Pre-treatment 18F-FDG-PET/CT parameters as biomarkers for progression free survival, best overall response and overall survival in metastatic melanoma patients undergoing first-line immunotherapy.

BACKGROUND: Checkpoint inhibitors have drastically improved the therapy of patients with advanced melanoma. 18F-FDG-PET/CT parameters might act as biomarkers for response and survival and thus can identify patients that do not benefit from immunotherapy. However, little literature exists on the association of baseline 18F-FDG-PET/CT parameters with progression free survival (PFS), best overall response (BOR), and overall survival (OS). MATERIALS AND METHODS: Using a whole tumor volume segmentation approach, we investigated in a retrospective registry study (n = 50) whether pre-treatment 18F-FDG-PET/CT parameters of three subgroups (tumor burden, tumor glucose uptake and non-tumoral hematopoietic tissue metabolism), can act as biomarkers for the primary endpoints PFS and BOR as well as for the secondary endpoint OS. RESULTS: Compared to the sole use of clinical parameters, baseline 18F-FDG-PET/CT parameters did not significantly improve a Cox proportional-hazard model for PFS (C-index/AIC: 0.70/225.17 and 0.68/223.54, respectively; p = 0.14). A binomial logistic regression analysis for BOR was not statistically significant (χ2(15) = 16.44, p = 0.35), with a low amount of explained variance (Nagelkerke's R2 = 0.38). Mean FDG uptake of the spleen contributed significantly to a Cox proportional-hazard model for OS (HR 3.55, p = 0.04). CONCLUSIONS: The present study could not confirm the capability of the pre-treatment 18F-FDG-PET/CT parameters tumor burden, tumor glucose uptake and non-tumoral hematopoietic tissue metabolism to act as biomarkers for PFS and BOR in metastatic melanoma patients receiving first-line immunotherapy. The documented potential of 18F-FDG uptake by immune-mediating tissues such as the spleen to act as a biomarker for OS has been reproduced.

Can Whole-Body Baseline CT Radiomics Add Information to the Prediction of Best Response, Progression-Free Survival, and Overall Survival of Stage IV Melanoma Patients Receiving First-Line Targeted Therapy: A Retrospective Register Study.

BACKGROUND: The aim of this study was to investigate whether the combination of radiomics and clinical parameters in a machine-learning model offers additive information compared with the use of only clinical parameters in predicting the best response, progression-free survival after six months, as well as overall survival after six and twelve months in patients with stage IV malignant melanoma undergoing first-line targeted therapy. METHODS: A baseline machine-learning model using clinical variables (demographic parameters and tumor markers) was compared with an extended model using clinical variables and radiomic features of the whole tumor burden, utilizing repeated five-fold cross-validation. Baseline CTs of 91 stage IV malignant melanoma patients, all treated in the same university hospital, were identified in the Central Malignant Melanoma Registry and all metastases were volumetrically segmented (n = 4727). RESULTS: Compared with the baseline model, the extended radiomics model did not add significantly more information to the best-response prediction (AUC [95% CI] 0.548 (0.188, 0.808) vs. 0.487 (0.139, 0.743)), the prediction of PFS after six months (AUC [95% CI] 0.699 (0.436, 0.958) vs. 0.604 (0.373, 0.867)), or the overall survival prediction after six and twelve months (AUC [95% CI] 0.685 (0.188, 0.967) vs. 0.766 (0.433, 1.000) and AUC [95% CI] 0.554 (0.163, 0.781) vs. 0.616 (0.271, 1.000), respectively). CONCLUSIONS: The results showed no additional value of baseline whole-body CT radiomics for best-response prediction, progression-free survival prediction for six months, or six-month and twelve-month overall survival prediction for stage IV melanoma patients receiving first-line targeted therapy. These results need to be validated in a larger cohort.

Combination of Whole-Body Baseline CT Radiomics and Clinical Parameters to Predict Response and Survival in a Stage-IV Melanoma Cohort Undergoing Immunotherapy.

