The purpose of our study was to investigate the risk factors of remnant tumor growth after incomplete resection (IR) of cervical dumbbell-shaped schwannomas (DS).
Twenty-one patients with IR of cervical DS with at least 2 years of follow-up were included and were divided into 2 groups: the remnant tumor growth (G) (n = 10) and no growth (NG) (n = 11) groups. The tumor location in the axial plane according to Toyama classification, the location of the remnant tumor margin, and the tumor growth rate (MIB-1 index) index were compared.
No significant differences in Toyama classification and MIB-1 index were found. Age was significantly higher in the G group (61.4 years vs. 47.6 years; p=0.030), but univariate logistic regression analysis revealed little correlation to the growth (odds ratio [OR], 1.08; 95% confidence interval [CI], 1.001–1.166; p=0.047). Seventeen patients (9 in the G and 8 in the NG group) underwent the posterior one-way approach, and significant differences in the location of the remnant tumor margin were confirmed: within the spinal canal in 1 and 0 case, at the entrance of the intervertebral foramen in 7 and 1 cases, and in the foramen distal from the entrance in 1 and 7 cases, in the G and NG groups, respectively (p=0.007). The proximal margin was identified as a significant predictor of the growth (OR, 56.0; 95% CI, 2.93–1,072; p=0.008).
Remnant tumors with margins distally away from the entrance of the foramen were less likely to grow after IR of cervical DS.
The incidence of dumbbell-shaped tumors accounts for 18% of all spinal cord tumors, and among these, 44% occur most commonly in the cervical spine [
Seventy-six patients with cervical DS who underwent surgery at a single academic institution between 1997 and 2015 were reviewed. Of the 76 patients, 28 underwent IR of cervical DS. Patients who underwent IR of cervical DS based on the findings of postoperative magnetic resonance imaging (MRI) and those who underwent postoperative MRI at more than 2 time points to investigate remnant tumor growth with a minimum of 2 years of follow-up were included in the study. Finally, 21 patients were enrolled in the study. IR was defined as resection of cervical DS with a remnant tumor at the intraforaminal or extraforaminal area. Patients with and without remnant tumor growth were divided into 2 groups: the growth (G) and no growth (NG) groups, respectively.
The patients’ clinical characteristics, including age, sex, the spinal segment of the tumor (the nerve root affected by the tumor), the tumor location in the axial plane according to Toyama classification (
Continuous variables were presented as mean±standard deviation (SD). The MIB-1 index was presented as median (first to third interquartile). A comparison of each independent variable between the 2 groups was performed using the Mann-Whitney U-test for the MIB-1 index and an independent t-test for other continuous variables. A chi-square test was used to analyze discrete variables. Univariate logistic regression analysis was performed to investigate the correlation of each aforementioned variable with remnant tumor growth. Regrowth-free probability was calculated using the Kaplan-Meier method. A p-value for comparison of regrowth-free probability between patients with surgical margins at zone 3 and those with surgical margins at 1 or 2 was determined by Log-rank test. IBM SPSS Statistics ver. 24.0 (IBM Co., Armonk, NY, USA) was used for all statistical analyses. Probability values of less than 0.05 were used to denote statistical significance.
We certify that all applicable institutional and governmental regulations concerning the ethical use of human participants and the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments were followed during the course of this research. Informed consent was obtained from all individual participants included in the study. This study was approved by the Institutional Review Board (IRB) of Keio University School of Medicine (IRB No. 20110142).
The patients’ characteristics are summarized in
The median MIB-1 index values were 5 (1.75–7.75) and 5 (3–10) in the G and NG groups, respectively. No significant difference in the MIB-1 index values was found between the 2 groups (p=0.863) (
During the period when the patients in this study underwent operations in our institution, the posterior one-way approach was mainly adopted for the resection of cervical DS. The anterior one-way approach was performed in one patient with Toyama type IIc (foraminal and paravertebral) (case 18 in
The mean regrowth-free period was 106 months (95% confidence interval [CI], 73–139 months). The regrowth-free probability at 2, 5 and 10 years was 95.2%, 58.3%, and 30.0%, respectively (
The anatomical location of the remnant tumor margin and age showed a significant correlation to remnant tumor growth, whereas the other variables did not. The proximal tumor margin at zone 1 or 2 had a higher risk of remnant tumor growth (odds ratio [OR], 56.0; 95% CI, 2.93–1,072; p=0.008) than higher age (OR, 1.08; 95% CI, 1.001–1.166; p=0.047).
