Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

BACKGROUND: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. METHODS: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. RESULTS: SVR24 rates were 46.1% (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1, 2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced 651 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with 651 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not 655. CONCLUSIONS: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginterferon alfa-2a/ribavirin

Clinical Perspectives for 18F-FDG PET Imaging in Pediatric Oncology: &Mu;etabolic Tumor Volume and Radiomics

Pediatric cancer, although rare, requires the most optimized treatment approach to obtain high survival rates and minimize serious long-term side effects in early adulthood. 18F-FDG PET/CT is most helpful and widely used in staging, recurrence detection, and response assessment in pediatric oncology. The well-known 18F-FDG PET metabolic indices of metabolic tumor volume (MTV) and tumor lesion glycolysis (TLG) have already revealed an independent significant prognostic value for survival in oncologic patients, although the corresponding cut-off values remain study-dependent and not validated for use in clinical practice. Advanced tumor &ldquo;radiomic&rdquo; analysis sheds new light into these indices. Numerous patterns of texture 18F-FDG uptake features can be extracted from segmented PET tumor images due to new powerful computational systems supporting complex &ldquo;deep learning&rdquo; algorithms. This high number of &ldquo;quantitative&rdquo; tumor imaging data, although not decrypted in their majority and once standardized for the different imaging systems and segmentation methods, could be used for the development of new &ldquo;clinical&rdquo; models for specific cancer types and, more interestingly, for specific age groups. In addition, data from novel techniques of tumor genome analysis could reveal new genes as biomarkers for prognosis and/or targeted therapies in childhood malignancies. Therefore, this ever-growing information of &ldquo;radiogenomics&rdquo;, in which the underlying tumor &ldquo;genetic profile&rdquo; could be expressed in the tumor-imaging signature of &ldquo;radiomics&rdquo;, possibly represents the next model for precision medicine in pediatric cancer management. This paper reviews 18F-FDG PET image segmentation methods as applied to pediatric sarcomas and lymphomas and summarizes reported findings on the values of metabolic and radiomic features in the assessment of these pediatric tumors

Έλεγχος με ποζιτρονική τομογραφία του μεταβολισμού του εγκεφαλικού παρεγχύματος σε ασθενείς με διατατική μυοκαρδιοπάθεια

