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Background: Many systemic therapies for advanced hepatocellular carcinoma (HCC) may cause hypothyroidism; however, in these patients, hypothyroidism prevalence before therapy and its prognostic impact remain unclear. Materials and Methods: We previously established a prospective cohort of patients who received sorafenib as first‐line therapy for advanced HCC. No patients had been clinically diagnosed with hypothyroidism before or during sorafenib treatment. We retrospectively determined the levels of thyrotropin and free thyroxine before initiation of systemic therapy. Hypothyroidism was defined as thyrotropin level higher than the upper limit of the normal range. Among patients with hypothyroidism, free thyroxine level less than the lower normal range was defined as overt hypothyroidism, and free thyroxine level within the normal range was defined as subclinical hypothyroidism. Results: In total, 79 patients were enrolled; of them, 16 (20%) had hypothyroidism (overt hypothyroidism, 10; subclinical hypothyroidism, 6). Patients with hypothyroidism, compared with those without hypothyroidism, were more likely to be older than 65 years (56% vs. 29%, p =.037), have a serum α‐fetoprotein level of >400 ng/mL (81% vs. 52%, p =.037), and have a significantly poorer overall survival (OS; median, 5.5 vs. 11.6 months, p =.043). After adjusting for other potential prognostic factors, hypothyroidism remained an independent predictor for poorer OS (hazard ratio, 2.53, p =.018). Patients with overt hypothyroidism and subclinical hypothyroidism exhibited similarly poor OS (p =.768). Conclusion: Underdiagnosis of hypothyroidism in patients with advanced HCC was common. Hypothyroidism, whether overt or subclinical, is associated with poor prognosis of advanced HCC. Implications for Practice: The results of this study showed the underdiagnosis of hypothyroidism in patients with advanced hepatocellular carcinoma (HCC) and its influence on prognosis. These findings implied the importance of thyroid function check before initiation of systemic therapy for patients with advanced HCC. Systemic therapies for advanced hepatocellular carcinoma (HCC) can cause hypothyroidism. This study examined the prevalence and prognostic impact of hypothyroidism in patients with HCC before receiving any systemic therapy. [ABSTRACT FROM AUTHOR]

Lessons Learned: For patients with advanced hepatocellular carcinoma after failure of first‐line sorafenib monotherapy, second‐line axitinib provides modest efficacy with tolerable toxicity.The discrepant tumor responses and survival outcomes in trials using axitinib as salvage therapy highlight the importance of optimal patient selection with the aid of clinical biomarkers. Background: Multikinase inhibitors have been effective treatment for hepatocellular carcinoma (HCC). This multicenter phase II study explored the efficacy and safety of second‐line axitinib for advanced HCC. Methods: Patients with advanced HCC and Child‐Pugh A liver function, experiencing progression on first‐line sorafenib monotherapy, were eligible. Axitinib 5 mg twice daily was given continuously with allowed dose escalation. Tumor assessment was performed according to RECIST version 1.1. The primary endpoint was rate of disease control. Results: From April 2011 to March 2016, 45 patients were enrolled. Thirty‐seven patients (82%) tested positive for hepatitis B surface antigen. The disease control rate was 62.2%, and the response rate was 6.7%, according to RECIST criteria. Median progression‐free survival (PFS) and overall survival (OS) were 2.2 months and 10.1 months, respectively. Treatment‐related adverse events were compatible with previous reports of axitinib. Conclusion: Second‐line axitinib has moderate activity and acceptable toxicity for patients with advanced HCC after failing the first‐line sorafenib monotherapy. [ABSTRACT FROM AUTHOR]

Background. In 2011, two national policies aiming to foster hospice services for terminal cancer patients took effect in Taiwan. The single-payer National Health Insurance of Taiwan started to reimburse full hospice services. The national hospital accreditation program, which graded all hospitals, incorporated hospice utilization in its evaluation. We assessed the impact of these national policies. Methods. A cohort of 249,394 patients aged ≥18 years who died of cancer between 2008 and 2013 were identified from the National Death Registry. We retrieved utilization data of medical services and compared the health care utilization in the final month of life before and after the implementation of the new policies. Results. After the policy changes, hospice utilization increased from 20.8% to 36.2%. In a multivariate analysis adjusting for patient demographics, cancer features, and hospital characteristics, hospice utilization significantly increased after 2011 (adjusted odds ratio [AOR] 2.35, p < .001), accompanied by a decrease in intensive care unit (ICU) admissions, invasive mechanical ventilation (IMV), and cardiopulmonary resuscitation (CPR; AORs 0.87, 0.75, and 0.80, respectively; all p < .001). The patients who received hospice services were significantly less likely to receive ICU admissions, IMV, and CPR (AORs 0.20, 0.12, and 0.10, respectively; all p < .001). Hospice utilization was associated with an adjusted net savings of U.S. $696.90 (25.2%, p < .001) per patient in the final month of life. Conclusion. The national policy changes fostering hospice care significantly increased hospice utilization, decreased invasive end-of-life care, and reduced the medical costs of terminal cancer patients. [ABSTRACT FROM AUTHOR]

