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Treatment Outcomes and Follow-Up Compliance after Less than Total and Total Resection of Vestibular Schwannomas in 294 Patients
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.304069
Keywords: Brain tumor, follow-up, outcome, radiosurgery, surgery
Management of vestibular schwannomas (VS) has seen a paradigm shift over the last two decades, with the focus shifting from eradication of the tumor to preservation of function with tumor control. The surgical strategy presently aims at the preservation of facial nerve function and hearing preservation, if there is serviceable hearing at presentation.[1],[2],[3],[4],[5],[6],[7],[8],[9],[10] Small VSs (<2.5 cm) can be treated primarily with stereotactic radiosurgery (SRS).[11],[12],[13],[14] However, the ideal management strategy for large and giant VSs is debatable. Facial nerve preservation is one of the main aims of microsurgery in such cases, but it becomes increasingly difficult to achieve this goal as the size of tumor increases. In an effort to preserve facial nerve function, some neurosurgeons advocate leaving a small residue along the facial nerve, which can then be treated with SRS at a later date.[15],[16],[17],[18],[19],[20] However, the therapy remains incomplete if patients undergoing less than total excision of a VS do not receive SRS or regular imaging follow-up. Although several authors have reported on the outcomes of a strategy of less than total excision of a large VS followed by SRS, none of these publications have focused on the quality of follow-up. There is also no consensus on the indications for SRS in these patients. We reviewed our data on planned subtotal (85–95%) and near-total (≥95%) resection (STR and NTR) as well as gross total resection (GTR) of VSs over a 10-year period with the specific objectives of determining their compliance with our follow-up advice, their facial function outcome and the proportion of patients who required SRS. We also reviewed the literature to determine the compliance with follow-up in large series of patients undergoing surgery for VS. Clinical material and methods Patient material A retrospective study of consecutive patients, who underwent excision of a previously untreated VS, over a 10-year period between 2005 and 2015, was performed. Several surgeons operated upon these patients. The demographic details of patients were noted, and their preoperative facial function was documented, using the House and Brackmann (HB) facial grading system.[21] Audiometric data was not included for these patients as none of our patients with large tumors had serviceable hearing. All patients underwent a retromastoid suboccipital craniectomy, retrosigmoid approach and excision of tumor, as detailed in a previous publication from our department.[22] Intraoperative electrophysiological facial nerve monitoring was used for all cases. Radiology The preoperative volume of the VS and postoperative volume of the residual tumor, if visualized on gadolinium-enhanced magnetic resonance imaging (MRI) or contrast-enhanced computed tomography (CT) scan, were measured. All patients had a preoperative gadolinium-enhanced MRI. The maximum length of the tumor in any dimension was considered as its size, and the VS was considered “large” if it measured more than 3 cm in its largest dimension, and “giant” if it measured more than 4 cm. The volume of these tumors was calculated on the gadolinium-enhanced T1-weighted images, using the following formula: Volume = A * B * C/2 Where, A: maximum anteroposterior dimension (cm) B: maximum mediolateral dimension (cm) C: maximum craniocaudal dimension (cm) In the postoperative period, all patients underwent a contrast-enhanced CT scan of the brain prior to discharge, and for patients who could not be followed up radiologically, this CT was used to assess the residual tumor volume. On serial follow-up, the T1-weighted MRI sequences with gadolinium were used to obtain volumes of the residual tumor, if any. For patients who underwent SRS a volumetric T1-weighted axial sequence with gadolinium injection (3 mm slice thickness) was performed in a 1.5 Tesla Siemens MRI machine (Siemens, Germany). The volumes of these tumors were calculated using the BrainLab software (BrainLab, Germany) used by us during SRS planning. Extent of resection The extent of resection (EOR) was categorized based on the size of the residual tumor as seen on postoperative contrast imaging, CT, or MRI. EOR was defined as follows:
Postoperative SRS Patients with incomplete resection of VS were typically followed up after 3–6 months to assess the size of the residual tumor on an MRI, and if a significant residue was seen, then these patients were subjected to SRS. Those who underwent GTR were often advised to follow-up after a year. Radiosurgery was performed using a linear accelerator (LINAC)-based system (BrainLab, Germany) using a micro-multileaf collimator. Stereotactic contrast-enhanced CT images with MR fusion was used to plan the radiosurgery. Typically, a dose of 10–12 Gray was delivered to the periphery of the tumor. Follow-up Patients were followed up during clinic visits, telephonically or using a postal questionnaire. Patients were advised yearly MRI scans, irrespective of whether they received SRS or not, at least for the first 5 years. Complications of SRS, if any, were noted. Facial function at follow-up The facial function at each follow-up was documented. We divided the follow-up facial nerve outcomes at final follow-up, into good outcome (HB grades 1–3) and poor outcome (HB grades 4–6). For patients who could not be followed up, their facial function at the time of discharge from the hospital was considered as their follow-up facial function. Data analysis We studied the differences in the outcomes between the group that underwent GTR and that underwent NTR/STR. We also studied the correlation between the residual tumor volume and the use of adjunctive SRS. Influence of age (≤40 years vs >40 years), gender, distance of place of residence from hospital (far and near; those belonging to states adjoining our state were categorized as residing near our hospital, as opposed to those from distant states or other countries, who were categorized as residing far from our hospital), preoperative volume of tumor, early postoperative residual tumor volume, postoperative facial nerve function and extent of resection on the compliance with follow-up was analyzed to using logistic regression. Data were entered into Microsoft Excel and analyzed using SPSS Statistics (IBM, Version 20). A P value of less than 0.05 was considered significant. Results of univariate and multivariate analyses were presented as odds ratios (OR) with a 95% confidence interval (CI) and P value.
