Purpose The purpose of this study was to evaluate 18F-FDG-PET/CT as an early and late interim imaging biomarker in patients with pancreatic ductal adenocarcinoma (PDAC) who undergo first-line systemic therapy. Methods This was a prospective, single-center, single-arm, open-label study (IRB12-000770). Patient receiving first line chemotherapy were planned to undergo a baseline 18F-FDG-PET/CT (PET1), early interim 18F-FDG PET/CT (PET2) and late interim 18F-FDG-PET/CT (PET3). ROC selected and established (mPERCIST / RECIST1.1) cut-offs for metabolic and radiographic tumor response assessment were applied. Patients were followed to collect data on further treatments and overall survival (OS). Results The study population consisted of 28 patients who underwent PET1. Twenty-three of these (82%) underwent PET2 and 21 (75%) PET3, respectively. Twenty-three deaths occurred during a median follow up period of 14 months (maximum follow up, 58.3 months). The median OS was 36.2 months (95%CI, 28-NYR) in early metabolic responders (6/23 (26%), P = 0.016) and 25.4 months (95%CI, 19.6-NYR) in early radiographic responders (7/23 (30%), P = 0.16). The median overall survival was 27.4 months (95%CI, 21.4-NYR) in late metabolic responders (10/21 (48%), P = 0.058) and 58.2 months (95%CI, 21.4-NYR) in late radiographic responders (7/21 (33%), P = 0.008). Conclusion 18F-FDG PET may serve as early interim imaging biomarker (~ at 4 weeks) for evaluation of response to first-line chemotherapy in patients with PDAC. Radiographic changes might be sufficient for response evaluation after the completion of first line chemotherapy.Background Tumor programmed-death ligand-1 (PD-L1) proportion score is the current method to select non-small-cell lung cancer (NSCLC) patients for single agent treatment with pembrolizumab, a programmed cell death-1 (PD-1) monoclonal antibody. However, not all patients respond to therapy. Better understanding of in vivo drug behavior may help to select patients that benefit most. Methods NSCLC patients eligible for pembrolizumab monotherapy as first or later line therapy were enrolled. Patients received two injections of 89Zr-pembrolizumab; one without a preceding dose of pembrolizumab and one with 200 mg pembrolizumab, directly prior to tracer injection. Up to four PET/CT scans were obtained after tracer injection. Post-imaging acquisition, patients were treated with 200 mg pembrolizumab, every three weeks. Tumor uptake and tracer biodistribution were visually assessed and quantified as standardized uptake value (SUV). Tumor tracer uptake was correlated with PD-1 and PD-L1 expression and response to pembrolizumab treatment. Results Twelve NSCLC patients were included. One patient experienced grade 3 myalgia after tracer injection. 89Zr-pembrolizumab was observed in the blood pool, liver and spleen. Tracer uptake was visualized in 47,2% of 72 tumor lesions measuring ≥20 mm long axis diameter, and substantial uptake heterogeneity was observed within and between patients. Uptake was higher in patients with response to pembrolizumab treatment (n = 3) compared to patients without a response (n = 9), although this was not statistically significant (median SUVpeak 11.4 vs 5.7, P = 0.066). No significant correlations were found with PD-L1 or PD-1 immunohistochemistry. Conclusion 89Zr-pembrolizumab injection was safe with only one grade 3 adverse event, possibly immune related, out of 12 patients. 89Zr-pembrolizumab tumor uptake was higher in patients with response to pembrolizumab treatment, but did not correlate with PD-L1 or PD-1 immunohistochemistry.
Radiomics features may predict outcome in diffuse large B-cell lymphoma (DLBCL). Currently, multiple segmentation methods are used to calculate metabolic tumor volume (MTV). We assessed the influence of segmentation method on the discriminative power of radiomics features in DLBCL for patient level and for the largest lesion.
