Surgery for liver metastases arising from gastric adenocarcinoma is reasonable if complete resection seems feasible after careful preoperative staging, even if complete resection is not actually achieved. Hepatic resection should be considered as an option for gastric cancer patients with hepatic metastases.
A B S T R A C T PurposeEpigenetic aberrations have been reported in hepatocellular carcinoma (HCC). In this study of patients with unresectable HCC and chronic liver disease, epigenetic therapy with the histone deacetylase inhibitor belinostat was assessed. The objectives were to determine dose-limiting toxicity and maximum-tolerated dose (MTD), to assess pharmacokinetics in phase I, and to assess activity of and explore potential biomarkers for response in phase II.
Patients and MethodsMajor eligibility criteria included histologically confirmed unresectable HCC, European Cooperative Oncology Group performance score Յ 2, and adequate organ function. Phase I consisted of 18 patients; belinostat was given intravenously once per day on days 1 to 5 every 3 weeks; dose levels were 600 mg/m 2 per day (level 1), 900 mg/m 2 per day (level 2), 1,200 mg/m 2 per day (level 3), and 1,400 mg/m 2 per day (level 4). Phase II consisted of 42 patients. The primary end point was progression-free survival (PFS), and the main secondary end points were response according to Response Evaluation Criteria in Solid Tumors (RECIST) and overall survival (OS). Exploratory analysis was conducted on pretreatment tumor tissues to determine whether HR23B expression is a potential biomarker for response.
ResultsBelinostat pharmacokinetics were linear from 600 to 1,400 mg/m 2 without significant accumulation. The MTD was not reached at the maximum dose administered. Dose level 4 was used in phase II. The median number of cycles was two (range, one to 12). The partial response (PR) and stable disease (SD) rates were 2.4% and 45.2%, respectively. The median PFS and OS were 2.64 and 6.60 months, respectively. Exploratory analysis revealed that disease stabilization rate (complete response plus PR plus SD) in tumors having high and low HR23B histoscores were 58% and 14%, respectively (P ϭ .036).
ConclusionEpigenetic therapy with belinostat demonstrates tumor stabilization and is generally welltolerated. HR23B expression was associated with disease stabilization.
Our results suggest that a positive microscopic margin is associated with a worse outcome in patients with node-negative disease. Therefore, a more aggressive treatment, such as re-operation, is needed in node-negative patients with a positive microscopic disease.
Mental adjustment and coping affect the physical outcome and survival as well as quality of life in cancer patients. The Mini-Mental Adjustment to Cancer (Mini-MAC) scale is a new refined, economical and reliable self-rating instrument measuring cognitive and behavioral responses to cancer. The aim of this study was to evaluate the psychometric properties of the Mini-MAC in Korean cancer patients. A total of 208 cancer patients recruited from the Yonsei Cancer Center were assessed with the Mini-MAC and the Hospital Anxiety and Depression Scale (HADS). Principal component analysis with varimax rotation for the Korean version of Mini-MAC (K-Mini-MAC) confirmed four factors. Three had psychometric properties similar to Helpless-Hopeless (HH), Anxious Preoccupation (AP) and Cognitive Avoidance (CA) of the original Mini-MAC. A novel factor, named Positive Attitude, included items of both Fatalism (FA) and Fighting Spirit (FS) from the original version. The five subscales from the original version (AP, HH, FS, FA and CA) and Positive Attitude had acceptable internal reliabilities in our sample (Cronbach's alpha coefficient 0.50-0.86; correlation coefficient of test-retest 0.68-0.88). For the validity, significant interscale correlation was observed in the original five subscales and Positive Attitude. Each subscale including Positive Attitude was also significantly related to Depression and Anxiety of HADS. As a whole, the K-Mini-MAC was a reliable, valid and acceptable tool for Korean cancer patients. These findings can provide information about the cross-cultural validity of Mini-MAC scale's factor structure. Cultural differences were also discussed.
Objective:The aim of this study was to analyze the clinicopathologic characteristics and prognosis of signet ring cell carcinoma (SRC) according to disease status (early vs advanced gastric cancer) in gastric cancer patients.Background:The prognostic implication of gastric SRC remains a subject of debate.Methods:A retrospective analysis was performed using the clinical records of 7667 patients including 1646 SRC patients who underwent radical gastrectomy between 2001 and 2010. A further analysis was also performed after dividing patients into three groups according to histologic subtype: SRC, well-to-moderately differentiated (WMD), and poorly differentiated adenocarcinoma.Results:SRC patients have younger age distribution and female predominance compared with other histologic subtypes. Notably, the distribution of T stage of SRC patients was distinct, located in extremes (T1: 66.2% and T4: 20%). Moreover, the prognosis of SRC in early gastric cancer and advanced gastric cancer was contrasting. In early gastric cancer, SRC demonstrated more favorable prognosis than WMD after adjusting for age, sex, and stage. In contrast, SRC in advanced gastric cancer displayed worse prognosis than WMD. As stage increased, survival outcomes of SRC continued to worsen compared with WMD.Conclusions:Although conferring favorable prognosis in early stage, SRC has worse prognostic impact as disease progresses. The longstanding controversy of SRC on prognosis may result from disease status at presentation, which leads to differing prognosis compared with tubular adenocarinoma.
Purpose: With growing evidence that inflammation and low muscularity play a role in the survival of cancer patients, we evaluated the prognostic implications of sarcopenia with systemic inflammation in patients who underwent definitive chemoradiotherapy (CCRT) for locally advanced head and neck cancer.Materials and Methods: We analyzed 221 patients with head and neck cancer who received definitive CCRT between 2006 and 2015. The skeletal muscle area was measured using a single computed tomography image slice at the level of the third lumbar vertebra (L3). Sarcopenia was defined as an L3 muscle index of <49 cm2/m2 for men and <31 cm2/m2 for women.Results: Patients with sarcopenia (n = 106) exhibited higher neutrophil/lymphocyte ratios (NLRs) than those without (n = 115); the former also had an inferior 3-year overall survival (OS) rate (62%) than the latter (76%, p = 0.037). Among patients with sarcopenia, those who also had high NLRs (n = 51) showed significantly poorer OS and progression-free survival (PFS). In the multivariate analysis, sarcopenia plus a high NLR remained the most significant predictor of poor OS and PFS. Patients with sarcopenia required more frequent interruption of RT; patients whose RT was interrupted for ≥5 days showed inferior disease control and OS.Conclusions: Sarcopenia accompanied by systemic inflammation at initial diagnosis is associated with significantly inferior OS and PFS. Additionally, patients with sarcopenia required RT interruption more frequently. Intensive nutritional support and additional treatment methods are required for these patients while undergoing RT.
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