Sequential eradication of Helicobacter pylori as a treatment for immune thrombocytopenia in patients with moderate thrombocytopenia: a multicenter prospective randomized phase 3 study.

Due to several issues, standard treatments are not recommended for asymptomatic patients with moderate immune thrombocytopenia (ITP). Since platelet responses are reported in some patients with Helicobacter pylori (H. pylori)-positive ITP after eradication, we conducted a multicenter, phase 3 study to evaluate the safety and efficacy of recently established sequential eradication for these patients having moderate thrombocytopenia. Persistent or chronic ITP patients with platelet count (30 × 103 ~ 80 × 103/µL) and confirmed active H. pylori infection were randomly assigned to a treatment and a control group. The former received 10-day sequential treatment. Eradication was assessed by urea breath test at 3 months after treatment. Primary endpoint was the overall platelet response rate at 3 months in successfully eradicated treatment group and control group. Secondary endpoints were platelet response time, H. pylori eradication success rate, etc. The patient enrollment terminated early because of the change of national insurance and treatment guideline for H. pylori-positive patients in Korea during the study. Of the 28 H. pylori-positive ITP patients, 17 were randomized to the treatment group, and eradication was achieved for 15 (88.2%) at 3 months, and seven in control group after withdrawal. Statistically, significant difference in platelet response rates between the two groups were observed (p = 0.017). Our study verifies that H. pylori eradication was an effective ITP treatment for patients with H. pylori-associated moderate ITP. This sequential eradication regimen showed not only a high H. pylori eradication rate, but also a remarkable platelet response for ITP patients. Trial registration number and date of registration for these prospectively registered trials is ClinicalTrials.gov number, NCT03177629 and June 6, 2017.

A Myelodysplastic Syndrome with Concurrent Basophilia and Eosinophilia Lacking Oncogenic Mutations in 54 Relevant Genes.

Myelodysplastic syndromes (MDS) with basophilia or eosinophilia are very rare and portend poor prognoses. We present a rare patient who had MDS with excess blasts as well as peripheral basophilia and concurrent bone marrow (BM) basophilia/eosinophilia. She had a complex karyotype including 5q and 7q deletions; however, no oncogenic mutations were observed on next-generation sequencing of 54 genes known to be frequently mutated in acute myeloid leukemia/MDS. Peripheral basophilia resolved after decitabine treatment. Ours is the first report to describe a genome-wide analysis and the use of decitabine to successfully treat basophilia in an MDS patient with concurrent BM basophilia/eosinophilia.

Correlation of Thyroid Transcription Factor-1 Expression with EGFR Mutations in Non-Small-Cell Lung Cancer: A Meta-Analysis.

OBJECTIVES: This meta-analysis investigated the relationship between thyroid transcription factor-1 (TTF-1) expression and epidermal growth factor receptor (EGFR) mutations in non-small-cell lung cancer (NSCLC) to clarify whether TTF-1 can be a potential surrogate marker for EGFR mutation status in advanced NSLCL. METHODS: A systematic searching of databases, including PubMed, EMBASE, Cochrane Library, and Google Scholar, was performed to identify studies assessing the correlation of TTF-1 expression with EGFR mutations. From 17 studies, 9764 patients were included in the combined analysis of odds ratio (OR) for the correlation between TTF-1 expression and EGFR mutations. RESULTS: Compared with NSCLCs showing negative TTF-1 expression, tumors harboring TTF-1 overexpression showed a significantly higher rate of EGFR mutations (OR = 5.19, 95% confidence interval: 3.60⁻7.47, p < 0.00001). This correlation was observed in both subgroups of East Asian (OR = 4.33, 95% CI: 3.46⁻5.41, p < 0.00001) and European patients (OR = 4.64, 95% CI: 1.41⁻15.28, p < 0.01). In addition, TTF-1 expression was significantly associated with EGFR mutations in exon 19 (OR = 4.63, 95% CI: 2.89⁻7.41, p < 0.00001) as well as exon 21 (OR = 3.16, 95% CI: 1.04⁻9.60, p = 0.04). CONCLUSIONS: This meta-analysis demonstrates a significant correlation between TTF-1 expression and EGFR mutations in patients with NSCLC. The status of TTF-1 expression may be a biomarker to guide anticancer treatment in patients with NSCLC and unknown EGFR mutation status.

