International Journal of Radiation Oncology*Biology*Physics
Clinical original contributionA randomized trial on dose-response in radiation therapy of low-grade cerebral glioma: European Organization for Research and Treatment of Cancer (EORTC) study 22844
Abstract
: Cerebral low-grade gliomas (LGG) in adults are mostly compose of astrocytomas, oligodendrogliomas, and mixed oligoastrocytomas. There is at present no consensus in the policy of treatment of these tumors. We sought to determine the efficacy of radiotherapy and the presence of a dose-response relationship for these tumors in two multicentric randomized trials conducted by the European Organization for Research and Treatment of Cancer (EORTC). The dose-response study is the subject of this article.
: For the dose-response trial, 379 adult patients with cerebral LGGs were randomized centrally at the EORTC Data Center to receive irradiation postoperatively (or postbiopsy) with either 45 Gy in 5 weeks or 59.4 Gy in 6.6 weeks with quality-controlled radiation therapy. All known parameters with possible influences on prognosis were prospectively recorded. Conventional treatment techniques were recommended.
: With 343 (91%) eligible and evaluable patients followed up for at least 50 months with a median of 74 months, there is no significant difference in terms of survival (58% for the low-dose arm and 59% for the high-dose arm) or the progression free survival (47% and 50%) between the two arms of the trial. However, this prospective trial has revealed some important facets about the prognostic parameters: The T of the TNM classifications as proposed in the protocol appears to be one of the most important prognostic factors (p < 0.0001) on multivariate analysis. Other prognostic factors, most of which are known, have now been quantified and confirmed in this prospective study.
: The EORTC trial 22844 has not revealed the presence of radiotherapeutic dose-response for patients with LGG for the two dose levels investigated with this conventional setup, but objective prognostic parameters are recognized. The tumor size or T parameter as used in this study appears to be a very important factor.
References (17)
- J.T. Fazekas
Treatment of grades 1 and 2 brain astrocytomas. The role of radiotherapy
Int. J. Radiat. Oncol. Biol. Phys.
(1977) - A.B.M.F. Karim
Stereotactic irradiations on the horizon: A challenge for multimodal developments
Int. J. Radiat. Oncol. Biol. Phys.
(1994) - D Afra et al.
Recurrent low grade gliomas: Dedifferentiation and prospects of reoperation
- M.S. Berger et al.
The effect of resection on recurrence in patients with low grade cerebral hemisphere gliomas
Cancer
(1994) - D.R. Cox
Regression models and life tables
J. R. Stat. Soc B
(1972) - D.M. Garcia et al.
The value of radiation therapy in addition to surgery for astrocytomas of the adult cerebrum
Cancer
(1985) - International Commission on Radiological Units and Measurements
Dose specification for reporting external beam therapy with photons and electrons
ICRU Rep.
(1978)
Cited by (604)
Effectiveness and Safety of Different Postoperative Adjuvant Regimens in Patients with Low-Grade Gliomas: A Network Meta-Analysis
2023, World NeurosurgeryThis study aimed to investigate the effectiveness and safety of various adjuvant regimens in patients with low-grade gliomas and to further explore the optimal adjuvant treatment for patients with low-grade gliomas and the differences in the efficacy of each treatment regimens in different tumor types.
A comprehensive search of the PubMed, Cochrane Library, Ovid, Embase, and Web of Science databases was conducted to screen randomized and nonrandomized controlled trials related to adjuvant therapy in patients with low-grade gliomas. The Cochrane quality assessment method and the Newcastle-Ottawa Scale were used to assess the quality of the included randomized and nonrandomized controlled trials, respectively. The data from previous studies were extracted using Excel and GetData Graph Digitizer 2.26 software, and network meta-analysis was performed using RevMan 5.3 and Stata 16.0 statistical software.
The specific ranking of 5-year progression-free survival (5-year PFS) for each treatment regimen from the best to the worst in patients with low-grade gliomas was surgery (S) combined with procarbazine, lomustine, and vincristine (S + PCV); surgery combined with standard radiotherapy and PCV multidrug chemotherapy (S + RT + PCV); surgery combined with standard radiotherapy and temozolomide monotherapy (S + RT + TMZ); surgery combined with enhanced radiotherapy (S + H-RT); surgery combined with standard radiotherapy (S + RT); surgery combined with TMZ (S + TMZ); and S. The 5-year overall survival (OS) ranking was S + RT + TMZ, S + RT + PCV, surgery combined with enhanced radiotherapy and TMZ monotherapy (S + H-RT + TMZ), S + H-RT, S + RT, and S. The 2-year progression-free survival ranking was S + RT + TMZ, S + PCV, S + RT, S + RT + PCV, S + TMZ, S + H-RT, and S. The 2-year overall survival ranking was S + RT + TMZ, S + H-RT + TMZ, S + RT, S + RT + PCV, S + H-RT, and S. The incidence of adverse events (≥3) was ranked from highest to lowest as follows: S + RT + PCV, S + RT + TMZ, S + PCV, S + H-RT, S + TMZ, and S + RT. In the isocitrate dehydrogenase 1/2 mutation nonchromosome 1p and 19q chromosome whole arm codeletion (IDHmt/noncoder) group, the S + RT + PCV and S + H-RT regimens had better 5-year PFS and 5-year OS. In the isocitrate dehydrogenase 1/2 mutation and chromosome 1p and 19q chromosome whole arm codeletion (IDHmt/coder) group, the 5-year PFS of each treatment regimen ranked from the best to the worst was S + RT + TMZ, S + RT + PCV, S + H-RT, S + RT, S + TMZ, and S. The order of 5-year OS from the best to the worst was S + H-RT, S + RT + TMZ, S + RT + PCV, S + RT, and S. In the isocitrate dehydrogenase 1/2 wild-type (IDHwt) group, the S + H-RT and S + TMZ regimens had better 5-year PFS.
