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This study investigates the cortical correlates of motor response control and monitoring, using the Theory of Event Coding (TEC) as a framework to investigate signals related to low‐level sensory processing of motor reafference and high‐level response monitoring, including verification of response outcomes with the internal model. We used a visuomotor paradigm with two targets at different distances from the participant. For the recorded movement‐related cortical potentials (MRCPs), we analyzed their different components and assessed the movement phases during which they are active. Residual iteration decomposition (RIDE) and multivariate pattern analysis (MVPA) were used for this analysis. Using RIDE, we separated MRCPs into signals related to different parallel processes of visuomotor transformation: stimulus processing (S‐cluster), motor response preparation and execution (R‐cluster), and intermediate processes (C‐cluster). We revealed sequential activation in the R‐cluster, with execution‐related negative components and positive contralateral peaks reflecting reafference processing. We also identified the motor post‐imperative negative variation within the R‐cluster, highlighting the response outcome evaluation process included in the action file. Our findings extend the understanding of C‐cluster signals, typically associated with stimulus–response mapping, by demonstrating C‐activation from the preparatory stages through to response termination, highlighting its participation in action monitoring. In addition, we highlighted the ability of MVPA to identify movement‐related attribute encoding: where statistical analysis showed independence of stimulus processing activity from movement distance, MVPA revealed distance‐related differences in the S‐cluster within a time window aligned with the lateralized readiness potential (LRP). This highlights the importance of integrating RIDE and MVPA to uncover the intricate neural dynamics of motor control, sensory integration, and response monitoring. [ABSTRACT FROM AUTHOR]

Objective: This single-centre retrospective study aims to determine the incidence of therapy-induced surgical benefit in patients with non-metastatic gastrointestinal stromal tumour (GIST) treated with neoadjuvant tyrosine kinase inhibitors (TKI) and evaluate whether this can be predicted by radiological response criteria. Methods: Thirty-nine non-metastatic GIST patients were treated with neoadjuvant TKI treatment, followed by curative-intended surgery, and monitored using contrast-enhanced computed tomography (CE-CT). Surgical benefit was independently assessed by two surgical oncologists and was defined by de-escalation of surgical strategy or reduced surgical complexity. Radiological response between baseline and the last preoperative scan was determined through RECIST 1.1, Choi and volumetric criteria. Results: In this patient cohort, median neoadjuvant treatment interval was 8.3 (IQR, 3.9–10.6) months. Surgical benefit was gained in 22/39 patients. When comparing radiological criteria to findings on surgical benefit, accuracy, sensitivity, and specificity for RECIST 1.1 (90 %, 100.0 % and 82 %), Choi (64 %, 24 %, and 96 %) and volumetry (95 %, 100.0 %, and 91 %) were calculated. In 30/39 patients, temporal changes in tumour size over the course of treatment was assessed. Tumour volume reduced significantly in the surgical-benefit group compared to the non-benefit group (72 % vs. 25 %, p

Previously, we showed that quantification of lymphoma‐associated miRNAs miR‐155‐5p, ‐127‐3p and let‐7a‐5p levels in plasma extracellular vesicles (EVs) report treatment response in patients with classic Hodgkin lymphoma (cHL). Prior to clinical implementation, quality control (QC) steps and validation are required to meet international regulatory standards. Most published EV‐based diagnostic assays have yet to meet these requirements. In order to advance the assay towards regulatory compliance (e.g., IVDR 2017/746), we incorporated three QC steps in our experimental EV‐miRNA quantitative real‐time reverse‐transcription PCR (q‐RT‐PCR) assay in an ISO‐13485 certified quality‐management system (QMS). Liposomes encapsulated with a synthetic (nematode‐derived) miRNA spike‐in controlled for EV isolation by automated size‐exclusion chromatography (SEC). Additional miRNA spike‐ins controlled for RNA isolation and cDNA conversion efficiency. After deciding on quality criteria, in total 107 out of 120 samples from 46 patients passed QC. Generalized linear mixed‐effect modelling with bootstrapping determined the diagnostic performance of the quality‐controlled data at an area under the curve (AUC) of 0.84 (confidence interval [CI]: 0.76–0.92) compared to an AUC of 0.87 (CI: 0.80–0.94) of the experimental assay. After the inclusion of QC steps, the accuracy of the assay was determined to be 78.5% in predicting active disease status in cHL patients during treatment. We demonstrate that a quality‐controlled plasma EV‐miRNA assay is technically robust, taking EV‐miRNA as liquid biopsy assay an important step closer to clinical evaluation. [ABSTRACT FROM AUTHOR]

Simple Summary: This study explores the potential of the relative wash-in rate (rWIR) in dynamic contrast-enhanced MRI as a prognostic factor for event-free survival (EFS) in osteosarcoma patients. Eighty-two patients were retrospectively included, and rWIR was determined based on preoperative imaging. Patients with rWIR < 2.3 were considered to have a poor radiological response, while those with rWIR ≥ 2.3 had a good response. This study identified that poor radiological response (rWIR < 2.3) was associated with shorter EFS, even when adjusted for traditional prognostic factors. The 2- and 5-year EFS rates for patients with rWIR ≥ 2.3 were 85% and 75%, compared to 55% and 50% for those with rWIR < 2.3. The findings suggest that the predicted poor chemo response with MRI is associated with shorter EFS and shows similar results to histological response evaluation. rWIR is a potential tool for future response-based individualized healthcare in osteosarcoma patients. Background: The decreased perfusion of osteosarcoma in dynamic contrast-enhanced (DCE) MRI, reflecting a good histological response to neoadjuvant chemotherapy, has been described. Purpose: In this study, we aim to explore the potential of the relative wash-in rate as a prognostic factor for event-free survival (EFS). Methods: Skeletal high-grade osteosarcoma patients, treated in two tertiary referral centers between 2005 and 2022, were retrospectively included. The relative wash-in rate (rWIR) was determined with DCE-MRI before, after, or during the second cycle of chemotherapy (pre-resection). A previously determined cut-off was used to categorize patients, where rWIR < 2.3 was considered poor and rWIR ≥ 2.3 a good radiological response. EFS was defined as the time from resection to the first event: local recurrence, new metastases, or tumor-related death. EFS was estimated using Kaplan–Meier's methodology. Multivariate Cox proportional hazard model was used to estimate the effect of histological response and rWIR on EFS, adjusted for traditional prognostic factors. Results: Eighty-two patients (median age: 17 years; IQR: 14–28) were included. The median follow-up duration was 11.8 years (95% CI: 11.0–12.7). During follow-up, 33 events occurred. Poor histological response was not significantly associated with EFS (HR: 1.8; 95% CI: 0.9–3.8), whereas a poor radiological response was associated with a worse EFS (HR: 2.4; 95% CI: 1.1–5.0). In a subpopulation without initial metastases, the binary assessment of rWIR approached statistical significance (HR: 2.3; 95% CI: 1.0–5.2), whereas its continuous evaluation demonstrated a significant association between higher rWIR and improved EFS (HR: 0.7; 95% CI: 0.5–0.9), underlining the effect of response to chemotherapy. The 2- and 5-year EFS for patients with a rWIR ≥ 2.3 were 85% and 75% versus 55% and 50% for patients with a rWIR < 2.3. Conclusion: The predicted poor chemo response with MRI (rWIR < 2.3) is associated with shorter EFS even when adjusted for known clinical covariates and shows similar results to histological response evaluation. rWIR is a potential tool for future response-based individualized healthcare in osteosarcoma patients before surgical resection. [ABSTRACT FROM AUTHOR]