Phase II study of oxaliplatin, irinotecan and S-1 therapy in patients with advanced gastric cancer: the Korean Cancer Study Group ST14-11.

BACKGROUND: Doublet chemotherapy of platinum and 5-fluorouracil is a standard first-line treatment for patients with unresectable gastric cancer. Although the addition of taxane or irinotecan to this regimen has yielded promising efficacy, its use has been limited due to severe toxicities. To overcome this limitation, we evaluated the efficacy and safety of the combination of irinotecan, oxaliplatin, and S-1 (OIS) for the treatment of advanced gastric cancer. METHODS: Chemotherapy-naïve patients with pathologically proven advanced gastric adenocarcinoma were assessed for eligibility. Irinotecan (135 mg/m2) and oxaliplatin (65 mg/m2) were administered intravenously on day 1, and S-1 (80 mg/m2/day) was administered orally on days 1-7 of every 2-week cycle. RESULTS: Forty-four patients (median age 57 years) were enrolled and all but one patient had a good performance status (ECOG 0 or 1). A total of 529 cycles were administered, with a median of 9.5 (range 1-31) cycles per patient. The overall response rate was 61.4% (95% confidence interval [CI] 46.6-74.3). The median progression-free survival and overall survival were 10.8 months (95% CI 7.6-14.0) and 15.4 months (95% CI 12.6-18.2), respectively. Major toxicities included grade 3/4 neutropenia (38.6%), febrile neutropenia (13.6%), abdominal pain (9.1%), and diarrhea (9.1%). CONCLUSION: These data suggest that the OIS regimen is effective and relatively well tolerated in patients with advanced gastric cancer. Given that all the patients treated, but one, had a good performance status, these results must be confirmed in a patient population more representative of regular clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02527785.

Clinicopathologic Significance of VHL Gene Alteration in Clear-Cell Renal Cell Carcinoma: An Updated Meta-Analysis and Review.

The von Hippel-Lindau (VHL) gene is inactivated frequently in sporadic clear-cell renal cell carcinomas (ccRCCs) by genetic alteration (mutation, loss of heterozygosity, or promoter hypermethylation). However, the pathological or prognostic significance of VHL gene alteration has not been well defined. We conducted this meta-analysis to evaluate the association between VHL alteration and clinopathologic findings in ccRCCs. We performed a systematic computerized search of online databases, including PubMed, EMBASE, Web of Science, and Google Scholar (up to July 2018). From ten studies, 1,082 patients were included in the pooled analyses of odds ratios (ORs) with 95% confidence intervals (CIs) for pathological features (nuclear grade and disease stage) or hazard ratios (HRs) with 95% CIs for overall survival (OS). VHL alteration was not significantly associated with nuclear grade (OR = 0.79, 95% CI: 0.59⁻1.06, p = 0.12) or disease stage (OR = 1.07, 95% CI: 0.79⁻1.46, p = 0.65). There was also no significant correlation between VHL alteration and OS (HR = 0.75, 95% CI: 0.43⁻1.29, p = 0.30). When we pooled HRs for OS according to the VHL alteration types, the combined HRs were 0.72 (95% CI: 0.47⁻1.11, p = 0.14) for VHL mutations and 1.32 (95% CI: 0.70⁻2.47, p = 0.39) for methylation. In conclusion, this meta-analysis indicates that VHL gene alteration is not significantly associated with the pathological features and survival in patients with ccRCC.

