Primary Objective:

Evaluate the role of ctDNA positivity in decision making for postoperative therapy for non-small cell lung cancer. The plan for postoperative therapy will be declared after pathology report review and before the ctDNA result. We will assess if ctDNA result changed the planned therapy.

Secondary Objectives:

Evaluate personalized postoperative Chemo/ICPI/Targeted Therapies/Radiation Therapy in clearing ctDNA Evaluate the disease-free survival (DFS) and overall survival (OS) of stage II/III lung cancer patients with postoperative ctDNA positive status

Exploratory Objective:

Evaluate radiomics features based on serial CT thoracic CT scans to determine if radiomic features can be associated with ctDNA positivity/negativity.

This is a pilot, single-arm interventional study evaluating the use of the Haystack™ circulating tumor DNA (ctDNA) assay to guide postoperative radiation therapy (PORT) and systemic therapy decisions for patients with Stage II-III non-small cell lung cancer (NSCLC) who have undergone surgical resection. The study aims to assess whether ctDNA monitoring can effectively detect minimal residual disease (MRD) and improve post-surgical treatment strategies.

Inclusion Criteria:

1. Have provided signed informed consent for the trial
2. Aged ≥18 years at the time of informed consent
3. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
4. Diagnosed with histologically confirmed Stage II-III NSCLC and undergone surgical resection of lung tumor
5. No active second cancers/malignancy
6. Patients that received preoperative therapy (including chemotherapy and immunotherapy or others) are eligible
7. Willing and able to comply with all aspects of the protocol
8. Standard of care therapy and methods as per institution and investigator discretion -

Exclusion Criteria:

Exclusion Criteria

1. Discontinued treatment due to a Grade 3 or higher AEs with chemotherapy or immunotherapy or targeted therapy agent
2. With a history of another primary malignancy within the past 2 years that is considered an active malignancy by the enrolling physician.
3. Have known active CNS metastases and/or carcinomatous meningitis.
4. Have a history of (non-infectious) pneumonitis that required steroids or have current pneumonitis.
5. Have a history of interstitial lung disease.
6. Have a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant's participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator. -