Therapy Response
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2021 ◽  
Vol 101 ◽  
pp. 108183
Zijun Zhao ◽  
Zairan Wang ◽  
Zihan Song ◽  
Yue Wu ◽  
Qianxu Jin ◽  

Diagnostics ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1902
Suraj Sakaram ◽  
Yehudit Hasin-Brumshtein ◽  
Purvesh Khatri ◽  
Yudong D. He ◽  
Timothy E. Sweeney

Background: Anti-TNF-alpha (anti-TNFα) therapies have transformed the care and management of inflammatory bowel disease (IBD). However, they are expensive and ineffective in greater than 50% of patients, and they increase the risk of infections, liver issues, arthritis, and lymphoma. With 1.6 million Americans suffering from IBD and global prevalence on the rise, there is a critical unmet need in the use of anti-TNFα therapies: a test for the likelihood of therapy response. Here, as a proof-of-concept, we present a multi-mRNA signature for predicting response to anti-TNFα treatment to improve the efficacy and cost-to-benefit ratio of these biologics. Methods: We surveyed public data repositories and curated four transcriptomic datasets (n = 136) from colonic and ileal mucosal biopsies of IBD patients (pretreatment) who were subjected to anti-TNFα therapy and subsequently adjudicated for response. We applied a multicohort analysis with a leave-one-study-out (LOSO) approach, MetaIntegrator, to identify significant differentially expressed (DE) genes between responders and non-responders and then used a greedy forward search to identify a parsimonious gene signature. We then calculated an anti-TNFα response (ATR) score based on this parsimonious gene signature to predict responder status and assessed discriminatory performance via an area-under-receiver operating-characteristic curve (AUROC). Results: We identified 324 significant DE genes between responders and non-responders. The greedy forward search yielded seven genes that robustly distinguish anti-TNFα responders from non-responders, with an AUROC of 0.88 (95% CI: 0.70–1). The Youden index yielded a mean sensitivity of 91%, mean specificity of 76%, and mean accuracy of 86%. Conclusions: Our findings suggest that there is a robust transcriptomic signature for predicting anti-TNFα response in mucosal biopsies from IBD patients prior to treatment initiation. This seven-gene signature should be further investigated for its potential to be translated into a predictive test for clinical use.

Aaron M. Goodman ◽  
Kimberly A. Holden ◽  
Ah-Reum Jeong ◽  
Lisa Kim ◽  
Kerry D. Fitzgerald ◽  

2021 ◽  
Hye Ryeong Kwon ◽  
Ji Hye Hwang ◽  
Goo-Hyun Mun ◽  
Seung Hyup Hyun ◽  
Seung Hwan Moon ◽  

Abstract Background We investigated whether preoperative lymphoscintigraphy could predict the treatment response of unilateral lymphovenous anastomosis (LVA) in patients with lower extremity lymphedema. Materials and methods A total of 17 patients undergoing lymphoscintigraphy subsequent to LVA was included. As qualitative lymphoscintigraphic indicators, ilioinguinal lymph node uptake, main lymphatic vessel, collateral vessel, and dermal backflow pattern were evaluated. Lymph node uptake ratio, extremity uptake ratio, and injection site clearance ratio were obtained as quantitative lymphoscintigraphic indicators at 1 and 2-h after injection. To evaluate therapy response, the volume difference ratio of the whole leg at 3 months (early response) and 1 year (late response) was measured. Results The group with whole leg dermal backflow had a greater volume change than the other groups (p=0.047). The group with dermal backflow in the whole leg OR only in the distal part had a higher rate of volume reduction than the group with dermal backflow only in the proximal part OR absent (p=0.050). The 2-h extremity uptake ratio was the only indicator that positively correlated with early and late volume difference ratio (p=0.016, p=0.001). The rate of volume decrease at 1 year was high in patients with high 2-h extremity uptake ratio (p=0.027). As the amount of dermal backflow increases, the postoperative therapeutic effect increases (p=0.040). Conclusions Preoperative lymphoscintigraphy is useful to predict both early and late therapy response in patients with lower extremity lymphedema undergoing LVA. Both dermal backflow pattern and extremity uptake ratio may be predictive lymphoscintigraphic indicators.

2021 ◽  
Vol 11 ◽  
Philipp Fervers ◽  
Erkan Celik ◽  
Grischa Bratke ◽  
David Maintz ◽  
Christian Baues ◽  

