Pantaleo Romanelli

Role of stereotactic radiosurgery and fractionated stereotactic radiotherapy for the treatment of recurrent glioblastoma multiforme

Glioblastoma multiforme (GBM) is a devastating malignant brain tumor characterized by resistance to available therapeutic approaches and relentless malignant progression that includes widespread intracranial invasion, destruction of normal brain tissue, progressive disability, and death. Stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (fSRT) are increasingly used in patients with recurrent GBM to complement traditional treatments such as resection, conventional external beam radiotherapy, and chemotherapy. Both SRS and fSRT are powerful noninvasive therapeutic modalities well suited to treat focal neoplastic lesions through the delivery of precise, highdose radiation. Although no randomized clinical trials have been performed, a variety of retrospective studies have been focused on the use of SRS and fSRT for recurrent GBMs. In addition, state-of-the-art neuroimaging techniques, such as MR spectroscopic imaging, diffusion tensor tractography, and nuclear medicine imaging, have enhanced treatment planning methods leading to potentially improved clinical outcomes. In this paper the authors reviewed the current applications and efficacy of SRS and fSRT in the treatment of GBM, highlighting the value of these therapies for recurrent focal disease.

Multistage epilepsy surgery: safety, efficacy, and utility of a novel approach in pediatric extratemporal epilepsy.

OBJECTIVE To evaluate the safety, efficacy, and utility of a novel surgical strategy consisting of multiple (more than two) operative stages performed during the same hospital admission with subdural grid and strip electrodes in selected pediatric extratemporal epilepsy. METHODS Subdural grid and strip electrodes were used for multistage chronic electroencephalographic monitoring in 15 pediatric patients (age, <19 yr) with refractory localization-related epilepsy and poor surgical prognostic factors. Initial resective surgery and/or multiple subpial transections were performed, followed by further monitoring and additional resection and/or multiple subpial transections. RESULTS Mean patient age was 9.7 years. Mean duration of total invasive monitoring was 10.5 days (range, 8-14 d). The first monitoring period averaged 6.5 days, and the second averaged 3.9 days. Additional surgery was performed in 13 of 15 patients. Two patients who did not undergo additional surgery had a Class I outcome. Rationales for reinvestigation included incomplete localization, multifocality, and proximity to eloquent cortex. Complications were minimal, including two transfusions. There were no cases of wound infection, cerebral edema, hemorrhage, or major permanent neurological deficit. Minimum duration of follow-up was 31 months. Outcomes were 60% Engel Class I (9 of 15 patients), 27% Class III (4 of 15 patients), and 13% Class IV (2 of 15 patients). CONCLUSION In a very select group of pediatric patients with poor surgical prognostic factors, the multistage approach can be beneficial. After failed epilepsy surgery, subsequent reoperation with additional intracranial investigation traditionally is used when a single residual focus is suspected. Our results, however, support the contention that multistage epilepsy surgery is safe, effective, and useful in a challenging and select pediatric population with extratemporal medically refractory epilepsy.

Epilepsy surgery in tuberous sclerosis: Multistage procedures with bilateral or multilobar foci

Refractory seizures are common in patients with tuberous sclerosis and can contribute to developmental delay and behavioral problems. Surgical intervention can reduce the seizure burden in selected patients with tuberous sclerosis and refractory epilepsy, thereby improving cognitive function, behavior, and quality of life. However, the risks of surgery are usually considered unacceptable when the epileptogenic focus lies over dominant hemisphere eloquent cortex or is multilobar. Multistage invasive monitoring can provide detailed data regarding the location and number of ictal foci and functional extraoperative mapping can precisely delineate the boundaries of eloquent areas of the brain. If independent ictal onsets are demonstrated, a staged surgical approach can allow a more aggressive yet safe procedure in selected patients. A combination of staged resection and multiple subpial transections may provide an opportunity to treat epileptogenic foci located over eloquent cortex. Bilateral staged resections can be used when independent bihemispheric foci are present in patients with tuberous sclerosis. This article presents two cases, one of which (case 2) was previously reported, on successful multistage surgical treatment of epileptogenic foci located over an eloquent cortex or in both hemispheres in children with tuberous sclerosis. This case is represented since there is additional follow-up available and the prior report was to a neurosurgical audience. This multistage approach permitted resection of epileptogenic foci that would traditionally have been considered inoperable. (J Child Neurol 2002;17:689-692).

CyberKnife radiosurgery for trigeminal neuralgia treatment: A preliminary multicenter experience

OBJECTIVERadiosurgery has gained acceptance as a treatment option for trigeminal neuralgia. We report our preliminary multicenter experience treating trigeminal neuralgia with the CyberKnife (Accuray, Inc., Sunnyvale, CA). METHODSA total of 95 patients were treated for idiopathic trigeminal neuralgia between May 2002 and October 2005. Radiosurgical dose and volume parameters were retrospectively analyzed in relation to pain response, complications, and recurrence of symptoms. Optimal treatment parameters were identified for patients who had excellent and sustained pain relief with no complications, including severe or moderate hypesthesia. RESULTSExcellent pain relief was initially experienced by 64 out of 95 patients (67%). The median time to pain relief was 14 days (range, 0.3–180 d). Posttreatment numbness occurred in 45 (47%) of the patients treated. Using higher radiation doses and treating longer segments of the nerve led to both better pain relief and a higher incidence of hypesthesia. The presence of posttreatment numbness was predictive of better pain relief. The overall rate of complications was 18%. At the mean follow-up time of 2 years, 47 of the 95 patients (50%) had sustained pain relief, all of whom were completely off pain medications. CONCLUSIONThe results of this study suggest the following optimal radiosurgical treatment parameters for treatment of idiopathic trigeminal neuralgia: a median maximal dose of 78 Gy (range, 70–85.4 Gy) and a median length of the nerve treated of 6 mm (range, 5–12 mm).