Purpose: To assess early tumor response with quantitated SPECT/CT and to correlate it with clinical outcome in metastatic castration–resistant prostate cancer (mCRPC) patients treated with 177Lutetium-PSMA I&T therapy. Methods: Single-center, observational study, part of the prospective Swiss national cancer registry study investigating the safety and efficacy of [177Lu]Lu-PSMA I&T (EKNZ: 2021–01271) in mCRPC patients treated with at least two cycles of [177Lu]Lu-PSMA I&T 6-weekly. After the first and second cycle quantitated SPECT/CT (Symbia Intevo, Siemens) was acquired 48 h after injection (three fields of view from head to thigh, 5 s/frame) and reconstructed using xQuant® (48i, 1 s, 10-mm Gauss). Image analysis: The PSMA-positive total tumor volumes (TTV) were semi-automatically delineated using a SUV threshold of 3 with MIMencore® (version 7.1.3, Medical Image Merge Software Inc.). Changes in TTV, highest tumor SUVmax, and total tumor SUVmean between cycles 1 and 2 were calculated and grouped into a) stable or decrease and b) increase. Serum PSA levels were assessed at each therapy cycle and at follow-up until progression or death. Changes in TTV, PSA, SUVmax, and SUVmean were correlated with PSA-progression-free survival (PSA-PFS) and the overall survival (OS) using the Kaplan–Meier methodology (log-rank test). Results: Between 07/2020 and 04/2022, 111 patients were screened and 73 finally included in the data analysis. The median follow-up was 8.9 months (range 1.4–26.6 months). Stable or decreased TTV at cycle 2 was associated with longer OS (hazard ratio (HR) 0.28, 95% confidence interval (CI) 0.09–0.86, p < 0.01). Similar, stable, or decreased PSA was associated with longer OS (HR 0.21; CI 0.07–0.62, p < 0.01) and PSA-PFS (HR 0.34; 95% CI 0.16–0.72, p < 0.01). Combining TTV and PSA will result in an augmented prognostic value for OS (HR 0.09; CI 0.01–0.63; p < 0.01) and for PSA-PFS (HR 0.11; CI 0.02–0.68; p < 0.01). A reduction of SUVmax or SUVmean was not prognostically relevant, neither for OS (p 0.88 and 0.7) nor for PSA-PFS (p 0.73 and 0.62, respectively). Conclusion: Six weeks after initiating [177Lu]Lu-PSMA I&T, TTV and serum PSA appear to be good prognosticators for OS. Combined together, TTV + PSA change demonstrates augmented prognostic value and can better predict PSA-PFS. Larger studies using TTV change prospectively as an early-response biomarker are warranted for implementing management change towards a more personalized clinical practice. [ABSTRACT FROM AUTHOR]

Objective: To identify which dynamic contrast-enhanced (DCE-)MRI features best predict histological response to neoadjuvant chemotherapy in patients with an osteosarcoma. Methods: Patients with osteosarcoma who underwent DCE-MRI before and after neoadjuvant chemotherapy prior to resection were retrospectively included at two different centers. Data from the center with the larger cohort (training cohort) was used to identify which method for region-of-interest selection (whole slab or focal area method) and which change in DCE-MRI features (time to enhancement, wash-in rate, maximum relative enhancement and area under the curve) gave the most accurate prediction of histological response. Models were created using logistic regression and cross-validated. The most accurate model was then externally validated using data from the other center (test cohort). Results: Fifty-five (27 poor response) and 30 (19 poor response) patients were included in training and test cohorts, respectively. Intraclass correlation coefficient of relative DCE-MRI features ranged 0.81–0.97 with the whole slab and 0.57–0.85 with the focal area segmentation method. Poor histological response was best predicted with the whole slab segmentation method using a single feature threshold, relative wash-in rate <2.3. Mean accuracy was 0.85 (95%CI: 0.75–0.95), and area under the receiver operating characteristic curve (AUC-index) was 0.93 (95%CI: 0.86–1.00). In external validation, accuracy and AUC-index were 0.80 and 0.80. Conclusion: In this study, a relative wash-in rate of <2.3 determined with the whole slab segmentation method predicted histological response to neoadjuvant chemotherapy in osteosarcoma. Consistent performance was observed in an external test cohort. [ABSTRACT FROM AUTHOR]

Background: While several methods have been proposed for automated assessment of breast‐cancer response to neoadjuvant chemotherapy on breast MRI, limited information is available about their performance across multiple institutions. Purpose: To assess the value and robustness of deep learning‐derived volumes of locally advanced breast cancer (LABC) on MRI to infer the presence of residual disease after neoadjuvant chemotherapy. Study Type: Retrospective. Subjects: Training cohort: 102 consecutive female patients with LABC scheduled for neoadjuvant chemotherapy (NAC) from a single institution (age: 25–73 years). Independent testing cohort: 55 consecutive female patients with LABC from four institutions (age: 25–72 years). Field Strength/Sequence: Training cohort: single vendor 1.5 T or 3.0 T. Testing cohort: multivendor 3.0 T. Gradient echo dynamic contrast‐enhanced sequences. Assessment: A convolutional neural network (nnU‐Net) was trained to segment LABC. Based on resulting tumor volumes, an extremely randomized tree model was trained to assess residual cancer burden (RCB)‐0/I vs. RCB‐II/III. An independent model was developed using functional tumor volume (FTV). Models were tested on an independent testing cohort and response assessment performance and robustness across multiple institutions were assessed. Statistical Tests: The receiver operating characteristic (ROC) was used to calculate the area under the ROC curve (AUC). DeLong's method was used to compare AUCs. Correlations were calculated using Pearson's method. P values <0.05 were considered significant. Results: Automated segmentation resulted in a median (interquartile range [IQR]) Dice score of 0.87 (0.62–0.93), with similar volumetric measurements (R = 0.95, P < 0.05). Automated volumetric measurements were significantly correlated with FTV (R = 0.80). Tumor volume‐derived from deep learning of DCE‐MRI was associated with RCB, yielding an AUC of 0.76 to discriminate between RCB‐0/I and RCB‐II/III, performing similar to the FTV‐based model (AUC = 0.77, P = 0.66). Performance was comparable across institutions (IQR AUC: 0.71–0.84). Data Conclusion: Deep learning‐based segmentation estimates changes in tumor load on DCE‐MRI that are associated with RCB after NAC and is robust against variations between institutions. Evidence Level: 2. Technical Efficacy: Stage 4. [ABSTRACT FROM AUTHOR]

Abstract Psychological fatigue includes mental fatigue and burnout. In order to investigate the impact of psychological fatigue on athletes' response monitoring, event-related potentials technique is typically used, and the most critical indicator is error-related negativity. Two experiments were carried out to explore cause-effect relationships of psychological fatigue and response monitoring. The event-related potentials data processing was based on Artificial Intelligence computing methods, including wavelet transform, grayscale transformation and other algorithms. The first experiment was done to explain mental fatigue and response monitoring. 15 participants operated continuously 60 min Flanker task, and then operated 15 min task accompanied by light music. From the results of behavioral performances, the fatigue period compared with the fatigue-free period showed significant differences, including reaction time (p = 0.029) and correct rate (p = 0.046). From the results of error-related negativity, the amplitude of the fatigue-free period was bigger than that of the music adjustment period, the latter was bigger than that of the fatigue period (p

