Gilteritinib and the risk of intracranial hemorrhage: a case series of a possible, under-reported side effect

Gilteritinib is currently approved for patients with relapsed/refractory AML with FLT3 mutations, based on the positive results of the pivotal ADMIRAL study. In ADMIRAL trial, no increased risk of bleeding was reported, but in the previous dose finding study, a single event of intracranial hemorrhage (ICH) was registered after exposure to subtherapeutic doses of gilteritinib. Here, we report the first case series on five ICHs diagnosed in patients with FLT3-mutated AML, occurred within the first month of exposure to gilteritinib. Our cohort included 24 patients treated in three Italian centers. Most of these ICH cases were non-severe and self-limiting, while one was fatal. This link with ICHs remains in any case uncertain for the presence of active AML. We further reported that an analysis of the post-marketing surveillance data (EudraVigilance) retrieved other 11 cases of ICHs present in the database after gilteritinib treatment. A causality assessment was performed according to the Dx3 method to evaluate the possibility that ICHs might be an actual side effect of gilteritinib. In conclusion, further research is needed to elucidate the potential role of gilteritinib in the pathogenesis of ICHs

Radioembolisation using yttrium 90 (Y-90) in patients affected by unresectable hepatic metastases.

This study was done to evaluate the effectiveness of radioembolisation of liver metastases with yttrium 90 (Y-90) in patients with no response to chemotherapy. From February 2005 to January 2008, we treated 110 patients affected by liver metastatic disease from colorectal, breast, gastric, pancreatic, pulmonary, oesophageal and pharyngeal cancers and from cholangiocarcinoma and melanoma. We excluded patients with bilirubin level >1.8 mg/dl and pulmonary shunt >20% but not patients with minor extrahepatic metastases. We obtained a complete /partial response in 45 patients, stable disease in 42 patients and progressive disease in 23 patients. In 90 cases, we obtained a decrease in specific tumour marker level. The technical success rate was 96%, and technical effectiveness estimated at 3 months after treatment was 83.6%. Side effects were grade 4 hepatic failure in one case, grade 2 gastritis in six cases and grade 2 cholecystitis in two cases. The median survival and progression-free survival calculated by Kaplan-Meier analysis were 323 days and 245 days, respectively. According to our 3-year experience, Y-90 radioembolisation (SIR-spheres) is a feasible and safe method to treat liver metastases with an acceptable level of complications and a good response rate

PET/CT with ¹⁸F-choline or ¹⁸F-FDG in Hepatocellular Carcinoma Submitted to ⁹⁰Y-TARE: A Real-World Study

Our aim was to assess the role of positron emission computed tomography (PET/CT) with 18F-choline (18F-FCH) or 18F-fluorodeoxyglucose (18F-FDG) in hepatocellular carcinoma (HCC) submitted to 90Y-radioembolization (90Y-TARE). We retrospectively analyzed clinical records of 21 HCC patients submitted to PET/CT with 18F-fluorocholine (18F-FCH) or 18F-fluodeoxyglucose (18F-FDG) before and 8 weeks after 90Y-TARE. On pre-treatment PET/CT, 13 subjects (61.9%) were 18F-FCH-positive, while 8 (38.1%) resulted 18F-FCH-negative and 18F-FDG-positive. At 8-weeks post 90Y-TARE PET/CT, 13 subjects showed partial metabolic response and 8 resulted non-responders, with a higher response rate among 18F-FCH-positive with respect to 18F-FDG-positive patients (i.e., 76.9% vs. 37.5%, p = 0.46). Post-treatment PET/CT influenced patients’ clinical management in 10 cases (47.6%); in 8 subjects it provided indication for a second 90Y-TARE targeting metabolically active HCC remnant, while in 2 patients it led to a PET-guided radiotherapy on metastatic nodes. By Kaplan–Meier analysis, patients’ age (≤69 y) and post 90Y-TARE PET/CT’s impact on clinical management significantly correlated with overall survival (OS). In Cox multivariate analysis, PET/CT’s impact on clinical management remained the only predictor of patients’ OS (p 18F-FCH or 18F-FDG influenced clinical management and affected the final outcome for HCC patients treated with 90Y-TARE

Selective Internal Radiation Therapy with SIR-Spheres for the Treatment of Unresectable Colorectal Hepatic Metastases

