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Terry Bunston, Deborah Mings, Normand Laperriere, Jacquey Malcolm, and Dorothy Williams

The diagnosis of cancer of the central nervous system (CNS) is often the diagnosis of an incurable, progressive disease with devastating effects on the physical, psychosocial, and cognitive functioning of patients. Because many of the treatment options are noncurative in nature, issues related to quality and quantity of life become paramount.

The purpose of the authors' research was to explore the prevalence of psychosocial needs in this cancer population and to determine whether these needs and their resolution impact on quality of life (QOL).

Telephone interviews were conducted with 75 patients in whom primary CNS cancer was diagnosed and who were able to pass the Mini-Mental Health Status Examination. Analysis of results indicated that the majority of patients (97.3%) had at least one concern; concerns over treatment side effects, controlling uncertainty, having a meaningful existence, self and body image, and family concerns were among the five most frequently cited need domains. Most patients (91.8%) received help. However, 75.3% reported needing additional help. The number of needs reported and the severity of fatigue most significantly impacted QOL.

The study identified the needs and experiences of the patient with CNS cancer. Quality of life and needs assessment information can be used to screen patients for distress and to measure the outcome of medical and psychosocial care and ultimately to ease the burden of illness.

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Joseph Bampoe, Normand Laperriere, Melania Pintilie, Jennifer Glen, Johann Micallef, and Mark Bernstein

Object. Until recently the assessment of outcome in patients treated for glioma has emphasized length of survival with the evaluation of quality of life (QOL) limited to unidimensional, mostly physical, measures. The authors report the multidimensional assessment of QOL as part of a randomized clinical trial of brachytherapy as a boost in the initial treatment of patients with glioblastoma multiforme.

Methods. A questionnaire previously developed by the senior authors and psychometrically validated was completed by patients on randomized entry into the study and at follow-up review every 3 months thereafter. The questionnaire was presented in a linear-analog self-assessment format. Karnofsky Performance Scale (KPS) scores were also recorded on each occasion.

No differences were found between patients in either arm of the study (conventional radiation therapy consisting of 50 Gy in 25 fractions or conventional radiation plus a brachytherapy boost of a minimum peripheral tumor dose of 60 Gy) in KPS and QOL scores during the 1st year of follow-up review. However, there was a statistically significant deterioration in patients' overall KPS scores during the 1st year of follow up compared with baseline scores. Of QOL items evaluated, statistically significant deteriorations were found in self care, speech, and concentration, and on subscale analyses, cognitive functioning and physical experience (symptoms) deteriorated significantly during the 1st year of follow up, compared with baseline values. The correlation between QOL and KPS scores was low.

Conclusions. Future studies in patients harboring malignant gliomas must incorporate measures assessing QOL because traditional measures focusing on physical or neurological functioning give an incomplete assessment of the patient's experience.

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Lucie Lafay-Cousin, Gillian Lindzon, Michael D. Taylor, Walter Hader, Cynthia Hawkins, Robert Nordal, Normand Laperriere, Suzanne Laughlin, Eric Bouffet, and Ute Bartels

OBJECT

Primary CNS sarcomas are very rare pediatric tumors with no defined standard of care.

METHODS

This study was a retrospective review of children diagnosed with a primary CNS sarcoma and treated at 2 Canadian tertiary care centers between 1995 and 2012. This report focuses on patients with cerebral hemispheric tumor location due to their specific clinical presentation.

RESULTS

Fourteen patients with nonmetastatic primary CNS sarcoma were identified; in 9 patients, tumors were located in the cerebral hemisphere and 7 of these patients presented with intratumoral hemorrhage. One infant who died of progressive disease postoperatively before receiving any adjuvant therapy was not included in this study. The final cohort therefore included 8 patients (4 males). Median patient age at diagnosis was 11.8 years (range 5.8–17 years). All tumors were located in the right hemisphere. Duration of symptoms prior to diagnosis was very short with a median of 2 days (range 3–7 days), except for 1 patient. Three (37.5%) patients had an underlying diagnosis of neurofibromatosis Type 1 (NF1). Gross-total resection was achieved in 5 patients. The dose of focal radiation therapy (RT) ranged between 54 Gy and 60 Gy. Concomitant etoposide was administered during RT. ICE (ifosfamide, carboplatin, etoposide) chemotherapy was administered prior to and after RT for a total of 6–8 cycles. Seven of the 8 patients were alive at a median time of 4.9 years (range 1.9–17.9 years) after treatment.