Suboptimal guideline adherence in chronic myeloid leukemia (CML) care is associated with worse treatment outcomes. Current study focused on adherence to seven quality indicators (QIs) based on the European Leukemia Network guideline (one diagnostic, one therapeutic, and five monitoring indicators). Data were obtained from population-based registries in the Netherlands of 405 newly diagnosed chronic phase CML patients between January 2008 and April 2013. Compliance rates regarding diagnostic and therapeutic indicator were 83% and 78%, respectively. Monitoring indicators rates were lower: 21–27% for indicators concerning the first year and 58% and 62% for the second and third year, respectively. Noncompliance occurred mostly due to non-timely monitoring. Twenty cases did not comply with any indicator, 6% complied with all indicators. After adjustment for age, overall survival rates did not differ significantly between the groups. Adherence to guideline-based QIs was suboptimal. This demonstrates the evidence-practice gap, shows room for improvement and underscores the need for real-world data. [ABSTRACT FROM AUTHOR]

Psychological fatigue includes mental fatigue and burnout. In order to investigate the impact of psychological fatigue on athletes' response monitoring, event-related potentials technique is typically used, and the most critical indicator is error-related negativity. Two experiments were carried out to explore cause-effect relationships of psychological fatigue and response monitoring. The event-related potentials data processing was based on Artificial Intelligence computing methods, including wavelet transform, grayscale transformation and other algorithms. The first experiment was done to explain mental fatigue and response monitoring. 15 participants operated continuously 60 min Flanker task, and then operated 15 min task accompanied by light music. From the results of behavioral performances, the fatigue period compared with the fatigue-free period showed significant differences, including reaction time (p = 0.029) and correct rate (p = 0.046). From the results of error-related negativity, the amplitude of the fatigue-free period was bigger than that of the music adjustment period, the latter was bigger than that of the fatigue period (p < 0.001). The second experiment was conducted to explore burnout and response monitoring. Twenty-four participants were separated averagely into two groups. One group was burnout group, the other group was no burnout group. They both operated 15 min task. From the results of behavioral performances, no burnout group was better than burnout group. From the results of error-related negativity, no burnout group's amplitude was bigger than that of burnout group, but the difference was marginally significant. The conclusions are as follows: Artificial intelligence technology is feasible for processing event-related potentials data. Psychological fatigue weakens athletes' response monitoring ability, and the effect of mental fatigue is significant. In future researches, the following topics should be concerned, including the mediating or moderating effects of third variables, different ways of recovering from mental fatigue, computer data simulator and date accuracy, brain-computer interfaces and error-related negativity, etc. [ABSTRACT FROM AUTHOR]

Children show marked improvements in executive functioning (EF) between 4 and 7 years of age. In many societies, this time period coincides with the start of formal school education, in which children are required to follow rules in a structured environment, drawing heavily on EF processes such as inhibitory control. This study aimed to investigate the longitudinal development of two aspects of inhibitory control, namely response inhibition and response monitoring and their neural correlates. Specifically, we examined how their longitudinal development may differ by schooling experience, and their potential significance in predicting academic outcomes. Longitudinal data were collected in two groups of children at their homes. At T1, all children were roughly 4.5 years of age and neither group had attended formal schooling. One year later at T2, one group (P1, n = 40) had completed one full year of schooling while the other group (KG, n = 40) had stayed in kindergarten. Behavioural and brain activation data (measured with functional near‐infrared spectroscopy, fNIRS) in response to a Go/No‐Go task and measures of academic achievement were collected. We found that P1 children, compared to KG children, showed a greater change over time in activation related to response monitoring in the bilateral frontal cortex. The change in left frontal activation difference showed a small positive association with math performance. Overall, the school environment is important in shaping the development of the brain functions underlying the monitoring of one own's performance. [ABSTRACT FROM AUTHOR]

The ability to regulate behaviors and emotions depends in part on the ability to flexibly monitor one's own progress toward a goal. Atypical patterns of response monitoring have been reported in individuals with autism spectrum disorders (ASD). In the current study we examined the error related negativity (ERN), an electrophysiological index of response monitoring, in relation to behavioral, social cognitive, and emotional presentation in higher functioning children (8-16 years) diagnosed with autism (HFA: N = 38) and an age- and IQ-matched sample of children without autism (COM: N = 36). Both HFA and COM participants displayed larger amplitude responses to error compared to correct response trials and these amplitudes did not differ by diagnostic group. For participants with HFA, larger ERN amplitudes were associated with more parent-reported autistic symptoms and more self-reported internalizing problems. However, across the full sample, larger ERN amplitudes were associated with better performance on theory of mind tasks. The results are discussed in terms of the utility of electrophysiological measures for understanding essential moderating processes that contribute to the spectrum of behavioral expression in the development of ASD.

Gastrointestinal stromal tumors (GISTs) are rare mesenchymal neoplasms. Tyrosine kinase inhibitor (TKI) therapy is currently part of routine clinical practice for unresectable and metastatic disease. It is important to assess the efficacy of TKI treatment at an early stage to optimize therapy strategies and eliminate futile ineffective treatment, side effects and unnecessary costs. This systematic review provides an overview of the imaging features obtained from contrast-enhanced (CE)-CT and 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) PET/CT to predict and monitor TKI treatment response in GIST patients. PubMed, Web of Science, the Cochrane Library and Embase were systematically screened. Articles were considered eligible if quantitative outcome measures (area under the curve (AUC), correlations, sensitivity, specificity, accuracy) were used to evaluate the efficacy of imaging features for predicting and monitoring treatment response to various TKI treatments. The methodological quality of all articles was assessed using the Quality Assessment of Diagnostic Accuracy Studies, v2 (QUADAS-2) tool and modified versions of the Radiomics Quality Score (RQS). A total of 90 articles were included, of which 66 articles used baseline [18F]FDG-PET and CE-CT imaging features for response prediction. Generally, the presence of heterogeneous enhancement on baseline CE-CT imaging was considered predictive for high-risk GISTs, related to underlying neovascularization and necrosis of the tumor. The remaining articles discussed therapy monitoring. Clinically established imaging features, including changes in tumor size and density, were considered unfavorable monitoring criteria, leading to under- and overestimation of response. Furthermore, changes in glucose metabolism, as reflected by [18F]FDG-PET imaging features, preceded changes in tumor size and were more strongly correlated with tumor response. Although CE-CT and [18F]FDG-PET can aid in the prediction and monitoring in GIST patients, further research on cost-effectiveness is recommended.

