Medically Inoperable Early-Stage Lung Cancer Patients with Organ Transplants Treated with SBRT Have Impaired Outcomes

Lung stereotactic body radiotherapy [SBRT] is the standard of care for curative management of medically inoperable early-stage lung cancer [ES-LC] due to its excellent local control and minimal treatment-related toxicity. Patients (pts) with organ transplants are chronically immunosuppressed, with increased risk of developing cancer. We wished to characterize outcomes for transplant pts with inoperable ES-LC treated with SBRT. We surveyed our institutional review board-approved prospective lung SBRT data registry from 2003 to 2023 for medically inoperable ES-LC solid organ transplant pts. Patterns of failure were assessed, as well as overall survival (OS) and disease-free survival (DFS). Univariable prognostic factors for OS and PFS were identified with Cox proportional hazards regression. For the 20-year interval, 28 of 1976 definitive pts (1.4%) met study criteria, with 17.9% alive at analysis. Median follow up was 12.4 months. Pt characteristics included: male (52.9%), median pack-years smoking 34; 7.1% smoking at SBRT; median age 70.0 years, median KPS 80. Organs transplanted were lung (57.1%), liver (21.4%), heart (21.4%). Median time from transplant to SBRT was 5.7 years. Tumor characteristics included: median size 2.4 cm, median PET SUVmax 7.8, 85.7% with biopsy proven cancer. The median SBRT schedule was 50 Gy/5 fractions (32.1%). Toxicity was reported in 9 (32.1%) pts: grade 1/2 in 8 pts (28.6%) and grade 5 (pneumonitis) in 1 pt (3.5%), with no differences in rates by organ transplanted. Failure patterns were: local 21.4%, lobar 7.1%, nodal 10.7% and distant 32.1%. First site of failure was distant [alone or in combination] in 50.1% pts. Median DFS and OS were 17.1 and 14.5 months, respectively. Metastatic cancer was the cause of death in 25% patients. Univariate analysis revealed increasing pack-years smoking was associated with increased disease failure [p = 0.0016], but not with any other patient, tumor or transplant factors. Multivariate analysis revealed OS significantly associated with KPS [p = 0.0075] and tumor size [p = 0.0181]. Compared to historical SBRT results for ES-LC, transplanted pts had higher local failure, decreased cancer control and poorer overall survival. To explain these findings, we hypothesize that transplant-associated immunosuppression promotes understaging at diagnosis, enhanced metastatic progression despite treatment and a tumor biology resistant to SBRT.