ctDNA-Guided CURB for OPD mNSCLC on TKI (CURB-TKI)

Inclusion criteria

• Age 18 or older.
• Able to do most daily activities (ECOG 0-2).
• Able and willing to sign an informed consent form to join the study.
• Metastatic non-small cell lung cancer (NSCLC) with either an EGFR mutation or ALK rearrangement confirmed by imaging and biopsy.
• Eligible for second-line therapy or targeted treatment (TKI) if in Group B.
• Willing to give a blood sample for ctDNA analysis.
• No limit to how many metastatic sites, but up to 5 progressive lesions that do not require immediate treatment.
• Prior radiation therapy near progressive lesions is allowed if applicable.
• Cancer lesions must be treatable with specific radiotherapy methods (like SBRT or ablative therapy).
• Oligoprogressive disease is evaluated independently for each lesion using specific criteria.
• Stable brain metastases allowed if asymptomatic and do not require corticosteroids.
• Prior treatment with radiation for oligoprogressive lesions is allowed as long as they remain asymptomatic and re-treatment is possible.
• Prior non-stereotactic radiation for palliative purposes is allowed, and if the lesion later progresses but is still asymptomatic and does not require immediate therapy, it can count towards the 5 oligoprogressive lesions.
• Able and willing to complete quality of life and health utility questionnaires in English, French, or Spanish.
• Accessible for treatment and follow-up.

Exclusion criteria

• More than 5 extracranial sites of progressive disease.
• Pregnant.
• Leptomeningeal disease.
• Serious health issues that prevent radiotherapy, like ataxia-telangiectasia or scleroderma.
• Prior radiation therapy near the progressive lesion that would prevent treatment with SBRT due to exceeding limits of healthy tissue tolerance.
• Any psychological, social, or geographic issues that could make it difficult to comply with the study.
• Any other condition that the investigator believes makes participation in the study inappropriate.