Discussion
NSCLC, tumor, triple-negative breast cancerThis
TUMOR, EX19DEL, SECONDARY, NSCLC, REGRESSION
For advanced NSCLC + , To our knowledge, the ORR of locally advanced NSCLCm+ treated with first-generation Furthermore, the number of NAT cycles and the role of surgery in inoperable stage III patients are crucial issues. The optimal number of neoadjuvant treatment cycle need to be addressed for inoperable stage III patients. In this trial, patients who received more than 2 cycles of neoadjuvant therapy demonstrated higher ORR (94% vs 69%), greater radiological regression of targeted lesions (45% vs 39%), and a higher rate of pathological tumor regression (59% vs 41%) compared to those who received only 2 cycles of NAT. These results suggest that extending the duration of NAT may improve efficacy. There is ongoing debate regarding surgical treatment for inoperable NSCLC patients who show downstaging after induction therapy, even if salvage surgery can improve the prognosis of these patientsBased on the findings of the CheckMate-816 studyBased on the distinct responses observed in Ex19Del and L858R NSCLC, they can be considered as two different diseasesThe T790M mutation has been identified as the primary mechanism of secondary resistance to first and second-generation ICIs-based immune therapy has become the standard therapy for advanced and locally advanced NSCLC, regardless of immune status such as PD-L1 expression and TME characteristics, and has shown excellent efficacy when combined with chemotherapyPrimary resistance to We identified CISH as a molecular biomarker for predicting Afatinib response. Previous studies have reported diverse functions of CISH in different cell types. In T lymphocytes, CISH is induced after TCR stimulation and has been implicated as a good prognostic factor in triple-negative breast cancerThis study has several limitations that should be acknowledged. Firstly, being a single-arm study, it was not possible to directly compare the efficacy of neoadjuvant treatment between Afatinib and other regimens. A randomized controlled trial with a larger sample size would be necessary for such comparisons. Secondly, being a single-center study, the evidence generated may be limited in its generalizability, and external validation through multicenter research is warranted to confirm the findings. Thirdly, the regimens of adjuvant therapy after complete resection have not been explored in locally advanced NSCLCm+, and this could potentially impact patient prognosis. Fourthly, due to the relatively short follow-up period, the relationship between ORR and prognosis could not be fully assessed. Fifthly, the sample size of paired longitudinal RNA-seq data is small. Therefore, the findings regarding TME changes need to be confirmed by other independent studies. Last, further investigations using WES and TCR sequencing would provide additional insights and should be considered in future studies. Overall, while the results are promising, the efficacy of neoadjuvant Afatinib therapy awaits validation with on long-term follow-up data, which is an important aspect for future research.In conclusion, Afatinib as a single-agent neoadjuvant therapy for stage III 