Review of 20 years of adult medulloblastoma treatment: Chemotherapy prescription trends and survival.

Background: The historic standard of care for adult medulloblastoma has been considered surgery and radiation, while chemotherapy is increasingly being prescribed. This study reviewed 20-year chemotherapy trends at a high-volume center, as well as overall and progression free-survival. Methods: Adults with medulloblastoma treated at an academic center from January 1, 1999 to -December 31, 2020 were reviewed. Patient baseline data were summarized and Kaplan-Meier estimators were used for survival. Results: Forty-nine patients were included; median age was 30 years and male: female ratio was 2:1. Desmoplastic and classical histologies were most common. Of all patients, 23 (47%) were high risk and 7 (14%) metastatic at diagnosis. Only 10 (20%) received initial chemotherapy, of which 70% were high risk and 30% metastatic, with most treated from 2010 to 2020. Forty percent of initial chemotherapy patients received salvage chemotherapy for recurrence or metastases (of all patients, 49% required salvage). Initial chemotherapy regimens were mainly cisplatin/lomustine/vincristine, and at recurrence cisplatin/etoposide. Median overall survival was 8.6 years (95% CI 7.5-∞), with 1-, 5-, and 10-year survival at 95.8%, 72%, and 46.7%. Median overall survival for those who did not receive initial chemotherapy was 12.4 years and 7.4 years for those who did (P-value .2). Conclusions: Twenty years of adult medulloblastoma treatment was reviewed. Initial chemotherapy patients, most of whom were high risk, trended towards worse survival, but this was nonsignificant. The ideal timing and choice of chemotherapy for adult medulloblastoma is unknown-challenges of administering chemotherapy following photon craniospinal irradiation may have prevented it from becoming routine.

Corrigendum to: Impact of lymphopenia on survival for elderly patients with glioblastoma: A secondary analysis of the CCTG CE.6 (EORTC 26062-22061, TROG 08.02) randomized clinical trial.

[This corrects the article DOI: 10.1093/noajnl/vdab153.].

Impact of lymphopenia on survival for elderly patients with glioblastoma: A secondary analysis of the CCTG CE.6 (EORTC 26062-22061, TROG03.01) randomized clinical trial.

BACKGROUND: Lymphopenia may lead to worse outcomes for glioblastoma patients. This study is a secondary analysis of the CCTG CE.6 trial evaluating the impact of chemotherapy and radiation on lymphopenia, and effects of lymphopenia on overall survival (OS). METHODS: CCTG CE.6 randomized elderly glioblastoma patients (≥ 65 years) to short-course radiation alone (RT) or short-course radiation with temozolomide (RT + TMZ). Lymphopenia (mild-moderate: grade 1-2; severe: grade 3-4) was defined per CTCAE v3.0, and measured at baseline, 1 week and 4 weeks post-RT. Preselected key factors for analysis included age, sex, ECOG, resection extent, MGMT methylation, Mini-Mental State Examination, and steroid use. Multinomial logistic regression and multivariable Cox regression models were used to identify lymphopenia-associated factors and association with survival. RESULTS: Five hundred and sixty-two patients were analyzed (281 RT vs 281 RT+TMZ). At baseline, both arms had similar rates of mild-moderate (21.4% vs 21.4%) and severe (3.2% vs 2.9%) lymphopenia. However, at 4 weeks post-RT, RT+TMZ was more likely to develop lymphopenia (mild-moderate: 27.9% vs 18.2%; severe: 9.3% vs 1.8%; p<0.001). Developing any lymphopenia post-RT was associated with baseline lymphopenia (P < .001). Baseline lymphopenia (hazard ratio [HR] 1.3) was associated with worse OS (HR: 1.30, 95% confidence interval [CI] 1.05-1.62; P = .02), regardless of MGMT status. CONCLUSIONS: Development of post-RT lymphopenia is associated with addition of TMZ and baseline lymphopenia and not with RT alone in patients treated with short-course radiation. However, regardless of MGMT status, only baseline lymphopenia is associated with worse OS, which may be considered as a prognostic biomarker for elderly glioblastoma patients.

Meningioma Screening With MRI in Childhood Leukemia Survivors Treated With Cranial Radiation.

