Case Report: PRRT in a patient with Zollinger-Ellison syndrome. The management of gastrointestinal complications

Zollinger-Ellison Syndrome (ZES) is a rare condition characterized by excessive gastric acid secretion due to gastrin-producing neuroendocrine tumors. Peptide Receptor Radionuclide Therapy (PRRT) with [177Lu]Lutetium Oxodotreotide is an effective treatment for advanced neuroendocrine tumors, including those associated with ZES. However, the gastrointestinal toxicity induced by ZES can complicate the administration of PRRT. We present a case of a patient with metastatic G2 neuroendocrine tumor of the duodenum and ampulla of Vater who experienced severe gastrointestinal complications after the first PRRT cycle due to exacerbated ZES. The implementation of a prophylactic treatment with high-dose proton pump inhibitors before and after the subsequent PRRT cycles allowed for the successful completion of the therapy. This case highlights the importance of considering ZES-related complications in patients undergoing PRRT. Proactive management with high dose acid-suppressing therapy can significantly improve patient tolerance and treatment outcomes. Further research is needed to optimize the management of ZES patients undergoing PRRT

Total Metabolic Tumor Volume Is a Strong Independent Prognostic Factor in Follicular Lymphomas: Results From a Sub-Study of the FOLL12 Trial

Discordant results have been generated regarding the prognostic role of Total Metabolic Tumor Volume (TMTV) in Follicular Lymphoma (FL). The use of prospective data and the adoption of the newly defined standardized SUV4 method for calculating TMTV may generate stronger evidence. We conducted a pre-planned post hoc analysis of the prospective multicenter randomized phase III FOLL12 trial for newly diagnosed high tumor burden FL (grade 1–3a), which mandated baseline staging with PET. Baseline PET/CT scans were reviewed centrally, and TMTV was calculated using the fixed threshold of SUV4. Kaplan–Meier and Cox regression were used for survival analysis. The primary study endpoint was Progression free Survival (PFS). A total of 689 FL patients were available for TMTV definition. Median TMTV was 161 mL (IQR 50 to 388 mL) and the best cutoff value was set at 180 mL. Patients with high TMTV had a significantly lower 5-year PFS compared to those with low TMTV: 59% (95% CI, 53–65%) vs. 74% (95% CI, 69–78%) HR 1.61 (95% CI, 1.24–2.09). Prognostic role of TMTV was independent of study arm, chemotherapy regimen, and FLIPI2. Combined with FLIPI-2, we identified three groups with different 5-yr PFS rates, with the lowest rates (51%) for patients with high TMTV and high FLIPI2. Combined TMTV and FLIPI model was also prognostic to predict the risk of early progression and of death. Applying the SUV4 standard method pre-treatment TMTV is confirmed as a strong and independent predictor of PFS in FL patients. Integrating TMTV with FLIPI-2 improves risk assessment

Glucocorticoid boluses followed by tocilizumab in giant cell arteritis patients: effects on peripheral blood monocytes and lymphocytes

IntroductionGiant Cell Arteritis (GCA) is the most common vasculitis in the elderly, characterized by granulomatous infiltration of immune cells in medium and large arteries. A therapeutic protocol that combines ultra-short glucocorticoids (GC) followed by tocilizumab (TCZ) monotherapy has been proven effective in GCA patients with extracranial large vessel involvement (LV-GCA). However, its effects on circulating immune cells are unknown. The aim of this study was to deepen the understanding of the immunological mechanisms behind this treatment regimen in patients with LV-GCA.Methods15 patients with active LV-GCA were included in this study. Blood samples were collected at baseline, after 3 days of GC treatment, at weeks 24 and 52 during TCZ monotherapy, and at week 78 after the suspension of TCZ. Peripheral blood mononuclear cells were isolated from blood samples. The percentages of lymphocyte and monocyte subsets and the expression of the monocyte markers CCR2, CX3CR1, and HLA-DR were analyzed by flow cytometry. Paired Student’s t-test and mixed-effects analysis were used for the comparison between and among groups, respectively.ResultsGC boluses increased the percentages of B lymphocytes and classical monocytes while decreased those of CD4+ T lymphocytes and intermediate and non-classical monocytes. Moreover, GC boluses increased CCR2 and decreased HLA-DR and CX3CR1 expression by monocytes. TCZ induced a reduction in CCR2 expression versus baseline in classical and intermediate monocytes. Patients with higher reduction in CCR2 expression in intermediate monocytes at 24 weeks and 52 weeks versus baseline showed signs of disease activity at 78 weeks.ConclusionGC boluses modified the relative percentages of lymphocyte and monocyte subsets and modified the expression levels of CCR2, CX3CR1, and HLA-DR in monocytes. These changes may contribute to the anti-inflammatory effects of GCs. TCZ monotherapy had more limited effects. Changes in CCR2 expression by intermediate monocytes might have a prognostic value in LVV

