Predictive Value For Response Research Articles

Tumor board presentation of a woman with metastatic, hormone receptor‐positive, mismatch repair‐deficient endometrial cancer

Tumor board presentation of a woman with metastatic, hormone receptor‐positive, mismatch repair‐deficient endometrial cancer

Response Surface Methodology for the Optimized and Validated Investigation of Ropivacaine in Bulk and Tablet Dosage form by RP – HPLC

This study explains the response surface methodology-based novel RP-HPLC method for determining and validating ropivacaine in bulk and tablet dosage form. The effect of three critical, independent variables, the volume of ACN (acetonitrile) in the mobile phase, flow rate and wavelength on the responses Retention time, tailing factor, and Theoretical plates, were studied using Box- Behnken designs. The design was statistically analyzed using ANOVA, normal plot of residual, Box-Cox plot, perturbation, and 3D response surface plots. The quadratic model was used to predict response values. Chromatographic separation was obtained by ODS C18,5µm column with Isocratic elution. The mobile phase used is Acetonitrile (ACN): Methanol: Water (40:30:30) v/v, with 0.1% TEA. The flow rate was 1.5ml/min, and detection was carried out at 270nm. Retention time, R2, was 6.670mins and 0.9892, respectively. The %RSD was not more than 2.0% in accuracy. The validation of the optimized chromatographic method was carried out as per ICH guidelines. The DOE using Box- Behnken design explained a significant effect of the mobile phase on the responses. The results show that the method is accurate, simple, reproducible, economical, robust, and rapid for routine qualitative analysis.

P181 IBD patients with early clinical and sonographic improvements achieve better long-term outcomes than patients with clinical improvements alone – one-year interim results of the TRUST BEYOND study

Abstract Background In the treat-to-target era, frequent and objective monitoring of disease activity in IBD patients is emphasized [1]. Over the past years, intestinal ultrasound (IUS) has become a useful modality to monitor and assess disease activity and response to therapy. (Trans)mural response and healing examined by IUS have emerged as outcome measures of growing interest and potential therapeutic goals in the IBD community [2–4]. However, the predictive value of a composite clinical/IUS improvement for the long-term outcome remains elusive. Methods TRUST BEYOND is an ongoing, prospective, observational, multi-centre study in patients with active CD or UC initiating a biologic- or Januskinase-inhibitor (JAKi)-therapy at baseline. The aim of this study is to assess the predictive value of IUS parameters evaluated at week 12 for the long-term outcome after 52 weeks (assessed by clinical+ sonographic endpoints). For this interim analysis, 89 IBD patients (39 CD, 50 UC) with a documented visit at week 52 until September were included. The predictive value of (trans)mural response (TR; reduction of ≥ 25% in bowel wall thickness, BWT) and clinical remission at W12 was evaluated for the outcome at W52. Results Eighty-nine IBD patients in clinical flare with increased BWT were included into this analysis. Patients were predominantly female (53.9%,n=48) with a median age of 34.3 years (29.0–51.5) and a median disease duration of 7.18 years (2.31–13.47). Following the induction of advanced therapy, the rate of IBD patients with a (trans)mural response increased from 67.4% (n=60) at W12 to 73.0% (n=65) at W52. Likewise, the proportion of IBD patients demonstrating a (trans)mural healing rose from 32.6% (n=29) at W12 to 41.6% (n=37) at W52. Of note, 53.5% (n=38) of IBD patients who achieved the composite endpoint “clinical remission and (trans)mural response” at W12 were in clinical remission at W52 while only 23.9% of patients who were only in clinical remission at W12 sustained clinical remission until W52 (p=0.007). Moreover, patients achieving both early clinical remission and (trans)mural response had better sonographic outcomes at W52. Fig 1: W52 outcomes of patients with either clinical remission and (trans)mural response or only clinical remission at W12. Conclusion IBD patients who reached the composite endpoint clinical remission and (trans)mural response at week 12 had better outcomes after 1 year compared to patients in early clinical remission only. Our results strongly suggest that it is worth treating patients to composite clinical and sonographic endpoints. Reference 1. Turner D et al. Gastroenterol. 2021; 2 Kucharzik T et al. Clin Gastroenterol Hepatol. 2017; 3 Maaser C et al. Gut 2020; 4 Wilkens R et al. Therap Adv Gastroenterol 2021

Correlation of CT radiomic features for GISTs with pathological classification and molecular subtypes: preliminary and monocentric experience.

