Early versus delayed postoperative radiotherapy for treatment of low-grade gliomas.
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ABSTRACT:
SUBMITTER: Dhawan S
PROVIDER: S-EPMC6984627 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Diffuse low grade gliomas are invasive and incurable brain tumors that inevitably transform into higher grade ones. A classical treatment to delay this transition is radiotherapy (RT). Following RT, the tumor gradually shrinks during a period of typically 6 months to 4 years before regrowing. To improve the patient's health-related quality of life and help clinicians build personalized follow-ups, one would benefit from predictions of the time during which the tumor is expected to decrease. The challenge is to provide a reliable estimate of this regrowth time shortly after RT (i.e. with few data), although patients react differently to the treatment. To this end, we analyze the tumor size dynamics from a batch of 20 high-quality longitudinal data, and propose a simple and robust analytical model, with just 4 parameters. From the study of their correlations, we build a statistical constraint that helps determine the regrowth time even for patients for which we have only a few measurements of the tumor size. We validate the procedure on the data and predict the regrowth time at the moment of the first MRI after RT, with precision of, typically, 6 months. Using virtual patients, we study whether some forecast is still possible just three months after RT. We obtain some reliable estimates of the regrowth time in 75% of the cases, in particular for all "fast-responders". The remaining 25% represent cases where the actual regrowth time is large and can be safely estimated with another measurement a year later. These results show the feasibility of making personalized predictions of the tumor regrowth time shortly after RT.
| S-EPMC10128962 | biostudies-literature
Project description:Background:Infiltrating low-grade gliomas (LGG; WHO grade 2) typically present with seizures in young adults. LGGs grow continuously and usually transform to higher grade of malignancy, eventually causing progressive disability and premature death. The effect of up-front surgery has been controversial and the impact of molecular biology on the effect of surgery is unknown. We now present long-term results of upfront surgical resection compared with watchful waiting in light of recently established molecular markers. Materials and methods:Population-based parallel cohorts were followed from two Norwegian university hospitals with different surgical treatment strategies and defined geographical catchment regions. In region A watchful waiting was favored while early resection was favored in region B. Thus, the treatment strategy in individual patients depended on their residential address. The inclusion criteria were histopathological diagnosis of supratentorial LGG from 1998 through 2009 in patients 18?years or older. Follow-up ended 1 January 2016. Making regional comparisons, the primary end-point was overall survival. Results:A total of 153 patients (66 from region A, 87 from region B) were included. Early resection was carried out in 19 (29%) patients in region A compared with 75 (86%) patients in region B. Overall survival was 5.8?years (95% CI 4.5-7.2) in region A compared with 14.4?years (95% CI 10.4-18.5) in region B (P?<?0.01). The effect of surgical strategy remained after adjustment for molecular markers (P?=?0.001). Conclusion:In parallel population-based cohorts of LGGs, early surgical resection resulted in a clinical relevant survival benefit. The effect on survival persisted after adjustment for molecular markers.
| S-EPMC5834105 | biostudies-literature
Project description:BACKGROUND:It has been reported that radiation therapy (RT) followed by procarbazine, lomustine, and vincristine (PCV) chemotherapy could improve progression-free survival (PFS) and overall survival (OS) in patients with high-risk World Health Organization (WHO) grade 2 gliomas after surgery. However, procarbazine is not available in China. In clinical practice, Chinese doctors often use radiotherapy combined with temozolomide (TMZ) to treat these patients, although large-scale prospective studies are lacking. This trial aims to confirm whether RT combined with temozolomide can improve PFS and OS in high-risk patients with low-grade gliomas (LGGs). METHODS/DESIGN:This is a two-group, randomized controlled trial (RCT) enrolling patients who have LGGs (WHO grade 2) and are aged 40?years or older without regard to the extent of resection or are aged younger than 40?years old with subtotal resection or biopsy. An estimated 250 patients will be enrolled. Eligible participants will be randomly assigned to receive RT alone or RT plus TMZ chemotherapy in a 1:1 ratio. The same RT will be given to all eligible participants regardless of whether they are randomly assigned to the RT group or the chemoradiotherapy (CRT) group. While in the CRT group, patients will receive adjuvant TMZ with or without concurrent radiochemotherapy. The primary outcome of this trial is PFS, and it will be analyzed by the intention-to-treat approach. Secondary outcomes include OS, adverse events, and cognitive function. DISCUSSION:The objective of our research is to assess the effect of radiotherapy coupled with TMZ in high-risk patients with LGGs after surgery, compared with RT alone. Different histological types and molecular subtypes will be examined, and a corresponding subgroup analysis will be conducted. Our data can provide evidence for postoperative adjuvant therapy in patients with high-risk LGGs in China. TRIAL REGISTRATION:Chinese Clinical Trial Registry, ChiCTR1800015199. Registered on 13 March 2018.
| S-EPMC6868800 | biostudies-literature
Project description:Low-grade gliomas (LGGs) are a diverse group of primary brain tumors that often arise in young, otherwise healthy patients and generally have an indolent course with longer-term survival in comparison with high-grade gliomas. Treatment options include observation, surgery, radiation, chemotherapy, or a combined approach, and management is individualized based on tumor location, histology, molecular profile, and patient characteristics. Moreover, in this type of brain tumor with a relatively good prognosis and prolonged survival, the potential benefits of treatment must be carefully weighed against potential treatment-related risks. We review in this article current management strategies for LGG, including surgery, radiotherapy, and chemotherapy. In addition, the importance of profiling the genetic and molecular properties of LGGs in the development of targeted anticancer therapies is also reviewed. Finally, given the prevalence of these tumors in otherwise healthy young patients, the impact of treatment on neurocognitive function and quality of life is also evaluated.
