Stéphane Fuentes

Correlation Between O6-Methylguanine-DNA Methyltransferase and Survival in Inoperable Newly Diagnosed Glioblastoma Patients Treated With Neoadjuvant Temozolomide

PURPOSEnThis phase II study evaluated the efficacy and safety of a 7-day on/7-day off regimen of temozolomide before radiotherapy (RT) in patients with inoperable newly diagnosed glioblastoma.nnnPATIENTS AND METHODSnPatients received temozolomide (150 mg/m2/d on days 1 to 7 and days 15 to 21 every 28 days; 7 days on/7 days off) for up to four cycles before conventional RT (2-Gy fractions to a total of 60 Gy) and for four cycles thereafter or until disease progression. The primary end point was tumor response. Tumor tissue from 25 patients was analyzed for O6-methylguanine-DNA methyltransferase (MGMT) expression.nnnRESULTSnTwenty-nine patients with a median age of 60 years were treated, and 28 were assessable for response. Seven (24%) of 29 patients had a partial response, nine patients (31%) had stable disease, and 12 patients (41%) had progressive disease. Median progression-free survival (PFS) time was 3.8 months, and median overall survival (OS) time was 6.1 months. Patients with low MGMT expression, compared with patients with high MGMT expression, had a significantly higher response rate (55% v 7%, respectively; P = .004) and improved PFS (median, 5.5 v 1.9 months, respectively; P = .009) and OS (median, 16 v 5 months, respectively; P = .003). The most common grade 3 and 4 toxicities were thrombocytopenia (20%) and neutropenia (17%).nnnCONCLUSIONnThis dose-dense temozolomide regimen resulted in modest antitumor activity with an acceptable safety profile in the neoadjuvant setting, and expression of MGMT correlated with response to temozolomide. However, this treatment approach seems to be inferior to standard concomitant RT plus temozolomide.

Gamma knife radiosurgical management of petroclival meningiomas results and indications.

Summary¶Background. Surgical treatment of petroclival meningiomas remains challenging. In order to refine indications for the use of stereotactic radiosurgery in the treatment of these tumours, we retrospectively evaluated our experience in this field.n Methods. Thirty-two patients harboring a petroclival meningioma were treated consecutively using a Gamma knife between December 92 and June 1998. Eight patients underwent radiosurgery after one or more attempted surgical removals and 24 had radiosurgery as the primary treatment. The main symptoms before radiosurgery were cranial nerve palsies, including a sixth nerve deficit in 10 patients and a trigeminal nerve disturbance in 9. All patients underwent a conformal multi-isocentric treatment (mean isocenter’s number 8.8) and the dose delivered at the tumour margin ranged from 10 to 15u2009Gy (mean dose 13u2009Gy).n Findings. The duration of follow-up varied from 24 to 118 months (mean clinical follow-up 56 months, mean radiological follow-up 52.6 months). All 32 patients survived. The tumour volume remained unchanged in 28 patients and decreased slightly in 4. Neurological status worsened permanently in 2 patients with a delayed hemiparesis due to focal pontine infarction. These complications were associated with large meningiomas with vascular involvement and ventral brainstem compression, and occurred at the very early stage of our experience. At last follow-up, preoperative fifth or sixth cranial nerve deficits had improved or recovered in 13 out of 19 patients and any delayed worsening or new cranial nerve deficits were not observed after radiosurgery.n Conclusions. Stereotactic radiosurgery with a Gamma knife provides effective management of small to middle sized petroclival meningiomas and is an alternative to microsurgery. Careful selection of patients and use of major technical refinements should improve the safety of this treatment.

Evaluation of fractionated radiotherapy and gamma knife radiosurgery in cavernous sinus meningiomas: treatment strategy.

OBJECTIVE:To investigate the respective role of fractionated radiotherapy (FR) and gamma knife stereotactic (GKS) radiosurgery in cavernous sinus meningioma (CSM) treatment. METHODS:The authors report the long-term follow-up of two populations of patients harboring CSMs treated either by FR (Group I, 38 patients) or GKS radiosurgery (Group II, 36 patients). There were 31 females with a mean age of 53 years in Group I and 29 females with a mean age of 51.2 years in Group II. In 20 patients (Group I) and 13 patients (Group II), FR and GKS radiosurgery were performed as an adjuvant treatment. In 18 patients (Group I) and in 23 patients (Group II), FR and GKS radiosurgery were performed as first line treatment. In our early experience with GKS radiosurgery (1992, date of gamma knife availability in the department), patients with tumors greater than 3 cm, showing close relationship with the optic apparatus (<3 mm) or skull base dural spreading, were treated by FR. Secondarily, with the advent of new devices and our growing experience, these criteria have evolved. RESULTS:The median follow-up period was 88.6 months (range, 42–168 mo) for Group I and 63.6 months (range, 48–92 mo) for Group II. According to Sekhars classification, 26 (68.4%) patients were Grade III to IV in Group I and 10 (27.8%) patients in Group II (P < 0.05); 23 (60.5%) patients had extensive lesions in Group I and 7 (19.4%) patients in Group II (P < 0.05). Mean tumor volume was 13.5 cm3 in Group I and 5.2 cm3 in Group II (P < 0.05). Actuarial progression-free survival was 94.7% and 94.4% in Group I and II, respectively. Clinically, improvement was seen for 24 (63.2%) patients in Group I and for 21 (53.8%) patients in Group II (P > 0.05). Radiologically, 11 (29%, Group I) patients and 19 (Group II, 52.7%) patients showed tumor shrinkage (P = 0.04). Transient morbidity was 10.5% in Group I and 2.8% in Group II. Permanent morbidity was 2.6% in Group I and 0% in Group II. CONCLUSION:FR and GKS radiosurgery are safe and efficient techniques in treatment of CSMs, affording comparable satisfactory long-term tumor control. However, GKS radiosurgery provides better radiological response, is far more convenient, and fits into most patients lives much better than FR. Therefore, in the authors opinion, GKS radiosurgery should be advocated in first intention for patients with CSMs, whereas conventional radiotherapy should be reserved for cases that are not amenable to this technique, thus making these two therapeutic modalities not alternative but complementary tools in CS meningioma treatment strategy.