Our primary purpose was to search for computed tomography (CT) radiomic features of gastrointestinal stromal tumors (GISTs) that could potentially correlate with the risk class according to the Miettinen classification. Subsequently, assess the existence of features with possible predictive value in differentiating responder from non-responder patients to first-line therapy with Imatinib. A retrospective study design was carried out using data from June 2009 to December 2020. We analyzed all the preoperative CTs of patients undergoing surgery for GISTs. We segmented non-contrast-enhanced CT (NCECT) and contrast-enhanced venous CT (CECT) images obtained either on three different CT scans (heterogeneous cohort) or on a single CT scan (homogeneous cohort). We then divided the patients into two groups according to Miettinen classification criteria and based on the predictive value of response to first-line therapy with Imatinib. We examined 54 patients with pathological confirmation of GISTs. For the heterogeneous cohort, we found a statistically significant relationship between 57 radiomic features for NCECT and 56 radiomic features for CECT using the Miettinen risk classification. In the homogeneous cohort, we found the same relationship between 8 features for the NCECT and 5 features for CECT, all included in the heterogeneous cohort. The various radiomic features are distributed with different values in the two risk stratification groups according to the Miettinen classification. We also found some features for groups predictive of response to first-line therapy with Imatinib. We found radiomic features that correlate with statistical significance for both the Miettinen risk classification and the molecular subtypes of response. All features found in the homogeneous study cohort were also found in the heterogeneous cohort. CT radiomic features may be useful in assessing the risk class and prognosis of GISTs.

Immune Effective Score as a Predictor of Response to Neoadjuvant Trastuzumab Therapy and a Prognostic Indicator for HER2-Positive Breast Cancer.

Background: HER2-positive breast cancer (BC) is a highly aggressive phenotype. The role of the host immune features in predictive response to anti-HER2 therapies and prognosis in BC has already been suggested. We aimed to develop a predictive and prognostic model and examine its relevance to the clinical outcomes of patients with HER2-positive BC. Methods: Immune effective score (IES) was constructed using principal component analysis algorithms. A bioinformatic analysis using four independent cohorts (GSE66305, n = 88; GSE130786, n = 110; TCGA, n = 123; METABRIC, n = 236) established associations between IES and clinical outcomes. Results: Genes associated with neoadjuvant trastuzumab therapy response were enriched in pathways related to antitumor immune activities. IES was demonstrated to be a predictive biomarker to neoadjuvant trastuzumab therapy benefits (GSE66305: area under the curve (AUC) = 0.804; GSE130786: AUC = 0.704). In addition, IES was identified as an independent prognostic factor for overall survival (OS) in the TCGA cohort (p = 0.036, hazard ratio (HR): 0.66, 95% confidence interval (CI): 0.449–0.97) and METABRIC cohort (p = 0.037, HR: 0.9, 95% CI: 0.81–0.99). Conclusion: IES has a predictive value for response to neoadjuvant trastuzumab therapy and independent prognostic value for HER2-positive breast cancer.

Stromal Tumor-Associated Macrophage Infiltration Predicts Poor Clinical Outcomes in Muscle-Invasive Bladder Cancer Patients.

This study aims to reveal the clinical significance of stromal-infiltrating tumor-associated macrophages (TAMs) in muscle-invasive bladder cancer (MIBC). This study included 288 patients from the TCGA database and 118 patients from Fudan University Shanghai Cancer Center with MIBC. The CIBERSORT model and immunohistochemistry were used to evaluate TAM infiltration. Cox regression analyses were employed to calculate their prognostic value. Among all 23 immune phenotypes analyzed in the TCGA cohort, pan-macrophage infiltration was significantly associated with poor prognosis (p = 0.001). Further analyses found that stromal TAM infiltration could be an independent prognostic predictor for recurrence-free survival (RFS; HR: 1.019, 95% CI: 1.006-1.033, p = 0.004). High stromal infiltration was related to unfavorable RFS. After stratification by adjuvant chemotherapy (ACT), patients without ACT could be differentiated by TAM infiltration (p = 0.036), while patients with ACT could not. Moreover, TAM infiltration was negatively associated with IFN-γ-related mRNA panel, which was shown to have strong predictive value for clinical response to programmed death-1 (PD-1) inhibition. Stromal TAM infiltration could be an independent prognosticator for MIBC patients. This might have potential to guide precise treatments such as ACT and immune checkpoint blockade in MIBC.

