This column alerts SIR members to abstracts that may have an impact on their practice and how they converse with referring clinicians. If you would like to suggest abstracts you feel should be included, email us at gandhi@baptisthealth.net or suvranu.ganguli@bmc.org.
Radioembolization with chemotherapy for colorectal liver metastases: A randomized, open-label, international, multicenter, phase III trial
J Clin Oncol 2021 Sep 20;JCO2101839. doi: 10.1200/JCO.21.01839.
Mulcahy M, Mahvash A, Pracht M, Montazeri A, Bandula S, Martin RCG, Herrmann K, Brown E, Zuckerman D, Wilson G, Kim T, Weaver A, Ross P, Harris WP, Graham J, Mills J, Esteban AY, Johnson MS, Sofocleous CT, Padia SA, Lewandowski RJ, Garin E, Sinclair P, Salem R, EPOCH investigators
Purpose: To study the impact of transarterial yttrium-90 radioembolization (TARE) in combination with second-line systemic chemotherapy for colorectal liver metastases (CLM).
Methods: In this international, multicenter, open-label phase III trial, patients with CLM who progressed on oxaliplatin- or irinotecan-based first-line therapy were randomly assigned 1:1 to receive second-line chemotherapy with or without TARE. The two primary end points were progression-free survival (PFS) and hepatic PFS (hPFS), assessed by blinded independent central review. Random assignment was performed using a web- or voice-based system stratified by unilobar or bilobar disease, oxaliplatin- or irinotecan-based first-line chemotherapy, and KRAS mutation status.
Results: Four hundred twenty-eight patients from 95 centers in North America, Europe and Asia were randomly assigned to chemotherapy with or without TARE; this represents the intention-to-treat population and included 215 patients in the TARE plus chemotherapy group and 213 patients in the chemotherapy alone group. The hazard ratio (HR) for PFS was 0.69 (95% CI, 0.54 to 0.88; 1-sided P = .0013), with a median PFS of 8.0 (95% CI, 7.2 to 9.2) and 7.2 (95% CI, 5.7 to 7.6) months, respectively. The HR for hPFS was 0.59 (95% CI, 0.46 to 0.77; 1-sided P < .0001), with a median hPFS of 9.1 (95% CI, 7.8 to 9.7) and 7.2 (95% CI, 5.7 to 7.6) months, respectively. Objective response rates were 34.0% (95% CI, 28.0 to 40.5) and 21.1% (95% CI, 16.2 to 27.1; 1-sided P = .0019) for the TARE and chemotherapy groups, respectively. Median overall survival was 14.0 (95% CI, 11.8 to 15.5) and 14.4 months (95% CI, 12.8 to 16.4; 1-sided P = .7229) with a HR of 1.07 (95% CI, 0.86 to 1.32) for TARE and chemotherapy groups, respectively. Grade 3 adverse events were reported more frequently with TARE (68.4% vs. 49.3%). Both groups received full chemotherapy dose intensity.
Conclusion: The addition of TARE to systemic therapy for second-line CLM led to longer PFS and hPFS. Further subset analyses are needed to better define the ideal patient population that would benefit from TARE.
Randomized trial comparing standard versus ultrasound-assisted thrombolysis for submassive pulmonary embolism: The SUNSET sPE trial
JACC Cardiovasc Interv. 2021 Jun 28;14(12):1364-1373. doi: 10.1016/j.jcin.2021.04.049.
Avgerinos ED, Jaber W, Lacomis J, Markel K, McDaniel M, Rivera-Lebron BN, Ross CR, Sechrist J, Toma C, Chaer R, SUNSET sPE collaborators
Objectives: The aim of this trial was to determine whether ultrasound-assisted thrombolysis (USAT) is superior to standard catheter-directed thrombolysis (SCDT) in pulmonary arterial thrombus reduction for patients with submassive pulmonary embolism (sPE).
Background: Catheter-directed therapy has been increasingly used in sPE and massive pulmonary embolism as a decompensation prevention and potentially lifesaving procedure. It is unproved whether USAT is superior to SCDT using traditional multiple-side-hole catheters in the treatment of patients with pulmonary embolism.
Methods: Adults with sPE were enrolled. Participants were randomized 1:1 to USAT or SCDT. The primary outcome was 48-hour clearance of pulmonary thrombus assessed by pre- and postprocedural computed tomographic angiography using a refined Miller score. Secondary outcomes included improvement in right ventricular-to-left ventricular ratio, intensive care unit and hospital stay, bleeding, and adverse events up to 90 days.
Results: Eighty-one patients with acute sPE were randomized and were available for analysis. The mean total dose of alteplase for USAT was 19 ± 7 mg and for SCDT was 18 ± 7 mg (P = 0.53), infused over 14 ± 6 and 14 ± 5 hours, respectively (P = 0.99). In the USAT group, the mean raw pulmonary arterial thrombus score was reduced from 31 ± 4 at baseline to 22 ± 7 (P < 0.001). In the SCDT group, the score was reduced from 33 ± 4 to 23 ± 7 (P < 0.001). There was no significant difference in mean thrombus score reduction between the 2 groups (P = 0.76). The mean reduction in right ventricular/left ventricular ratio from baseline (1.54 ± 0.30 for USAT, 1.69 ± 0.44 for SCDT) to 48 hours was 0.37 ± 0.34 in the USAT group and 0.59 ± 0.42 in the SCDT group (P = 0.01). Major bleeding (1 stroke and 1 vaginal bleed requiring transfusion) occurred in 2 patients, both in the USAT group.