Prognostic impact of O6-methylguanine-DNA methyltransferase silencing in patients with recurrent glioblastoma multiforme who undergo surgery and carmustine wafer implantation: a prospective patient cohort.

O6‐methylguanine‐DNA methyltransferase (MGMT) is a key enzyme in the DNA repair process after alkylating agent action. Epigenetic silencing of the MGMT gene by promoter methylation has been associated with longer survival in patients with newly diagnosed glioblastoma multiforme (GBM) who receive alkylating agents. In this study, the authors evaluated the prognostic value of different biomarkers in recurrent GBM and analyzed the changes in MGMT status between primary tumors and recurrent tumors.

Brainstem metastases: management using gamma knife radiosurgery.

OBJECTIVE:Brainstem metastasis is an uncommon complication of systemic cancer, generally considered to have a highly unfavorable prognosis. Surgical risks are high and standard radiation or chemotherapy have little effect. The purpose of this study is to evaluate our experience using Gamma Knife radiosurgery (GKRS) for the management of brainstem metastasis. METHODS:Between July 1992 and March 2001, we treated 28 patients with brainstem metastasis using GKRS. Lesions were located in the pons in 17 patients, midbrain in nine, and medulla oblongata in two. At time of the radiosurgery, eight patients presented with another supratentorial metastasis. The most frequent primary tumor site was the lung (13 cases) followed by the melanoma in four cases, the kidney in two, and other locations in six. Only six patients underwent fractionated whole-brain radiation therapy. Mean marginal radiation dose for GKRS was 19.6 Gy (range, 11–30). Mean maximum diameter was 17.2 mm (range, 10–30). RESULTS:No GKRS-related morbidity was observed. Local tumor control was achieved in 92% of patients. Twenty-six patients have died. Death was related to the progression of the brainstem lesion in two cases. Mean and median survival after GKRS were 10.2 and 12 months, respectively. Follow-up periods in the two surviving patients were 12 and 13 months. CONCLUSION:The results of this small series demonstrate that GKRS can be a valuable modality for safe and effective management of brain stem metastasis. Owing to the high risk of surgical resection and low efficacy of medical treatment, radiosurgery can be proposed upfront.

Noninvasive diagnostic assessment of brain tumors using combined in vivo MR imaging and spectroscopy

To determine the potential value of multimodal MRI for the presurgical management of patients with brain tumors, we performed combined magnetic resonance imaging (MRI) and proton MR spectroscopy (MRS) in 164 patients who presented with tumors of various histological subtypes confirmed by surgical biopsy. Univariate statistical analysis of metabolic ratios carried out on the first 121 patients demonstrated significant differences in between‐group comparisons, but failed to provide sufficiently robust classification of individual cases. However, a multivariate statistical approach correctly classified the tumors using linear discriminant analysis (LDA) of combined MRI and MRS data. After initial separation of contrast‐enhancing and non‐contrast‐enhancing lesions, 91% of the former and 87% of the latter were correctly classified. The results were stable when this diagnostic strategy was tested on the additional 43 patients included for validation after the initial statistical analysis, with over 90% of correct classification. Combined MRI and MRS had superior diagnostic value compared to MRS alone, especially in the contrast‐enhancing group. This study shows the clinical value of a multivariate statistical analysis based on multimodal MRI and MRS for the noninvasive evaluation of intracranial tumors. Magn Reson Med, 2006.

Retrospective study of 77 patients harbouring lumbar synovial cysts: functional and neurological outcome.

