Lung cancer is the first cause of death by cancer in both men and women worldwide. Among all type of lung cancer, small-cell lung cancer (SCLC) is the most aggressive form and is associated with a dismal prognosis and a rapid evolution. Systemic chemotherapy significantly improved survival, but brain metastases are a frequent event during the course of SCLC. In old outdated clinical trials, prophylactic cranial irradiation (PCI) in patients responding to chemotherapy demonstrated a significant impact on brain metastases occurrence and survival. However, a recent study comparing PCI to active brain MRI (magnetic resonance-imaging) surveillance showed no positive effect on survival in extensive disease SCLC. Further, recent data are suggesting a negative effect of PCI on neurological functions, mainly memory loss, and short-term quality of life (QoL).
Our hypothesis is that active MRI surveillance alone, while keeping brain irradiation in case of metastasis is at least as effective as PCI with less neurological deterioration. If the trial confirms this hypothesis, a strategy of MRI surveillance alone will replace PCI both for limited and extensive SCLC. As MRI has virtually no clinically significant toxicity, a modification in the therapeutic strategy from PCI to MRI surveillance may have a positive medico-economic impact at the society level by reducing the costs associated with PCI and neurological toxicities and, at the individual level, lead to better quality of life and increased patients ability to work and be active in society
| Title |
PRophylactic cerebral Irradiation or active MAgnetic resonance imaging surveillance in small-cell Lung cancer patients (PRIMALung study) |
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Participants (P) |
Histologically proven SCLC: a. Limited-stage (LS) (Stage I-III) and Extensive-stage (ES) (Stage IV and tumour not encompassed in a radiation plan). b. Having completed platinum-based chemotherapy (and definitive thoracic RT for LS) with no evidence of progression on imaging (CT or PET/CT including the chest and abdomen, brain MRI) c. No brain metastases or leptomeningeal disease at diagnosis and before randomisation on brain MRI d. No prior cerebral irradiation Note: a minimum of 200 patients with LS to be recruited |
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Intervention (I) |
MRI active surveillance: Brain MRI evaluation will be performed in both arms before randomisation and at 3, 6, 9, 12, 18, and 24 months. Brain MRI is currently used for assessing brain involvement in lung cancer patients at diagnosis, during treatment, and follow up. Brain MRI is performed in dedicated radiology department |
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Control (C) |
Prophylactic cerebral irradiation (PCI): PCI will be delivered to a dose of 25 Gy in 10 fractions to the whole brain. Patients may be treated with conventional PCI or hippocampal sparing PCI using intensity-modulated radiation therapy at the physician’s discretion. PCI is performed in dedicated radiotherapy departments. |
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Outcome (O) |
Overall survival (time interval between the date of randomisation and the date of death from any cause). |
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Trial Design |
Open-label, multicentre, randomized phase III trial assessing the feasibility of MRI active surveillance in small cell lung cancer. Randomisation will be centrally performed using a dynamic balancing algorithm with randomization stratified by stage of disease (LS-SCLC or ES-SCLC), immunotherapy delivery (yes/no), and Performance Status (0 or 1 versus 2). |
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Sample Size |
600 in Europe, 61 planned in Belgium |
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Trial duration |
72 months from FPI to CSR |
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Budget |
400,000€ from KCE Trials of a global budget of around 2,400,000 € |
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Sponsor |
EORTC |
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Chief Investigator |
Prof Corinne Faivre-Finn, NC in Belgium Prof Thierry Berghmans |
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External partners |
Other participating countries: UK, CH, FR, ES, IT, AT, DE, PL and NL |
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Number of participating sites |
5 sites: Institut Jules Bordet, GZA - Sint-Augustinus, UCL St Luc, CHU Liège and AZ Groeninge |
