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Background The efficacy of modified FOLFIRINOX (mFOLFIRINOX) as a second-line chemotherapy treatment for metastatic pancreatic adenocarcinoma (mPAC), remains unclear. This multi-center randomised phase III trial aimed to elucidate the efficacy of mFOLFIRINOX as a second-line chemotherapy treatment for mPAC patients with good performance status. Patients and methods Eighty mPAC patients (age, 19–75 years) refractory to first-line gemcitabine-based chemotherapy were randomly selected to receive mFOLFIRINOX or S-1. mFOLFIRINOX comprised oxaliplatin (65 mg/m2), irinotecan (135 mg/m2), and leucovorin (400 mg/m2) on day 1 and continuous 5-FU infusion (1000 mg/m2) over 24 h on days 1–2 every 2 weeks. S-1 comprised body surface area-dependent oral S-1, divided into two doses per day on days 1–28 every 6 weeks. Results Overall survival was the primary endpoint. The objective response and disease control rates were higher in the mFOLFIRINOX than in the S-1 group (15% versus 2%; p = .04 and 67% versus 37%; p = .007). The median progression-free survival rates were 5.2 and 2.2 months in the mFOLFIRINOX and S-1 groups, respectively (adjusted hazard ratio [HR]: .4; 95% confidence interval [CI]: .2-.6; p Conclusion Administration of mFOLFIRINOX as a second-line chemotherapy treatment for mPAC patients refractory to gemcitabine-based chemotherapy resulted in increased survival rates than S-1 treatment alone.

The standard of treatment for completely resected limited-stage diffuse large B cell lymphoma (DLBCL) in patients without residual lesions has not yet been established. Previously, we designed a phase II trial to evaluate the safety and efficacy of three cycles of abbreviated R-CHOP in patients with completely resected limited-stage DLBCL and reported favorable survival outcomes. We present the long-term follow-up results to taking into account the importance of delayed relapse in patients with limited-stage DLBCL. With a median follow-up duration of 62.7 months (range, 60.2–75.5 months), the 5-year OS and DFS rates were both 95.0% (95% confidence interval, 85.59–104.11%). Only one patient experienced disease progression which was confirmed at 12.3 months, and one patient with primary intestinal DLBCL developed non-small cell lung cancer 6 years after treatment. The long-term results of our data support the use of three cycles of abbreviated R-CHOP for patients with completely resected limited-stage DLBCL. The study was reviewed and approved by the review boards of the participating institutes and registered at ClinicalTrials.gov , number NCT01279902, in August 3, 2010.

Background/Aims: The multidisciplinary team (MDT) approach is a cornerstone of clinical oncology. This study investigated the current state of MDT care, in cluding patient satisfaction, in Korea. Methods: We obtained the annual number of cancer patients who have received MDT care since 2014 from the registry of the Health Insurance Review and As sessment Service (HIRA). In addition, patients who received MDT care from Au gust 2014 to May 2017 at four university hospitals were further characterized, and patient satisfaction was measured prospectively using a patient-reported ques tionnaire. Results: The total number of patients who received MDT care increased from 2014 to 2016 (2,113 to 9,998 patients, respectively) in the HIRA Cohort. The type of cancer that most often required MDT was breast cancer (23.8%), followed by col orectal cancer (19.1%). In the Representative Cohort (n = 1,032), MDT was request ed by the surgeon more than half the time (55.7%). The main focus of MDT was decision making for further treatment planning (99.0%). The number of doctors participating in the MDT was usually five (70.0%). After initiating an MDT ap proach, the treatment plan changed for 17.4% of patients. Among these patients, 359 completed a prospective satisfaction survey regarding their MDT care. The overall satisfaction with the MDT approach was very high, with an average score of 9.6 out of 10 points. Conclusions: The application of MDT care is a rapidly growing trend in clini cal oncology, and shows high patient satisfaction. Further research is needed to determine which types of cancer patients could benefit most from MDT, and to enable MDT care to operate more efficiently so that it may expand successfully throughout Korea.

Background Systemic inflammatory response can be associated with the prognosis of diffuse large B cell lymphoma (DLBCL). We investigated the systemic factors significantly related to clinical outcome in relapsed/refractory DLBCL. Methods In 242 patients with DLBCL, several factors, including inflammatory markers were analyzed. We assessed for the correlation between the survivals [progression-free survival (PFS) and overall survival (OS)] and prognostic factors. Results In these patients, a high derived neutrophil/lymphocyte ratio (dNLR) (PFS, HR=2.452, P=0.002; OS, HR=2.542, P=0.005), high Glasgow Prognostic Score (GPS) (PFS, HR=2.435, P=0.002; OS, HR=2.621, P=0.002), and high NCCN-IPI (PFS, HR=2.836, P=0.003; OS, HR=2.928, P=0.003) were significantly associated with survival in multivariate analysis. Moreover, we proposed a risk stratification model based on dNLR, GPS, and NCCN-IPI, thereby distributing patients into 4 risk groups. There were significant differences in survival among the 4 risk groups (PFS, P

Erythropoiesis-stimulating agents (ESAs), such as erythropoietin (EPO) and darbepoetin, may alleviate anemia in diffuse large B-cell lymphoma (DLBCL) patients. However, many cancer cells express EPO receptors (EPOR), through which exogenously administered ESAs potentially promote cancer cell growth. We conducted preclinical/phase II studies to investigate the safety and efficacy of ESAs for managing chemotherapy-related anemia in DLBCL patients. We examined EPOR expression in germinal center B-cell (GCB)- and activated B-cell (ABC)-DLBCL cell lines, and investigated the effects of ESAs on cell proliferation, and rituximab-mediated complement-dependent cytotoxicity (CDC). The clinical study enrolled 50 histologically confirmed DLBCL patients receiving rituximab/cyclophosphamide/doxorubicin/vincristine/prednisolone (R-CHOP) who had hemoglobin levels

