FET-PET-Guided Management of Pseudoprogression in Glioblastoma
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 发起方
- 入组人数
- 144
- 试验地点
- 10
- 主要终点
- Health-related quality of life: general
研究概览
简要总结
The goal of this diagnostic randomised clinical trial is to determine, in glioblastoma patients with diagnostic uncertainty between pseudoprogression and tumor progression on follow-up MRI after chemoradiation, the added value of a direct [¹⁸F] FET-PET scan for clinical management.
The main questions it aims to answer are:
- Does the clinical management guided by an additional FET-PET scan leads to fewer unnecessary interventions, compared with management based on MRI only?
- Does the clinical management guided by an additional FET-PET scan leads to better health-related quality of life after 12 weeks, compared with management based on MRI only?
- Does the clinical management guided by an additional FET-PET scan leads to reduced net healthcare costs, compared with management based on MRI only?
Researchers will compare the investigational arm, where clinical management is based on the index MRI scan and an additional FET-PET scan, with the control arm, where clinical management is based solely on the index MRI scan, to investigate the added value of the FET PET scan for clinical management.
Participants in the investigational arm will undergo the FET PET scan. All participants will complete health-related quality of life questionnaires at four different timepoints.
详细描述
During follow-up of glioblastoma patients after chemoradiation, expert teams often observe MRI abnormalities with difficulty in distinguishing between tumor growth and pseudoprogression. Although techniques such as perfusion MRI provide additional information, diagnostic uncertainty often remains, leading to incorrect or delayed diagnosis and, inappropriate treatment, such as unnecessary surgery. Despite the good discriminating power of [¹⁸F] Fluoro-ethyl-tyrosine-PET (FET-PET), this diagnostic tool is not used frequently in the Netherlands due to costs, logistics, and misconceptions about clinical benefit. In the FET POPPING study we aim to determine the added value of [¹⁸F] FET-PET for clinical management. A multicenter diagnostic randomised clinical trial will be performed, from July 2024 until December 2027. 144 adult patients with isocitrate dehydrogenase (IDH)-wildtype glioblastoma will be included, who, after the concomitant phase of chemoradiation, have increased contrast enhancement on MRI, causing doubt between tumor growth or pseudoprogression. Included patients will be randomised 1:1 in two arms. The investigational arm receives an additional [¹⁸F] FET-PET scan, and clinical management is based on the index MRI and [¹⁸F] FET-PET together. Clinical management of the control arm is based on the index MRI alone. Exact clinical management, following from the available imaging, is chosen at the discretion of a multidisciplinary board. The primary study endpoints are (a) the percentage of patients undergoing unnecessary interventions and (b) health-related quality of life after 12 weeks. Secondary endpoints include time-to-diagnosis, overall survival and cost-effectiveness. We hypothesize that the clinical management guided by an additional [¹⁸F] FET-PET scan leads to fewer unnecessary interventions, better health-related quality of life after 12 weeks and among others reduced net healthcare costs, compared with management based on MRI only.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with a glioblastoma, IDH-wildtype, World Health Organization (WHO) grade 4, according to WHO 2021 criteria.
- •Age ≥18 years
- •New or increased enhancement within the high-dose radiation field (defined as within the 80% isodose line) on follow-up MRI
- •Follow up MRI ≥3 months after the end of the standard-of-care temozolomide-based concomitant chemoradiation (60 Gy/30 fractions or 40 Gy/15 fractions). Of note, very early increase - within 3 months of last radiation - will not be grounds for inclusion because of the high rate of pseudoprogression and slightly lower diagnostic performance of FET-PET compared to the situation of increase beyond 3 months after last radiation. Patients with such very early increase may have subsequent further increase after 3 months post-radiation, causing (further) diagnostic doubt; these may be included at that later timepoint if they meet the other inclusion criteria.
- •First moment of clinicoradiological uncertainty regarding the diagnosis (≥3 months after the end of chemoradiation): pseudoprogression or tumor recurrence. The determination of 'uncertainty' is made by the treating physician, preferably in the multidisciplinary tumor board, based on available clinical and standard-of-care MRI-data, which generally includes perfusion-MRI.
- •Previous usage of bevacizumab as a symptom treatment is allowed. However, inclusion is only allowed at the first moment of clinical doubt between pseudoprogression and tumor recurrence, not at later timepoints.
排除标准
- •Previous treatment for recurrence of disease
- •An enhanced lesion size of less than 1 cm on the index MRI. In the newest RANO PET criteria, it is advised to use FET-PET for increasing lesions only in cases with a minimum lesion size.
- •Life expectancy of less than 6 months, determined by the treating physician
- •Contra-indications for PET (claustrophobia, inability to lay still)
- •Women of childbearing potential without adequate contraception
- •Any other concomitant disease that may influence PET imaging or clinical outcomes of this study, this includes but is not limited to: cerebral inflammatory diseases and other cancers with brain- or leptomeningeal metastases
结局指标
主要结局
Health-related quality of life: general
时间窗: at twelve weeks
This will be reported by the questionnaire EQ5D. The EQ5D is a generic utility questionnaire which allows for comparison of quality of life between indications, and is considered the golden standard by the Dutch National Heath Care Institute. Both the total score of the questionnaire is used as the individual scores to analyse individual patients' changes over time.
Health-related quality of life: brain tumor specific
时间窗: at twelve weeks
This will be reported by the questionnaire European Organization for Research and Treatment of Cancer Quality of Life Brain Cancer Module (EORTC-QLQ-BN20). The EORTC-QLQ-BN20 is a brain tumor specific questionnaire and is a reliable tool to capture changes in specific health domains for this population. Both the total score of the questionnaire is used as the individual scores to analyse individual patients' changes over time.
Health-related quality of life: productivity
时间窗: at twelve weeks
This will be reported by the questionnaire iMTA Productivity Cost Questionnaire (iPCQ). The iPCQ questionnaire measures productivity losses and is applicable to national and international studies. Both the total score of the questionnaire is used as the individual scores to analyse individual patients' changes over time.
Composite score of proportion (0-100%) of patients undergoing unnecessary interventions.
时间窗: at six months
Determination of 'unnecessary interventions' will be done retrospectively, by the researchers and the treating physician. An 'unnecessary intervention' is defined as: * Biopsy or debulking for diagnostic uncertainty and/or with pseudoprogression as the final pathological diagnosis * The administration of one or more cycles of (temozolomide) chemotherapy as continued treatment for presumed pseudoprogression, in cases with a final diagnosis of tumor progression * The administration of one or more doses of bevacizumab for presumed pseudoprogression, in cases with a final diagnosis of tumor progression
Health-related quality of life: medical consumption
时间窗: at twelve weeks
This will be reported by the questionnaire iMTA Medical Consumption Questionnaire (iMCQ). The iMCQ questionnaire is an instrument for measuring medical consumption. Both the total score of the questionnaire is used as the individual scores to analyse individual patients' changes over time.
次要结局
- Overall survival(Through study completion (expected median of less than 1.5 year))
- Health-related quality of life: general(at six weeks and six months)
- Number of unnecessary treatment cycles(at six months)
- Cost-effectiveness(at six months)
- Time-to-diagnosis(During the study period (but expected within three months))
- Health-related quality of life: brain tumor specific(at six weeks and six months)
- Health-related quality of life: productivity(at six weeks and six months)
- Health-related quality of life: medical consumption(at six weeks and six months)
研究者
Veerle Ruijters
Medical researcher
UMC Utrecht