Asynchronous Alterations of Muscle Force and Tendon Stiffness Following 8 Weeks of Resistance Exercise with Whole-Body Vibration in Older Women.

This study aimed to examine whether muscle force and tendon stiffness in a muscle-tendon complex alter synchronously following 8-week whole-body vibration (WBV) training in older people. Forty older women aged 65 years and older were randomly assigned into control (CON, n = 15) and whole-body vibration (WBV) training groups (exposure time, n = 13; vibration intensity, n = 12). For the training groups, a 4-week detraining period was completed following the training period. Throughout the training/detraining period, force of the medial gastrocnemius (MG) muscle and stiffness of the Achilles tendon were assessed four times (0, 4, 8, and 12 weeks) using a combined system of dynamometer and ultrasonography. While muscle force gradually increased throughout the training period (p < .05), a significant increase in tendon stiffness was observed after 8 weeks (p < .05). These findings indicated that, during the early phase of WBV training, muscle force and tendon stiffness changed asynchronously, which might be a factor in possible musculotendinous injuries.

Phase II study of docetaxel, oxaliplatin, and S-1 therapy in patients with metastatic gastric cancer.

BACKGROUND: Although the docetaxel, 5-fluorouracil, and cisplatin triplet has yielded significant improvements in time to progression, overall survival, and overall response rate, the high incidence of severe adverse events limits the use of the docetaxel, 5-fluorouracil, and cisplatin triplet. To overcome this limitation, we evaluated the efficacy and safety of the combination of docetaxel, oxaliplatin, and S-1 for the treatment of metastatic gastric cancer. METHODS: Chemotherapy-naive patients with pathologically proven unresectable recurrent or metastatic gastric adenocarcinoma were assessed for eligibility. Docetaxel at 52.5 mg/m(2) and oxaliplatin at 105 mg/m(2) were administered intravenously on day 1, and S-1 was administered orally at 80 mg/m(2) on days 1-14 of every 21-day cycle. RESULTS: Forty-four patients (median age 54.5 years) were enrolled. All patients had metastatic disease. A total of 340 cycles of chemotherapy were administered (median of eight cycles per patient; range 1-36 cycles). Toxicities were evaluated in 43 patients, and the responses were evaluated in 40 patients. Major toxicities included grade 3/4 neutropenia (37.2 %) and leukopenia (27.9 %). The overall response rate was 54.5 % [95 % confidence interval (CI) 40.1-68.3 %] in the intention-to-treat population. The median progression-free survival and overall survival were 7.6 months (95 % CI 6.2-9.0 months) and 12.0 months (95 % CI 6.9-17.2 months), respectively. CONCLUSION: These data suggest that the docetaxel, oxaliplatin, and S-1 combination regimen is effective and relatively well tolerable, and it seems to have potential to be a reasonable therapeutic strategy in patients with metastatic or recurrent gastric cancer.

Effect of nutritional status on survival outcome of diffuse large B-cell lymphoma patients treated with rituximab-CHOP.

The impact of pretreatment nutritional status on the treatment outcome of non-Hodgkin lymphoma has never been explored. Among the 953 patients who were registered in a prospective cohort at Samsung Medical Center., we analyzed 262 patients who had been treated with Ruximab-cyclophosphamide, doxorubicin, vincristine, and prednisone for newly diagnosed diffuse large B-cell lymphoma (DLBCL) and for whom data were available regarding pretreatment nutritional status. Nutritional status at diagnosis was assessed by triceps skin fold (TSF), mid-arm muscle circumference (MAMC), body mass index (BMI), serum albumin, prealbumin, and transferrin. For patients aged 60 yr and older, poor performance and higher tumor burden were associated with malnourishment represented by albumin <3.5 g/dL, prealbumin < 17 g/dL, and transferrin <170 mg/L. Lower BMI (<20), serum albumin, prealbumin, and transferrin were identified as risk factors for febrile neutropenia in univariate analysis, but not in multivariate analysis. In the univariate analysis for OS, all nutritional parameters except MAMC showed a significant association with survival. However, BMI was the only parameter that was independently prognostic for OS in the multivariate analysis (P = 0.031; hazards ratio = 3.32). Nutritional insufficiency encountered in DLBCL patients might influence the occurrence of treatment-related toxicity and poor survival outcome of patients.

