# Divergent outcomes of neoadjuvant therapy for locally advanced small-cell lung cancer: two cases report and literature review

## TL;DR

Two patients with advanced small-cell lung cancer had very different outcomes after the same treatment, highlighting the importance of genetic testing for personalized care.

## Contribution

The study presents two distinct clinical outcomes linked to genetic changes, emphasizing the role of genetic testing in guiding treatment.

## Key findings

- Case 1 achieved a complete response with reduced tumor mutations after treatment.
- Case 2 showed disease progression with increased tumor mutations despite the same therapy.
- Genetic testing before and after treatment revealed critical differences in molecular profiles.

## Abstract

This article reports two cases of stage IIIB small cell lung cancer (SCLC) patients who underwent neoadjuvant immunotherapy combined with chemotherapy, resulting in markedly different clinical outcomes, and explores the potential molecular mechanisms behind these differences. Both patients were diagnosed with stage IIIB small cell lung cancer through imageological examination and CT-guided percutaneous lung biopsy. They received three cycles of neoadjuvant treatment with “etoposide + carboplatin + serplulimab” followed by surgical resection of the lesions. Genetic testing for solid tumors was conducted before and after treatment. The results showed that Case 1 exhibited multiple gene mutations, including FBXW7 and KRAS, with a tumor mutational burden (TMB) of 17.65 muts/Mb before treatment. After neoadjuvant therapy, only the PTEN mutation remained, and TMB decreased to 0.00 muts/Mb, with no cancer cells observed in the postoperative pathology, leading to an assessment of pathological complete response (pCR). In contrast, Case 2 showed MET and PTEN mutations and MYC gene amplification both before and after treatment, with TMB increasing from 23.72 muts/Mb to 28.13 muts/Mb, resulting in an assessment of disease progression (PD) post-surgery. This study emphasizes the potential value of neoadjuvant therapy in locally advanced SCLC patients and highlights the importance of genetic testing in predicting treatment responses and guiding personalized treatment strategies. Further research is needed to explore more effective therapeutic strategies to improve the prognosis of SCLC patients.