Double lung transplantation in patients with metastatic lung-limited non-small cell lung carcinoma (NSCLC): A case series

Background: The role of double lung transplantation (DLT) in patients with advanced bilateral lung-limited non-small cell lung cancer (NSCLC) has been a subject of debate. We present prospective data from the DLT registry for lung-limited malignancies (DREAM) study (NCT05671887) cohort A evaluating DLT as a therapeutic strategy for this patient population. Methods: Patients with advanced bilateral lung-limited NSCLC who underwent DLT at Northwestern Memorial Hospital between September 2021 and December 2025 were included in the DREAM study cohort A. Patients with extrapulmonary disease were excluded. The primary indications for DLT were disease refractory to systemic therapies, with or without respiratory failure. Clinical outcomes, perioperative safety, and recurrence patterns were evaluated. Results: In total, 18 patients with advanced bilateral lung-limited NSCLC were included. The median age was 58.5 years (range 28-74). 14 patients (78%) were White, one was Asian (6%), one was Black (6%), and two were others (11%). 11 (61%) were female. Nine (50%) had a history of smoking. 12 patients (67%) had invasive mucinous adenocarcinoma histology. All patients experienced disease progression on standard-of-care treatments, with or without participation in clinical trials. 16 patients remain alive at the cut-off date of January 1st, 2026. The median follow-up duration and overall survival since DLT is 15.5 months (range: 1-49). The median duration on the DLT waitlist was 12 days (range: 3-59). There was no 30-day post-transplant mortality. One patient developed acute humoral rejection, which was successfully treated. All patients were discharged on room air after DLT. Three patients had lymph node-positive disease at explant and received adjuvant chemotherapy. Six patients developed recurrence (cases #1, 6, 8, 9, 11, 13). Two patients (cases #1 and 13) had lung recurrence. The other four patients (cases #6, 8, 9, 11) had bone metastases (case #6 also with brain metastasis). One achieving remission of pulmonary recurrence after SBRT (case #1) but died of COVID-19 infection at 49 months post-DLT. One patient died of presumed massive pulmonary embolism during adjuvant chemotherapy at 5 months post-DLT. Conclusions: DLT for bilateral lung-limited NSCLC is feasible, with acceptable perioperative safety, absence of early cancer-related deaths, and meaningful gains in respiratory function and quality of life. Recurrence remains a concern but can be managed with post-transplant therapies. These prospective results suggest that DLT may provide functional and survival benefits in a highly selected population otherwise facing terminal outcomes. The DREAM cohort A continues to define the safety of DLT in this population prospectively.