Background. Many studies have shown that type 2 diabetes mellitus (DM) increases the risk for several types of cancer but not cervical cancer (CC). Although DM and insulin-like growth factor 1 have preclinical and clinical implications for CC, less is known about the prognostic impact of DM on patients with early stage CC. Patients and Methods. We used the nationwide Taiwan Cancer Registry database to collect the characteristics of stage I-IIA cervical cancer patients diagnosed between 2004 and 2008. DM and other comorbidities were retrieved from the National Health Insurance database. Cervical cancer-specific survival (CSS) and overall survival (OS) times of patients according to DM status were estimated using the Kaplan-Meier method. We used a Cox proportional hazards model to calculate adjusted hazard ratios (HRs) for the effects of DM and other risk factors on mortality. Results. A total of 2,946 patients had primary stage I-IIA CC and received curative treatments, and 284 (9.6%) had DM. The 5-year CSS and OS rates for patients with DM were significantly lower than those without DM (CSS: 85.4% vs. 91.5%; OS: 73.9% vs. 87.9%). After adjusting for clinicopathologic variables and comorbidities, DM remained an independent unfavorable prognostic factor for CSS (adjusted HR: 1.46) and OS (adjusted HR:1.55). Conclusion. In Asian patients with early cervical cancer, DM is an independent unfavorable prognostic factor influencing both OS and CSS, even after curative treatments. [ABSTRACT FROM AUTHOR]

BACKGROUND: We investigated the association between diabetes mellitus (DM) and the prognosis of patients with early colon cancer who had undergone curative surgery. METHODS: From three national databases of patients in Taiwan, we selected a cohort of colon cancer patients who had been newly diagnosed with stage I or stage II colon cancer between January 1, 2004 and December 31, 2008 and had undergone curative surgery. We collected information regarding DM (type 2 DM only), the use of antidiabetic medications, other comorbidities, and survival outcomes. The colon cancer-specific survival (CSS) and the overall survival (OS) were compared between patients with and without DM. RESULTS: We selected 6,937 colon cancer patients, among whom 1,371 (19.8%) had DM. The colon cancer patients with DM were older and less likely to receive adjuvant chemotherapy but had a similar tumor stage and grade, compared with colon cancer patients without DM. Compared with colon cancer patients without DM, patients with DM had significantly shorter OS (5-year OS: 71.0% vs. 81.7%) and CSS (5-year CSS: 86.7% vs. 89.2%). After adjusting for age, sex, stage, adjuvant chemotherapy, and comorbidities in our multivariate analysis, DM remained an independent prognostic factor for overall mortality (adjusted hazards ratio: 1.32, 95% confidence interval: 1.18-1.49), but not for cancer-specific mortality. Among the colon cancer patients who had received antidiabetic drug therapy, patients who had used insulin had significantly shorter CSS and OS than patients who had not. CONCLUSION: Among patients who receive curative surgery for early colon cancer, DM is a predictor of increased overall mortality. [ABSTRACT FROM AUTHOR]

Background. Asian ethnicity is associated with a distinct molecular etiology, treatment response, and survival outcome among patients with non-small cell lung cancer (NSCLC). This study examines the survival impact of platinum-based adjuvant chemotherapy for Asian patients with stage I–IIIA NSCLC. Methods. This study recruited patients aged ≥18 years with histologically proven stage IA–IIIA NSCLC registered in the Taiwan Cancer Registry database in January 2004 to December 2007. Platinum-containing adjuvant chemotherapy had to be started within 90 days of the primary surgery. Kaplan–Meier survival curves, log-rank tests, and the Cox proportional hazards regression model were used to assess the influence of various risk factors on survival time. Results. This study included 2,231 patients with stage IA–IIIA NSCLC who underwent primary surgery with a clear surgical margin. The percentages of all causes of death were significantly lower for the chemotherapy group for both stage II and stage IIIA patients. Multivariate analysis identified platinum-based adjuvant chemotherapy as an independent prognostic factor for the overall survival outcome of stage II (hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.39–0.94; p .024) and IIIA (HR, 0.71; 95% CI, 0.52– 0.96; p .029) patients. Among these patients, those who received adjuvant chemotherapy had a superior overall survival outcome for both genders, for the subgroup of patients aged ≥70 years, and for those with adenocarcinoma. Conclusion. Platinum-based adjuvant chemotherapy should be considered in the treatment plan for Asian patients with resected stage II and stage IIIA NSCLC. The Oncologist 2012;17:1294–1302 [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus (DM) is closely associated with hepatocarcinogenesis. This study explores the prognostic impact of DM in patients who received curative therapy for localized hepatocellular carcinoma (HCC)., Methods: Patients who had been diagnosed with stage I or II HCC in 2003 and 2004 and received surgical resection or local ablation therapy were identified from the population-based Taiwan National Cancer Registry. Data pertaining to DM and other comorbidities were retrieved from the Taiwan National Health Insurance database. Liver cancer-specific survival (LCS), liver disease-related survival (LDS) and overall survival (OS) rates were compared between patients with and without DM. The presence of other comorbidities and tumor status were adjusted using multivariate analysis., Results: A total of 931 patients who fulfilled the study criteria were analyzed; 185 (20%) of them had DM (type 1 or type 2). The LCS, LDS, and OS rates were significantly worse for patients with DM than patients without DM (all p < .001). After adjusting for age, sex, tumor stage, treatment, and the presence of other comorbidities, DM remained an independent predictor of poorer LCS (hazard ratio [HR] = 1.57; p < .001), LDS (HR = 1.70; p < .001), and OS (HR = 1.69; p < .001). The associations between DM and mortality were consistent among subgroups, irrespective of tumor size, stage, treatment modality, and liver cirrhosis., Conclusions: DM is an independent factor for poorer prognosis in patients who received curative therapy for localized HCC.

