scholarly journals Radiotherapy versus radiotherapy combined with temozolomide in high-risk low-grade gliomas after surgery:Study protocol for a randomized controlled clinical trial

2019 ◽  
Author(s):  
Jingjing Wang ◽  
Ying Wang ◽  
Yan He ◽  
Hui Guan ◽  
Ling He ◽  
...  

Abstract Background It has been reported that radiation therapy followed by PCV chemotherapy (procarbazine, lomustine and vincristine) could improve progression-free survival (PFS) and overall survival (OS) in patients with high-risk WHO grade 2 gliomas after surgery. However, procarbazine is not available in China. In clinical practice, Chinese doctors often use radiotherapy combined with temozolomide to treat these patients, though large-scale prospective studies are lacking. This trial aims to confirm whether RT combined with temozolomide (TMZ) can improve PFS and OS in patients with high-risk low-grade gliomas (LGGs). Methods/design This is a two-group, randomized controlled trial (RCT) enrolling patients who have low-grade (WHO grade 2) gliomas aged 40 years or older without regard to the extent of resection or 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 radiation therapy (RT) alone or RT plus temozolomide chemotherapy in a 1:1 ratio. The same RT will be given to all eligible participants regardless of whether they are randomly assigned to RT group or 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 progression-free survival and it will be analyzed by intention-to-treat (ITT). Secondary outcomes include OS, adverse events and cognitive function (CF). Discussion The objective of our research is to assess the effect of radiotherapy coupled with temozolomide in high-risk LGGs after surgery, compared with RT alone. Different histological types and molecular subtypes will be examined and subgroup analysis will be conducted based on them. Our data can provide evidence for postoperative adjuvant therapy in Chinese high-risk LGGs.

2019 ◽  
Author(s):  
Jingjing Wang ◽  
Xingchen Peng ◽  
Yan He ◽  
Hui Guan ◽  
Xiaoli Mu ◽  
...  

Abstract Abstract Background It has been reported that radiation therapy followed by PCV chemotherapy (procarbazine, lomustine and vincristine) could improve progression-free survival (PFS) and overall survival (OS) in patients with high-risk WHO grade 2 gliomas after surgery. However, procarbazine is not available in China. In clinical practice, Chinese doctors often use radiotherapy combined with temozolomide to treat these patients, though large-scale prospective studies are lacking. This trial aims to confirm whether RT combined with temozolomide (TMZ) can improve PFS and OS in patients with high-risk low-grade gliomas (LGGs). Methods/design This is a two-group, randomized controlled trial (RCT) enrolling patients who have low-grade (WHO grade 2) gliomas aged 40 years or older without regard to the extent of resection or younger than 40 years old with subtotal resection or biopsy. Eligible participants will be randomly assigned to receive radiation therapy (RT) alone or RT plus temozolomide chemotherapy in a 1:1 ratio. The same RT will be given to all eligible participants regardless of whether they are randomly assigned to RT group or 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 progression-free survival and it will be analyzed by intention-to-treat (ITT). Secondary outcomes include OS, adverse events and cognitive function (CF). Discussion The objective of our research is to assess the effect of radiotherapy coupled with temozolomide in high-risk LGGs after surgery, compared with RT alone. Different histological types and molecular subtypes will be examined and subgroup analysis will be conducted based on them. Our data can provide evidence for postoperative adjuvant therapy in Chinese high-risk LGGs. Trial Registration Chinese Clinical Trial Registry, ChiCTR1800015199. Registered on 13th March, 2018. http://www.chictr.org.cn


2012 ◽  
Vol 30 (25) ◽  
pp. 3065-3070 ◽  
Author(s):  
Edward G. Shaw ◽  
Meihua Wang ◽  
Stephen W. Coons ◽  
David G. Brachman ◽  
Jan C. Buckner ◽  
...  

