Fax: (011) 49-40-42803-5192
Value of postoperative stereotactic radiosurgery and conventional radiotherapy for incompletely resected typical neurocytomas
Article first published online: 6 JAN 2006
Copyright © 2006 American Cancer Society
Volume 106, Issue 5, pages 1140–1143, 1 March 2006
How to Cite
Rades, D. and Schild, S. E. (2006), Value of postoperative stereotactic radiosurgery and conventional radiotherapy for incompletely resected typical neurocytomas. Cancer, 106: 1140–1143. doi: 10.1002/cncr.21628
- Issue published online: 17 FEB 2006
- Article first published online: 6 JAN 2006
- typical neurocytoma;
- incomplete resection;
- radiation therapy;
- stereotactic radiosurgery;
Two groups of central neurocytomas have been identified: typical and atypical neurocytomas. The more benign typical neurocytomas have a better prognosis. Complete resection of typical neurocytomas results in significantly better outcome than incomplete resection. The current study investigated whether the outcome after incomplete resection can be improved by postoperative stereotactic radiosurgery (SRS) or by conventional radiotherapy.
The data of all neurocytoma patients reported since 1997, when the first neurocytoma patient treated with SRS was described, were reviewed. Patients who underwent complete resection or those with atypical neurocytoma were excluded from the analysis. Three different therapies were compared for overall survival (OS) and local control (LC): incomplete resection alone (ITR), ITR followed by conventional radiotherapy (ITR+cRT), and ITR followed by stereotactic radiosurgery (ITR+SRS).
Data were complete in 121 patients (59 ITR, 41 ITR+cRT, and 21 ITR+SRS). The 5-year-LC after ITR was 51%. LC was significantly better after ITR+cRT (87%, P = 0.001) and after ITR+SRS (100%, P = 0.004). The difference between ITR+cRT and ITR+SRS was not significant (P = 0.45). The 5-year-OS was 93% after ITR, 100% after ITR+cRT, and 100% after ITR+SRS. The differences between the various groups were not significant. The P-values were 0.13 for ITR versus ITR+cRT, 0.29 for ITR versus ITR+SRS, and 1.0 for ITR+cRT versus ITR+SRS.
After ITR of typical neurocytomas, LC is significantly improved by both conventional radiotherapy and SRS. The results of both radiation treatments were similar. SRS is a reasonable alternative to conventional radiotherapy in selected patients. Cancer 2006. © 2006 American Cancer Society.
Central neurocytomas are generally described as benign central nervous system tumors. They can be divided into two groups: typical and atypical neurocytomas. Typical neurocytomas have a significantly better prognosis than atypical neurocytomas.1 They are characterized by an MIB-1 labeling index ≤ 3% and the absence of histologic atypia.2 Complete resection of typical neurocytomas is associated with significantly better rates of survival and local control (LC) than incomplete resection.1 If only an incomplete resection can be achieved, LC but not survival is improved with postoperative conventional radiotherapy. However, LC is quite desirable because recurrent typical neurocytomas can cause intracerebral hemorrhage, neurologic sequelae, and hydrocephalus. Recurrent typical lesions also may degenerate into atypical lesions with clinically malignant behavior such as craniospinal dissemination.3–7
The current study investigated whether the outcome after incomplete resection of typical neurocytomas can be improved either with conventional radiotherapy or with stereotactic radiosurgery (SRS). SRS is administered in a single fraction. It has to be distinguished from fractionated stereotactic radiotherapy (SRT), which may take several weeks of treatment, similar to conventional radiotherapy. SRS has some potential benefits when compared with conventional radiotherapy. SRS is more precise, requires less treatment time, and reduces the volume of surrounding normal brain tissue being irradiated. A reduction of the treatment volume may result in less toxicity. Patients with a typical neurocytoma have an excellent prognosis and live long enough to be at risk for late radiation effects such as leukoencephalopathy or secondary malignancies.8–10 This study also compares postoperative SRS and conventional radiotherapy with respect to outcome because SRS can be recommended only if it provides the favorable outcome associated with conventional radiotherapy.
MATERIALS AND METHODS
To our knowledge, the first case of an incompletely resected typical neurocytoma treated with postoperative SRS was reported in 1997.11 All neurocytoma patients in the literature from that point in time onward were included in this retrospective study. Data were collected for each patient with regard to age, gender, extent of resection, MIB-1-labeling index, histology, radiotherapy, LC, and overall survival (OS). Patients with completely resected tumors and those with atypical neurocytomas (defined as tumors with either atypical histologic features or an MIB-1 labeling index > 3%) were excluded from this analysis.
If the reported data were incomplete with respect to the information noted above, the authors were contacted for additional data by telephone, mail, fax, or E-mail. Approximately 80% of the contacted authors provided relevant additional data. This approach provided more information than the available literature with respect to the extent of resection, histology, details of radiotherapy, and follow-up. Only patients with a minimum follow-up of 12 months were included.