50 baseline
F-fluorodeoxyglucose positron emission tomography computed tomography (PET/CT) scans of DLBCL patients who progressed or relapsed within 2 years after diagnosis were matched on uptake time and reconstruction method with 50 baseline PET/CT scans of DLBCL patients without progression. Scans were analysed using 6 semi-automatic segmentation methods (standardized uptake value (SUV)4.0, SUV2.5, 41% of the maximum SUV, 50% of the SUVpeak, majority vote (MV)2 and MV3, respectively). Based on these segmentations, 490 radiomics features were extracted at patient level and 486 features for the largest lesion. To quantify the agreement between features extracted from different sered to the SUV4.0 segmentation was lowest for A50P both at patient level and for the largest lesion, with 77.3% and 66.7% of the features yielding an ICC ≥0.75, respectively. Features were not highly correlated with MTV, with at least 435 features at patient level and 409 features for the largest lesion for all segmentation methods with a correlation coefficient less then 0.7. Features were highly correlated with SUVpeak (at least 190 and 134 were uncorrelated, respectively). CV-AUCs ranged between 0.69±0.11 and 0.84±0.09 for patient level, and between 0.69±0.11 and 0.73±0.10 for lesion level. Conclusion Even though there are differences in the actual radiomics feature values derived and selected features between segmentation methods, there is no substantial difference in the discriminative power of radiomics features between segmentation methods.Comorbid anxiety and depressive symptoms in chronic pain are a common health problem, but the underlying mechanisms remain unclear. Previously, we have demonstrated that sensitization of the CeA neurons via decreased GABAergic inhibition contributes to anxiety-like behaviors in neuropathic pain rats. In this study, by using male Sprague Dawley rats, we reported that the CeA plays a key role in processing both sensory and negative emotional-affective components of neuropathic pain. https://www.selleckchem.com/mTOR.html Bilateral electrolytic lesions of CeA, but not lateral/basolateral nucleus of the amygdala (LA/BLA), abrogated both pain hypersensitivity and aversive and depressive symptoms of neuropathic rats induced by spinal nerve ligation (SNL). Moreover, SNL rats showed structural and functional neuroplasticity manifested as reduced dendritic spines on the CeA neurons and enhanced LTD at the LA/BLA-CeA synapse. Disruption of GluA2-containing AMPAR trafficking and endocytosis from synapses using synthetic peptides, either pep2-EVKI or Tat-GluA2(3Y), restored the enhanced LTD at the LA/BLA-CeA synapse, and alleviated the mechanical allodynia and comorbid aversive and depressive symptoms in neuropathic rats, indicating that the endocytosis of GluA2-containing AMPARs from synapses is probably involved in the LTD at the LA/BLA-CeA synapse and the comorbid aversive and depressive symptoms in neuropathic pain in SNL-operated rats.
Purpose The purpose of this study was to evaluate 18F-FDG-PET/CT as an early and late interim imaging biomarker in patients with pancreatic ductal adenocarcinoma (PDAC) who undergo first-line systemic therapy. Methods This was a prospective, single-center, single-arm, open-label study (IRB12-000770). Patient receiving first line chemotherapy were planned to undergo a baseline 18F-FDG-PET/CT (PET1), early interim 18F-FDG PET/CT (PET2) and late interim 18F-FDG-PET/CT (PET3). ROC selected and established (mPERCIST / RECIST1.1) cut-offs for metabolic and radiographic tumor response assessment were applied. Patients were followed to collect data on further treatments and overall survival (OS). Results The study population consisted of 28 patients who underwent PET1. Twenty-three of these (82%) underwent PET2 and 21 (75%) PET3, respectively. Twenty-three deaths occurred during a median follow up period of 14 months (maximum follow up, 58.3 months). The median OS was 36.2 months (95%CI, 28-NYR) in early metabolic responders (6/23 (26%), P = 0.016) and 25.4 months (95%CI, 19.6-NYR) in early radiographic responders (7/23 (30%), P = 0.16). The median overall survival was 27.4 months (95%CI, 21.4-NYR) in late metabolic responders (10/21 (48%), P = 0.058) and 58.2 months (95%CI, 21.4-NYR) in late radiographic responders (7/21 (33%), P = 0.008). Conclusion 18F-FDG PET may serve as early interim imaging biomarker (~ at 4 weeks) for evaluation of response to first-line chemotherapy in patients with PDAC. Radiographic changes might be sufficient for response evaluation after the completion of first line chemotherapy.Background Tumor programmed-death ligand-1 (PD-L1) proportion score is the current method to select non-small-cell lung cancer (NSCLC) patients for single agent treatment with pembrolizumab, a programmed cell death-1 (PD-1) monoclonal antibody. However, not all patients respond to therapy. Better understanding of in vivo drug behavior may help to select patients