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

IDENTIFICAZIONE DI PARAMETRI PET/CT VOLUMETRICI E DI RADIOMICA PREDITTORI DI RISPOSTA ALLA CHEMIOTERAPIA E DI PROGNOSI IN PAZIENTI CON LINFOMA

La PET/CT con FDG ha un ruolo fondamentale nella gestione dei pazienti affetti da linfoma, dalla stadiazione alla risposta terapeutica. Recentemente, nuovi parametri FDG PET/CT come il volume metabolico totale del tumore (TMTV), un surrogato del carico tumorale e la distanza maggiore tra due lesioni (Dmax), una misura radiomica che riflette la diffusione della malattia, sono stati introdotti come fattori prognostici nel linfoma diffuso a grandi cellule B. Lo scopo di questa tesi era di valutare il ruolo prognostico di TMTV e Dmax ottenuti dalla PET/CT basale in due diversi tipi di linfoma: A) linfoma di Hodgkin (HL) e B) linfoma Follicolare (FL). A) Abbiamo valutato il ruolo prognostico di Dmax in una coorte retrospettiva di pazienti con HL. Abbiamo anche esplorato le basi molecolari alla base di Dmax attraverso un'analisi dell'espressione genica dalle biopsie diagnostiche. Dmax è stato dedotto dalle coordinate tridimensionali del TMTV ed è stato valutato il suo effetto sulla sopravvivenza libera da progressione (PFS). I profili di espressione genica sono stati correlati con Dmax e analizzati utilizzando l'algoritmo CIBERSORTx per eseguire la deconvoluzione. Lo studio è stato condotto su 155 pazienti eleggibili con cHL. Utilizzando il suo valore mediano di 20 cm, Dmax era l'unica variabile associata indipendentemente alla PFS (HR= 2,70, IC 95% 1,1–6,63, pValue= 0,03) sia per tutti i pazienti, sia del sottogruppo con risposta metabolica precoce completa (iPET-). Tra i pazienti con iPET-, Dmax basso era associato a una PFS a 4 anni del 90% (IC 95% 82,0-98,9), significativamente migliore rispetto al gruppo con Dmax alto (PFS a 4 anni 72,4%, IC 95% 61,9-84,6). Dall'analisi dei profili di espressione genica, le differenze di Dmax erano per lo più associate a variazioni nell'espressione di componenti microambientali. B) Abbiamo studiato il valore prognostico di TMTV e Dmax in un'ampia coorte prospettica di pazienti FL naïve al trattamento arruolati nello studio FOLL12 (NCT02063685). Dmax è stato normalizzato in base alla superficie corporea (SDmax). L'endpoint principale dello studio era la sopravvivenza libera da progressione. Dallo studio FOLL12, sono stati inclusi 692 pazienti. Il cutoff ottimale identificato per l'analisi di sopravvivenza era 200 ml per TMTV e 0,4 m-1 per SDmax. Nell'analisi univariata, la PFS a 5 anni era significativamente più bassa per i pazienti con TMTV alto (60% vs 70%; HR=1,87 [IC 95%: 1,41-2,49], p0,4 m-1 (56% vs 69%; HR=1,67 [IC 95%: 1,24-2,25], p=0,001). TMTV e SDmax hanno mantenuto il ruolo prognostico quando aggiustati per braccio di randomizzazione, FLIPI-2 e immunochemioterapia con HR rispettivamente di 1,48 (IC 95%: 1,09-2-01) e 1,42 (IC 95%: 1,05-1,92). Combinando SDmax con TMTV siamo stati in grado di mostrare un ruolo di SDmax nell'identificazione di pazienti a diverso rischio di progressione tra i casi di TMTV elevati: i pazienti con TMTV>200ml e SDmax200 e SDmax>0,4m-1. Nell'analisi multivariata, un TMTV elevato (p=0,043) e un SDmax elevato (p=0,031) hanno mantenuto un valore prognostico indipendente in termini di PFS. In sintesi, TMTV e SDmax alla stadiazione, che riflettono il carico tumorale e la sua diffusione, sono predittori di PFS e potrebbero guidare un approccio terapeutico basato sul rischio nei