Abstract Minimally‐invasive tools to assess tumour presence and burden may improve clinical management. FDG‐PET (metabolic) imaging is the current gold standard for interim response assessment in patients with classical Hodgkin Lymphoma (cHL), but this technique cannot be repeated frequently. Here we show that microRNAs (miRNA) associated with tumour‐secreted extracellular vesicles (EVs) in the circulation of cHL patients may improve response assessment. Small RNA sequencing and qRT‐PCR reveal that the relative abundance of cHL‐expressed miRNAs, miR‐127‐3p, miR‐155‐5p, miR‐21‐5p, miR‐24‐3p and let‐7a‐5p is up to hundred‐fold increased in plasma EVs of cHL patients pre‐treatment when compared to complete metabolic responders (CMR). Notably, in partial responders (PR) or treatment‐refractory cases (n = 10) the EV‐miRNA levels remain elevated. In comparison, tumour specific copy number variations (CNV) were detected in cell‐free DNA of 8 out of 10 newly diagnosed cHL patients but not in patients with PR. Combining EV‐miR‐127‐3p and/or EV‐let‐7a‐5p levels, with serum TARC (a validated protein cHL biomarker), increases the accuracy for predicting PET‐status (n = 129) to an area under the curve of 0.93 (CI: 0.87‐0.99), 93.5% sensitivity, 83.8/85.0% specificity and a negative predictive value of 96%. Thus the level of tumour‐associated miRNAs in plasma EVs is predictive of metabolic tumour activity in cHL patients. Our findings suggest that plasma EV‐miRNA are useful for detection of small residual lesions and may be applied as serial response prediction tool.

This study examined the impact of a school readiness intervention on external response monitoring in children in foster care. Behavioral and event-related potential (ERP) data were collected during a flanker task from children who received the Kids In Transition to School (KITS) Program (n = 26) and children who received services as usual (n = 19) before and after the intervention. While there were no significant group differences on the behavioral data, the ERP data for the two groups of children significantly differed. Specifically, in contrast to the children who received services as usual, the children who received the KITS Program displayed greater amplitude differences between positive and negative performance feedback over time for the N1, which reflects early attention processes, and feedback-related negativity, which reflects evaluation processes. In addition, although the two groups did not differ on amplitude differences between positive and negative performance feedback for these ERP components before the intervention, the children who received the KITS Program displayed greater amplitude differences than the children who received services as usual after the intervention. These results suggest that the KITS Program had an effect on responsivity to external performance feedback, which may be beneficial during the transition into kindergarten. [ABSTRACT FROM AUTHOR]

Minimally‐invasive tools to assess tumour presence and burden may improve clinical management. FDG‐PET (metabolic) imaging is the current gold standard for interim response assessment in patients with classical Hodgkin Lymphoma (cHL), but this technique cannot be repeated frequently. Here we show that microRNAs (miRNA) associated with tumour‐secreted extracellular vesicles (EVs) in the circulation of cHL patients may improve response assessment. Small RNA sequencing and qRT‐PCR reveal that the relative abundance of cHL‐expressed miRNAs, miR‐127‐3p, miR‐155‐5p, miR‐21‐5p, miR‐24‐3p and let‐7a‐5p is up to hundred‐fold increased in plasma EVs of cHL patients pre‐treatment when compared to complete metabolic responders (CMR). Notably, in partial responders (PR) or treatment‐refractory cases (n = 10) the EV‐miRNA levels remain elevated. In comparison, tumour specific copy number variations (CNV) were detected in cell‐free DNA of 8 out of 10 newly diagnosed cHL patients but not in patients with PR. Combining EV‐miR‐127‐3p and/or EV‐let‐7a‐5p levels, with serum TARC (a validated protein cHL biomarker), increases the accuracy for predicting PET‐status (n = 129) to an area under the curve of 0.93 (CI: 0.87‐0.99), 93.5% sensitivity, 83.8/85.0% specificity and a negative predictive value of 96%. Thus the level of tumour‐associated miRNAs in plasma EVs is predictive of metabolic tumour activity in cHL patients. Our findings suggest that plasma EV‐miRNA are useful for detection of small residual lesions and may be applied as serial response prediction tool. [ABSTRACT FROM AUTHOR]

Currently, it is difficult to predict effective therapy response to molecular therapies for the treatment of lung cancer based solely on anatomical images. 31P MR spectroscopic imaging could provide as a non‐invasive method to monitor potential biomarkers for early therapy evaluation, a necessity to improve personalized care and reduce cost. However, surface coils limit the imaging volume in conventional 31P MRSI. High‐energetic adiabatic RF pulses are required to achieve flip angle homogeneity but lead to high SAR. Birdcage coils permit use of conventional amplitude modulated pulses, even over large FOV, potentially decreasing overall SAR massively. Here, we investigate the feasibility of 3D 31P MRSI at 7 T in lung carcinoma patients using an integrated 31P birdcage body coil in combination with either a dual‐coil or a 16‐channel receiver. Simulations showed a maximum decrease in SNR per unit of time of 8% for flip angle deviations in short TR low flip‐angle excitation 3D CSI. The minimal SNR loss allowed for fast 3D CSI without time‐consuming calibration steps (>10:00 min.). 31P spectra from four lung carcinoma patients were acquired within 29:00 minutes and with high SNR using both receivers. The latter allowed discrimination of individual phosphodiesters, inorganic phosphate, phosphocreatine and ATP. The receiver array allowed for an increased FOV compared to the dual‐coil receiver. 3D 31P‐CSI were acquired successfully in four lung carcinoma patients using the integrated 31P body coil at ultra‐high field. The increased spectral resolution at 7 T allowed differentiation of multiple 31P metabolites related to phospholipid and energy metabolism. Simulations provide motivation to exclude 31P B1 calibrations, potentially decreasing total scan duration. Employing large receiver arrays improves the field of view allowing for full organ coverage. 31P MRSI is feasible in lung carcinoma patients and has potential as a non‐invasive method for monitoring personalized therapy response in lung tumors. [ABSTRACT FROM AUTHOR]

