Evolving interest in meningioma, the most common primary brain tumor, has refined contemporary management of these tumors. Problematic, however, is the paucity of prospective clinical trials that ...provide an evidence-based algorithm for managing meningioma. This review summarizes the published literature regarding the treatment of newly diagnosed and recurrent meningioma, with an emphasis on outcomes stratified by WHO tumor grade. Specifically, this review focuses on patient outcomes following treatment (either adjuvant or at recurrence) with surgery or radiation therapy inclusive of radiosurgery and fractionated radiation therapy. Phase II trials for patients with meningioma have recently completed accrual within the Radiation Therapy Oncology Group and the European Organisation for Research and Treatment of Cancer consortia, and Phase III studies are being developed. However, at present, there are no completed prospective, randomized trials assessing the role of either surgery or radiation therapy. Successful completion of future studies will require a multidisciplinary effort, dissemination of the current knowledge base, improved implementation of WHO grading criteria, standardization of response criteria and other outcome end points, and concerted efforts to address weaknesses in present treatment paradigms, particularly for patients with progressive or recurrent low-grade meningioma or with high-grade meningioma. In parallel efforts, Response Assessment in Neuro-Oncology (RANO) subcommittees are developing a paper on systemic therapies for meningioma and a separate article proposing standardized end point and response criteria for meningioma.
Surgical resection represents the standard of care in diffuse glioma, and more extensive tumour resection appears to be associated with favourable outcome. Up to now, terminology to describe extent ...of resection has been inconsistently applied across clinical trials which hampers comparative analysis of cohorts between different studies. Based on a comprehensive literature review, we developed evidence-based expert recommendations on categories for extent of resection. Recommendations are formulated for the categories ‘biopsy’, ‘partial resection’, ‘subtotal resection’, ‘near total resection’, ‘complete resection’ and ‘supramaximal resection’. Definitions rest on reduction of contrast- and non–contrast-enhancing tumour in glioblastoma, and on reduction of T2/FLAIR-hyperintense tumour in gliomas WHO grade 2 or 3. Both relative reduction of tumour volume (in percentage) as a measurement of surgical efficacy and absolute residual tumour volume (in cm3) as a measurement of remaining tumour burden are incorporated into the categories for extent of resection. Class of evidence for the proposed categories ranges from class IIB to IV. Limitations of the suggested categories are discussed. The proposed categories on extent of resection offer a framework to standardize nomenclature based on previous studies, and will need to be evaluated in prospective, molecularly well-defined cohorts. Our categories may eventually help as a stratification factor for future clinical trials.
•Nomenclature to describe extent of resection in diffuse glioma is inconsistent.•Categories are formulated based on an extensive literature review.•Definitions rest on relative reduction of tumour and absolute residual tumour.•Class of evidence for the proposed categories ranges from class IIB-IV.•Our categories offer a framework to standardize nomenclature in diffuse glioma.
To provide guidance to clinicians regarding therapy for patients with brain metastases from solid tumors.
ASCO convened an Expert Panel and conducted a systematic review of the literature.
Thirty-two ...randomized trials published in 2008 or later met eligibility criteria and form the primary evidentiary base.
Surgery is a reasonable option for patients with brain metastases. Patients with large tumors with mass effect are more likely to benefit than those with multiple brain metastases and/or uncontrolled systemic disease. Patients with symptomatic brain metastases should receive local therapy regardless of the systemic therapy used. For patients with asymptomatic brain metastases, local therapy should not be deferred unless deferral is specifically recommended in this guideline. The decision to defer local therapy should be based on a multidisciplinary discussion of the potential benefits and harms that the patient may experience. Several regimens were recommended for non-small-cell lung cancer, breast cancer, and melanoma. For patients with asymptomatic brain metastases and no systemic therapy options, stereotactic radiosurgery (SRS) alone should be offered to patients with one to four unresected brain metastases, excluding small-cell lung carcinoma. SRS alone to the surgical cavity should be offered to patients with one to two resected brain metastases. SRS, whole brain radiation therapy, or their combination are reasonable options for other patients. Memantine and hippocampal avoidance should be offered to patients who receive whole brain radiation therapy and have no hippocampal lesions and 4 months or more expected survival. Patients with asymptomatic brain metastases with either Karnofsky Performance Status ≤ 50 or Karnofsky Performance Status < 70 with no systemic therapy options do not derive benefit from radiation therapy.Additional information is available at www.asco.org/neurooncology-guidelines.