that benefit most. Methods NSCLC patients eligible for pembrolizumab monotherapy as first or later line therapy were enrolled. Patients received two injections of 89Zr-pembrolizumab; one without a preceding dose of pembrolizumab and one with 200 mg pembrolizumab, directly prior to tracer injection. Up to four PET/CT scans were obtained after tracer injection. Post-imaging acquisition, patients were treated with 200 mg pembrolizumab, every three weeks. Tumor uptake and tracer biodistribution were visually assessed and quantified as standardized uptake value (SUV). Tumor tracer uptake was correlated with PD-1 and PD-L1 expression and response to pembrolizumab treatment. Results Twelve NSCLC patients were included. One patient experienced grade 3 myalgia after tracer injection. 89Zr-pembrolizumab was observed in the blood pool, liver and spleen. Tracer uptake was visualized in 47,2% of 72 tumor lesions measuring ≥20 mm long axis diameter, and substantial uptake heterogeneity was observed within and between patients. Uptake was higher in patients with response to pembrolizumab treatment (n = 3) compared to patients without a response (n = 9), although this was not statistically significant (median SUVpeak 11.4 vs 5.7, P = 0.066). No significant correlations were found with PD-L1 or PD-1 immunohistochemistry. Conclusion 89Zr-pembrolizumab injection was safe with only one grade 3 adverse event, possibly immune related, out of 12 patients. 89Zr-pembrolizumab tumor uptake was higher in patients with response to pembrolizumab treatment, but did not correlate with PD-L1 or PD-1 immunohistochemistry. Radiomics features may predict outcome in diffuse large B-cell lymphoma (DLBCL). Currently, multiple segmentation methods are used to calculate metabolic tumor volume (MTV). We assessed the influence of segmentation method on the discriminative power of radiomics features in DLBCL for patient level and for the largest lesion. 50 baseline F-fluorodeoxyglucose positron emission tomography computed tomography (PET/CT) scans of DLBCL patients who progressed or relapsed within 2 years after diagnosis were matched on uptake time and reconstruction method with 50 baseline PET/CT scans of DLBCL patients without progression. Scans were analysed using 6 semi-automatic segmentation methods (standardized uptake value (SUV)4.0, SUV2.5, 41% of the maximum SUV, 50% of the SUVpeak, majority vote (MV)2 and MV3, respectively). Based on these segmentations, 490 radiomics features were extracted at patient level and 486 features for the largest lesion. To quantify the agreement between features extracted from different sered to the SUV4.0 segmentation was lowest for A50P both at patient level and for the largest lesion, with 77.3% and 66.7% of the features yielding an ICC ≥0.75, respectively. Features were not highly correlated with MTV, with at least 435 features at patient level and 409 features for the largest lesion for all segmentation methods with a correlation coefficient less then 0.7. Features were highly correlated with SUVpeak (at least 190 and 134 were uncorrelated, respectively). CV-AUCs ranged between 0.69±0.11 and 0.84±0.09 for patient level, and between 0.69±0.11 and 0.73±0.10 for lesion level. Conclusion Even though there are differences in the actual radiomics feature values derived and selected features between segmentation methods, there is no substantial difference in the discriminative power of radiomics features between segmentation methods.Comorbid anxiety and depressive symptoms in chronic pain are a common health problem, but the underlying mechanisms remain unclear. Previously, we have demonstrated that sensitization of the CeA neurons via decreased GABAergic inhibition contributes to anxiety-like behaviors in neuropathic pain rats. In this study, by using male Sprague Dawley rats, we reported that the CeA plays a key role in processing both sensory and negative emotional-affective components of neuropathic pain. https://www.selleckchem.com/mTOR.html Bilateral electrolytic lesions of CeA, but not lateral/basolateral nucleus of the amygdala (LA/BLA), abrogated both pain hypersensitivity and aversive and depressive symptoms of neuropathic rats induced by spinal nerve ligation (SNL). Moreover, SNL rats showed structural and functional neuroplasticity manifested as reduced dendritic spines on the CeA neurons and enhanced LTD at the LA/BLA-CeA synapse. Disruption of GluA2-containing AMPAR trafficking and endocytosis from synapses using synthetic peptides, either pep2-EVKI or Tat-GluA2(3Y), restored the enhanced LTD at the LA/BLA-CeA synapse, and alleviated the mechanical allodynia and comorbid aversive and depressive symptoms in neuropathic rats, indicating that the endocytosis of GluA2-containing AMPARs from synapses is probably involved in the LTD at the LA/BLA-CeA synapse and the comorbid aversive and depressive symptoms in neuropathic pain in SNL-operated rats.
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