PURPOSE: Radiation-induced meningioma is a known late effect of cranial radiation therapy. Cranial magnetic resonance imaging (MRI) can detect small meningiomas, but its potential value as a screening tool is unknown. METHODS AND MATERIALS: MRI was used to screen asymptomatic survivors of childhood acute lymphoblastic leukemia (ALL) treated with cranial radiation therapy ≥10 years previously. The incidence of radiation-induced meningioma and outcomes of this group were compared with a historical cohort of survivors with the same exposure who underwent imaging only to investigate clinical signs or symptoms. RESULTS: One hundred seventy-six childhood leukemia survivors were included in this study: 70 in the screening group and 106 unscreened. Screening MRI was performed a median of 25 years after radiation therapy and detected meningioma in 15 (21.4%). In the unscreened group, 17 patients (16.0%) had neurologic symptoms leading to an MRI a median interval of 24 years after radiation therapy, 9 of whom (8.5%) were diagnosed with meningioma. There was no significant difference between screened versus unscreened patients in the size of meningioma (mean diameter, 1.6 cm vs 2.6 cm; P = .13), meningioma incidence (7.4% vs 4.0% at 25 years; P = .19), or extent of resection. Three patients had persistent neurologic symptoms in the unscreened group versus none among screened patients (P = .28). CONCLUSIONS: Screening MRI was able to detect small meningiomas that were not clinically apparent; however, we could not demonstrate a significant improvement in the chance of total resection or a significant decrease in morbidity. A larger sample could clarify potential reduction in neurologic sequelae associated with screening.

MGMT promoter methylation status testing to guide therapy for glioblastoma: refining the approach based on emerging evidence and current challenges.

Glioblastoma (GBM) is the most common primary malignant brain tumor, with a universally poor prognosis. The emergence of molecular biomarkers has had a significant impact on histological typing and diagnosis, as well as predicting patient survival and response to treatment. The methylation status of the O6-methylguanine-DNA methyl-transferase (MGMT) gene promoter is one such molecular biomarker. Despite the strong evidence supporting the role of MGMT methylation status in prognostication, its routine implementation in clinical practice has been challenging. The methods and optimal cutoff definitions for MGMT status determination remain controversial. Variation in detection methods between laboratories presents a major challenge for consensus. Moreover, consideration of other clinical and genetic/epigenetic factors must also be incorporated into treatment decision making. In this review, we distill the available evidence to summarize our position on the optimal use of available assays, and propose strategies for resolving cases with equivocal methylation status and a framework for incorporating this important assay into research and clinical practice.

Therapeutic radiation for childhood cancer drives structural aberrations of NF2 in meningiomas.

Cranial radiotherapy improves survival of the most common childhood cancers, including brain tumors and leukemia. Unfortunately, long-term survivors are faced with consequences of secondary neoplasia, including radiation-induced meningiomas (RIMs). We characterized 31 RIMs with exome/NF2 intronic sequencing, RNA sequencing and methylation profiling, and found NF2 gene rearrangements in 12/31 of RIMs, an observation previously unreported in sporadic meningioma (SM). Additionally, known recurrent mutations characteristic of SM, including AKT1, KLF4, TRAF7 and SMO, were not observed in RIMs. Combined losses of chromosomes 1p and 22q were common in RIMs (16/18 cases) and overall, chromosomal aberrations were more complex than that observed in SM. Patterns of DNA methylation profiling supported similar cell of origin between RIMs and SMs. The findings indicate that the mutational landscape of RIMs is distinct from SMs, and have significant therapeutic implications for survivors of childhood cranial radiation and the elucidation of the molecular pathogenesis of meningiomas.Radiation-induced meningiomas are often more aggressive than sporadic ones. In this study, the authors perform an exome, methylation and RNA-seq analysis of 31 cases of radiation-induced meningioma and show NF2 rearrangement, an observation previously unreported in the sporadic tumors.

Image-guided, intensity-modulated radiation therapy (IG-IMRT) for skull base chordoma and chondrosarcoma: preliminary outcomes.

