Taeeun Kim

Pan-Asian adapted ESMO consensus guidelines for the management of patients with metastatic colorectal cancer: A JSMO-ESMO initiative endorsed by CSCO, KACO, MOS, SSO and TOS

The most recent version of the European Society for Medical Oncology (ESMO) consensus guidelines for the treatment of patients with metastatic colorectal cancer (mCRC) was published in 2016, identifying both a more strategic approach to the administration of the available systemic therapy choices, and a greater emphasis on the use of ablative techniques, including surgery. At the 2016 ESMO Asia Meeting, in December 2016, it was decided by both ESMO and the Japanese Society of Medical Oncology (JSMO) to convene a special guidelines meeting, endorsed by both ESMO and JSMO, immediately after the JSMO 2017 Annual Meeting. The aim was to adapt the ESMO consensus guidelines to take into account the ethnic differences relating to the toxicity as well as other aspects of certain systemic treatments in patients of Asian ethnicity. These guidelines represent the consensus opinions reached by experts in the treatment of patients with mCRC identified by the Presidents of the oncological societies of Japan (JSMO), China (Chinese Society of Clinical Oncology), Korea (Korean Association for Clinical Oncology), Malaysia (Malaysian Oncological Society), Singapore (Singapore Society of Oncology) and Taiwan (Taiwan Oncology Society). The voting was based on scientific evidence and was independent of both the current treatment practices and the drug availability and reimbursement situations in the individual participating Asian countries.

Subgroup analysis in RAISE: a randomized, double-blind phase III study of irinotecan, folinic acid, and 5-fluorouracil (FOLFIRI) plus ramucirumab or placebo in patients with metastatic colorectal carcinoma progression

The RAISE phase III trial demonstrated ramucirumab + FOLFIRI improved survival compared with placebo + FOLFIRI for second-line metastatic colorectal carcinoma patients previously treated with first-line bevacizumab, oxaliplatin, and a fluoropyrimidine. Analyses reported here found similar efficacy and safety in patients regardless of KRAS mutational status, time to first-line progression, and age.

500OCONCUR: A RANDOMIZED, PLACEBO-CONTROLLED PHASE 3 STUDY OF REGORAFENIB (REG) MONOTHERAPY IN ASIAN PATIENTS WITH PREVIOUSLY TREATED METASTATIC COLORECTAL CANCER (MCRC)

ABSTRACT Aim: Regorafenib, an oral multi-kinase inhibitor, improves overall survival (OS) in patients with mCRC who progressed after standard therapies. CONCUR (NCT01584830) was designed to evaluate the efficacy and safety of REG in Asian patients with mCRC. Methods: Patients with mCRC who progressed Results: Demographics and baseline characteristics were balanced in patients randomized to REG (n = 136) or placebo (n = 68). The median age was 57 yrs, all were ECOG PS 0–1, 53% had received >3 treatments for CRC, and 41% had no prior anti-VEGF or anti-EGFR therapy. Treatment with REG resulted in a 45% reduction in the risk of death (median OS 8.8 vs 6.3 months; one-sided p = 0.0002; Table), and improved PFS (HR 0.311; 95%CI 0.222–0.435; one-sided p Subgroups by prior targeted therapy N HR (95% CI) All patients 204 0.550 (0.395–0.765) No targeted therapy 84 0.359 (0.215–0.601) Anti-VEGF, or anti-EGFR, or both 120 0.747 (0.488–1.145) Anti-VEGF only 45 0.987 (0.482–2.025) Anti-EGFR only 39 0.719 (0.340–1.523) Both anti-VEGF and anti-EGFR 36 0.484 (0.217–1.081) Conclusions: Regorafenib provides a statistically significant improvement in OS in Asian patients with mCRC who progressed after standard therapies. Adverse events are consistent with the known safety profile of REG. Disclosure: T.W. Kim: Member of Pharma Advisory Boards for Merck and Abbvie. Received research funding from Bayer; T.C.C. Yau: Advisory Board member for Bayer; B. Ma: Advisory Board member for Bayer. Received research funding from Novartis, and Merck Serono; J. Shapiro: Employee of Sponsor (Bayer Pharma AG) J. Kalmus: Employee of Sponsor (Bayer Pharma AG); J. Li: Advisory Board member for Roche and Merck. Received research funding from Merck and Amgen. All other authors have declared no conflicts of interest.

Factors predicting life-threatening infections with respiratory syncytial virus in adult patients.