PurposeA prior Radiation Therapy Oncology Group (RTOG) clinical trial in anaplastic oligodendroglioma suggested a progression-free survival benefit for procarbazine, lomustine, and vincristine (PCV) chemotherapy in addition to radiation therapy (RT), as have smaller trials in low-grade glioma (LGG).Patients and MethodsEligibility criteria included supratentorial WHO grade 2 LGG, age 18 to 39 years with subtotal resection/biopsy, or age ≥ 40 years with any extent resection. Patients were randomly assigned to RT alone or RT followed by six cycles of PCV. Survival was compared by using the modified Wilcoxon and log-rank tests.ResultsIn all, 251 patients were accrued from 1998 to 2002. Median overall survival (OS) time and 5-year OS rates for RT versus RT + PCV were 7.5 years versus not reached and 63% versus 72%, respectively (hazard ratio [HR]; 0.72; 95% CI, 0.47 to 1.10; P = .33; log-rank P = .13). Median progression-free survival (PFS) time and 5-year PFS rates for RT versus RT + PCV were 4.4 years versus not reached and 46% versus 63%, respectively (HR, 0.6; 95% CI, 0.41 to 0.86; P = .06; log-rank P = .005). OS and PFS were similar for all patients between years 0 and 2. After 2 years, OS and PFS curves separated significantly, favoring RT + PCV. For 2-year survivors (n = 211), the probability of OS for an additional 5 years was 74% with RT + PCV versus 59% with RT alone (HR, 0.52; 95% CI, 0.30 to 0.90; log-rank P = .02).ConclusionPFS but not OS was improved for adult patients with LGG receiving RT + PCV versus RT alone. On post hoc analysis, for 2-year survivors, the addition of PCV to RT conferred a survival advantage, suggesting a delayed benefit for chemotherapy.


Trials ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Jingjing Wang ◽  
Ying Wang ◽  
Yan He ◽  
Hui Guan ◽  
Ling He ◽  
...  

Abstract 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.


2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii194-ii194
Author(s):  
Ingo Mellinghoff ◽  
Martin van den Bent ◽  
Jennifer Clarke ◽  
Elizabeth Maher ◽  
Katherine Peters ◽  
...  

Abstract BACKGROUND Low-grade gliomas (LGGs; WHO grade II) are incurable and ultimately progress to high-grade gliomas. The current treatment options are surgery followed by observation (“watch and wait”) for patients with lower risk for disease progression or postoperative chemoradiotherapy (high-risk population). There are no approved targeted therapies. IDH1 and IDH2 mutations (mIDH1/2) occur in approximately 80% and 4% of LGGs, respectively, and promote tumorigenesis via neomorphic production of D-2-hydroxyglutarate. Vorasidenib, an oral, potent, reversible, brain-penetrant pan-inhibitor of mIDH1/2, was evaluated in 76 patients with glioma in two phase 1 studies (dose escalation and perioperative) and was associated with a favorable safety profile at daily doses below 100 mg. Preliminary clinical activity was observed in non-enhancing glioma patients in both studies, with an objective response rate (ORR) of 18.2% and median progression-free survival of 31.4 months in the dose escalation study. METHODS Approximately 366 patients will be randomized 1:1 to vorasidenib (50 mg QD) or matched placebo and stratified by 1p19q status (intact vs co-deleted). Key eligibility criteria: age ≥ 12 years; grade II oligodendroglioma or astrocytoma (per WHO 2016 criteria) not in need of immediate treatment and without high-risk features; centrally confirmed mIDH1/2 status; ≥ 1 surgery for glioma with most recent ≥ 1 year but ≤ 5 years before randomization, and no other anticancer therapy; Karnofsky performance status ≥ 80%; and centrally confirmed measurable, non-enhancing disease evaluable by magnetic resonance imaging. Crossover from placebo to the vorasidenib arm is permitted upon centrally confirmed radiographic progression per RANO-LGG criteria. Primary endpoint: progression-free survival assessed by independent review. Secondary endpoints: safety and tolerability, tumor growth rate assessed by volume, ORR, overall survival, and quality of life. Clinical data will be reviewed regularly by an independent data monitoring committee. The study is currently enrolling patients in the US, with additional countries planned (NCT04164901).


2018 ◽  
Vol 6 (4) ◽  
pp. 249-258 ◽  
Author(s):  
Timothy J Brown ◽  
Daniela A Bota ◽  
Martin J van Den Bent ◽  
Paul D Brown ◽  
Elizabeth Maher ◽  
...  