Conclusions: In the SUNSET sPE (Standard vs. Ultrasound-Assisted Catheter Thrombolysis for Submassive Pulmonary Embolism) trial, patients undergoing USAT had similar pulmonary arterial thrombus reduction compared with those undergoing SCDT, using comparable mean lytic doses and durations of lysis.
Transarterial chemoembolization plus lenvatinib versus transarterial chemoembolization plus sorafenib as first-line treatment for hepatocellular carcinoma with portal vein tumor thrombus: A prospective randomized study
Cancer. 2021 Oct 15;127(20):3782-3793. doi: 10.1002/cncr.33677. Epub 2021 Jul 8.
Ding X, Sun W, Li W, Shen Y, Guo X, Teng Y, Liu X, Zheng L, Li W, Chen J
Background: The efficacy and safety of transarterial chemoembolization (TACE) plus lenvatinib in patients with hepatocellular carcinoma (HCC) and portal vein tumor thrombus (PVTT) have not been evaluated.
Methods: In this open-label, single-center, randomized trial (clinicaltrials.gov identifier: NCT04127396), participants with previously untreated HCC and type I-IV PVTT were randomized 1:1 to receive TACE plus lenvatinib (arm L; orally once daily, 12 mg for body weight ≥60 kg or 8 mg for body weight <60 kg) or TACE plus sorafenib (arm S; 400 mg orally twice daily in 28-day cycles). The primary end point was time-to-progression (TTP; time from randomization to disease progression) and secondary end points included objective response rate and toxicity. Prognostic factors were evaluated using a multivariable Cox proportional hazards model.
Results: Between December 30, 2018, and May 31, 2020, 64 patients were randomized (arm L, n = 32; arm S, n = 32); most patients had type I/II PVTT (71.9%), and the median target tumor diameter was 9.8 cm (range, 3.8-21.8). After a median follow-up of 16.1 months, patients in arm L had a higher median TTP (4.7 vs 3.1 months; hazard ratio [HR], 0.55; 95% CI, 0.32-0.95; P = .029) and objective response rate (53.1% vs 25.0%, P = .039) versus arm S. Multivariable analysis showed that TACE plus lenvatinib was significantly associated with higher TTP versus TACE plus sorafenib (HR, 0.50; 95% CI, 0.28-0.90; P = .021). Comparable safety profiles were observed in arms L and S.
Conclusions: TACE plus lenvatinib was safe, well tolerated, and had favorable efficacy versus TACE plus sorafenib in patients with advanced HCC with PVTT and large tumor burden.
Bleeding risk and mortality associated with uninterrupted antithrombotic therapy during percutaneous endoscopic gastrostomy tube placement
Am J Gastroenterol. 2021 Sep 1;116(9):1868-1875. doi: 10.14309/ajg.0000000000001348.
Thosani N, Rashtak S, Kannadath BS, Munjal A, Meriwether M, Yoon ED, Hermann A, Ali S, Haddad PG, Patil P, Ramireddy S, Badillo R, DaVee RT, Guha S
Introduction: Antithrombotic therapy is often interrupted before the placement of a percutaneous endoscopic gastrostomy (PEG) tube because of potentially increased risk of hemorrhagic events. The aim of our study was to evaluate the risk of bleeding events and overall complication rates after PEG in patients on uninterrupted antiplatelet and anticoagulation therapy in a high-volume center.
Methods: Data regarding demographics, diagnoses, comorbidities, and clinical outcomes pertinent to PEG were collected from 2010 to 2016. Furthermore, data regarding antithrombotic therapy along with the rate of minor or major complications including bleeding associated with this procedure were analyzed. Significant bleeding was defined as post procedure bleeding from PEG site requiring a blood transfusion and/or surgical/endoscopic intervention.
Results: We included 1,613 consecutive PEG procedures in this study, of which 1,540 patients (95.5%) received some form of uninterrupted antithrombotic therapy. Of those patients, 535 (34.7%) were on aspirin, 256 (16.6%) on clopidogrel, and 119 (7.7%) on both aspirin and clopidogrel. Subcutaneous heparin was uninterrupted in 980 (63.6%), intravenous heparin in 34 (2.1%), warfarin in 168 (10.9%), and direct-acting oral anticoagulation in 82 (5.3%) patients who overlapped on multiple drugs. We observed 6 significant bleeding events in the entire cohort (0.39%), and all were in subcutaneous heparin groups either alone or in combination with aspirin. No clinically significant bleeding was noted in patients on uninterrupted aspirin, warfarin, clopidogrel or direct-acting oral anticoagulation groups. Only 5 patients (0.31%) had PEG-related mortality.
Discussion: The risk of significant bleeding associated with the PEG placement was minimal in patients on uninterrupted periprocedural antithrombotic therapy.