Abstract Background: Respiratory syncytial virus (RSV) is a significant cause of acute respiratory illness with a clinical spectrum ranging from self-limiting upper respiratory infection to severe lower respiratory infection in elderly persons as well as young children. However, there are limited data on risk factors for life-threatening infections that could guide the appropriate use of antiviral agents in adult patients with RSV. Methods: We conducted a retrospective cohort study from October 2013 to September 2015. Adult patients with RSV who visited the emergency department were enrolled. Primary outcome was life-threatening infection (admission to intensive care unit, need for ventilator care or in-hospital death). Results: A total of 227 patients were analysed. Thirty-four (15%) were classified as having life-threatening infections. By logistic regression, lower respiratory infection, chronic lung disease and bacterial co-infection were independent predictors of life-threatening infections. We developed a simple clinical scoring system using these variables (lower respiratory tract infection = score 4, chronic respiratory disease = score 3, bacterial co-infection = score 3 and fever ≥38 °C = score 2) to predict life-threatening infection. A score of >5 differentiated life-threatening RSV from non-life-threatening RSV with 82% sensitivity (95% CI, 66–93) and 72% specificity (95% CI, 65–78). Conclusions: The use of a clinical scoring system based on lower respiratory infection, chronic respiratory disease, bacterial co-infection and fever appears to be useful for outcome prediction and risk stratification in order to select patients who may need early antiviral therapy.

Diagnostic performance of the (1–3)-β-D-glucan assay in patients with Pneumocystis jirovecii compared with those with candidiasis, aspergillosis, mucormycosis, and tuberculosis, and healthy volunteers

Background Diagnosis of pneumocystis pneumonia (PCP) relies on microscopic visualization of P. jirovecii, or detection of Pneumocystis DNA in respiratory specimens, which involves invasive procedures such as bronchoalveolar lavage. The (1–3)-β-D-glucan (BG) assay has been proposed as a less invasive and less expensive diagnostic test to rule out PCP. We therefore compared blood levels of BG in patients with PCP with those of patients with candidemia, chronic disseminated candidiasis (CDC), invasive aspergillosis, mucormycosis, and tuberculosis and those of healthy volunteers. Methods Adult patients who were diagnosed with PCP, candidemia, CDC, invasive aspergillosis, mucormycosis, and tuberculosis whose blood samples were available, and healthy volunteers were enrolled in a tertiary hospital in Seoul, South Korea, during a 21-month period. The blood samples were assayed with the Goldstream Fungus (1–3)-β-D-glucan test (Gold Mountain River Tech Development, Beijing, China). Results A total of 136 individuals including 50 patients P. jirovecii,15 candidemia, 6 CDC, 15 invasive aspergillosis, 10 mucormycosis, and 40 controls (20 TB and 20 healthy volunteers) were included. The mean±SD of the concentration of 1–3-β-D-glucan in the patients with PCP (290.08 pg/mL±199.98) were similar to those of patients with candidemia (314.14 pg/mL±205.60, p = 0.90 at an α = 0.005) and CDC (129.74 pg/mL±182.79, p = 0.03 at an α = 0.005), but higher than those of patients with invasive aspergillosis (131.62 pg/mL±161.67, p = 0.002 at an α = 0.005), mucormycosis (95.08 pg/mL±146.80, p<0.001 at an α = 0.005), and tuberculosis (103.31 pg/mL±140.81, p<0.001 at an α = 0.005) as well as healthy volunteers (101.18 pg/mL±197.52, p<0.001 at an α = 0.005). At a cut-off value > 31.25 pg/mL, which is highly sensitive for PCP versus tuberculosis plus healthy volunteers at the expense of specificity, the BG assay had a sensitivity of 92% (95% CI 81%-98%) and a specificity of 55% (95% CI 39%-71%). Conclusions The BG assay appears to be a useful adjunct test for PCP.

Comparison of the Commercial QuantiFERON-CMV and Overlapping Peptide-based ELISPOT Assays for Predicting CMV Infection in Kidney Transplant Recipients

Cytomegalovirus (CMV) is one of the most important opportunistic infections in transplant recipients. Tests for CMV-specific T cell responses have been proposed to change the current risk stratification strategy using CMV assays. We evaluated the usefulness of pre-transplant CMV-specific T cell assays in kidney transplant (KT) candidates for predicting the development of CMV infection after transplantation comparing the results of the overlapping peptides (OLPs)-based enzyme-linked immunospot (ELISPOT) assay and the commercial QuantiFERON-CMV assay. We prospectively enrolled all cases of KT over a 5-month period, except donor CMV-seropositive and recipient seronegative transplants that are at highest risk of CMV infection. All the patients underwent QuantiFERON-CMV, CMV OLPs-based pp65, and immediate-early 1 (IE-1)-specific ELISPOT assays before transplantation. The primary outcome was the incidence of CMV infection at 6 months after transplant. The total of 47 KT recipients consisted of 45 living-donor KTs and 2 deceased-donor KTs. There was no association between positive QuantiFERON-CMV results and CMV infection. However, 10 of 34 patients with phosphoprotein 65 (pp65)- or IE-1-specific ELISPOT results higher than cut-off value developed CMV infections compared with none of 13 patients with results lower than cut-off value developed CMV. The OLPs-based ELISPOT assays are more useful than the QuantiFERON-CMV assay for predicting CMV infection. Patients with higher CMV-specific T cell immunity at baseline appear to be more likely to develop CMV infections after KT, suggesting that the abrupt decline in CMV-specific T cell responses after immunosuppression, or high CMV-specific T cell responses due to frequent CMV activation before KT, may promote CMV infection.

