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.

Are there consistent relationships between major connective tissue components, intramuscular fat content and muscle fibre types in cattle muscle?

Intramuscular connective tissue (IMCT) is mainly composed of several fibrils (known as total collagen (TCol)) linked between each other by different chemical cross-links (CLs), the whole being embedded in a matrix of proteoglycans (PGs). In the field of beef quality, there is limited information on the role of CLs and PGs. Accordingly, several authors suggest that, to investigate the role of IMCT, it is important to investigate them just like TCol and insoluble collagen (ICol). In muscle, there are two other components, the muscle fibres and intramuscular fat (IMF) content. There are limited data on the relationships between these three components of muscle and then on possibility to independently manipulate these characteristics in order to control the final quality of meat. The present study aimed to investigate whether consistent relationships exist between these different components of muscle. Therefore, the present study compared four muscles of two cattle types (dairy and beef) to determine associations between TCol, ICol, CLs and PGs. Data were analysed across and within muscle (M) and animal type (AT) based on residuals. There was a strong M and AT effect for all muscle characteristics and an interaction M × AT for type I muscle fibres and IMF. Correlations between TCol, ICol and their CLs were M- and AT-independent. Total proteoglycans were positively correlated with TCol and ICol in a muscle-dependent manner irrespective of AT, but no correlation was found with CLs. On the contrary, CLs were negatively correlated with the ratio TPGs : TCol in an M-dependent manner, irrespective of AT. TCol, ICol and CLs were positively and negatively correlated with type IIA and IIB+X muscle fibres only in longissimus thoracis (LT) muscle, regardless the AT. Insoluble collagen was the only parameter of IMCT to be correlated with type I muscle fibres but only in LT muscle, irrespective of AT. There was no correlation between PGs and muscle fibre types, but PGs were the only IMCT component to be related with IMF in an M-dependent manner, irrespective of AT. Finally, there was no correlation between muscle fibre types and IMF content within M and AT. This study revealed that there is a strong relationship between IMCT components irrespective of M, an M-dependent relationship between the IMCT components and muscle fibre types and few (only with PGs) or no relationship between IMF and IMCT and muscle fibres.

Prediction of beef meat fatty acid composition by visible-near-infrared spectroscopy was improved by preliminary freeze-drying.

The aim of this study was to compare visible-near-infrared spectroscopy (VIS/NIRS) models developed from fresh or freeze-dried samples for predicting the fatty acid (FA) composition of beef samples. The hypothesis tested is that the removal of water from samples could improve the VIS/NIRS model performance. A total of 454 beef samples obtained from different bovine muscles were used. No significant differences were found in the performance of VIS/NIRS models developed from fresh or freeze-dried samples for predicting both major individual FAs and families of FAs and for some FAs (16:0, 18:0, 18:1 n-9, 18:2 n-6, 20:4 n-6, 22:5 n-3, 22:6 n-3, saturated, mono-unsaturated FA, and total n-3 long chain poly-unsaturated FAs (PUFA)). In contrast, the standard error of predictions for total PUFAs, total n-3 PUFAs, total conjugated linoleic acid, 20:5 n-3, and 18:3 n-3 were improved (by 21% on average; P < .05) in freeze-dried samples compared with fresh samples.

A scoping review of mental health prevention and intervention initiatives for infants and preschoolers at risk for socio-emotional difficulties.