The purpose of this study was to evaluate the effectiveness of colorectal cancer (CRC) liver metastasis radioembolization with yttrium-90 (Y90), assessing toxicity and survival rates in patients with no response to chemotherapy through our 3-year experience. From February 2005 to January 2008, we treated 41 patients affected by CRC from a cohort of selective internal radiation therapy patients treated at our institution. All patients examined showed disease progression and arrived for our observation with an abdominal CT, a body PET, and a hepatic angiography followed by gastroduodenal artery coiling previously performed by us. We excluded patients with a bilirubin level > 1.8 mg/dl and pulmonary shunt > 20% but not patients with minor extrahepatic metastases. On treatment day, under fluoroscopic guidance, we implanted a dose of Y90 microspheres calculated on the basis of liver tumoral involvement and the body surface area formula. All patients were discharged the day after treatment. We obtained, according to Response Evaluation Criteria on Solid Tumors, a complete response in 2 patients, a partial response in 17 patients, stable disease in 14 patients, and progressive disease in 8 patients. In all cases, we obtained a carcinoembryonic antigen level decrease, especially in the week 8 evaluation. Technical success rate was 98% and technical effectiveness estimated at 3 months after treatment was 80.5%. Side effects graded by Common Terminology Criteria on Adverse Events were represented by one grade 4 hepatic failure, two grade 2 gastritis, and one grade 2 cholecystitis. The median survival and the progression-free survival calculated by Kaplan-Meier analysis were 354 and 279 days, respectively. In conclusion, according to our 3-year experience, Y90 SIR-Spheres radioembolization is a feasible and safe method to treat CRC liver metastases, with an acceptable level of complications and a good response rate

Un caso di epatocarcinoma trattato con chemio-embolizzazione arteriosa transcatetere con sopravvivenza di 11 anni

Il carcinoma epatocellulare (HCC) rappresenta quasi il 90% di tutti i tumori epatici, la quarta neoplasia più comune nel mondo e la terza causa di morte. L’aumentato rischio di HCC è stato associato all’infezione epatica cronica da HBV e HCV. Il trapianto di fegato (LT) rappresenta il gold standard nel trattamento del “piccolo” HCC in paziente cirrotico, in classe A di Child-Pugh. Il principale ostacolo al trapianto è la scarsità dei donatori. La resezione epatica (HR) è indicata nei pazienti con nodulo unico in classe A di Child-Pugh. Negli ultimi 20 anni le procedure ablative percutanee e transcatetere hanno rivoluzionato il trattamento dei tumori epatici primitivi e metastatici non resecabili. Gli Autori presentano il caso di un paziente di 61 anni cui viene diagnosticato, durante il follow-up per neoplasia vescicale, un HCC su fegato cirrotico (classe A di Child-Pugh). Per l’età e il pregresso carcinoma vescicale, il paziente non era eleggibile per LT e d’altra parte rifiutava l’intervento di HR, per cui gli veniva proposta la chemioembolizzazione associata a termoablazione e tamoxifene. Le procedure sono state ben tollerate. Il decorso è stato caratterizzato da una fase di progressione locale della malattia, cui ha fatto seguito una regressione con diminuzione del numero e delle dimensioni delle lesioni epatiche. Nonostante l’HCC sia una neoplasia a prognosi molto sfavorevole, nel caso riportato il paziente è in buone condizioni generali a 11 anni di distanza dalla diagnosi, nonostante la persistenza locale di malattia

Emoperitoneo massivo da rottura di epatocarcinoma multifocale del lobo destro. Case report

Il trauma epatico, importante causa di morte nei pazienti di età inferiore ai 40 anni, rappresenta ancora un problema irrisolto. Raramente isolato, è di più frequente riscontro nei politraumatizzati dove è causa possibile di emoperitoneo massivo. Gli Autori riportano il caso di una paziente con massivo sanguinamento intraperitoneale da neoformazione misconosciuta del lobo destro del fegato. La TC spirale mostrava una neoformazione con segni di stravaso perilesionale del mezzo di contrasto nell’VIII segmento epatico. L’instabilità emodinamica indicava una laparotomia d’urgenza con accesso sottocostale destro. All’apertura della cavità addominale si dimostrava massivo emoperitoneo (3000 ml di sangue) per una lesione del VI segmento epatico. Coesisteva neoformazione estesa dal VI all’VIII segmento epatico. Si tentava il controllo locale dell’emostasi con adesivo tissutale in gel (Floseal) con scarsi risultati. Si procedeva quindi al confezionamento di un packing mediante pezze laparotomiche, cui seguiva una chiusura temporanea dell’addome. La necessaria embolizzazione dei rami dell’arteria epatica destra completava l’emostasi e nel corso dell’esame angiografico si dimostrava un epatocarcinoma multifocale insorto su base malformativa angiomatosa in paziente affetta da cirrosi HCV-correlata. A 72 ore di distanza si procedeva al depacking. In conclusione: a) l’angio-TC spirale è la procedura diagnostica elettiva; b) la gestione, conservativa o chirurgica, dipende dallo stato emodinamico; c) le procedure di angio-embolizzazione arteriosa contribuiscono all’azione emostatica; d) la nostra preferenza va al packing periepatico con interposizione di “steril drape” da rimuovere entro le 72 ore

