Lung transplantation has been a well-established treatment for patients suffering from a variety of end-stage pulmonary diseases, including chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, and cystic fibrosis. For lung cancer, there have been five reported studies of lung transplantation in carefully selected subsets of patients with proven bilateral, limited, multifocal lung adenocarcinoma including adenocarcinoma in situ (AIS), bronchioalveolar carcinoma (BAC), invasive mucinous adenocarcinoma (IMA), lepidic predominant adenocarcinoma, and minimally invasive adenocarcinoma (MIA) (2,3). They are associated with frequent intrapulmonary progression and rare extrapulmonary metastases compared with other types of adenocarcinoma. BAC is known to frequently progress within the lung (4) while rarely spreading to the brain (5). Also, a subset of BAC is known to rapidly involve multilobe of lung diffusely, leading to a high mortality rate (6).
All five studies have reported that the 5-year survival rate of bilateral sequential lung transplantation was more than 50%. In 1999, a case series reported durable response without evidence of recurrence until post-transplant 23 to 56 months in three patients (7). According to subsequent studies, the 5-year survival rate of bilateral sequential lung transplantation was estimated at over 50% in patients with multifocal BAC, invasive adenocarcinoma, and NSCLC (6,8,9,10). In our study group, a 54-year-old man recently underwent bilateral non-sequential double lung transplantation for bilateral IMA which was not responsive to chemotherapy, immunotherapy, and targeted therapy [unpublished]. Since the surgery, he has been stable with no minimal residual disease (MRD) measured by circulating tumor DNA (ctDNA) for more than six months.
According to a consensus document from the International Society for Heart and Lung Transplantation (ISHLT), AIS and MIA are listed as ‘special circumstances’ for lung transplantation when patients suffer from significant respiratory compromise and reduction of quality of life and conventional medical therapies fail (11). Other than AIS and MIA, there is a paucity of evidence on the potential benefits of lung transplantation in lung cancer patients.
The need for lung transplantation is not only confined to patients with primary lung cancers. There are unmet needs for patients who have lung-limited metastasis after successful treatment for primary tumors such as sarcomas or colorectal cancer (CRC). In 2019, the Norwegian trials firstly demonstrated that highly selected patients with nonresectable CRC with liver-only metastases can gain benefit in survival and recurrence from the liver transplant (12). After that, liver transplantation has been emerging as a viable treatment strategy based on durable long-term survival in colorectal cancer (CRC) patients who have liver-confined metastases, emerging as a viable treatment strategy (13).
Thus, this study aims to investigate the clinical outcome of patients who undergo lung transplantation for treatment of a select group of medically refractory cancers affecting the lungs alone without extrapulmonary nodal and distant metastases. Patients who have failed standard of care treatments including systemic therapies and do not have further treatment/trials options for either primary lung cancers or metastatic cancers in lungs will be included. Their clinical courses including overall survival, disease-free survival, and graft failure will be monitored as well as the molecular and genetic biomarkers to investigate the correlation with the prognosis.
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