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Proposed therapeutic strategy for adult low-grade glioma based on aggressive tumor resection

Masayuki Nitta, Yoshihiro Muragaki, Takashi Maruyama, Soko Ikuta, Takashi Komori, Katsuya Maebayashi, Hiroshi Iseki, Manabu Tamura, Taiichi Saito, Saori Okamoto, Mikhail Chernov, Motohiro Hayashi, and Yoshikazu Okada

OBJECT

There is no standard therapeutic strategy for low-grade glioma (LGG). The authors hypothesized that adjuvant therapy might not be necessary for LGG cases in which total radiological resection was achieved. Accordingly, they established a treatment strategy based on the extent of resection (EOR) and the MIB-1 index: patients with a high EOR and low MIB-1 index were observed without postoperative treatment, whereas those with a low EOR and/or high MIB-1 index received radiotherapy (RT) and/or chemotherapy. In the present retrospective study, the authors reviewed clinical data on patients with primarily diagnosed LGGs who had been treated according to the above-mentioned strategy, and they validated the treatment policy. Given their results, they will establish a new treatment strategy for LGGs stratified by EOR, histological subtype, and molecular status.

METHODS

One hundred fifty-three patients with diagnosed LGG who had undergone resection or biopsy at Tokyo Women's Medical University between January 2000 and August 2010 were analyzed. The patients consisted of 84 men and 69 women, all with ages ≥ 15 years. A total of 146 patients underwent surgical removal of the tumor, and 7 patients underwent biopsy.

RESULTS

Postoperative RT and nitrosourea-based chemotherapy were administered in 48 and 35 patients, respectively. Extent of resection was significantly associated with both overall survival (OS; p = 0.0096) and progression-free survival (PFS; p = 0.0007) in patients with diffuse astrocytoma but not in those with oligodendroglial subtypes. Chemotherapy significantly prolonged PFS, especially in patients with oligodendroglial subtypes (p = 0.0009). Patients with a mutant IDH1 gene had significantly longer OS (p = 0.034). Multivariate analysis did not identify MIB-1 index or RT as prognostic factors, but it did identify chemotherapy as a prognostic factor for PFS and EOR as a prognostic factor for OS and PFS.

CONCLUSIONS

The findings demonstrated that EOR was significantly correlated with patient survival; thus, one should aim for maximum tumor resection. In addition, patients with a higher EOR can be safely observed without adjuvant therapy. For patients with partial resection, postoperative chemotherapy should be administered for those with oligodendroglial subtypes, and repeat resection should be considered for those with astrocytic tumors. More aggressive treatment with RT and chemotherapy may be required for patients with a poor prognosis, such as those with diffuse astrocytoma, 1p/19q nondeleted tumors, or IDH1 wild-type oligodendroglial tumors with partial resection.

In Neurosurgical Focus Volume 38 (2015): Issue 1 (Jan 2015): Low Grade Gliomas: Pathophysiology and Management Strategies

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Intraoperative cortico-cortical evoked potentials for the evaluation of language function during brain tumor resection: initial experience with 13 cases

Clinical article

Taiichi Saito, Manabu Tamura, Yoshihiro Muragaki, Takashi Maruyama, Yuichi Kubota, Satoko Fukuchi, Masayuki Nitta, Mikhail Chernov, Saori Okamoto, Kazuhiko Sugiyama, Kaoru Kurisu, Kuniyoshi L. Sakai, Yoshikazu Okada, and Hiroshi Iseki

Object

The objective in the present study was to evaluate the usefulness of cortico-cortical evoked potentials (CCEP) monitoring for the intraoperative assessment of speech function during resection of brain tumors.

Methods

Intraoperative monitoring of CCEP was applied in 13 patients (mean age 34 ± 14 years) during the removal of neoplasms located within or close to language-related structures in the dominant cerebral hemisphere. For this purpose strip electrodes were positioned above the frontal language area (FLA) and temporal language area (TLA), which were identified with direct cortical stimulation and/or preliminary mapping with the use of implanted chronic subdural grid electrodes. The CCEP response was defined as the highest observed negative peak in either direction of stimulation. In 12 cases the tumor was resected during awake craniotomy.

Results

An intraoperative CCEP response was not obtained in one case because of technical problems. In the other patients it was identified from the FLA during stimulation of the TLA (7 cases) and from the TLA during stimulation of the FLA (5 cases), with a mean peak latency of 83 ± 15 msec. During tumor resection the CCEP response was unchanged in 5 cases, decreased in 4, and disappeared in 3. Postoperatively, all 7 patients with a decreased or absent CCEP response after lesion removal experienced deterioration in speech function. In contrast, in 5 cases with an unchanged intraoperative CCEP response, speaking abilities after surgery were preserved at the preoperative level, except in one patient who experienced not dysphasia, but dysarthria due to pyramidal tract injury. This difference was statistically significant (p < 0.01). The time required to recover speech function was also significantly associated with the type of intraoperative change in CCEP recordings (p < 0.01) and was, on average, 1.8 ± 1.0, 5.5 ± 1.0, and 11.0 ± 3.6 months, respectively, if the response was unchanged, was decreased, or had disappeared.

