A stage IV lung squamous cell cancer patient with brain metastases, high PD-L1 & TMB, achieves pCR and long-term survival after immune-chemotherapy and radical surgery: a case report and literature review
Brain metastases occur in 40% of advanced NSCLC patients, with poorer prognosis in squamous subtypes. Immune checkpoint inhibitors (ICIs) combined with chemotherapy have revolutionized treatment, yet data on the systematic treatment of stage IV squamous non-small cell lung cancer with surgery remain...
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1601125/full |
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| author | Xiangyu Xu Zheng Ma |
| author_facet | Xiangyu Xu Zheng Ma |
| author_sort | Xiangyu Xu |
| collection | DOAJ |
| description | Brain metastases occur in 40% of advanced NSCLC patients, with poorer prognosis in squamous subtypes. Immune checkpoint inhibitors (ICIs) combined with chemotherapy have revolutionized treatment, yet data on the systematic treatment of stage IV squamous non-small cell lung cancer with surgery remain limited. A 59-year-old male smoker presented with stage cT4N2M1b IVA squamous NSCLC and a solitary brain metastasis. Next-generation sequencing revealed programmed cell death ligand 1 (PD-L1) high expression (TPS=75%) and TMB-High (28.49 Mut/Mb) without driver mutations. After pembrolizumab plus platinum-based chemotherapy induced conversion therapy for 3 cycles, the brain lesion achieved pathological complete response (pCR) following resection, while the primary lung tumor showed major pathological response (MPR) post-surgery. Postoperative adjuvant chemoimmunotherapy and 2-year pembrolizumab maintenance were administered. Serial circulating tumor DNA (ctDNA) monitoring remained negative, with no recurrence observed over 50 months. This is the first reported case of long-term survival (PFS >50 months) in a PD-L1-high/TMB-High squamous NSCLC patient with brain metastasis treated with immunotherapy-based multimodal therapy. Our findings suggest that biomarker-guided strategies integrating systemic therapy, surgery, and MRD monitoring may enable curative potential in select advanced NSCLC patients. Further studies are warranted to validate this “sandwich” approach (drug-surgery-drug) and optimize treatment duration. |
| format | Article |
| id | doaj-art-76461ee7dccd4560b67a8be8a8f7e3f7 |
| institution | Matheson Library |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj-art-76461ee7dccd4560b67a8be8a8f7e3f72025-07-22T07:59:52ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-07-011610.3389/fimmu.2025.16011251601125A stage IV lung squamous cell cancer patient with brain metastases, high PD-L1 & TMB, achieves pCR and long-term survival after immune-chemotherapy and radical surgery: a case report and literature reviewXiangyu XuZheng MaBrain metastases occur in 40% of advanced NSCLC patients, with poorer prognosis in squamous subtypes. Immune checkpoint inhibitors (ICIs) combined with chemotherapy have revolutionized treatment, yet data on the systematic treatment of stage IV squamous non-small cell lung cancer with surgery remain limited. A 59-year-old male smoker presented with stage cT4N2M1b IVA squamous NSCLC and a solitary brain metastasis. Next-generation sequencing revealed programmed cell death ligand 1 (PD-L1) high expression (TPS=75%) and TMB-High (28.49 Mut/Mb) without driver mutations. After pembrolizumab plus platinum-based chemotherapy induced conversion therapy for 3 cycles, the brain lesion achieved pathological complete response (pCR) following resection, while the primary lung tumor showed major pathological response (MPR) post-surgery. Postoperative adjuvant chemoimmunotherapy and 2-year pembrolizumab maintenance were administered. Serial circulating tumor DNA (ctDNA) monitoring remained negative, with no recurrence observed over 50 months. This is the first reported case of long-term survival (PFS >50 months) in a PD-L1-high/TMB-High squamous NSCLC patient with brain metastasis treated with immunotherapy-based multimodal therapy. Our findings suggest that biomarker-guided strategies integrating systemic therapy, surgery, and MRD monitoring may enable curative potential in select advanced NSCLC patients. Further studies are warranted to validate this “sandwich” approach (drug-surgery-drug) and optimize treatment duration.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1601125/fullnon-small cell lung cancer (NSCLC)brain metastasisprogrammed cell death ligand 1tumor mutational burden (TMB)pathological complete response (PCR)circulating tumor DNA (ctDNA) |
| spellingShingle | Xiangyu Xu Zheng Ma A stage IV lung squamous cell cancer patient with brain metastases, high PD-L1 & TMB, achieves pCR and long-term survival after immune-chemotherapy and radical surgery: a case report and literature review Frontiers in Immunology non-small cell lung cancer (NSCLC) brain metastasis programmed cell death ligand 1 tumor mutational burden (TMB) pathological complete response (PCR) circulating tumor DNA (ctDNA) |
| title | A stage IV lung squamous cell cancer patient with brain metastases, high PD-L1 & TMB, achieves pCR and long-term survival after immune-chemotherapy and radical surgery: a case report and literature review |
| title_full | A stage IV lung squamous cell cancer patient with brain metastases, high PD-L1 & TMB, achieves pCR and long-term survival after immune-chemotherapy and radical surgery: a case report and literature review |
| title_fullStr | A stage IV lung squamous cell cancer patient with brain metastases, high PD-L1 & TMB, achieves pCR and long-term survival after immune-chemotherapy and radical surgery: a case report and literature review |
| title_full_unstemmed | A stage IV lung squamous cell cancer patient with brain metastases, high PD-L1 & TMB, achieves pCR and long-term survival after immune-chemotherapy and radical surgery: a case report and literature review |
| title_short | A stage IV lung squamous cell cancer patient with brain metastases, high PD-L1 & TMB, achieves pCR and long-term survival after immune-chemotherapy and radical surgery: a case report and literature review |
| title_sort | stage iv lung squamous cell cancer patient with brain metastases high pd l1 tmb achieves pcr and long term survival after immune chemotherapy and radical surgery a case report and literature review |
| topic | non-small cell lung cancer (NSCLC) brain metastasis programmed cell death ligand 1 tumor mutational burden (TMB) pathological complete response (PCR) circulating tumor DNA (ctDNA) |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1601125/full |
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