Cyberknife Radiosurgery for Trigeminal Neuralgia

Background: We present preliminary results using Cyberknife radiosurgery as a noninvasive treatment for trigeminal neuralgia (TN). Methods: Ten patients with medically refractory TN who were deemed unsuitable for conventional surgery underwent Cyberknife radiosurgery using CT cisternography for localization. Results: Pain relief was achieved in 7 patients, in 5 of them within 24–72 h after irradiation. Conclusion: Cyberknife radiosurgery can achieve early-onset pain relief in a subset of TN patients. Improvements using this technique include the absence of a stereotactic ring, potentially improved targeting accuracy produced by CT cisternography and improved dose homogeneity.

Late Seizure Recurrence after Multiple Subpial Transections

Summary: We studied long‐term outcome (range, 28–89 months; mean, 56 months) after multiple subpial transections (MSTs) for medically refractory epilepsy. Forty‐three (79.6%) of 54 patients had a consistent significant reduction in seizure frequency, and 27 (50%) of the 54 were either entirely seizure free or virtually so. However, 10 (18.6%) patients sustained an increase in seizure frequency several years after surgery, after showing initial postoperative improvement. This suggests that late seizure recurrence is a more important problem in cases in which MST has been performed than for pure resections.

Surgical treatment of multifocal epilepsy involving eloquent cortex.

Summary:  Purpose: This report describes our long‐term follow‐up for combined resective surgery and multiple subpial transections (MSTs) in patients with refractory epilepsy involving eloquent and noneloquent cortex in multiple lobes. Multiple independent seizure foci made these patients poor candidates for conventional surgery.

Image-Guided Radiosurgical Ablation of Intra- and Extra-Cranial Lesions

For decades since its introduction, stereotactic radiosurgery (SRS) was used only to treat intracranial lesions because intracranial targets could be immobilized and located relative to a rigid metal frame affixed to the patients head. Lesions outside the head were generally not treated with SRS because it is difficult to immobilize extracranial lesions and to attach stereotactic frames elsewhere on the body. Advances in computerized image guidance and robotics allowed the development of systems, such as the CyberKnife SRS System (Accuray, Inc, Sunnyvale, CA), that could target intracranial lesions without the stereotactic frame. Enhancements have resulted in a radiation delivery system that can accurately deliver high-dose, focal radiation to lesions in the spine, chest, and abdomen, even if they move during respiration. In this review we will describe the technical features of frameless SRS systems and briefly review their application to treating intracranial and extracranial lesions, focusing in particular on spinal lesions.

The syndrome gelastic seizures-hypothalamic hamartoma: Severe, potentially reversible encephalopathy

Hypothalamic hamartoma (HH) is the pathologic hallmark of a spectrum of epileptic conditions, ranging from a mild form of epilepsy, whose seizures are an urge to laugh without cognitive defects, to the fully developed syndrome of early onset gelastic seizures (GS) associated with precocious puberty and the evolution to a catastrophic epilepsy syndrome. However, a refractory focal or generalized epilepsy develops during the clinical course in nearly all cases. Neurophysiologic and neuroimaging studies have assessed the role of HH in the generation of the GS as well as in the process of secondary epileptogenesis. Electrophysiologic properties of small γ‐aminobutyric acid (GABA)ergic, spontaneously firing neurons might explain the intrinsic epileptogenicity of HH. Surgical ablation of the HH can reverse both epilepsy and encephalopathy. Gamma‐knife radiosurgery and image‐guided robotic radiosurgery can be useful and safe approaches for treatment, in particular of small HH.

A PHASE I DOSE-ESCALATION STUDY (ISIDE-BT-1) OF ACCELERATED IMRT WITH TEMOZOLOMIDE IN PATIENTS WITH GLIOBLASTOMA

PURPOSE To determine the maximum tolerated dose (MTD) of fractionated intensity-modulated radiotherapy (IMRT) with temozolomide (TMZ) in patients with glioblastoma. METHODS AND MATERIALS A Phase I clinical trial was performed. Eligible patients had surgically resected or biopsy-proven glioblastoma. Patients started TMZ (75 mg/day) during IMRT and continued for 1 year (150-200 mg/day, Days 1-5 every 28 days) or until disease progression. Clinical target volume 1 (CTV1) was the tumor bed +/- enhancing lesion with a 10-mm margin; CTV2 was the area of perifocal edema with a 20-mm margin. Planning target volume 1 (PTV1) and PTV2 were defined as the corresponding CTV plus a 5-mm margin. IMRT was delivered in 25 fractions over 5 weeks. Only the dose for PTV1 was escalated (planned dose escalation: 60 Gy, 62.5 Gy, 65 Gy) while maintaining the dose for PTV2 (45 Gy, 1.8 Gy/fraction). Dose limiting toxicities (DLT) were defined as any treatment-related nonhematological adverse effects rated as Grade >or=3 or any hematological toxicity rated as >or=4 by Radiation Therapy Oncology Group (RTOG) criteria. RESULTS Nineteen consecutive glioblastoma were treated with step-and-shoot IMRT, planned with the inverse approach (dose to the PTV1: 7 patients, 60 Gy; 6 patients, 62.5 Gy; 6 patients, 65 Gy). Five coplanar beams were used to cover at least 95% of the target volume with the 95% isodose line. Median follow-up time was 23 months (range, 8-40 months). No patient experienced DLT. Grade 1-2 treatment-related neurologic and skin toxicity were common (11 and 19 patients, respectively). No Grade >2 late neurologic toxicities were noted. CONCLUSION Accelerated IMRT to a dose of 65 Gy in 25 fractions is well tolerated with TMZ at a daily dose of 75 mg.