Conclusions

Monitoring CCEP is feasible during the resection of brain tumors affecting language-related cerebral structures. In the intraoperative evaluation of speech function, it can be a helpful adjunct or can be used in its direct assessment with cortical and subcortical mapping during awake craniotomy. It can also be used to predict the prognosis of language disorders after surgery and decide on the optimal resection of a neoplasm.

In Journal of Neurosurgery Volume 121 (2014): Issue 4 (Oct 2014)

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Outcome after Gamma Knife surgery for intracranial arteriovenous malformations in children

Clinical article

Noriko Tamura, Motohiro Hayashi, Mikhail Chernov, Manabu Tamura, Ayako Horiba, Yoshiyuki Konishi, Yoshihiro Muragaki, Hiroshi Iseki, and Yoshikazu Okada

Object

The focus of the present study was the evaluation of outcomes after unstaged and staged-volume Gamma Knife surgery (GKS) in children harboring intracranial arteriovenous malformations (AVMs).

Methods

Twenty-two children (median age 9.5 years) underwent GKS for AVMs and were followed up for at least 2 years thereafter. The disease manifested with intracranial hemorrhage in 77% of cases. In 68% of patients the lesion affected eloquent brain structures. The volume of the nidus ranged from 0.1 to 6.7 cm3. Gamma Knife surgery was guided mainly by data from dynamic contrast-enhanced CT scans, with preferential targeting of the junction between the nidus and draining vein. The total prescribed isodose volume was kept below 4.0 cm3, and the median margin dose was 22 Gy (range 20–25 Gy). If the volume of the nidus was larger than 4.0 cm3, a second radiosurgical session was planned for 3–4 years after the first one. Nine patients in the present series underwent unstaged radiosurgery, whereas staged-volume treatment was scheduled in 13 patients.

Results

Complete obliteration of the AVM was noted in 17 (77%) of 22 patients within a median period of 47 months after the last radiosurgical session. Complete obliteration of the lesion occurred in 89% of patients after unstaged treatment and in 62.5% after staged GKS. Four (67%) of 6 high-grade AVMs were completely obliterated. Complications included 3 bleeding episodes, the appearance of a region of hyperintensity on T2-weighted MR images in 2 patients who had no symptoms, and reappearance of the nidus in the vicinity of the completely obliterated AVM in 1 patient.

Conclusions

Radiosurgery is a highly effective management option for intracranial AVMs in children. For larger lesions, staged GKS may be applied successfully. Initial targeting of the nidus adjacent to the draining vein and application of a sufficient radiation dose to a relatively small volume (≤ 4 cm3) provides a good balance between a high probability of obliteration and a low risk of treatment-related complications.

In Journal of Neurosurgery Volume 117: Issue Special_Suppl (Dec 2012)

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Gamma Knife surgery for abducent nerve schwannoma

Report of 4 cases

Motohiro Hayashi, Mikhail Chernov, Noriko Tamura, Shoji Yomo, Taku Ochiai, Mariko Nagai, Manabu Tamura, Masahiro Izawa, Yoshihiro Muragaki, Hiroshi Iseki, Yoshikazu Okada, and Kintomo Takakura

Abducent nerve schwannomas are extremely rare. The authors recently performed Gamma Knife surgery (GKS) in 4 patients with such tumors and describe their experiences with these cases.

The patients consisted of 3 women and 1 man whose ages varied from 31 to 60 years (mean 46 years). Two patients had no symptoms, 1 complained of slight visual disturbances, and the other 1 had abducent nerve palsy. Neurofibromatosis was not diagnosed in any case. All 4 tumors were located in the cavernous sinus: 2 of these tumors within the borders of the sinus, 1 tumor extending into the orbit, and 1 tumor extending into the prepontine cistern. The volume of the neoplasms varied from 1.7 to 4.9 cm3 (mean 3.0 cm3). No patient underwent tumor resection. Treatment was delivered with the aid of a Leksell Gamma Knife model C unit and the automatic positioning system. The dose directed to the tumor margin was 12 Gy in all cases. The dose directed to the anterior visual pathways was kept below 10 Gy and that to the brainstem below 14 Gy. The length of follow-up varied between 7 and 43 months (mean 27 months).

There were no acute complications or side effects. Imaging studies showed temporary enlargement of all tumors during the 1st posttreatment year, but thereafter, there was a trend toward reduction in volume. None of the neoplasms displayed regrowth. In the 3 patients who did not have abducent nerve palsy before GKS, it appeared, at least temporarily, after the procedure. Purely intracavernous neoplasms in general followed uneventful posttreatment courses, but dumbbell-shaped tumors were associated with significant morbidity. The cisternocavernous schwannoma underwent cystic degeneration 2 years after GKS, and the patient developed diplopia. After GKS, the patient treated for an orbitocavernous schwannoma experienced a significant deterioration in vision, temporary blindness in 1 eye, and late development of permanent abducent nerve palsy, which were seemingly caused by compression of neurovascular structures within the anulus of Zinn during a temporary increase in the lesion's volume after irradiation.

Gamma Knife surgery controls the growth of abducent nerve schwannomas and may be effectively used to manage intracavernous neoplasms. Caution, however, should be used in cases of dumbbell-shaped tumors, particularly those extending through the superior orbital fissure.

In Journal of Neurosurgery Volume 113: Issue Special_Supplement (Dec 2010)