DREAM：针对肺局限性恶性肿瘤的双肺移植登记研究——一项针对医学难治性癌症的前瞻性登记研究

Background: Primary lung adenocarcinoma in situ and minimally invasive adenocarcinoma are listed as ‘special circumstances' for lung transplantation in the consensus document from the International Society for Heart and Lung Transplantation (ISHLT). Multiple studies have reported the successful outcomes on lung transplantation in carefully selected subsets of patients with multifocal lung adenocarcinoma, with the estimated 5-year survival rate of over 50% in patients with bronchoalveolar carcinoma, invasive adenocarcinoma, and non-small cell lung cancer. Furthermore, there is an unmet need for patients who have lung-limited metastases after successful treatment for primary tumors. Moreover, patients with respiratory failure who were excluded from lung transplantation consideration due to a history of cancer in the last 5 years may also attain the benefit of lung transplantation while having adequate cancer control. With liver transplantation for colorectal cancer patients being established to improve survival outcomes in patients with colorectal cancer and liver-confined metastases, we aim to evaluate the feasibility of lung transplantation in patients with lung-limited metastatic cancer and those who were previously excluded from lung transplantation due to a history of recent localized cancer. Methods: This is a prospective registration trial to evaluate outcomes in patients who undergo double lung transplantation for the treatment of select groups of medically refractory cancers (primary lung cancers or metastatic cancers to the lungs). Overall survival (OS), disease-free survival (DFS), allograft rejection (AR), and allograft survival (AS), along with molecular and genetic biomarkers, will be studied. The study duration, including surveillance, will be 10 years. The goal is to enroll 125 participants through the Northwestern Medicine Clinical Programs. Essential inclusion criteria: • The tumor should be without extrapulmonary metastasis, as determined by standard-of-care diagnostic and staging workup. • All standard-of-care or experimental oncological treatments known to improve survival should have failed or been deemed infeasible. • Patients should meet the general criteria for lung transplant evaluation and listing. Study cohorts: • Cohort A: Lung-limited metastatic lung cancers - Examples include, but are not limited to, invasive mucinous/non-mucinous non-small cell lung cancers and multifocal carcinomas. • Cohort B: Metastatic cancers to the lungs only - Examples include, but are not limited to, germ cell tumors, testicular, head & neck, colorectal, and renal cell cancers. • Cohort C: Respiratory failure with a history of cancer in the last 5 years - Examples include, but are not limited to, interstitial lung disease (ILD), pulmonary fibrosis (idiopathic or secondary), advanced chronic obstructive pulmonary disease (COPD), bronchiectasis, emphysema, cystic fibrosis (CF), emphysema due to alpha-1 antitrypsin deficiency, and pulmonary arterial hypertension (PAH). Clinical trial registry number : NCT05671887. Enrollment began November 16, 2022. Trial is open and continues to enroll participants as of January 1, 2026.