Bronchial Artery Interventional Therapy and Sequential Radiotherapy in the Treatment of Non-resectable, Non-metastatic Central-type Squamous Lung Cancer
Central-type lung cancer refers to lung malignancies originating from the segmental bronchi and above. The most common tissue type is squamous cell carcinoma. Patients often present with cough, hemoptysis, hoarseness and also some critical conditions including superior vena caval obstruction syndrome. Therefore, effective treatment should be implemented as early as possible to rapidly reduce tumor burden and control the progression of the disease. Most of the central-type NSCLC are classified into T3-4, N1-2 stage and are non-resectable. The PACIFIC study changed the standard treatment model for inoperable locally advanced lung cancer with synchronous chemoradiotherapy and sequential PD-L1 immunotherapy. In clinical practice, Chinese patients often failed to finish concurrent chemoradiotherapy for high toxicity. In addition, combination with PD-1/PD-L1 inhibitors increased the risk of immune related pneumonia. Bronchial artery infusion (BAI), that directly infused drugs (chemo and PD-1 inhibitor) through tumor-nourishing arteries, has potential advantages in the treatment of central-type lung cancer. The drug concentration in tumor region increased to potentiate the antitumoral effect and also reduced the systemic adverse reactions. In this study, bronchial artery interventional therapy is conducted with precedence. The protocol for bronchial artery intervention includes infusion of chemo and PD-1 inhibitor followed by bronchial artery embolism (Chemo-Immulo-embolization via Tumor arterial, CIETAI). Followed CIETAI, two cycles of chemo/PD-1 therapy are planned to carried out before radiotherapy. After radiotherapy, maintenance PD-1 inhibitor are initiated for 1 year or until progression.
• Patients volunteered to participate in the study and signed the informed consent.
• Age 18-80, both male and female.
• Histologically or cytologically confirmed squamous lung cancer staging T3-4, Nany, and M0 (according to the American Joint Committee on Cancer Staging (AJCC) 2017 Edition 8 TNM Staging System). Central-type classified according to chest imaging or bronchoscopy.
• At least one measurable lesion according to RECIST 1.1.
• ECOG PS 0-1.
• Expected survival ≥ 6 months.
• Patients who never received systemic therapy in the past, including radiotherapy, chemotherapy, targeted therapy and immunotherapy, or patients who relapsed more than 6 months after adjuvant chemotherapy.
• The main organ functions accorded with the following criteria within 7 days before treatment:
‣ Blood routine examination ( without blood transfusion in 14 days): hemoglobin (HB) ≥ 90 g/L; neutrophil absolute value (ANC) ≥ 1.5 \*109/L; platelet (PLT) ≥80 \*109/L.
⁃ Biochemical tests should meet the following criteria: 1) total bilirubin (TBIL) ≤1.5 times of upper limit of normal (ULN); 2) alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 \*ULN, if accompanied by liver metastasis, ALT and AST ≤ 5\* ULN; 3) serum creatinine (Cr) ≤ 1.5\* ULN or creatinine clearance rate (CCr) ≥ 60 ml/min;4) Serum albumin (≥35g/L). (3) Doppler echocardiography: left ventricular ejection fraction (LVEF) ≥the low limit of normal value (50%).
• Tissue samples should be provided for biomarker analysis (such as PD-L1) Patients who could not provide new tissues could provide 5-8 paraffin sections of 3-5 μm by archival preservation. Blood sample should be collected at a pre-specified time point to complete the continuous dynamic MRD analysis. (non-mandatory).