Radiomic signatures to predict survival in patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib +/- doxorubicin: Correlative science from CALGB 80802 (Alliance).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 343-343
Author(s):  
Laurent Dercle ◽  
Susan Michelle Geyer ◽  
Andrew B. Nixon ◽  
Federico Innocenti ◽  
Qian Shi ◽  
...  
Keyword(s):  
Error Rate ◽  
Tumor Volume ◽  
Quantitative Imaging ◽  
Measurement Techniques ◽  
Tumor Burden ◽  
Phase Iii ◽  
Advanced Hepatocellular Carcinoma ◽  
Imaging Features ◽  
Time Points ◽  
Validation Set

343 Background: Alliance/CALGB 80802, a randomized phase III trial, evaluated sorafenib plus doxorubicin vs. doxorubicin in pts with HCC and showed no improvement in median overall survival (OS) (HR[95CI] 1.05[0.83-1.31]) or PFS (HR[95CI] 0.93[0.75-1.16]). In HCC surrogacy of tumor response with OS remains controversial, in part due to varying criteria used for response evaluation (e.g., RECIST1.1 and mRECIST). We evaluated the performance of several models to predict OS using pretreatment clinical and radiomic variables. Methods: In CALBG 80802, we segmented all measurable tumor lesions on sequential CT scans. A lesion’s imaging phenotype was deciphered with 23 uncorrelated quantitative imaging features measured at baseline and week (wk) 10 (first follow-up). An OS landmark survival analysis was conducted at wk 10. Patients were randomly assigned (3:1) to training (n = 92) and validation (n = 37) sets. In a training set, 6 random forest predictive models (6 signatures) used features that best predicted OS using 3 sets of variables: radiomics only (n = 23), clinical only (n = 9), radiomics and clinical (n = 32). Two time points (baseline only or baseline + wk 10) were assessed. Each signature's output was an individualized prediction and a continuous value ranging from 0 to 1 (from most to least favorable predicted OS). The primary endpoint was to compare these models' performance to predict OS using error rate (Harrell's concordance-index) in the validation set. Results: Of the 6 training signatures evaluated, the one achieving the highest performance in the validation set was an 8-feature signature combining radiomics and clinical variables measured at two time points (baseline + wk 10) with an error rate of 35.6%. The variables [rank of importance] (table) selected by the signature included baseline clinical features (albumin[1], AFP[2], Child-Pugh[4]), baseline radiomics features (component 17[3], component 1[5], component 9[7], tumor volume[8]) and wk 10 radiomics features (delta tumor volume[6]). Variable delta tumor volume [6] used a more enhanced estimation of tumor burden at baseline and a delta tumor volumetric measurement; compared to RECIST1.1 measurement of percentage change in unidimensional measurement of a subset of target lesions. The four quartiles of the signature were significantly associated with OS (Log-Rank, P < 0.0001). Conclusions: The selected combined radiomic and clinical composite signature provided the best prediction for OS in the 80802 study patients’ population. It is a suggested way forward to go beyond single anatomic measurement techniques such as RECIST or mRECIST. [Table: see text]

Prognostic Value Of Plasma Biomarkers Compared To Urinary Proteome Patterns

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4593-4593
Author(s):  
Christin Human ◽  
Sylvia Borchers ◽  
Michael Stadler ◽  
Helmut Diedrich ◽  
Jürgen Krauter ◽  
...  
Keyword(s):  
Clinical Diagnosis ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Phase Iii ◽  
Test Set ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Plasma Biomarkers ◽  
Time Points ◽  
Validation Set

