Safety, Efficacy, and Survival Outcomes of Neoadjuvant/Induction Immunotherapy in Surgical and Radiotherapeutic Management of Non-Small Cell Lung Cancer

Safety, Efficacy, and Survival Outcomes of Neoadjuvant/Induction Immunotherapy in Surgical and Radiotherapeutic Management of Non-Small Cell Lung Cancer: A Multicenter Real-World Study

This multicenter retrospective real-world study aims to evaluate the safety, efficacy and survival outcomes of neoadjuvant/induction immunotherapy in patients with non-small cell lung cancer (NSCLC). The study covers diverse treatment pathways, including surgery, definitive radiotherapy, and non-surgical strategies. It addresses gaps in existing trials by establishing a comprehensive cohort spanning neoadjuvant/induction therapy, perioperative management, and follow-up, providing real-world evidence to support treatment decisions in both operable and inoperable cases.

Study Overview

• Status: Recruiting
• Conditions: Radiotherapy; Neoadjuvant Immunotherapy; Lung Surgery; Lung Cancer (NSCLC)
• Intervention / Treatment: Drug: neoadjuvant immunotherapy

Detailed Description

Lung cancer is the leading cause of cancer-related deaths in both China and the world. In recent years, neoadjuvant immunotherapy has achieved breakthrough advancements in the treatment of non-small cell lung cancer (NSCLC). Evidence from multiple Phase III randomized controlled trials (RCTs), such as CheckMate 816, KEYNOTE-671, and AEGEAN, has demonstrated clear benefits of this therapy in improving survival. However, these studies exhibited several limitations: first, stringent selection criteria resulting in limited heterogeneity among participants challenge the generalizability of their conclusions; Second, some studies and clinical observations have preliminarily suggested that neoadjuvant immunotherapy may increase technical surgical difficulty; however, large-sample, real-world data on its perioperative safety remain limited; third, clinical practice involves numerous borderline resectable and unresectable cases, leading to highly complex treatment decisions (such as timing of surgical intervention after conversion therapy, radiotherapy strategies, etc.), with none of the existing guidelines reach clear consensus.

This study employs a multicenter real-world design, establishing a retrospective cohort covering from neoadjuvant/induction therapy period to the surveillance period. It evaluates the safety, efficacy, and survival outcomes of neoadjuvant/induction immunotherapy across diverse treatment strategies including both surgery and radiotherapy, providing real-world evidence to inform clinical decision-making.

• Study Type: Observational
• Enrollment (Estimated): 500

Contacts and Locations

• Study Contact: Name: Nan Wu, MD; Phone Number: 0086-10-88196569; Email: nanwu@bjmu.edu.cn

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100142
      • Recruiting
      • Peking University Cancer Hospital & Institute
      • Contact: Nan Wu, MD; Phone Number: 0086-10-88196569; Email: nanwu@bjmu.edu.cn
      • Contact: Nan Wu, MD
    • Beijing, Beijing, China
      • Recruiting
      • Peking University Third Hospital
      • Contact: Guangliang Qiang, MD; Phone Number: 86-010-82267600; Email: pkudd@bjmu.edu.cn
      • Contact: Guangliang Qiang, MD
  • Inner Mongolia
    • Hohhot, Inner Mongolia, China
      • Recruiting
      • Inner Mongolia Hospital of Peking University Cancer Hospital
      • Contact: Bateer Han, MD; Phone Number: 86-13948120033; Email: hanbateer_2004@163.com
      • Contact: Bateer Han, MD
  • Yunnan
    • Kunming, Yunnan, China
      • Recruiting
      • The Third Affliated Hospital of Kunming Medical University
      • Contact: Yujie Lei, MD; Phone Number: 86-0871-68173760; Email: 583271025@qq.com
      • Contact: Yujie Lei, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

This study will include real-world patients diagnosed with stage IA-IIIC non-small cell lung cancer (NSCLC) who received at least one cycle of neoadjuvant immunotherapy (with or without chemotherapy). According to surgical evaluation, patients eligible for inclusion were assessed as either resectable or potentially resectable before treatment. Subsequent treatment following the neoadjuvant therapy may include surgical resection, radiotherapy, or non-localized therapy.

Description

Inclusion Criteria:

1. Histologically confirmed non-small cell lung cancer (NSCLC), regardless of the presence of EGFR or ALK sensitive driver gene mutations;
2. Clinical staging of IA-IIIC according to the AJCC 8th Edition before neoadjuvant treatment;
3. Received at least one cycle of neoadjuvant immunotherapy (with or without chemotherapy);
4. Assessed as resectable or potentially resectable by surgical experts prior to treatment.

Exclusion Criteria:

1. Confirmed M1 disease;
2. History of previous lung malignancy or other metastatic malignant tumors;
3. Participation in other randomized controlled trials involving neoadjuvant treatment;
4. Significant missing clinical data.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Technical Dissection Difficulty (TDD) Rate	Defined as the intraoperative presence of fibrosis and/or tight adhesion between lymph nodes and surrounding structures around the hilar and fissure. TDD is considered present if either fibrosis or significant adhesion is noted, potentially increasing surgical complexity. Surgical difficulty is assessed based on operative reports and predefined intraoperative criteria, as documented by the operating surgeon.	During the radical surgery (Day 0 of surgery)
Disease-Free Survival (DFS)	Defined as the time from the date of radical surgery to the first occurrence of disease recurrence, progression, or death from any cause. Patients without an event will be censored at the date of the last follow-up. Disease status is determined through radiological, pathological, or clinical assessment as documented during follow-up.	From the date of radical surgery to the date of disease recurrence, progression, death, or last follow-up, up to 5 years.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative Complications Incidence (Clavien- Dindo ≥ III)	Defined as the proportion of patients experiencing postoperative complications graded as Clavien-Dindo classification grade III or higher within 30 days after radical surgery. Complication data are collected from postoperative records, discharge summaries, and follow-up documentation.	Within 30 days after surgery
Treatment-Related Adverse Events (TRAEs) Incidence (CTCAE Grade ≥ 3)	The incidence of treatment-related adverse events (TRAEs) graded ≥3 according to the Common Terminology Criteria for Adverse Events (CTCAE), v5.0, occurring during the neoadjuvant/induction phase and within 90 days following the initiation of definitive local therapy (surgery or radiotherapy). TRAEs are assessed based on clinical presentation, laboratory findings, imaging results, and physician judgment, with causality reviewed by the research team.	From the start of neoadjuvant or induction therapy to 90 days after the initiation of definitive local treatment (surgery or radiotherapy).
Immune-Related Adverse Events (irAEs) Incidence	Defined as the incidence of immune-related adverse events (irAEs) occurring from the start of neoadjuvant immunotherapy until 90 days after radical surgery or the initiation of definitive radiotherapy, whichever applies. irAEs are adverse events potentially attributable to immune checkpoint inhibitors and may involve organs such as the lung, liver, skin, or endocrine system. Events are graded according to CTCAE v5.0, and diagnosis is based on clinical presentation, laboratory/imaging findings, and expert clinical judgment.	From the start of neoadjuvant or induction therapy to 90 days after the initiation of definitive local treatment (surgery or radiotherapy).
Progression-Free Survival (PFS)	Defined as the time from the initiation of neoadjuvant immunotherapy to the first documented disease progression or death from any cause, whichever occurs first. Disease progression includes local recurrence, regional relapse, distant metastasis, or any clinically or radiologically confirmed progression. Patients without an event will be censored at the date of the last follow-up.	From the start of neoadjuvant immunotherapy to the date of disease progression, death, or last follow-up, up to 5 years.
Overall Survival (OS)	Defined as the time from the initiation of neoadjuvant therapy to death from any cause. For patients who remain alive at the end of follow-up, OS will be censored at the date of the last known contact. Survival status is confirmed through electronic medical records, follow-up visits, or telephonic interviews. OS is measured in days and analyzed using time-to-event methods.	From the date of treatment initiation to death from any cause or last follow-up, up to 5 years
Conversion Rate to Thoracotomy	Defined as the proportion of patients initially planned for video-assisted thoracoscopic surgery (VATS) who required unplanned conversion to open thoracotomy during radical resection. Conversion events and their intraoperative causes will be extracted from operative records and confirmed by surgical documentation. The outcome reflects intraoperative difficulty and is used as a surrogate marker of surgical complexity.	During the radical surgery (Day 0)
Operative Time (minutes)	Defined as the total operative time, measured in minutes, from the initial skin incision to the completion of skin closure during radical lung resection. Time data are extracted from intraoperative anesthesia or surgical records. Operative time is used as a continuous variable and may reflect the technical complexity of surgery.	During the radical surgery (Day 0)
pathologic Complete Response (pCR) Rate	Defined as the proportion of patients achieving a pathologic complete response (pCR), which is characterized by the absence of any viable tumor cells in the resected primary tumor and all sampled regional lymph nodes (ypT0N0), as confirmed by postoperative pathological examination. Pathologic assessments are conducted by experienced thoracic pathologists according to standardized criteria.	At the time of postoperative pathological assessment
Major Pathologic Response (MPR) Rate	Defined as the proportion of patients achieving a major pathologic response (MPR), characterized by ≤10% residual viable tumor cells in the resected primary tumor specimen after neoadjuvant therapy, regardless of lymph node status. The percentage of residual tumor is assessed by experienced thoracic pathologists according to standardized pathological evaluation protocols.	At the time of postoperative pathological assessment
Number of Dissected Lymph Nodes (N1, N2)	Defined as the total number of lymph nodes dissected and pathologically examined from N1 and N2 stations during radical lung cancer resection. The counts are recorded separately for N1 and N2 regions based on operative and pathological reports. This outcome reflects the extent of mediastinal and hilar lymphadenectomy and may serve as an indicator of surgical thoroughness and potential prognostic value.	During radical surgery (Day 0)
Number of Dissected Lymph Node Stations (N1, N2)	Defined as the number of lymph node stations sampled or dissected from the N1 and N2 regions during radical lung cancer surgery. The count is recorded separately for N1 and N2 stations based on operative and pathological reports. This measure reflects the anatomical extent of lymphadenectomy and is used to evaluate surgical thoroughness and adherence to oncologic guidelines.	During radical surgery (Day 0)
Reduction Rate of Surgical Resection Extent	Among patients whose anticipated surgical resection before neoadjuvant immunotherapy involved more than one pulmonary lobe, this outcome measures the proportion whose actual surgical resection was less extensive than originally planned. The anticipated extent is based on pre-treatment multidisciplinary evaluations, including imaging and bronchoscopy.	During the radical surgery (Day 0 of surgery)

Collaborators and Investigators

• Sponsor: Peking University Cancer Hospital & Institute

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2024
• Primary Completion (Estimated): March 31, 2026
• Study Completion (Estimated): March 31, 2028

Study Registration Dates

• First Submitted: April 7, 2025
• First Submitted That Met QC Criteria: April 7, 2025
• First Posted (Actual): April 13, 2025

Study Record Updates

• Last Update Posted (Actual): April 16, 2025
• Last Update Submitted That Met QC Criteria: April 11, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: lung cancer; radiotherapy; thoracic surgery; real-world study; neoadjuvant immunotherapy
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Immunologic Factors; Physiological Effects of Drugs; Immunomodulating Agents
• Other Study ID Numbers: 10412 (DAIDS-ES)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No