Yu-Shin Hung

Clinical bleeding events and laboratory coagulation profiles in acute promyelocytic leukemia

Background:  Bleeding is the leading cause of death for patients with acute promyelocytic leukemia (APL). Blood component transfusion to correct coagulopathy is the keystone in reducing bleeding. The benefit of fresh frozen plasma transfusion is unproven. Using laboratory profiles to predict bleeding is important guidance for the determination of transfusion policies in the treatment of APL.

Chromogranin A is a reliable biomarker for gastroenteropancreatic neuroendocrine tumors in an Asian population of patients.

Purpose: To evaluate the significance of plasma chromogranin A (CgA) levels in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NET) in terms of disease status and treatment responses. Materials and Methods: Forty-four GEP-NET patients comprising 15 disease-free patients and 29 patients with active disease, as well as 26 healthy participants were enrolled in this study between April 2010 and April 2011. Clinicopathological factors were collected and serial plasma CgA levels were measured. Results: Plasma CgA levels were significantly higher in GEP-NET patients with active disease than in disease-free patients (p = 0.011) or healthy participants (p = 0.001). No difference in CgA levels was observed in terms of primary tumor location, tumor grade, and functional status in patients with active disease. CgA values at 94 U/l distinguished healthy individuals or disease-free patients from patients with active disease. Sensitivity and specificity rates were 86 and 88%, respectively. CgA levels at 110 U/l differentiated patients without recurrence from those with recurrence, with a sensitivity rate of 100% and a specificity rate of 80%. Patients (5/5, 100%) with stable disease and who showed partial response after treatment had a more than 20% decrease in CgA levels compared with the baseline values. Patients (6/6, 100%) with progressive disease showed a less than 20% decrease or increase in CgA levels. Conclusion: The plasma CgA level is a reliable biomarker for GEP-NET. We conclude that changes in CgA levels are associated with disease status and treatment responses.

Combination of Initial Palliative Prognostic Index and Score Change Provides a Better Prognostic Value for Terminally Ill Cancer Patients: A Six-Year Observational Cohort Study

CONTEXT The Palliative Prognostic Index (PPI) is among the most popular scores used to predict life expectancy in terminally ill patients worldwide. PPI assessed on the first day of palliative care might be inappropriate because the contribution from subsequent changes in a patients condition are not taken into account. OBJECTIVES The aim of this study is to determine the utility of sequential PPI assessments as a better prognostic tool for patients with terminal cancer. METHODS In total, 2392 terminally ill cancer patients with initial and one-week PPI assessments under the palliative care consultation service between January 2006 and December 2011 at a single medical center in Taiwan were selected. Patients were categorized into initial PPI, Week 1 PPI, score change (initial PPI - Week 1 PPI; Δscore), and combined initial PPI and Δscore subgroups for survival analysis. RESULTS Overall median survival was 32 days (range eight to 180 days), and 2183 patients (91.3%) died within 180 days of palliative care consultation service care. A significant difference in survival was observed among patient subgroups (P < 0.001). Subgroup survival analysis showed significant difference in patients with Δscores >0, 0, and <0 in each prognostic group categorized by initial PPI. The c-statistic for predicting life expectancy <30 days was significantly higher with the combined initial PPI and Δscore (c-statistic, 0.71; 95% CI, 0.694-0.731) than with the initial PPI (c-statistic, 0.63; 95% CI, 0.61-0.65), Week 1 PPI (c-statistic, 0.67; 95% CI, 0.652-0.690), or Δscore (c-statistic, 0.64; 95% CI, 0.62-0.66). CONCLUSION Combination of initial PPI and score change is more useful than initial PPI for identifying patients with poor outcomes in good prognostic groups and patients with better outcomes in poor prognostic groups.

Characteristics of patients with hematologic malignancies who received palliative care consultation services in a medical center.

This study aimed to compare the characteristics of patients with hematologic malignancies and solid cancers who received palliative care. A total of 124 patients with hematologic malignancy and 3032 patients with solid cancer, who received palliative care consultation services between 2006 and 2010 in a medical center in Taiwan, were retrospectively analyzed. Higher prevalence of oral stomatitis, diarrhea, and hematologic symptoms including infection, fever, severe anemia, and bleeding, and lower prevalence of constipation, abdominal distension, and pain were observed in patients with hematologic malignancies compared to that in patients with solid cancer. The interval from hospital admission to palliative care referral was longer for patients with hematologic malignancy than that for patients with solid cancer. Hematologists should refer patients earlier, and palliative care specialists should understand the specific needs of patients with hematologic malignancy.