Patients were divided into three treatment groups that were compared with respect to LC and OS. These groups included patients who had an incomplete resection alone (ITR), an incomplete resection followed by conventional radiotherapy (ITR+cRT), or an incomplete resection followed by stereotactic radiosurgery (ITR+SRS). For each group, the LC and OS at 5 years after surgery were calculated with the Kaplan–Meier method.12 The outcomes were compared using the log-rank test. Results were considered significant if the P value was < 0.05. LC was defined as the absence of a progression of the original tumor.
A total of 121 patients (53 females and 68 males) met the criteria for inclusion and were included in this analysis. The median age of the patients was 27 years (range, 3–76 yrs). Follow-up in survivors ranged from 12–158 months (median, 42 mos). Fifty-nine patients were treated with ITR, 41 patients with ITR+cRT, and 21 patients with ITR+SRS. The patient characteristics related to the three treatment groups are summarized in Table 1.
|Median age in yrs||26||28||27|
|Median follow-up in survivors in mos||36||48||42|
In the ITR+cRT group, the radiation doses ranged between 43–60 grays (Gy) (median dose, 54 Gy). Five patients treated with ITR-cRT developed a disease recurrence. The median time to disease recurrence was 20 months after radiotherapy (range, 12–96 mos). The median total dose in these 5 patients was 54 Gy (range, 45–55 Gy).
In the ITR+SRS group, the median total dose applied to the tumor margin was 15 Gy (range, 10–24 Gy). SRS was either performed with the Leksell gamma knife (Elekta Instruments, Norcross, GA) (n = 15 patients) or with a linear accelerator (6–10-megavolt photons) (n = 6 patients). Only 1 patient in the ITR+SRS group developed a disease recurrence (72 mos after ITR plus 10 Gy applied with a gamma knife) and no patients died during the follow-up period. Therefore, no valid comparisons could be performed with regarding to the type (gamma knife vs. linear accelerator) or dose of SRS.
The Kaplan–Meier curves for the three treatment groups with respect to LC and OS are shown in the Figures 1 and 2. The P-values of the intergroup comparisons with respect to LC and OS according to the log-rank test are summarized in Table 2. Toxicity was not adequately described by the authors and therefore cannot be commented on based on the available data.
|ITR alone vs. ITR+cRT||ITR alone vs. ITR+SRS||ITR+cRT vs. ITR+SRS|
Typical neurocytomas account for approximately 75% of all central neurocytomas and represent the more benign variant when compared with atypical neurocytomas. The prognosis of patients with typical neurocytomas is excellent, with long-term survival rates of 93–100%. However, LC is also an important endpoint because recurrence of a typical neurocytoma may cause intracerebral hemorrhage, malignant degeneration into an atypical neurocytoma, neurologic deterioration, or craniospinal dissemination.3–7 Furthermore, a second resection entails significant risk. Long-term LC is approximately 80% if complete resection is achieved.1 However, LC is significantly worse if incomplete resection is performed. After incomplete resection, postoperative radiotherapy is associated with improved LC.1 Therefore, postoperative radiotherapy has been recommended after incomplete resection of typical neurocytomas.
To our knowledge, the role of SRS as an alternative to conventional radiotherapy has not been clarified to date. The advantage of SRS would be that a high radiation dose with a steep fall-off can be administered.13 SRS is more precise than conventional radiotherapy. SRS requires a smaller margin of normal brain tissue to be included around the tumor and, therefore, a smaller treatment volume. A smaller treatment volume may result in less toxicity. These patients generally will live long enough to be at risk of developing late radiation toxicities such as cognitive dysfunction, leukoencephalopathy, and secondary malignancies.8–10 This risk may be reduced with SRS compared with conventional radiotherapy. In addition, SRS is performed in a single fraction, compared with approximately 6 weeks of treatment with conventional radiotherapy. In spite of these potential benefits, SRS can only be recommended if it provides an outcome that is similar to conventional radiotherapy.
The results of the current study demonstrate that both ITR+cRT and ITR+SRS are associated with significantly better LC than ITR alone. This review of the literature suggests a significant benefit for SRS in the treatment of patients with incompletely resected typical neurocytomas, the results of which were comparable to those of conventional radiotherapy.
SRS also may be effective for patients with recurrent or atypical neurocytomas. However, no conclusion can be reached because to our knowledge there are very little data currently available in these patient groups.14–16
The results presented herein are based on data from the literature supplemented by additional data from the authors. This approach provides a more detailed analysis, with longer follow-up than literature alone. However, when interpreting the results of the current study, it should to be taken into account that the analysis was based on data from patients treated in many different institutions. However, the applied methodology appears to be the only way to accumulate a relatively large cohort of patients with this rare tumor.
In conclusion, after incomplete resection of a typical neurocytoma, SRS is a reasonable alternative to conventional radiotherapy because both options improve LC to a similar degree compared with incomplete resection alone.