Between January 2005 and January 2015, a total of 294 patients with VS underwent microsurgical excision of their tumors. There were more males than females (157 patients; 53.4%). Extent of resection A GTR was performed in 239 patients (81.3%). A less than total excision of the VS was performed in 55 patients (18.7%). NTR was performed in 36 patients (65%) and STR in 19 patients (35%). The average age of the cohort was 42.6 years (±12.3, range: 6–73 years). There was no significant difference between the ages of patients undergoing GTR versus those undergoing a less than total resection (44.6 years vs 42.1 years, P = 0.16). The mean diameter of the tumors was 4.2 cm (range: 2.2–7.5 cm; SD ± 0.8 cm). Eight tumors were partly multicystic and none of the tumors were entirely cystic. The mean diameter of the tumor in the GTR group was 4.2 cm (±0.8 cm) and that in the NTR/STR group was 4.3 cm (±0.9 cm). There was no significant difference in the size of tumors among the two groups (P = 0.41). [Table 1] highlights the demographic details of those patients undergoing GTR vs those who underwent a less than total excision.
Facial nerve function In the GTR group, 97.9% of patients (n = 234) had a good facial function preoperatively (HB grades 1–3). 26 patients (10.9%) had a normal facial function (HB grade 1), 175 patients (73.2%) had an HB grade 2 facial function, and 33 patients (13.8%) had an HB grade 3 facial function. The remaining five patients had poor facial function preoperatively with three of these having an HB grade 4 facial function and the remaining two patients having an HB grade 5 facial function. The mean preoperative facial function was 2.08 in this group of patients. On the last follow-up, only 29.3% (n = 70) had a good facial function whereas the vast majority had a poor facial function (70.7%). The mean follow-up facial function in this group of patients was 4.28. In the NTR/STR group, all patients had a good facial function preoperatively, with 18 patients having an HB grade 1 facial function, 32 patients having an HB grade 2 facial function, and only 5 patients having an HB grade 3 facial function. The mean preoperative facial function (HB grade) in this group of patients was 1.8 while the mean follow-up facial function HB grade was 2.4 (P = 0.0008). On follow-up, 81.8% of the cases (n = 45) had a good facial outcome and the remaining 18.2% had a poor outcome. Patients with larger tumors were more likely to have a worse postoperative facial function (P < 0.0001). There was no difference in the volume of the residual tumor in patients with good facial outcomes as compared to those with poor outcomes (mean volume 1.1 cm3 as compared to 0.9 cm3; P = 0.8). There was also no significant difference in the facial outcomes of patients who underwent SRS as against those who did not (P = 0.2). There was no instance of worsening of facial function after receiving SRS. In contrast, the group of patients who underwent GTR had a worse preoperative facial function (2.08 vs 1.8, P value = 0.002), and only 29.3% (n = 70/239) had a good facial outcome at last follow-up. [Table 2] highlights the facial function of the entire cohort of patients, comparing the GTR versus the NTR/STR group.