Purpose: Current response assessment systems for cancer patients receiving immunotherapy are limited. This is due to the associated inflammatory response that may confound the conventional morphological response evaluation criteria in solid tumors and metabolic positron emission tomography (PET) response criteria in solid. Recently, novel PET imaging techniques using radiolabeled antibodies and fragments have emerged as a particularly sensitive and specific modality for quantitative tracking of immune cell dynamics. Therefore, we sought to investigate the utility of Cu-64 labeled F(ab)'2 fragments for in vivo detection of CD8a+ T cells as a prognostic imaging biomarker of response to immunotherapy in an immunocompetent mouse model of colorectal cancer.Procedures: [64Cu]NOTA-CD8a was produced by enzymatic digestion of rat-anti-mouse CD8a antibody (clone YTS169.4), purified yielding isolated CD8a-F(ab)'2 fragments and randomly conjugated with the 2-S-(isothiocyanatbenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (p-SCN-Bn-NOTA) chelator. NOTA-CD8a was radiolabeled with Cu-64 and injected into CT26 tumor-bearing mice for longitudinal assessment. To investigate the value of [64Cu]NOTA-CD8a PET imaging for assessment of treatment response, CT26 tumor-bearing mice were subjected to external radiation therapy (XRT) in combination with anti-CTLA-4 therapy. Imaging data was supported by flow cytometry and immunohistochemistry (IHC).Results: Combination treatment with XRT and anti-CTLA-4 effectively inhibited tumor growth until day 22 post-therapy initiation (p = 0.0025) and increased the overall survival of mice compared to control (p = 0.0017). The [64Cu]NOTA-CD8a tumor-to-heart ratio was increased in XRT + anti-CTLA-4-treated mice on day 8 after initiation of therapy (p = 0.0246). Flow cytometry and IHC confirmed the increase in tumor-infiltrating CD8a+ cells in XRT + anti-CTLA-4-treated mice. Furthermore, [64Cu]NOTA-CD8a PET imaging distinguished responders and non-responders prior to treatment-induced changes in tumor volume among mice.Conclusion: In the present study, we demonstrated that [64Cu]NOTA-CD8a was able to detect treatment-induced changes in CD8a+ infiltration in murine CT26 colon tumors following a common preclinical combination treatment protocol. Overall, [64Cu]NOTA-CD8a exhibited good prognostic and predictive value. We suggest that [64Cu]NOTA-CD8a PET imaging can be used as an early biomarker of response to therapy in preclinical models. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study was to identify plasma microRNA (miRNA) biomarkers for stratifying and monitoring patients with locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) treated with FOLFIRINOX, and to investigate their functional roles. Summary background data: FOLFIRINOX has become a standard therapy for patients with advanced PDAC and can be used to potentially downstage disease. However, only a subset of patients respond, and biomarkers to guide decision-making are urgently needed. Methods: We used microarray-based profiling to discover deregulated miRNAs in pre- and postchemotherapy plasma samples from patients based on their progression-free survival (PFS) after FOLFIRINOX. Nine candidate plasma miRNAs were validated in an independent cohort (n = 43). The most discriminative plasma miRNA was correlated with clinicopathological factors and survival, and also investigated in an additional cohort treated with gemcitabine plus nab-paclitaxel. Expression patterns were further evaluated in matched tumor tissues. In vitro studies explored its function, key downstream gene-targets, and interaction with 5-fluorouracil, irinotecan, and oxaliplatin. Results: Plasma miR-181a-5p was significantly downregulated in non-progressive patients after FOLFIRINOX. In multivariate analysis, this decline correlated with improved PFS and overall survival, especially when combined with CA19-9 decline [hazard ratio (HR) = 0.153, 95% confidence interval (CI), 0.067-0.347 and HR = 0.201, 95% CI, 0.070-0.576, respectively]. This combination did not correlate with survival in patients treated with gemcitabine plus nab-paclitaxel. Tissue expression of miR-181a-5p reflected plasma levels. Inhibition of miR-181a-5p coupled with oxaliplatin exposure in pancreatic cell lines decreased cell viability. Conclusions: Plasma miR-181a-5p is a specific biomarker for monitoring FOLFIRINOX response. Decline in plasma miR-181a-5p and CA19-9 levels is associated with better prognosis after FOLFIRINOX and may be useful for guiding therapeutic choices and surgical exploration. [ABSTRACT FROM AUTHOR]

Background: To determine whether 18F‐PET/CT is able to identify treatment response as early as 1 week after the end of chemoradiotherapy, whether 18F‐PET/CT can identify prognostic markers concerning progression free survival and can identify patients who need additional consolidation therapy. Methods: A total of 54 patients with head and neck cancer were prospectively enrolled in this single‐center, randomized study from 03/2012‐04/2015. Patients underwent FDG‐PET/CT imaging at three predefined time points: pretreatment (PET/CT1), 1 week postprimary radiochemotherapy (PET/CT2) and 3 months postprimary radiochemotherapy (PET/CT3). Tumors were assessed quantitatively based on size and glucose uptake (SUVmax) concerning response at each time point. Response assessment was correlated with progression free survival. All patients had a minimum follow‐up period of 18 months. Multivariate regression analysis was performed to find independent predictors for progression free survival (PFS). Results: Thirty‐two (32) patients (64%) overall remained disease free, 11 patients (22%) had recurrence and 7 patients (14%) had persistent disease. There was no significantly different metabolic parameter ratio found concerning responders and nonresponders at posttreatment (PET/CT2 and 3) time points (P >.05) during clinical follow‐up. Multivariate regression analysis demonstrated both SUVmax and diameter assessed at time point PET/CT3 represent independent predictors of progression free survival (PFS). There was also no statistically significant difference in PFS between responders and nonresponders by means of PET/CT2 in both study arms (P >.05). Imaging responders at time point PET/CT3 showed a significantly longer PFS compared to nonresponders after the end of consolidation therapy (P <.01). Conclusions: Early response of head/neck cancer after radiochemotherapy can be accurately assessed with PET/CT 1 week after RCT. SUVmax and lesion diameter are independent predictors of PFS at time point PET/CT3. PET/CT2 has no prognostic value concerning PFS and cannot identify high risk patients for consolidation therapy. Imaging responders showed a significantly longer PFS compared to nonresponders and therefore PET/CT might serve as a prognostic biomarker. Trial registration: Clinical Trials.gov identifier: NCT01435252. [ABSTRACT FROM AUTHOR]

We examine whether math anxiety is related to altered response monitoring in an arithmetic task. Response-locked event-related brain potentials (ERPs) were evaluated in 23 highly (HMA) and 23 low math-anxious (LMA) individuals while they performed an arithmetic verification task. We focused on two widely studied ERPs elicited during error processing: error-related negativity (ERN) and error positivity (Pe). Correct-related negativity (CRN), an ERP elicited after a correct response, was also studied. The expected ERN following errors was found, but groups did not differ in its amplitude. Importantly, LMA individuals showed less negative CRN and more positive Pe amplitudes than their more anxious peers, suggesting more certainty regarding response accuracy and better adaptive behavioral adjustment after committing errors in an arithmetic task in the LMA group. The worse control over response performance and less awareness of correct responses in the HMA group might reduce their ability to 'learn from errors'. • Math anxiety is related to altered response monitoring in an arithmetic task. • Math-anxious individuals could be less aware of their mistakes in an arithmetic task. • Math-anxious individuals could be less certain about the accuracy of their answer. • These impairments might reduce their ability to 'learn from errors'. [ABSTRACT FROM AUTHOR]

There is sufficient evidence to believe that variations in the error-related negativity (ERN) are linked to dispositional characteristics in individuals. However, explanations of individual differences in the amplitude of the ERN cannot be derived from functional theories of the ERN. The ERN has a counterpart that occurs after correct responses (correct-response negativity, CRN). Based on the assumption that ERN and CRN reflect an identical cognitive process, variations in CRN might be associated with dispositional characteristics as well. Higher CRN amplitudes have been found to reflect task engagement. In the present study, a simple-choice-reaction task was used to investigate ERN and CRN amplitudes in relation to their score on a conscientiousness scale. The task consisted of a simple rule that required pressing the left or right key when a circle or square appeared, respectively. During alternative conditions that occur infrequently, participants were instructed to violate or reverse the previously established response rules. Smaller ΔERN amplitudes (manifested in almost equal CRN and ERN amplitudes) and a tendency of better task performance from participants scoring high on the conscientiousness scale might indicate a greater focus on the task and higher motivation of responding correctly. In addition, higher Pc amplitudes directly following the CRN indicated that the response monitoring system of less conscientious participants showed a higher disengagement. The role of individual differences in CRN amplitude should be studied in future experiments on performance monitoring.

