Sub-lobectomy vs Lobectomy in IIA-IIIB NSCLC After Neoadjuvant IO+Chemo

Sub-lobectomy Versus Lobectomy in IIA-IIIB Non-small-cell Lung Cancer After Neoadjuvant Immunochemotherapy: a Multicentre, Open-label, Randomised, Controlled, Non-inferiority Trial

This study is a prospective, randomized controlled multicenter clinical trial. The study population consisted of non-small cell lung cancer（NSCLC） patients in stage IIA-IIIB (IASLC 9th edition) who received immunotherapy combined with platinum based dual drug chemotherapy before neoadjuvant therapy and were evaluated by the committee to be feasible for sub lobectomy R0 resection. After entering the study, they were randomly divided into a sub lobectomy group (study group) and a lobectomy group (control group). Follow up will be conducted after surgery.

The study includes screening/baseline period, perioperative period, and follow-up period.

Screening/Baseline Period: The screening period is 28 days prior to receiving surgery. After the patient signs the informed consent form (ICF), the inclusion and exclusion criteria are reviewed during the screening/baseline period to include patients who meet the inclusion and exclusion criteria, with specific reference to the inclusion and exclusion criteria. During the screening period of this study, if laboratory and imaging tests that do not meet the inclusion criteria are found during the first screening, patients are allowed to undergo re examination and re screening. When re screening, informed consent must be signed and a new participant screening number must be obtained through re registration.

Perioperative period: During the perioperative period, patients were randomized into a sub lobectomy group (study group) and a lobectomy group (control group). The research group used thin-layer CT imaging and 3D reconstruction to accurately plan the surgical resection range before surgery, and underwent subpulmonary lobectomy+hilar/mediastinal lymph node dissection; The control group patients underwent direct lobectomy and lymph node dissection of the pulmonary hilum/mediastinum.

Follow up period: The follow-up period includes a safety follow-up period and a survival follow-up period. Safety follow-up will be conducted 30 days (+5 days) after surgery or before receiving the first postoperative adjuvant therapy medication. Survival follow-up will be conducted every 3 months (± 14 days) in the first year after surgery and every 6 months (± 14 days) in the second year after surgery. Participants' chest CT scan results, survival status, follow-up anti-tumor treatment, and drug-related SAEs (including lung function tests at 6 months, 12 months, and 3 years after surgery) will be collected until the 3-year follow-up time/(participant death, loss to follow-up, voluntary withdrawal from clinical study, or end of study) (whichever occurs first). The research plan can be found in the research flowchart.

Main objective:

Evaluate the prognostic differences between sub lobectomy and lobectomy in NSCLC patients after neoadjuvant immunotherapy and chemotherapy;

Secondary objective:

1. Evaluate the lung function preservation of NSCLC patients after neoadjuvant immunotherapy and chemotherapy with sub lobectomy compared to lobectomy; Evaluate the safety of sub lobectomy compared to lobectomy in NSCLC patients after neoadjuvant immunotherapy and chemotherapy, including postoperative complications, length of hospital stay, etc; Evaluate the postoperative quality of life of NSCLC patients after neoadjuvant immunotherapy and chemotherapy with sub lobectomy compared to lobectomy.

Inclusion Criteria:

• Voluntarily participate in the research and sign an informed consent form;
• Age ≥ 18 years old,<75 years old, both male and female;
• The physical fitness status score of the Eastern Cooperative Oncology Group (ECOG) in the United States is 0 or 1;
• Expected survival period ≥ 12 months;
• Peripheral non-small cell lung cancer (NSCLC) confirmed by histology/pathology, with TNM staging of IIA~IIIB before neoadjuvant therapy (IASLC 9th edition), without known EGFR mutations/ALK rearrangements;
• No solid lesions involving different lung lobes;
• No history of ipsilateral open chest surgery;
• Prior to enrollment, the patient has received 2-4 cycles of neoadjuvant therapy, which includes PD-1/PD-L1 inhibitors and platinum based dual drug chemotherapy;
• Having sufficient organ function
• According to the researcher's assessment, the cardiovascular and pulmonary function meets the criteria for accepting surgery; The forced expiratory volume in the first second (FEV1) of the lung function test should be at least 1.5 L or the diffusion volume of carbon monoxide (DLCO) in the lungs should be at least 40%; The researchers determined that there was no other impact on the heart and lung function impairment during the surgery;
• Based on preoperative CT diagnosis, the distance between the tumor and the bronchial opening is greater than 2cm;
• After evaluation by the evaluation committee, the lesion can be treated with sub lobe R0 resection after neoadjuvant therapy.

Exclusion Criteria:

• Expected intolerance to lobectomy;
• Received chest radiation therapy before starting surgical treatment;
• Have undergone allogeneic tissue/solid organ transplantation;
• Diagnosed with autoimmune disease or undergoing long-term systemic steroid therapy (prednisone or equivalent dosage exceeding 10 mg/day) or any other form of immunosuppressive therapy within 3 months prior to surgery;
• There is a history of interstitial lung disease (non infectious) that requires steroid treatment or currently has interstitial lung disease that requires steroid treatment;
• Viral infectious disease in screening period:

Positive for human immunodeficiency virus (HIV) serum reaction; Active hepatitis B: Hepatitis B virus surface antigen (HBsAg) positive and HBV-DNA quantitative detection>500 IU/mL or>2000 copies/mL; Active hepatitis C: Hepatitis C (HCV) antibody positive and HCV-RNA quantitative detection above the upper limit of normal;

• Hypertension participants with poor drug treatment control are defined as systolic blood pressure>150 mmHg or diastolic blood pressure>90 mmHg (it is allowed to adjust the treatment of hypertension drugs before the start of the study, but the average value of the latest three consecutive blood pressure records before enrollment in the study should be ≤ 150/90 mmHg) (each measurement should be at least 2 minutes apart);
• During screening, there are still active infections that require intravenous anti infective treatment;
• Other malignant tumors, excluding cured skin basal cell cancer, cervical or breast cancer in situ, superficial bladder cancer cancer, localized prostate cancer, etc., within 3 years before signing the informed consent; Participants with low-risk early prostate cancer (T1-T2a stage, Gleason score ≤ 6, PSA<10 ng/mL) who have received curative treatment or are under active monitoring with stable condition, regardless of whether they have received treatment, are allowed to be enrolled;
• There are situations that may interfere with the interpretation of research results or may affect participants' ability to complete the entire research process, or based on the judgment of the treatment researcher, participation in the research is not in the best interests of the participants;
• Pregnancy, lactation, or planned pregnancy; Positive blood pregnancy test within 7 days prior to the first study treatment;
• Participants have poor compliance and are unwilling or unable to follow the research protocol.