Oligoprogression (OPD) of non-small-cell lung cancer (NSCLC) occurs in approximately half of patients under targeted compounds (TKI) and facilitates use of regional therapies that can prolong survival. In order to characterize OPD in immunotherapy (IO)-treated NSCLC, we analyzed the failure pattern under PD-1/PD-L1 inhibitors (n = 297) or chemoimmunotherapy (n = 75). Under IO monotherapy, OPD was more frequent (20% vs. 10%, p < 0.05), occurred later (median 11 vs. 5 months, p < 0.01), affected fewer sites (mean 1.1 vs. 1.5, p < 0.05), and involved fewer lesions (1.4 vs. 2.3, p < 0.05) in the first compared to later lines. Lymph nodes (42%, mainly mediastinal) and the brain (39%) were mostly affected, followed by the lung (24%) and other organs. Compared to multifocal progression, OPD occurred later (11 vs. 4 months, p < 0.001) and was associated with longer survival (26 vs. 13 months, p < 0.001) and higher tumor PD-L1 expression (p < 0.001). Chemoimmunotherapy showed a similar incidence of OPD as IO monotherapy (13% vs. 11% at 2 years). Local treatments were applied regularly for brain but only in 50% for extracranial lesions. Thus, NSCLC oligoprogression is less common under IO than under TKI, but also favorable. Since its frequency drops later in the disease, regular restaging and multidisciplinary evaluation are essential in order to exploit the full therapeutic potential.

Background: To explore the prognostic value of serial dynamic contrast-enhanced (DCE) MRI in patients with advanced pulmonary adenocarcinoma undergoing first-line therapy with either tyrosine-kinase inhibitors (TKI) or platinum-based chemotherapy (PBC). Methods: Patients underwent baseline (day 0, n = 98), and post-therapeutic DCE MRI (PBC: day + 1, n = 52); TKI: day + 7, n = 46) at 1.5T. Perfusion curves were acquired at 10, 40, and 70 s after contrast application and analysed semiquantitatively. Treatment response was evaluated at 6 weeks by CT (RECIST 1.1); progression-free survival (PFS) and overall survival were analysed with respect to clinical and perfusion parameters. Relative uptake was defined as signal difference between contrast and non-contrast images, divided by the non-contrast signal. Predictors of survival were selected using Cox regression analysis. Median follow-up was 825 days. Results: In pre-therapeutic and early post-therapeutic MRI, treatment responders (n = 27) showed significantly higher relative contrast uptake within the tumor at 70 s after application as compared to non-responders (n = 71, p ≤ 0.02), response defined as PR by RECIST 1.1 at 6 weeks. There was no significant change of perfusion at early MRI after treatment. In multivariate regression analysis of selected parameters, the strongest association with PFS were relative uptake at 40 s in the early post-treatment MRI and pre-treatment clinical data (presence of liver metastases, ECOG performance status). Conclusion: Higher contrast uptake within the tumor at pre-treatment and early post-treatment MRI was associated with treatment response and better prognosis. DCE MRI of pulmonary adenocarcinoma may provide important prognostic information.

Computed tomography (CT) scans are the gold standard to measure treatment success of non-small cell lung cancer (NSCLC) therapies. Here, we investigated the very early tumor response of patients receiving chemotherapy or targeted therapies using a panel of already established and explorative liquid biomarkers. Blood samples from 50 patients were taken at baseline and at three early time points after therapy initiation. DNA mutations, a panel of 17 microRNAs, glycodelin, glutathione disulfide, glutathione, soluble caspase-cleaved cytokeratin 18 (M30 antigen), and soluble cytokeratin 18 (M65 antigen) were measured in serum and plasma samples. Baseline and first follow-up CT scans were evaluated and correlated with biomarker data. The detection rate of the individual biomarkers was between 56% and 100%. While only keratin 18 correlated with the tumor load at baseline, we found several individual markers correlating with the tumor response to treatment for each of the three time points of blood draws. A combination of the five best markers at each time point resulted in highly significant marker panels indicating therapeutic response (R² = 0.78, R² = 0.71, and R² = 0.71). Our study demonstrates that an early measurement of biomarkers immediately after therapy start can assess tumor response to treatment and might support an adaptation of treatment to improve patients’ outcome.

Background: To explore the prognostic value of serial dynamic contrast-enhanced (DCE) MRI in patients with advanced pulmonary adenocarcinoma undergoing first-line therapy with either tyrosine-kinase inhibitors (TKI) or platinum-based chemotherapy (PBC). Methods: Patients underwent baseline (day 0, n = 98), and post-therapeutic DCE MRI (PBC: day + 1, n = 52); TKI: day + 7, n = 46) at 1.5T. Perfusion curves were acquired at 10, 40, and 70s after contrast application and analysed semiquantitatively. Treatment response was evaluated at 6 weeks by CT (RECIST 1.1); progression-free survival (PFS) and overall survival (OS) were analysed with respect to clinical and perfusion parameters. Relative uptake was defined as signal difference between contrast and non-contrast images, divided by the non-contrast signal. Predictors of survival were selected using Cox regression analysis. Median follow-up was 825 days. Results: In pre-therapeutic and early post-therapeutic MRI, responders for PBC (n = 4) and TKI (n = 23) treatment (PR by RECIST 1.1 at 6 weeks) showed significantly higher relative contrast uptake within the tumor at 70 s after application as compared to non-responders (n = 71, p ≤ 0.02). There was no significant change of perfusion at early MRI after treatment. Independent parameters showing the strongest association with PFS were relative uptake at 40 s in the early post-treatment MRI and pre-treatment clinical data (presence of liver metastases, ECOG performance status). Conclusion: Higher contrast uptake within the tumor at pre-treatment and early post-treatment MRI was associated with treatment response and better prognosis. DCE MRI of pulmonary adenocarcinoma may provide independent prognostic information.