Enterorragia massiva da diverticolosi sigmoidea in corso di terapia antiaggregante. Caso clinico

Di frequente riscontro nei Paesi Occidentali, la malattia diverticolare nel 5% dei casi può essere causa di grave sanguinamento, instabilità emodinamica e rischio di vita per il paziente. Gli Autori riportano il caso di una paziente di 74 anni giunta alla loro osservazione con segni e sintomi da grave enterorragia. La paziente era in trattamento antiaggregante con acido acetilsalicilico clopidogrel per la prevenzione della restenosi dopo posizionamento di stent coronarici automedicati per sindrome coronarica acuta. Assumeva contemporaneamente rosuvastatina per il controllo della ipercolesterolemia primaria. La gravità del sanguinamento ha richiesto la stabilizzazione emodinamica mediante infusione di colloidi e sangue intero. Le emorragie iterative, in numero di sette, hanno consigliato l’esecuzione di un’arteriografia selettiva che ha dimostrato un sanguinamento nel territorio di distribuzione delle arterie sigmoidee e dell’arteria rettale superiore. Nel corso della metodica interventistica si è proceduto ad embolizzazione del tronco comune dell’arteria mesenterica inferiore con spirale metallica tipo BALT, seguita da arresto dell’emorragia. La rettosigmoidocolonscopia eseguita a distanza di 15 giorni dalla procedura embolizzante ha dimostrato la presenza di malattia diverticolare del sigma. Sicuramente la terapia con acido acetilsalicilico e clopidogrel ha contribuito in maniera determinante alla gravità dell’episodio emorragico che ha messo a rischio di vita la paziente. Alla luce di recenti evidenze sperimentali e cliniche è inoltre ipotizzabile un ruolo delle statine nel favorireil sanguinamento mediante un effetto ipoaggregante piastrinico

Selective Internal Radiation Therapy with SIR-Spheres for the Treatment of Unresectable Colorectal Hepatic Metastases

The purpose of this study was to evaluate the effectiveness of colorectal cancer (CRC) liver metastasis radioembolization with yttrium-90 (Y90), assessing toxicity and survival rates in patients with no response to chemotherapy through our 3-year experience. From February 2005 to January 2008, we treated 41 patients affected by CRC from a cohort of selective internal radiation therapy patients treated at our institution. All patients examined showed disease progression and arrived for our observation with an abdominal CT, a body PET, and a hepatic angiography followed by gastroduodenal artery coiling previously performed by us. We excluded patients with a bilirubin level > 1.8 mg/dl and pulmonary shunt > 20% but not patients with minor extrahepatic metastases. On treatment day, under fluoroscopic guidance, we implanted a dose of Y90 microspheres calculated on the basis of liver tumoral involvement and the body surface area formula. All patients were discharged the day after treatment. We obtained, according to Response Evaluation Criteria on Solid Tumors, a complete response in 2 patients, a partial response in 17 patients, stable disease in 14 patients, and progressive disease in 8 patients. In all cases, we obtained a carcinoembryonic antigen level decrease, especially in the week 8 evaluation. Technical success rate was 98% and technical effectiveness estimated at 3 months after treatment was 80.5%. Side effects graded by Common Terminology Criteria on Adverse Events were represented by one grade 4 hepatic failure, two grade 2 gastritis, and one grade 2 cholecystitis. The median survival and the progression-free survival calculated by Kaplan-Meier analysis were 354 and 279 days, respectively. In conclusion, according to our 3-year experience, Y90 SIR-Spheres radioembolization is a feasible and safe method to treat CRC liver metastases, with an acceptable level of complications and a good response rate