pazienti con HL e FL.FDG PET/CT has a pivotal role in the management of lymphoma patients, from the staging to the therapy response. Recently, new FDG PET/CT parameters as total metabolic tumor volume (TMTV), a surrogate of tumor burden and the largest distance between two lesions (Dmax), a radiomic feature reflecting the spread of the disease, have been introduced as prognostic factors in diffuse large B cell lymphoma. The aim of this thesis was to evaluate the prognostic role of TMTV and Dmax extracted from baseline PET/CT in two different types of lymphoma: A) Hodgkin Lymphoma (HL) and B) Follicular Lymphoma (FL). A) We evaluated the prognostic role of Dmax in a retrospective cohort of HL patients. We also explored the molecular bases underlying Dmax through a gene expression analysis of diagnostic biopsies. Dmax was deduced from the three-dimensional coordinates of the TMTV and its effect on progression free survival (PFS) was evaluated. Gene expression profiles were correlated with Dmax and analyzed using CIBERSORTx algorithm to perform deconvolution. The study was conducted on 155 eligible cHL patients. Using its median value of 20 cm, Dmax was the only variable independently associated with PFS (HR= 2.70, 95% CI 1.1–6.63, pValue= 0.03) in multivariate analysis of PFS for all patients and for those with early complete metabolic response (iPET-). Among patients with iPET- low Dmax was associated with a 4-year PFS of 90 % (95% CI 82.0-98.9) significantly better compared to high Dmax (4-year PFS 72.4%, 95% CI 61.9-84.6). From the analysis of gene expression profiles differences in Dmax were mostly associated with variations in the expression of microenvironmental components. B) We studied the prognostic value of TMTV and Dmax in a large prospective cohort of treatment-naïve FL patients from the FOLL12 trial (NCT02063685). Dmax was normalized according to body surface area (SDmax). Univariate and multivariate analyses were performed using Cox proportional hazard model. Main study endpoint was Progression Free Survival. From the FOLL12 trial, 692 patients were included. The optimal cutoff identified for the survival analysis were 200 ml for TMTV and 0.4 m-1 for SDmax. In univariate analysis, 5-year PFS was significantly lower for patients with high TMTV (60% vs 70%; HR=1.87 [95%CI: 1.41-2.49], p0.4 m-1 ( 56% vs 69%; HR=1.67 [95%CI: 1.24-2.25], p=0.001). TMTV and SDmax remained significant prognosticators when adjusted by randomized arm, FLIPI-2, and immunochemotherapy with HR respectively of 1.48 (95%CI: 1.09-2-01) and 1.42 (95%CI: 1.05-1.92). Combining SDmax with TMTV we were able to show a role of SDmax in the identification of patients at different risk of progression among high TMTV cases: patients with TMTV>200ml and SDmax200 and SDmax>0.4m-1. In multivariate analysis, high TMTV (p=0.043) and high SDmax (p=0.031) retained independent prognostic value for predicting PFS. In summary, pre-treatment TMTV and SDmax, reflecting tumor burden and its spread, are predictors of PFS and could improve a risk guided therapeutic strategy in patients with HL and FL

18F-choline PET/CT incidental thyroid uptake in patients studied for prostate cancer

Thyroid incidental uptake is defined as a thyroid uptake incidentally detected by imaging examinations performed for non-thyroid disease. The aim of this study was to establish the prevalence and the pathological nature of focal thyroid incidental uptake (FTIU) among patients studied with 18F-choline-PET/CT