A protocol for a systematic review with prospective individual patient data meta-analysis in EGFR mutant NSCLC with brain metastases to assess the effect of SRS + Osimertinib compared to Osimertinib alone: the STARLET collaboration
Bibliographic record
Abstract
ABSTRACT Background Patients with advanced non-small-cell lung cancer (NSCLC) with activating mutations in the epidermal growth factor receptor ( EGFR ) gene are a heterogenous population who often develop brain metastases (BM). The optimal management of patients with asymptomatic brain metastases is unclear given the activity of newer generation targeted therapies in the central nervous system. We present a protocol for an individual patient data prospective meta-analysis (IPD-PMA) to evaluate whether the addition of stereotactic radiosurgery (SRS) before Osimertinib treatment will lead to better control of intracranial metastatic disease. This is a clinically relevant question that will inform practice. Methods Randomised controlled trials (RCTs) will be eligible if they included: participants with BM arising from EGFR mutant NSCLC and suitable to receive Osimertinib both in the first- and second-line settings (P); comparisons of SRS followed by Osimertinib versus Osimertinib alone (I, C); and intracranial disease control included as an endpoint (O). Systematic searches of Medline (Ovid), Embase (Ovid), Cochrane Central Register of Controlled Trials (CENTRAL), CINAHL (EBSCO), PsychInfo, ClinicalTrials.gov and the World Health Organisation’s International Clinical Trials Registry Platform’s Search Portal will be undertaken. An IPD meta-analysis will be performed using methodologies recommended by the Cochrane Collaboration. The primary outcome is intra-cranial progression free survival, as determined by RANO-BM criteria. Secondary outcomes include overall survival, time to whole brain radiotherapy, quality of life and adverse events of special interest. Effect differences will be explored among pre-specified subgroups. Ethics and dissemination Approved by each trials ethics committee. Results will be relevant to clinicians, researchers, policymakers and patients, and will be disseminated via publications, presentations and media releases. Prospero registration CRD42022330532 Strengths and Limitations of this study The use of an individual patient data (IPD) meta-analysis will give increased statistical power for the relative comparison of SRS followed by Osimertinib versus Osimertinib alone on intracranial progression-free survival. Such a meta-analysis will also enable the exploration of subgroups. Frequency of outcome assessment and outcome measures may be collected and reported differently across included trials, which may lead to some imprecision. Harmonisation of clinical trial protocols through prospective meta-analysis will address some of these limitations. A limitation of this study is that the searches will only be conducted until late 2023 and any studies that are registered after this time will not be included.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.085 | 0.144 |
| Meta-epidemiology (narrow) | 0.006 | 0.005 |
| Meta-epidemiology (broad) | 0.020 | 0.023 |
| Bibliometrics | 0.010 | 0.012 |
| Science and technology studies | 0.003 | 0.004 |
| Scholarly communication | 0.007 | 0.007 |
| Open science | 0.005 | 0.005 |
| Research integrity | 0.008 | 0.007 |
| Insufficient payload (model declined to judge) | 0.130 | 0.013 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".