A novel peripheral biomarker for depression and antidepressant response.

In contrast to healthy controls, the heterotrimeric G protein, Gsalpha (Gsα) is ensconced predominantly in lipid rafts in subjects with major depressive disorder (MDD) resulting in impaired stimulation of adenylyl cyclase. In this small proof-of-concept study, we examined the hypothesis that translocation of Gsα from lipid rafts toward a more facile activation of adenylyl cyclase is a biomarker for clinical response to antidepressants.There were 49 subjects with MDD (HamD17 score ≥15) and 59 healthy controls at the screen visit. The AlphaScreen (PerkinElmer) assay measured both basal activity and prostaglandin E1 (PGE1) stimulation of Gsα-adenylyl cyclase to assess the extent of coupling of Gsα with adenylyl cyclase.At screen, platelet samples obtained from MDD subjects revealed significantly lower PGE1 activation of adenylyl cyclase activity than controls (p =0.02). Subsequently, 19 consenting MDD subjects completed a 6-week open label antidepressant treatment trial. The 11 antidepressant responders (HamD17 improvement ≥50% from screen) revealed significant increase in PGE1-stimulated adenylyl cyclase compared to non-responders (p=0.05) with an effect size of 0.83 for the PGE1/Gsα lipid-raft biomarker. PGE1 stimulation increased by ≥30% from screen assessment in 8 responders (72.7%) and 2 non-responders (25.0%) [Fisher exact= 0.07] with a positive predictive value for response of 80.0%.In this small, pilot study, increased PGE1 stimulated adenylyl cyclase was associated with antidepressant response in MDD subjects. These data suggest that a simple, high-throughput-capable assay for depression and antidepressant response can be developed. Future studies are needed to evaluate the utility of this biomarker for the treatment of MDD.

Characterization of an Autophagy-Immune Related Genes Score Signature and Prognostic Model and its Correlation with Immune Response for Bladder Cancer.

PurposeThe study aimed to identify an autophagy-related molecular subtype and characterize a novel defined autophagy-immune related genes score (AI-score) signature and prognosis model in bladder cancer (BLCA) patients using public databases.MethodsThe transcriptome cohorts downloaded from TCGA and GEO database were carried out with genomic analysis and unsupervised methods to obtain autophagy-related molecular subtypes. The single-sample gene-set enrichment analysis (ssGSEA) was utilized to perform immune subtype clustering. We defined a novel autophagy subtype and evaluated the role in TME cell infiltration. Then, the principal-component analysis (PCA) was applied to construct an AI-score signature. Subsequently, two immunotherapeutic cohorts were used to evaluate the predictive value in immunotherapeutic benefits and immune response. Finally, univariate, Lasso and multivariate Cox regression algorithm were used to construct and evaluate an autophagy-immune-related genes prognosis model. Also, qRT-PCR and IHC was applied to validate the expression of the 6 genes in the model.ResultsThree distinct autophagy clusters and immune-related clusters were identified, and a novel autophagy-related molecular subtypes were defined. Furthermore, the roles in TME cell infiltration and clinical traits for the autophagy subtypes were characterized. Meanwhile, we constructed an AI-score signature and demonstrated it could predict genetic mutation, clinicopathological traits, prognosis, and TME stromal activity. We found that it could accurately predict the clinicopathological characteristics and immune response of individual BLCA patients and provide guidance for selecting immunotherapy. Ultimately, we constructed and verified an autophagy-immune-related prognostic model of BLCA patients and established a prognostic nomogram with a good prediction accuracy.ConclusionWe constructed AI-score signatures and prognosis risk model to characterize their role in clinical features and TME immune cell infiltration. It revealed that the AI-score signature and prognosis model could be a valid predictive tool, which could accurately predict the prognosis of BLCA patients and contribute to choosing effective personalized immunotherapy strategies.