Introduction Graft-versus-host disease (GvHD) is a major complication and cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Prediction of acute GvHD is essential to optimize treatment. An effective method for early investigator independent diagnosis of aGvHD is under investigation in a phase III clinical trial. A urinary proteomic pattern – aGvHD-MS17 – is evaluated in a preemptive treatment trial, administering steroids at the time of pattern positivity. Here we present our data for early diagnosis of GvHD by monitoring easily accessible samples like urine for the presence of a specific proteom pattern and compare the data to published plasma biomarkers. Methods Plasma and urine were collected from patients after HSCT at defined time points (Weissinger et al., Blood 2007). Capillary electrophoresis and mass spectometry (CE-MS) analyses were done according to Weissinger et al., Blood 2007 and Leukemia, 2013. Two peptides found to be highly specific in urine for development of aGvHD were β2-microglobulin (β2m) and CD99. For both, antibodies are available and thus they can be analyzed in plasma samples from the same patients with ready-to-use ELISA-kits (Pasnecey et al., 2010). Plasma biomarkers were first analyzed in a test set based on 34 patients, followed by validation in 31 patients. As a further contribution to harmonization, published plasma biomarkers elafin, soluble IL-2-receptor alpha (IL-2sRα), REG3α, ST2 (IL-1 receptor 4) and sTNFRI were added to the ELISA-panel. Using the angiogenesis panel for bioluminex analyses, IL-8 and hepatocyte growth factor (HGF) were analyzed in addition and the outcomes were compared to the urinary proteomic analyses. Results & Discussion While the urine derived CE-MS pattern was able to predict an upcoming GvHD prior to the development of clinical signs, most of the plasma biomarkers could not predict pending GvHD. The test set for analysis of plasma consisted of 20 patients with aGvHD, from whom samples from the time of clinical diagnosis of aGvHD were used, and 14 controls without aGvHD at any time. Receiver operated characteristic curves were generated, areas under the curve (AUC) were more than 80% for β2m, CD99, sIL2Rα and sTNFRI (p<0.01). The validation set consisted of samples from 31 patients at different time points (7 samples each patient). In the validation set some markers did not reach their established cut-off point for aGvHD-diagnosis prior to or at the day of clinical diagnosis of aGvHD. Especially REG3α and elafin did not turn positive in any samples of patients with acute GvHD. Both markers presumably are organ-specific, but also limiting the analysis to patients with isolated GvHD of the intestine (REG3α) or skin (elafin) did not increase the sensitivity of these markers. CD99 and β2m discriminated patients with aGvHD from controls and CD99 was even specific for chronic GvHD and could distinguish between patients with acute and chronic GvHD with high sensitivity (89%) and specificity (95%); AUC was 86% (p<0.001). Additional problems with the ELISA-technique were the need to dilute samples prior to testing due to highly diverse concentrations of the biomarkers. The concentrations sometimes varied by the factor of 10 or more which required preparation of each sample in different dilutions. This made diagnosis based on ELISA data more time consuming and costly as envisioned. Urine on the other hand has shown to be stable and to provide a reliable proteome pattern. Furthermore, urinary proteom analysis can be normalized within each sample by using internal standards. Conclusion and future perspectives Prediction of pending aGvHD in patients post-allogeneic HSCT is possible with urine monitoring using CE-MS analyses with a sensitivity of 82% and specificity of 77% for aGvHD (Weissinger et al., Leukemia 2013). In contrast, published plasma biomarkers in our hands lack reliable sensitivity and specificity in the validation set. In addition, the markers detected in plasma do not appear to predict development of aGvHD. Biomarkers identified in urine (CD99 and β2m) can be found in plasma as well and are predictive for aGvHD-development. CD99 is also predictive for cGvHD development which can be explained by its function as an activation marker of (donor) T-cells. In conclusion, our results demonstrate that plasma monitoring post-allogeneic HSCT seems less reliable than urinary proteomics for prediction of aGvHD. Disclosures: No relevant conflicts of interest to declare.

scholarly journals MRI-based Radiomics Model Can Improve the Predictive Performance of Postlaminar Optic Nerve Invasion in Retinoblastoma

2021 ◽  
Author(s):  
Zhenzhen Li ◽  
Jian Guo ◽  
Xiaolin Xu ◽  
Wenbin Wei ◽  
Junfang Xian
Keyword(s):  
Optic Nerve ◽  
Quantitative Imaging ◽  
Area Under The Curve ◽  
Predictive Performance ◽  
Visual Assessment ◽  
Recursive Feature Elimination ◽  
Imaging Features ◽  
Training Set ◽  
Nerve Invasion ◽  
Validation Set

Abstract Purpose: To develop an MRI-based radiomics model to predict postlaminar optic nerve invasion (PLONI) in retinoblastoma (RB) and to compare its predictive performance with that of subjective radiologists’ assessment.Methods: We retrospectively enrolled 124 patients with pathologically proven RB (90 in the training set and 34 in the validation set) who had MRI scans before surgery in this retrospective study. A radiomics model for predicting PLONI was developed by extracting 2058 quantitative imaging features from axial T2-weighted images and contrast-enhanced T1-weighted images in the training set. The Kruskal-Wallis test, least absolute shrinkage and selection operator regression, and recursive feature elimination were used for feature selection, whereupon a radiomics model was built with a logistic regression (LR) classifier. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve and the accuracy were assessed to evaluate the predictive performance of PLONI in the training set and validation set. The performance of the radiomics model was compared to radiologists’ assessment.Results: The AUC of the radiomics model for the prediction of PLONI according to ROC analysis was 0.928 in the training set and 0.841 in the validation set. In all 124 patients, the AUC of the radiomics model was 0.897, while that of radiologists’ assessment was 0.674 (p< 0.001).Conclusions: By incorporating MRI-based radiomics features, we constructed a radiomics model to predict PLONI in patients with RB, and it was shown to be superior to visual assessment and may serve as a potential tool to guide personalized treatment.

