Abstract
BackgroundThe PET-derived metabolic tumor volume (MTV) is an independent prognosticator in non-small cell lung cancer (NSCLC) patients. We analyzed the prognostic value of residual MTV (rMTV) after completion of chemoradiotherapy (CRT) in inoperable stage III NSCLC patients with and without immune checkpoint inhibition (ICI).MethodsFifty-six inoperable stage III NSCLC patients (16 female, median 65.0 years) underwent 18F-FDG PET/CT after completion of standard CRT. rMTV was delineated on 18F-FDG PET/CT using a standard threshold (liver SUVmean + 2 × standard deviation). 21/56 patients underwent additional ICI (CRT-IO, 21/56 patients) thereafter. Patients were divided in volumetric subgroups using median split dichotomization (MTV ≤ 4.3 ml vs. > 4.3 ml). rMTV, clinical features, and ICI-application were correlated with clinical outcome parameters (progression-free survival (PFS), local PFS (LPFS), and overall survival (OS).ResultsOverall, median follow-up was 52.0 months. Smaller rMTV was associated with longer median PFS (29.3 vs. 10.5 months, p = 0.015), LPFS (49.9 vs. 13.5 months, p = 0.001), and OS (63.0 vs. 23.0 months, p = 0.003). CRT-IO patients compared to CRT patients showed significantly longer median PFS (29.3 vs. 11.2 months, p = 0.034), LPFS (median not reached vs. 14.0 months, p = 0.016), and OS (median not reached vs. 25.2 months, p = 0.007). In the CRT subgroup, smaller rMTV was associated with longer median PFS (33.5 vs. 8.6 months, p = 0.001), LPFS (49.9 vs. 10.1 months, p = 0.001), and OS (63.0 vs. 16.3 months, p = 0.004). In the CRT-IO subgroup, neither PFS, LPFS, nor OS were associated with MTV (p > 0.05 each). The findings were confirmed in subsequent multivariate analyses.ConclusionIn stage III NSCLC, smaller rMTV is highly associated with superior clinical outcome, especially in patients undergoing CRT without ICI. Patients with CRT-IO show significantly improved outcome compared to CRT patients. Of note, clinical outcome in CRT-IO patients is independent of residual MTV. Hence, even patients with large rMTV might profit from ICI despite extensive tumor load.
Highlights
MethodsAdvanced stage III non-small cell lung cancer (NSCLC) represents a heterogenous tumor entity regarding patient and tumor features [1,2,3,4,5] leading to interdisciplinary treatment strategies and regimens in these mostly inoperable patient cohort [6,7,8,9,10]
In the overall outcome analysis, we found that a smaller residual MTV (rMTV) after therapy completion and the subsequent application of immune checkpoint inhibition (ICI)
What is a clinical implementation of our findings? Our study suggests a role of the ICI maintenance treatment after concurrently or sequentially to thoracic irradiation (CRT) as a “stabilizer” of the local–regional and distant tumor control as well as local PFS (LPFS) and overall survival (OS)
Summary
Advanced stage III non-small cell lung cancer (NSCLC) represents a heterogenous tumor entity regarding patient and tumor features [1,2,3,4,5] leading to interdisciplinary treatment strategies and regimens in these mostly inoperable patient cohort [6,7,8,9,10]. Standard treatment in stage III NSCLC consisted of a combination of platinum-based chemotherapy applied concurrently or sequentially to thoracic irradiation (CRT) leading to improved clinical outcome in terms of local control, metastasis free, and overall survival compared to irradiation alone [11]. Beyond this combined approach, immune checkpoint inhibition (ICI) has evolved as additional treatment option NSCLC patients [12], especially with regard to the first US Food and Drug Administration (FDA) approval for PD-1 inhibition (nivolumab) in 2015 in advanced or metastatic NSCLC [13, 14]. Beyond the PET-derived MTV, further clinical parameters were assessed including age, sex, histological subtypes, UICC stage (IIIA-C), planning target volume (PTV), reached radiation dose at radiotherapy (RT), application of RCT-IO, and application of previous induction chemotherapy. Statistical significance was defined as two-tailed p-values < 0.05
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