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Nicolas Dea, Martin Borduas, Brendan Kenny, David Fortin and David Mathieu

Object

Brain metastases are the most frequently occurring cerebral tumors. Tumors that are located in eloquent cerebral parenchyma can cause considerable morbidity and may pose a significant challenge during surgery. Gamma Knife surgery (GKS) is a recognized treatment modality for brain metastases. This study was undertaken to assess the safety and efficacy of GKS, specifically for brain metastases in eloquent locations.

Methods

Charts of patients harboring brain metastases that were treated by GKS at the Centre Hospitalier Universitaire de Sherbrooke between August 2004 and April 2008 were reviewed. Planning images were assessed by an independent neurosurgeon to assess tumor location. Eloquent locations included the primary motor, somatosensory, speech, and visual cortices; the basal ganglia; the thalamus; and the brainstem. Data on survival, tumor response, and complications were analyzed and compared with data published on surgical treatment of these lesions.

Results

During the study period, 650 metastases in 295 patients were treated with GKS; of these, 164 metastases in 95 patients were located in eloquent areas. In this subgroup, the median age of patients was 59 years and women constituted 57.9% of the population. The median Karnofsky Performance Scale score was 80% (range 50%–100%). Patients were categorized according to their recursive partitioning analysis class: Class 1, 22.1%; Class 2, 70.5%; and Class 3, 7.4% of patients. Non–small cell lung cancer was the most common primary tumor (63.2% of metastases), followed by small cell lung (8.4%), breast (7.4%), colorectal (5.3%), and renal cell (4.2%) cancers, as well as melanoma (4.2%). The median dose to the tumor margin was 18 Gy (range 14–24 Gy). The median duration of survival after GKS was 8.2 months. The recursive partitioning analysis class was the most significant variable affecting survival (p < 0.0001). Immediate control was achieved in 92.9% of tumors, and 68.6% of tumors were still controlled at the last follow-up. The median time to tumor progression was 16 months. Higher margin dose (p = 0.002), the absence of edema (p = 0.009), and the non–small cell lung cancer tissue type (p = 0.035) positively affected response rates. Steroid medications were no longer used in 46% of patients after GKS. New neurological deficits occurred in 5.7% of patients and seizures in 5.7%. All these deficits were transient and patients completely recovered in response to a temporary course of steroids. Imaging studies showed that new edema occurred in 8.6% of treated metastases and biopsy-proven radiation necrosis in 1.4%.

Conclusions

Gamma Knife surgery is safe and effective for brain metastases located in eloquent areas.

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David Mathieu, Mathieu Beaudry, René Martin, Hans McLelland, Bruno Robert and Brendan Kenny

Object. The authors conducted a double-blind prospective randomized study to determine whether infiltration of Mayfield skull-pin sites with 0.5% bupivacaine, compared with placebo, would prevent hemodynamic stimulation, thus allowing for a reduction in the quantity of anesthetic agents required.

Methods. Thirty patients were randomized into two groups. There was a significant increase in blood pressure (mean systolic blood pressure 10 mm Hg, p = 0.003) in patients in the placebo group compared with that in patients in the bupivacaine group 1 minute after securing the head holder.

Conclusions. The local administration of bupivacaine for anesthetic purposes before skull-pin application may prevent potentially hazardous hemodynamic stimulation.

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David Mathieu, Khaled Effendi, Jocelyn Blanchard and Mario Séguin

Object

Among patients with multiple sclerosis (MS) there is a high incidence of trigeminal neuralgia (TN), and outcomes after treatment seem inferior to those in patients suffering from idiopathic TN. The goal of this study was to evaluate clinical outcomes in patients with MS-related TN after Gamma Knife surgery (GKS) and compare them with those obtained using percutaneous retrogasserian glycerol rhizotomy (PRGR).

Methods

The authors retrospectively reviewed the charts of 45 patients with MS-related TN. The first procedure undertaken was GKS in 27 patients and PRGR in 18 patients. Pain had been present for a median of 60 months (range 12–276 months) in patients who underwent GKS and 48 months (range 12–240 months) in patients who underwent PRGR. The following outcome measures were assessed in both groups of patients: pain relief (using the Barrow Neurological Institute [BNI] Pain Scale), procedure-related morbidity, time to pain relief and recurrence, and subsequent procedures that were performed.