Background: The purpose of this study was to determine the prognostic significance of clinical factors and staging systems for survival of hepatocellular carcinoma (HCC) patients who are candidates for therapeutic clinical trials., Methods: From December 1990 to July 2005, 236 patients with unresectable HCC were enrolled into six published phase II trials assessing various therapeutic regimens. Of these, 156 chemotherapy-naive patients with Child-Pugh class A and Barcelona Clinic Liver Cancer stage C disease were included in this analysis. Twenty-seven relevant clinical characteristics were analyzed to identify prognostic factors of survival. Beyond these prognosticators, the predictive ability of eight staging systems (the tumor-node-metastasis, Okuda, Cancer of the Liver Italian Program [CLIP], Chinese University Prognostic Index, Japanese Integrated Staging, Tokyo, National Taiwan University Risk Estimation, and Advanced Liver Cancer Prognostic System [ALCPS] score) were compared using the Akaike information criteria., Results: The median overall survival time was 129 days (95% confidence interval, 111-147 days). Significant predictors of a shorter overall survival time were an Eastern Cooperative Oncology Group performance status score ≥2, the presence of symptoms, ascites, an aspartate transaminase level more than two times the upper limit of normal, and regional lymph node involvement. The ALCPS and CLIP scores were superior to the other systems for predicting survival., Conclusions: The prognosis of patients with advanced HCC who are candidates for therapeutic clinical trials is affected by several factors related to the patient, liver function, and the tumor. The ALCPS and CLIP scores appear to be superior to the other systems for predicting survival.

Background: Diabetes mellitus (DM) has been implicated in influencing the survival duration of patients with breast cancer. However, less is known about the impact of DM and other comorbidities on the breast cancer-specific survival (BCS) and overall survival (OS) outcomes of Asian patients with early-stage breast cancer., Patients and Methods: The characteristics of female patients with newly diagnosed, early-stage breast cancer were collected from the Taiwan Cancer Registry database for 2003-2004. DM status and other comorbidities were retrieved from Taiwan's National Health Insurance database. The BCS and OS times of patients according to DM status were estimated via the Kaplan-Meier method. Cox's proportional hazard model was used to estimate adjusted hazard ratios (HRs) for the effects of DM, comorbidities, and other risk factors on mortality., Results: In total, 4,390 patients were identified and 341 (7.7%) presented with DM. The 5-year BCS and OS rates were significantly greater in DM patients than in non-DM patients (BCS, 85% versus 91%; OS, 79% versus 90%). Furthermore, after adjusting for clinicopathologic variables and comorbidities, DM remained an independent predictor of shorter BCS (adjusted HR, 1.53) and OS (adjusted HR, 1.71) times. Subgroup analyses also demonstrated a consistent prognostic influence of DM across different groups., Conclusion: In Asian patients with early-stage breast cancer, DM is an independent predictor of lower BCS and OS rates, even after adjusting for other comorbidities. The integration of DM care as part of the continuum of care for early-stage breast cancer should be emphasized.

Aim: Brain metastasis was regarded, until recently, as a rare and late-stage event in patients with hepatocellular carcinoma (HCC). With the prolongation of survival in patients with advanced HCC by molecular targeted agents, this may have changed. We aimed to examine whether or not the incidence of brain metastasis in these patients has increased., Methods: Between June 2005 and May 2009, 158 advanced HCC patients in total with either metastatic or locally advanced disease untreatable by locoregional therapies were enrolled in clinical trials of first-line antiangiogenic therapies. The clinicopathologic features and survival times of those who developed brain metastasis were analyzed., Results: Eleven (7%) of 158 advanced HCC patients, with a median follow-up of 26.6 months, were diagnosed with brain metastasis as a result of compatible symptoms, confirmed by brain imaging. All 11 patients had extrahepatic metastasis upon enrollment, and 10 of them had lung metastasis. The median time to brain metastasis was 9.6 months (range, 0.6-19.6 months). The median overall survival (OS) time after diagnosis of brain metastasis was 4.6 months (range, 0.7-12.6 months). Four patients received brain tumor excision, and their survival duration after brain metastasis tended to be longer than that of those who did not (median OS time, 6.1 months versus 3.1 months)., Conclusions: In the era of antiangiogenic targeted therapy, the importance of brain metastasis for advanced HCC patients may have increased.