Quality assurance in the EORTC 22033–26033/CE5 phase III randomized trial for low grade glioma: The digital individual case review

Fairchild, Alysa; Weber, Damien Charles; Bar-Deroma, R.; Gulybán, Ákos; Fenton, Paul; Stupp, Roger; Baumert, Brigitta G.

doi:10.1016/j.radonc.2012.04.002

Cited by 36 publications

(21 citation statements)

References 19 publications

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“…It is not likely that all assessed parameters (eg target volume, normal tissue dose constraints, beam arrangement) have an equal probability of affecting clinical outcomes, and yet in most trial reports, different deviations are weighted equally. The required degree of compliance to avoid assignment of deviations may be too strict or not strict enough (16,23,30). In the EORTC 22922 trial, variation in planning methods between centres and individualization of RT to patient anatomy were not considered deviations as long as planning aims were achieved (31), but this leniency has not been commonly permitted by other clinical trial groups.…”

Section: Discussionmentioning

confidence: 99%

Does Quality of Radiation Therapy Predict Outcomes of Multicenter Cooperative Group Trials? A Literature Review

Fairchild¹,

Straube

Laurie³

et al. 2013

International Journal of Radiation Oncology*Biology*Physics

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Central review of radiotherapy (RT) delivery within multicentre clinical trials was initiated in the early 1970’s in the USA. Early quality assurance (QA) publications often focused on metrics related to process, logistics and timing. Our objective was to review the available evidence supporting correlation of RT quality with clinical outcomes within cooperative group trials. Medline search was performed to identify multicentre studies which described central subjective assessment of RT protocol compliance (quality). Data abstracted included method of central review, definition of deviations, and clinical outcomes. Seventeen multicentre studies (1980–2012) were identified, plus one Patterns of Care Study. Disease sites were hematologic, head and neck, lung, breast and pancreas. Between 0% and 97% of treatment plans received an overall grade of acceptable. In seven trials, failure rates were significantly higher after inadequate versus adequate RT. 5/9 and 2/5 trials reported significantly worse overall and progression-free survival after poor quality RT, respectively. One reported a significant correlation and two reported non-significant trends towards increased toxicity with non-compliant RT. Although more data are required, protocol-compliant RT may decrease failure rates and increase overall survival and likely contributes to the ability of collected data to answer the central trial question.

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Section: Discussionmentioning

confidence: 99%

Does Quality of Radiation Therapy Predict Outcomes of Multicenter Cooperative Group Trials? A Literature Review

Fairchild¹,

Straube

Laurie³

et al. 2013

International Journal of Radiation Oncology*Biology*Physics

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129

100

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“…All participating sites had to comply with an extensive quality assurance program including dosimetry, dummy run and individual patient radiotherapy plan review (level III). 16–18 …”

Section: Methodsmentioning

confidence: 99%

Temozolomide chemotherapy versus radiotherapy in high-risk low-grade glioma (EORTC 22033-26033): a randomised, open-label, phase 3 intergroup study

