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Project description:Molecular classification of meningioma predicts the response to surgical resection and adjuvant radiotherapy.
| PRJNA1126283 | ENA
Project description:BackgroundThe impact of adjuvant radiotherapy (RT) on atypical meningioma (AM) underwent a gross total resection (GTR) remains unclear, showing conflicting results from various studies. The objective of this study was to perform an updated meta-analysis for observational studies to determine the effect of adjuvant RT after GTR on local recurrence and survival outcomes compared to observation after GTR.MethodsPubMed, Embase, and Web of Science were searched to identify comparative studies that reported outcomes of adjuvant RT versus observation for AM patients after GTR. Local recurrence rate, progression-free survival (PFS), overall survival (OS), and toxicities related to RT were considered as outcomes of interest. Differences between two cohorts were estimated by calculating odds ratios (OR) for LR rate and hazard ratios (HR) for survival outcomes with 95% confidence intervals (CIs) for meta-analysis, using R version 4.0.3 software. Included studies were appraised with the Risk of Bias Assessment tool for Non-Randomized Studies. Outcome ratios were combined with the Mantel-Haenszel method and the inverse variance-weighted method, appropriately.ResultsData from 30 studies involving 2904 patients (adjuvant RT: n = 737; observation: n = 2167) were eventually included. Significant reduction of local recurrence rate was seen in the adjuvant RT cohort compare to that in the observation cohort (OR 0.50; 95% CI 0.36-0.68; p < 0.0001). Pooled HRs of PFS at 1-year, 3-year, 5-year, and > 5-year revealed that adjuvant RT was superior to observation. There was no significant difference in OS between the two cohorts during any period. Most toxicities were tolerable with grade 1 or 2. There was no documented grade 5 toxicity.ConclusionsFor AM patients who underwent GTR, evidence suggested that adjuvant RT could potentially decrease local recurrence and improve PFS better than observation.
| S-EPMC7890913 | biostudies-literature
Project description:For atypical meningiomas (AM), the combination of gross total resection (GTR) and adjuvant radiotherapy (ART) is still a controversial therapeutic strategy to improve prognosis. This study analysed the factors influencing the prognosis on AM patients treated with GTR+ART by investigating both clinical characteristics and the change in microRNA (miRNA) expression.Adult AM patients who were admitted to the Tiantan hospital from 2008 to 2015 and underwent GTR+ART were included. Patients who suffered recurrence within 3 years after operation were considered radioresistant, while the others were considered radiosensitive. Clinical characterizations were compared between these two groups. The miRNAs expression was detected via miRNA microarray in 10 patients, 5 from the radiosensitive group and 5 from the radioresistant group.No significant difference was found in the clinical characteristics. between radiosensitive and radioresistant patients. We found 7 significantly upregulated miRNAs and 7 significantly downregulated miRNAs in patients resistant to radiotherapy. The differentially expressed miRNAs were enriched mostly in the Fatty acid metabolic pathways (hsa00061, hsa01212) and TGF-β signalling pathway (hsa04350). For AM patients treated with GTR+ART, the changes in miRNA expression discovered in this study may be a potential predictor of individual sensitivity to adjuvant radiotherapy. Further research is needed regarding the predictive power and mechanism by which these miRNAs influence prognosis.
2020-01-23 | GSE144037 | GEO
Project description:BACKGROUND:Meningiomas are the most common primary tumors of the central nervous system. In patients with WHO grade I meningiomas no adjuvant therapy is recommended after resection. In case of anaplastic meningiomas (WHO grade III), adjuvant fractionated radiotherapy is generally recommended, regardless of the extent of surgical resection. For atypical meningiomas (WHO grade II) optimal postoperative management has not been clearly defined yet. METHODS:We conducted a retrospective analysis of patients treated for intracranial atypical meningioma at Charité Universitätsmedizin Berlin from March 1999 to October 2018. Considering the individual circumstances (risk of recurrence, anatomical location, etc.), patients were either advised to follow a wait-and-see approach or to undergo adjuvant radiotherapy. Primary endpoint was progression-free survival (PFS). RESULTS:This analysis included 99 patients with atypical meningioma (WHO grade II). Nineteen patients received adjuvant RT after primary tumor resection (intervention group). The remaining 80 patients did not receive any further adjuvant therapy after surgical resection (control group). Median follow-up was 37?months. Median PFS after primary resection was significantly longer in the intervention group than in the control group (64?m vs. 37?m, p?=?0.009, HR?=?0.204, 95% CI?=?0.062-0.668). The influence of adjuvant RT was confirmed in multivariable analysis (p?=?0.041, HR?=?0.192, 95% CI?=?0.039-0.932). CONCLUSIONS:Our study adds to the evidence that RT can improve PFS in patients with atypical meningioma.