PD-1 Relevant Genes Predict the Prognosis of Breast Cancer and Their Prediction Effect in Tumor Response to Immunotherapy

Background: Immunotherapy is becoming a powerful approach in the treatment of breast cancer. However, high response rates in the majority of breast cancer patients have yet to be achieved. Materials and Methods: Based on public data sources, we identified 22 genes that are correlated with PD-1 expression as well as differentially expressed between tumor tissues and normal tissues, and high expression of all the key genes was correlated with a superior survival outcome. Using the least absolute shrinkage and selection operator Cox regression model, a risk score was constructed. Results: A multivariate Cox analysis showed that the constructed risk score was an independent prognostic factor (AUC of risk score: 0.63, HR of risk score: 11.7, C-index: 0.69). Furthermore, an analysis of TILs in the TCGA BRCA cohort identified 28 distinct immune cell types. T lymphocytes and myeloid-derived suppressor cells were enriched in low-risk patients. The risk score was positively correlated with immune checkpoint genes for PD-1, PD-L1, PD-L2, and CTLA4 (P < 0.05). In addition, two independent cohorts validated the prognostic value and the predictive value of the immunotherapy response of the risk score. Conclusions: The risk score demonstrated a stable predictive ability in breast cancer prognosis and a predictive value in tumor response to immunotherapy. The analysis of TILs revealed the correlation between risk score and immune cells, which also helps elucidate the complexity of the relationship between TILs and immunotherapy response.

Predictive Value of Abnormal Hemodynamic Response to Dobutamine Stress Echocardiography in Liver Transplant Recipients

Predictive Value of Abnormal Hemodynamic Response to Dobutamine Stress Echocardiography in Liver Transplant Recipients

Good Clinical Responders to Topical Timolol in Patients with Infantile Hemangiomas: A 7-Year Retrospective Study of 328 Korean Patients.

BackgroundTopical timolol is widely used for treatment of superficial infantile hemangioma (IH). However, little is known about factors that affect the response to topical timolol treatment.ObjectiveThis study aimed to investigate the efficacy, safety, and predictive value for good response to topical timolol for IH.MethodsA retrospective review of medical records and clinical photos of 328 patients with IH treated with topical timolol 0.5% solution was conducted. Serial clinical photographs were compared with those at the initial visit using a 100-mm visual analogue scale (VAS). Treatment response was defined as an improvement of at least 75% from baseline in IH lesions within 12 months of treatment.ResultsOverall, IH patients treated with topical timolol showed significant improvement from baseline, showing that the final VAS score within 12 months of treatment was 69.7±20.4. The multivariable logistic regression analysis showed age at initiation of treatment (p=0.007), length of gestation and fetal growth (p=0.03), depth (p=0.01), and flexural area (p=0.007) were significantly associated with treatment response. Only four patients (1.1%) reported local irritation.ConclusionThis study demonstrated that topical timolol treatment was an effective and well-tolerated treatment for IHs. Physicians are encouraged to consider several patient- or lesional factors that might affect treatment response to achieve better clinical outcomes.

Effect of Previous Caudal Block to Predict Successful Outcome after Adhesiolysis using a Steerable Catheter in Lumbar Failed Back Surgery Syndrome: A Retrospective Study.

Adhesiolysis is minimally invasive and commonly used for pain associated with adhesion after lumbar spine surgery. Caudal epidural block may be used for radiating pain due to failed back surgery syndrome. We evaluated the predictive value of response to caudal block performed prior to adhesiolysis in failed back surgery syndrome. Between January 1, 2013 and June 30, 2020, 150 patients with failed back surgery syndrome were treated with adhesiolysis using a steerable catheter at the pain clinic of a tertiary hospital after failed conservative treatment (including caudal block). Patient demographics, pain duration, and lumbar magnetic resonance imaging findings were examined. Response to previous caudal block was determined as a binary result (yes or no). Patients were followed up 3 months after adhesiolysis. Successful outcome was defined as a ≥2-point reduction in the numeric rating scale scores for radicular pain 3 months after adhesiolysis, evident in 81/150 (46%) patients. Multivariable logistic regression analysis revealed that caudal block response was an independent predictor of successful adhesiolysis (odds ratio = 4.403; p = 0.015). Response to prior caudal block is a positive predictor of successful adhesiolysis.

HMGA1 Has Predictive Value in Response to Chemotherapy in Gastric Cancer.