The First Case of Adult Granular Acute Lymphoblastic Leukemia with DNMT3A Mutation and Monosomy 7.

Granular acute lymphoblastic leukemia (ALL) is defined by the presence of intracytoplasmic granules in lymphoblastic blasts, mimicking acute myeloblastic leukemia. The disease is extremely rare in adults, and hence, the characteristics thereof are poorly understood. We report a case of a 70-year-old man diagnosed with granular ALL. Bone marrow examination showed blasts with azurophilic granules in the cytoplasm, but immunophenotyping showed B-ALL with aberrant expression of myeloid antigens CD13 and CD33. Karyotyping revealed monosomy 7, and targeted NGS showed DNMT3A mutation, which suggested poor prognosis. Despite conventional chemotherapy treatment, the patient did not achieve complete remission. He declined further chemotherapy treatment and was maintained on only supportive care. This is the first report of adult granular ALL with DNMT3A mutation and monosomy 7.

Acute Promyelocytic Leukemia with a BCR-ABL1 Rearrangement in a Minor Clone.

Acute promyelocytic leukemia (APL) is a type of acute myeloid leukemia characterized by predominating abnormal promyelocytes with a PML-RARA rearrangement or a variant thereof. BCR-ABL1 rearrangement is an oncogenic event that is usually associated with chronic myeloid leukemia but also occurs in both acute lymphoblastic and acute myeloid leukemias and in healthy individuals. However, APL with concurrent PML-RARA and BCR-ABL1 rearrangements has rarely been reported. Herein, we describe a patient with APL exhibiting a BCR-ABL1 rearrangement in a minor clone and discuss the importance of evaluating this genetic alteration in terms of pathogenesis and treatment.

Incidence of FGFR2 Amplification and FGFR2 Fusion in Patients with Metastatic Cancer Using Clinical Sequencing.

Aberrations in the fibroblast growth factor receptor2 (FGFR2) gene, including genetic alterations and chromosomal rearrangements, lead to the development and progression of cancer with poor prognosis. However, the mechanisms underlying the FGFR2 signaling pathway to facilitate the development of FGFR2-targeted therapies have not been fully explored. Here, we examined the clinicopathological features of FGFR2 amplification and fusion in gastrointestinal tract/genitourinary tract cancers. FGFR2 amplification and fusion were identified in approximately 1.5% and 1.1% of all cancer types in 1,373 patients, respectively, with both FGFR2 amplification and fusion occurring together at a rate of approximately 0.6%. Of all cancer types screened, gastric cancer (GC) was the most common cancer type with FGFR2 amplification (87.5% of all FGFR2 amplification case) or fusion (46.7% of all cases). In addition, FGFR2 alteration had poorer overall survival (OS, 13.7 months vs. 50.2 months, P = 0.0001) and progression-free survival (PFS, 5.6 months vs. 11.4 months, P = 0.0005) than did those without FGFR2 alteration, respectively. Taken together, our data underscore to screen solid cancer patients for FGFR2 aberrations in oncology clinic.

A phase II study of chemotherapy in combination with telomerase peptide vaccine (GV1001) as second-line treatment in patients with metastatic colorectal cancer.