Background and Objectives While tyrosine kinase inhibitors (TKIs) have transformed CP-CML management, limited data exist on their use in clinical practice. Methods SIMPLICITY (NCT01244750) is an observational study in CP-CML patients, exploring first‑line (1L) TKI use and management patterns in the US and Europe. Over half of the patients recruited in Europe are from Italy (n=266). This is an analysis of the Italian cohort and a comparison with the rest of the European SIMPLICITY population. Baseline demographic, factors influencing choice of first-line TKI, response monitoring patterns and predictors of monitoring, and treatment interruptions, discontinuations and switching by index TKIs are presented for the Italian cohort in the first year of treatment and compared with that for the overall European SIMPLICITY cohort. Results Italian patients received 1L imatinib (IM; retrospective [(n=31]; prospective [n=106]), dasatinib (DAS; n=56) or nilotinib (NIL; n=73). Documented cytogenetic response monitoring by 12 months was lower than expected, but almost all patients had documented molecular response monitoring. Fewer patients discontinued first-line TKI by 12 months in Italy compared with the rest of the European SIMPLICITY population (p=0.003). Of those with ≥12 months follow-up since start of 1L TKI, only 7.1% (n=19) of Italian patients switched to a second-line TKI, a third less than in the rest of the European SIMPLICITY population. Of interest, intolerance as opposed to resistance, was the main reason for switching. Conclusion This analysis provides valuable insights into management and treatment patterns in Italian patients with CML within routine clinical practice.

Background: We aimed to examine the feasibility and potential benefit of applying PET Response Criteria in Solid Tumors (PERCIST) for response monitoring in metastatic breast cancer (MBC). Further, we introduced the nadir scan as a reference. Methods: Response monitoring FDG-PET/CT scans in 37 women with MBC were retrospectively screened for PERCIST standardization and measurability criteria. One-lesion PERCIST based on changes in SULpeak measurements of the hottest metastatic lesion was used for response categorization. The baseline (PERCISTbaseline) and the nadir scan (PERCISTnadir) were used as references for PERCIST analyses. Results: Metastatic lesions were measurable according to PERCIST in 35 of 37 (94.7%) patients. PERCIST was applied in 150 follow-up scans, with progression more frequently reported by PERCISTnadir (36%) than PERCISTbaseline (29.3%; p = 0.020). Reasons for progression were (a) more than 30% increase in SULpeak of the hottest lesion (n = 7, 15.9%), (b) detection of new metastatic lesions (n = 28, 63.6%), or both (a) and (b) (n = 9, 20.5%). Conclusions: PERCIST, with the introduction of PERCISTnadir, allows a graphical interpretation of disease fluctuation that may be beneficial in clinical decision-making regarding potential earlier termination of non-effective toxic treatment. PERCIST seems feasible for response monitoring in MBC but prospective studies are needed to come this closer.

There is sufficient evidence to believe that variations in the error-related negativity (ERN) are linked to dispositional characteristics in individuals. However, explanations of individual differences in the amplitude of the ERN cannot be derived from functional theories of the ERN. The ERN has a counterpart that occurs after correct responses (correct-response negativity, CRN). Based on the assumption that ERN and CRN reflect an identical cognitive process, variations in CRN might be associated with dispositional characteristics as well. Higher CRN amplitudes have been found to reflect task engagement. In the present study, a simple-choice-reaction task was used to investigate ERN and CRN amplitudes in relation to their score on a conscientiousness scale. The task consisted of a simple rule that required pressing the left or right key when a circle or square appeared, respectively. During alternative conditions that occur infrequently, participants were instructed to violate or reverse the previously established response rules. Smaller ΔERN amplitudes (manifested in almost equal CRN and ERN amplitudes) and a tendency of better task performance from participants scoring high on the conscientiousness scale might indicate a greater focus on the task and higher motivation of responding correctly. In addition, higher Pc amplitudes directly following the CRN indicated that the response monitoring system of less conscientious participants showed a higher disengagement. The role of individual differences in CRN amplitude should be studied in future experiments on performance monitoring. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the use of 68Ga-PSMA PET/CT for monitoring response to 177Lu-617 PSMA radioligand therapy in patients with metastatic castrate-resistant prostate cancer (mCRPC). Methods: Patients from the University Hospital Bonn and the University Hospital Aachen were retrospectively reviewed for this study. We included 48 patients with mCRPC who were treated with 177Lu-PSMA-617 and whose records included 68Ga-PSMA PET/CT imaging before the first and after the third or fourth treatment cycle. A treatment response based on 68Ga-PSMA PET/CT was defined according to a modified version of the PERCIST criteria. A decline in PSA level of ≥50% was considered the reference standard. The sensitivity, specificity, positive and negative predictive values, and ROC curves were calculated, and patient survival times in relation to the PET results were also analysed. Results: 68Ga-PSMA PET/CT had a sensitivity of about 85% and a specificity of between 55% and 65%. The negative and positive predictive values ranged between 70% and 78%. The fitted ROC area was 0.70. The survival time was about 19.6 months in patients with a treatment response, while nonresponders had a survival time of about 15.9 months. However, this difference between the groups was not statistically significant. Conclusion: Our results indicate that 68Ga-PSMA PET/CT could be a useful tool for the evaluation of response to 177Lu-PSMA-617 radioligand therapy within a theranostic framework. [ABSTRACT FROM AUTHOR]

The term liquid biopsy (LB) refers to the study of circulating tumor cells, circulating tumors nucleic acids free of cells or contained in exosomes, and information about platelets associated with tumors. LB can be performed in different biofluids and allows the limitations of tissue biopsy to be overcome offering possibilities of tumor identification reflecting in real time tumor heterogeneity. In addition, LB allows screening and early detection of cancer, real-time monitoring of therapy, stratification and therapeutic intervention, a therapeutic target and resistance mechanism, and a risk of metastatic relapse. Currently, LB has been shown to be effective for its application in different types of tumors including lung, colorectal, prostate, melanoma, breast and pancreatic cancer, by the determination and identification of biomarkers that with a high probability have the potential to change the way in which medical oncology could predict the course of the disease. These biomarkers make it possible to capture the heterogeneity of the cancer, monitor its clonal evolution, indicate new treatments or retreatments and evaluate the responses to different evolutionary and/or therapeutic pressures in the cancer disease.

Abstract: The error‐related negativity (ERN) is a negative deflection in the event‐related potential occurring when individuals make mistakes. The ERN has been proposed as a biomarker for anxiety and a substantial amount of research suggests the ERN increases across development. Further, the ERN may relate to individual differences and the development of cognitive control. Despite the large quantity of research on this topic, there have been no studies focusing on the relationship between pubertal hormones and the ERN. Previous work suggests developmental increases may begin sooner for girls than for boys, suggesting that puberty may impact the ERN. The current study examined the relationship between pubertal hormones and the ERN amplitude in a sample of 99 females between 8 and 14 years old. Each participant and the parent who accompanied them completed the Pubertal Developmental Scale (PDS) to assess the degree to which pubertal indicators are present. Participants also completed a Go/NoGo Task while EEG was recorded and participants provided saliva samples for hormone assays. Results indicated that ERN was significantly related to both the dehydroepiandrosterone (DHEA) hormone and PDS scores. A simultaneous multivariate regression suggested that DHEA levels significantly predict the ERN, even when controlling for age, behavioral variables, and PDS. These findings suggest that ERN amplitude is related to DHEA levels, further linking puberty to developmental increases in the ERN. Future research should examine this relationship in the context of developmental increases in anxiety symptoms. [ABSTRACT FROM AUTHOR]