Gastric cancer is a serious health problem worldwide. Although its incidence is decreasing, the five-year survival rate remains low. Thus, it is essential to identify new biomarkers that could promote better diagnosis and treatment of patients with gastric cancer. High-mobility group AT-hook 1 (HMGA1) is a non-histone, chromatin-binding protein that has been found overexpressed in several tumor types. It has been correlated with invasion, metastasis, and drug resistance, leading to worse patient survival. The aim of this work was to evaluate the clinical value of HMGA1 in gastric cancer. HMGA1 expression was analyzed by immunohistochemistry in a single hospital series (n = 323) of gastric adenocarcinoma cases (stages I to IV) with clinicopathological and treatment data. In this series, HMGA1 expression showed no significant relevance as a prognostic biomarker. Nevertheless, a significantly better overall survival was observed in cases with high levels of HMGA1 when they were treated with chemotherapy, compared to the nontreated ones, implying that they can benefit more from treatment than patients with low expression of HMGA1. We thereby show for the first time that HMGA1 expression has a substantial value as a biomarker of response to chemotherapy in gastric cancer.

The prognostic role of miR-31 in colorectal cancer: the results of a meta-analysis of 4720 patients.

Aims: To study the association between miR-31 expression and clinical outcomes in colorectal cancer. Methods: A systematic search was performed and 16 studies were found eligible. To calculate the combined hazard ratio (HR), the DerSimonian and Laird random-effects model was used. Results: Pooled analysis revealed significant associations between high miR-31 expression and poor overall (HR: 0.68; 95% CI: 0.47-0.97; I2: 68.6%) and progression-free survival (HR: 0.49; 95% CI: 0.33-0.73; I2: 81.1%). High expressers were more likely to have a BRAF mutation. Therapeutic regimen and the mutational status significantly affected the observed associations. Conclusion: We identified that high miR-31 expression is associated with poor overall survival and progression-free survival and has a significant predictive value for anti-EGFR response.

Use of Artificial Intelligence as a Predictor of the Response to Treatment in Alopecia Areata

Background Artificial intelligence (AI) has emerged in dermatology with some studies focusing on skin disorders such as skin cancer, atopic dermatitis, psoriasis, and onychomycosis. Alopecia areata (AA) is a dermatological disease whose prevalence is 0.7%-3% in the United States, and is characterized by oval areas of nonscarring hair loss of the scalp or body without evident clinical variables to predict its response to the treatment. Nonetheless, some studies suggest a predictive value of trichoscopic features in the evaluation of treatment responses. Assuming that black dots, broken hairs, exclamation marks, and tapered hairs are markers of negative predictive value of the treatment response, while yellow dots are markers of no response to treatment according to recent studies, the absence of these trichoscopic features could indicate favorable disease evolution without treatment or even predict its response. Nonetheless, no studies have reportedly evaluated the role of AI in AA on the basis of trichoscopic features. Objective This study aimed to develop an AI algorithm to predict, using trichoscopic images, those patients diagnosed with AA with a better disease evolution. Methods In total, 80 trichoscopic images were included and classified in those with or without features of negative prognosis. Using a data augmentation technique, they were multiplied to 179 images to train an AI algorithm, as previously carried out with dermoscopic images of skin tumors with a favorable response. Subsequently, 82 new images of AA were presented to the algorithm, and the algorithm classified these patients as responders and non-responders; this process was reviewed by an expert trichologist observer and presented a concordance higher than 90% with the algorithm identifying structures described previously. Evolution of the cases was followed up to truly determine their response to treatment and, therefore, to assess the predictive value of the algorithm. Results In total, 32 of 40 (80%) images of patients predicted as nonresponders scarcely showed response to the treatment, while 34 of 42 (81%) images of those predicted as responders showed a favorable response to the treatment. Conclusions The development of an AI algorithm or tool could be useful to predict AA evolution and its response to treatment. However, further research is needed, including larger sample images or trained algorithms, by using images previously classified in accordance with the disease evolution and not with trichoscopic features. Conflicts of Interest None declared.

Early Improvement with Vortioxetine Predicts Response and Remission: A Post Hoc Analysis of Data from a Clinical Trial Conducted in Japan.