A 74-year-old male with Toyama type IIIa schwannoma derived from the right C7 nerve root (
A 32-year-old male with Toyama type IIIa schwannoma derived from the left C3 nerve root (
In this study, we examined the growth of remnant tumors after IR of cervical DS and investigated its predictive factors. Our findings revealed that the anatomical location of the remnant tumor margin was the most significant predictor of remnant tumor growth. This result suggests that remnant tumors with its surgical margin distally away from the entrance of the intervertebral foramen were less likely to grow into the spinal canal even when the extraforaminal components are involuntarily left after a posterior one-way surgery.
Reportedly, the occurrence rate of remnant tumor growth after IR ranged from 16.7% to 60% [
In this study, 10 of the 21 patients (47.6%) showed remnant tumor growth during the mean follow-up period of 61 months. The directions of the residual tumor growth were bidirectional both extraforaminally and into the spinal canal in 8 patients and unidirectional into the spinal canal in 2 patients. Note that the growth was directed at least into the spinal canal in all patients, whereas 11 of the 21 patients (NG group, 52.4%) showed no growth during the mean follow-up period of 74 months. This obvious difference in the fate of the remnant tumors between the 2 groups prompted us to investigate the predictive factors of their growth.
As far as we investigated, the MIB-1 index is the only one factor used as a prognostic marker of remnant tumor growth after IR of spinal DS. Sohn reported that the average MIB-1 index was significantly higher in patients with remnant tumor growth (6.3%±5.6%) than in those without growth (2.0%±1.6%) [
Fukuda et al. [
Though we revealed that the G group had a significantly higher age than the NG group (61.4 years vs. 47.6 years; p=0.04), higher age had a smaller influence on remnant tumor growth (OR, 1.08; 95% CI, 1.001–1.166; p=0.047) than the remnant tumor margin, and previous studies have not described significant correlations between age and remnant tumor growth. However, these findings at least support the importance of frequent MRI follow-up in elderly patients as well, especially when the remnant tumor margin is proximal. We unfortunately failed to explain the higher age in the G group, and this should be considered a limitation of this study.
Another limitation of this study is the small sample size and possible sample bias. Multivariate logistic regression analysis was not performed to investigate the independent predictors of remnant tumor growth because of the small sample size, and the univariate analysis performed in this study cannot exclude possible confounding factors. Additionally, another limitation of this study is the lack of quantitative analyses of preoperative and postoperative tumor size. Previous studies measured tumor size as the longest diameter of the tumor on axial MRI [
To the best of our knowledge, this is the first study to provide a predictive factor of remnant tumor growth after IR of cervical DS using the posterior one-way approach. No significant difference in the MIB-1 index was found between patients with and without remnant tumor growth contrary to other studies. The entrance of the intervertebral foramen, defined as the posterolateral corner of the intervertebral disc or the vertebral body, could be used as an anatomical landmark to help us know the surgical margin to lower the risk of the remnant tumor growth into the spinal canal.
The authors have nothing to disclose.
This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Conceptualization: KK, NN; Data curation: KK; Formal analysis: KK, NN; Methodology: KK, NN; Project administration: KK, NN; Visualization: KK; Writing - original draft: KK; Writing - review & editing: KK, NN, OT, SS, SN, EO, MY, MM, MN, KW.
The location of the dumbbell-shaped tumor in the axial plane by Toyama classification [
The anatomical locations of the remnant tumor margins. Zone 1, in the spinal canal; zone 2, at the entrance of the intervertebral foramen, touching the posterolateral corner of the intervertebral disc or vertebral body; and zone 3, in the intervertebral foramen distally away from its entrance. Dotted lines indicate the entrance of the intervertebral foramen.
Kaplan-Meier curves of regrowth-free probability. Overall patients (A) and comparison between the patients with surgical margins at zone 3 and those with surgical margins at zone 1 or 2 (B).
T2 axial magnetic resonance images of the foraminal remnant tumor with postoperative growth. (A) Toyama type IIIa (case 9 in Table 2). (A, C) Dotted arrows indicate the posterolateral corner of the vertebral body defined as the entrance of the intervertebral foramen. The remnant tumor margin was on the corner (B, arrow). The tumor growth 11 months (C, arrow) and 54 months (D) after surgery.
T2 axial magnetic resonance images of the foraminal remnant tumor with no postoperative growth. (A-C) The dotted arrows and solid arrows indicate the posterolateral corner of the vertebral body defined as the entrance of the intervertebral foramen and the remnant tumor margin, respectively. (A) Toyama type IIIa (case 19 in Table 2). (B) The remnant tumor margin was in the foramen (arrow) distally away from the posterolateral corner of the intervertebral disc (dotted arrow). (C) No obvious evidence of tumor growth 55 months after surgery.
