BackgroundEribulin is a non-taxane, microtubule dynamics inhibitor that increases survival of patients with metastatic breast cancer. Although eribulin is well tolerated in patients with heavily pretreated disease, eribulin-induced liver dysfunction (EILD) can occur, resulting in treatment modification and subsequent poor disease control. We aimed to clarify the effect of EILD on patient survival.MethodsThe medical records of 157 metastatic breast cancer patients treated with eribulin between July 2011 and November 2013 at Cancer Institute Hospital were retrospectively analyzed. EILD was defined as 1) an increase in alanine aminotransferase or aspartate aminotransferase levels >3 times the upper limit of normal, and/or 2) initiation of a liver-supporting oral drug therapy such as ursodeoxycholic acid or glycyron. Fatty liver was defined as a decrease in the liver-to-spleen attenuation ratio to <0.9 on a computed tomography scan.ResultsEILD occurred in 42 patients, including one patient for whom eribulin treatment was discontinued due to severe EILD. The patients who developed EILD had significantly higher body mass indices (BMIs) than those who did not develop EILD (24.5 vs. 21.5, respectively; P < 0.0001), with no difference in the dose intensity of eribulin between the two groups (P = 0.76). Interestingly, the patients with EILD exhibited significantly longer progression-free survival (PFS) and overall survival (OS) than those without EILD (P = 0.010 and P = 0.032, respectively). Similarly, among 80 patients without liver metastasis, 19 with EILD exhibited significantly longer PFS and OS than the others (P = 0.0012 and P = 0.044, respectively), and EILD was an independent prognostic factor of PFS (P = 0.0079) in multivariate analysis. During eribulin treatment, 18 patients developed fatty liver, 11 of whom developed EILD, with a median BMI of 26.7.ConclusionsAlthough EILD and fatty liver occurred at a relatively high frequency in our study, most of the patients did not experience severe adverse effects. Surprisingly, the development of EILD was positively associated with patient survival, especially in patients without liver metastases. EILD may be a clinically useful predictive biomarker of survival, but further studies are needed to confirm these findings in another cohort of patients.

Background: Pheochromocytoma (PCC) and paraganglioma (PGL) are rare tumors occurring in the adrenal medulla and extra-adrenal tissues, respectively. The clinicopathological features have not been fully elucidated, especially in Asian cohorts. Methods:We retrospectively reviewed 65 patients with PCC/PGL between 1983 and 2020. Patient characteristics and clinical outcomes (overall survival [OS] and relapsefree survival [RFS]) were analyzed based on the medical records. Morphological assessment and immunostaining of Ki-67 and succinate dehydrogenase complex subunit B (SDHB) were performed in the available specimens. Subsequently, the influence of the grading system for pheochromocytoma and paraganglioma (GAPP) score and SDHB negativity on the clinical outcomes was evaluated.Results: The median age of the patients was 51 years, and PGL accounted for 69% of the cases. Initial stage was localized disease in 83% of the patients, and the major primary lesions were in the adrenal gland (31%), retroperitoneum (24%), and bladder (15%). Fifty-three patients with localized disease underwent curative resection, and six and two patients with metastatic disease underwent surgery and chemotherapy, respectively. Morphologically, the GAPP score was 0-2 (low-risk) in nine, 3-6 (intermediate-risk) in 33, and 7-10 (high-risk) in three specimens. SDHB immunostaining was performed in 41 specimens, and the negativity rate was 19%. The 3-year OS rate in all 65 patients was 95%, and was significantly better in patients with localized than metastatic disease (3-year OS 98% vs. 80%, P ¼ 0.008). The 3-year RFS rate in the 53 patients with localized disease was 87%. The rate was significantly different among patients in the low-risk, intermediate-risk, and high-risk groups (3-year rate 100% vs. 96% vs. 33%, P < 0.0001), and between those in the SDHB-positive and SDHBnegative groups (3-year rate 100% vs. 57%, P ¼ 0.03).Conclusions: While the general outcome of PCC/PGL was favorable, our analysis suggested that high-risk GAPP score and SDHB negativity were predictors of subsequent relapse in patients with localized disease who underwent resection. The correlation between lack of SDHB expression and SDH-related mutations should be assessed in future studies.Legal entity responsible for the study: The authors.