Σκοπός: Η κατάθλιψη είναι συχνή συννοσηρότητα στην καρδιακή ανεπάρκεια και γνωστός ανεξάρτητος αρνητικός προγνωστικός παράγοντας. Η έγκαιρη και ακριβής διάγνωσή της και η κατάλληλη αντιμετώπισή της είναι σημαντική. Σκοπός της μελέτης ήταν η ανάλυση του εγκεφαλικού μεταβολισμού σε ασθενείς με χρόνια καρδιακή ανεπάρκεια, με χρήση 18F-FDG PET/CT και η συσχέτισή της με την συνύπαρξη καταθλιπτικής συνδρομής. Μέθοδος: Στην μελέτη συμπεριλήφθηκαν 29 νοσηλευόμενοι ασθενείς, ηλικίας 55.5±12.0 ετών, με συμπτωματική συστολική χρόνια καρδιακή ανεπάρκεια (κλάσμα εξώθησης &lt;40%) και λειτουργικό στάδιο κατά NYHA II έως ΙV. Κατά την έξοδό τους, όλοι οι ασθενείς είχαν υπερηχογραφικό και αιματολογικό έλεγχο και απάντησαν σε ψυχομετρικά ερωτηματολόγια και τεστ. Μετά την έξοδό τους, όλοι οι ασθενείς υποβλήθηκαν σε 18F-FDG PET/CT εγκεφάλου. Ημιαυτόματη κατάτμηση και ανάλυση των εικόνων πραγματοποιήθηκε τόσο στους ασθενείς με καρδιακή ανεπάρκεια όσο και σε 30 αντίστοιχους μάρτυρες. Ο μεταβολικός δείκτης «SUVmean» (mean standardized uptake value) υπολογίσθηκε για όλο τον εγκέφαλο («whole-brain SUVmean») και για τρεις περιοχές («regional-brain SUVmean»), γνωστές για την συμμετοχή τους στην εμφάνιση της κατάθλιψης (προμετωπιαίος φλοιός, αμυγδαλή, ιππόκαμπος). Ως «std-SUVmean» (standardized SUVmean) ορίσθηκε το πηλίκο «regional-brain SUVmean» με «whole-brain SUVmean». Αποτελέσματα: Ο μέσος όρος των μεταβολικών παραμέτρων «whole-brain SUVmean» (3.90±1.49 vs 5.10±1.35, p=0.001) και «regional-brain SUVmean» (4.57±2.31 vs 9.96±3.58, p&lt;0.001) ήταν μικρότερος στους ασθενείς με καρδιακή ανεπάρκεια σε σχέση με τους μάρτυρες. Ο μεταβολικός δείκτης «whole-brain SUVmean» παρουσίασε στατιστικά σημαντική συσχέτιση με την ηλικία των ασθενών (r=-0.39, p=0.031), το λειτουργικό στάδιο κατά ΝΥΗΑ (p=0.027), τα επίπεδα κρεατινίνης (r=-0.49, p=0.005), την συνύπαρξη σακχαρώδη διαβήτη (p=0.001) και την συνύπαρξη κατάθλιψης (r=-0.36, p=0.049). Ο μεταβολικός δείκτης «regional-brain SUVmean» παρουσίασε στατιστικά σημαντική συσχέτιση με το δείκτη «whole-brain SUVmean» (r=0.53, p=0.002) και την κατάθλιψη (r=0.46, p=0.011). Η παράμετρος «std-SUVmean» ήταν το πιο σημαντικό εργαλείο, στη διαφοροδιάγνωση μεταξύ «πραγματικής» (≤0.93) ή «επιφαινόμενης» (&gt;0.93) καταθλιπτικής συνδρομής. Συμπεράσματα: Οι ασθενείς με την σοβαρότερη καρδιακή ανεπάρκεια παρουσίασαν εγκεφαλικό υπομεταβολισμό, τόσο όσον αφορά τον εγκεφαλικό φλοιό στο σύνολό του («whole-brain»), όσο και τις επιλεγμένες περιοχές («regional-brain»). Οι ασθενείς με συννοσηρότητα κατάθλιψης (Beck Depression Inventory &gt;13) είχαν διαφορετικά προφίλ εγκεφαλικού μεταβολισμού, τα οποία μπορούν να συνηγορήσουν υπέρ διαφορετικής παθογένεσης της καταθλιπτικής συνδρομής. Πιο συγκεκριμένα, η εγκατάσταση «whole-brain» υπομεταβολισμού συνηγορεί υπέρ «επιφαινόμενης» ενώ η απουσία «whole-brain» υπομεταβολισμού υπέρ «πραγματικής» κατάθλιψης. Όταν όμως, το προφίλ του «whole-brain» υπομεταβολισμού περιλαμβάνει σημαντικό σχετικό «regional-brain» υπομεταβολισμό («std-SUVmean» ≤0.93), η περίπτωση «πραγματικής» καταθλιπτικής συνδρομής είναι η πιο πιθανή διάγνωση.Aims: Depression is an important issue in heart failure (HF). The study investigated whole-brain and regional-brain glucose metabolism in HF patients and its association with depression comorbidity. Methods and results: Twenty-nine hospitalized patients with symptomatic systolic HF disease (LVEF&lt;40%), NYHA class II-IV and mean age of 55.5±12.0 years, had psychometric questionnaires before discharge and an 18F-FDG PET/CT brain scan after discharge. Semi-automated image analysis was performed on all cases and 30 matched controls. The metabolic parameter SUVmean was calculated for the whole-brain and three brain regions, implicated in depression pathogenesis. A standardized SUVmean was also estimated by dividing regional-brain SUVmean with the whole-brain SUVmean. Cases had lower average whole-brain SUVmean (3.90±1.49 vs 5.10±1.35, p=0.001) and average regional-brain SUVmean (4.57±2.31 vs 9.96±3.58, p&lt;0.001) compared to controls. Whole-brain SUVmean had a statistically significant correlation to patient age, NYHA class, diabetes comorbidity, creatinine levels, depression, and cognitive impairment. Regional-brain SUVmean was correlated to whole-brain SUVmean and depression. The standardized SUVmean, in particular, was found to be a robust index that could differentiate HF patients with “epiphenomenal” (&gt;0.93) or “real” (≤0.93) depression. Conclusion: HF patients with more severe disease showed whole-brain and regional-brain hypometabolism in 18F-FDG PET/CT. Depressed HF patients (Beck Depression Inventory score &gt;13) exhibited different metabolic patterns that could be used to differentiate between “epiphenomenal” and “real” depression. Namely, presence of whole-brain hypometabolism suggested “epiphenomenal” depression while absence suggested “real” depression. Presence of significant relative, regional hypometabolism enhanced the likelihood of “real” depression diagnosis

