DeCure for Acinar lung adenocarcinoma

In acinar-predominant stage IA lung adenocarcinoma, the proportion of the lepidic subtype carries prognostic weight. A review of 215 patients found that those with 20% or more lepidic component had significantly lower recurrence (p = 0.008), better disease-free survival (p = 0.007) and overall survival (p = 0.046) than those with less. Multivariate analysis identified lymphovascular invasion (p = 0.006) and a lepidic proportion below 20% (p = 0.036) as independent predictors of worse disease-free survival. In a separate cohort of 752 stage I patients, acinar-predominant tumours were the most common (44.7%), and an acinar subtype size greater than 1 cm, or the mere presence of micropapillary or solid subtypes, independently predicted recurrence (area under the ROC curve 0.710, p < 0.001). For stage IA non-small cell lung cancer generally, a 2004 study of 224 patients reported 1-, 3- and 5-year survival rates of 89%, 76% and 66%, with better survival for tumours ≤ 2 cm, in females, and in bronchoalveolar adenocarcinoma; limited resections carried a higher local recurrence rate.

For advanced disease with specific molecular drivers, a 2024 case report describes a patient with class III BRAF G466V mutation who achieved a partial response after three months of dabrafenib and trametinib, with marked symptomatic improvement enabling self-care. This is a single case, and the authors note that class III BRAF mutations generally lack approved targeted options and carry unfavourable outcomes. In EGFR-mutant resectable disease, a 2025 multicentre retrospective study of 24 patients receiving neoadjuvant targeted therapy reported an objective response rate of 83.3% (20/24), a major pathologic response rate of 37.5% (9/24), and pathological complete response in 2 patients (8.3%). All achieved R0 resection, with no grade 3 or higher adverse events; the 1-year and 2-year disease-free survival rates were 91.1% and 86.2%, with no deaths at a median follow-up of 33 months. Adverse events were grade 1–2 in 54.2% of patients, most commonly rash (16.7%), mouth sores (8.3%) and diarrhoea (8.3%).

Preclinical work on SUN1 silencing in A549 and 95D lung adenocarcinoma cells showed reduced proliferation and colony formation, with G0/G1 cell cycle arrest and decreased expression of Cyclin D1, CDK6 and CDK2. This is in vitro evidence only, with no clinical data. Regarding surgical strategy, an authors’ response to a prior study defends the value of investigating lobectomy versus segmentectomy for stage I acinar and papillary predominant tumours, citing acceptable intraoperative frozen section accuracy for acinar pattern (sensitivity 87.6%, specificity 65.4%) and papillary predominant tumours (sensitivity 50%, specificity 96.6%). They acknowledge that chemotherapy data from the SEER database are incomplete, and cite evidence that adjuvant chemotherapy did not improve disease-specific survival or recurrence in stage IB patients without solid or micropapillary patterns, nor in those with minor solid or micropapillary components, after propensity-score matching.

What remains missing is prospective validation of the lepidic proportion and acinar size thresholds as reproducible clinical tools, and confirmation of the surgical equivalence findings in other centres. The dabrafenib and trametinib result in class III BRAF is a single anecdote requiring larger series. The neoadjuvant targeted therapy data come from only 24 patients with short follow-up and no comparator arm. No randomised trial has yet established whether neoadjuvant targeted therapy improves survival over surgery alone in EGFR-mutant resectable disease, and the SUN1 findings have not progressed beyond cell lines.