Background: GV1001 is a human telomerase peptide vaccine that induces a CD4/CD8 T-cell response against cancer cells, thereby affording an immunological anti-tumor effect. Here, we evaluated the efficacy and safety of GV1001 in combination with chemotherapy in patients with metastatic colorectal cancer who had failed first-line chemotherapy. Methods: This multicenter, non-randomized, single-arm phase II study recruited recurrent or metastatic colorectal cancer patients with measurable disease who had failed first-line chemotherapy. Patients received GV1001 and chemotherapy concomitantly based on a pre-established schedule. Cytotoxic chemotherapy and targeted agents (bevacizumab, cetuximab, or aflibercept) were allowed to be used at the discretion of the investigator. The primary endpoint was the disease control rate; secondary endpoints were the objective response rate, progression-free survival, overall survival, and safety outcomes. The baseline serum eotaxin level (a potential predictive biomarker of GV1001) was analyzed. To determine whether an adequate immune response had been induced, a delayed-type hypersensitivity test and a T-cell proliferation test were performed. Results: From May 13, 2015 to October 13, 2020, 56 patients with recurrent or metastatic colorectal cancer treated in seven hospitals of South Korea were enrolled. The median patient age was 64 years (range, 29-82 years); 67.9% were men. Of all patients, 66.1% had left-side colorectal cancer and the RAS mutation was present in 25%. The disease control rate and the objective response rates were 90.9% (95% confidence interval [CI]: 82.4-99.4%) and 34.1% (95% CI, 20.1-48.1%), respectively. The median progression-free survival was 7.1 months (95% CI, 5.2-9.1 months) and the median overall survival was 12.8 months (95% CI, 9.9-15.8 months). The most common all-grade adverse events were neutropenia (48.2%), nausea (26.8%), neuropathy (25.0%), stomatitis (21.4%), and diarrhea (21.4%). Immune response analysis showed that no patient had positive delayed-type hypersensitivity test results; antigen-specific T-cell proliferation was observed in only 28% of patients. The baseline eotaxin level was not associated with any efficacy outcome. Conclusion: Although no clear GV1001-specific immune response was observed, the addition of GV1001 vaccination to chemotherapy was tolerable and associated with modest efficacy outcomes.

High-dose ifosfamide as second- or third-line chemotherapy in refractory bone and soft tissue sarcoma patients.

INTRODUCTION: For patients with refractory bone and soft tissue sarcoma (STS), treatment options have been limited. Ifosfamide is an alkylating agent with well-demonstrated efficacy against STS, and dose-dependent activity. The aim of this retrospective study was to evaluate the response rate, progression-free survival (PFS), progression-free rate (PFR), and median duration of response to high-dose ifosfamide (HDI) as at least second-line chemotherapy for patients with advanced bone sarcoma and STS. PATIENTS AND METHODS: Thirty metastatic, unresectable sarcoma patients who were treated with HDI chemotherapy between May 1999 and November 2007 were included in the analysis. In total, 106 cycles (median 3 cycles; range 1-8 cycles) were administered. Twenty-one patients received treatment as second-line chemotherapy, and 9 patients as third-line treatment. HDI was given at a dose of 2 g/m(2) over 3 h, and at a dose of 2 g/m(2) per day; continuous infusion was administered on 6 consecutive days (2 g/m(2)/6 days) every 3 weeks. RESULTS: After a median follow-up of 49 months (range 10-114), median PFS was 2.9 months (range 0.4-9.3) and median overall survival 8.7 months (range 0.4-57.8). The 3- and 6-month PFR were 47% (SE 9.1%) and 20% (SE 7.3%), respectively. Median response duration of HDI was 2.9 months (range 0.7-7.6). Of the 28 evaluable patients, 2 (7%) achieved complete response, 5 (18%) partial response, and 4 (14%) stable disease, and overall disease control was 39%. Two responders out of 7 (28.5%) and 4 patients out of 11 (36%) with controlled disease by HDI had a synovial sarcoma. Two patients were not evaluable because they were switched to another treatment due to ifosfamide-induced encephalopathy. Grade 3-4 neutropenia was seen in 13 (43%) patients, and treatment-related death was observed in one patient. CONCLUSION: HDI at a total dose of 14 g/m(2) with mesna is still an active salvage regimen, particularly in patients with synovial sarcomas.