Development and Validation of a Prognostic Score to Predict Survival in Adult Patients With Solid Tumors and Bone Marrow Metastases.

Abstract Bone marrow metastasis (BMM) in patients with solid cancers is indicative of advanced-stage disease with a poor prognosis. The clinical features and outcomes remain unclear. We aimed to develop a scoring system to predict survival in these patients to help with clinical decision making. A total of 165 adult patients diagnosed with solid cancers and BMM between 2000 and 2014 were selected as the derivation cohort. A risk model was developed using multivariate logistic regression from the derivation cohort and a marrow metastases prognostic score (MMPS) was generated. An independent cohort of 156 patients from 3 other hospitals was selected using the same recruiting criteria to validate the MMPS as a predictor of survival. The MMPS was calculated based on 4 independent prognostic variables: the Eastern Cooperative Oncology Group performance scale, site of cancer, platelet count, and neutrophil-to-lymphocyte ratio. Patients in both the derivation and validation cohorts were stratified into good, intermediate, and poor prognostic groups based on their MMPS. The median survival in each risk group of the derivation cohort was 241, 58, and 11 days for the good, intermediate, and poor prognostic groups, respectively, and 305, 65, and 9 days, respectively, in the validation cohort. The c-statistic values for prediction of mortality at 3, 6, and 12 months were significantly higher for the MMPS than for the Eastern Cooperative Oncology Group performance scale in both cohorts. We developed a risk model that accurately predicted survival in adult patients with solid cancers and BMM. This scoring system may help patients and clinicians with treatment decisions.

Sequential Assessments of the Eastern Cooperative Oncology Group Performance Scale Enhance Prognostic Value in Patients With Terminally Ill Cancer Receiving Palliative Care

This study aimed to assess the utility of the Eastern Cooperative Oncology Group (ECOG) performance scale assessments on days 1 and 8 of palliative care, as well as scale change between these assessments, as prognostic tools for patients with terminally ill cancer. A total of 2392 patients with terminally ill cancer who received palliative care between January 2006 and December 2011 at a single medical center were analyzed. Our study showed that the ECOG scale is a useful prognostic tool to predict life expectancy in patients with terminally ill cancer. The ECOG scale assessments at different time points under palliative care were independent predictors for overall survival. The combined ECOG scale assessments on days 1 and 8 predicted survival more precisely than using day 1 ECOG scale assessment alone.

Acute promyelocytic leukemia-associated thrombosis.

Patients with acute promyelocytic leukemia (APL) are prone to both bleeding and thrombosis. The bleeding complications are well known. In contrast, APL-associated thrombosis is relatively underappreciated. We aimed to explore the issue of APL-associated thrombosis events. In the past 20 years, 127 cases with APL were found in our hospital database. We collected their coagulation laboratory profiles, including leukemia burdens, white blood cell and platelet counts, prothrombin time, activated partial thromboplastin time, fibrinogen levels, and disseminated intravascular coagulation scores. Data were compared between patients with or without thrombosis. Clinical outcomes and potential risk factors were obtained for analysis. Ten cases with APL-associated thrombosis were found. The incidence of thrombosis was 7.9% in our cohort. Five patients had cerebral infarction, 5 had catheter-related thrombosis and 1 had acute myocardial infarction. No laboratory data were associated with clinical thrombosis. Three patients died during the induction phase but thrombosis was not the direct cause of death for any of them. We conclude that patients with APL are susceptible to thrombosis in addition to bleeding. Laboratory coagulation parameters did not predict thrombosis in our series. Ischemic stroke and catheter-related thrombosis were the most common events in our Taiwanese cohort. Such a thrombosis pattern is unique and worth further investigation.

Impact of Palliative Care Consultation Service on Terminally Ill Cancer Patients: A 9-Year Observational Cohort Study in Taiwan.