This study revealed that both the S + RT + TMZ and S + RT + PCV regimens might be effective therapies for treating patients with low-grade gliomas. Among these, the S + RT + TMZ regimen seemed to be safer but might lead to tumor deterioration. In the IDHmt/coder type, the S + RT + TMZ scheme might have a significant advantage. In the IDHmt/noncoder type, the S + RT + PCV scheme might be more dominant, while in the IDHwt type, the S + H-RT and S + TMZ schemes also might be good treatment options.
Analysis of Prognostic Factors and Surgical Management of Elderly Patients with Low-Grade Gliomas
2023, World NeurosurgeryThe number of elderly patients with low-grade glioma (LGG) is increasing, but their prognostic factors and surgical treatment are still controversial. This paper aims to investigate the prognostic factors of overall survival and cancer-specific survival in elderly patients with LGG and analyze the optimal surgical treatment strategy.
Patients in the study were obtained from the Surveillance, Epidemiology, and End Results database and patients were randomized into a training and a test set (7:3). Clinical variables were analyzed by univariate and multivariate Cox regression analysis to screen for significant prognostic factors, and nomograms visualized the prognosis. In addition, survival analysis of elderly patients regarding different surgical management was also analyzed by Kaplan-Meier curves.
Six prognostic factors were screened by univariate and multivariate Cox regression analysis on the training set: tumor site, laterality, histological type, the extent of surgery, radiotherapy, and chemotherapy, and all factors were visualized by nomogram. And we evaluated the accuracy of the nomogram model using consistency index, calibration plots, receiver operator characteristic curves, and decision curve analysis, showing that the nomogram has strong accuracy and applicability. We also found that gross total resection improved overall survival and cancer-specific survival in patients with LGG aged ≥65 years relative to those who did not undergo surgery (P < 0.001).
Based on the Surveillance, Epidemiology, and End Results database, we created and validated prognostic nomograms for elderly patients with LGG, which can help clinicians to provide personalized treatment services and clinical decisions for their patients. More importantly, we found that older age alone should not preclude aggressive surgery for LGGs.
Thirty years of progress in the management of low-grade gliomas
2023, Revue NeurologiqueThis paper reviews 30 years of developments in the area of low-grade gliomas. This includes the changes in diagnostics with the incorporation of 1p/19q and IDH mutations in the diagnostic classifier, the improved surgical techniques, improved delivery of radiotherapy and chemotherapy. More recently, the better understanding of the altered cellular processes has lead to the development of novel drugs that may alter completely alter the management of patients early in the course of their disease.
Low grade gliomas guide-lines elaborated by the tumor section of Spanish Society of Neurosurgery
2023, NeurocirugiaLos gliomas de bajo grado (Low Grade Gliomas, LGG) del adulto son tumores que se originan a partir de las células gliales del cerebro y cuyo manejo implica gran controversia a día de hoy, comenzando desde el diagnóstico, hasta el tratamiento y seguimiento posterior de estos pacientes. Es por ello que el grupo de tumores de la Sociedad Española de Neurocirugía (GT-SENEC) ha llevado a cabo una reunión de consenso, en la que se han debatido las cuestiones neuroquirúrgicas más relevantes, llegando a recomendaciones basadas en la mejor evidencia científica. Con el fin de obtener el máximo beneficio a estos tratamientos se debe hacer una valoración individualizada de cada paciente por un equipo multidisciplinar, constituido por aquellas especialidades involucradas tanto en el diagnóstico como en el tratamiento.
El objetivo de este trabajo es elaborar unas recomendaciones de tratamiento para los pacientes con LGG, para lo cual un experto en cada campo ha descrito lo más relevante de dicha área basado tanto en su experiencia como en la literatura.
Se han desarrollado los apartados más relevantes en el manejo de los LGG basados en la mejor evidencia publicada.