Patient characteristics
Characteristic | G group (n = 10) | NG group (n = 11) | p-value |
---|---|---|---|
Age (yr) | 0.030 |
||
Mean ± SD | 61.4 ± 14.6 | 47.6 ± 12.3 | |
Range | 37–83 | 32–72 | |
Sex | 0.665 | ||
Male | 5 | 4 | |
Female | 6 | 7 | |
Follow-up period (mo), mean ± SD | 61.0 ± 31.8 | 73.9 ± 53.5 | 0.515 |
Affected nerve root (n) | 0.745 | ||
1 | 1 | 0 | |
2 | 1 | 2 | |
3 | 1 | 1 | |
4 | 1 | 1 | |
5 | 2 | 2 | |
6 | 0 | 2 | |
7 | 3 | 3 | |
8 | 1 | 0 | |
Toyama classification (n) | 0.756 | ||
1 | 0 | 0 | |
2a | 0 | 1 | |
2b | 2 | 1 | |
2c | 0 | 1 | |
3a | 5 | 4 | |
3b | 3 | 3 | |
4 | 0 | 0 | |
5 | (1) |
(1) |
|
6 | 0 | 1 | |
Extent of tumor resection (n) | 0.178 | ||
Subtotal resection (≥ 90%) | 0 | 2 | |
Partial resection (< 90%) | 9 | 9 | |
Surgical margin (n) | 0.007 |
||
Zone 1 | 1 | 0 | |
Zone 2 | 7 | 1 | |
Zone 3 | 1 | 7 | |
MIB-1 index (%) | 0.863 | ||
Median (IQR) | 5 (1.75–7.75) | 5 (3–10) | |
Range | 1–15 | 1–15 |
G group, patients with remnant tumor growth; NG group, patients without remnant tumor growth; SD, standard deviation; IQR, interquartile range.
p<0.05, statistically significance using the independent t-test.
p<0.05, statistically significance using the chi-square test for independence.
Number in the paragraphs indicates type III+V.
Details of the preoperative and postoperative characteristics of the tumor
Group | Case No. | Sex | Age (yr) | Follow-up period (mo) | Affected nerve root | Toyama classification | Surgical approach | Extent of tumor resection | Remnant tumor Margin (zone) | MIB-1 index (%) | Regrowth direction |
---|---|---|---|---|---|---|---|---|---|---|---|
G | 1 | F | 49 | 106 | 4 | IIIb | P | PR | 2 | 1 | SC+EF |
2 | F | 66 | 112 | 5 | IIIa | P | PR | 2 | 5 | SC+EF | |
3 | M | 83 | 50 | 5 | IIb | P | PR | 1 | 5 | SC+EF | |
4 | F | 69 | 96 | 8 | IIIb | P | PR | 2 | 15 | SC+EF | |
5 | F | 53 | 24 | 2 | IIb | P | PR | 2 | 5 | SC+EF | |
6 | M | 75 | 32 | 3 | IIIa | P | PR | 2 | 5 | SC | |
7 | M | 37 | 51 | 1 | IIIa+V | P | PR | 3 | 2 | SC+EF | |
8 | M | 61 | 47 | 7 | IIIb | P | PR | 2 | 10 | SC+EF | |
9 | M | 74 | 55 | 7 | IIIa | P | PR | 2 | 1 | SC | |
10 | F | 47 | 37 | 7 | IIIa | P | Unknown | Unknown | 7 | SC | |
NG | 11 | M | 45 | 193 | 5 | IIa | P | PR | 3 | 15 | - |
12 | M | 62 | 96 | 7 | IIIb | A+P | PR | NA | 5 | - | |
13 | F | 32 | 122 | 5 | IIIb | P | PR | 3 | 5 | - | |
14 | F | 56 | 125 | 6 | VI | A+P | PR | NA | 1 | - | |
15 | M | 48 | 55 | 2 | IIIa+V | P | PR | 3 | 10 | - | |
16 | F | 41 | 34 | 6 | IIIa | P | PR | 3 | 3 | - | |
17 | F | 72 | 24 | 4 | IIIa | P | STR | 2 | 5 | - | |
18 | F | 43 | 33 | 7 | IIc | A | STR | NA | 5 | - | |
19 | M | 32 | 55 | 3 | IIIa | P | PR | 3 | 2 | - | |
20 | F | 40 | 41 | 2 | IIa | P | PR | 3 | 5 | - | |
21 | F | 53 | 35 | 7 | IIIb | P | PR | 3 | 10 | - |
P, posterior one-way approach; A, anterior one-way approach; A+P, combined anterior and posterior approaches; PR, partial resection; STR, subtotal resection; NA, not applicable because case 12 and 14 underwent the combined anterior and posterior approach and case 18 underwent the anterior one-way approach; SC, spinal canal; EF, extraforaminal direction.