Different organ-specific response to nivolumab to determine the survival outcome of patients with advanced hepatocellular carcinoma (aHCC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4584-4584
Author(s):  
Han Sang Kim ◽  
Jung Yong Hong ◽  
Jaekyung Cheon ◽  
Ilhwan Kim ◽  
Chang Gon Kim ◽  
...  
Keyword(s):  
Lymph Node ◽  
Liver Function ◽  
Tumor Burden ◽  
Phase Iii ◽  
Survival Outcomes ◽  
Specific Response ◽  
Advanced Hepatocellular Carcinoma ◽  
Clinicopathological Factors ◽  
Organ Specific ◽  
Intrahepatic Tumor

4584 Background: Previously, two phase III clinical trials of immune checkpoint inhibitors (ICI) failed to meet their primary endpoints, leading to doubts regarding the clinical activity of ICI monotherapy in patients with aHCC. Here, we comprehensively examined clinicopathological factors and estimated their association with survival outcomes in aHCC patients treated with nivolumab. Methods: A total of 261 eligible patients from 5 high-volume centers who were treated with nivolumab between June 9, 2012 and March 14, 2018 and had measurable diseases were reviewed. We reviewed more than 80 clinicopathological factors and categorized them into 6 areas: 1) demographics (n = 16); 2) baseline laboratory values (n = 19); 3) tumor burden (n = 12); 4) previous treatment (n = 12); 5) treatment response (n = 5); 6) toxicity profiles (n = 18). Their association with survival outcomes were evaluated, and organ-specific response evaluation, adapted from RECIST 1.1, was conducted. Results: Of the 261 patients, 218 (84%) had extrahepatic spread. The median follow-up time was 4.5 months. The median progression-free survival (PFS) and overall survival (OS) were 2.3 months (95% CI, 1.8-2.8) and 6.3 months (95% CI, 5.0-8.2). Objective response rate was 15%. Subgroup analyses revealed that compensated liver function (Child-Pugh score A5/6), surrogate markers for low tumor burden (low AFP, low PIVKA, and low LDH level), inflammatory markers (low C-reactive protein [CRP], low erythrocyte sedimentation rate [ESR], low neutrophil-to-lymphocyte ratio [NLR], high lymphocyte-to-monocyte ratio [LMR]), and low intrahepatic tumor burden were significantly associated with longer OS. A total of 456 individual lesions (liver, n = 249; lung, n = 124; lymph node, n = 35; others such as boner soft tissues, n = 48) were examined. Organ-specific response rates (hepatic tumor, 9%; lung, 25%; lymph node, 37%; others metastasis, 15%) were different, of which intrahepatic tumor was the least responsive organ to ICI treatment in aHCC. Conclusions: Underlying liver function, the tumor extent and burden, and the degree of plasma lymphocytes are crucial for determining tumor response to ICI in aHCC. Antitumor immune response to ICI differs in an organ-specific manner. The hepatic tumors of HCC may be less responsive to nivolumab than extrahepatic lesions.

Real-world efficacy and safety of lenvatinib-base therapy for patients with unresectable hepatocellular carcinoma in China: A multicenter retrospective analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16192-e16192
Author(s):  
Qicong Mai ◽  
Song Chen ◽  
Feng Shi ◽  
Zhiqiang Mo ◽  
Jian He ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Real World ◽  
Objective Response ◽  
Progression Free Survival ◽  
Tumor Burden ◽  
Phase Iii ◽  
Advanced Hepatocellular Carcinoma ◽  
First Line ◽  
Grade 3