Brain glucose metabolism in heart failure patients by 18F-FDG PET/CT

Aims: Depression is an important issue in heart failure (HF). The study investigated whole-brain and regional-brain glucose metabolism in HF patients and its association with depression comorbidity. Methods and results: Twenty-nine hospitalized patients with symptomatic systolic HF disease (LVEF0.93) or “real”(≤0.93) depression. Conclusion: HF patients with more severe disease showed whole-brain and regional-brain hypometabolism in 18F-FDGPET/CT. Depressed HF patients (Beck Depression Inventory score >13) exhibited different metabolic patterns that could be used to differentiate between “epiphenomenal” and “real” depression. Namely, presence of whole-brain hypometabolism suggested “epiphenomenal” depression while absence suggested “real”depression. Presence of significant relative, regional hypometabolism enhanced the likelihood of “real” depression diagnosis.Σκοπός: Η κατάθλιψη είναι συχνή συννοσηρότητα στην καρδιακή ανεπάρκεια και γνωστός ανεξάρτητος αρνητικός προγνωστικός παράγοντας. Η έγκαιρη και ακριβής διάγνωσή της και η κατάλληλη αντιμετώπισή της είναι σημαντική. Σκοπός της μελέτης ήταν η ανάλυση του εγκεφαλικού μεταβολισμού σε ασθενείς με χρόνια καρδιακή ανεπάρκεια, με χρήση 18F-FDG PET/CT και η συσχέτισή της με την συνύπαρξη καταθλιπτικής συνδρομής. Μέθοδος: Στην μελέτη συμπεριλήφθηκαν 29 νοσηλευόμενοι ασθενείς, ηλικίας 55.5±12.0 ετών, με συμπτωματική συστολική χρόνια καρδιακή ανεπάρκεια (κλάσμα εξώθησης 0.93) καταθλιπτικής συνδρομής. Συμπεράσματα: Οι ασθενείς με την σοβαρότερη καρδιακή ανεπάρκεια παρουσίασαν εγκεφαλικό υπομεταβολισμό, τόσο όσον αφορά τον εγκεφαλικό φλοιό στο σύνολό του («whole brain»), όσο και τις επιλεγμένες περιοχές («regional-brain»). Οι ασθενείς με συννοσηρότητα κατάθλιψης (Beck Depression Inventory >13) είχαν διαφορετικά προφίλ εγκεφαλικού μεταβολισμού, τα οποία μπορούν να συνηγορήσουν υπέρ διαφορετικής παθογένεσης της καταθλιπτικής συνδρομής. Πιο συγκεκριμένα, η εγκατάσταση «whole-brain» υπομεταβολισμού συνηγορεί υπέρ «επιφαινόμενης» ενώ η απουσία «whole brain» υπομεταβολισμού υπέρ «πραγματικής» κατάθλιψης. Όταν όμως, το προφίλ του «whole-brain» υπομεταβολισμού περιλαμβάνει σημαντικό σχετικό «regional-brain» υπομεταβολισμό («std-SUVmean» ≤0.93), η περίπτωση «πραγματικής» καταθλιπτικής συνδρομής είναι η πιο πιθανή διάγνωση

Tumor Size Measurements for Predicting Hodgkin&rsquo;s and Non-Hodgkin&rsquo;s Lymphoma Response to Treatment

The purpose of this study was to investigate the value of tumor size measurements as prognostic indicators of treatment outcome of Hodgkin&rsquo;s and Non-Hodgkin&rsquo;s lymphomas. 18F-FDG PET/CT exams before and after treatment were analyzed and metabolic and anatomic parameters&mdash;tumor maximum diameter, tumor maximum area, tumor volume, and maximum standardized uptake value (SUVmax)&mdash;were determined manually by an expert and automatically by a computer algorithm on PET and CT images. Results showed that the computer algorithm measurements did not correlate well with the expert&rsquo;s standard maximum tumor diameter measurements but yielded better three dimensional metrics that could have clinical value. SUVmax was the strongest prognostic indicator of the clinical outcome after treatment, followed by the automated metabolic tumor volume measurements and the expert&rsquo;s metabolic maximum diameter measurements. Anatomic tumor measurements had poor prognostic value. Metabolic volume measurements, although promising, did not significantly surpass current standard of practice, but automated measurements offered a significant advantage in terms of time and effort and minimized biases and variances in the PET measurements. Overall, considering the limited value of tumor size in predicting response to treatment, a paradigm shift seems necessary in order to identify robust prognostic markers in PET/CT; radiomics, namely combinations of anatomy, metabolism, and imaging, may be an option