BACKGROUND: Infant mental health has emerged as a unique area of practice and research distinguished from child and youth sub-specialties by its advocacy for a relational practice framework with an emphasis on parents/caregivers being integral to assessment, treatment, and prevention initiatives. A diverse array of initiatives offered across a broad spectrum of delivery methods is available to clinicians. However, to date, a large-scale mapping of the research evidence regarding these interventions has yet to be completed to help inform clinician's decisions regarding the best approaches for their clients. To address this knowledge gap, this study aimed to report on the landscape of research pertaining to mental health interventions for infants and preschoolers (0-5 years), and their families at risk for socio-emotional difficulties and negative developmental outcomes. METHOD: A scoping review methodology was used to conduct a large-scale mapping of the intervention research pertaining to infants and preschoolers (0-5) at risk for socio-emotional difficulties. We searched MEDLINE, PsycINFO, EMBASE, Web of Science, The Cochrane Library, CINAHL, LILACS, ProQuest Nursing & Allied Health Source, World Cat, and ClinicalTrials.gov , from inception to December 31, 2012. We extracted information regarding publication date, geographical location, study design, level of risk, population, key intervention mechanism, and outcome measures. RESULTS: We identified 533 potential studies from 1233 title and abstracts after the first round of screening. Full text article review in the second round of screening resulted in a total of 162 included articles for the final analysis. Results indicated that over 50% of interventions evaluated were randomized controlled trials conducted in Westernized countries. Most studies could be subdivided by level of risk within a preventative public health framework including universal, selected, indicated, and direct treatment for children formally diagnosed with a mental disorder. Risk factors experienced by children and their families were heterogeneously defined and numerous outcome measures across included studies. The results of this study are limited to the last search date of 2012. CONCLUSIONS: Key intervention mechanisms spanned a range of approaches including parenting groups, dyadic, in-home, cognitive-behavioral therapy, and day care-based interventions. The findings are discussed in terms of implications for broad trends and gaps in research and policy for this population.

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.

A scoping review of evidence-based interventions available to parents of maltreated children ages 0-5 involved with child welfare services.

Parents referred to child welfare services for child maltreatment often struggle against chronic risk factors including violence, substance abuse, mental health concerns, and poverty, which impinge upon their ability to be sensitive caregivers. The first line of intervention within the child welfare context is to modify parenting behavior. This scoping review comprehensively surveyed all available literature to map the extent and range of research activity around the types of interventions available within a child welfare context to parents of infants and toddlers (0-5 years of age), to identify the facilitators and/or barriers to the uptake of interventions, and to check that interventions match the risk factors faced by parents. This scoping review engaged in stringent screening of studies based upon inclusion/exclusion criteria. Sixty-five articles involving forty-two interventions met inclusion criteria. Interventions generally aimed to improve parenting practices, the relationship between parent and child, and/or attachment security, along with reducing child abuse and/or neglect. A notable finding of this scoping review is that at present, interventions for parents of children ages 0-5 involved with the child welfare system are most frequently measured via case study and quasi-experimental designs, with randomized control trials making up 26.2% of included study designs.

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.

Embedding mental health interventions in early childhood education systems for at-risk preschoolers: an evidence to policy realist review.

BACKGROUND: Current early childhood systems of care are not geared to respond to the complex needs of preschoolers at risk for mental health problems in a timely, coordinated, multidisciplinary, and comprehensive fashion. Evidence-informed policy represents an opportunity for implementing prevention, promotion, and early intervention at the population or at-risk level. Exposure to risk factors as well as the presence of clinical disorders can derail the developmental trajectories of preschoolers, and problems may persist if left untreated. One way to address these multiple research-to-policy gaps are systematic reviews sensitive to context and knowledge user needs, such as the realist review. The realist review is an iterative process between research teams and knowledge users to build mid-level program theories in order to understand which interventions work best for whom and under what context. METHODS/DESIGN: The realist review employs five 'iterative' steps: (1) clarify scope, (2) search for evidence, (3) appraise primary studies and extract data, (4) synthesize the evidence, and (5) disseminate, implement, and evaluate evidence, to answer two research questions: What interventions improve mental health outcomes for preschoolers at risk for socio-emotional difficulties and under what circumstances do they work? and what are the best models of care for integrating mental health interventions within pre-existing early childhood education (ECE) services for at-risk children? Knowledge users and researchers will work together through each stage of the review starting with refining the questions through to decisions regarding program theory building, data extraction, analysis, and design of a policy dissemination plan. The initial questions will guide preliminary literature reviews, but subsequent more focused searches will be informed by knowledge users familiar with local needs and further building of explanatory program theories. DISCUSSION: Policy makers want to know what works best for whom, but are faced with a wide and disparate intervention literature for at-risk children. Applying evidence-based standards is a good start, but the chain of implementation between research results and how to match interventions sensitive to local context are ongoing challenges. TRIAL REGISTRATION: Prospero registration number: CRD42014007301.

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.