Normand Laperriere

Radiotherapy for newly diagnosed malignant glioma in adults: a systematic review.

PURPOSEnA systematic review was conducted to develop guidelines for radiotherapy in adult patients with newly diagnosed malignant glioma.nnnMETHODSnMEDLINE, CANCERLIT, the Cochrane Library, and relevant conference proceedings were searched to identify randomized trials and meta-analyses.nnnRESULTSnPooling of six randomized trials detected a significant survival benefit favouring post-operative radiotherapy compared with no radiotherapy (risk ratio, 0.81; 95% confidence interval, 0.74 to 0.88, P<0.00001). Two randomized trials demonstrated no significant difference in survival rates for whole brain radiation versus more local fields that encompass the enhancing primary plus a 2 cm margin. A randomized trial detected a small improvement in survival with 60 Gy in 30 fractions over 45 Gy in 20 fractions. Radiation dose intensification and radiation sensitizer approaches have not demonstrated superior survival rates compared with conventionally fractionated doses of 50-60 Gy.nnnCONCLUSIONSnPost-operative external beam radiotherapy is recommended as standard therapy for patients with malignant glioma. The high-dose volume should incorporate the enhancing tumour plus a limited margin (e.g. 2 cm) for the planning target volume, and the total dose delivered should be in the range of 50-60 Gy in fraction sizes of 1.8-2.0 Gy. Radiation dose intensification and radiation sensitizer approaches are not recommended as standard care. For patients older than age 70, preliminary data suggest that the same survival benefit can be achieved with less morbidity using a shorter course of radiotherapy. Supportive care alone is a reasonable therapeutic option in patients older than age 70 with a poor performance status.

Symptom response after palliative radiotherapy for patients with brain metastases.

Whole brain radiotherapy (RT) is frequently used to palliate symptoms in patients with brain metastases, but the palliative benefit to patients has not been well documented. We conducted a longitudinal observational prospective study of patients receiving standard RT (20 Gray (Gy)/5 fractions) for symptomatic brain metastases. End-points were observer rating of neurological symptoms, patient-rated symptoms, performance status, neurological functional status, cognitive function and quality of life (QOL). Median survival for the 75 patients was 86 days (95% confidence interval (CI): 65-101 days). At 1 month, 19% of patients showed an improvement or resolution of presenting symptoms, 23% were stable and 55% had progressed or died. Patient-rated symptoms were increased at 1 month in comparison to baseline data. Only 4 patients had an improved performance status and 22 were stable. Many patients with brain metastases have a short life expectancy and may not benefit from even short duration radiation schedules. Further effort is needed to optimise patient selection and tailor treatment appropriately.

A 2011 Updated Systematic Review and Clinical Practice Guideline for the Management of Malignant Extradural Spinal Cord Compression

PURPOSEnTo update the 2005 Cancer Care Ontario practice guidelines for the diagnosis and treatment of adult patients with a suspected or confirmed diagnosis of extradural malignant spinal cord compression (MESCC).nnnMETHODSnA review and analysis of data published from January 2004 to May 2011. The systematic literature review included published randomized control trials (RCTs), systematic reviews, meta-analyses, and prospective/retrospective studies.nnnRESULTSnAn RCT of radiation therapy (RT) with or without decompressive surgery showed improvements in pain, ambulatory ability, urinary continence, duration of continence, functional status, and overall survival. Two RCTs of RT (30 Gy in eight fractions vs. 16 Gy in two fractions; 16 Gy in two fractions vs. 8 Gy in one fraction) in patients with a poor prognosis showed no difference in ambulation, duration of ambulation, bladder function, pain response, in-field failure, and overall survival. Retrospective multicenter studies reported that protracted RT schedules in nonsurgical patients with a good prognosis improved local control but had no effect on functional or survival outcomes.nnnCONCLUSIONSnIf not medically contraindicated, steroids are recommended for any patient with neurologic deficits suspected or confirmed to have MESCC. Surgery should be considered for patients with a good prognosis who are medically and surgically operable. RT should be given to nonsurgical patients. For those with a poor prognosis, a single fraction of 8 Gy should be given; for those with a good prognosis, 30 Gy in 10 fractions could be considered. Patients should be followed up clinically and/or radiographically to determine whether a local relapse develops. Salvage therapies should be introduced before significant neurologic deficits occur.

