Inconsistencies in predictive models based on exhaled volatile organic compounds for distinguishing between benign pulmonary nodules and lung cancer: a systematic review
Bibliographic record
Abstract
BACKGROUND: There is a general rise in incidentally found pulmonary nodules (PNs) requiring follow-up due to increased CT use. Biopsy and repeated CT scan are the most useful methods for distinguishing between benign PNs and lung cancer, while they are either invasive or involves radiation exposure. Therefore, there has been increasing interest in the analysis of exhaled volatile organic compounds (VOCs) to distinguish between benign PNs and lung cancer because it's cheap, noninvasive, efficient, and easy-to-use. However, the exact value of breath analysis in this regard remains unclear. METHODS: A PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses)-oriented systematic search was performed to include studies that established exhaled VOC-based predictive models to distinguish between benign PNs and lung cancer and reported the exact VOCs used. Data regarding study characteristics, performance of the models, which predictors were incorporated, and methodologies for breath collection and analysis were independently extracted by two researchers. The exhaled VOCs incorporated into the predictive models were narratively synthesized, and those compounds that were reported in > 2 studies and reportedly exhibited consistent associations with lung cancer were considered key breath biomarkers. A quality assessment was independently performed by two researchers using both the Newcastle-Ottawa Scale (NOS) and the Prediction Model Risk of Bias Assessment Tool (PROBAST). RESULTS: A total of 11 articles reporting on 46 VOC-based predictive models were included. The majority relied solely on exhaled VOCs (n = 44), while two incorporated VOCs, demographical factors, and radiological signs. The variation in the sensitivity, specificity, and AUC indicators of the models that incorporated multiple factors was lower compared with those of the models that relied solely on exhaled VOCs. A total of 84 VOCs were incorporated. Of these, 2-butanone, 3-hydroxy-2-butanone, and 2-hydroxyacetaldehyde were identified as key predictors that had significantly higher concentrations in the exhaled breath samples of patients with lung cancer. Substantial heterogeneity was observed in terms of the modeling and validation methods used, as well as the approaches to breath collection and analysis. Many of the reports were missing certain key pieces of clinical and methodological information. CONCLUSIONS: Although exhaled VOC-based models for predicting cancer risk might be a conceivable role as monitoring tools for PNs risk, there has been little overall change in the accuracy of these tests over time, and their role in routine clinical practice has not yet been established. CLINICAL TRIAL NUMBER: PROSPERO registration number CRD42023381458.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.058 | 0.233 |
| Meta-epidemiology (narrow) | 0.004 | 0.002 |
| Meta-epidemiology (broad) | 0.013 | 0.035 |
| Bibliometrics | 0.015 | 0.012 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.005 | 0.004 |
| Open science | 0.006 | 0.003 |
| Research integrity | 0.003 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
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".