AbstractThe palliative care consultation service (PCCS) that has been enthusiastically promoted in Taiwan since 2005 was designed to provide comprehensive end-of-life care for terminally ill patients with qualified interdisciplinary specialists in acute care ward setting. This study aims to evaluate the impact of PCCS on terminally ill cancer patients.A total of 10,594 terminal cancer patients who were referred to PCCS from a single medical center in Taiwan between 2006 and 2014 were enrolled. The percentages of patients’ and their families’ disease awareness, do-not-resuscitate (DNR) designation, refusal and acceptance of palliative care among terminally ill cancer patients were analyzed retrospectively.At the beginning of PCCS, the percentages of disease awareness among patients and their family were increased from 25.4% to 37.9% (P = 0.007) and from 61.2% to 84.7% between 2006 and 2014 (P = 0.001), respectively. Patients’ disease awareness after PCCS referral between 2006 and 2014 was increased from 47.1% to 64.5% (P = 0.016). Familys awareness of diagnosis and prognosis after PCCS referral researched to a steady plateau, 94.1% to 97.8% in different year cohort (P = 0.34). The percentage of DNR designation rate at the beginning of PCCS (in 2006) was 15.5%, and the designation rate was increased annually and finally reached to 42.0% in 2014 (P = 0.004). The percentage of DNR consents after PCCS was also improved from 44.0% in 2006 up to 80.0% in 2014 (P = 0.005). PCCS refusal rate decreased gradually and dropped to 1.6% in 2014 (P = 0.005). The percentage of PCCS utilization was increased 5-fold during the 9-year period after the promotion of PCCSIn the program of PCCS promotion, an increasing trend of PCCS utilization, better patients’ and their families’ awareness of diagnosis and prognosis, more consent to DNR, more patients were discharged with stable condition at the end of PCCS and a decrease refusal rate of end-of-life palliative care among terminal cancer patients were observed in Taiwan between 2006 and 2014.

A Simple Risk Model to Predict Survival in Patients With Carcinoma of Unknown Primary Origin.

AbstractCarcinoma of unknown primary origin (CUP) is characterized by diverse histological subtypes and clinical presentations, ranging from clinically indolent to frankly aggressive behaviors. This study aimed to identify prognostic factors of CUP and to develop a simple risk model to predict survival in a cohort of Asian patients.We retrospectively reviewed 190 patients diagnosed with CUP between 2007 and 2012 at a single medical center in Taiwan. The clinicopathological parameters and outcomes of our cohort were analyzed. A risk model was developed using multivariate logistic regression and a prognostic score was generated.The prognostic score was calculated based on 3 independent prognostic variables: the Eastern Cooperative Oncology Group (ECOG) scale (0 points if the score was 1, 2 points if it was 2–4), visceral organ involvement (0 points if no involvement, 1 point if involved), and the neutrophil-to-lymphocyte ratio (0 points if ⩽3, 1 point if >3). Patients were stratified into good (score 0), intermediate (score 1–2), and poor (score 3–4) prognostic groups based on the risk model. The median survival (95% confidence interval) was 1086 days (500–1617, n = 42), 305 days (237–372, n = 75), and 64 days (44–84, n = 73) for the good, intermediate, and poor prognostic groups, respectively. The c-statistics using the risk model and ECOG scale for the outcome of 1-year mortality were 0.80 and 0.70 (P = 0.038), respectively.In this study, we developed a simple risk model that accurately predicted survival in patients with CUP. This scoring system may be used to help patients and clinicians determine appropriate treatments.

Primary breast lymphoma: A single-institute experience in Taiwan

Background: Breast is an uncommon location of lymphoma involvement. The most common type of primary breast lymphoma (PBL) is diffuse large B-cell lymphoma (DLBCL). Rituximab is the widely used monoclonal antibody against CD20+ B-cell lymphoma, especially DLBCL. We aimed to analyze the clinical features, prognostic factors, and treatment outcome with or without rituximab in primary breast DLBCL. Methods: We retrospectively analyzed patients diagnosed with PBL from October 1987 to March 2012 in our hospital, excluding metastasis by whole-body computed tomography and bone marrow study. Results: Twenty-three patients were diagnosed with PBL. All were females. Eighteen patients were stage IE and five were stage IIE according to the Ann Arbor staging system. Two patients had lymphoma other than DLBCL. The median age of primary breast DLBCL patients was 48 years (range 27-79). Two were excluded from the analysis due to refusal or ineligibility for chemotherapy. No significant prognostic factor was found. Patients receiving chemotherapy with (RC) or without (C) rituximab were not significantly different in the 5-year overall survival (RC: 57.1%; C: 58.3%; p = 0.457) or progression-free survival (RC: 57.1%; C: 50.0%; p = 0.456). A high incidence of relapse in the central nervous system (CNS) (17.6%) was observed. Conclusions: In accordance with prior literature reports, our Taiwanese cohort of primary breast DLBCL seemed younger than those reported in Japan, Korea, and Western societies. Relapse in the CNS was not uncommon. The benefit of rituximab in addition to chemotherapy was not statistically significant. Treatment modality remained to be defined by further large-scale studies.