Primary CNS lymphoma other than DLBCL: a descriptive analysis of clinical features and treatment outcomes.

Diffuse large B-cell lymphoma (DLBCL) constitutes most primary central nervous system (CNS) lymphoma (PCNSL), whereas T-cell, low-grade and Burkitt's lymphomas (BL) are rarely encountered. Due to the paucity of cases, little is known about the clinical features and treatment outcomes of PCNSL other than DLBCL. The objective of this study was to describe the clinical characteristics and outcomes for patients with PCNSL other than DLBCL. Fifteen patients, newly diagnosed with PCNSLs other than DLBCL between 2000 and 2010, were included. The male to female ratio was 0.67:1 with a median age of diagnosis of 31 years (range 18-59). Pathologic distributions were as follows: peripheral T-cell lymphoma (PTCL; n=7), marginal zone B-cell lymphoma (MZBCL; n=1), lymphoplasmacytic lymphoma (LPL; n=2), Burkitt's lymphoma (n=1), other unspecified (T-cell lineage, n=2; B-cell lineage, n=2). Thirteen patients (87%) showed Eastern Cooperative Oncology Group performance score (ECOG PS) 1-2. The remaining two were one PTCL patient and one Burkitt's lymphoma patient. Of the nine patients with T-cell lymphoma, five (56%) had multifocal lesions, and one (20%) with LPL of the five patients with B-cell lymphoma showed a single lesion. Leptomeningeal lymphomatosis was identified in two patients (one with Burkitt's lymphoma and one with unspecified B-cell lymphoma). Two patients (22%) with T-cell lymphoma died 7.7 and 23.3 months later, respectively, due to disease progression, despite HD-MTX-based therapy. Six patients with T-cell lymphoma (6/9, 66.7%) and four patients with low-grade B-cell lymphoma (4/5, 80%) achieved complete response and have survived without relapse (Table 3). One patient with Burkitt's lymphoma showed poor clinical features with ECOG PS 3, deep structure, multifocal, and leptomeningeal lymphomatosis, and died 7.6 months after the initiation of treatment. In comparison with previously reported DLBCLs (median OS 6.4 years, 95% CI 3.7-9.1 years), T-cell lymphoma showed equivocal or favorable clinical outcomes and low-grade B-cell lymphomas, such as MZBCL and LPL, had a good prognosis. However, primary CNS Burkitt's lymphoma presented poor clinical outcomes and showed a comparatively aggressive clinical course. In conclusion, primary CNS lymphoma other than DLBCL occurred more in younger patients and showed a generally good prognosis, except for Burkitt's lymphoma. Further research on treatment strategies for Burkitt's lymphoma is needed.

Clinical insights into hematologic malignancies and comparative analysis of molecular signatures of acute myeloid leukemia in different ethnicities using an artificial intelligence offering.

ABSTRACT: Next generation sequencing generates copious amounts of genomics data, causing manual interpretation to be laborious and non-scalable while remaining subjective (even for highly trained specialists). We evaluated the performance of the artificial intelligence-based offering Watson for Genomics (WfG), a variant interpretation platform, in hematologic malignancies for the first time.Next generation sequencing was performed for patients treated for various hematological malignancies at Hallym University Sacred Heart Hospital, South Korea, between December 2017 and August 2020 using a 54-gene panel. Both WfG and expert manual curation were used to evaluate the performance of WfG. Acute myeloid leukemia (AML) molecular profiles were compared between Koreans and other ethnic groups using a publicly available dataset.Seventy-seven patients were analyzed (AML: 45, myeloproliferative neoplasms: 12, multiple myeloma: 7, myelodysplastic syndromes: 6, and others: 7). The concordance between the manual and WfG interpretations of 35 variants in 11 random patients was 94%. Among all patients, WfG identified 39 (51%) with at least 1 clinically actionable therapeutic alteration (i.e., a variant targeted by a United States Food and Drug Administration [US FDA]-approved drug, off-label drug, or clinical trial). Moreover, 46% of these patients (18/39) had genes that were targeted by a US FDA-approved therapy. WfG identified diagnostic or prognostic insights in 65% of the patients with no targetable alterations. In those with AML, FLT3-internal tandem duplications or tyrosine kinase domain mutations were less frequent among Koreans than among Caucasians (6.7% vs 30.2%, P < .001) or Hispanics (6.7% vs 28.3%, P = .005), suggesting ethnic differences.Variant interpretation using WfG correlated well with manually curated expert opinions. WfG provided therapeutic insights (including variant-specific drugs and clinical trials that cannot easily be provided by expert manual curation), as well as diagnostic and/or prognostic information.