Clinical Features and Outcomes of Spontaneous Bacterial Peritonitis Caused by Streptococcus pneumoniae: A Matched Case-Control Study.

AbstractStreptococcus pneumoniae is a well-known cause of spontaneous bacterial peritonitis (SBP) in cirrhotic patients. However, little information is available regarding clinical characteristics and outcomes of SBP caused by S. pneumoniae. It has been suggested that spontaneous pneumococcal peritonitis (SPP) often spreads hematogenously from concomitant pneumococcal pneumonia, and is associated with a higher rate of mortality.During the period between January 1997 and December 2013, 50 SPP cases were identified. These cases were then age/sex-matched with 100 patients with SBP due to causes other than S. pneumoniae (controls).SPP accounted for 4.3% (50/1172) of all culture-proven SBPs. The baseline Child-Pugh class, etiology of cirrhosis, and model for end-stage liver disease scores were comparable for the 2 groups. SPP patients were more likely than control patients to have a community-acquired infection (90.0% vs. 76.0%; P = 0.04), concurrent bacteremia (84.0% vs. 59.0%; P = 0.002), and to present with variceal bleeding (10.0% vs. 1.0%; P = 0.02). None of the study patients had pneumococcal pneumonia. The most common initial empirical therapy for both groups was third-generation cephalosporins (96.0% vs. 91.0%; P = 0.34) which was active against a significantly higher proportion of the cases than of the controls (97.8% vs. 78.7%; P = 0.003). Thirty-day mortality was significantly lower in the case group than in the control group (10.0% vs. 24.0%; P = 0.04).SPP was not associated with pneumococcal pneumonia and showed lower mortality than SBP caused by other organisms. However, the present study was constrained by the natural limitations characteristic of a small, retrospective study. Therefore, large-scale, well-controlled studies are required to demonstrate the influence of SPP on mortality, which was marginal in the present study.

Sensitivity of the Cytomegalovirus Antigenemia Assay to Diagnose Cytomegalovirus Retinitis

Background Cytomegalovirus (CMV) retinitis is one of the most important tissue-invasive CMV diseases in immunocompromised patients. Since 1980, non-invasive diagnostic methods, notably the CMV antigenemia assay, have been widely used as adjunct tests to diagnose tissue-invasive CMV diseases. However, there are limited data on the diagnostic value of the CMV antigenemia assay for diagnosing CMV retinitis. Materials and Methods We performed a retrospective review of all cases of CMV retinitis at Asan Medical Center, Seoul, South Korea over a 9-year period. The diagnosis of CMV retinitis was made by experienced ophthalmologists according to medical history and an ophthalmoscopic appearance of typical retinopathy, together with absence of an alternative diagnosis. Results We analyzed 44 patients with CMV retinitis (affecting 57 eyes) for whom the CMV antigenemia assay was performed. Of the 44 patients, 31 (70%) were HIV-uninfected and 13 (30%) were HIV-infected. The overall sensitivity of the CMV antigenemia assay was 66% (95% confidence interval [CI] 50–80%). The test’s sensitivity showed a non-significant trend towards being higher in HIV-infected patients than in HIV-uninfected patients (sensitivity 85% vs 58%, respectively, P = 0.16). In a subgroup analysis of the 35 patients without other concurrent tissue-invasive CMV disease, the sensitivity of the CMV antigenemia assay was 57% (95% CI 40–74%). Conclusions The CMV antigenemia assay has limited value as a non-invasive diagnostic adjunct test for CMV retinitis. Therefore, the results of the assay need to be interpreted in the context of underlying disease, clinical presentation, and ophthalmoscopic findings.

Multidisciplinary approach for treatment of primary hepatic choriocarcinoma in adult male patient

Choriocarcinoma is a rare malignant germ cell tumor and it usually occurs in the gonads (ovary or testis) and uterus. Primary hepatic choriocarcinoma (PHC) is a variant of choriocarcinoma featuring sole liver presentation without any evidence of gonodal involvements. Adult male patients with PHC carry dismal prognosis and their median survival period was less than 5 months. We herein present a first Korean case of a 54-year-old male patient with adult PHC, who was treated by surgical resection and chemotherapy through a multidisciplinary approach.