CONCLUSIONS

In this retrospective series, patients with primary CNS sarcomas located in the cerebral hemisphere most commonly presented with symptomatic acute intratumoral hemorrhage. Patients with NF1 were overrepresented. The combination of adjuvant ICE chemotherapy and focal RT provided encouraging outcomes.

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Alireza Mansouri, Soroush Larjani, George Klironomos, Normand Laperriere, Michael Cusimano, Fred Gentili, Michael Schwartz, and Gelareh Zadeh

OBJECT

In this paper, the authors’ aim was to determine short-term volumetric and diametric tumor growth and identify clinical, radiological, and dosimetric predictors of adverse radiation events (AREs) following stereotactic radiosurgery (SRS) for intracranial WHO Grade I meningiomas.

METHODS

This is a retrospective review of all WHO Grade I meningiomas that were treated with SRS (primary or adjuvant) between December 2005 and June 2012 at the University Health Network. Seventy-five patients had at least 24 months of both clinical and radiological follow-up and were, therefore, included in this study. Tumor growth was defined as any volumetric or diametric change greater than 10% per year. Any variation less than +10% was considered growth stability. Volumetric measurements were made using T1-weighted gadolinium-enhanced 3-T MRI scans and ITK-SNAP software. Tumor growth rates were calculated using the specific growth rate (SGR). Univariate statistics were used to identify predictors of post-SRS AREs. All statistical analyses were performed using IBM SPSS.

RESULTS

Women accounted for 69.3% of patients, and the mean treatment age was 58.6 years. Median follow-up was 36.2 months. Twenty-one (28%) patients had undergone prior resection. Two (3%) patients required salvage surgical intervention following SRS. The majority of the lesions (56%) were skull base tumors. Median tumor volume and diameter were 5.2 cm3 and 27.5 mm, respectively. The absence of tumor growth was observed in 39 cases (52%) based on the volumetric measurements, while the absence of tumor growth was observed in 69 cases (92%) based on the diametric measurements. Twenty-six patients (34.6%) experienced new-onset AREs, including headache (17.3%), cranial neuropathy (10.6%), speech impairment (2.7%), tremors (2.7%), and ataxia (1.3%). Fourteen patients (18.7%) experienced new-onset edema, and 4 of these patients were symptomatic. A lower conformity index (1.24 vs 1.4) was significantly associated with the development of edema (p < 0.001 power > 0.8). Patients with meningiomas that had growth rates of more than 10% per year were more likely to experience long-term headaches after SRS (p = 0.022).

CONCLUSIONS

Volume-based reporting of SRS outcomes for meningiomas may be a more accurate method given the complex morphology of some lesions. The conformity index was identified as a predictor of edema following radiosurgery.

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Adriana Fonseca, Palma Solano, Vijay Ramaswamy, Uri Tabori, Annie Huang, James M. Drake, Derek S. Tsang, Normand Laperriere, Ute Bartels, Abhaya V. Kulkarni, and Eric Bouffet

OBJECTIVE

There is no consensus on the optimal clinical management of ventriculomegaly and hydrocephalus in patients with diffuse intrinsic pontine glioma (DIPG). To date, the impact on survival in patients with ventriculomegaly and CSF diversion for hydrocephalus in this population remains to be elucidated. Herein, the authors describe their institutional experience.

METHODS

Patients diagnosed with DIPG and treated with up-front radiation therapy (RT) at The Hospital for Sick Children between 2000 and 2019 were identified. Images at diagnosis and progression were used to determine the frontal/occipital horn ratio (FOR) as a method to measure ventricular size. Patients with ventriculomegaly (FOR ≥ 0.36) were stratified according to the presence of symptoms and categorized as follows: 1) asymptomatic ventriculomegaly and 2) symptomatic hydrocephalus. For patients with ventriculomegaly who did not require CSF diversion, post-RT imaging was also evaluated to assess changes in the FOR after RT. Proportional hazards analyses were used to identify clinical and treatment factors correlated with survival. The Kaplan-Meier method was used to perform survival estimates, and the log-rank method was used to identify survival differences between groups.