| S-EPMC3983820 | biostudies-literature
Project description:Categorisation of LGGs related to their lesion site (infratentorial vs. supratentorial)
2013-09-21 | GSE28238 | GEO
Project description:Categorisation of LGGs related to their lesion site (infratentorial vs. supratentorial) 40 Low grade gliomas samples
2013-09-21 | E-GEOD-28238 | biostudies-arrayexpress
Project description:Background and purposePatients with lower-grade gliomas are long-term survivors after radiotherapy and may benefit from the reduced dose to normal tissue achievable with proton therapy. Here, we aimed to quantify differences in dose to the uninvolved brain and contralateral hippocampus and compare the risk of radiation-induced secondary cancer for photon and proton plans for lower-grade glioma patients.Materials and methodsTwenty-three patients were included in this in-silico planning comparative study and had photon and proton plans calculated (50.4 Gy(RBE = 1.1), 28 Fx) applying similar dose constraints to the target and organs at risk. Automatically calculated photon plans were generated with a 3 mm margin from clinical target volume (CTV) to planning target volume. Manual proton plans were generated using robust optimisation on the CTV. Dose metrics of organs at risk were compared using population mean dose-volume histograms and Wilcoxon signed-rank test. Secondary cancer risk per 10,000 persons per year (PPY) was estimated using dose-volume data and a risk model for secondary cancer induction.ResultsCTV coverage (V95%>98%) was similar for the two treatment modalities. Mean dose (Dmean) to the uninvolved brain was significantly reduced from 21.5 Gy (median, IQR 17.1-24.4 Gy) with photons compared to 10.3 Gy(RBE) (8.1-13.9 Gy(RBE)) with protons. Dmean to the contralateral hippocampus was significantly reduced from 6.5 Gy (5.4-11.7 Gy) with photons to 1.5 Gy(RBE) (0.4-6.8 Gy(RBE)) with protons. The estimated secondary cancer risk was reduced from 6.7 PPY (median, range 3.3-10.4 PPY) with photons to 3.0 PPY (1.3-7.5 PPY) with protons.ConclusionA significant reduction in mean dose to uninvolved brain and contralateral hippocampus was found with proton planning. The estimated secondary cancer risk was reduced with proton therapy.
| S-EPMC8637131 | biostudies-literature
Project description:Brain tumors constitute the largest source of oncologic mortality in children and low-grade gliomas are among most common pediatric central nervous system tumors. Pediatric low-grade gliomas differ from their counterparts in the adult population in their histopathology, genetics, and standard of care. Over the past decade, an increasingly detailed understanding of the molecular and genetic characteristics of pediatric brain tumors led to tailored therapy directed by integrated phenotypic and genotypic parameters and the availability of an increasing array of molecular-directed therapies. Advances in neuroimaging, conformal radiation therapy, and conventional chemotherapy further improved treatment outcomes. This article reviews the current classification of pediatric low-grade gliomas, their histopathologic and radiographic features, state-of-the-art surgical and adjuvant therapies, and emerging therapies currently under study in clinical trials.
| S-EPMC7281318 | biostudies-literature
Project description:Purpose: The present study aimed to evaluate the performance of radiomics features in the preoperative prediction of epileptic seizure following surgery in patients with LGG. Methods: This retrospective study collected 130 patients with LGG. Radiomics features were extracted from the T2-weighted MR images obtained before surgery. Multivariable Cox-regression with two nested leave-one-out cross validation (LOOCV) loops was applied to predict the prognosis, and elastic net was used in each LOOCV loop to select the predictive features. Logistic models were then built with the selected features to predict epileptic seizures at two time points. Student's t-tests were then used to compare the logistic model predicted probabilities of developing epilepsy in the epilepsy and non-epilepsy groups. The t-test was used to identify features that differentiated patients with early-onset epilepsy from their late-onset counterparts. Results: Seventeen features were selected with the two nested LOOCV loops. The index of concordance (C-index) of the Cox model was 0.683, and the logistic model predicted probabilities of seizure were significantly different between the epilepsy and non-epilepsy groups at each time point. Moreover, one feature was found to be significantly different between the patients with early- or late-onset epilepsy. Conclusion: A total of 17 radiomics features were correlated with postoperative epileptic seizures in patients with LGG and one feature was a significant predictor of the time of epilepsy onset.
| S-EPMC7360821 | biostudies-literature
Project description:AimsTo identify molecular genetic factors that influence preoperative seizure occurrence and postoperative seizure control in patients with low-grade gliomas (LGGs).MethodsFifty-four WHO grade II astrocytomas were used for microarray analysis under strict inclusion criteria. The primary endpoint was seizure control at 12 months after surgery. Biological processes were investigated by gene ontology (GO) analysis. Quantitative RT-PCR and immunohistochemistry were used to validate key genes.ResultsDifferentially expressed genes correlated with seizure occurrence failed to significantly distinguish patients with and without a history of seizures. With respect to postoperative seizure control, a transcript profile of 92 genes was identified, which successfully separated patients with good and poor seizure prognosis. GO analysis revealed that the most striking overrepresentation of genes was found in a category of anti-apoptotic genes and their regulation. Increased expression was also observed for genes involved in immune and inflammatory responses. BCL2A1 was proven to be a novel marker associated with seizure prognosis.ConclusionIncreased anti-apoptotic activity of tumor cells appears to contribute to seizure recurrence after surgery in patients with LGGs. These findings provide insights that may lead to the development of effective treatment strategies for prolonging the survival of patients with LGG in the future.
| S-EPMC6493500 | biostudies-literature