Ancient Mongolian aurochs genomes reveal sustained introgression and management in East Asia.

Societies in East Asia have utilized domesticated cattle for over 5000 years, but the genetic history of cattle in East Asia remains understudied. Genome-wide analyses of 23 ancient Mongolian cattle reveal that East Asian aurochs and ancient East Asian taurine cattle are closely related, but neither are closely related to any modern East Asian breeds. We observe binary variation in aurochs diet throughout the early Neolithic, and genomic evidence shows millennia of sustained male-dominated introgression. We identify a unique connection between ancient Mongolian aurochs and the European Hereford breed. These results point to the likelihood of human management of aurochs in Northeast Asia prior to and during the initial adoption of taurine cattle pastoralism.

Temozolomide and Radiotherapy versus Radiotherapy Alone in Patients with Glioblastoma, IDH-wildtype: Post Hoc Analysis of the EORTC Randomized Phase III CATNON Trial.

PURPOSE: In a post hoc analysis of the CATNON trial (NCT00626990), we explored whether adding temozolomide to radiotherapy improves outcome in patients with IDH1/2 wildtype (wt) anaplastic astrocytomas with molecular features of glioblastoma [redesignated as glioblastoma, isocitrate dehydrogenase-wildtype (IDH-wt) in the 2021 World Health Organization (WHO) classification of central nervous system tumors]. PATIENTS AND METHODS: From the randomized phase III CATNON study examining the addition of adjuvant and concurrent temozolomide to radiotherapy in anaplastic astrocytomas, we selected a subgroup of IDH1/2wt and H3F3Awt tumors with presence of TERT promoter mutations and/or EGFR amplifications and/or combined gain of chromosome 7 and loss of chromosome 10. Molecular abnormalities including MGMT promoter methylation status were determined by next-generation sequencing, DNA methylation profiling, and SNaPshot analysis. RESULTS: Of the 751 patients entered in the CATNON study, 670 had fully molecularly characterized tumors. A total of 159 of these tumors met the WHO 2021 molecular criteria for glioblastoma, IDH-wt. Of these patients, 47 received radiotherapy only and 112 received a combination of radiotherapy and temozolomide. There was no added effect of temozolomide on either overall survival [HR, 1.19; 95% confidence interval (CI), 0.82-1.71] or progression-free survival (HR, 0.87; 95% CI, 0.61-1.24). MGMT promoter methylation was prognostic for overall survival, but was not predictive for outcome to temozolomide treatment either with respect to overall survival or progression-free survival. CONCLUSIONS: In this cohort of patients with glioblastoma, IDH-wt temozolomide treatment did not add benefit beyond that observed from radiotherapy, regardless of MGMT promoter status. These findings require a new well-powered prospective clinical study to explore the efficacy of temozolomide treatment in this patient population.

Evolution of postoperative pituitary adenoma resection cavities assessed by magnetic resonance imaging and implications regarding radiotherapy timing and modality.

PURPOSE: This study evaluates the temporal evolution of the spatial relationship between the pituitary adenoma transsphenoidal surgical cavity and the adjacent optic chiasm and discusses implications on timing and choice of radiotherapy modality. METHODS: This retrospective observational review analyzed factors that might influence the postoperative relationship between the surgical cavity and the optic chiasm, including tumor type, craniocaudal tumor and resection cavity dimensions, the preoperative distance between tumor and the optic chiasm, the presence of cavernous sinus invasion, and the choice of intraoperative packing material. Changes observed on magnetic resonance imaging in the preoperative, immediate (within 72 h), and delayed (≥3 months) postoperative periods were compared. RESULTS: Sixty-five patient histories were analyzed. Preoperatively, the pituitary adenoma was apposed to the optic chiasm in 43 patients (66%). Postoperatively, 34 patients (52%) in the immediate postoperative period and 54 patients (83%) in the delayed postoperative period had a distance ≥2 mm between the resection cavity and the optic chiasm. This distance provides a greater margin of safety with adjuvant radiosurgery. Preoperative tumor size showed a strong association with postoperative descent of the optic chiasm. CONCLUSIONS: Preoperative tumor size and degree of mass effect on the optic chiasm predict postoperative changes. In this study, the distance between the resection cavity and the optic chiasm was greater at ≥3 months postoperatively than in the immediate postoperative period, regardless of preoperative mass effect, indicating radiotherapy planning should be deferred to ≥3 months postoperatively when not precluded by aggressive histological characteristics that necessitate more immediate treatment. PRECIS: To investigate the temporal relationship between the postoperative sellar surgical cavity and the adjacent optic apparatus after transsphenoidal resection of pituitary adenomas and the implications for radiotherapy.

