Background: Factors associated with response to lenvatinib have not been clarified in patients with hepatocellular carcinoma (HCC). Patients and Methods: This study retrospectively analyzed 50 patients treated with lenvatinib as first-line therapy between March 2018 and March 2019. Patients were divided into two groups by the Modified Response Evaluation Criteria in Solid Tumours (mRECIST) (responders and non-responders, whose best overall responses were complete (CR)/partial response (PR) and stable (SD)/progressive disease (PD), respectively). Factors associated with response were assessed, including the relative dose intensity 8 weeks after lenvatinib induction (8W-RDI). Results:The best overall responses were 0/22/14/14 of CR/PR/SD/PD. Multivariate analysis revealed that only 8W-RDI was significantly associated with response. The receiver operating characteristic curve for 8W-RDI in differentiating responders from non-responders revealed a cut-off value of 75%. Patients with 8W-RDI ≥75% experienced a higher response rate and longer progression-free survival than patients with 8W-RDI <75%. Conclusion: Our results suggest that maintaining an RDI ≥75% during the initial 8 weeks of lenvatinib treatment has a favorable impact on response.Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide and the second leading cause of cancer-related death, resulting in more than 700,000 deaths 5149
It has been reported that polymorphisms of human leukocyte antigen (HLA) genes and several cytokine genes are associated with an increased risk of developing gastric cancer (GC). However, the results of studies from different geographic regions, ethnic groups and study groups are inconsistent. The aim of this study was to evaluate the influence of H. pylori infection and host genetic factors on GC susceptibility in Japanese patients with GC. We analyzed genotypes for HLA class I and II, tumor necrosis factor a, interleukin (IL)-1b, IL-1 receptor, IL-4, IL-4Ra and IL-10 in 330 H. pyloriinfected noncardia patients with GC and 190 H. pylori-infected nonulcer dyspeptic controls. Haplotype analyses indicated that the frequencies of the HLA DRB1*0405 and DQB1*0401 alleles were increased in the patients with intestinal-type GC when compared with controls (both DRB1*0405 and DQB1*0401: p 5 0.015, OR 5 1.57, 95% CI 5 1.09-2.26), but the changes were not statistically significant after correction for multiple comparisons. None of the cytokine gene polymorphisms were associated with GC susceptibility, whether patients with GC were analyzed as a group according to the histological subtype. Of interest was the comparison of controls and patients with intestinal-type GC. The frequency of an IL-10-592AA homozygote showing concomitant carriage of the HLA DRB1*0405-DQB1*0401 haplotype was significantly higher in patients with intestinal-type GC (v 2 5 6.369, p 5 0.0116, p c 5 0.0464, OR 5 2.43, 95% CI 5 1.21-4.48). Our results suggest that the HLA class II and IL-10-592A/C polymorphisms synergistically affect the susceptibility to GC development of H. pylori-infected individuals in the Japanese population. ' 2009 UICC Key words: gastric cancer; Helicobacter pylori; polymorphic variation; HLA class II alleles; cytokines Gastric cancer (GC) remains one of the most frequently diagnosed malignant diseases worldwide, and even more so in Japan. Several studies have shown that Helicobacter pylori infection is an important risk factor for GC. [1][2][3][4] Although about half of the world's population is believed to be infected with H. pylori, only a small proportion of those people develop GC, suggesting that additional factors such as host genetic factors and environmental factors, as well as the diversity of H. pylori virulence genes, must be involved in the development and progression of GC. Therefore, this belief has generated interest in host factors, especially immune-and inflammatory-related host genetic factors.Human leukocyte antigen (HLA) genes play a key role in the body's immune response and exhibit very high degrees of polymorphism. HLA molecules bind antigen peptides and present them to T cells, which differentiate into cytotoxic or helper T cells upon specific recognition of the antigen peptide-HLA molecule complexes. Many investigators have reported an association of GC risk and HLA class II (DR and/or DQ) type in several ethnic populations. 5-14 However, different results have been obtained in different ethnic groups an...
We investigated the association between early tumor shrinkage (ETS) and treatment outcome in patients with hepatocellular carcinoma treated with lenvatinib (LEN). A retrospective analysis was performed in 104 patients. ETS was defined as tumor shrinkage at the first evaluation in the sum of target lesions’ longest diameters from baseline according to the Response Evaluation Criteria in Solid Tumors (RECIST). The median overall survival (OS) was not reached, whereas the median progression-free survival (PFS) was 5.0 months. The receiver operating characteristic curve analysis in differentiating long-term responders (PFS ≥ 5.0 months) from short-term responders (PFS < 5.0 months) revealed an ETS cut-off value of 10%. ETS ≥ 10% was significantly correlated with better PFS and OS compared with ETS < 10%. Additionally, ETS ≥ 10% showed a better discrimination ability on prognosis compared with modified RECIST-based objective response at the first evaluation. Multivariate analysis confirmed ETS ≥ 10% as an independent predictor of better OS, as well as a Child–Pugh score of 5 and macrovascular invasion. In conclusion, ETS ≥ 10% was strongly associated with outcome in patients treated with LEN. This biomarker could allow earlier assessment of the treatment response and guide treatment decision-making for HCC.
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