BackgroundLife expectancy of patients with multiple myeloma (MM) has increased over the past decades, underlining the importance of local tumor control and avoidance of dose-dependent side effects of palliative radiotherapy (RT). Virtual noncalcium (VNCa) imaging from dual-energy computed tomography (DECT) has been suggested to estimate cellularity and metabolic activity of lytic bone lesions (LBLs) in MM.ObjectiveTo explore the feasibility of RT response monitoring with DECT-derived VNCa attenuation measurements in MM.MethodsThirty-three patients with 85 LBLs that had been irradiated and 85 paired non-irradiated LBLs from the same patients were included in this retrospective study. Irradiated and non-irradiated LBLs were measured by circular regions of interest (ROIs) on conventional and VNCa images in a total of 216 follow-up measurements (48 before and 168 after RT). Follow-ups were rated as therapy response, stable disease, or local progression according to the MD Anderson criteria. Receiver operating characteristic (ROC) analysis was performed to discriminate irradiated vs. non-irradiated and locally progressive vs. stable/responsive LBLs using absolute attenuation post-irradiation and percentage attenuation change for patients with pre-irradiation DECT, if available.ResultsAttenuation of LBLs decreased after RT depending on the time that had passed after irradiation [absolute thresholds for identification of irradiated LBLs 30.5–70.0 HU [best area under the curve [AUC] 0.75 (0.59–0.91)] and -77.0 to -22.5 HU [best AUC 0.85 (0.65–1.00)]/-50% and -117% to -167% proportional change of attenuation on conventional and VNCa images, respectively]. VNCa CT was significantly superior for identification of RT effects in LBLs with higher calcium content [best VNCa AUC 0.96 (0.91–1.00), best conventional CT AUC 0.64 (0.45–0.83)]. Thresholds for early identification of local irradiation failure were >20.5 HU on conventional CT [AUC 0.78 (0.68–0.88)] and >-27 HU on VNCa CT [AUC 0.83 (0.70–0.96)].ConclusionTherapy response of LBLs after RT can be monitored by VNCa imaging based on regular myeloma scans, which yields potential for optimizing the lesion-specific radiation dose for local tumor control. Decreasing attenuation indicates RT response, while above threshold attenuation of LBLs precedes local irradiation failure.

Biomedicines ◽  
2021 ◽  
Vol 9 (9) ◽  
pp. 1249
Gabriela M Almeida ◽  
Carla Pereira ◽  
Ji-Hyeon Park ◽  
Carolina Lemos ◽  
Sofia Campelos ◽  

In gastric cancer (GC), biomarkers that define prognosis and predict treatment response remain scarce. We hypothesized that the extent of CD44v6 membranous tumor expression could predict prognosis and therapy response in GC patients. Two GC surgical cohorts, from Portugal and South Korea (n = 964), were characterized for the extension of CD44v6 membranous immuno-expression, clinicopathological features, patient survival, and therapy response. The value of CD44v6 expression in predicting response to treatment and its impact on prognosis was determined. High CD44v6 expression was associated with invasive features (perineural invasion and depth of invasion) in both cohorts and with worse survival in the Portuguese GC cohort (HR 1.461; 95% confidence interval 1.002–2.131). Patients with high CD44v6 tumor expression benefited from conventional chemotherapy in addition to surgery (p < 0.05), particularly those with heterogeneous CD44v6-positive and -negative populations (CD44v6_3+) (p < 0.007 and p < 0.009). Our study is the first to identify CD44v6 high membranous expression as a potential predictive marker of response to conventional treatment, but it does not clarify CD44v6 prognostic value in GC. Importantly, our data support selection of GC patients with high CD44v6-expressing tumors for conventional chemotherapy in addition to surgery. These findings will allow better stratification of GC patients for treatment, potentially improving their overall survival.

2021 ◽  
Vol 7 (1) ◽  
Giulia Di Lazzaro ◽  
Mariachiara Ricci ◽  
Giovanni Saggio ◽  
Giovanni Costantini ◽  
Tommaso Schirinzi ◽  

AbstractEarly noninvasive reliable biomarkers are among the major unmet needs in Parkinson’s disease (PD) to monitor therapy response and disease progression. Objective measures of motor performances could allow phenotyping of subtle, undetectable, early stage motor impairments of PD patients. This work aims at identifying prognostic biomarkers in newly diagnosed PD patients and quantifying therapy-response. Forty de novo PD patients underwent clinical and technology-based kinematic assessments performing motor tasks (MDS-UPDRS part III) to assess tremor, bradykinesia, gait, and postural stability (T0). A visit after 6 months (T1) and a clinical and kinematic assessment after 12 months (T2) where scheduled. A clinical follow-up was provided between 30 and 36 months after the diagnosis (T3). We performed an ANOVA for repeated measures to compare patients’ kinematic features at baseline and at T2 to assess therapy response. Pearson correlation test was run between baseline kinematic features and UPDRS III score variation between T0 and T3, to select candidate kinematic prognostic biomarkers. A multiple linear regression model was created to predict the long-term motor outcome using T0 kinematic measures. All motor tasks significantly improved after the dopamine replacement therapy. A significant correlation was found between UPDRS scores variation and some baseline bradykinesia (toe tapping amplitude decrement, p = 0.009) and gait features (velocity of arms and legs, sit-to-stand time, p = 0.007; p = 0.009; p = 0.01, respectively). A linear regression model including four baseline kinematic features could significantly predict the motor outcome (p = 0.000214). Technology-based objective measures represent possible early and reproducible therapy-response and prognostic biomarkers.

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