AimSeveral weeks of treatment with an antidepressive agent may be required before efficacy is demonstrated in patients with major depressive disorder. This study investigated the predictive value of early partial improvement with vortioxetine for treatment response and remission.MethodsThis was a post hoc analysis of an 8-week, randomized, double-blind, placebo-controlled, Phase 3 study of vortioxetine (10 mg or 20 mg) in Japanese patients aged 20–75 years with recurrent major depressive disorder and a Montgomery–Åsberg Depression Rating Scale (MADRS) score of at least 26. The key outcomes were the predictive value of early partial improvement (reduction in MADRS total score of ≥20% from baseline to week 2) with vortioxetine for MADRS response (≥50% decrease in score from baseline) and remission (decrease in score to ≤10) at week 8.ResultsRelevant data were available for 478 patients; 62/158 patients receiving placebo, 71/162 receiving vortioxetine 10 mg, and 66/158 receiving vortioxetine 20 mg were early improvers. Early improvers receiving vortioxetine (10 mg or 20 mg) were more likely than non-early improvers to achieve a week 8 response (71.2–73.2% vs 29.7–38.0%) or remission (50.7–51.5% vs 17.4–18.7%). Positive predictive values for response and remission with vortioxetine were ~70% and ~50%, respectively; negative predictive values were ~70% and ~80%, respectively.ConclusionImprovement with vortioxetine may be predicted by early partial improvement in MADRS score. Some patients may benefit from longer-term treatment even without early improvement, another finding that may aid clinical decision-making. ClinicalTrials.gov registration for primary study: NCT02389816.

Metabolic Tumor Volume and Total Lesion Glycolysis Can Predict Response to Very Low Dose Radiotherapy (4 Gy) in Indolent B-Cell Lymphomas

Numerous studies have established the role of very low dose radiotherapy (VLDRT), only 4 Gy in 2 fractions, in the management of indolent non-Hodgkin's lymphoma (NHL). While objective response rates to VLDRT are excellent, there are no widely accepted biomarkers of the depth and the durability of response after VLDRT. Radiosensitivity to VLDRT is not clearly linked to clinical features, such as tumor grade, histology, prior treatments or [18F]-FDG-PET standardized uptake values (SUV). Our group has recently demonstrated that pre-treatment tumor size greater than 6 cm may predict suboptimal response to VLDRT; however, this remains an imperfect predictor, and the majority of patients selected for VLDRT have lesions smaller than 6 cm. [18F]-FDG-PET metrics like baseline metabolic tumor volume (MTV) and total lesion glycolysis (TLG) are shown to stratify patient response to chemotherapy for some NHLs, but neither has been shown to predict radiotherapy response to VLDRT. Therefore, we aimed to determine if these features could predict response to VLDRT in indolent B-cell NHLs.Between 2005 and 2018, 250 patients with follicular or marginal zone lymphoma were locally irradiated to 299 sites using 2 Gy x2. Response was assessed within 1.5-6 months of VLDRT (n=231), and local failure (LF) was assessed over a median follow-up of 29 months. Out of the 299 treated sites, 254 (85%) had a corresponding [18F]-FDG-PET/CT scan performed prior to radiotherapy. PET scans were imported into MIM, a radiotherapy contouring and planning software program, and pre-radiotherapy disease was manually defined. A uniform expansion of 0.5 cm was performed to define a larger region of interest containing the contoured lesion but accounting for technical variability in defining the tumor edges. Of the 254 lesions, 207 (81%) had a maximum SUV (SUVmax) greater than 2.5 and were considered for further analysis. PET parameters were obtained using an SUV of 2.5 as a cutoff for MTV (MTV2.5) and TLG (TLG2.5), which capture lesion bulk, and using 41% of the SUVmax as a cutoff for MTV (MTV41%) and TLG (TLG41%), which capture the most metabolically active parts of a lesion. Maximum lesion size was analyzed using 4 cm and 6 cm as predetermined cutoffs. Lesion response was analyzed using multivariate logistic LASSO regression to account for predictor multicollinearity, and receiver operating characteristic curve analysis to obtain estimates of the area under the curve (AUC). To analyze time to LF, we performed Cox proportional hazards multivariate regression using stepwise selection. PET parameters were divided in quartiles to aid in interpretability. Estimates are shown with 95% confidence intervals.A complete response (CR) was seen in 156 (68%) lesions and LF was seen in 81 (27%) lesions after VLDRT. Using size alone had similar predictive value for response (AUC: 0.57(0.49-0.65) compared to MTV2.5 (AUC:0.66 (0.57-0.74)), MTV41% (AUC:0.64 (0.56-0.73)), TLG2.5 (AUC:0.64 (0.54-0.74)), and TLG41% (AUC:0.64 (0.54,0.75)). Through LASSO logistic regression, we determined that only MTV41% > 75 th percentile was associated with lower odds of CR (odds ratio (OR):0.21 (0.08-0.53)) versus size ≥4 (OR: 0.94 (0.32, 2.73) ) with no interaction noted. Likewise, in a multivariate model of LF, TLG2.5> 75 th percentile was shown to be a better predictor of worse LF (HR: 2.44 (1.32, 4.52)) than size when considering lesions < 6 cm.In stratifying response and local control for patients receiving VLDRT for indolent lymphomas, MTV and TLG may aid in patient selection, especially for lesions smaller than 6 cm. As PET-based radiotherapy planning is routinely performed in the treatment of indolent lymphomas, these parameters are easily attained after contouring and may have immediate clinical utility. These findings may also be applicable to radiotherapy response with higher doses, and the incorporation of [18F]-FDG-PET metrics into treatment decisions is an area of active research. It remains to be seen in ongoing work whether higher-order PET radiomic features (which for instance capture heterogeneity of tumor glucose metabolism) can further improve the accuracy of [18F]-FDG-PET-based radiotherapy outcome prediction. DisclosuresMayerhoefer: Siemens: Other: Speaker Honoraria; General Electric: Other: Speaker Honoraria; Bristol Myers Squibb: Other: Speaker Honoraria.