Results

The median duration of follow-up was 39 months (range 13–69 months) in the GKS group and 38 months (range 2–75 months) in the PRGR group. Reasonable pain control (BNI Pain Scale Scores I–IIIb) was noted in 22 patients (81.5%) who underwent GKS and in 18 patients (100%) who underwent PRGR. For patients who underwent GKS, the median time to pain relief was 6 months; for those who underwent PRGR, pain relief was immediate. In the GKS group12 patients required subsequent procedures (3 patients for absence of response and 9 patients for pain recurrence), whereas in the PRGR group 6 patients required subsequent procedures (all for pain recurrence). As of the last follow-up, complete or reasonable pain control was finally achieved in 23 patients (85.2%) in the GKS group and in 16 patients (88.9%) in the PRGR group. The morbidity rate was 22.2% in the GKS group (all due to sensory loss and paresthesia) and 66.7% in the PRGR group (mostly hypalgesia, with 2 patients having corneal reflex loss and 1 patient suffering from meningitis).

Conclusions

Both GKS and PRGR are satisfactory strategies for treating MS-related TN. Gamma Knife surgery has a lower rate of sensory and overall morbidity than PRGR, but requires a delay before pain relief occurs. The authors propose that patients with extreme pain in need of fast relief should undergo PRGR. For other patients, both management strategies can lead to satisfactory pain relief, and the choice should be made based on patient preference and expectations.

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Nadia Veilleux, Philippe Goffaux, Marie Boudrias, David Mathieu, Kathya Daigle and David Fortin

Object

Due partly to therapeutic improvements and prolonged patient survival, the field of neurooncology is gradually undergoing a philosophical shift, progressively moving toward a more functional approach to patient welfare. This shift includes, as one of its defining objectives, the promotion of elevated levels of quality of life (QOL) and quality of health (QOH) for patients of all ages. Unfortunately, an adult life-stage perspective has never been used to study the long-lasting impact of age on well-being in neurooncology patients.

Methods

In this study, the authors assessed and compared the QOL and QOH scores of 42 younger adults (≤ 40 years of age) and 88 older adults (> 40 years of age) presenting with a primary supratentorial tumor.

Results

After having controlled for biomedical and treatment-related factors, the authors discovered that older adults reported lower functional well-being and poorer neurocognitive functioning than younger adults. This age difference appeared earlier than expected (developing as early as middle age), suggesting an accelerated effect of disease on the aging process. Importantly, it was also found that the variables that predict QOL and QOH differed depending on patient age. For example, support from friends was a significant predictor of QOL for younger adults, whereas the capacity to continue enjoying life was a significant predictor for older adults. Moreover, the presence of a high-grade tumor and increased physical pain had a negative impact on the QOH of younger adults, whereas increased difficulty with concentration negatively impacted the QOH of older adults.

Conclusions

These age differences clearly warn against consolidating the QOL or QOH scores of younger and older adults, and instead suggest that age at diagnosis is essential when considering patient perspective, and when establishing tailored support programs.

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Christian Iorio-Morin, Laurence Masson-Côté, Youssef Ezahr, Jocelyn Blanchard, Annie Ebacher and David Mathieu

Object

Optimal case management after surgical removal of brain metastasis remains controversial. Although postoperative whole-brain radiation therapy (WBRT) has been shown to prevent local recurrence and decrease deaths, this modality can substantially decrease neurocognitive function and quality of life. Stereotactic radiosurgery (SRS) can theoretically achieve the same level of local control with fewer side effects, although studies conclusively demonstrating such outcomes are lacking. To assess the effectiveness and safety profile of tumor bed SRS after resection of brain metastasis, the authors performed a retrospective analysis of 110 patients who had received such treatment at the Centre Hospitalier Universitaire de Sherbrooke. They designed the study to identify risk factors for local recurrence and placed special emphasis on factors that could potentially be addressed.