BACKGROUND: This study investigated whether a machine-learning-based combination of radiomics and clinical parameters was superior to the use of clinical parameters alone in predicting therapy response after three months, and overall survival after six and twelve months, in stage-IV malignant melanoma patients undergoing immunotherapy with PD-1 checkpoint inhibitors and CTLA-4 checkpoint inhibitors. METHODS: A random forest model using clinical parameters (demographic variables and tumor markers = baseline model) was compared to a random forest model using clinical parameters and radiomics (extended model) via repeated 5-fold cross-validation. For this purpose, the baseline computed tomographies of 262 stage-IV malignant melanoma patients treated at a tertiary referral center were identified in the Central Malignant Melanoma Registry, and all visible metastases were three-dimensionally segmented (n = 6404). RESULTS: The extended model was not significantly superior compared to the baseline model for survival prediction after six and twelve months (AUC (95% CI): 0.664 (0.598, 0.729) vs. 0.620 (0.545, 0.692) and AUC (95% CI): 0.600 (0.526, 0.667) vs. 0.588 (0.481, 0.629), respectively). The extended model was not significantly superior compared to the baseline model for response prediction after three months (AUC (95% CI): 0.641 (0.581, 0.700) vs. 0.656 (0.587, 0.719)). CONCLUSIONS: The study indicated a potential, but non-significant, added value of radiomics for six-month and twelve-month survival prediction of stage-IV melanoma patients undergoing immunotherapy.

Is a single portal venous phase in contrast-enhanced CT sufficient to detect metastases or recurrence in clear cell renal cell carcinoma? - a single-center retrospective study.

BACKGROUND: This study aims at describing the imaging features of the metastatic presentation of clear cell renal cell carcinoma (ccRCC) in arterial (AP) and portal venous phase (PVP) of contrast-enhanced-computed-tomography (CECT) during clinical follow-up (FU) and to evaluate the necessity of a dual phase approach for metastasis detection. METHODS: We identified a total of 584 patients that were diagnosed with ccRCC between January 2016 and April 2020. Inclusion criteria were histologically proven ccRCC with metastatic spread, proven by histology or interim follow-up of at least 2 years and follow-up CT examination with AP and PVP CECT including thorax/abdomen and pelvis. Exclusion criteria were defined by missing or incomplete CT-scans or lack of sufficient follow-up. CT studies of 43 patients with histologically proven ccRCCs were analyzed in retrospect. AP and PVP images were analyzed by two radiologists for metastases, two additional independent radiologists analyzed PVP images only. A 5-point Likert scale was used to evaluate the likelihood off the presence of metastasis. Imaging patterns of the metastases were analyzed visually. RESULTS: 43 patients (16 female; mean age: 67±10 years) with recurrent ccRCC and metastatic disease were included. Three imaging patterns were observed (solid, heterogeneous or cystic metastases), which rarely exhibited calcifications (2%). All metastases showed hyperenhancement in AP and PVP. Inter-reader agreement was substantial (Fleiss' κ 0.6-0.8, p<0.001). No significant differences in sensitivity or specificity between readers (AP and PVP images vs. PVP images only) were present (79.4-85.2%, 97.1-99.6%, p ≥ 0.05). The area under the receiver-operating-characteristic (ROC) curve was between 0.901and 0.922 for all four radiologists. CONCLUSIONS: Similar rates for detection, sensitivity and specificity of metastasis and local recurrence in ccRCC were observed irrespective of using a dual-phase protocol with AP and PVP or a single PVP protocol only. Thus, a single-phase examination of PVP can be sufficient for experienced radiologists to detect metastatic disease in the follow-up of ccRCC patients.

Early Tumor Size Reduction of at least 10% at the First Follow-Up Computed Tomography Can Predict Survival in the Setting of Advanced Melanoma and Immunotherapy.

RATIONALE AND OBJECTIVES: Early tumor size reduction (TSR) has been explored as a prognostic factor for survival in patients with advanced melanoma in clinical trials. The purpose of this analysis is to validate, in a routine clinical milieu, the predictive capacity of TSR by 10% for overall survival (OS) and progression-free survival (PFS) and to compare its predictive performance with the RECIST 1.1 criteria. MATERIALS AND METHODS: This retrospective study was approved by the local ethics committee. A total of 152 patients with both CT before immunotherapy initiation and at first response evaluation after immunotherapy initiation were included. Prior to statistical analysis, treatment response was trichotomized as follows: Complete response and/or partial response, stable disease and progressive disease. Furthermore, response was dichotomized regarding TSR (TSR ≥ 10% and TSR < 10%). Kaplan-Meier survival estimates, Cox regression and Harrel's concordance index (C-index) were computed for prediction of overall survival and progression-free survival. RESULTS: Tumor size reduction by at least 10% significantly differentiated between patients with increased survival from the ones with decreased survival (median OS: TSR ≥ 10%: 2137 days vs. TSR < 10%: 263 days) (p < 0.001) (median PFS: TSR ≥ 10%: 590 days vs. TSR < 10%: 11 days) (p < 0.001). RECIST 1.1. criteria had a slightly higher C-index for overall survival reflecting a slight superior predictive capacity (RECIST: 0.69 vs TSR: 0.64) but a similar predictive capacity regarding progression-free survival (both: 0. 63). CONCLUSION: Early tumor size reduction serves as a simple-to-use metric which can be implemented on the first follow-up CT. Tumor size reduction by at least 10% can be considered an additional biomarker predictive of overall survival and progression-free survival in routine clinical care and not only in the context of clinical trials in patients with advanced melanoma undergoing immunotherapy. Nevertheless, RECIST-based criteria should remain the main tool of treatment response assessment until results of prospective studies validating the TSR method are available.