Abstract: The error‐related negativity (ERN) is a negative deflection in the event‐related potential waveform that occurs when an individual makes a mistake, and an increased ERN has been proposed as a biomarker for anxiety. However, previous work suggests that fearful children are characterized by a smaller ERN. We have proposed that this may reflect the changing phenomenology of anxiety across development. In the current study, we investigate this possibility using a longitudinal within‐subject design. In 271 children, we completed observational measures of fear when the children were 3 years old, and then measured the ERN when the children were 6 and 9 years old. Fearful children were characterized by a decreased ERN when they were 6‐year‐old; by age 9, the same children who were fearful at age 3 had increased ERNs—a pattern that closely resembles that of anxious adolescents and adults. [ABSTRACT FROM AUTHOR]

Background and purpose A FDG-PET/CT image feature with optimal prognostic potential for locally-advanced non-small cell lung cancer (LA-NSCLC) patients has yet to be identified, and neither has the optimal time for FDG-PET/CT response assessment; furthermore, nodal features have been largely ignored in the literature. We propose to identify image features or imaging time point with maximal prognostic power. Materials and methods Consecutive consenting patients with LA-NSCLC receiving curative intent CRT were enrolled. 4DPET/4DCT scans were acquired 0, 2, 4, and 7 weeks during IMRT treatment. Eleven image features and their rates of change were recorded for each time point and tested for each of the possible outcome 2 years post CRT using the Kaplan–Meier method. Results 32 consecutive patients were recruited, 27 completing all scans. Restricting analysis to 4DPET/4DCT features and rates of change with p  < 0.005, several volume-based features and their rates of change reached significance. Image features involving nodal disease were the only ones associated with overall survival. Conclusions Several 4DPET/CT features and rates of change can reach significant association ( p  < 0.005) with outcomes, including overall survival, at many time points. The optimal time for adaptive CRT is therefore not constrained uniquely on imaging. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate whole-body MRI (WB-MRI) parameters significantly associated with treatment response in multiple myeloma (MM).Methods: Twenty-one MM patients underwent WB-MRI at diagnosis and after two cycles of chemotherapy. Scans acquired at 3.0 T included T2, diffusion-weighted-imaging (DWI) and mDixon pre- and post-contrast. Twenty focal lesions (FLs) matched on DWI and post-contrast mDixon were selected for each time point. Estimated tumour volume (eTV), apparent diffusion coefficient (ADC), enhancement ratio (ER) and signal fat fraction (sFF) were derived. Clinical treatment response to chemotherapy was assessed using conventional criteria. Significance of temporal parameter change was assessed by the paired t test and receiver operating characteristics/area under the curve (AUC) analysis was performed. Parameter repeatability was assessed by interclass correlation (ICC) and Bland-Altman analysis of 10 healthy volunteers scanned at two time points.Results: Fifteen of 21 patients responded to treatment. Of 254 FLs analysed, sFF (p < 0.0001) and ADC (p = 0.001) significantly increased in responders but not non-responders. eTV significantly decreased in 19/21 cases. Focal lesion sFF was the best discriminator of treatment response (AUC 1.0). Bone sFF repeatability was excellent (ICC 0.98) and better than bone ADC (ICC 0.47).Conclusion: WB-MRI derived focal lesion sFF shows promise as an imaging biomarker of treatment response in newly diagnosed MM.Key Points: • Bone signal fat fraction using mDixon is a robust quantifiable parameter • Fat fraction and ADC significantly increase in myeloma lesions responding to treatment • Bone lesion fat fraction is the best discriminator of myeloma treatment response. [ABSTRACT FROM AUTHOR]

The error-related negativity (ERN) is an electrophysiological response to errors. Individual differences in the ERN have been posited to reflect sensitivity to threat and linked with risk for anxiety disorders. Attention bias modification is a promising computerized intervention that has been shown to decrease threat biases and anxiety symptoms. In the present study, we examined the impact of a single session of attention bias modification, relative to a control task, on the neural correlates of response monitoring, including the ERN, correct response negativity (CRN), and their difference (i.e., the ERN – CRN or ΔERN). The final sample included 60 participants who first completed a flanker task to elicit the ERN and CRN, and were then randomly assigned to attention bias modification ( n = 30) or a control task ( n = 30). After completing the attention bias modification or control task, participants completed the same flanker task to again elicit the ERN and CRN. Among participants who completed attention bias modification training, the ERN, CRN, and ΔERN decreased from the pre- to post-training assessment. In contrast, in participants who completed the control task, the CRN, ERN, and ΔERN did not differ between the pre- and post-training assessment. The presents study suggests that a single session of attention bias modification reduces neural correlates of response monitoring, including error-related brain activity. These results also support attention bias modification as a potential mechanistic-based intervention for the prevention and treatment of anxiety pathology. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the study was to investigate the potential of diffusion-weighted magnetic resonance imaging (DW-MRI) and 3'-dexoy-3'-[18F]fluorothymidine ([18F]FLT) positron emission tomography (PET) as early biomarkers of treatment response of 5-fluorouracil (5-FU) in a syngeneic rat model of colorectal cancer liver metastases.Procedures: Wag/Rij rats with intrahepatic syngeneic CC531 tumors were treated with 5-FU (15, 30, or 60 mg/kg in weekly intervals). Before treatment and at days 1, 3, 7, and 14 after treatment rats underwent DW-MRI and [18F]FLT PET. Tumors were analyzed immunohistochemically for Ki67, TK1, and ENT1 expression.Results: 5-FU inhibited the growth of CC531 tumors in a dose-dependent manner. Immunohistochemical analysis did not show significant changes in Ki67, TK1, and ENT1 expression. However, [18F]FLT SUVmean and SUVmax were significantly increased at days 4 and 7 after treatment with 5-FU (60 mg/kg) and returned to baseline at day 14 (SUVmax at days -1, 4, 7, and 14 was 1.1 ± 0.1, 2.3 ± 0.5, 2.3 ± 0.6, and 1.5 ± 0.4, respectively). No changes in [18F]FLT uptake were observed in the nontreated animals. Furthermore, the apparent diffusion coefficient (ADCmean) did not change in 5-FU-treated rats compared to untreated rats.Conclusion: This study suggests that 5-FU treatment induces a flare in [18F]FLT uptake of responsive CC531 tumors in the liver, while the ADCmean did not change significantly. Future studies in larger groups are warranted to further investigate whether [18F]FLT PET can discriminate between disease progression and treatment response. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant treatment of HER2-positive breast cancer frequently leads to a pathologic complete response (pCR), which is associated with favourable long-term outcome. Treatment regimens typically consist of 6-9 cycles of trastuzumab-based chemotherapy, although many patients achieve early radiologic complete response (rCR). If rCR accurately predicts pCR, the number of chemotherapy cycles can possibly be reduced. Methods: We performed a diagnostic accuracy study to determine the association between rCR and pCR in patients with stage II-III HER2-positive breast cancer treated with neoadjuvant trastuzumab-based chemotherapy at the Netherlands Cancer Institute. RCR was defined as the disappearance of pathologic contrast enhancement in the original tumour region on repeated magnetic resonance imaging (MRI). PCR was defined as the absence of invasive tumour cells in the resected breast specimen (ypT0/is). Diagnostic accuracy was estimated in the overall population and in subgroups based on hormone receptor (HR) status. The prognostic value of rCR for recurrence-free interval was evaluated as an exploratory analysis. Results: We identified 296 eligible patients with 297 HER2-positive tumours (154 HR-negative and 143 HR-positive) treated with neoadjuvant trastuzumab-based chemotherapy between 2004 and 2016. Overall, the rCR rate was 69% (206/297) and the pCR rate was 61% (181/297). Among 206 patients with rCR, 150 also had pCR (negative predictive value [NPV] = 150/206 = 73%). Among 91 patients without rCR, 60 had residual tumour at pathology (positive predictive value [PPV] = 60/91 = 66%). The NPV was better in HR-negative compared to HR-positive tumours (88 vs. 57%), while the PPV was better in HR-positive tumours (50 vs. 78%). Achieving rCR was associated with a 5-year recurrence-free interval of 88% compared to 68% without rCR (hazard ratio 0.34, 95% confidence interval 0.17-0.65, P = 0.001). Conclusion: Achieving rCR corresponds well with pCR in HER2-positive breast cancer, particularly in the HR-negative subgroup. RCR is also associated with improved long-term outcome. [ABSTRACT FROM AUTHOR]

