An 50-year-old male was admitted to hospital on August 22th, 2021 for cough and expectoration without obvious cause. He had 35 years history of smoking a pack a day, and history of drinking 100ml/day. He had no history of infectious diseases such as dysentery, malaria, viral hepatitis or tuberculosis. His father died of esophageal cancer, denying a family history of the disease.
As the timeline of the clinical course in this patient ( Supplementary Figure 1 ), On August 23th, 2021, a positron emission tomography-computed tomography (PET-CT) revealed a large cystic solid lesion (8.6 x 5.9 x 9.9 cm) in the lung field from the right hilum to the right upper lobe, which was considered to be a right thoracic malignant tumor. The lesion invaded mediastinum adjacent superior vena cava and main right pulmonary artery. Additionally, multiple enlarged lymph nodes were observed in both hilum, mediastinum and right supraclavicular fossa, with the largest being 1.5x1.4 cm, with mild to moderate increase in metabolism, which was considered as multiple lymph node inflammation ( Figure 1A ). On August 26th, 2021, an electronic bronchoscopy revealed stenosis of the right upper lobe opening and obstruction of the lumen by necrotic material ( Figure 1B ). An electronic bronchoscopy biopsy of the superior lobe of right lung led to a pathological diagnosis of PSC ( Figure 1C ). The malignancy was consistent with stage III (cT4N0M0) disease. Upon NGS analysis of the biopsy tissue sample, the patient was identified to harbor EGFR mutations (EGFR exon21 p.L861Q, EGFR exon18 p.G719C) ( Supplementary Figure 2 ), TP53 mutation (exon8 p.R273C), BCORL1 amplification, and CCNE1 amplification. In addition, the patient was identified as having microsatellite stable (MSS) and tumor mutation burden (TMB) of 6.15Muts/Mb by NGS. In addition, immunohistochemistry (IHC) for PD-L1 was strong positive (TPS=80%).
Considering the patient's PET-CT results showed that the tumor was large and adjacent to the mediastinum and main pulmonary artery, which made it difficult to resect. The patient had no indications for surgery, and chemotherapy plus immunotherapy (albumin paclitaxel 400mg d1+ cisplatin 90mg dl+ tislelizumab 200mg dl) was subsequently started on September 4th and September 30th, 2021. After two cycles of chemotherapy plus immunotherapy, on October 27, 2021, a chest computed tomography (CT) scan showed that the size of the lesion in the lung field from the right hilum to the right upper lobe was 6.6 x 4.6 x 6.0 cm, and the largest enlarged lymph node was 1.5 x 1.3 cm, but the lesion was still close to the mediastinum and the main pulmonary artery, which was difficult to be surgically removed ( Figure 2A ). In addition, the patient's transaminase increased during the treatment period, indicating abnormal liver function, liver protection treatment returned to normal after a period of time. Moreover, it has been reported that immunotherapy may cause abnormal liver function in NSCLC patients, in which transaminases are increased. Considering that immunotherapy may cause liver injury, immunization was discontinued. Immediately after, the patient received chemotherapy plus EGFR-TKI (albumin paclitaxel 400mg d1+ cisplatin 50mg dl+ osimertinib 30mg dl-14) on October 30th, 2021. On December 6, 2021, after one cycle of chemotherapy plus EGFR-TKI, a chest CT scan showed that the size of the lesion in the lung field from the right hilum to the right upper lobe was 6.6 x 4.6 x 6.0 cm, and the largest enlarged lymph node was 1.7 x 0.8 cm ( Figure 2B ). After chemotherapy plus EGFR-TKI treatment, there was a gap between the lesion and the mediastinum, as well as between the lesion and the right pulmonary trunk, indicating that the lesion may be resected by surgery. Since no obvious contraindications were found, the patient underwent thoracoscopic radical resection of right upper lung cancer on December 15th, 2021. Postoperative pathology showed no residual tumor cells in the right upper lung lesion, no residual tumor cells in the resection margins of the trachea and blood vessels, and no tumor metastasis in the lymph nodes, reached pathological complete response (pCR) ( Figure 3 ). On February 27th and May 23th, 2022, about 2.5 months and 5.5 months after surgical resection, chest CT scan showed no evidence of malignant tumor recurrence ( Figures 4A, B ).