Abstract Background Optimum management of low-grade gliomas remains controversial, and widespread practice variation exists. This evidence-based meta-analysis evaluates the association of extent of resection, radiation, and chemotherapy with mortality and progression-free survival at 2, 5, and 10 years in patients with low-grade glioma. Methods A quantitative systematic review was performed. Inclusion criteria included controlled trials of newly diagnosed low-grade (World Health Organization Grades I and II) gliomas in adults. Eligible studies were identified, assigned a level of evidence for every endpoint considered, and analyzed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The relative risk of mortality and of progression at 2, 5, and 10 years was calculated for patients undergoing resection (gross total, subtotal, or biopsy), radiation, or chemotherapy. Results Gross total resection was significantly associated with decreased mortality and likelihood of progression at all time points compared to subtotal resection. Early radiation was not associated with decreased mortality; however, progression-free survival was better at 5 years compared to patients receiving delayed or no radiation. Chemotherapy was associated with decreased mortality at 5 and 10 years in the high-quality literature. Progression-free survival was better at 5 and 10 years compared to patients who did not receive chemotherapy. In patients with isocitrate dehydrogenase 1 gene (IDH1) R132H mutations receiving chemotherapy, progression-free survival was better at 2 and 5 years than in patients with IDH1 wild-type gliomas. Conclusions Results from this review, the first to quantify differences in outcome associated with surgery, radiation, and chemotherapy in patients with low-grade gliomas, can be used to inform evidence-based management and future clinical trials.


2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii379-iii379
Author(s):  
Regina M Navarro-Martin del Campo ◽  
Erika Casillas-Toral ◽  
Ana L Orozco-Alvarado ◽  
Fernando Sanchez-Zubieta ◽  
Luis A Arredondo-Navarro ◽  
...  

Abstract BACKGROUND Brain tumors are the most common solid tumors in childhood, 35% of them being low-grade gliomas (LGGs). Few data is available regard LGGs in low-and-middle-income countries. This study evaluates LGGs in a tertiary center in Mexico. DESIGN: A retrospective review of clinical files of 105 children diagnosed with LGG other than optic nerve glioma from 2007 to 2019 was done. RESULTS Median age at diagnosis was 7.2 years (from 5 months to 18 years). Male to female ratio was 0.75:1. WHO Grade I represented 68% of the cases. Anatomic sites were: posterior fossa (41%), supratentorial (43.5 %), spinal (8.5%), subependymal (6 %) and pineal (1%). Ten percent of patients had a diagnosed phacomatosis. Treatment was observation without surgery in 3.8%, surgery followed by observation in 49.5%, only chemotherapy in 2.8%, only radiotherapy in 6.7%, and surgery combined with chemotherapy or radiotherapy in 37.2% of cases. Among patients who had surgical intervention, 40% achieved gross total resection, 44% subtotal resection and 16% only biopsy. One or more recurrences were found in 20 % of patients. The 5 and 10-year overall survival (OS) was 83% and 73% respectively. The 5 and 10-year progression-free survival (PFS) was 66 % and 44 % respectively. CONCLUSIONS In this series the OS were lower compared with countries with high income, reflecting the need to improve surgery, since only 40% achieved complete resection that is a determining factor for the prognosis. We observed a decrease in OS until 10-year follow and the PFS was even lower due to recurrence/progression.


2013 ◽  
Vol 71 (1) ◽  
pp. 31-34 ◽  
Author(s):  
André de Macedo Bianco ◽  
Flavio Key Miura ◽  
Carlos Clara ◽  
Jose Reynaldo W. Almeida ◽  
Clemar Correa da Silva ◽  
...  

A retrospective study of 81 patients with low-grade astrocytoma (LGA) comparing the efficacy of aggressive versus less aggressive surgery in eloquent and non-eloquent brain areas was conducted. Extent of surgical resection was analyzed to assess overall survival (OS) and progression- free survival (PFS). Degree of tumor resection was classified as gross total resection (GTR), subtotal resection (STR) or biopsy. GTR, STR and biopsy in patients with tumors in non-eloquent areas were performed in 31, 48 and 21% subjects, whereas in patients with tumors in eloquent areas resections were 22.5, 35 and 42.5%. Overall survival was 4.7 and 1.9 years in patients with tumors in non-eloquent brain areas submitted to GTR/STR and biopsy (p=0.013), whereas overall survival among patients with tumors in eloquent area was 4.5 and 2.1 years (p=0.33). Improved outcome for adult patients with LGA is predicted by more aggressive surgery in both eloquent and non-eloquent brain areas.


1997 ◽  
Vol 2 (3) ◽  
pp. E1
Author(s):  
Roger J. Packer ◽  
Joanne Ater ◽  
Jeffrey Allen ◽  
Peter Phillips ◽  
Russell Geyer ◽  
...  