| S-EPMC6719347 | biostudies-literature
Project description:Background and purposeConsensus regarding the need for adjuvant radiotherapy (RT) in patients with atypical meningiomas (AMs) is lacking. We compared the effects of adjuvant RT after surgery, gross total resection (GTR), and subtotal resection (STR) on progression-free survival (PFS) and overall survival (OS) in patients with AMs, respectively.MethodsWe performed a systematic review and meta-analysis of the literature published in PubMed, Embase, and the Cochrane Library from inception to February 1, 2021, to identify articles comparing the PFS and OS of patients receiving postoperative RT after surgery, GTR and STR.ResultsWe identified 2307 unique studies; 24 articles including 3078 patients met the inclusion criteria. The sensitivity analysis results showed that for patients undergoing undifferentiated surgical resection, adjuvant RT reduced tumor recurrence (HR=0.70, p<0.0001) with no significant effect on survival (HR=0.89, p=0.49). Postoperative RT significantly increased PFS (HR=0.69, p=0.01) and OS (HR=0.55, p=0.007) in patients undergoing GTR. The same improvement was observed in patients undergoing STR plus RT (PFS: HR=0.41, p<0.00001; OS: HR=0.47, p=0.01). A subgroup analysis of RT in patients undergoing GTR showed no change in PFS in patients undergoing Simpson grade I and II resection (HR=1.82, p=0.22) but significant improvement in patients undergoing Simpson grade III resection (HR=0.64, p=0.02).ConclusionRegardless of whether GTR or STR was performed, postoperative RT improved PFS and OS to varying degrees. Especially for patients undergoing Simpson grade III or IV resection, postoperative RT confers the benefits for recurrence and survival.
| S-EPMC8674463 | biostudies-literature
Project description:BackgroundThe role of chemotherapy in high-risk soft tissue sarcoma is controversial. Though many patients undergo initial curative resection, distant metastasis is a frequent event, resulting in 5-year overall survival rates of only 50-60%. Neo-adjuvant and adjuvant chemotherapy (CTX) has been applied to achieve pre-operative cytoreduction, assess chemosensitivity, and to eliminate occult metastasis. Here we report on the results of our non-randomized phase II study on neo-adjuvant treatment for high-risk STS.MethodPatients with potentially curative high-risk STS (size ≥ 5 cm, deep/extracompartimental localization, tumor grades II-III [FNCLCC]) were included. The protocol comprised 4 cycles of neo-adjuvant chemotherapy (EIA, etoposide 125 mg/m(2) iv days 1 and 4, ifosfamide 1500 mg/m2 iv days 1 - 4, doxorubicin 50 mg/m(2) day 1, pegfilgrastim 6 mg sc day 5), definitive surgery with intra-operative radiotherapy, adjuvant radiotherapy and 4 adjuvant cycles of EIA.ResultBetween 06/2005 and 03/2010 a total of 50 subjects (male = 33, female = 17, median age 50.1 years) were enrolled. Median follow-up was 30.5 months. The majority of primary tumors were located in the extremities or trunk (92%), 6% originated in the abdomen/retroperitoneum. Response by RECIST criteria to neo-adjuvant CTX was 6% CR (n = 3), 24% PR (n = 12), 62% SD (n = 31) and 8% PD (n = 4). Local recurrence occurred in 3 subjects (6%). Distant metastasis was observed in 12 patients (24%). Overall survival (OS) and disease-free survival (DFS) at 2 years was 83% and 68%, respectively. Multivariate analysis failed to prove influence of resection status or grade of histological necrosis on OS or DFS. Severe toxicities included neutropenic fever (4/50), cardiac toxicity (2/50), and CNS toxicity (4/50) leading to CTX dose reductions in 4 subjects. No cases of secondary leukemias were observed so far.ConclusionThe current protocol is feasible for achieving local control rates, as well as OS and DFS comparable to previously published data on neo-/adjuvant chemotherapy in this setting. However, the definitive role of chemotherapy remains unclear in the absence of large, randomized trials. Therefore, the current regimen can only be recommended within a clinical study, and a possibly increased risk of secondary leukemias has to be taken into account.Trial registrationClinicalTrials.gov NCT01382030, EudraCT 2004-002501-72.
