1095 - Predictors of Failure to Undergo Planned Resection after Neoadjuvant Chemoimmunotherapy for LA-NSCLC
Presenter(s)
J. McDonald1, C. Friedes2, M. Locolano1, N. Yegya-Raman1, J. C. Kucharczuk3, T. Pechet3, C. Aggarwal4, M. E. Marmarelis4, W. P. Levin1, K. A. Cengel1,2, C. A. Ciunci4, C. D'Avella4, A. P. Singh4, C. W. Davis4, C. Langer4, J. D. Bradley1, L. Sun4, and S. J. Feigenberg1; 1Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 2Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, 3Division of Thoracic Surgery, University of Pennsylvania, Philadelphia, PA, 4Department of Hematology and Oncology, University of Pennsylvania, Philadelphia, PA
Purpose/Objective(s): To identify factors associated with not proceeding with planned surgical resection among patients with stage II-III NSCLC treated with neoadjuvant chemoimmunotherapy (nCIO).
Materials/Methods: We evaluated a prospectively maintained single-institution database of patients with stage II-III NSCLC undergoing nCIO between January 2022–December 2025 with intent for resection. The primary endpoint was not proceeding to surgery. Two a priori multivariable logistic regression models were constructed: a clinical model including age, ECOG performance status, T stage, and radiographic change in the sum of tumor diameters; and a care-process model including pre-nCIO surgical consultation, pre-nCIO tumor board discussion, and planned extent of surgery (bilobectomy or pneumonectomy vs. lobectomy). Models were constructed separately to limit overfitting given the number of events and to distinguish biologic predictors from care-process factors. Penalized likelihood (Firth) logistic regression was used for care-process analyses due to complete separation. Statistical significance was defined as two-sided p<0.05.
Results: Among 78 patients treated with nCIO with intent for resection, 25 (32%) did not undergo surgery. Reasons included requirement for pneumonectomy (48%), disease progression or unresectable disease (36%), worsening performance status or treatment-related toxicity (12%); 4% were other/unknown. Rates of non-resection increased with planned extent of surgery (18.6% lobectomy, 44.4% bilobectomy, 100% pneumonectomy). Histology and PD-L1 expression were not associated with non-resection. Median radiographic tumor reduction was -34% among surgical patients versus -13% among non-surgical patients (p<0.001). In multivariable analysis, older age (OR 1.09 per year, 95% CI 1.01–1.21; p=0.035), T3–4 stage (OR 5.98, 95% CI 1.69–25.24; p=0.005), and lesser tumor reduction (OR 1.56 per 10% lesser decrease, 95% CI 1.10–2.40; p=0.009) were associated with higher odds of not proceeding to surgery. In penalized regression, planned pneumonectomy was strongly associated with non-resection (OR 135, 95% CI 12.5–19,474; p<0.001). Pre-nCIO tumor board discussion was associated with higher odds of non-resection (OR 5.71, 95% CI 1.47–32.03; p=0.01), while pre-nCIO surgical consultation was associated with lower odds of non-resection (OR 0.11, 95% CI 0.01–0.97; p=0.046).
Conclusion: In this single-institution cohort, nearly one-third of patients treated with nCIO planned for resection did not receive surgery. Diversion from planned resection was associated with both tumor-related and care-process variables, especially planned pneumonectomy. These findings highlight the importance of multidisciplinary planning including pre-treatment surgical consultation and careful patient selection when considering nCIO with planned resection.