Delta-radiomics features of ADC maps as early predictors of treatment response in lung cancer.

OBJECTIVE: Investigate the feasibility of detecting early treatment-induced tumor tissue changes in patients with advanced lung adenocarcinoma using diffusion-weighted MRI-derived radiomics features. METHODS: This prospective observational study included 144 patients receiving either tyrosine kinase inhibitors (TKI, n = 64) or platinum-based chemotherapy (PBC, n = 80) for the treatment of pulmonary adenocarcinoma. Patients underwent diffusion-weighted MRI the day prior to therapy (baseline, all patients), as well as either + 1 (PBC) or + 7 and + 14 (TKI) days after treatment initiation. One hundred ninety-seven radiomics features were extracted from manually delineated tumor volumes. Feature changes over time were analyzed for correlation with treatment response (TR) according to CT-derived RECIST after 2 months and progression-free survival (PFS). RESULTS: Out of 14 selected delta-radiomics features, 6 showed significant correlations with PFS or TR. Most significant correlations were found after 14 days. Features quantifying ROI heterogeneity, such as short-run emphasis (p = 0.04(pfs)/0.005(tr)), gradient short-run emphasis (p = 0.06(pfs)/0.01(tr)), and zone percentage (p = 0.02(pfs)/0.01(tr)) increased in patients with overall better TR whereas patients with worse overall response showed an increase in features quantifying ROI homogeneity, such as normalized inverse difference (p = 0.01(pfs)/0.04(tr)). Clustering of these features allows stratification of patients into groups of longer and shorter survival. CONCLUSION: Two weeks after initiation of treatment, diffusion MRI of lung adenocarcinoma reveals quantifiable tissue-level insights that correlate well with future treatment (non-)response. Diffusion MRI-derived radiomics thus shows promise as an early, radiation-free decision-support to predict efficacy and potentially alter the treatment course early. CRITICAL RELEVANCE STATEMENT: Delta-Radiomics texture features derived from diffusion-weighted MRI of lung adenocarcinoma, acquired as early as 2 weeks after initiation of treatment, are significantly correlated with RECIST TR and PFS as obtained through later morphological imaging. KEY POINTS: Morphological imaging takes time to detect TR in lung cancer, diffusion-weighted MRI might identify response earlier. Several radiomics features are significantly correlated with TR and PFS. Radiomics of diffusion-weighted MRI may facilitate patient stratification and management.

Dynamic contrast enhanced MRI of pulmonary adenocarcinomas for early risk stratification: higher contrast uptake associated with response and better prognosis.

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.

Earlier extracranial progression and shorter survival in ALK-rearranged lung cancer with positive liquid rebiopsies.

BACKGROUND: Liquid rebiopsies can detect resistance mutations to guide therapy of anaplastic lymphoma kinase-rearranged (ALK+) non-small-cell lung cancer (NSCLC) failing tyrosine kinase inhibitors (TKI). Here, we analyze how their results relate to the anatomical pattern of disease progression and patient outcome. METHODS: Clinical, molecular, and radiologic characteristics of consecutive TKI-treated ALK+ NSCLC patients were analyzed using prospectively collected plasma samples and the 17-gene targeted AVENIO kit, which covers oncogenic drivers and all TP53 exons. RESULTS: In 56 patients, 139 instances of radiologic changes were analyzed, of which 133 corresponded to disease progression. Circulating tumor DNA (ctDNA) alterations were identified in most instances of extracranial progression (58/94 or 62%), especially if concomitant intracranial progression was also present (89%, P<0.001), but rarely in case of isolated central nervous system (CNS) progression (8/39 or 21%, P<0.001). ctDNA detectability correlated with presence of "short" echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion variants (mainly V3, E6:A20) and/or TP53 mutations (P<0.05), and presented therapeutic opportunities in <50% of cases. Patients with extracranial progression and positive liquid biopsies had shorter survival from the start of palliative treatment (mean 52 vs. 69 months, P=0.002), regardless of previous and subsequent therapy and initial ECOG performance status. Furthermore, for patients with extracranial progression, ctDNA detectability was associated with shorter next-line progression-free survival (PFS) (3 vs. 13 months, P=0.003) if they were switched to another systemic therapy (49/86 samples), and with shorter time-to-next-treatment (TNT) (3 vs. 8 months, P=0.004) if they were continued on the same treatment due to oligoprogression (37/86). In contrast, ctDNA detectability was not associated with the outcome of patients showing CNS-only progression. In 6/6 cases with suspicion of non-neoplastic radiologic lung changes (mainly infection or pneumonitis), ctDNA results remained negative. CONCLUSIONS: Positive blood-based liquid rebiopsies in ALK+ NSCLC characterize biologically more aggressive disease and are common with extracranial, but rare with CNS-only progression or benign radiologic changes. These results reconcile the increased detection of ALK resistance mutations with other features of the high-risk EML4-ALK V3-associated phenotype. Conversely, most oligoprogressive patients with negative liquid biopsies have a more indolent course without need for early change of systemic treatment.

Image quality evaluation of dual-layer spectral CT in comparison to single-layer CT in a reduced-dose setting.