Adjuvant and concurrent temozolomide for 1p/19q non-co-deleted anaplastic glioma (CATNON; EORTC study 26053-22054): second interim analysis of a randomised, open-label, phase 3 study.

BACKGROUND: The CATNON trial investigated the addition of concurrent, adjuvant, and both current and adjuvant temozolomide to radiotherapy in adults with newly diagnosed 1p/19q non-co-deleted anaplastic gliomas. The benefit of concurrent temozolomide chemotherapy and relevance of mutations in the IDH1 and IDH2 genes remain unclear. METHODS: This randomised, open-label, phase 3 study done in 137 institutions across Australia, Europe, and North America included patients aged 18 years or older with newly diagnosed 1p/19q non-co-deleted anaplastic gliomas and a WHO performance status of 0-2. Patients were randomly assigned (1:1:1:1) centrally using a minimisation technique to radiotherapy alone (59·4 Gy in 33 fractions; three-dimensional conformal radiotherapy or intensity-modulated radiotherapy), radiotherapy with concurrent oral temozolomide (75 mg/m2 per day), radiotherapy with adjuvant oral temozolomide (12 4-week cycles of 150-200 mg/m2 temozolomide given on days 1-5), or radiotherapy with both concurrent and adjuvant temozolomide. Patients were stratified by institution, WHO performance status score, age, 1p loss of heterozygosity, the presence of oligodendroglial elements on microscopy, and MGMT promoter methylation status. The primary endpoint was overall survival adjusted by stratification factors at randomisation in the intention-to-treat population. A second interim analysis requested by the independent data monitoring committee was planned when two-thirds of total required events were observed to test superiority or futility of concurrent temozolomide. This study is registered with ClinicalTrials.gov, NCT00626990. FINDINGS: Between Dec 4, 2007, and Sept 11, 2015, 751 patients were randomly assigned (189 to radiotherapy alone, 188 to radiotherapy with concurrent temozolomide, 186 to radiotherapy and adjuvant temozolomide, and 188 to radiotherapy with concurrent and adjuvant temozolomide). Median follow-up was 55·7 months (IQR 41·0-77·3). The second interim analysis declared futility of concurrent temozolomide (median overall survival was 66·9 months [95% CI 45·7-82·3] with concurrent temozolomide vs 60·4 months [45·7-71·5] without concurrent temozolomide; hazard ratio [HR] 0·97 [99·1% CI 0·73-1·28], p=0·76). By contrast, adjuvant temozolomide improved overall survival compared with no adjuvant temozolomide (median overall survival 82·3 months [95% CI 67·2-116·6] vs 46·9 months [37·9-56·9]; HR 0·64 [95% CI 0·52-0·79], p<0·0001). The most frequent grade 3 and 4 toxicities were haematological, occurring in no patients in the radiotherapy only group, 16 (9%) of 185 patients in the concurrent temozolomide group, and 55 (15%) of 368 patients in both groups with adjuvant temozolomide. No treatment-related deaths were reported. INTERPRETATION: Adjuvant temozolomide chemotherapy, but not concurrent temozolomide chemotherapy, was associated with a survival benefit in patients with 1p/19q non-co-deleted anaplastic glioma. Clinical benefit was dependent on IDH1 and IDH2 mutational status. FUNDING: Merck Sharpe & Dohme.

Prognostic significance of genome-wide DNA methylation profiles within the randomized, phase 3, EORTC CATNON trial on non-1p/19q deleted anaplastic glioma.