Modeling the early temporal dynamics of viral load in respiratory tract specimens of COVID-19 patients in Incheon, the Republic of Korea.

OBJECTIVE: To investigate the duration and peak of severe acute respiratory syndrome coronavirus 2 shedding as infectivity markers for determining the isolation period. METHODS: A total of 2,558 upper respiratory tract (URT) and lower respiratory tract (LRT) specimens from 138 patients with laboratory-confirmed coronavirus disease were analyzed. Measurements of sequential viral loads were aggregated using the cubic spline smoothing function of a generalized additive model. The time to negative conversion was compared between symptom groups using survival analysis. RESULTS: In URT samples, viral RNA levels peaked on day 4 after symptom onset and rapidly decreased until day 10 for both E and RdRp genes, whereas those in LRT samples immediately peaked from symptom onset and decreased until days 15.6 and 15.0 for E and RdRp genes, respectively. Median (interquartile range) time to negative conversion was significantly longer in symptomatic (18.0 [13.0-25.0] days) patients than in asymptomatic (13.0 [9.5-17.5] days) patients. The more types of symptoms a patient had, the longer the time to negative conversion. CONCLUSIONS: The viral load rapidly changes depending on the time after symptom onset; the viral shedding period may be longer with more clinical symptoms. Different isolation policies should be applied depending on disease severity.

A phase II study of gemcitabine, erlotinib and S-1 in patients with advanced pancreatic cancer.

Background: We evaluated the efficacy and safety of gemcitabine in combination with erlotinib and S-1 for the treatment of advanced pancreatic cancer. Methods: Chemotherapy-naïve patients with pathologically-proven locally advanced, recurrent, or metastatic pancreatic adenocarcinoma were assessed for eligibility. Gemcitabine was administered at 1,000 mg/m2 intravenously on days 1 and 8, erlotinib was administered at 100 mg/day on days 1-21, and S-1 was administered at 60 mg/m2 on days 1-14 every 21 days and continued to a maximum of 8 cycles of treatment. Dose escalation of S-1 to 80 mg/m2 was permitted from the second cycle for pre-defined tolerable patients. Results: Thirty-seven patients (median age 61.5 years) were enrolled. A total of 140 cycles of chemotherapy were administered (median of 3.8; range 1-8 cycles). Toxicities were evaluated in 36 patients, and the responses were evaluated in 32 patients. Major grade 3/4 toxicities included neutropenia (25%), febrile neutropenia (2.8%), fatigue (22.2%), infection (8.3%), vomiting (5.6%), and mucositis (5.6%). The confirmed overall response rate was 12.5% [95% confidence interval (CI), 5.1-28.9%] and the disease control rate was 71.9% (95% CI, 56.8-86.3%). The median progression-free survival and overall survival were 3.7 months (95% CI, 2.8-4.6 months) and 6.7 months (95% CI, 3.4-9.9 months), respectively. Conclusion: The combination of gemcitabine, erlotinib, and S-1 provided an acceptable toxicity profile and modest clinical benefits in patients with advanced pancreatic cancer.

Evolving global and national criteria for identifying a suspected case of COVID-19.