OBJECTIVES: To quantitatively and qualitatively evaluate image quality in dual-layer CT (DLCT) compared to single-layer CT (SLCT) in the thorax, abdomen, and pelvis in a reduced-dose setting. METHODS: Intraindividual, retrospective comparisons were performed in 25 patients who received at least one acquisition of all three acquisition protocols SLCTlow (100 kVp), DLCThigh (120 kVp), and DLCTlow (120 kVp), all covering the venous-phase thorax, abdomen, and pelvis with matched CTDIvol between SLCTlow and DLCTlow. Reconstruction parameters were identical between all scans. Image quality was assessed quantitatively at 10 measurement locations in the thorax, abdomen, and pelvis by two independent observers, and subjectively with an intraindividual forced choice test between the three acquisitions. Dose-length product (DLP) and CTDIvol were extracted for dose comparison. RESULTS: Despite matched CTDIvol in acquisition protocols, CTDIvol and DLP were lower for SLCTlow compared to DLCTlow and DLCThigh (DLP 408.58, 444.68, 647.08 mGy·cm, respectively; p < 0.0004), as automated tube current modulation for DLCTlow reached the lower limit in the thorax (mean 66.1 mAs vs limit 65 mAs). Noise and CNR were comparable between SLCTlow and DLCTlow (p values, 0.29-0.51 and 0.05-0.20), but CT numbers were significantly higher for organs and vessels in the upper abdomen for SLCTlow compared to DLCTlow. DLCThigh had significantly better image quality (Noise and CNR). Subjective image quality was superior for DLCThigh, but no difference was found between SLCTlow and DLCTlow. CONCLUSIONS: DLCTlow showed comparable image quality to SLCTlow, with the additional possibility of spectral post-processing. Further dose reduction seems possible by decreasing the lower limit of the tube current for the thorax. KEY POINTS: • Clinical use of reduced-dose DLCT is feasible despite the required higher tube potential. • DLCT with reduced dose shows comparable objective and subjective image quality to reduced-dose SLCT. • Further dose reduction in the thorax might be possible by adjusting mAs thresholds.

Novel Liquid Biomarker Panels for A Very Early Response Capturing of NSCLC Therapies in Advanced Stages.

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.

Oligoprogressive Non-Small-Cell Lung Cancer under Treatment with PD-(L)1 Inhibitors.

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.

Balloon-Expandable Stent Graft for Treating Uretero-Iliac Artery Fistula.

PURPOSE: To evaluate the safety, efficacy and outcome of percutaneous balloon-expandable covered stent graft placement for uretero-iliac artery fistula (UAF) treatment. METHODS: This retrospective study evaluated the single-center experience of percutaneous balloon-expandable covered stent graft placement (ADVANTA™, Atrium Hudson, NH, USA) in UAF. Data were obtained from a prospective institutional database. Patient follow-up included complications, symptoms recurrence and mortality rate. RESULTS: Ten UAFs in eight patients (3 males; 5 females) with a mean age of 64.5 (35-77) years were identified. All patients had a history pelvic malignancy, extirpative surgery (n = 6), long-term ureteral stenting (n = 7) and pelvic radiation (n = 5). All procedures were completed successfully without complications. Thirty-day mortality rate was zero. At a median follow-up of 6 (1-60) months, one patient suffered recurrent hematuria requiring a secondary stent graft placement 26 months after the initial treatment. During follow-up, five patients died of the underlying disease (43, 66, 105, and 183 and 274 days after the last procedure). CONCLUSION: Percutaneous balloon-expandable stent graft placement in UAF is a safe and effective treatment option. Implantation of stent grafts should be considered as treatment of choice in UAF.

Assessment of right atrium volume by conventional CT or MR techniques: Which modality resembles in vivo reality?

PURPOSE: Right atrial volume (RAV) is a prognostic factor of the right heart function. This retrospective study evaluates the comparability of computed tomography (CT) and magnetic resonance imaging (MRI) for right atrial volumetry with conventional planimetric and diametric methods. MATERIAL AND METHODS: 29 retrospectively included patients (18 male, 47±12years) underwent CT and 1.5 Tesla MRI within 17±20days. RAV was measured using biplane and ellipsoid method (MRI and CT) and Simpson's method (CT). For interobserver comparison measurements were carried out by two observers. Pearson's correlation, Lin's concordance coefficient, and Bland-Altman statistics were calculated. RESULTS: There is a correlation of RAV between CT and MRI, r [ellipsoid]=0.65; r [biplane]=0.64 (p<0.001). MRI volumes were significantly lower than CT volumes, [mean±SD] 43±19ml versus 27±9ml, (p<0.002). There was a close interobserver correlation (CT: r=0.83, MRI: r=0.73; p<0.001) but a relatively wide range in Bland-Altman analysis; limits of agreement from ±13ml up to ±29ml. CONCLUSIONS: Compared to left atrial volumes, a higher variability was found for RAV values both in interobserver statistiscs and in intermodality comparison. Complex shape of the right atrium, artifacts due to contrast material (CT), high venous return in inspiration (CT), high flow contrast media administration (CT) and increased heart rate (MRI) might cause these clinically relevant variations.