Baumert

Hegi

Bent

et al. 2016

The Lancet Oncology

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Background Outcome of low-grade glioma (LGG, WHO grade II) is highly variable reflecting molecular heterogeneity of the disease. We compared two different single modality treatment strategies: standard radiotherapy (RT) versus primary temozolomide (TMZ) chemotherapy with the aim of tailoring treatment and identifying predictive molecular factors. Methods 477 patients (2005 – 2012, median FU 48 months) with a low-grade glioma (astrocytoma, oligoastrocytoma, oligodendroglioma, WHO grade II) with at least one high-risk feature (age > 40 years, progressive disease, tumor > 5 cm or crossing the midline, neurological symptoms (e.g. focal or mental deficits, increased intracranial pressure or intractable seizures)) were, after stratification by chromosome 1p-status, randomized to either conformal RT (50.4 Gy/28 fractions) or dose-dense TMZ (75 mg/m2 daily × 21 days, q28 days, max. 12 cycles). Random treatment allocation was performed online using a minimization technique. A planned analysis was performed after 246 progression events. All analyses are intent to treat. Primary clinical endpoint was progression-free survival (PFS), correlative analyses included molecular markers (1p/19q co-deletion, MGMT methylation status, IDH1+2 mutations). The trial has been registered at the European Trials Registry (EudraCT 2004-002714-11) and at ClinicalTrials.gov (NCT00182819). Findings Four hundred seventy-seven patients were randomized. Severe hematological toxicity occurred in 14% of TMZ-treated patients, infections in 3% of TMZ-treated patients, and 1% of RT-treated patients. Moderate to severe fatigue was recorded in 3% of patients in the RT group and 7% in the TMZ group. At a median follow-up of 48 months (IQR:31–56), median PFS was 39 months (IQR:16–46) in the TMZ arm and 46 months (IQR:19–48) in the RT group (hazard ratio 1.16, 95% CI, 0.9–1.5; p=0.22). Median OS has not been reached. Exploratory analyses identified treatment-dependent variation in outcome of molecular LGG subgroups (n=318). Interpretation There was no significant difference in outcome of the overall patient population treated with either radiotherapy alone or TMZ chemotherapy alone. Further data maturation is needed for overall survival analyses and evaluation of the full predictive impact of the molecular subtypes for individualized treatment choices. Funding Merck & Co, Swiss-Bridge Award 2011, Swiss Cancer League.

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“…Contouring uncertainties are regarded as one of the largest contributors to poor quality radiotherapy . Quality assurance investigations during large clinical trials have revealed contouring quality to be poor, with amendments required in over 80% of audited cases . Non‐compliant contouring has been shown to impact patient treatment outcomes during clinical trials …”

Section: Introductionmentioning

confidence: 99%

Multi‐observer contouring of male pelvic anatomy: Highly variable agreement across conventional and emerging structures of interest

et al. 2019

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Introduction: This study quantified inter-observer contouring variations for multiple male pelvic structures, many of which are of emerging relevance for prostate cancer radiotherapy progression and toxicity response studies. Methods: Five prostate cancer patient datasets (CT and T2-weighted MR) were distributed to 13 observers for contouring. CT structures contoured included the clinical target volume (CTV), seminal vesicles, rectum, colon, bowel bag, bladder and peri-rectal space (PRS). MR contours included CTV, trigone, membranous urethra, penile bulb, neurovascular bundle and multiple pelvic floor muscles. Contouring variations were assessed using the intraclass correlation coefficient (ICC), Dice similarity coefficient (DSC), and multiple additional metrics. Results: Clinical target volume (CT and MR), bladder, rectum and PRS contours showed excellent inter-observer agreement (median ICC = 0.97; 0.99; 1.00; 0.95; 0.90, DSC = 0.83 AE 0.05; 0.88 AE 0.05; 0.93 AE 0.03; 0.81 AE 0.07; 0.80 AE 0.06, respectively). Seminal vesicle contours were more variable (ICC = 0.75, DSC = 0.73 AE 0.14), while colon and bowel bag contoured volumes were consistent (ICC = 0.97; 0.97), but displayed poor overlap (DSC = 0.58 AE 0.22; 0.67 AE 0.21). Smaller MR structures showed significant inter-observer variations, with poor overlap for trigone, membranous urethra, penile bulb, and left and right neurovascular bundles (DSC = 0.44 AE 0.22; 0.41 AE 0.21; 0.66 AE 0.21; 0.16 AE 0.17; 0.15 AE 0.15). Pelvic floor muscles recorded moderate to strong inter-observer agreement (ICC = 0.50-0.97), although large outlier variations were observed. Conclusions: Inter-observer contouring variation was significant for multiple pelvic structures contoured on MR.

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Quality assurance in the EORTC 22033–26033/CE5 phase III randomized trial for low grade glioma: The digital individual case review

Cited by 36 publications

References 19 publications

Does Quality of Radiation Therapy Predict Outcomes of Multicenter Cooperative Group Trials? A Literature Review

Does Quality of Radiation Therapy Predict Outcomes of Multicenter Cooperative Group Trials? A Literature Review

Temozolomide chemotherapy versus radiotherapy in high-risk low-grade glioma (EORTC 22033-26033): a randomised, open-label, phase 3 intergroup study

Multi‐observer contouring of male pelvic anatomy: Highly variable agreement across conventional and emerging structures of interest

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