e16192 Background: Lenvatinib has been approved as a first-line systemic for advanced hepatocellular carcinoma (HCC) after the randomized phase III REFLECT trial. The aim of this study was to assess the lenvatinib-base treatment patterns and safety in real-world clinical settings in China. Methods: In this multicenter retrospective study, A total of 278 patients with unresectable HCC were treated with lenvatinib-base treatment between October 2018 and November 2020 were analyzed. Therapeutic effect was determined using the RECIST 1.1 and mRECIST criteria. Progression free survival (PFS), overall survival (OS) and treatment-related adverse events (TRAE) were also evaluated. Results: Of 278 unresectable HCC patients (median age: 56.1±11.9 years), 220 (79.1%) had cirrhosis caused by HBV infection. 215 (77.3%) and 63 (22.7%) patients were classified as Child-pugh A and B class, respectively. 233 (83.8%) and 45 (16.2%) patients received lenvatinib in first-line and second-line systemic therapies, respectively. 223 (80.2%) patients were treated with lenvatinib plus arterially directed therapy (TACE or HAIC of FOLFOX) and 55 (19.8%) were treated with lenvatinib alone. The objective response rate were 34.9% (RECIST) and 47.5% (mRECIST), while the disease control rate were 75.5%. With a median follow-up period of 12.8 months, the median PFS and OS were 7.8 months (95% CI 7.1–8.4) and 17.2 months (95% CI 14.9–19.6), respectively. Results from the multivariate analysis showed that the significant independent favorable prognosis factors were tumor burden< 50% (P=0.033), Child–Pugh A class (P<0.01), AFP level <200ng/mL (P=0.045), the combination with lenvatinib and arterially directed therapy (P<0.01). TRAE occurred in 219 of 278 patients (78.8%), most common TRAE were hypertension (n=118; 42.4%) and hand-foot skin reaction (n=91; 32.7%). The most common grade 3–4 TARE were hypertension (n=23; 8.3%), decreased appetite (n=18; 6.5%), AST elevation (n=14; 5%), and diarrhea (n=14; 5%) across all study patients. Conclusions: In this multicenter real-world study, lenvatinib-base treatment could be accomplished with well tolerated and response for unresectable HCC patients. Combination with arterially directed therapy could likely improve the overall survival.

scholarly journals MRI-based radiomics model can improve the predictive performance of postlaminar optic nerve invasion in retinoblastoma

2021 ◽  
Author(s):  
Zhenzhen Li ◽  
Jian Guo ◽  
Xiaolin Xu ◽  
Wenbin Wei ◽  
Junfang Xian
Keyword(s):  
Optic Nerve ◽  
Quantitative Imaging ◽  
Area Under The Curve ◽  
Predictive Performance ◽  
Visual Assessment ◽  
Recursive Feature Elimination ◽  
Imaging Features ◽  
Training Set ◽  
Nerve Invasion ◽  
Validation Set

Objectives: To develop an MRI-based radiomics model to predict postlaminar optic nerve invasion (PLONI) in retinoblastoma (RB) and compare its predictive performance with subjective radiologists’ assessment. Methods: We retrospectively enrolled 124 patients with pathologically proven RB (90 in training set and 34 in validation set) who had MRI scans before surgery. A radiomics model for predicting PLONI was developed by extracting quantitative imaging features from axial T2-weighted images and contrast-enhanced T1-weighted images in the training set. The Kruskal-Wallis test, least absolute shrinkage and selection operator regression, and recursive feature elimination were used for feature selection, whereupon a radiomics model was built with a logistic regression (LR) classifier. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve and the accuracy were assessed to evaluate the predictive performance in the training and validation set. The performance of the radiomics model was compared to radiologists’ assessment by DeLong test. Results: The AUC of the radiomics model for the prediction of PLONI was 0.928 in the training set and 0.841 in the validation set. Radiomics model produced better sensitivity than radiologists’ assessment (81.1% vs  43.2% in training set, 82.4vs 52.9% in validation set). In all 124 patients, the AUC of the radiomics model was 0.897, while that of radiologists’ assessment was 0.674 (p < 0.001, DeLong test). Conclusion: MRI-based radiomics model to predict PLONI in RB patients was shown to be superior to visual assessment with improved sensitivity and AUC, may serve as a potential tool to guide personalized treatment.

