The goal of this clinical trial is to learn if spatially fractionated radiotherapy (SFRT) combined with standard systemic therapy can treat oligoprogressive non-small cell lung cancer (NSCLC) in patients who have progressed after at least one line of systemic therapy. The main question it aims to answer is:

- Can the combination of SFRT and standard systemic therapy improve progression-free survival (PFS) compared to standard systemic therapy alone?

Participants will:

• Undergo SFRT treatment for oligoprogressive lesions, with specific dose fractionation determined by the radiation oncologist based on clinical parameters.
• Continue their standard systemic therapy, which may include chemotherapy, targeted therapy, or immunotherapy, as adjusted by their treating physician.
• Have regular follow-up assessments, including imaging studies to evaluate treatment response and monitor for disease progression.

Inclusion Criteria

• Age 18 years or older, regardless of sex.
• Eastern Cooperative Oncology Group (ECOG) performance status score of 2 or less, with an expected survival of more than 3 months.
• Histologically or cytologically confirmed non-small cell lung cancer (NSCLC) with oligometastatic disease (up to 5 separate progressive lesions), having received and progressed after at least one line of systemic therapy (chemotherapy, targeted therapy, or immunotherapy).
• The target lesion for radiotherapy has not been previously irradiated, or it has been more than 6 months since the last radiotherapy.
• The diameter of the target lesion is at least 4.5 cm, suitable for lattice radiotherapy planning.
• No new or enlarged brain metastases; if brain metastases were previously treated with standard radiotherapy, they must be stable.
• Adequate hematologic and biochemical profiles, including hemoglobin ≥9.0 g/dL, absolute neutrophil count (ANC) ≥1500/mm³, platelet count ≥100,000/mm³, total bilirubin ≤1.5 times the upper limit of normal (ULN) (or direct bilirubin ≤ULN if total bilirubin >1.5 times ULN), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 times ULN (or ≤5 times ULN if liver involvement is present), and creatinine ≤1.5 times ULN (or glomerular filtration rate [GFR] >60 mL/min if creatinine >1.5 times ULN).
• For women of childbearing potential, a negative pregnancy test within 7 days prior to registration.

Exclusion Criteria

• Presence of other systemic diseases or severe comorbidities that the investigator believes would make the patient unsuitable for the study or significantly interfere with the assessment of the safety and toxicity of the study regimen.
• Active autoimmune diseases requiring systemic treatment, or a history of severe autoimmune diseases, such as interstitial lung disease.
• Uncontrolled concurrent diseases, including but not limited to: infections requiring systemic treatment, active tuberculosis (TB), severe or chronic gastrointestinal diseases associated with diarrhea (e.g., Crohn's disease), active hepatitis B (defined by positive hepatitis B surface antigen [HBsAg]), active hepatitis C (defined by positive hepatitis C virus [HCV] RNA), symptomatic congestive heart failure, unstable angina, unstable cardiac arrhythmias, myocardial infarction within the past 6 months, or congestive heart failure requiring continuous maintenance therapy for life-threatening ventricular arrhythmias.
• Mental illness or social situations that might limit the patient's ability to comply with study requirements (e.g., drug abuse).
• Participation in other interventional clinical trials with experimental drugs that could be considered treatment for the primary tumor.
• Allergy to immunotherapy drugs, or discontinuation of immunotherapy drugs due to adverse events in the past, or grade 3 or higher immune-related adverse events during previous immunotherapy, or any grade of immune-related neurological or ocular adverse events.
• History of other active malignancies within the past 6 months, except for non-melanoma skin cancer, papillary thyroid cancer, prostate cancer, or cervical carcinoma in situ that have been treated with curative intent and are currently considered to have a recurrence risk of less than 30%.
• History of allogeneic organ transplantation or active primary immunodeficiency.
• Any other condition that the investigator deems a valid reason for exclusion, such as potential situations inconsistent with the clinical protocol.