Follow-up In the GTR group, follow-up could be obtained in merely 69.5% of the patients (n = 166/239). The mean follow-up in those patients was 32.8 months, ranging from 3 months to 12 years. In the NTR/STR group, follow-up could be obtained in 94.5% of the patients (n = 52/55) with a mean follow-up of 37.4 months, ranging from 6 months to 10.5 years. The average follow-up for patients who underwent SRS was 31 months, whereas it was 43 months for those who did not undergo SRS (P = 0.09). Rationale for SRS in patients undergoing NTR/STR We offered SRS to all patients who underwent STR (n = 19) and to 15 patients who underwent NTR (n = 36). Thus, a total of 34 patients were advised SRS. However, of the 19 patients who underwent STR, four (21.1%) did not undergo SRS. The reasons for not performing SRS in these four patients are as follows: two patients did not return after surgery and could be followed up only telephonically; in one patient who was aged >60 years, the family decided against further intervention; one patient was detected to have a fairly large residual tumor measuring 6.34 cm3 and was offered fractionated stereotactic radiotherapy (SRT). He then underwent SRT and was administered 54 Gray in 30 fractions. He had stable residue on an MR done 3 years following SRT. Of the 15 patients who underwent NTR and were advised SRS, four (26.7%) did not undergo SRS. Three out of these patients did not return for follow-up stating that they were doing well clinically and did not feel the need to return for a checkup, although they were informed otherwise. One patient was on very irregular follow-up and cited financial constraints as the only reason for being unable to undergo SRS. SRS Of the 55 patients undergoing a less than total resection, SRS was performed in 26 (47.3%) patients at an average interval of 7.7 months (range: 3–16 months) after microsurgery. The mean preoperative volume of the tumor in patients who underwent SRS was 24.8 cm3, whereas the mean volume of the tumor in others was 25.7 cm3 (P = 0.8). The mean volume of the residual tumors undergoing SRS (n = 26) was 2 cm3 (range: 0.4–6.3 cm3), which was a 92.1% reduction in the preoperative volumes [Figure 1].
Of the patients who did not undergo SRS (n = 29), the mean follow-up volume of the tumors was 0.5 cm3 (range, 0 to 6.3 cm3) at an average follow-up duration of 44 months (range: 6 months to 10.5 years) [Figure 2]. The mean postoperative volume of tumors in patients who underwent SRS was significantly larger than in those who did not undergo SRS (P = 0.001).
In the subgroup of patients undergoing GTR (n = 239), seven patients (3%) ultimately went on to receive SRS on follow-up, after a mean duration of nearly 55 months (4.5 years) from the date of surgery. Compliance with follow-up and completion of therapy Patients who underwent GTR of their tumors (n = 239) were considered to have received complete therapy. A follow-up after surgery was available only for 166 patients (69.5%). As many as 73 patients (30.5%) had a maximum follow-up of only 12 months and were subsequently lost to follow-up. The others (93 patients) had a follow-up of 14 months or more. Two patients returned for the first follow-up 9 years and 11 years after surgery, both of whom were detected to have a recurrence of the tumor. One patient underwent SRS and another required surgery. Six other patients on regular follow-up required SRS for recurrent tumors [Figure 3], and one patient required reoperation after 8 years. Tumor recurrence was thus detected in a total of nine patients (3.7%) at a mean interval of 67.3 months (nearly 5.5 years).
In the group undergoing NTR/STR, we could identify two distinct groups of patients based on compliance with our advice:
Summarizing, the patients in the first category have been compliant with our advice, while patients in the second category have either been partially compliant with or noncompliant with our advice and hence their treatment outcome is considered suboptimal. A flowchart depicting the management and follow-up of all patients is shown in [Figure 4].
Factors associated with noncompliance We analyzed the possible causes of noncompliance with follow-up in the NTR/STR group [Table 3]. Interestingly, the geographical residence of these patients did not significantly influence their compliance with our advice. Almost all patients (90.5%) who were not fully compliant with follow-up had undergone an NTR of their tumors and consequently had a significantly smaller residual tumor volume, as measured on their first follow-up imaging. On multivariate analysis, the factors associated with poor compliance were the preoperative volume of the tumor (OR 1.10, 95% CI 1.00–1.21; P = 0.05) and early postoperative volume of the tumor (EOR) (OR 0.02, 95% CI 0.002–0.25; P = 0.002) [Table 4]. The mean postoperative volume of the tumors in patients who complied with follow-up advice was 1.76 cm3 vs 0.23 cm3 in patients who did not comply. Therefore, patients with larger tumors and those who had undergone a more extensive resection were more likely to default on follow-up advice.
In the GTR subgroup, there was no significant correlation between the size of tumor and follow-up compliance (OR 0.97, 95% CI 0.69–1.36; P = 0.87).