BACKGROUND: We report our preliminary outcomes following high-dose image-guided intensity modulated radiotherapy (IG-IMRT) for skull base chordoma and chondrosarcoma. METHODS: Forty-two consecutive IG-IMRT patients, with either skull base chordoma (n = 24) or chondrosarcoma (n = 18) treated between August 2001 and December 2012 were reviewed. The median follow-up was 36 months (range, 3-90 mo) in the chordoma cohort, and 67 months (range, 15-125) in the chondrosarcoma cohort. Initial surgery included biopsy (7% of patients), subtotal resection (57% of patients), and gross total resection (36% of patients). The median IG-IMRT total doses in the chondrosarcoma and chordoma cohorts were 70 Gy and 76 Gy, respectively, delivered with 2 Gy/fraction. RESULTS: For the chordoma and chondrosarcoma cohorts, the 5-year overall survival and local control rates were 85.6% and 65.3%, and 87.8% and 88.1%, respectively. In total, 10 patients progressed locally: 8 were chordoma patients and 2 chondrosarcoma patients. Both chondrosarcoma failures were in higher-grade tumors (grades 2 and 3). None of the 8 patients with grade 1 chondrosarcoma failed, with a median follow-up of 77 months (range, 34-125). There were 8 radiation-induced late effects-the most significant was a radiation-induced secondary malignancy occurring 6.7 years following IG-IMRT. Gross total resection and age were predictors of local control in the chordoma and chondrosarcoma patients, respectively. CONCLUSIONS: We report favorable survival, local control and adverse event rates following high dose IG-IMRT. Further follow-up is needed to confirm long-term efficacy.

Benefit from procarbazine, lomustine, and vincristine in oligodendroglial tumors is associated with mutation of IDH.

PURPOSE: Patients with 1p/19q codeleted anaplastic oligodendroglial tumors who participated in RTOG (Radiation Therapy Oncology Group) 9402 lived much longer after chemoradiotherapy (CRT) than radiation therapy (RT) alone. However, some patients with noncodeleted tumors also benefited from CRT; survival curves separated after the median had been reached, and significantly more patients lived ≥ 10 years after CRT than RT. Thus, 1p/19q status may not identify all responders to CRT. PATIENTS AND METHODS: Using trial data, we inquired whether an IDH mutation or germ-line polymorphism associated with IDH-mutant gliomas identified the patients in RTOG 9402 who benefited from CRT. RESULTS: IDH status was evaluable in 210 of 291 patients; 156 (74%) had mutations. rs55705857 was evaluable in 245 patients; 76 (31%) carried the G risk allele. Both were associated with longer progression-free survival after CRT, and mutant IDH was associated with longer overall survival (9.4 v 5.7 years; hazard ratio [HR], 0.59; 95% CI, 0.40 to 0.86; P = .006). For those with wild-type tumors, CRT did not prolong median survival (1.3 v 1.8 years; HR, 1.14; 95% CI, 0.63 to 2.04; P = .67) or 10-year survival rate (CRT, 6% v RT, 4%). Patients with codeleted mutated tumors (14.7 v 6.8 years; HR, 0.49; 95% CI, 0.28 to 0.85; P = .01) and noncodeleted mutated tumors (5.5 v 3.3 years; HR, 0.56; 95% CI, 0.32 to 0.99; P < .05) lived longer after CRT than RT. CONCLUSION: IDH mutational status identified patients with oligodendroglial tumors who did (and did not) benefit from alkylating-agent chemotherapy with RT. Although patients with codeleted tumors lived longest, patients with noncodeleted IDH-mutated tumors also lived longer after CRT.

Salvage radiosurgery for brain metastases: prognostic factors to consider in patient selection.

