Neoplasms

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Antineoplastic Agents

All Drugs and Chemicals

Central Nervous System Depressants

Paclitaxel

Albumin-Bound Paclitaxel

Anesthetics

Immune Checkpoint Inhibitors

Cisplatin

Immunomodulating Agents

Immunologic Factors

1. Phase I:

1. Chemo-Immulo-embolization via Tumor Arterial, CIETAI:

   DSA guided tumor artery infusion of nano-paclitaxel 200 mg+PD-1 inhibitor (Tirelizumab) 200mg, followed by gelatin sponge particles (350-560um) embolization
2. two cycles of chemotherapy combined with immune checkpoint inhibitors (q3w): Nano-paclitaxel 260 mg/m2, d1, ivgtt; Cisplatin 75mg/m2, d1, ivgtt; PD-1 inhibitor (Tirelizumab) 200mg, d1, ivgtt, 30-60min 2. phase II: Chest radiotherapy: 60Gy/2Gy/30f 3. phase III: PD-1 inhibitor (Tirelizumab) 200mg, d1, ivgtt, 30-60min Maintenance for 1 year

After successful anesthesia, right femoral artery puncture was performed by Seldinger method. 5F-Yashrio catheter is chosen to locate the bronchial artery of the diseased side at the level of the thoracic aortotracheal bifurcation. Angiography was performed (Osu 300mg/ml, 3ml/s, total 8ml, 200Psi) to visualize tumor blood supply artery before infusion of chemo+PD-1 inhibitor and embolism.

bronchial artery interventional therapy

Nano-paclitaxel 260 mg/m2, d1, ivgtt, q3w+Cisplatin 75mg/m2, d1, ivgtt,q3w.

Chemotherapy drug

IMRT

PD-1 inhibitor (Tirelizumab) 200mg, d1, ivgtt, 30-60min, q3w.

Immunotherapy

Dong Wang, ph.D

Dong Wang, PH.D.

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.

PD-1/PD-L1 immune checkpoint inhibitor (ICI), which has been introduced in the treatment of lung cancer, gastric cancer, colorectal cancer and other solid tumors, changed the strategy of cancer treatment. The more widely biomarkers for its efficacy include tumor PD-L1 proportional score (TPS), tumor mutation burden (TMB), DNA mismatch repair defect (dMMR), genomic instability (MSI-H) which were used to assess PD-L1 expression in tumor cells and the presence and density of T cells in the tumor microenvironment (TME). However, the overall efficacy of PD-1/PD-L1 remain unsatisfactory. To increase the concentration of PD-1/PD-L1 inhibitor in tumor and TME is a potential strategy to increase the efficacy. In this study, perfusion of PD-1/PD-L1 via bronchial arterial was harnessed to maximize the concentration of drugs in the tumor. We proposed a surgical procedure called Chemo-Immuno-embolization via Tumor Arterial Intervention (CIETAI). This study mainly included inoperable patients with central-type lung squamous cell carcinoma who received CIETAI at the initial treatment, followed by radiotherapy and PD-1/PD-L1 maintenance.

CIETAI and Sequential Radiotherapy in Squamous Lung Cancer

Bronchial Artery Interventional Therapy and Sequential Radiotherapy in the Treatment of Non-resectable, Non-metastatic Central-type Squamous Lung Cancer

ctDNA MRD detection by liquid biopsy change during treatment

MDT to discuss surgery after phase I treatment and phase II treatment

complete response(CR)+partial response(PR) according to RECIST 1.1

NSCLC related symptoms evaluated by NSCLC-SAQ v1.0

progression-free survival is defined as the time from enrollment to the date of first document disease progression or death from any cause

overall survival is defined as the time from randomization to death from any cause

Summary of the adverse events experienced by study participants as evaluated by Common Terminology Criteria for Adverse Events (CTCAE) v5.0

Spots Global Cancer Trial Database for bronchial artery interventional therapy