The optimum treatment of nonresectable low-grade gliomas of childhood remains undecided. There has been increased interest in the use of chemotherapy for young children, but little information concerning the long-term efficacy of such treatment. Seventy-eight children with a mean age of 3 years (range 3 months-16 years) who had newly diagnosed, progressive low-grade gliomas were treated with combined carboplatin and vincristine chemotherapy. The patients were followed for a median of 30 months from diagnosis, with 31 patients followed for more than 3 years. Fifty-eight children had diencephalic tumors, 12 had brainstem gliomas, and three had diffuse leptomeningeal gliomas. Forty-four (56%) of 78 patients showed an objective response to treatment. Progression-free survival rates were 75 ± 6% at 2 years and 68 ± 7% at 3 years. There was no statistical difference in progression-free survival rates between children with neurofibromatosis Type 1 and those without the disease (2-year, progression-free survival 79 ± 11% vs. 75 ± 6%, respectively). The histological subtype of the tumor, its location, and its maximum response to chemotherapy did not have an impact on the duration of disease control. The only significant prognostic factor was age: children 5 years old or younger at the time of treatment had a 3-year progression-free survival rate of 74 ± 7% compared with a rate of 39 ± 21% in older children (p < 0.01). Treatment with carboplatin and vincristine is effective, especially in younger children, in controlling newly diagnosed progressive low-grade gliomas.


2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Ningning Zhang ◽  
Hailong Tian ◽  
Dezhang Huang ◽  
Xianbing Meng ◽  
Wenqiang Guo ◽  
...  

Objective. Sodium fluorescein (FL) had been safely used in fluorescence-guided microsurgery for imaging various brain tumors. Under the YELLOW 560 nm surgical microscope filter, low-dose FL as a fluorescent dye helps in visualization. Our study investigated the safety and efficacy of this innovative technique in malignant glioma (MG) patients. Patients and Method. 38 patients suffering from MGs confirmed by pathology underwent FL-guided resection under YELLOW 560 nm surgical microscope filter. We retrospectively analyzed the clinical characters, microsurgery procedure, extent of resection, pathology of MGs, progression-free survival (PFS), and overall survival (OS). Results. Thirty-eight patients had MGs (10 WHO grade III, 28 WHO grade IV). With YELLOW 560 nm surgical microscope filter combined with neuronavigation, sodium fluorescein-guided gross total resection (GTR) was achieved in 35 (92.1%) patients and subtotal resection in 3 (7.69%). The sensitivity and specificity of FL were 94.4% and 88.6% regardless of radiographic localization. Intraoperatively, 10 biopsies (10/28 FL[+]) showed “low” or “high” fluorescence in non-contrast-enhancement region and are also confirmed by pathology. Our data showed 6-month PFS of 92.3% and median survival of 11 months. Conclusion. FL-guided resection of MGs under the YELLOW 560 nm surgical microscope filter combined with neuronavigation was safe and effective, especially in non-contrast-MRI regions. It is feasible for improving the extent of resection in MGs especially during emergency cases.


2019 ◽  
Vol 1 (Supplement_2) ◽  
pp. ii36-ii36
Author(s):  
Dai Kamamoto ◽  
Hikaru Sasaki ◽  
Ryota Sasao ◽  
Takumi Fujiyama ◽  
Kazunari Yoshida

Abstract The optimal treatment for grade II/III meningioma is operation with or without radiation therapy. However, their natural course is sometimes aggressive with high recurrent rate. There is no effective treatment other than operation and radiation therapy, therefore, a new therapeutic strategy for grade II/III meningioma is urgently required.PD-1 and PD-L1 play important roles as immune-checkpoint mediators within tumor microenvironment and the antibodies to these molecules are now approved for the treatment of various kinds of cancers. In Japan, anti-PD-1 antibody and anti-CTLA-4 antibody are approved for unresectable melanoma or advanced / recurrent non-small cell lung cancer and their high effectiveness has been reported. We investigated the expression of PD-L1 (clone:28-8) in 51 cases of grade II/III meningioma by immunohistochemistry and analyzed the relationship between the expression with overall survival, progression free survival and initial WHO grade. For now, we have evaluated 25 cases of PD-L1 immunohistochemistry and PD-L1 showed positivity in 15 cases. There is no correlation observed between PD-L1 expression and patients’ prognosis. Although it does not reach a significant difference, the WHO grade at the time of initial operation tends to be high in those with high PD-L1 staining rate.Similar studies that were previously reported did not use antibodies targeting clone 28-8, which was used as a companion diagnosis for nivolumab administration, but “Correlation between PD-L1 expression and WHO grade”, or “PD-L1 expression is an independent prognostic factor” have been reported. In our investigation, which was using antibodies for companion diagnosis, PD-L1 was positive in more than half of Grade II / III meningiomas and it also related to WHO grade. These results suggest the possibility that tumor immune evasion mechanisms are also working in meningiomas. At the conference, we will report it with the specific data from all cases with a literature review.


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