PURPOSE: Stereotactic radiosurgery (SRS) is offered to patients for recurrent brain metastases after prior brain radiation therapy (RT), but few studies have evaluated the efficacy of salvage SRS or factors to consider in selecting patients for this treatment. This study reports overall survival (OS), intracranial progression-free survival (PFS), and local control (LC) after salvage SRS, and factors associated with outcomes. METHODS AND MATERIALS: This is a retrospective review of patients treated from 2009 to 2011 with salvage SRS after prior brain RT for brain metastases. Survival from salvage SRS and from initial brain metastases diagnosis (IBMD) was calculated. Univariate and multivariable (MVA) analyses included age, performance status, recursive partitioning analysis (RPA) class, extracranial disease control, and time from initial RT to salvage SRS. RESULTS: There were 106 patients included in the analysis with a median age of 56.9 years (range 32.5-82 years). A median of 2 metastases were treated per patient (range, 1-12) with a median dose of 21 Gy (range, 12-24) prescribed to the 50% isodose. With a median follow-up of 10.5 months (range, 0.1-68.2), LC was 82.8%, 60.1%, and 46.8% at 6 months, 1 year, and 3 years, respectively. Median PFS was 6.2 months (95% confidence interval [CI]=4.9-7.6). Median OS was 11.7 months (95% CI=8.1-13) from salvage SRS, and 22.1 months from IBMD (95% CI=18.4-26.8). On MVA, age (P=.01; hazard ratio [HR]=1.04; 95% CI=1.01-1.07), extracranial disease control (P=.004; HR=0.46; 95% CI=0.27-0.78), and interval from initial RT to salvage SRS of at least 265 days (P=.001; HR=2.46; 95% CI=1.47-4.09) were predictive of OS. CONCLUSIONS: This study demonstrates that patients can have durable local control and survival after salvage SRS for recurrent brain metastases. In particular, younger patients with controlled extracranial disease and a durable response to initial brain RT are likely to benefit from salvage SRS.

Dosimetric and late radiation toxicity comparison between iodine-125 brachytherapy and stereotactic radiation therapy for juxtapapillary choroidal melanoma.

PURPOSE: To 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. METHODS: Ninety-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 were calculated. Kaplan-Meier estimates determined the actuarial rates of late toxicities, and the log-rank test compared the estimates. RESULTS: The 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. CONCLUSIONS: Late 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.

Long-term outcomes for adult craniopharyngioma following radiation therapy.

BACKGROUND: We report long-term outcomes in adult patients with craniopharyngioma following surgery and radiation therapy (RT). MATERIAL AND METHODS: Fifty-three patients treated with RT (median, 50 Gy in 25 fractions) between 1980 and 2009 with pathologically confirmed craniopharyngioma were reviewed (53% solid and 47% cystic/solid). The median age was 53 years (range, 22-76), 53% were female, 83% were sub-totally resected, 6% were gross totally resected and 11% had a biopsy and/or cyst aspiration alone. RT was delivered adjuvantly in 53% of patients as opposed to salvage intent upon progression. RESULTS: Median follow-up was seven years (86 months, range, 8-259). The 5- and 10-year progression-free survival (PFS) rates were 85% and 69%, overall survival (OS) rates were 76% and 70%, and cause-specific survival (CSS) rates were both 88%, respectively. Both univariable and multivariable analysis identified age (<53 or ≥53) as a prognostic factor for OS (p =0.0003) and CSS (p =0.05). PFS was observed to be worse in patients with >2 surgeries prior to RT (p =0.01). Neither the intent of radiation or tumor type (cystic vs. solid/cystic) were prognostic or predictive. New endocrinopathies and visual dysfunction were observed in 53% and 17% of patients post-surgery, and in 11% and 6% post-RT, respectively. CONCLUSION: We report long-term favorable PFS, CSS and OS for craniopharyngioma post-RT. We observe age as a significant prognostic factor, however, timing of radiation was not.

Gamma knife radiosurgery for the treatment of cystic cerebral metastases.

PURPOSE: To assess the role of Gamma Knife radiosurgery (GKRS) in the treatment of nonsurgical cystic brain metastasis, and to determine predictors of response to GKRS. METHODS: We 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. RESULTS: A 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. CONCLUSIONS: This 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.

Volume specific response criteria for brain metastases following salvage stereotactic radiosurgery and associated predictors of response.

BACKGROUND: We aimed to derive three-dimensional volume-based (V(3D)) response criteria that approximate those based on Response Evaluation Criteria in Solid Tumours (RECIST) in patients with brain metastases (BM) treated with salvage stereotactic radiosurgery (SRS). MATERIAL AND METHODS: Seventy patients with 178 BM were treated with SRS. Each BM was characterised at baseline and at each follow-up MRI according to its widest diameter and V(3D) using ITK-SNAP image segmentation software. RESULTS: The median tumour diameter was 1.2 cm (range, 0.2-4.5 cm) and V(3D) was 0.73 cm(3) (range, 0.01-22.7 cm(3)). The V(3D) percent changes that best matched RECIST response criteria were: an increase of ≥71.5% for progressive disease, a ≥58.5% decrease for partial response and a <58.5% decrease or increase of <71.5% for stable disease (k =0.85). A baseline diameter >3.0 cm (p =0.006) and a V(3D) >6.0 cm(3) (p =0.043) predicted for local failure, and a baseline cumulative V(3D) of >3.0 cm(3) (p =0.02) was adversely prognostic for survival. CONCLUSIONS: We define 3D volume specific criteria to base response upon for brain metastases treated with salvage SRS. Tumours with a V(3D) of greater than 6 cm(3) are at a higher risk of local failure.