BACKGROUND: Survival in patients with IDH1/2-mutant (mt) anaplastic astrocytomas is highly variable. We have used the prospective phase 3 CATNON trial to identify molecular factors related to outcome in IDH1/2mt anaplastic astrocytoma patients. METHODS: The CATNON trial randomized 751 adult patients with newly diagnosed 1p/19q non-codeleted anaplastic glioma to 59.4 Gy radiotherapy +/- concurrent and/or adjuvant temozolomide. The presence of necrosis and/or microvascular proliferation was scored at central pathology review. Infinium MethylationEPIC BeadChip arrays were used for genome-wide DNA methylation analysis and the determination of copy number variations (CNV). Two DNA methylation-based tumor classifiers were used for risk stratification. Next-generation sequencing (NGS) was performed using 1 of the 2 glioma-tailored NGS panels. The primary endpoint was overall survival measured from the date of randomization. RESULTS: Full analysis (genome-wide DNA methylation and NGS) was successfully performed on 654 tumors. Of these, 432 tumors were IDH1/2mt anaplastic astrocytomas. Both epigenetic classifiers identified poor prognosis patients that partially overlapped. A predictive prognostic Cox proportional hazard model identified that independent prognostic factors for IDH1/2mt anaplastic astrocytoma patients included; age, mini-mental state examination score, treatment with concurrent and/or adjuvant temozolomide, the epigenetic classifiers, PDGFRA amplification, CDKN2A/B homozygous deletion, PI3K mutations, and total CNV load. Independent recursive partitioning analysis highlights the importance of these factors for patient prognostication. CONCLUSION: Both clinical and molecular factors identify IDH1/2mt anaplastic astrocytoma patients with worse outcome. These results will further refine the current WHO criteria for glioma classification.

Non-IDH1-R132H IDH1/2 mutations are associated with increased DNA methylation and improved survival in astrocytomas, compared to IDH1-R132H mutations.

Somatic mutations in the isocitrate dehydrogenase genes IDH1 and IDH2 occur at high frequency in several tumour types. Even though these mutations are confined to distinct hotspots, we show that gliomas are the only tumour type with an exceptionally high percentage of IDH1R132H mutations. Patients harbouring IDH1R132H mutated tumours have lower levels of genome-wide DNA-methylation, and an associated increased gene expression, compared to tumours with other IDH1/2 mutations ("non-R132H IDH1/2 mutations"). This reduced methylation is seen in multiple tumour types and thus appears independent of the site of origin. For 1p/19q non-codeleted glioma (astrocytoma) patients, we show that this difference is clinically relevant: in samples of the randomised phase III CATNON trial, patients harbouring tumours with IDH mutations other than IDH1R132H have a better outcome (hazard ratio 0.41, 95% CI [0.24, 0.71], p = 0.0013). Such non-R132H IDH1/2-mutated tumours also had a significantly lower proportion of tumours assigned to prognostically poor DNA-methylation classes (p < 0.001). IDH mutation-type was independent in a multivariable model containing known clinical and molecular prognostic factors. To confirm these observations, we validated the prognostic effect of IDH mutation type on a large independent dataset. The observation that non-R132H IDH1/2-mutated astrocytomas have a more favourable prognosis than their IDH1R132H mutated counterpart indicates that not all IDH-mutations are identical. This difference is clinically relevant and should be taken into account for patient prognostication.

Treatment planning system and beam data validation for the ZAP-X: A novel self-shielded stereotactic radiosurgery system.

