57P Clinical characteristics and outcomes in non-small cell lung cancer (NSCLC) with tumour and germline BRCA1/2 mutations
Bibliographic record
Abstract
Expanded use of tumour molecular testing to enable targeted treatment across multiple cancers has increased identification of potential pathogenic germline variants (pPGVs). In NSCLC, BRCA1 and BRCA2 are two potentially targetable pPGVs that are not well described despite BRCA-mutated lung cancer accounting for 1%-14% of cases. This study evaluates the frequency of BRCA1/2-mutated NSCLC identified via tumour sequencing and describes patient and tumour characteristics, family history, clinical course, and germline BRCA mutational status. NSCLC patients who underwent tumour testing between January 1, 2018 and June 30, 2021 were identified. Next generation sequencing was used to screen for 46 tumour gene mutations including BRCA1/2, with subsequent referral for germline testing via gene specific intronic polymerase chain reaction amplification if pPGVs were identified. Of 2784 patients with NSCLC who had tumour sequencing, 44 (1.6%) had pPGVs in BRCA1/2. The majority of patients had metastatic disease at diagnosis (59.1%) and a family history of cancer in a first-degree relative (56.8%), while 34.1% had personal history of a second primary cancer. Frequently co-mutated genes were TP53 (68.2%), KRAS (40.1%), and EGFR (20.5%). Of patients who had confirmatory testing, 60% (12/20) were confirmed germline BRCA1/2 carriers. Patients with stage IV disease at time of diagnosis with germline BRCA1/2 mutation had shortened overall survival (18.7 ± 4.6 months) when compared to the 8 patients with confirmed somatic BRCA1/2 mutation (63.8 ± 21.8 months, p = 0.027). BRCA1/2 tumour mutations were detected with frequency consistent with prior reports and exhibit high likelihood of associated germline mutation. The observed difference in survival of patients with advanced disease harbouring somatic versus germline mutation warrants further study and highlights the importance of confirmatory germline testing as targeted therapies emerge in order to adequately prognosticate and inform families of at-risk status.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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 teacher head, 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".