A Machine learning model trained on dual-energy CT radiomics significantly improves immunotherapy response prediction for patients with stage IV melanoma.

BACKGROUND: To assess the additive value of dual-energy CT (DECT) over single-energy CT (SECT) to radiomics-based response prediction in patients with metastatic melanoma preceding immunotherapy. MATERIAL AND METHODS: A total of 140 consecutive patients with melanoma (58 female, 63±16 years) for whom baseline DECT tumor load assessment revealed stage IV and who were subsequently treated with immunotherapy were included. Best response was determined using the clinical reports (81 responders: 27 complete response, 45 partial response, 9 stable disease). Individual lesion response was classified manually analogous to RECIST 1.1 through 1291 follow-up examinations on a total of 776 lesions (6.7±7.2 per patient). The patients were sorted chronologically into a study and a validation cohort (each n=70). The baseline DECT was examined using specialized tumor segmentation prototype software, and radiomic features were analyzed for response predictors. Significant features were selected using univariate statistics with Bonferroni correction and multiple logistic regression. The area under the receiver operating characteristic curve of the best subset was computed (AUROC). For each combination (SECT/DECT and patient response/lesion response), an individual random forest classifier with 10-fold internal cross-validation was trained on the study cohort and tested on the validation cohort to confirm the predictive performance. RESULTS: We performed manual RECIST 1.1 response analysis on a total of 6533 lesions. Multivariate statistics selected significant features for patient response in SECT (min. brightness, R²=0.112, padj. ≤0.001) and DECT (textural coarseness, R²=0.121, padj. ≤0.001), as well as lesion response in SECT (mean absolute voxel intensity deviation, R²=0.115, padj. ≤0.001) and DECT (iodine uptake metrics, R²≥0.12, padj. ≤0.001). Applying the machine learning models to the validation cohort confirmed the additive predictive power of DECT (patient response AUROC SECT=0.5, DECT=0.75; lesion response AUROC SECT=0.61, DECT=0.85; p<0.001). CONCLUSION: The new method of DECT-specific radiomic analysis provides a significant additive value over SECT radiomics approaches for response prediction in patients with metastatic melanoma preceding immunotherapy, especially on a lesion-based level. As mixed tumor response is not uncommon in metastatic melanoma, this lends a powerful tool for clinical decision-making and may potentially be an essential step toward individualized medicine.

CT hepatic arterial perfusion index does not allow stratification of the degree of esophageal varices and bleeding risk in cirrhotic patients in Child-Pugh classes A and B.

PURPOSE: To evaluate if the hepatic arterial perfusion index (HPI) in liver parenchyma of cirrhotic patients can serve as a surrogate parameter for stratifying the degree of esophageal varices and related bleeding risks. METHODS: CT image data of sixty-six patients (59 men; mean age 68 years ± 10 years) with liver cirrhosis (Child-Pugh class A (35/66, 53%), B (25/66, 38%), and C (6/66, 9%) who underwent perfusion CT (PCT) for hepatocellular carcinoma (HCC) screening between April 2010 and January 2019 were retrospectively identified. HPI, a parameter calculated by a commercially available CT liver perfusion analysis software that is based on the double maximum slope model, using time attenuation curve to determine perfusion, was correlated with the degree of esophageal varices diagnosed at endoscopy and the number of bleeding events. RESULTS: Eta correlation coefficient for HPI/presence of esophageal varices was very weak (0.083). Spearman-Rho for HPI/grading of esophageal varices was very weak (0.037 (p = 0.804)). Kendall-Tau-b for HPI/grading of esophageal varices was very weak (0.027 (p = 0.807)). ANOVA and Bonferroni post-hoc-tests showed no significant difference of HPI between different grades of esophageal varices (F (3, 62) = 1.676, p = 0.186). Eta correlation coefficient for HPI/bleeding event was very weak (0.126). CONCLUSION: The stratification of the degree of esophageal varices and the related bleeding risk by correlation with the HPI as a surrogate parameter for portal venous hypertension was not possible for patients with liver cirrhosis in Child-Pugh class A and B.