RESULTS

Eighty-two patients met the inclusion criteria. At diagnosis, 28% (n = 23) of patients presented with ventriculomegaly, including 8 patients who had symptomatic hydrocephalus and underwent CSF diversion. A ventriculoperitoneal shunt was placed in the majority of patients (6/8). Fifteen asymptomatic patients were managed without CSF diversion. Six patients had resolution of ventriculomegaly after RT. Of 66 patients with imaging at the time of progression, 36 (55%) had ventriculomegaly, and 9 of them required CSF diversion. The presence of ventriculomegaly at diagnosis did not correlate with survival on univariate analysis. However, patients with symptomatic hydrocephalus at the time of progression who underwent CSF diversion had a survival advantage (p = 0.0340) when compared to patients with ventriculomegaly managed with conservative approaches.

CONCLUSIONS

Although ventriculomegaly can be present in up to 55% of patients with DIPG, the majority of patients present with asymptomatic ventriculomegaly and do not require surgical interventions. In some cases ventriculomegaly improved after medical management with steroids and RT. CSF diversion for hydrocephalus at the time of diagnosis does not impact survival. In contrast, our results suggest a survival advantage in patients who undergo CSF diversion for hydrocephalus at the time of progression, albeit that advantage is likely to be confounded by biological and individual patient factors. Further research in this area is needed to understand the best timing and type of interventions in this population.

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May N. Tsao, Michael L. Schwartz, Mark Bernstein, William C. Halliday, Alex W. Lightstone, Mark G. Hamilton, Satish Jaywant, and Normand Laperriere

✓ Capillary hemangiomas are rare benign vascular tumors that tend to occur in children. Whereas the majority of hemangiomas may regress spontaneously, those associated with functional sequelae or severe symptoms may require treatment. Two patients with capillary hemangiomas of the cavernous sinus that caused neurological symptoms were treated with fractionated stereotactic radiation therapy. Both hemangiomas had shown a progressive increase in size during observation before radiation therapy; both tumors regressed after radiotherapy. Up to the time of the last follow-up evaluation both patients experienced symptomatic relief after radiation. One patient's tumor remains in complete remission and the second tumor continues to demonstrate minor residual contrast enhancement without progression.

The authors conclude that fractionated stereotactic radiation therapy is a useful treatment modality in the management of symptomatic capillary hemangiomas when these tumors arise in regions of the brain or skull base in which a complete resection cannot be accomplished.

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Iska Moxon-Emre, Eric Bouffet, Michael D. Taylor, Normand Laperriere, Michael B. Sharpe, Suzanne Laughlin, Ute Bartels, Nadia Scantlebury, Nicole Law, David Malkin, Jovanka Skocic, Logan Richard, and Donald J. Mabbott

OBJECTIVE

Craniospinal irradiation damages the white matter in children treated for medulloblastoma, but the treatment-intensity effects are unclear. In a cross-sectional retrospective study, the effects of treatment with the least intensive radiation protocol versus protocols that delivered more radiation to the brain, in addition to the effects of continuous radiation dose, on white matter architecture were evaluated.

METHODS

Diffusion tensor imaging was used to assess fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity. First, regional white matter analyses and tract-based spatial statistics were conducted in 34 medulloblastoma patients and 38 healthy controls. Patients were stratified according to those treated with 1) the least intensive radiation protocol, specifically reduced-dose craniospinal irradiation plus a boost to the tumor bed only (n = 17), or 2) any other dose and boost combination that delivered more radiation to the brain, which was also termed the “all-other-treatments” group (n = 17), and comprised patients treated with standard-dose craniospinal irradiation plus a posterior fossa boost, standard-dose craniospinal irradiation plus a tumor bed boost, or reduced-dose craniospinal irradiation plus a posterior fossa boost. Second, voxel-wise dose-distribution analyses were conducted on a separate cohort of medulloblastoma patients (n = 15).

RESULTS

The all-other-treatments group, but not the reduced-dose craniospinal irradiation plus tumor bed group, had lower fractional anisotropy and higher radial diffusivity than controls in all brain regions (all p < 0.05). The reduced-dose craniospinal irradiation plus tumor bed boost group had higher fractional anisotropy (p = 0.05) and lower radial diffusivity (p = 0.04) in the temporal region, and higher fractional anisotropy in the frontal region (p = 0.04), than the all-other-treatments group. Linear mixed-effects modeling revealed that the dose and age at diagnosis together 1) better predicted fractional anisotropy in the temporal region than models with either alone (p < 0.005), but 2) did not better predict fractional anisotropy in comparison with dose alone in the occipital region (p > 0.05).

CONCLUSIONS

Together, the results show that white matter damage has a clear association with increasing radiation dose, and that treatment with reduced-dose craniospinal irradiation plus tumor bed boost appears to preserve white matter in some brain regions.

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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.