Methods

Patients who had received treatment from 2004 through 2013 were included if they had undergone surgical removal of 1 or more brain metastases and if the tumor bed was treated by SRS regardless of the extent of resection or prior WBRT. All cases were retrospectively analyzed for patient and tumor-specific factors, treatment protocol, adverse outcomes, cavity outcomes, and survival for as long as follow-up was available. Univariate and multivariate Cox regression analyses were performed to identify risk factors for local recurrence and predictors of increased survival times.

Results

Median patient age at first SRS treatment was 58 years (range 37–84 years). The most frequently diagnosed primary tumor was non–small cell lung cancer. The rate of gross-total resection was 81%. The median Karnofsky Performance Scale score was 90%. Tumor bed SRS was performed at a median of 3 weeks after surgery. Median follow-up and survival times were 10 and 11 months, respectively. Actuarial local control of the cavity at 12 months was 73%; median time to recurrence was 6 months. According to multivariate analysis, risk factors for recurrence were a longer surgery-to-SRS delay (HR 1.625, p = 0.003) and a lower maximum radiation dose delivered to the cavity (HR 0.817, p = 0.006). Factors not associated with increased recurrence were subtotal or piecemeal resections, prior WBRT, histology of the primary tumor, and larger cavity volume. No factors predictive of survival were identified. Symptomatic radiation-induced enhancement occurred in 6% of patients and leptomeningeal dissemination in 11%. Pathologically confirmed radiation-induced necrosis occurred in 1 (0.9%) patient.

Conclusions

Adjuvant tumor bed SRS after the resection of brain metastasis is a valuable alternative to adjuvant WBRT. Risk factors for local recurrence are lower maximum radiation dose and a surgery-to-SRS delay longer than 3 weeks. Outcomes were not worse for patients who had undergone prior WBRT and subtotal or piecemeal resections. Pending the results of prospective randomized controlled trials, the authors' study supports the safety and efficacy of adjuvant SRS after resection of brain metastasis. SRS should be performed as early as possible, ideally within 3 weeks of the surgery.

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David Mathieu, Charles Deacon, Catherine-Andrée Pinard, Brendan Kenny and Julie Duval

Object

Hypothalamic hamartomas (HHs) are congenital lesions typically presenting with medically refractory epilepsy. Open or endoscopic surgical procedures to remove or disconnect the hamartoma have been reported to be effective but are associated with significant morbidity. The authors of studies on Gamma Knife surgery for HHs have reported an encouraging rate of epilepsy resolution with minimal side effects. At the Centre Hospitalier Universitaire de Sherbrooke, the authors have undertaken a prospective observational study of the outcomes of patients who underwent radiosurgery for HHs.

Methods

Patients were included in the study if they had an HH, refractory epilepsy, and no other suspected seizure focus. After radiosurgery, seizure status was assessed every 3 months and reported using the Engel Classification. Quality of life evaluation was performed annually using a standardized questionnaire, and neuropsychological evaluation was performed after 2 years.

Results

Nine patients were included in the study. They ranged in age from 12 to 57 years. Epilepsy began in infancy in all cases and was refractory to standard antiepileptic drugs. The patients received an average of 2 antiepileptic drugs before undergoing radiosurgery. Using the Régis Classification, 6 patients had smaller hamartomas (Grade I–III) and underwent treatment of the entire lesion, using a margin dose of 14–20 Gy. Treatment volume ranged from 0.3 to 1.0 ml. Three patients had larger lesions (Grade IV–VI) for which a radiosurgical disconnection was attempted, targeting the area of attachment to the hypothalamus. For those patients, the margin dose was 15 or 16 Gy, with treatment volume ranging from 0.8 to 1.8 ml. In all patients, the radiation dose received by the optic pathways was kept below 10 Gy. Disconnection led to no improvement in epilepsy (Engel Class IV). Four patients in whom the entire lesion was treated are now seizure free (Engel Class I), with another having only rare seizures (Engel Class II). Quality of life and verbal memory were improved in those patients with more than 3 years of follow-up. No adverse event occurred after radiosurgery.

Conclusions

Radiosurgery safely and effectively controlled the epileptic disorder in patients with HHs when the entire lesion could be targeted. Radiosurgical disconnection is ineffective and cannot be recommended.

