NSCLC (Advanced Non-small Cell Lung Cancer), Post Surgical
Conditions
Keywords
Radiotherapy, Adjuvant therapy, Lymph node
Brief summary
Patients with stage III non-small-cell lung cancer (NSCLC) who receive neoadjuvant chemoimmunotherapy may achieve good response in the primary tumor but still have residual nodal disease after surgery (ypTanyN⁺M0), which is associated with poor prognosis in retrospective analyses from our center. In prior trials such as LungART and PORT-C, postoperative radiotherapy (PORT) did not improve disease-free survival in completely resected stage IIIA-N2 NSCLC after adjuvant chemotherapy, suggesting that PORT should not be used indiscriminately. However, recent preclinical and translational data indicate that radiotherapy can enhance antitumor immunity, remodel the tumor microenvironment, and synergize with immune checkpoint inhibitors via immunogenic cell death, improved T-cell trafficking, and tertiary lymphoid structure formation. This single-center randomized phase II study will evaluate whether adding postoperative involved-field nodal radiotherapy to standard PD-1 maintenance therapy can improve disease-free survival compared with PD-1 maintenance alone in patients with ypTanyN⁺M0 NSCLC after neoadjuvant chemoimmunotherapy and R0 resection.
Interventions
RADIATIONradiotherapy
Postoperative external beam radiotherapy to regional draining lymph nodes (e.g., ipsilateral mediastinal and hilar nodal stations involved or at high risk), based on pre-treatment imaging and surgical/pathologic findings. Suggested dose: 50-54 Gy in 25-27 fractions (2.0-2.16 Gy per fraction, once daily, 5 days per week), delivered with 3D-CRT or IMRT per institutional standards.
Anti-PD-1 monoclonal antibody administered intravenously every 3 weeks for up to 1 year (or until disease recurrence, unacceptable toxicity, or withdrawal). The specific agent and dose will follow the neoadjuvant regimen and local regulatory approval.
Sponsors
Shanghai Zhongshan Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Age 18-75 years, male or female. * Histologically confirmed NSCLC (adenocarcinoma, squamous cell carcinoma, or other NSCLC subtypes). * Clinical stage IIIA/IIIB at initial diagnosis, deemed suitable for neoadjuvant chemoimmunotherapy followed by surgery according to MDT. * Completed 2-4 cycles of platinum-based doublet chemotherapy plus PD-1 inhibitor as neoadjuvant therapy. * Underwent R0 resection (anatomical lobectomy or pneumonectomy with mediastinal lymph node dissection). * Postoperative pathological stage ypT\_anyN⁺M0 (residual nodal metastasis in mediastinal or hilar lymph nodes). * ECOG performance status 0-1. * Adequate hematologic, hepatic, and renal function per protocol-defined lab thresholds. * Able to start postoperative radiotherapy and/or PD-1 maintenance within 4-10 weeks after surgery (or after recovery from postoperative complications, as clinically appropriate). * Signed written informed consent.
Exclusion criteria
* Positive surgical margins (R1 or R2) or incomplete resection. * Prior thoracic radiotherapy that would overlap with planned treatment fields. * Active, uncontrolled infection or unresolved ≥ Grade 2 immune-related adverse events. * History of severe autoimmune disease requiring systemic immunosuppression. * Uncontrolled interstitial lung disease or significant pulmonary fibrosis. * Symptomatic or untreated central nervous system metastases at enrollment. * Any condition that, in the investigator's judgment, would compromise patient safety or protocol compliance.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease-Free Survival (DFS) | 3 years | Time from date of surgery to first documented recurrence (locoregional or distant) or death from any cause, whichever occurs first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | 5 years | Time from surgery to death from any cause (up to 5 years). |
| Incidence of Treatment-Emergent Adverse Events | Through treatment completion, an average of 1 year | Incidence, type, and severity of adverse events graded by CTCAE v5.0, including radiation pneumonitis and immune-related toxicities. |
Outcome results
None listed