A 2011 updated systematic review and clinical practice guideline for the management of malignant extradural spinal cord compression.

PURPOSE: To 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). METHODS: A 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. RESULTS: An 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. CONCLUSIONS: If 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.

Evaluation of early imaging response criteria in glioblastoma multiforme.

BACKGROUND: Early and accurate prediction of response to cancer treatment through imaging criteria is particularly important in rapidly progressive malignancies such as Glioblastoma Multiforme (GBM). We sought to assess the predictive value of structural imaging response criteria one month after concurrent chemotherapy and radiotherapy (RT) in patients with GBM. METHODS: Thirty patients were enrolled from 2005 to 2007 (median follow-up 22 months). Tumor volumes were delineated at the boundary of abnormal contrast enhancement on T1-weighted images prior to and 1 month after RT. Clinical Progression [CP] occurred when clinical and/or radiological events led to a change in chemotherapy management. Early Radiologic Progression [ERP] was defined as the qualitative interpretation of radiological progression one month post-RT. Patients with ERP were determined pseudoprogressors if clinically stable for ≥6 months. Receiver-operator characteristics were calculated for RECIST and MacDonald criteria, along with alternative thresholds against 1 year CP-free survival and 2 year overall survival (OS). RESULTS: 13 patients (52%) were found to have ERP, of whom 5 (38.5%) were pseudoprogressors. Patients with ERP had a lower median OS (11.2 mo) than those without (not reached) (p < 0.001). True progressors fared worse than pseudoprogressors (median survival 7.2 mo vs. 19.0 mo, p < 0.001). Volume thresholds performed slightly better compared to area and diameter thresholds in ROC analysis. Responses of > 25% in volume or > 15% in area were most predictive of OS. CONCLUSIONS: We show that while a subjective interpretation of early radiological progression from baseline is generally associated with poor outcome, true progressors cannot be distinguished from pseudoprogressors. In contrast, the magnitude of early imaging volumetric response may be a predictive and quantitative metric of favorable outcome.

Upfront observation versus radiation for adult pilocytic astrocytoma.

BACKGROUND: Although pilocytic astrocytoma accounts for up to 40% of all childhood brain tumors, it is a rare disease in adults. Consequently, there are few mature data on the impact of up-front treatment options after surgery that include observation or adjuvant radiotherapy. METHODS: Ten women and 20 men were identified who were diagnosed with pilocytic astrocytoma from 1971 to 2007 and were retrospectively reviewed. The median patient age was 30 years (range, 18-64 years), and the median follow-up was 87 months (range, 16-420 months). Initial surgery included biopsy (10% of patients), subtotal resection (57% of patients), or gross-total resection (33% of patients). Nineteen patients were observed postoperatively, whereas 11 patients received up-front postoperative adjuvant radiotherapy (50 grays in 25 fractions). No patient received adjuvant or concurrent chemotherapy. Progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. Differences between survival curves were analyzed with the log-rank test. RESULTS: For the entire cohort, the 5-year and 10-year OS rates were 95% and 85%, respectively, and the 5-year and 10-year PFS rates were 63% and 35%, respectively. The median PFS was 8.4 years. Initial radiation, compared with observation, did not have an impact on OS but significantly improved PFS. The 5-year PFS rate for patients who were observed versus those who received radiation was 42% versus 91%, respectively; and, at 10 years, the PFS rate was 17% versus 60%, respectively (P = .005). Patients who progressed after observation (11 of 19 patients) received various salvage therapies, resulting in a 2-year PFS rate of 68% compared with 33% for patients who progressed after initial radiation (3 of 11 patients) and were salvaged with either chemotherapy or surgery (P = .1). CONCLUSIONS: Adjuvant radiotherapy for pilocytic astrocytoma significantly prolonged PFS at both 5 years and 10 years compared with observation. However, equivalent OS was observed, which reflected the efficacy of salvage therapies.