A retrospective analysis of 52 cases of spinal cord glioma managed with radiation therapy

PURPOSEnTo describe the outcome of primary spinal cord glioma treated with radiation therapy after surgery and to identify variables predictive of outcome.nnnMETHODS AND MATERIALSnA chart review of 52 patients with a diagnosis of spinal cord non-ependymoma glioma at the Princess Margaret Hospital was conducted. Thirty-two patients (62%) were male and 20 (38%) were female. Median age was 32 years (2-76 years). Median follow-up was 3.7 years (2 months to 27 years). Initial surgical management consisted of biopsy alone in 27 (52%) cases, subtotal resection in 20 (38%) cases, and gross total resection in 5 (10%) cases. All patients received postoperative radiation therapy; median total dose was 50 Gy, given in 25 daily fractions (20-60 Gy). Actuarial survival rates were calculated and the influence of patient-, tumor-, and treatment-related variables on outcome was determined.nnnRESULTSnFive-year overall, cause-specific, and progression-free survivals were 54%, 62%, and 58%, respectively. Ten-year survivals were 45%, 50%, and 43%, respectively. A total of 29 (56%) patients died during the period of review. For 23 (79%) of these patients, death was cancer specific. Progression of tumor was documented in 28 of 52 (54%) patients. The following factors predicted for improved outcome on univariate analysis: age < 18 years, low-grade histology, and length of symptoms prior to diagnosis > 6 months.nnnCONCLUSIONnThe outcome of patients in this series is consistent with that of other similar published reports. Specific recommendations are made for the management of this tumor.

Radiotherapy for brain metastases: defining palliative response

BACKGROUND AND PURPOSEnMost patients with brain metastases are treated with palliative whole brain radiotherapy (WBRT). There is no established definition of palliative response. The aim of this study was to develop and test clinically useful criteria for response following palliative WBRT.nnnMATERIALS AND METHODSnA prospective study was conducted of patients with symptomatic brain metastases treated with WBRT (20 Gy/5 fractions) and standardised steroid tapering. Assessments included observer rating of neurological symptoms, patient-completed symptom checklist and performance status (PS). Response criteria were operationally defined based on a combination of neurological symptoms, PS and steroid dose.nnnRESULTSnSeventy-five patients were accrued. At 1 month, presenting neurological symptoms were improved in 14 patients, stable in 17, and worse in 21; 23 patients were not assessed, mainly due to death or frailty. Using response criteria defined a priori, 15% (95% CI 7-23%) of patients were classified as having a response to RT, 25% no response, and 29% progression; 27% were deceased at or soon after 1 month. A revised set of criteria was tested, with less emphasis on complete tapering of steroids: they increased the proportion of patients responding to 39% (95% CI 27-50%) but didnt change the large proportion who did not benefit (44%).nnnCONCLUSIONSnClinical response to RT of patients with brain metastases is multifactorial, comprising symptoms, PS and other factors. Assessment of degree of palliation depend on the exact definition used. More research is needed in this important area, to help validate criteria for assessing palliation after WBRT.

Clinical Controversies: Proton Radiation Therapy for Brain and Skull Base Tumors

Proton radiotherapy offers distinct physical properties that could lead to an improvement of dose distribution with subsequent reduction of integral dose to the patient. This supports the potential use of proton beams in tumors close to sensitive structures, such as the skull base and the brain. In the present manuscript, the literature on proton therapy for brain and skull base tumors is critically reviewed and compared with results obtained with modern photon techniques. Treatment planning comparisons demonstrate that dose distributions within the target are comparable. In terms of normal tissue dose distribution, protons offer an advantage in the intermediate- and low-dose regions, and this may result in long-term clinical benefit, although to date no randomized or long-term follow-up data demonstrate this. Considering the excellent long-term results seen with photons in localized tumors, this benefit may be modest and difficult to demonstrate. Protons may allow for safe delivery of higher local doses with the potential to improve local control in some tumors. However, improvements in photon techniques also enable safe dose escalation, and therefore, the comparison of the techniques of delivery is likely to need randomized trials. Proton therapy offers effective treatment for a range of brain tumors. However, the limited availability, the cost, and the lack of evidence of superiority mean that advanced photon radiotherapy continues to be the treatment of choice. It is hoped that advances in technology, both in proton and photon radiotherapy delivery, and increasing information on the efficacy and toxicity of the two modalities will lead to further improvement in radiotherapy approaches and provide the basis for the best choice of treatment for the individual patient.

Neovascular Glaucoma After Stereotactic Radiotherapy for Juxtapapillary Choroidal Melanoma: Histopathologic and Dosimetric Findings

