mr-linac guided adaptive fsrt for brain metastases from non-small cell lung cancer

Conditions: Non-small Cell Lung Cancer

Summary: this phase ii study is to determine the efficacy and safety of mr-linac guided adaptive fractionated stereotactic radiotherapy (fsrt) in patients with brain metastases in non-small cell lung cancer.

this phase ii study is to determine the efficacy and safety of mr-linac guided adaptive fractionated stereotactic radiotherapy (fsrt) in patients with brain metastases in non-small cell lung cancer. patients will receive fsrt (30gy in 5 fractions) on the mr-linac treatment machine. the primary end point is 1-year intracranial progression-free survival. the secondary end points are objective response rate, 1-y pfs, 1-y os, perilesional edema of brain metastases, quality of life, safety of treatment, dose coverage of targets and dose to normal organs.

Eligibility criteria:
inclusion criteria: * aged 18-75 years * histologically or cytologically confirmed non-small cell lung cancer * 1-10 metastases on contrast-enhanced mri * radiotherapy for extracranial lesions is permitted * tyrosine kinase inhibitors (tki) are permitted in patients with progression of intracranial metastases during previous tki therapy * patients have measurable or evaluable lesions based on the response evaluation criteria in solid tumors (recist) criteria * eastern cooperative oncology group (ecog) performance status 0-1 * normal function of organs and bone marrow within 14 days: total bilirubin 1.5 times or less the upper limits of normal (uln); ast and alt 1.5 times or less the uln; absolute neutrophil count≥ 500 cells/mm3; creatinine clearance rate(ccr) ≥45 ml/min; platelet count≥50,000 cells/mm3; international normalized ratio(inr) ≤1.5#prothrombin time (pt)≤ 1.5 × uln * informed-consent exclusion criteria: * small cell carcinoma of lung * intracranial metastases needed surgical decompression * patients with contraindications for mri * previous radiotherapy or excision for intracranial metastases * the tumor has completely approached, encircled, or invaded the intravascular space of the great vessels (e.g., the pulmonary artery or the superior vena cava) * a cavity over 2cm in diameter of primary tumor or metastasis * bleeding tendency or coagulation disorder * hemoptysis (1/2 teaspoon blood/day) happened within 1 month * the use of full-dose anticoagulation within the past 1 month * severe vascular disease occurred within 6 months * gastrointestinal fistula, perforation or abdominal abscess occurred within 6 months * hypertensive crisis, hypertensive encephalopathy, symptomatic heart failure (new york class ii or above), active cerebrovascular disease or cardiovascular disease occurred within 6 months * uncontrolled hypertension (systolic \> 150mmhg and/or diastolic \> 100mmhg) * major surgery within 28 days or minor surgery or needle biopsy within 48 hours * urine protein 3-4+, or 24h urine protein quantitative \>1g * severe uncontrolled disease * uncontrollable seizure or psychotic patients without self-control ability * women in pregnancy, lactation period * other not suitable conditions determined by the investigators

Keywords: non-small cell lung cancer mr-linac fractionated stereotactic radiation therapy brain metastase