Pretreatment Tumor Growth Rate and Radiological Response as Predictive Markers of Pathological Response and Survival in Patients with Resectable Lung Cancer Treated by Neoadjuvant Treatment

SIMPLE SUMMARY: For patients with resectable non-small cell lung carcinoma (NSCLC), neoadjuvant nivolumab and chemotherapy are associated with increased major pathological responses and better event-free survival. Identification of earlier biomarkers associated with progression precluding surgery or disease recurrence after surgery is of importance in this population. The aim of our retrospective study was to assess the potential added value of pretreatment tumor growth rate (TGR(0)) using computed tomography (CT) and/or positron emission tomography (PET)-CT scans before and at baseline. We confirmed in 32 patients with resectable stage IB (≥4 cm) to IIIA NSCLC that the assessment of TGR(0) helps identify patients who would benefit from neoadjuvant treatment and outperforms RECIST assessments for survival outcomes. TGR(0) may be an early noninvasive marker for more favorable genetic and/or biological profiles, leading to improved disease control and overall survival. ABSTRACT: Introduction: Predictive biomarkers associated with pathological response, progression precluding surgery, and/or recurrence after surgery are needed for patients with resectable non-small cell lung carcinoma (NSCLC) treated by neoadjuvant treatment. We evaluated the clinical impact of the pretreatment tumor growth rate (TGR(0)) and radiological response for patients with resectable NSCLC treated with neoadjuvant therapies. Methods: Consecutive patients with resectable stage IB (≥4 cm) to IIIA NSCLC treated by neoadjuvant platinum-doublet chemotherapy with or without nivolumab at our tertiary center were retrospectively analyzed. TGR(0) and RECIST objective responses were determined. Multivariable analyses identified independent predictors of event-free survival (EFS), overall survival (OS), and major pathological response (MPR). Results: Between November 2017 and December 2022, 32 patients (mean [SD] age, 63.8 [8.0] years) were included. At a median follow-up of 54.8 months (95% CI, 42.3–60.4 months), eleven patients (34%) experienced progression or recurrence, and twelve deaths (38%) were recorded. The TGR(0) cutoff of 30%/month remained the only independent factor associated with EFS (HR = 0.04; 95% CI, 0.01–0.3; p = 0.003) and OS (HR = 0.2; 95% CI, 0.03–0.7; p = 0.01). The TGR(0) cut-off had a mean time-dependent AUC of 0.83 (95% CI, 0.64–0.95) and 0.80 (95% CI, 0.62–0.97) for predicting EFS and OS, respectively. Fifteen of 26 resection cases (58%) showed MPR including nine with pathological complete responses (35%). Only the objective response of the primary tumor was associated with MPR (OR = 27.5; 95% CI, 2.6–289.1; p = 0.006). Conclusions: Assessment of TGR(0) can identify patients who should benefit from neoadjuvant treatment. A tumor objective response might be a predictor of MPR after neoadjuvant treatment, which will help to adapt surgical management.