Goals of surgical resection With a low operative mortality rate of around 1%[2],[5],[6],[23] and the absence of effective adjuvant therapy for a residual tumor, GTR became the gold standard for surgery for VS. The widespread availability of SRS[11],[12],[13],[24],[25],[26],[27],[28],[29]and emphasis on quality of life (QoL) outcomes in recent years have led to an acceptance of less than total resection in exchange for preservation of facial function and, if possible, preservation of hearing.[9],[30],[31],[32],[33],[34],[35] The tumor residue is typically treated with SRS to achieve good long-term tumor control. We are mostly confronted with patients harboring large and giant VSs, with such tumors constituting nearly 90% of all VS managed by us. All patients with large and giant tumors are given the option of less than total excision of the tumor with a greater possibility of preservation of facial nerve function. Those who opt for the same undergo “incomplete” resection of the tumor. Surprisingly, due to financial constraints and/or logistic issues in complying with periodic follow-up, a significant proportion of patients opted for a GTR of the tumor, even if it meant that there would be a significant risk of postoperative facial nerve dysfunction. This is evident from the fact that out of 294 patients operated by us for VS over the last 10 years, only 55 (18.7%) patients underwent a planned incomplete resection of the tumor. Of the patients undergoing total excision of the VS (n = 239), only 29.3% had a good facial outcome (HB grades 1–3), as compared to 81.8% of patients who underwent an incomplete resection. Facial nerve preservation after subtotal excision It has been established that the size of the VS is the main predictor of postoperative facial nerve outcome and that the risk of facial nerve dysfunction is 6-fold higher in large VSs (>3 cm in diameter) as compared to smaller ones.[36],[37],[38] The rate of facial nerve preservation in large VSs varies from 80 to 93%, but in cases of giant VSs (>4 cm in diameter), this figure falls significantly into the range of 38–62%.[37],[38] In our series, we achieved good facial nerve function (HB grades 1–3) in 81.8% of patients with mostly large and giant tumors (mean tumor diameter, 4.2 cm). Our results are in consonance with that achieved in most series.[5],[15],[18],[32],[34],[37],[39] However, 18.2% of our cases had a poor facial functional outcome (HB grades 4–6) in spite of a planned STR or NTR to preserve facial nerve function. There could be several reasons for the loss of facial nerve function. Multiple surgeons with varying levels of expertise in VS surgery were involved in the management of the patients. Another reason for the poor facial outcome is possibly related to an overenthusiastic removal of the tumor in an attempt to reduce the tumor volume for subsequent SRS. Finally, the ischemia of an anatomically preserved facial nerve could lead to loss of function. Whether facial nerve function affects the QoL significantly has been a matter of debate, with some studies supporting it while others disputing it.[40],[41],[42],[43] In a recent study published by us, we found that although facial function does not significantly affect the overall QoL, it does have a significant bearing on the social domain of QoL.[44],[45] Defining EOR There has been no uniformity in the definition of the EOR for a VS. Some authors have used a percentage of the preoperative tumor volume to determine the EOR whereas others have relied on absolute measurement of residual tumor. Some authors have defined NTR as a residual thin capsule of tumor left on the facial nerve or the brainstem with a postoperative MRI showing a thin streak of enhancement.[31] Others have considered 1–2% or <5% residue of the preoperative tumor volume as NTR.[35],[46] STR has been defined by some authors as a few millimeters of tumor that represents nearly 5–10% volume of the preoperative tumor volume (80–90% resection of tumor).[35],[46],[47],[48],[49] Fukuda et al.[50] have defined EOR in their series as GTR when there is no residue, STR when the resection was 90–99% and partial resection (PR), as <90% resection. An absolute volume of less than 5 Õ 5 Õ 2 mm has been defined by some authors as NTR.[48],[49],[51] In a consensus meeting on reporting surgical results in VS in 2003, it was agreed to define NTR as tumor remnant of up to 2%, PR up to 5%, and STR as more than 5% of the preoperative tumor volume.[52] However, there is still significant heterogeneity in the reporting of EOR of VS. The mean volume of the residual tumor in different series reporting on combined therapy ranges from 0.22 cm3 to 9.35 cm3.[2],[16],[17],[18],[19],[31],[53],[54],[55],[56],[57] It is evident that there is a wide variation in the volume of the residual tumor that is left in situ in an attempt to preserve function. In our series, the mean volume of the residual tumor was 1.18 cm3 that is closer to the lower end of the reported range. SRS after incomplete excision A combination of microsurgical excision and SRS has been shown to provide good tumor control as well as functional outcomes.[2],[15],[16],[17],[18],[19],[20],[28],[38],[53],[54],[55],[58],[59] A summary of the published literature on SRS as an adjuvant treatment is presented in [Table 4]. It is unclear whether all residual tumors should be treated with SRS. Most authors do not clearly define the indications for SRS for a residual tumor. Some authors have recommended SRS only if there is a documented growth in the size of residual tumor on follow-up imaging[18] whereas some have advised SRS only if the residual tumor volume exceeds 1.5 cm3.