A pesar de que existe controversia en algunos aspectos del manejo de los LGG, cada vez hay más datos para poder hacer recomendaciones de tratamiento consensuadas. El neurocirujano debe conocer las distintas opciones de tratamientos, sus indicaciones y riesgos para poder participar activamente en la toma de decisiones y poder ofrecer un tratamiento neuroquirúrgico oportuno a cada situación.
Adult low-grade gliomas (Low Grade Gliomas, LGG) are tumors that originate from the glial cells of the brain and whose management involves great controversy, starting from the diagnosis, to the treatment and subsequent follow-up. For this reason, the Tumor Group of the Spanish Society of Neurosurgery (GT-SENEC) has held a consensus meeting, in which the most relevant neurosurgical issues have been discussed, reaching recommendations based on the best scientific evidence. In order to obtain the maximum benefit from these treatments, an individualized assessment of each patient should be made by a multidisciplinary team.
Experts in each LGG treatment field have briefly described it based in their experience and the reviewed of the literature.
Each area has been summarized and focused on the best published evidence.
LGG have been surrounded by treatment controversy, although during the last years more accurate data has been published in order to reach treatment consensus. Neurosurgeons must know treatment options, indications and risks to participate actively in the decision making and to offer the best surgical treatment in every case.
Radiation Therapy for IDH-Mutant Grade 2 and Grade 3 Diffuse Glioma: An ASTRO Clinical Practice Guideline
2022, Practical Radiation OncologyThis guideline provides evidence-based recommendations for adults with isocitrate dehydrogenase (IDH)–mutant grade 2 and grade 3 diffuse glioma, as classified in the 2021 World Health Organization (WHO) Classification of Tumours. It includes indications for radiation therapy (RT), advanced RT techniques, and clinical management of adverse effects.
The American Society for Radiation Oncology convened a multidisciplinary task force to address 4 key questions focused on the RT management of patients with IDH-mutant grade 2 and grade 3 diffuse glioma. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for grading evidence quality and recommendation strength.
A strong recommendation for close surveillance alone was made for patients with oligodendroglioma, IDH-mutant, 1p/19q codeleted, WHO grade 2 after gross total resection without high-risk features. For oligodendroglioma, WHO grade 2 with any high-risk features, adjuvant RT was conditionally recommended. However, adjuvant RT was strongly recommended for oligodendroglioma, WHO grade 3. A conditional recommendation for close surveillance alone was made for astrocytoma, IDH-mutant, WHO grade 2 after gross total resection without high-risk features. Adjuvant RT was conditionally recommended for astrocytoma, WHO grade 2, with any high-risk features and strongly recommended for astrocytoma, WHO grade 3. Dose recommendations varied based on histology and grade. Given known adverse long-term effects of RT, consideration for advanced techniques such as intensity modulated radiation therapy/volumetric modulated arc therapy or proton therapy were given as strong and conditional recommendations, respectively. Finally, based on expert opinion, the guideline recommends assessment, surveillance, and management for toxicity management.
Based on published data, the American Society for Radiation Oncology task force has proposed recommendations to inform the management of adults with IDH-mutant grade 2 and grade 3 diffuse glioma as defined by WHO 2021 classification, based on the highest quality published data, and best translated by our task force of subject matter experts.
Radiation-induced contrast enhancement following proton radiotherapy for low-grade glioma depends on tumor characteristics and is rarer in children than adults
2022, Radiotherapy and OncologyProton beam radiotherapy (PRT) is used in the treatment of low-grade glioma (LGG) to mitigate long-term sequelae. Following PRT, increased rates of radiation-induced contrast enhancements (RICE) are suspected but poorly understood.
We analyzed consecutive 227 patients (42 children and 185 adults) treated with PRT (54 Gy RBE) for LGG from 2010 to 2020 and followed with serial clinical exams and magnetic resonance imaging for in median 5.6 years.
Tumors were graded WHO 1 in a minority (n = 22, 12%) of adults, but a majority of children (n = 29, 69%). In contrast, tumors were graded WHO 2 in the majority (n = 160, 87%) of adults and a minority of children (n = 10, 24%). Five-year overall survival following PRT was 81% in adults and 91% in children. The risk of RICE was 5-fold more frequent in adults (25%) vs. children (5%; p = 0.0043). In children and adults, RICE were symptomatic in 50% and 55% (n = 1 and 26) of cases with CTCAE grade 0 in 47% (n = 23), grade 1 in 25% (n = 12), 0% grade 2 (n = 0) and 29% grade 3 (n = 14), respectively. In adults, RICE risk was associated to WHO grading (8% in WHO grade 1 vs. 24% in WHO grade 2, p = 0.026), independent of age (p = 0.44) and irradiation dose (p = 0.005), but not independent of IDH mutational status.
These data demonstrate effectiveness of PRT for LGG in both children and adults. The RICE risk is lower in children which are a main target group for PRT and differs with WHO grading.