PURPOSEnEnucleation after stereotactic radiotherapy (SRT) for juxtapapillary choroidal melanoma may be required because of tumor progression (TP) or the development of intractable radiation-induced neovascular glaucoma (NVG). We compare pathologic changes and dosimetric findings in those eyes enucleated secondary to NVG as opposed to TP to better understand potential mechanisms.nnnMETHODS AND MATERIALSnPatients with juxtapapillary choroidal melanoma treated with SRT (70 Gy in 5 fractions, alternate days over a total of 10 days) at the Princess Margaret Hospital, Toronto, Ontario, Canada, who underwent enucleation between 1998 and 2006 were selected. We correlated dosimetric data based on the patients original SRT treatment plan with histopathologic findings in the retina, optic nerve head, and anterior chamber. A dedicated ocular pathologist reviewed each case in a blinded fashion.nnnRESULTSnTen eyes in ten patients were enucleated after SRT. Six were enucleated secondary to NVG and four secondary to because of TP. Aggressive tumor features such as invasion of the sclera and epithelioid cell type were observed predominantly in the TP group. Retinal damage was more predominant in the NVG group, as were findings of radiation-related retinal vascular changes of fibrinoid necrosis and hyalinization. No conclusive radiation-related effects were found in the anterior chamber. The maximum point dose and dose to 0.1 cc were lower for the anterior chamber as compared with the dose to the tumor, retina, and optic nerve head. The mean 0.1-cc doses to the retina were 69.4 Gy and 73.5 Gy and to the anterior chamber were 4.9 Gy and 17.3 Gy for the NVG group and tumor progression group, respectively.nnnCONCLUSIONSnOur findings suggest that NVG is due to radiation damage to the posterior chamber of the eye rather than primary radiation damage to the anterior segment.

Dosimetric and Late Radiation Toxicity Comparison Between Iodine-125 Brachytherapy and Stereotactic Radiation Therapy for Juxtapapillary Choroidal Melanoma

PURPOSEnTo compare the dose distributions and late radiation toxicities for (125)I brachytherapy (IBT) and stereotactic radiation therapy (SRT) in the treatment of juxtapapillary choroidal melanoma.nnnMETHODSnNinety-four consecutive patients with juxtapapillary melanoma were reviewed: 30 have been treated with IBT and 64 with SRT. Iodine-125 brachytherapy cases were modeled with plaque simulator software for dosimetric analysis. The SRT dosimetric data were obtained from the Radionics XKnife RT3 software. Mean doses at predetermined intraocular points werexa0calculated. Kaplan-Meier estimates determined the actuarial rates of late toxicities, and the log-rank test compared the estimates.nnnRESULTSnThe median follow-up was 46 months in both cohorts. The 2 cohorts were balanced with respect to pretreatment clinical and tumor characteristics. Comparisons of radiation toxicity rates between the IBT and SRT cohorts yielded actuarial rates at 50 months for cataracts of 62% and 75% (P=.1), for neovascular glaucoma 8% and 47% (P=.002), for radiation retinopathy 59% and 89% (P=.0001), and for radiation papillopathy 39% and 74% (P=.003), respectively. Dosimetric comparisons between the IBT and SRT cohorts yielded mean doses of 12.8 and 14.1 Gy (P=.56) for the lens center, 17.6 and 19.7 Gy (P=.44) for the lens posterior pole, 13.9 and 10.8 Gy (P=.30) for the ciliary body, 61.9 and 69.7 Gy (P=.03) for optic disc center, and 48.9 and 60.1 Gy (P<.0001) for retina at 5-mm distance from tumor margin, respectively.nnnCONCLUSIONSnLate radiation-induced toxicities were greater with SRT, which is secondary to the high-dose exposure inherent to the technique as compared with IBT. When technically feasible, IBT is preferred to treat juxtapapillary choroidal melanoma.

Gamma Knife Radiosurgery for the Treatment of Cystic Cerebral Metastases

PURPOSEnTo assess the role of Gamma Knife radiosurgery (GKRS) in the treatment of nonsurgical cystic brain metastasis, and to determine predictors of response to GKRS.nnnMETHODSnWe reviewed a prospectively maintained database of brain metastases patients treated at our institution between 2006 and 2010. All lesions with a cystic component were identified, and volumetric analysis was done to measure percentage of cystic volume on day of treatment and consecutive follow-up MRI scans. Clinical, radiologic, and dosimetry parameters were reviewed to establish the overall response of cystic metastases to GKRS as well as identify potential predictive factors of response.nnnRESULTSnA total of 111 lesions in 73 patients were analyzed; 57% of lesions received prior whole-brain radiation therapy (WBRT). Lung carcinoma was the primary cancer in 51% of patients, 10% breast, 10% colorectal, 4% melanoma, and 26% other. Fifty-seven percent of the patients were recursive partitioning analysis class 1, the remainder class 2. Mean target volume was 3.3 mL (range, 0.1-23 mL). Median prescription dose was 21 Gy (range, 15-24 Gy). Local control rates were 91%, 63%, and 37% at 6, 12, and 18 months, respectively. Local control was improved in lung primary and worse in patients with prior WBRT (univariate). Only lung primary predicted local control in multivariate analysis, whereas age and tumor volume did not. Lesions with a large cystic component did not show a poorer response compared with those with a small cystic component.nnnCONCLUSIONSnThis study supports the use of GKRS in the management of nonsurgical cystic metastases, despite a traditionally perceived poorer response. Our local control rates are comparable to a matched cohort of noncystic brain metastases, and therefore the presence of a large cystic component should not deter the use of GKRS. Predictors of response included tumor subtype. Prior WBRT decreased effectiveness of SRS for local control rates.