SummaryBackground. Synovial cysts represent an uncommon and probably underestimated pathological entity of the degenerative lumbar spine. The authors report a retrospective analysis of the clinical presentation, radiological studies and operative findings in 77 patients surgically treated for symptomatic lumbar synovial cysts at their institution.n Materials and method. Between January 1992 and June 1998, a total of 77 patients presenting with symptomatic lumbar synovial cysts were operated on in the author’s department. Operative procedure, complications, results and pathological findings were correlated with preoperative assessment. There were 41 men and 36 women with an average age of 63 years (range 44–90 years).n Results. On the basis of their symptom complex on presentation, two populations were identified: patients who presented with a single radicular pain (group I = 51 patients), and patients who presented with bilateral neurogenic claudication (group II = 26 patients). Neurological examination on presentation demonstrated motor deficit (12%), sensory loss (26%) and reflex changes (35%). Degenerative disc disease and facet joint osteoarthritis was a frequent finding in patients with pre-operative MRI. Facet joint orientation was >45° in 76.6% of patients. Preoperative spondylolisthesis was found in 48% on radiological studies. All the patients were treated surgically with resection of the cyst. No fusion was performed as a first line procedure. However subsequent fusion was necessary in one patient who developed symptomatic spondylolisthesis. Mean follow-up period was of 45 months ranging from 18 to 105 months. Only one recurrence occurred during the follow-up period. An excellent or good functional outcome was seen in 97.4% of cases, and 89% of the patients with motor deficit recovered.n Conclusions. Surgical resection of lumbar synovial cysts is an effective treatment associated with very low morbidity. Synovial cysts are associated with increased grade and frequency of facet joint asteoarthritis but not with increased grade or frequency of degenerative disc disease compared with patients without cysts. In the author’s opinion, at the present time, there is no reliable criterion which allows the development of a symptomatic spinal instability to be predicted in patients with a preoperative spondylolisthesis and therefore fusion as a first line procedure is still debatable.

Solitary fibrous tumors of the central nervous system: Clinicopathological and therapeutic considerations of 18 cases - Commentary

OBJECTIVEThis is a retrospective study of 18 patients harboring a solitary fibrous tumor of the central nervous system. Therapeutic management and outcome were analyzed. METHODSBetween 1999 and 2004, 18 patients harboring central nervous system solitary fibrous tumors were surgically treated at our two institutions. There were nine men and nine women. The patient ages ranged from 33 to 75 years, with a median age of 56.1 years. The locations were spinal in six cases (33.3%), the posterior fossa in six cases (33.3%), supratentorial in four cases (22.2%), and orbital in two cases (11.2%). RESULTSThe median follow-up period was 45.3 months. Gross total resection was achieved in 10 cases (55.6%); tumor recurrence or progression occurred in nine cases (50%). Incomplete surgical resection was significantly associated with recurrence (P = 0.018). On univariate analysis, extent of surgery was also associated with a longer progression-free survival (P = 0.05). No statistically significant correlation can be found between histological features and recurrence. CONCLUSIONPrognosis of solitary fibrous tumors of the central nervous system remains unclear; consequently, careful and close monitoring of patients and long-term follow-up are mandatory. Radical surgical excision seems to be a significant and reliable prognosis factor, although pathological prognostic features must be defined. In other respects, the role of postoperative radiotherapy in atypical or incompletely resected solitary fibrous tumors of the central nervous system remains to be determined and, therefore, warrants larger series with longer follow-up periods.

Management of Large Vestibular Schwannomas by Combined Surgical Resection and Gamma Knife Radiosurgery

In this report, we evaluated the treatment results of a combination of surgery and radiosurgery for large vestibular schwannomas. The series of 8 patients included in this study underwent surgery followed by radiosurgical treatment between January 2000 and January 2006. The patients included 5 males and 3 females aged 24-78 years (mean age: 53 years). The average maximum diameter of the tumor was 40 (35-45) mm. At the time of radiosurgery, the treatment size became 18 (9-20) mm. The mean peripheral dose administered was 11.8 (range 11-13) Gy, and the mean dose administered in the centre of the tumor was 23.75 (22-26) Gy. The mean follow-up period was 46 months after radiosurgery. Excellent facial nerve function (House-Brackmann grade 1 or 2) was preserved in 7/8 patients (87.5%). In the case of large vestibular schwannomas, the combined management is one option for maintaining cranial nerve function and tumor growth control.

Traumatic atlantoaxial rotatory dislocation with odontoid fracture: case report and review.

Study Design. A case of traumatic rotatory dislocation associated with odontoid fracture is reported. Objectives. To report a rare case of traumatic rotatory dislocation associated with odontoid fracture, and to discuss the mechanism underlying spinal instability and management. Summary of Background Data. This case is a cross between traumatic rotatory fixation and atlantoaxial rotatory dislocation. Classification of rotatory subluxation change after osteosynthesis of the odontoid process was undertaken. Methods. A 24-year-old man sustained head and cervical injury after jumping. A Type 2 odontoid fracture without displacement was noted. Results. Without further traumatic event, 1 month after injury, computed tomography scan showed posterior displacement of the odontoid fracture and Type 4 or B atlantoaxial rotatory luxation. After surgical fixation and reduction of the odontoid fracture, the rotatory subluxation classification changed and became Type 1 or A. Posterior C1–C2 arthrodesis was performed. The patient wore a Philadelphia cervical collar for 3 months and underwent physiotherapy. Conclusions. As the pivot of rotatory subluxation changed after odontoid process osteosynthesis, posterior C1–C2 arthrodesis was performed. The patient probably could have been treated in a single-stage procedure using posterior C1–C2 transarticular fixation with bicortical interspinous graft.