Tumor Size Measurements for Predicting Hodgkin’s and Non-Hodgkin’s Lymphoma Response to Treatment

The purpose of this study was to investigate the value of tumor size measurements as prognostic indicators of treatment outcome of Hodgkin’s and Non-Hodgkin’s lymphomas. 18F-FDG PET/CT exams before and after treatment were analyzed and metabolic and anatomic parameters—tumor maximum diameter, tumor maximum area, tumor volume, and maximum standardized uptake value (SUVmax)—were determined manually by an expert and automatically by a computer algorithm on PET and CT images. Results showed that the computer algorithm measurements did not correlate well with the expert’s standard maximum tumor diameter measurements but yielded better three dimensional metrics that could have clinical value. SUVmax was the strongest prognostic indicator of the clinical outcome after treatment, followed by the automated metabolic tumor volume measurements and the expert’s metabolic maximum diameter measurements. Anatomic tumor measurements had poor prognostic value. Metabolic volume measurements, although promising, did not significantly surpass current standard of practice, but automated measurements offered a significant advantage in terms of time and effort and minimized biases and variances in the PET measurements. Overall, considering the limited value of tumor size in predicting response to treatment, a paradigm shift seems necessary in order to identify robust prognostic markers in PET/CT; radiomics, namely combinations of anatomy, metabolism, and imaging, may be an option

Lymphatic Path of the Inguinal Lymph Node Metastases in Anorectal Cancer The Springbok Pattern

Sentinel lymph node biopsy has been established as a feasible and effective method for defining the inguinal node status in patients with anal adenocarcinoma exceeding the dentate line. We present the axial lymphoscintigraphic image that depicts thoroughly the injection site around the anus, the lymphatic path, and the inguinal sentinel lymph nodes, bilaterally. The distinct springbok pattern was named after the unique horn shape of the African gazelle. This image puts on the map the anoinguinal lymphatic path and highlights the need for complete inguinal lymph node and related lymphatic path dissection in metastatic anal cancer

Impact of safety-related dose reductions or discontinuations on sustained virologic response in HCV-infected patients: Results from the GUARD-C Cohort

Background: Despite the introduction of direct-acting antiviral agents for chronic hepatitis C virus (HCV) infection, peginterferon alfa/ribavirin remains relevant in many resource-constrained settings. The non-randomized GUARD-C cohort investigated baseline predictors of safety-related dose reductions or discontinuations (sr-RD) and their impact on sustained virologic response (SVR) in patients receiving peginterferon alfa/ribavirin in routine practice. Methods: A total of 3181 HCV-mono-infected treatment-naive patients were assigned to 24 or 48 weeks of peginterferon alfa/ribavirin by their physician. Patients were categorized by time-to-first sr-RD (Week 4/12). Detailed analyses of the impact of sr-RD on SVR24 (HCV RNA <50 IU/mL) were conducted in 951 Caucasian, noncirrhotic genotype (G)1 patients assigned to peginterferon alfa-2a/ribavirin for 48 weeks. The probability of SVR24 was identified by a baseline scoring system (range: 0-9 points) on which scores of 5 to 9 and <5 represent high and low probability of SVR24, respectively. Results: SVR24 rates were 46.1 % (754/1634), 77.1% (279/362), 68.0% (514/756), and 51.3% (203/396), respectively, in G1,2, 3, and 4 patients. Overall, 16.9% and 21.8% patients experienced ≥1 sr-RD for peginterferon alfa and ribavirin, respectively. Among Caucasian noncirrhotic G1 patients: female sex, lower body mass index, pre-existing cardiovascular/pulmonary disease, and low hematological indices were prognostic factors of sr-RD; SVR24 was lower in patients with ≥1 vs. no sr-RD by Week 4 (37.9% vs. 54.4%; P = 0.0046) and Week 12 (41.7% vs. 55.3%; P = 0.0016); sr-RD by Week 4/12 significantly reduced SVR24 in patients with scores <5 but not ≥5. Conclusions: In conclusion, sr-RD to peginterferon alfa-2a/ribavirin significantly impacts on SVR24 rates in treatment-naive G1 noncirrhotic Caucasian patients. Baseline characteristics can help select patients with a high probability of SVR24 and a low probability of sr-RD with peginter-feron alfa-2a/ribavirin