Epicardial Adipose Tissue Measured From Computed Tomography Predicts Cardiac Resynchronization Therapy Response in Patients With Non-ischemic Systolic Heart Failure.

Background: Epicardial adipose tissue (EAT) has been linked with the pathogenesis of heart failure (HF). Limited data have been reported about the clinical value of EAT for cardiac resynchronization therapy (CRT) in non-ischemic systolic HF. We aimed to explore the values of EAT measured from CT to predict the response to CRT in patients with non-ischemic systolic HF.Methods: Forty-one patients with CRT were consecutively recruited for our study. All patients received both gated resting Single Photon Emission CT (SPECT) myocardial perfusion imaging (MPI) and dual-source multi-detector row CT scans. EAT thickness was assessed on both the parasternal short and horizontal long-axis views. The area of EAT was calculated at the left main coronary artery level. Left ventricular systolic mechanical dyssynchrony (LVMD) was measured by phase standard deviation (PSD) and phase histogram bandwidth (PBW). The definition of CRT response was an improvement of 5% in left ventricular ejection fraction (LVEF) at 6 months after CRT implantation.Results: After 6 months of follow-up, 58.5% (24 of 41) of patients responded to CRT. A greater total perfusion deficit (TPD) was observed in the left ventricle, and a narrower QRS complex was observed in the nonresponse group than in the response group (p < 0.05). Meanwhile, the systolic PSD and systolic PBW were statistically greater in the CRT group with no response than in the response group (p < 0.05). Meanwhile, the baseline QRS duration, TPD, systolic PSD, systolic PBW, EAT thicknesses of the left ventricular (LV) apex, right atrioventricular (AV) groove, and left AV groove were all significantly related to the CRT response in the univariate logistic regression analysis. Furthermore, the QRS duration and EAT thicknesses of the right AV groove and left AV groove were independent predictors of CRT response in the multivariate logistic regression analysis.Conclusions: The EAT thickness of the left AV groove in patients with non-ischemic systolic HF is associated with the TPD of LV and LV systolic dyssynchrony. The EAT thickness of the AV groove has a good predictive value for the CRT response in patients with non-ischemic systolic HF.

Association of CLDN18 Protein Expression with Clinicopathological Features and Prognosis in Advanced Gastric and Gastroesophageal Junction Adenocarcinomas.