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Douglas Kondziolka, Ricky Madhok, L. Dade Lunsford, David Mathieu, Juan J. Martin, Ajay Niranjan and John C. Flickinger

Object

Meningiomas of the cerebral convexity are often surgically curable because both the mass and involved dura mater can be removed. Stereotactic radiosurgery has become an important primary or adjuvant treatment for patients with intracranial meningiomas. The authors evaluated clinical and imaging outcomes in patients with convexity meningiomas after radiosurgery.

Methods

The patient cohort consisted of 125 patients with convexity meningiomas managed using radiosurgery at some point during an 18-year period. The patient series included 76 women, 55 patients who had undergone prior resection, and 6 patients with neurofibromatosis Type 2. Tumors were located in frontal (80 patients), parietal (24 patients), temporal (12 patients), and occipital (9 patients) areas. The WHO tumor grades in patients with prior resections were Grade I in 34 patients, Grade II in 15 patients, and Grade III in 6 patients. Seventy patients underwent primary radiosurgery and therefore had no prior histological tumor diagnosis. The mean tumor volume was 7.6 ml. Radiosurgery was performed using the Leksell Gamma Knife with a mean tumor margin dose of 14.2 Gy.

Results

Serial imaging was evaluated in 115 patients (92%). After primary radiosurgery, the tumor control rate was 92%. After adjuvant radiosurgery, the control rate was 97% for Grade I tumors. The actuarial tumor control rates at 3 and 5 years for the entire series were 86.1 ± 3.8% and 71.6 ± 8.6%, respectively. For patients with benign tumors (Grade I) and those without prior surgery, the actuarial tumor control rate was 95.3 ± 2.3% and 85.8 ± 9.3%, respectively. Delayed resection after radiosurgery was performed in 9 patients (7%) at an average of 35 months. No patient developed a subsequent radiation-induced tumor. The overall morbidity rate was 9.6%. Symptomatic peritumoral imaging changes compatible with edema or adverse radiation effects developed in 5%, at a mean of 8 months.

Conclusions

Stereotactic radiosurgery provides satisfactory control rates either after resection or as an alternate to resection, particularly for histologically benign meningiomas. Its role is most valuable for patients whose tumors affect critical neurological regions and who are poor candidates for resection. Both temporary and permanent morbidity are related to brain location and tumor volume.

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Shobhan Vachhrajani, Charbel Fawaz, David Mathieu, Cynthia Ménard, Michael D. Cusimano, Fred Gentili, Mojgan Hodaie, Brendan Kenny, Abhaya V. Kulkarni, Normand Laperriere, Michael Schwartz, May Tsao and Mark Bernstein

Object

Gamma Knife surgery (GKS) is used to treat benign and malignant brain tumors, arteriovenous malformations, trigeminal neuralgia, and other conditions. Patients experience reduced neurological morbidity from GKS compared with open microneurosurgery, but risks of radiation injury and technical limitations persist. The authors report treatment complications from the early experience of 2 Canadian GKS programs in Toronto and Sherbrooke.

Methods

In Toronto, a prospective administrative database was searched for adverse events and incomplete treatment administrations. In Sherbrooke, data were acquired by chart review. Patients were accrued until August 1, 2007, and a total of 973 patients were included in this report.

Results

During the radiosurgical procedure, 19 patients (2%) suffered anxiety or syncopal episodes, and 2 patients suffered acute coronary events. Treatments were incompletely administered in 12 patients (1.2%). Severe pain was a delayed complication: 8 patients suffered unexpected headaches, and 9 patients developed severe facial pain. New motor deficits developed in 11 patients, including edema-induced ataxia in 4 and one case of facial weakness after treatment of a vestibular schwannoma. Four patients required shunt placement for symptomatic hydrocephalus, and 16 patients suffered delayed seizures.

Conclusions

Gamma Knife surgery is a minimally invasive treatment modality for many intracranial diseases. Treatment is not risk free, and some patients will develop complications; these are likely to decrease as institutional experience matures. Expanding availability and indications necessitate discussion of these risks with patients considering treatment.