PURPOSE: To evaluate the treatment planning system (TPS) performance of the ZAP-X stereotactic radiosurgery (SRS) system through nondosimetric, dosimetric, and end-to-end (E2E) tests. METHODS: A comprehensive set of TPS commissioning and validation tests was developed using published guidelines. Nondosimetric validation tests included information transfer, computed tomography-magnetic resonance (CT-MR) image registration, structure/contouring, geometry, dose tools, and CT density. Dosimetric validation included comparisons between TPS and water tank/Solid Water measurements for various geometries and beam arrangements and end-to-end (E2E) tests. Patient-specific quality assurance was performed with an ion chamber in the Lucy phantom and with Gafchromic EBT3 film in the CyberKnife head phantom. RadCalc was used for independent verification of monitor units. Additional E2E tests were performed using the RPC Gamma Knife thermoluminescent dosimeter (TLD) phantom, MD Anderson SRS head phantom, and PseudoPatient gel phantom for independent absolute dose verification. RESULTS: CT-MR image registrations with known translational and rotational offsets were within tolerance (<0.5 × maximum voxel dimension). Slice thickness and distance accuracy were within 0.1 mm, and volume accuracy was within 0 to 0.11 cm3 . Treatment planning system volume measurement uncertainty was within 0.1 to 0.4 cm3 . Ion chamber point-dose measurements for a single beam in a water phantom agreed to TPS-calculated values within ±4% for collimator diameters 10 to 25 mm, and ±6% for 7.5 mm, for all measured depths (7, 50, 100, 150, and 200 mm). In homogeneous Solid Water, point-dose measurements agreed to within ±4% for cones sizes 7.5 to 25 mm. With 1-cm high/low density inserts, measurements were within ±4.2% for cone sizes 10 to 25 mm. Film-based E2E using 4/5-mm cones resulted in a gamma passing rate (%GP) of 99.8% (2%/1.5 mm). Point-dose measurements in a Lucy phantom with an ion chamber using 36 beams distributed along three noncoplanar arcs agreed to within ±4% for cone sizes 10 to 25 mm. The RPC Gamma Knife TLD phantom yielded passing results with a measured-to-expected TLD dose ratio of 1.02. The MD Anderson SRS head phantom yielded passing results, with 4% TLD agreement and %GP of 95%/93% (5%/3 mm) for coronal/sagittal film planes. The RTsafe gel phantom gave %GP of >95% (5%/2 mm) for all four targets. For our first 58 patients, film-based patient-specific quality assurance has resulted in an average %GP of 98.7% (range, 94-100%) at 2%/2 mm. CONCLUSIONS: Core ZAP-X features were found to be functional. On the basis of our results, point-dose and planar measurements were in agreement with TPS calculations using multiple phantoms and setup geometries, validating the ZAP-X TPS beam model for clinical use.

Resection and Surgically Targeted Radiation Therapy for the Treatment of Larger Recurrent or Newly Diagnosed Brain Metastasis: Results From a Prospective Trial.

Introduction Achieving durable local control (LC) for larger (e.g., >2-3 cm) brain metastasis whether newly diagnosed or recurrent remains problematic. Resection (R) alone is typically insufficient and adding radiation therapy (RT) still results in a 12-month recurrence rate of 20% or more in many series. Hypothesizing that R plus immediate radiation utilizing brachytherapy may improve outcomes for this cohort of patients, we designed and prospectively evaluated a permanently implanted surgically targeted radiation therapy (STaRT) device consisting of cesium-131 (Cs-131) seeds positioned within a collagen carrier (GammaTile, GT Medical Technologies, Tempe, AZ). The device was designed to prevent direct source-to-brain contact and maintain inter-source spacing after closure. Methods This was a subgroup analysis of a cohort of patients with either recurrent or previously untreated brain metastases enrolled in a prospective, multi-histology single-arm trial (ClinicalTrials.gov, NCT#03088579), conducted between February 2013 and February 2018, of resection and tumor bed brachytherapy with Cs-131 containing permanently implanted collagen tiles to deliver 60 Gray (Gy) at .5 cm depth. No additional local therapy was given without progression. Results A total of 16 metastases in 11 patients were treated; 12 tumors were recurrent and four were previously untreated. The median preoperative maximum diameter was 3.2 cm (range: 1.9-5.1 cm). Histology was seven breasts, six lungs, and three sarcomas. The median age was 60 years (range: 41-80 years); the Karnofsky Performance Status (KPS) was 70 (range: 70-90). The cohort consisted of seven females and four males. The mean time for implantation completion was five minutes. The median overall survival (OS) was 9.3 months. At a median radiographic follow-up of 9.5 months' treatment, site progression was found in 1/16 (6%) at 10.9 months, and the median treatment site time-to-progression (TTP) has not been reached [95% confidence interval (CI): >10.9 months]. At 12 months, the Kaplan-Meier (K-M) estimates for LC after R+STaRT for all tumors was 83%; for previously untreated tumors, LC at 12 months was 100% and for recurrent tumors, it was 80%. Two tumor beds (12.5%) experienced radiation brain changes: one had grade two and the other grade three. No surgical adverse events occurred. Conclusion In this single-arm precommercial study, R+STaRT demonstrated excellent safety and LC in this cohort. The device has recently received FDA clearance for use in newly diagnosed and recurrent brain metastasis, and randomized clinical trials vs. standard of care treatments in both settings are scheduled to open in 2020.

