ≥18 Gy delivered by (single fraction) GKRS. The typical tumor margin dose in VS is 11 to 13 Gy at the 50% isodose line, yielding a maximum dose of 22 to 26 Gy to the tumor center. In the early days of radiosurgery, high tumor periphery doses led to cranial nerve and brainstem damage, but such adverse events are nowadays rare.s. Literatur The histological appearance of postirradiated VS is reported by several authors: Lee et al, Iwai et al, and Hong et al did not see any histological changes attributable to radiation in their cases of postirradiated VS.s. Literatur ^,​ s. Literatur ^,​ s. Literatur Pollock and coworkers on the other hand saw collagen and hemosiderin deposits and sclerotic vessels that they ascribed to radiation in most cases.s. Literatur Understandably, histology specimens from the interphase between tumor and adjacent nervous structures may not be obtained. Still, it is possible that even low-dose single-fraction SRS may induce fibrosis, gliosis, and damage to normal cells and thus render irradiated patients more vulnerable than others if they need surgery later on. Many authors report that when operating on previously irradiated VS patients, they find unusual amounts of fibrous scarring causing adherence between the tumor and adjacent neural tissue.s. Literatur ^,​ s. Literatur ^,​ s. Literatur

44.4 When Is Salvage Surgery Indicated?

In order to decide whether radiation for VS has been a success or a failure, the clinician has to review MRI findings and monitor for possible development of new clinical symptoms over a certain time frame. Some patients may experience an increase in symptomatology due to transient tumor expansion, but if tolerable this does not indicate the need for salvage treatment. In these cases, closer radiological and clinical follow-up, for instance, every 6 months instead of annually, may be necessary until stabilization. If the tumor continues to grow on several serial imaging intervals or starts growing after 2 years postradiation, this is likely to imply failed SRS (Fig. 44‑1 ).s. Literatur If salvage treatment is decided upon, the first choice is usually surgery. Factors favoring surgery are young age, large tumor size, and symptom progression. In select cases, older patients and smaller tumors may be considered for reirradiation instead.s. Literatur ^,​ s. Literatur ^,​ s. Literatur ^,​ s. Literatur ^,​ s. Literatur

44.5 Review of Literature

The main bulk of studies dealing with patient outcomes from postradiation VS surgery are presented in Table 44‑1 .s. Literatur ^,​ s. Literatur ^,​ s. Literatur The results are not reported in a homogeneous way, and most publications contain few cases: neurofibromatosis type 2 and sporadic VS are frequently grouped together and in some cases, the criteria used to denote “previous radiosurgery” include patients who had microsurgery plus radiosurgery before final surgery.s. Literatur ^,​ s. Literatur ^,​ s. Literatur ^,​ s. Literatur Similarly, various radiation treatments, usually SRS and fractionated radiotherapy (FRT), are grouped together as “radiation” and dose plan details are often missing or incomplete.s. Literatur ^,​ s. Literatur ^,​ s. Literatur ^,​ s. Literatur All are retrospective and there is an obvious risk of bias in the reporting on operative difficulties. Allegedly, in centers where SRS is advocated as the primary treatment of choice, the authors may be less prone to describe particular difficulties encountered when operating on tumors after radiation. Still, the majority of studies conclude that in irradiated cases, surgery is more difficult because of arachnoid scarring (Table 44‑1 ). Separating the tumor from the facial nerve (FN) is reported as being particularly difficult. Authors disagree on the importance of achieving gross total removal (GTR) in these cases, and FN outcomes vary.s. Literatur ^,​ s. Literatur Any increased risk of recurrence associated with subtotal removal (STR) versus GTR has not been established.

The five largest series on surgery for VS following single radiation treatment are as follows: two from the House Institute in Los Angeles; one from Hannover, Germany; one from the Gruppo Otologico in Italy; and a joint study between Bergen, Norway, and Rochester, MN.s. Literatur ^,​ s. Literatur ^,​ s. Literatur ^,​ s. Literatur ^,​ s. Literatur These five studies comprising altogether 114 cases include matched control groups.s. Literatur ^,​ s. Literatur ^,​ s. Literatur ^,​ s. Literatur ^,​ s. Literatur The studies by Limb et al and Wise et al describe dose plan details, but these data are incomplete or missing in the others. Patients treated by SRS and FRT are grouped together in all except the study from Hannover.s. Literatur Friedman et al found severe arachnoid adherence in 89% of cases in the radiation group.s. Literatur Although this was significantly higher than in the control group, as much as 63% of the control cases showed similar findings. FN outcomes were poorer in the irradiated series, but when the authors reviewed only those with normal preoperative House–Brackmann (HB) grade, FN function was not significantly different between groups.s. Literatur Limb et al as well as Gerganov et al encountered extensive arachnoid scarring during surgery in all previously irradiated patients. Limb et al reported poorer “average” FN outcomes, whereas Gerganov et al found that FN function and complication rates were not significantly different between irradiated and nonirradiated cases. The proportion of control cases showing adherence is not reported in the latter. Several of the publications mentioned earlier report only patients undergoing gross total tumor removal, and conclude that surgery became more difficult than usual if the patient had undergone previous radiosurgery.s. Literatur ^,​ s. Literatur ^,​ s. Literatur In their follow-up study, Friedman and colleagues were less aggressive in removing all tumors at the FN interface.s. Literatur They showed that if aiming at a STR, the FN outcomes improved significantly (85.7% in STR group, 50% in GTR group). The patients were followed up for 1 year postsurgery and the authors reported that none had received any additional treatment at their institution. To avoid FN damage, STR was used in a significantly larger proportion of irradiated than control cases in the study by Wise and coworkers.s. Literatur FN outcomes were similar in both groups following this strategy. In the study by Husseini et al, GTR was achieved in 13 out of 14, with good FN results, although more cases of facial paresis were found in the irradiated group. The remaining studies presented in Table 44‑1 are without matched controls or contain less than 10 patients and are not reviewed further.

Surgeons operating on previously irradiated VS cases may have assumed a cause-and-effect relation between radiation and scarring, although it is only an association from a strictly scientific standpoint. It is established that conventional radiotherapy causes fibrosis.s. Literatur A cause-and-effect relation between VS radiosurgery and adherences is thus likely, but adherences are common findings in large nonirradiated tumors as well. It must be remembered that radioresistance is uncommon in VS; only a few percentage of those undergoing radiosurgery need additional surgery. These tumors may be more difficult to operate on than others not only because they have been irradiated but also because they constitute a biologically separate group.