Summary The SPine response assessment In Neuro-Oncology (SPINO) group is a committee of the Response Assessment in Neuro-Oncology working group and comprises a panel of international experts in spine ...stereotactic body radiotherapy (SBRT). Here, we present the group's first report on the challenges in standardising imaging-based assessment of local control and pain for spinal metastases. We review current imaging modalities used in SBRT treatment planning and tumour assessment and review the criteria for pain and local control in registered clinical trials specific to spine SBRT. We summarise the results of an international survey of the panel to establish the range of current practices in assessing tumour response to spine SBRT. The ultimate goal of the SPINO group is to report consensus criteria for tumour imaging, clinical assessment, and symptom-based response criteria to help standardise future clinical trials.
Abstract
Background
Emerging evidence suggests survival benefit from resection beyond all MRI abnormalities present on T1-enhanced and T2‒fluid attenuated inversion recovery (FLAIR) modalities in ...glioma (supratotal resection); however, the quality of evidence is unclear. We addressed this question via systematic review of the literature.
Methods
EMBASE, MEDLINE, Scopus, and Web of Science databases were queried. Case studies, reviews or editorials, non-English, abstract-only, brain metastases, and descriptive works were excluded. All others were included.
Results
Three hundred and nine unique references yielded 41 studies for full-text review, with 7 included in the final analysis. Studies were mostly of Oxford Center for Evidence-Based Medicine Level 4 quality. A total of 88 patients underwent supratotal resection in a combined cohort of 492 patients (214 males and 278 females, age 18 to 82 years). Fifty-one supratotal resections were conducted on high-grade gliomas, and 37 on low-grade gliomas. Karnofsky performance status, overall survival, progression-free survival, neurological deficits postoperatively, and anaplastic transformation were the main measured outcomes. No randomized controlled trials were identified. Preliminary low-quality support was found for supratotal resection in increasing overall survival and progression-free survival for both low-grade and high-grade glioma.
Conclusion
The literature suggests insufficient evidence for carte blanche application of supratotal resection, particularly in lower-grade gliomas where neurological deficits can result in long-term disability. While the preliminary studies discussed here, containing data from only a few centers, have reported increased progression-free and overall survival, these claims require validation in prospective research studies involving larger patient populations with clearly defined appropriate outcome metrics in order to reduce potential bias.
The impact of extent of resection (EOR) on survival for patients with glioblastoma (GBM) continues to be a point of debate despite multiple studies demonstrating that increasing EOR likely extends ...survival for these patients. In addition, contrast-enhancing residual tumor volume (CE-RTV) alone has rarely been analyzed quantitatively to determine if it is a predictor of outcome. The purpose of this study was to evaluate the effect of CE-RTV and T2/FLAIR residual volume (T2/F-RV) on overall survival.
A retrospective review of 128 patients who underwent primary resection of supratentorial GBM followed by standard radiation/chemotherapy was undertaken utilizing quantitative, volumetric analysis of pre- and postoperative MR images. The results were compared with clinical data obtained from the patients' medical records.
At analysis, 8% of patients were alive, and no patients were lost to follow-up. The overall median survival was 13.8 months, with a median Karnofsky Performance Scale (KPS) score of 90 at presentation. The median contrast-enhancing preoperative tumor volume (CE-PTV) was 29.0 cm(3), and CE-RTV was 1.2 cm(3), equating to a 95.8% median EOR. The median T2/F-RV was 36.8 cm(3). CE-PTV, CE-RTV, T2/F-RV, and EOR were all statistically significant predictors of survival when controlling for age and KPS score. A statistically significant benefit in survival was seen with a CE-RTV less than 2 cm(3) or an EOR greater than 98%. Evaluation of the volumetric analysis methodology was performed by observers of varying degrees of experience-an attending neurosurgeon, a fellow, and a medical student. Both the medical student and fellow recorded correlation coefficients of 0.98 when compared with the attending surgeon's measured volumes of CE-PTV, while for CE-RTV, correlation coefficients of 0.67 and 0.71 (medical student and fellow, respectively) were obtained.
CE-RTV and EOR were found to be significant predictors of survival after GBM resection. CERTV was the more significant predictor of survival compared with EOR, suggesting that the volume of residual contrast-enhancing tumor may be a more accurate and meaningful reflection of the pathobiology of GBM.
Effective treatment of glioblastoma (GBM) remains a formidable challenge. Survival rates remain poor despite decades of clinical trials of conventional and novel, biologically targeted therapeutics. ...There is considerable evidence that most of these therapeutics do not reach their targets in the brain when administered via conventional routes (intravenous or oral). Hence, direct delivery of therapeutics to the brain and to brain tumors is an active area of investigation. One of these techniques, convection-enhanced delivery (CED), involves the implantation of catheters through which conventional and novel therapeutic formulations can be delivered using continuous, low-positive-pressure bulk flow. Investigation in preclinical and clinical settings has demonstrated that CED can produce effective delivery of therapeutics to substantial volumes of brain and brain tumor. However, limitations in catheter technology and imaging of delivery have prevented this technique from being reliable and reproducible, and the only completed phase III study in GBM did not show a survival benefit for patients treated with an investigational therapeutic delivered via CED. Further development of CED is ongoing, with novel catheter designs and imaging approaches that may allow CED to become a more effective therapeutic delivery technique.