U5a1 Mitochondrial DNA Haplotype Identified in Eneolithic Skeleton from Shatar Chuluu, Mongolia.

The mitochondrial haplotype U5a1 was identified from an Eneolithic grave associated with the Afanasievo archaeological culture in Bayankhongor Province, Erdenetsogt Township, at the site of Shatar Chuluu. This is the earliest appearance of an mtDNA haplotype associated with modern European populations on the Mongol Steppe. This evidence demonstrations that people with "western" mtDNA lived on the Mongol Steppe east of the Altai Mountains before the Bronze Age and refutes the notion that the Altai Mountains were a substantial barrier to gene flow, and definitively expands the acknowledged range of the Afanasievo archaeological culture.

External beam radiation therapy for meningioma.

Radiation therapy (RT) plays an important role in the management of meningioma. Surgery often remains the initial treatment of choice as it reduces mass effect and confirms the diagnosis and grade. However, RT has frequently been successful in the primary setting and is commonly employed as adjuvant therapy for incompletely resected tumors as well as for high-grade meningiomas regardless of resection extent. Some meningiomas develop in locations less amenable to resection or in patients who are poor surgical candidates, in which circumstances RT is particularly appropriate as primary treatment. Recent cooperative group studies including RTOG 0539 have better established the role of RT for meningioma. These studies suggest a role for adjuvant RT for completely resected Grade II meningioma, which was less clear historically. Ongoing clinical trials such as NRG BN 003 and ROAM will further clarify this. This chapter reviews the role of fractionated external beam RT for various grades of meningioma.

Proposed response assessment and endpoints for meningioma clinical trials: report from the Response Assessment in Neuro-Oncology Working Group.

No standard criteria exist for assessing response and progression in clinical trials involving patients with meningioma, and there is no consensus on the optimal endpoints for trials currently under way. As a result, there is substantial variation in the design and response criteria of meningioma trials, making comparison between trials difficult. In addition, future trials should be designed with accepted standardized endpoints. The Response Assessment in Neuro-Oncology Meningioma Working Group is an international effort to develop standardized radiologic criteria for treatment response for meningioma clinical trials. In this proposal, we present the recommendations for response criteria and endpoints for clinical trials involving patients with meningiomas.

Intermediate-risk meningioma: initial outcomes from NRG Oncology RTOG 0539.

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: knowledge base, treatment outcomes, and uncertainties. A RANO review.

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.

Historical benchmarks for medical therapy trials in surgery- and radiation-refractory meningioma: a RANO review.

BACKGROUND: The outcomes of patients with surgery- and radiation-refractory meningiomas treated with medical therapies are poorly defined. Published reports are limited by small patient numbers, selection bias, inclusion of mixed histologic grades and stages of illness, and World Health Organization (WHO) criteria changes. This analysis seeks to define outcome benchmarks for future clinical trial design. METHODS: A PubMed literature search was performed for all English language publications on medical therapy for meningioma. Reports were tabulated and analyzed for number of patients, histologic grade, prior therapy, overall survival, progression-free survival (PFS), and radiographic response. RESULTS: Forty-seven publications were identified and divided by histology and prior therapies, including only those that treated patients who were surgery and radiation refractory for further analysis. This included a variety of agents (hydroxyurea, temozolomide, irinotecan, interferon-α, mifepristone, octreotide analogues, megestrol acetate, bevacizumab, imatinib, erlotinib, and gefitinib) from retrospective, pilot, and phase II studies, exploratory arms of other studies, and a single phase III study. The only outcome extractable from all studies was the PFS 6-month rate, and a weighted average was calculated separately for WHO grade I meningioma and combined WHO grade II/III meningioma. For WHO I meningioma, the weighted average PFS-6 was 29% (95% confidence interval [CI]: 20.3%-37.7%). For WHO II/III meningioma, the weighted average PFS-6 was 26% (95% CI: 19.3%-32.7%). CONCLUSIONS: This comprehensive review confirms the poor outcomes of medical therapy for surgery- and radiation-refractory meningioma. We recommend the above PFS-6 benchmarks for future trial design.