Intraprocedural cone-beam CT with parenchymal blood volume assessment for transarterial chemoembolization guidance: Impact on the effectiveness of the individual TACE sessions compared to DSA guidance alone.

PURPOSE: The objective of this retrospective single centre study was to evaluate the impact of intraprocedural cone-beam CT with parenchymal blood volume assessment (PBV-CBCT) for guidance of transarterial chemoembolization with drug-eluting beads (DEB-TACE) in HCC patients on the effectiveness (local tumour response, survival and number of individual TACE sessions) compared to guidance solely by digital subtraction angiography (DSA). METHOD: n = 179 HCC patients (mean age, 77.4 y) undergoing DEB-TACE, with (n = 28) and without (n = 151) PBV-CBCT, using 100-300 µm microspheres loaded with epirubicin were retrospectively analysed. Tumour response according to mRECIST, overall survival and number of TACE interventions as well as laboratory parameters for liver function and inflammation were recorded. The analysis of the influence of intraprocedural PBV-CBCT was based on matched pair analysis (CBCT n = 28 vs. DSA n = 28). Gender, tumour number, tumour size and HCC risk factors were equally distributed between both groups. RESULTS: Response rates according to mRECIST:CBCT: PD: 7%, SD: 28 %, PR: 46 %, CR: 18 %; DSA: PD: 7 %, SD: 32 %, PR: 39 %, CR: 21 % (p = 0.174). Median OS: CBCT: 44.1 months; DSA: 28.8 months (p = 0.815). Median TACE number: CBCT: 2.0; DSA: 3.0 (p = 0.046). CONCLUSIONS: The use of intraprocedural PBV-CBCT for TACE guidance reduced the number of re-interventions, with no negative effects on tumour response and overall survival. The study findings support the use of PBV-CBCT for DEB-TACE guidance as the improved immediate feedback leads to a considerable increase of the treatment efficiency and helps to avoid unnecessary re-interventions.

Simulated Radiation Dose Reduction in Whole-Body CT on a 3rd Generation Dual-Source Scanner: An Intraindividual Comparison.

To evaluate the effect of radiation dose reduction on image quality and diagnostic confidence in contrast-enhanced whole-body computed tomography (WBCT) staging. We randomly selected March 2016 for retrospective inclusion of 18 consecutive patients (14 female, 60 ± 15 years) with clinically indicated WBCT staging on the same 3rd generation dual-source CT. Using low-dose simulations, we created data sets with 100, 80, 60, 40, and 20% of the original radiation dose. Each set was reconstructed using filtered back projection (FBP) and Advanced Modeled Iterative Reconstruction (ADMIRE®, Siemens Healthineers, Forchheim, Germany) strength 1-5, resulting in 540 datasets total. ADMIRE 2 was the reference standard for intraindividual comparison. The effective radiation dose was calculated using commercially available software. For comparison of objective image quality, noise assessments of subcutaneous adipose tissue regions were performed automatically using the software. Three radiologists blinded to the study evaluated image quality and diagnostic confidence independently on an equidistant 5-point Likert scale (1 = poor to 5 = excellent). At 100%, the effective radiation dose in our population was 13.3 ± 9.1 mSv. At 20% radiation dose, it was possible to obtain comparably low noise levels when using ADMIRE 5 (p = 1.000, r = 0.29). We identified ADMIRE 3 at 40% radiation dose (5.3 ± 3.6 mSv) as the lowest achievable radiation dose with image quality and diagnostic confidence equal to our reference standard (p = 1.000, r > 0.4). The inter-rater agreement for this result was almost perfect (ICC ≥ 0.958, 95% CI 0.909-0.983). On a 3rd generation scanner, it is feasible to maintain good subjective image quality, diagnostic confidence, and image noise in single-energy WBCT staging at dose levels as low as 40% of the original dose (5.3 ± 3.6 mSv), when using ADMIRE 3.