Background: In alcohol use disorder, deficits in cognitive control (i.e., inhibition and response monitoring) might underlie the loss of self-control and, thereby, failure to adjust alcohol consumption in response to associated negative consequences. According to the continuum hypothesis, the magnitude of these deficits should be related in a stair-case manner, with the greatest deficits among its heaviest consumers. The current study aims at investigating this association in the general population. Methods: This is a cross-sectional study of 397 participants aged 18-64 years, who self-reported their mean weekly alcohol consumption and were assessed with the stop-signal task, estimating inhibitory efficiency (stop-signal reaction time; SSRT) and response monitoring (post-error slowing; PES). Set-shifting ability was investigated by the intra-extra dimensional (IED) set-shifting task. Three ANCOVAs were performed with SSRT, PES, and IED as the dependent variables (DV), respectively, and alcohol consumption levels as the independent variable. Covariates were included when they were significantly associated with the DV. Results: Compared to the teetotalers, all levels of alcohol consumption were significantly associated to lower SSRT, which implies more efficient inhibitory control; however, there was no significant difference in SSRT between other consumption levels. The two highest consumption groups had significantly shorter PES when compared to teetotalers and/or the lowest consumption group, implying less behavioral adjustment after failures. IED was not significantly related to the alcohol consumption levels. Conclusions: There was no stair-case relation between weekly consumption levels and cognitive control functions within this general population, which might be due to the limited consumption range investigated. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is characterized by a monoclonal plasma cell population in the bone marrow. Lytic lesions occur in up to 90 % of patients. For many years, whole-body X-ray (WBX) was the method of choice for detecting skeleton abnormalities. However, the value of WBX in relapsing disease is limited because lesions persist post-treatment, which restricts the capacity to distinguish between old, inactive skeletal lesions and new, active ones. Therefore, alternative techniques are necessary to visualize disease activity. Modern imaging techniques such as magnetic resonance imaging, positron emission tomography and computed tomography offer superior detection of myeloma bone disease and extramedullary manifestations. In particular, the properties of nuclear imaging enable the identification of disease activity by directly targeting the specific cellular properties of malignant plasma cells. In this review, an overview is provided of the effectiveness of radiopharmaceuticals that target metabolism, surface receptors and angiogenesis. The available literature data for commonly used nuclear imaging tracers, the promising first results of new tracers, and our pilot work indicate that a number of these radiopharmaceutical applications can be used effectively for staging and response monitoring of relapsing MM patients. Moreover, some tracers can potentially be used for radio immunotherapy. [ABSTRACT FROM AUTHOR]

This study aimed to compare contrast-enhanced CT (CE-CT) and 18 F-FDG PET/CT for response monitoring in metastatic breast cancer using the standardized response evaluation criteria RECIST 1.1 and PERCIST. The objective was to examine whether progressive disease was detected systematically earlier by one of the modalities. Methods: Women with biopsy-verified metastatic breast cancer were enrolled prospectively and monitored using combined CE-CT and 18 F-FDG PET/CT every 9-12 wk to evaluate response to first-line treatment. CE-CT scans and RECIST 1.1 were used for clinical decision-making without accessing the 18 F-FDG PET/CT scans. At study completion, 18 F-FDG PET/CT scans were unmasked and assessed according to PERCIST. Visual assessment was used if response criteria could not be applied. The modality-specific time to progression was defined as the time from the baseline scan until the first scan demonstrating progression. Paired comparative analyses for CE-CT versus 18 F-FDG PET/CT were applied, and the primary endpoint was earlier detection of progression by one modality. Secondary endpoints were time to detection of progression, response categorization, visualization of changes in response over time, and measurable disease according to RECIST and PERCIST. Results: In total, 87 women were evaluable, with a median of 6 (1-11) follow-up scans. Progression was detected first by 18 F-FDG PET/CT in 43 (49.4%) of 87 patients and first by CE-CT in 1 (1.15%) of 87 patients ( P  < 0.0001). Excluding patients without progression ( n  = 32), progression was seen first on 18 F-FDG PET/CT in 78.2% (43/55) of patients. The median time from detection of progression by 18 F-FDG PET/CT to that of CE-CT was 6 mo (95% CI, 4.3-6.4 mo). At baseline, 76 (87.4%) of 87 patients had measurable disease according to PERCIST and 51 (58.6%) of 87 patients had measurable disease according to RECIST 1.1. Moreover, 18 F-FDG PET/CT provided improved visualization of changes in response over time, as seen in the graphical abstract. Conclusion: Disease progression was detected earlier by 18 F-FDG PET/CT than by CE-CT in most patients, with a potentially clinically relevant median 6-mo delay for CE-CT. More patients had measurable disease according to PERCIST than according to RECIST 1.1. The magnitude of the final benefit for patients is a perspective for future research., (© 2023 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: Response-guided neoadjuvant chemotherapy (RG-NACT) with magnetic resonance imaging (MRI) is effective in treating oestrogen receptor positive/human epidermal growth factor receptor-2 negative (ER-positive/HER2-negative) breast cancer. We estimated the expected cost-effectiveness and resources required for its implementation compared to conventional-NACT.Methods: A Markov model compared costs, quality-adjusted-life-years (QALYs) and costs/QALY of RG-NACT vs. conventional-NACT, from a hospital perspective over a 5-year time horizon. Health services required for and health outcomes of implementation were estimated via resource modelling analysis, considering a current (4 %) and a full (100 %) implementation scenario.Results: RG-NACT was expected to be more effective and less costly than conventional NACT in both implementation scenarios, with 94 % (current) and 95 % (full) certainty, at a willingness to pay threshold of €20.000/QALY. Fully implementing RG-NACT in the Dutch target population of 6306 patients requires additional 5335 MRI examinations and an (absolute) increase in the number of MRI technologists, by 3.6 fte (full-time equivalent), and of breast radiologists, by 0.4 fte. On the other hand, it prevents 9 additional relapses, 143 cancer deaths, 23 congestive heart failure events and 2 myelodysplastic syndrome/acute myeloid leukaemia events.Conclusion: Considering cost-effectiveness, RG-NACT is expected to dominate conventional-NACT. While personnel capacity is likely to be sufficient for a full implementation scenario, MRI utilization needs to be intensified. [ABSTRACT FROM AUTHOR]