Background: Ibrutinib is a Bruton tyrosine kinase inhibitor approved for the treatment of chronic lymphocytic leukemia (CLL) in 2014. Ibrutinib is often used to treat patients who are younger than the patients originally included in theclinical trials have additional unfavorable prognostic factors and suffer from additional comorbidities excluded from the original phase III trials. Our objective was to examine current clinical practices and their impact in this expanded population of CLL patients who often require adjustments in the standard prescribed dose and schedule of therapy. Materials and methods: An extensive review of the medical literature was conducted to establish the consensus on ibrutinib dose modifications in patients with CLL. Twenty-nine studies were reviewed including fourteen clinical trials and fifteen "real-world practice" studies. Results: The average discontinuation rate was similar between clinical trials and "real-world practice" studies though the reasons for discontinuation differed. CLL progression was a more common reason for discontinuation in clinical trial studies while toxicity was a more common reason for discontinuation in "real-world practice" studies. Some studies have suggested worse outcomes in patients requiring dose reductions in ibrutinib while others have shown no change in treatment efficacy in patients requiring dose reductions due to concomitant CYP medications or increased immunosuppression post-transplant. Conclusion: The impact of ibrutinib dose modifications on clinical outcome remains unclear. Patients on concomitant CYP3A inhibitors should be prescribed a lower dose than the standard 420 mg daily, in order to maintain comparable pharmacologic properties. Further research is required to establish definitive clinical practice guidelines.

Background: Antibiotic exposure has been associated with worse outcomes with immune checkpoint inhibitors (ICIs) in cancer patients, likely due to disruption of the gut microbiome. Other commonly prescribed medications, such as proton pump inhibitors (PPIs) and histamine-2-receptor antagonists (H2RAs), are also known to disrupt the microbiome, but data on their association with ICI outcomes are conflicting. Methods: We conducted a retrospective, multicenter, international cohort study including 314 hepatocellular carcinoma (HCC) patients treated with ICIs from 2017 to 2019 to assess the association between PPI or H2RA exposure (up to 30 days before ICI) and overall survival. Secondary outcomes included overall response rate (ORR) and development of any treatment-related adverse events (AEs). Results: Baseline PPI/H2RA exposure was not associated with overall survival in univariable (HR 1.01, 95% CI 0.75–1.35) or multivariable analysis (HR 0.98, 95% CI 0.71–1.36). Baseline PPI/H2RA exposure was not associated with either ORR (OR 1.32, 95% CI 0.66–2.65) or AEs (OR 1.07, 95% CI 0.54–2.12) in multivariable analysis. Conclusions: Our results suggest that exposure to PPI/H2RA prior to ICIs does not adversely affect outcomes in HCC patients.

Purpose: With increasing use of radiation for hepatocellular carcinoma (HCC) through transarterial radioembolization (TARE) and stereotactic body radiation therapy (SBRT), there is concern for increased radiation-related complications when using SBRT after TARE. This study compares safety of SBRT after segmental TARE versus transarterial chemoembolization (TACE). Methods and Materials: A retrospective review identified patients receiving SBRT after TACE or TARE for HCC from 2011 to 2017. TARE was delivered subselectively to individual segments using yttrium-90 with Theraspheres. Patients were assessed over time for Child-Turcott-Pugh (CTP)/albumin-bilirubin (ALBI) scores, and Common Terminology Criteria for Adverse Events version 4.0 grade !3 events. Linear mixed models were used to examine the trend of CTP and ALBI over time and compare groups. Secondary endpoints were objective response rate via modified Response Evaluation Criteria in Solid Tumors (RECIST), local control, and overall survival. Results: Ninety-nine patients met criteria with median follow-up of 9.8 months (range, 0.9-47): 31 had SBRT after segmental TARE and 68 patients post-TACE. The groups were well balanced with regard to etiology of HCC, baseline CTP and ALBI scores, and SBRT dose, but there were significant differences in baseline Eastern Cooperative Oncology Group performance status, Barcelona Clinic Liver Cancer staging, and median follow-up. There was a significant increase in post-SBRT CTP and ALBI scores (P < .0001) for both groups. However, there was no significant difference in rise in CTP (P Z .11) or ALBI score (P Z .82) over time between SBRT post-TACE versus postesegmental TARE. There was no significant increase in !grade 3 toxicity postsegmental TARE. There was also no significant difference in local controls (P Z 1.0) and overall survival (P Z .26) between cohorts, but objective response rate was worse post-TARE. Conclusions: SBRT after segmental TARE with Theraspheres appears to have acceptable tolerability and is effective compared with SBRT after TACE. Longer follow-up with larger numbers is needed to verify these data.

In the present cohort, SBRT to the CL-HCC produced excellent treatment response with acceptable HBT and LC. Select HCC patients who are not candidates for surgery or other locoregional therapies can be considered for SBRT to the central liver.

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