Retroperitoneal Fibrosis and its Differential Diagnoses: The Role of Radiological Imaging. / Retroperitoneale Fibrose und ihre Differenzialdiagnosen: Die Rolle der radiologischen Bildgebung.

BACKGROUND: Retroperitoneal fibrosis is a rare disease with an incidence of 0-1/100 000 inhabitants per year and is associated with chronic inflammatory fibrosis of the retroperitoneum and the abdominal aorta. This article sheds light on the role of radiological imaging in retroperitoneal fibrosis, names various differential diagnoses and provides an overview of drug and surgical treatment options. METHODS: A literature search for the keywords "retroperitoneal fibrosis" and "Ormond's disease" was carried out in the PubMed database between January 1, 1995 and December 31, 2019 (n = 1806). Mainly original papers were selected, but also reviews, in English and German language, with a focus on publications in the last 10 years, without excluding older publications that the authors believe are relevant to the topic discussed in the review (n = 40). RESULTS AND CONCLUSION: Ormond's disease is a rare but important differential diagnosis for nonspecific back and flank pain. Imaging diagnostics using CT or MRI show a retroperitoneal mass, which must be differentiated from lymphoma, sarcoma, multiple myeloma and Erdheim-Chester disease. Patients have an excellent prognosis under adequate therapy. FDG-PET/CT or FDG-PET/MRT should be considered as potential modalities, as hybrid imaging can evaluate both the morphological changes and the inflammation. KEY POINTS: · Ormond's disease is a differential diagnosis for nonspecific back and flank pain.. · Radiological imaging is essential and the gold standard in the diagnosis and follow-up of RPF.. · Patients have an excellent prognosis under adequate therapy.. CITATION FORMAT: · Peisen F, Thaiss WM, Ekert K et al. Retroperitoneal Fibrosis and its Differential Diagnoses: The Role of Radiological Imaging. Fortschr Röntgenstr 2020; 192: 929 - 936.

Predictive performance of the mHAP-II score in a real-life western cohort with hepatocellular carcinoma following trans-arterial chemoembolisation with drug-eluting beads (DEB-TACE).

OBJECTIVES: To evaluate the predictive performance of the modified hepatoma arterial embolisation prognostic II (mHAP-II) score in a real-life western hepatocellular carcinoma (HCC) cohort treated with drug-eluting bead-TACE and compare the mHAP-II with other scores in this cohort. METHODS: One hundred seventy-nine HCC patients (mean age 77 (± 9) years, 87% male) with one or more drug-eluting bead (DEB)-TACE sessions using 100-300 µm microspheres were retrospectively analysed. Performance analysis of the mHAP-II score was based on Mann-Whitney U tests, the Kaplan-Meier method, log-rank tests, receiver operating characteristics, Akaike's information criterion and Cox regression models. RESULTS: In this population, HCC risk factors were mainly alcohol abuse (31%) and hepatitis C (28%). The median survival of the entire cohort was 29.4 months. mHAP-II classification of the cohort was mHAP-II B (30%), C (41%) and D (23%) respectively. Survival of all subgroups differed significantly from each other (each p < 0.05). Area under the curve for receiver operating characteristic was 0.60 and Akaike's information criterion was 21.8 (p = 0.03), indicating a superior performance of mHAP-II score compared with HAP score and BCLC. Tumour number ≥ two (HR 1.54), alpha-fetoprotein > 400 µg/l (HR 1.14), serum albumin < 3.6 g/dl (HR 1.63) and total bilirubin > 0.9 mg/dl (HR 1.58) contributed significantly in Cox proportional hazards regression (each p < 0.05). CONCLUSION: The mHAP-II score can predict survival outcomes of western HCC patients undergoing DEB-TACE and further subdivide this heterogeneous group; however, certain limitations concerning the predictive power of mHAP-II score must be taken into account. KEY POINTS: • This retrospective study evaluated the predictive performance of the modified hepatoma arterial embolisation prognostic II (mHAP-II) score in a real-life western HCC cohort treated with drug-eluting bead-TACE. • Survival of all mHAP-II subgroups differed significantly, area under the curve for mHAP-II was 0.60 and Akaike's information criterion was 21.8. • The mHAP-II score can predict survival outcomes of western HCC patients undergoing DEB-TACE and further subdivide this heterogeneous group. However, because the study is underpowered, true survival prediction may be more difficult to infer.