Technique for stereotactic body radiotherapy for spinal metastases.

Stereotactic body radiotherapy (SBRT) is an emerging technique for spinal tumours that is a natural succession to brain radiosurgery. The spine is an ideal site for SBRT due to its relative immobility and the potential clinical benefits of high dose delivery, particularly to optimise local control and avoid disease progression that can result in spinal cord compression. However, the proximity of the tumour to the spinal cord, with the potential for radiation myelopathy if the dose is delivered inaccurately or if the spinal cord dose limit is set too high, demands technical accuracy with radiation myelopathy a feared complication. Spine SBRT has been delivered with either a robotic-based linac system such as the Cyberknife, or with linac-based systems equipped with a multileaf collimator and image guidance system. Regardless of the technology, spine SBRT demands sophisticated treatment planning and delivery. This case-based technical review outlines the SBRT apparatus, planning and treatment delivery in use at the University of Toronto, Toronto, Canada.

Apparatus-dependent dosimetric differences in spine stereotactic body radiotherapy.

The purpose of this investigation was to study apparatus-dependent dose distribution differences specific to spine stereotactic body radiotherapy (SBRT) treatment planning. This multi-institutional study was performed evaluating an image-guided robotic radiosurgery system (CK), intensity modulated protons (IMP), multileaf collimator (MLC) fixed-field IMRT with 5 mm (11 field), 4 mm (9 field), and 2.5 mm (8- and 9-field) leaf widths and intensity modulated volumetric arc therapy (IMVAT) with a 2.5 mm MLC. Treatment plans were systematically developed for targets consisting of one, two and three consecutive thoracic vertebral bodies (VBs) with the esophagus and spinal cord contoured as the organs at risk. It was found that all modalities achieved acceptable treatment planning constraints. However, following normalization fixed field IMRT with a 2.5 mm MLC, IMVAT and IMP systems yielded the smallest ratio of maximum dose divided by the prescription dose (MD/PD) for one-, two- and three-VB PTVs (ranging from 1.1-1.16). The 2.5 mm MLC 9-field IMRT, IMVAT and CK plans resulted in the least dose to 0.1 cc volumes of spinal cord and esophagus. CK plans had the greatest degree of target dose inhomogeneity. As the level of complexity increased with an increasing number of vertebral bodies, distinct apparatus features such as the use of a high number of beams and a finer leaf size MLC were favored. Our study quantified apparatus-dependent dose-distribution differences specific to spine SBRT given strict, but realistic, constraints and highlights the need to benchmark physical dose distributions for multi-institutional clinical trials.

Equivalence in dose fall-off for isocentric and nonisocentric intracranial treatment modalities and its impact on dose fractionation schemes.

PURPOSE: To investigate whether dose fall-off characteristics would be significantly different among intracranial radiosurgery modalities and the influence of these characteristics on fractionation schemes in terms of normal tissue sparing. METHODS AND MATERIALS: An analytic model was developed to measure dose fall-off characteristics near the target independent of treatment modalities. Variations in the peripheral dose fall-off characteristics were then examined and compared for intracranial tumors treated with Gamma Knife, Cyberknife, or Novalis LINAC-based system. Equivalent uniform biologic effective dose (EUBED) for the normal brain tissue was calculated. Functional dependence of the normal brain EUBED on varying numbers of fractions (1 to 30) was studied for the three modalities. RESULTS: The derived model fitted remarkably well for all the cases (R(2) > 0.99). No statistically significant differences in the dose fall-off relationships were found between the three modalities. Based on the extent of variations in the dose fall-off curves, normal brain EUBED was found to decrease with increasing number of fractions for the targets, with alpha/beta ranging from 10 to 20. This decrease was most pronounced for hypofractionated treatments with fewer than 10 fractions. Additionally, EUBED was found to increase slightly with increasing number of fractions for targets with alpha/beta ranging from 2 to 5. CONCLUSION: Nearly identical dose fall-off characteristics were found for the Gamma Knife, Cyberknife, and Novalis systems. Based on EUBED calculations, normal brain sparing was found to favor hypofractionated treatments for fast-growing tumors with alpha/beta ranging from 10 to 20 and single fraction treatment for abnormal tissues with low alpha/beta values such as alpha/beta = 2.