American Brachytherapy Society consensus guidelines for high-dose-rate prostate brachytherapy.

PURPOSE: A well-established body of literature supports the use of high-dose-rate (HDR) brachytherapy as definitive treatment for localized prostate cancer. Most of the articles describe HDR as a boost with adjuvant external beam radiation, but there is a growing experience with HDR monotherapy. METHODS AND MATERIALS: The American Brachytherapy Society has convened a group of expert practitioners and physicists to develop guidelines for the use of HDR in the management of prostate cancer. This involved an extensive literature review and input from an expert panel. RESULTS: Despite a wide variation in doses and fractionation reported, HDR brachytherapy provides biochemical control rates of 85-100%, 81-100%, and 43-93% for low-, intermediate-, and high-risk prostate cancers, respectively. Severe toxicity is rare, with most authors reporting less than 5% Grade 3 or higher toxicity. Careful attention to patient evaluation for appropriate patient selection, meticulous technique, treatment planning, and delivery are essential for successful treatment. CONCLUSION: The clinical outcomes for HDR are excellent, with high rates of biochemical control, even for high-risk disease, with low morbidity. HDR monotherapy, both for primary treatment and salvage, are promising treatment modalities.

New pathology classification, imagery techniques and prospective trials for meningiomas: the future looks bright.

PURPOSE OF REVIEW: Advances in functional and metabolic imaging have been added to the diagnostic armamentarium for meningioma. New prospective trials have been initiated, and it is foreseen that American Society of Clinical Oncology evidence-level II will be soon available for this brain tumor. This review will focus on recent advances in radiology and their significance for clinical care. The new WHO classification will be detailed. RECENT FINDINGS: Brain invasion is an important criterion in the 2007 WHO classification for atypical meningioma. Apparent diffusion coefficient values on MRI observed with grade II and grade III meningiomas are significantly decreased when compared to benign tumors. [F]fluorodeoxyglucose PET may also predict tumor grade and tumor recurrence. Radio-labeled amino acid PET may be used to delineate target volume for radiotherapy planning. Stereotactic biopsy guidance and functional therapy monitoring could be foreseen using PET-MRI. One phase II study is assessing the benefit of dose escalation for nonbenign meningioma and another evaluates the therapeutic strategy of observation, standard- and high-dose radiotherapy for low-risk, intermediate-risk and high-risk patients. SUMMARY: The use of functional MRI, with or without PET imaging, may be useful in assessing the potential clinical outcome of meningioma. Various therapeutic strategies, including observation and high-dose radiotherapy, are evaluated in two ongoing phase II studies.

Intracranial meningiomas of atypical (WHO grade II) histology.

Atypical (WHO grade II) meningiomas occupy an intermediate risk group between benign (WHO grade I) and anaplastic (WHO grade III) meningiomas. Although grade II meningiomas have traditionally been recognized in only about 5% of cases, after changes in diagnostic criteria with the current 2007 WHO standards, they now comprise approximately 20-35% of all meningiomas. Given the magnitude of this change, much work is now needed to solidify the adoption of these standards, to render inter-observer and inter-institutional comparisons more uniform, and to more carefully define the incidence of grade II histology. However, it is clear that they carry a several-fold increased risk of recurrence, as well as an increased rate of mortality. We will discuss the definition, diagnosis, and treatment of patients with atypical meningioma; review the current phase II cooperative trials; and draw attention to some questions timely for pre-clinical and clinical research.