BACKGROUND: The outbreak of coronavirus disease 2019 (COVID-19) began in December 2019 and continues to spread worldwide. Rapid and accurate identification of suspected cases is critical in slowing spread of the virus that causes the disease. We aimed to highlight discrepancies in the various criteria used by international agencies and highly impacted individual countries around the world. METHODS: We reviewed the criteria for identifying a suspected case of COVID-19 used by two international public health agencies and 10 countries across Asia, Europe, and North America. The criteria included information on the clinical causes of illness and epidemiological risk factors. Non-English language guidelines were translated into English by a co-author who is fluent in that particular language. RESULTS: Although most criteria are modifications of World Health Organization recommendations, the specific clinical features and epidemiological risks for triggering evaluation of patients with suspected COVID-19 differed widely among countries. The rationale for these differences may be related to each country's resources, politics, experience with previous outbreaks or pandemics, health insurance system, COVID-19 outbreak severity, and other undetermined factors. CONCLUSION: We found no consensus regarding the best diagnostic criteria for identifying a suspected case of COVID-19.

Novel genes exhibiting DNA methylation alterations in Korean patients with chronic lymphocytic leukaemia: a methyl-CpG-binding domain sequencing study.

Chronic lymphocytic leukaemia (CLL) exhibits differences between Asians and Caucasians in terms of incidence rate, age at onset, immunophenotype, and genetic profile. We performed genome-wide methylation profiling of CLL in an Asian cohort for the first time. Eight Korean patients without somatic immunoglobulin heavy chain gene hypermutations underwent methyl-CpG-binding domain sequencing (MBD-seq), as did five control subjects. Gene Ontology, pathway analysis, and network-based prioritization of differentially methylated genes were also performed. More regions were hypomethylated (2,062 windows) than were hypermethylated (777 windows). Promoters contained the highest proportion of differentially methylated regions (0.08%), while distal intergenic and intron regions contained the largest number of differentially methylated regions. Protein-coding genes were the most abundant, followed by long noncoding and short noncoding genes. The most significantly over-represented signalling pathways in the differentially methylated gene list included immune/cancer-related pathways and B-cell receptor signalling. Among the top 10 hub genes identified via network-based prioritization, four (UBC, GRB2, CREBBP, and GAB2) had no known relevance to CLL, while the other six (STAT3, PTPN6, SYK, STAT5B, XPO1, and ABL1) have previously been linked to CLL in Caucasians. As such, our analysis identified four novel candidate genes of potential significance to Asian patients with CLL.

Outcomes of decitabine treatment for newly diagnosed acute myeloid leukemia in older adults​.

PURPOSE: We evaluated the outcomes of decitabine as first-line treatment in older patients with acute myeloid leukemia (AML) and investigated the predictors, including a baseline mini nutritional assessment short form (MNA-SF) score, of response and survival. PATIENTS AND METHODS: Between 2010 and 2018, 96 AML patients aged 65 and above who received decitabine treatment at 6 centers in Korea were retrospectively evaluated. Response rates, hematologic improvements (HI), progression-free survival (PFS), and overall survival (OS) were analyzed. RESULTS: The median age at diagnosis was 73.9 years, and the median number of decitabine treatments administered to the patients was 4 (range, 1-29). Of 85 patients, 15 patients (17.6%) achieved complete remission (CR) or CR with incomplete blood count recovery. Twelve patients (14.1%) showed partial remission (PR), and 18 (21.2%) demonstrated HI without an objective response. The median PFS and OS were 7.0 (95% confidence interval [CI], 4.9-9.0) and 10.6 (95% CI, 7.7-13.5%) months, respectively. In multivariate analyses, MNA-SF score ≥ 8 and the absence of peripheral blood (PB) blasts were significant predictors for improved PFS and OS. CONCLUSIONS: For older patients with newly diagnosed AML, a high MNA-SF score and the absence of PB blasts were independently associated with improved survival.