[38] Younger age at presentation and evidence of rapid tumor growth preoperatively have also been used as an indication for subjecting the residue to SRS soon after microsurgery.[48] The interval between microsurgery and SRS in different series ranges from as early as 1 month to as late as 13 months. It has been shown that early adjuvant SRS (within 6 months of microsurgery) can provide better tumor control as opposed to SRS later than that.[55] We advocate a minimum waiting period of 3 months after surgery before performing SRS to allow the tumor to “fold” on itself to form a more optimal radiosurgery target. It also allows for possible improvement in facial nerve function if it has deteriorated after surgery. Need for periodic follow-up Several authors[2],[46],[48],[60],[61],[62],[63] have noted that patients undergoing STR and NTR of VS had a higher risk of recurrence of their tumors than those undergoing GTR. But recurrence following GTR is also documented and in one series occurred at a median of 7.5 years following surgery (range: 2–22.5 years).[61] Some have also considered a higher proliferative index of more than 3.5% as a risk factor for recurrence.[64] Histological variation (Antoni-A or Antoni-B) has not been conclusively proven to be of any prognostic significance.[65] In our study, nine patients (3.7%) who underwent GTR were subsequently detected to have tumor recurrence after a mean interval of 5.5 years from surgery either requiring reoperation or SRS. Thus, periodic and long-term radiological follow-ups are mandatory in the management of VS, especially when STR has been performed. Compliance with follow-up Most of the literature available on “incomplete” resections of VS—with or without adjuvant SRS—comprises retrospective studies, uniformly limited by the relatively short duration of follow-up (mean duration ranging from 28 months to 3.9 years).[2],[15],[17],[18],[20],[23],[48],[53],[54],[55],[58],[66] Although some authors have reported a 100% “compliance” with follow-up,[15],[17],[18],[20],[51],[53],[67] these reports typically come from Gamma Knife centers and, therefore, the data only pertains to patients referred to them after surgery was done in another center. Therefore, it is impossible to determine the compliance with follow-up after planned NTR or STR. [Table 5] shows the rates of noncompliance with follow-up advice in several large surgical series of VS. It is clear that the attrition rate with follow-up is substantial all over the world and this could lead to incomplete therapy in patients who undergo NTR or STR of a VS. The noncompliance with follow-up ranges from 7% to 45%. This is noted even in reports from centers in developed countries.
Interestingly, one of the two independent factors associated with noncompliance, in our series, was the extent of resection, with patients having smaller residues more likely to be noncompliant. It is possible that patients with very small residues believe that they are “cured” of their disease and this misunderstanding leads to poor compliance with follow-up advice. An additional factor associated with the lack of compliance with follow-up advice was the preoperative volume of the tumor. Patients with larger tumors were less compliant which could represent their propensity to delay seeking medical therapy. Hence, patients subjected to “incomplete” resection of VSs must be carefully selected after having a detailed preoperative discussion regarding the need for periodic and long-term follow-up. This need for periodic follow-up is also mandatory in the group of patients undergoing a total excision of their tumor, despite knowing the fact that those patients mostly opt for GTR at the expense of a higher risk of facial nerve dysfunction, citing difficulty to follow-up as the main reason. This was evident from our cohort of patients undergoing total excision of the VS during the same period, of whom only 69.5% could be followed up. More so, at least nine patients (3.7%) required retreatment in the form of either reoperation or SRS on long-term follow-up. Although the combined treatment strategy of surgery ± SRS is being practiced worldwide, we wanted to highlight the fact that compliance with follow-up can be a major issue not only with our patient population but with patients all over the world.[2],[15],[17],[18],[20],[23],[48],[53],[54],[55],[58],[66] This could lead to a patient presenting several years later with a large recurrence and the need for repeat surgery. This defeats the purpose of providing a recurrence-free, good functional outcome in these patients with the use of hybrid surgery (less than total excision of the tumor to preserve function with SRS for residue if needed).
“Incomplete” microsurgical excision of large and giant VSs followed by SRS is an effective strategy that fulfills the twin objectives of preserving function and long-term tumor control. We advocate the use of SRS only for “significant” residual tumor seen on a follow-up imaging and periodic follow-up alone in patients with small residues, provided there has been a discussion about each individual patient's willingness for regular follow-up. Our results show that patients with larger tumors and smaller postoperative residues are more likely to default on follow-up, hence an upfront SRS at the first follow-up (3–6 months) might be a safer strategy in these patients. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5]
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