Spontaneous regression of recurrent pulmonary large cell neuroendocrine carcinoma with alteration of PD-L1 expression after surgical resection: A case report.

Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare and aggressive subtype of non-small cell lung cancer with a poor prognosis. Spontaneous regression, that is, partial or complete disappearance of a malignancy without medical intervention, is extremely rare in LCNEC. Herein, we present a case of spontaneous complete regression in a 71-year-old male patient with recurrent LCNEC after surgical resection. The patient was diagnosed with stage IB LCNEC and underwent surgical resection. At 1-year follow-up, chest computed tomography revealed a recurrent lesion next to the stump site and enlargement of lymph nodes 4R and 7; recurrent LCNEC was confirmed. The patient declined chemoradiation therapy. One year after recurrence, the patient experienced severe multifocal necrotizing pneumonia and was treated with antibiotics, resulting in a gradual decrease in the size of the recurrent lesion. Five years after the initial diagnosis, positron emission tomography/computed tomography revealed no hypermetabolic lesions, indicating the spontaneous complete regression of LCNEC.

Dynamic changes in pathology and PD-L1 expression in a patient with metastatic lung adenocarcinoma who received pembrolizumab therapy followed by two salvage surgeries two years later: A case report.

During chemotherapy, certain cancer cells undergo cell death, which alters the properties of remaining cells and leads to numerous changes in the constituent cells of lung cancer. Immunotherapy has been used as neoadjuvant therapy, and several studies have reported changes in lung cancer tissue following treatment with immuno-anticancer drugs in early stage disease. However, no research has currently discussed the pathological and PD-L1 expression changes in metastatic lung cancer. Here, we describe a patient with lung adenocarcinoma and multiple metastases who achieved complete remission after receiving initial carboplatin/pemetrexed followed by pembrolizumab treatment for 2-years. The initial biopsy revealed adenocarcinoma with high PD-L1 expression, and next-generation sequencing (NGS) identified KRAS, RBM10, and STAG2 mutations. After 2-years of treatment with pembrolizumab, the patient achieved complete response (CR). The patient underwent first salvage surgery for the oligo-relapse lesion, and the pathology result showed a large cell neuroendocrine tumor (NET) with adenocarcinoma and no PD-L1 expression. NGS revealed KRAS and TP53 mutations. After one year, a chest computed tomography (CT) scan revealed a small nodule in the right lower lobe, and the patient underwent second salvage surgery. Pathology results showed minimally invasive adenocarcinoma with no PD-L1 expression and no significant genetic mutations. This case report demonstrates the dynamic changes cancer cells undergo following pembrolizumab treatment and salvage surgeries and is the first report to compare pathological changes after immunotherapy and two subsequent salvage surgeries in metastatic lung adenocarcinoma. Clinicians must remain vigilant to these dynamic changes throughout treatment and consider salvage surgery for oligo-relapse lesions. By understanding these changes, new strategies can be developed to improve the long-term efficacy of immunotherapy.

Plasma GDF15 levels associated with circulating immune cells predict the efficacy of PD-1/PD-L1 inhibitor treatment and prognosis in patients with advanced non-small cell lung cancer.

PURPOSE: Although increased plasma growth differentiation factor-15 (GDF15) levels have been reported in patients with various cancers, the predictive role of PD-1/PD-L1 inhibitors in advanced cancers remains unknown. This study aimed to investigate GDF15 levels as a predictive marker in advanced non-small cell lung cancer (NSCLC) treated with PD-1/PD-L1 inhibitors and analyze their association with immune cell populations. METHODS: This study included 87 patients with advanced NSCLC receiving anti-PD-1/PD-L1 inhibitors between March 2018 and May 2020. Blood samples were obtained immediately before and months after PD-1/PD-L1 inhibitor administration. RESULTS: The objective response rate (ORR) was significantly higher in the low GDF15 than in the high GDF15 group (39.2% vs. 15.3%, P = 0.013). The median progression-free survival (PFS) was significantly longer in the low GDF15 than in the high GDF15 group (13.2 [95% CI 7.6-18.9] vs. 7.2 [95% CI 4.8-9.6] months, P = 0.048). Moreover, plasma GDF15 levels negatively correlated with PD-1+/CD8+ T cells (r = - 0.399, P = 0.003) and positively with PD-1+/Treg cells (r = 0.507, P < 0.001) and PD-1+Treg/CD4+ T cells (r = 0.439, P < 0.001). The ORR was significantly higher in the group with decreased GDF15 from baseline than in the increased GDF15 group (37.2% vs. 10.0%, P = 0.026). The median PFS was significantly longer in the decreased GDF15 group (14.8 [95% CI 10.4-19.2] vs. 5.9 [95% CI 2.8-9.0] months, P = 0.002). Plasma GDF15 levels were associated with PD-1+CD8+ T cells and PD-1+ Treg cells. CONCLUSION: Plasma GDF15 could be a potential biomarker for predicting the efficacy and survival benefit of immunotherapy in advanced NSCLC.