Simple SummaryClaudin-18 is a tight junction protein expressed in various cancer types including gastric and gastroesophageal junction cancer. The claudin-18.2 isoform represents a promising target for novel experimental drugs such as zolbetuximab (IMAB362), currently under investigation in several clinical trials of advanced gastrointestinal tumors. In this study, we aim to evaluate the immunohistochemical profile of CLDN18 in a real-world and mono-institutional series of gastric and gastroesophageal carcinomas. The association of CLDN18 expression with clinicopathological features and survival outcomes was investigated.The tight junction protein claudin-18 (CLDN18), is often expressed in various cancer types including gastric (GC) and gastroesophageal adenocarcinomas (GECs). In the last years, the isoform CLDN18.2 emerged as a potential drug target in metastatic GCs, leading to the development of monoclonal antibodies against this protein. CLDN18.2 is the dominant isoform of CLDN18 in normal gastric and gastric cancer tissues. In this work, we evaluated the immunohistochemical (IHC) profile of CLDN18 and its correlation with clinical and histopathological features including p53, E-cadherin, MSH2, MSH6, MLH1, PMS2, HER2, EBER and PD-L1 combined positive score, in a large real-world and mono-institutional series of advanced GCs (n = 280) and GECs (n = 70). The association of IHC results with survival outcomes was also investigated. High membranous CLDN18 expression (2+ and 3+ intensity ≥75%) was found in 117/350 (33.4%) samples analyzed. CLDN18 expression correlated with age <70 (p = 0.0035), positive EBV status (p = 0.002), high stage (III, IV) at diagnosis (p = 0.003), peritoneal involvement (p < 0.001) and lower incidence of liver metastases (p = 0.013). CLDN18 did not correlate with overall survival. The predictive value of response of CLDN18 to targeted agents is under investigation in several clinical trials and further studies will be needed to select patients who could benefit from these therapies.

Prediction of Response to Very Low Dose Radiotherapy (4 Gy) in Mature B-Cell Lymphomas Using Metabolic Tumor Volume

Numerous studies established the role of palliative very low dose radiotherapy (VLDRT) of only 4 Gy in 2 fractions for indolent non-Hodgkin's lymphoma (NHL). While objective response rates to VLDRT are excellent, we have no clear biomarkers of depth and durability of response. Radiosensitivity to VLDRT is not clearly linked to clinical features, such as tumor grade, histology, and PET SUV. Our group has recently demonstrated that pre-treatment tumor size may predict response to VLDRT; however, this remains an imperfect predictor. Radiomic features like baseline metabolic tumor volume (MTV) and total lesion glycolysis (TLG) stratify patient response to chemotherapy for some NHLs. Therefore, we aimed to determine if these features could predict response to VLDRT in indolent NHL.Between 2005 and 2018, 250 patients with follicular or marginal zone lymphoma were locally irradiated to 299 sites using 2 Gy x2. Response was assessed within 1.5-6 months of VLDRT (n = 231), and local failure (LF) was assessed over a median follow-up of 29 months. Out of the 299 sites, 254 had a PET/CT scan performed prior to radiotherapy. Scans were imported into MIM, and pre-radiotherapy disease was contoured with liver for normalization. PET parameters including MTV and TLG were extracted. Lesion size was analyzed using 4 cm and 6 cm as predetermined cutoffs. Lesion response was analyzed using multivariate logistic LASSO regression to account for predictor multicollinearity and area under the curve (AUC) analysis. To analyze time to LF, we performed Cox proportional hazards multivariate regression using ridge regression. PET parameters were divided in quartiles, and for significant predictors, optimal cutoffs were determined using maximally selected rank statistics. Estimates are shown with 95% confidence intervals.A complete response (CR) was seen in 156 (68%) lesions and LF was seen in 81 (27%) lesions after VLDRT. Using size alone had similar predictive value for response (AUC: 0.64 (0.59,0.70)) compared to MTV (AUC:0.70 (0.62,0.77)) and TLG (AUC:0.68 (0.61,0.75)). For lesions less than 6 cm, size, MTV and TLG had comparable predictive value for response (AUC: 0.58 (0.51,0.64), AUC:0.65 (0.56,0.75), and AUC:0.66 (0.57,0.75), respectively); however, through multivariate modeling we determined that TLG was not as robust as MTV, and MTV > 75th percentile was an improved predictor of no CR versus size ≥4 (OR: 0.26 (0.11,0.57) vs 0.77(0.30,2.08), respectively) with no interaction noted. Likewise, in a multivariate model of LF, MTV was shown to be a better predictor than size for lesions < 6 cm with an MTV ≥45 associated with worse LF (HR: 1.84 (1.14, 2.00)) compared to size > 4 cm (HR:1.31 (0.80, 2.15)).In stratifying response and local control for patients receiving VLDRT for indolent lymphomas, MTV may aid in patient selection. It remains to be seen whether higher order PET radiomic parameters can further improve the accuracy of PET-based radiotherapy outcome prediction.