| S-EPMC3248452 | biostudies-literature
Project description:BackgroundThe current World Health Organization (WHO) classification of brain tumors distinguishes 3 malignancy grades in meningiomas, with increasing risk of recurrence from CNS WHO grades 1 to 3. Radiotherapy is recommended by current EANO guidelines for patients not safely amenable to surgery or after incomplete resection in higher grades. Despite adequately predicting recurrence probability for the majority of CNS WHO grade 2 meningioma patients, a considerable subset of patients demonstrates an unexpectedly early tumor recurrence following radiotherapy.MethodsA retrospective cohort of 44 patients with CNS WHO grade 2 meningiomas were stratified into 3 risk groups (low, intermediate, and high) using an integrated morphological, CNV- and methylation family-based classification. Local progression-free survival (lPFS) following radiotherapy (RT) was analyzed and total dose of radiation was correlated with survival outcome. Radiotherapy treatment plans were correlated with follow-up images to characterize the pattern of relapse. Treatment toxicities were further assessed.ResultsRisk stratification of CNS WHO grade 2 meningioma into integrated risk groups demonstrated a significant difference in 3-year lPFS following radiotherapy between the molecular low- and high-risk groups. Recurrence pattern analysis revealed that 87.5 % of initial relapses occurred within the RT planning target volume or resection cavity.ConclusionsIntegrated risk scoring can identify CNS WHO grade 2 meningioma patients at risk or relapse and dissemination following radiotherapy. Therapeutic management of CNS WHO grade 2 meningiomas and future clinical trials should be adjusted according to the molecular risk-groups, and not rely on conventional CNS WHO grading alone.
| S-EPMC10246580 | biostudies-literature
Project description:Examine gene expression for meningioma cases by hormone receptor status and indicate a stronger association with progesterone than with estrogen receptors Experiment Overall Design: The data are surgical specimens from 31 meningioma patients undergoing neuro-surgical resection at Brigham and Womenâs Hospital from 3/15/2004-5/10/2005. Progesterone (PR) and estrogen (ER) hormone receptors were measured via immunohistochemistry and compared with gene expression profiling results.
2008-06-16 | E-GEOD-9438 | biostudies-arrayexpress
Project description:Patients with drug-resistant epilepsy often require surgery to become seizure-free. While laser ablation and implantable stimulation devices have lowered the morbidity of these procedures, seizure-free rates have not dramatically improved, particularly for patients without focal lesions. This is in part because it is often unclear where to intervene in these cases. To address this clinical need, several research groups have published methods to map epileptic networks but applying them to improve patient care remains a challenge. In this study we advance clinical translation of these methods by: (i) presenting and sharing a robust pipeline to rigorously quantify the boundaries of the resection zone and determining which intracranial EEG electrodes lie within it; (ii) validating a brain network model on a retrospective cohort of 28 patients with drug-resistant epilepsy implanted with intracranial electrodes prior to surgical resection; and (iii) sharing all neuroimaging, annotated electrophysiology, and clinical metadata to facilitate future collaboration. Our network methods accurately forecast whether patients are likely to benefit from surgical intervention based on synchronizability of intracranial EEG (area under the receiver operating characteristic curve of 0.89) and provide novel information that traditional electrographic features do not. We further report that removing synchronizing brain regions is associated with improved clinical outcome, and postulate that sparing desynchronizing regions may further be beneficial. Our findings suggest that data-driven network-based methods can identify patients likely to benefit from resective or ablative therapy, and perhaps prevent invasive interventions in those unlikely to do so.
| S-EPMC6885672 | biostudies-literature
Project description:Endometrial cancer is primarily treated with surgery. Adjuvant treatment strategies for endometrial cancer, such as external beam pelvic radiotherapy, vaginal brachytherapy, chemotherapy, and combined chemotherapy and radiotherapy, have been studied in several randomized trials. Adjuvant treatment is currently based on the presence of clinico-pathological risk factors. Low-risk disease is adequately managed with surgery alone. In high-intermediate risk endometrial cancer, adjuvant vaginal brachytherapy is recommended to maximize local control, with only mild side effects and without impact on quality of life. For high-risk endometrial cancer, recent large randomized trials support the use of pelvic radiotherapy, especially in stage I-II endometrial cancer with risk factors. For women with serous cancers and those with stage III disease, chemoradiation increased both recurrence-free and overall survival, while GOG-258 showed similar recurrence-free survival compared with six cycles of chemotherapy alone, but with better pelvic and para-aortic nodal control with combined chemotherapy and radiotherapy. Recent molecular studies, most notably the work from The Cancer Genome Atlas (TCGA) project, have shown that four endometrial cancer molecular classes can be distinguished; POLE ultra-mutated, microsatellite instable hypermutated, copy-number-low, and copy-number-high. Subsequent studies, using surrogate markers to identify groups analogous to TCGA sub-classes, showed that all four endometrial cancer sub-types are found across all stages, histological types, and grades. Moreover, the molecular sub-groups have proved to have a stronger prognostic impact than histo-pathological tumor characteristics. This introduces an new era of molecular classification based diagnostics and treatment approaches. Integration of the molecular factors and new therapeutic targets will lead to molecular-integrated adjuvant treatment including targeted treatments, which are the rationale of new and ongoing trials. This review presents an overview of current adjuvant treatment strategies in endometrial cancer, highlights the development and evaluation of a molecular-integrated risk profile, and briefly discusses ongoing developments in targeted treatment.
| S-EPMC8020082 | biostudies-literature