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Hideyuki Kano, Jason Sheehan, Penny K. Sneed, Heyoung L. McBride, Byron Young, Christopher Duma, David Mathieu, Zachary Seymour, Michael W. McDermott, Douglas Kondziolka, Aditya Iyer and L. Dade Lunsford

OBJECT

Stereotactic radiosurgery (SRS) is a potentially important option for patients with skull base chondrosarcomas. The object of this study was to analyze the outcomes of SRS for chondrosarcoma patients who underwent this treatment as a part of multimodality management.

METHODS

Seven participating centers of the North American Gamma Knife Consortium (NAGKC) identified 46 patients who underwent SRS for skull base chondrosarcomas. Thirty-six patients had previously undergone tumor resections and 5 had been treated with fractionated radiation therapy (RT). The median tumor volume was 8.0 cm3 (range 0.9–28.2 cm3), and the median margin dose was 15 Gy (range 10.5–20 Gy). Kaplan-Meier analysis was used to calculate progression-free and overall survival rates.

RESULTS

At a median follow-up of 75 months after SRS, 8 patients were dead. The actuarial overall survival after SRS was 89% at 3 years, 86% at 5 years, and 76% at 10 years. Local tumor progression occurred in 10 patients. The rate of progression-free survival (PFS) after SRS was 88% at 3 years, 85% at 5 years, and 70% at 10 years. Prior RT was significantly associated with shorter PFS. Eight patients required salvage resection, and 3 patients (7%) developed adverse radiation effects. Cranial nerve deficits improved in 22 (56%) of the 39 patients who deficits before SRS. Clinical improvement after SRS was noted in patients with abducens nerve paralysis (61%), oculomotor nerve paralysis (50%), lower cranial nerve dysfunction (50%), optic neuropathy (43%), facial neuropathy (38%), trochlear nerve paralysis (33%), trigeminal neuropathy (12%), and hearing loss (10%).

CONCLUSIONS

Stereotactic radiosurgery for skull base chondrosarcomas is an important adjuvant option for the treatment of these rare tumors, as part of a team approach that includes initial surgical removal of symptomatic larger tumors.

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Donald N. Liew, Hideyuki Kano, Douglas Kondziolka, David Mathieu, Ajay Niranjan, John C. Flickinger, John M. Kirkwood, Ahmad Tarhini, Stergios Moschos and L. Dade Lunsford

Object

To evaluate the role of stereotactic radiosurgery (SRS) in the management of brain metastases from melanoma, the authors assessed clinical outcomes and prognostic factors for survival and tumor control.

Methods

The authors reviewed 333 consecutive patients with melanoma who underwent SRS for 1570 brain metastases from cutaneous and mucosal/acral melanoma. The patient population consisted of 109 female and 224 male patients with a median age of 53 years. Two hundred eleven patients (63%) had multiple metastases. One hundred eighteen patients (35%) underwent whole-brain radiation therapy (WBRT). The target volume ranged from 0.1 cm3 to 37.2 cm3. The median marginal dose was 18 Gy.

Results

Actuarial survival rates were 70% at 3 months, 47% at 6 months, 25% at 12 months, and 10% at 24 months after radiosurgery. Factors associated with longer survival included controlled extracranial disease, better Karnofsky Performance Scale score, fewer brain metastases, no prior WBRT, no prior chemotherapy, administration of immunotherapy, and no intratumoral hemorrhage before radiosurgery. The median survival for patients with a solitary brain metastasis, controlled extracranial disease, and administration of immunotherapy after radiosurgery was 22 months. Sustained local tumor control was achieved in 73% of the patients. Sixty-four (25%) of 259 patients who had follow-up imaging after SRS had evidence of delayed intratumoral hemorrhage. Sixteen patients underwent a craniotomy due to intratumoral hemorrhage. Seventeen patients (6%) had asymptomatic and 21 patients (7%) had symptomatic radiation effects. Patients with ≤ 8 brain metastases, no prior WBRT, and the recursive partitioning analysis Class I had extended survivals (median 54.3 months).

Conclusions

Stereotactic radiosurgery is an especially valuable option for patients with controlled systemic disease even if they have multiple metastatic brain tumors.