OBJECTIVE This is the first clinical outcomes report of NRG Oncology RTOG 0539, detailing the primary endpoint, 3-year progression-free survival (PFS), compared with a predefined historical control ...for intermediate-risk meningioma, and secondarily evaluating overall survival (OS), local failure, and prospectively scored adverse events (AEs). METHODS NRG Oncology RTOG 0539 was a Phase II clinical trial allocating meningioma patients to 1 of 3 prognostic groups and management strategies according to WHO grade, recurrence status, and resection extent. For the intermediate-risk group (Group 2), eligible patients had either newly diagnosed WHO Grade II meningioma that had been treated with gross-total resection (GTR; Simpson Grades I-III) or recurrent WHO Grade I meningioma with any resection extent. Pathology and imaging were centrally reviewed. Patients were treated with radiation therapy (RT), either intensity modulated (IMRT) or 3D conformal (3DCRT), 54 Gy in 30 fractions. The RT target volume was defined as the tumor bed and any nodular enhancement (e.g., in patients with recurrent WHO Grade I tumors) with a minimum 8-mm and maximum 15-mm margin, depending on tumor location and setup reproducibility of the RT method. The primary endpoint was 3-year PFS. Results were compared with historical controls (3-year PFS: 70% following GTR alone and 90% with GTR + RT). AEs were scored using NCI Common Toxicity Criteria. RESULTS Fifty-six patients enrolled in the intermediate-risk group, of whom 3 were ineligible and 1 did not receive RT. Of the 52 patients who received protocol therapy, 4 withdrew without a recurrence before 3 years leaving 48 patients evaluable for the primary endpoint, 3-year PFS, which was actuarially 93.8% (p = 0.0003). Within 3 years, 3 patients experienced events affecting PFS: 1 patient with a WHO Grade II tumor died of the disease, 1 patient with a WHO Grade II tumor had disease progression but remained alive, and 1 patient with recurrent WHO Grade I meningioma died of undetermined cause without tumor progression. The 3-year actuarial local failure rate was 4.1%, and the 3-year OS rate was 96%. After 3 years, progression occurred in 2 additional patients: 1 patient with recurrent WHO Grade I meningioma and 1 patient with WHO Grade II disease; both remain alive. Among 52 evaluable patients who received protocol treatment, 36 (69.2%) had WHO Grade II tumors and underwent GTR, and 16 (30.8%) had recurrent WHO Grade I tumors. There was no significant difference in PFS between these subgroups (p = 0.52, HR 0.56, 95% CI 0.09-3.35), validating their consolidation. Of the 52 evaluable patients, 44 (84.6%) received IMRT, and 50 (96.2%) were treated per protocol or with acceptable variation. AEs (definitely, probably, or possibly related to protocol treatment) were limited to Grade 1 or 2, with no reported Grade 3 events. CONCLUSIONS This is the first clinical outcomes report from NRG Oncology RTOG 0539. Patients with intermediate-risk meningioma treated with RT had excellent 3-year PFS, with a low rate of local failure and a low risk of AEs. These results support the use of postoperative RT for newly diagnosed gross-totally resected WHO Grade II or recurrent WHO Grade I meningioma irrespective of resection extent. They also document minimal toxicity and high rates of tumor control with IMRT. Clinical trial registration no.: NCT00895622 (clinicaltrials.gov).
Meningiomas are the most frequent nonglial primary brain tumors and represent about 30% of brain tumors. Usually, diagnosis and treatment planning are based on neuroimaging using mainly MRI or, ...rarely, CT. Most common treatment options are neurosurgical resection and radiotherapy (eg, radiosurgery, external fractionated radiotherapy). For follow-up after treatment, a structural imaging technique such as MRI or CT is used. However, these structural imaging modalities have limitations, particularly in terms of tumor delineation as well as diagnosis of posttherapeutic reactive changes. Molecular imaging techniques such as PET can characterize specific metabolic and cellular features which may provide clinically relevant information beyond that obtained from structural MR or CT imaging alone. Currently, the use of PET in meningioma patients is steadily increasing. In the present article, we provide recommendations for the use of PET imaging in the clinical management of meningiomas based on evidence generated from studies being validated by histology or clinical course.
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