Reassessing Perioperative Risks: Impact of Neoadjuvant Therapy on Mortality in Pneumonectomy

C. S. Boutros¹, A. Bassiri², E. L.. Risa³, B. Jiang⁴, J. Sinopoli⁵, L. Tapias⁶, P. Linden², C. Towe^7
1University Hospitals Cleveland Medical Center/ Case Western Reserve University, University Heights, Ohio ²University Hospitals Cleveland Medical Center, Cleveland, Ohio ³University Hospitals.org, Cleveland, Ohio ⁴University Hospitals Cleveland Medical Center, Strongsville, Ohio ⁵University Hospital Cleveland Medical Center, University Heights, Ohio ⁶University Hospitals Cleveland Medical Center, Shaker Heights, Ohio ⁷University Hospital Cleveland Medical Center, Division of Thoracic Su, Cleveland, Ohio

Purpose: The higher-than-expected death rate after pneumonectomy in the SWOG-8805 trial prompted widespread concern regarding the perioperative safety of pneumonectomy after chemoradiation. More recently, neoadjuvant treatment has become the standard of care for stage Ib or greater lung cancer. We hypothesized that neoadjuvant treatment does not increase the risk of pneumonectomy.

Methods: We queried the 2021 iteration of the National Cancer Database for adult patients with nonmetastatic non-small cell lung cancer (NSCLC). Patients were included if they underwent a pneumonectomy, had recorded laterality, and had known 90-day mortality information. Patients with non-adenocarcinoma or squamous histology and patients who received pneumonectomy after neoadjuvant radiation alone were excluded. The outcome of interest was 90-day mortality. Multivariate logistic regression was performed to determine independent risk factors for 90-day mortality, including an interaction analysis of laterality and neoadjuvant treatment.

Results: We identified 14,522 patients that met inclusion criteria, 8,505 (58.6%) right pneumonectomies and 6,017 (41.4%) left pneumonectomies. There were 2,164 (14.9%) patients that received neoadjuvant treatment (1,008 patients underwent systemic therapy alone and 1,156 underwent systemic therapy plus radiation). The 90-day mortality rate was 12.9% percent after pneumonectomy, and was higher in right pneumonectomy compared to left pneumonectomy (1,035/6,017, 17.2% vs 837/8505, 9.8% p = < 0.001). Receipt of neoadjuvant therapy was not associated with inferior 90-day mortality in comparison to pneumonectomy alone (105/1,008, 10.4% vs 1609/12,358, 13% p= 0.04). Factors independently associated with 90-day mortality after pneumonectomy were right sided pneumonectomy (OR 2.01, 95% CI 1.78-2.28, p < 0.001), advanced age (OR 1.05, 95% CI 1.04 – 1.06, p = < 0.001), and Charlson-Deyo comorbidity index ≥ 3 (OR 1.98, 95% CI 1.53 – 2.57, p = < 0.001). We also performed an interaction analysis which included all combinations of pneumonectomy laterality and neoadjuvant treatment. This showed no increased risk associated with neoadjuvant chemotherapy or chemoradiation therapy for both left and right pneumonectomy (Table 1).

Conclusion: This multicenter analysis of the NCDB reiterates known elevated risk associated with right pneumonectomy but disputes the dogma that neoadjuvant treatment increases the risk of right or left pneumonectomy. In this setting, we believe neoadjuvant treatment is not a contraindication to receipt of pneumonectomy.

Identify the source of the funding for this research project: Departmental