Intra-scanner repeatability of quantitative imaging features in a 3D printed semi-anthropomorphic CT phantom

2021 ◽  
pp. 109818
Author(s):  
Hanna Muenzfeld ◽  
Claus Nowak ◽  
Stefanie Riedlberger ◽  
Alexander Hartenstein ◽  
Bernd Hamm ◽  
...  
Keyword(s):  
Quantitative Imaging ◽  
Imaging Features ◽  
3D Printed

Brivanib in Patients With Advanced Hepatocellular Carcinoma Who Were Intolerant to Sorafenib or for Whom Sorafenib Failed: Results From the Randomized Phase III BRISK-PS Study

2013 ◽  
Vol 31 (28) ◽  
pp. 3509-3516 ◽  
Author(s):  
Josep M. Llovet ◽  
Thomas Decaens ◽  
Jean-Luc Raoul ◽  
Eveline Boucher ◽  
Masatoshi Kudo ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Growth Factor ◽  
Controlled Trial ◽  
Objective Response ◽  
Phase Iii ◽  
Advanced Hepatocellular Carcinoma ◽  
Time To Progression ◽  
Fibroblast Growth Factor Receptors ◽  
Double Blind ◽  
Dual Inhibitor

Purpose Brivanib is a selective dual inhibitor of vascular endothelial growth factor and fibroblast growth factor receptors implicated in tumorigenesis and angiogenesis in hepatocellular carcinoma (HCC). An unmet medical need persists for patients with HCC whose tumors do not respond to sorafenib or who cannot tolerate it. This multicenter, double-blind, randomized, placebo-controlled trial assessed brivanib in patients with HCC who had been treated with sorafenib. Patients and Methods In all, 395 patients with advanced HCC who progressed on/after or were intolerant to sorafenib were randomly assigned (2:1) to receive brivanib 800 mg orally once per day plus best supportive care (BSC) or placebo plus BSC. The primary end point was overall survival (OS). Secondary end points included time to progression (TTP), objective response rate (ORR), and disease control rate based on modified Response Evaluation Criteria in Solid Tumors (mRECIST) and safety. Results Median OS was 9.4 months for brivanib and 8.2 months for placebo (hazard ratio [HR], 0.89; 95.8% CI, 0.69 to 1.15; P = .3307). Adjusting treatment effect for baseline prognostic factors yielded an OS HR of 0.81 (95% CI, 0.63 to 1.04; P = .1044). Exploratory analyses showed a median time to progression of 4.2 months for brivanib and 2.7 months for placebo (HR, 0.56; 95% CI, 0.42 to 0.76; P < .001), and an mRECIST ORR of 10% for brivanib and 2% for placebo (odds ratio, 5.72). Study discontinuation due to treatment-related adverse events (AEs) occurred in 61 brivanib patients (23%) and nine placebo patients (7%). The most frequent treatment-related grade 3 to 4 AEs for brivanib included hypertension (17%), fatigue (13%), hyponatremia (11%), and decreased appetite (10%). Conclusion In patients with HCC who had been treated with sorafenib, brivanib did not significantly improve OS. The observed benefit in the secondary outcomes of TTP and ORR warrants further investigation.

Total tumor burden in lymphoma – an evolving strong prognostic parameter

2021 ◽  
pp. 20210448
Author(s):  
Michel Meignan ◽  
Anne-Segolene Cottereau ◽  
Lena Specht ◽  
N. George Mikhaeel
Keyword(s):  
Tumor Volume ◽  
Cell Lymphoma ◽  
Strong Predictor ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Risk Groups ◽  
Metabolic Tumor Volume ◽  
Tumor Burden ◽  
Interim Pet ◽  
Fdg Pet Ct

Total metabolic tumor volume (TMTV), a new parameter extracted from baseline FDG-PET/CT, has been recently proposed by several groups as a prognosticator in lymphomas before first-line treatment. TMTV, the sum of the metabolic volume of each lesion, is an index of the metabolically most active part of the tumor and highly correlates with the total tumor burden. TMTV measurement is obtained from PET images processed with different software and techniques, many being now freely available. In the various lymphoma subtypes where it has been measured, such as diffuse large B-cell lymphoma, Hodgkin lymphoma, Follicular Lymphoma, and Peripheral T-cell lymphoma, TMTV has been reported as a strong predictor of outcome (progression-free survival and overall survival) often outperforming the clinical scores, molecular predictors, and results of interim PET. Combined with these scores, TMTV improves the stratification of the populations into risk groups with different outcomes. TMTV cut-off separating the high-risk from the low-risk population impacts the outcome whatever the technique used for its measurement and an international harmonization is ongoing. TMTV is a unique and easy tool that could replace the surrogate of tumor burden included in the prognostic indexes used in lymphoma and help tailor therapy. Other parameters extracted from the baseline PET may give an information on the dissemination of this total tumor volume such as the maximum distance between the lesions. Trials based on TMTV would probably demonstrate its predictive value.

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