Purpose Primary effusion lymphoma (PEL) is a type of body cavity-based lymphoma (BCBL). Most patients with PEL are severely immunocompromised and seropositive for human immunodeficiency virus (HIV). We investigated the distinctive clinicopathologic characteristics of BCBL in a country with low HIV burden. Materials and methods We retrospectively collected data on the clinicopathologic characteristics, treatments, and outcomes of 17 consecutive patients with BCBL at nine institutions in Korea. Results Latency-associated nuclear antigen 1 (LANA1) immunostaining indicated that six patients had PEL, six patients had human herpesvirus 8 (HHV8)-unrelated BCBL, and five patients had HHV8-unknown BCBL. The patients with PEL exhibited no evidence of immunodeficiency except for one who was HIV positive. One (20%) and four (80%) patients with PEL and six (100%) and zero (0%) patients with HHV8-unrelated BCBL were positive for CD20 and CD30 expression, respectively. The two patients with PEL (one HIV-positive and one HIV-negative patient) with the lowest proliferation activity as assessed by the Ki-67 labeling index survived for > 1 and > 4 years without chemotherapy, respectively, in contrast to the PEL cases in the literature, which mostly showed a high proliferation index and poor survival. Conclusion PEL mostly occurred in ostensibly immunocompetent individuals and had a favorable outcome in Korea. A watchful waiting approach may be applicable for managing HIV-seronegative patients with PEL with a low Ki-67 labeling index. A possible trend was detected among LANA1, CD20, and CD30 expression in BCBL.

The VIKTORY (targeted agent eValuation In gastric cancer basket KORea) trial was designed to classify patients with metastatic gastric cancer based on clinical sequencing and focused on eight different biomarker groups (RAS aberration, TP53 mutation, PIK3CA mutation/amplification, MET amplification, MET overexpression, all negative, TSC2 deficient, or RICTOR amplification) to assign patients to one of the 10 associated clinical trials in second-line (2L) treatment. Capivasertib (AKT inhibitor), savolitinib (MET inhibitor), selumetinib (MEK inhibitor), adavosertib (WEE1 inhibitor), and vistusertib (TORC inhibitor) were tested with or without chemotherapy. Seven hundred seventy-two patients with gastric cancer were enrolled, and sequencing was successfully achieved in 715 patients (92.6%). When molecular screening was linked to seamless immediate access to parallel matched trials, 14.7% of patients received biomarker-assigned drug treatment. The biomarker-assigned treatment cohort had encouraging response rates and survival when compared with conventional 2L chemotherapy. Circulating tumor (ctDNA) analysis demonstrated good correlation between high MET copy number by ctDNA and response to savolitinib. Significance: Prospective clinical sequencing revealed that baseline heterogeneity between tumor samples from different patients affected response to biomarker-selected therapies. VIKTORY is the first and largest platform study in gastric cancer and supports both the feasibility of tumor profiling and its clinical utility. This article is highlighted in the In This Issue feature, p. 1325

Background: Although biliary tract cancer (BTC) has a very aggressive nature, some patients maintain a relatively good performance status after failure with first-line treatment of gemcitabine plus cisplatin (GC). Thus, tolerable, feasible, and useful second-line treatments are needed for these patients. We investigated the efficacy of capecitabine plus oxaliplatin (XELOX) as a second-line therapy for patients with advanced BTC who failed first-line GC treatment. Methods: In this prospective, phase II trial, we investigated XELOX (capecitabine 1,000 mg/m2 twice daily on days 1-14 and oxaliplatin 130 mg/m2 on day 1) as a second-line treatment, given every 3 weeks, totaling 8 cycles in patients with metastatic BTC who failed first-line GC treatment. The primary outcome was progression-free survival (PFS). Results: From December 2015 to November 2016, 50 patients with metastatic intrahepatic or extrahepatic cholangiocarcinoma or gall bladder (GB) cancer were enrolled. The regimen was well tolerated. Toxicities mainly consisted of grade 1 or 2 events, and thrombocytopenia and neuropathy had the highest incidence. In intent-to-treat analysis, one complete response (CR) and six partial responses (PRs) were recorded with XELOX treatment. The overall response rate and the disease control rate from the intent-to-treat analysis were 14% and 52%, respectively. With a median follow-up of 15.6 months, PFS after XELOX was a median of 15.4 weeks (95% CI, 8.5-22.3). This PFS value supported the statistical hypothesis of this study. The median overall survival was 32.7 weeks (95% CI, 21.4-43.9). Conclusion: This phase II trial showed that XELOX treatment was efficacious and had a tolerable toxicity profile in patients with advanced BTC who failed first-line treatment of gemcitabine and cisplatin.

Cutaneous T-cell lymphomas (CTCLs) are a group of T-cell lymphomas with low incidence. Due to their indolent characteristics, treatment strategies have not yet been established for advanced CTCLs. In this study, relative incidence of CTCLs in Asia was estimated and the therapeutic outcomes presented based on various treatments currently used in clinics for advanced CTCLs. As part of a prospective registry study of peripheral T-cell lymphoma (PTCL) conducted across Asia, including Korea, China, Taiwan, Singapore, Malaysia, and Indonesia, subgroup analysis was performed for patients with CTCLs. Among 486 patients with PTCL, 37 with CTCL (7.6%) were identified between April 2016 and February 2019. Primary cutaneous ALK-negative anaplastic large cell lymphoma (ALCL, 35.1%) was the most common subtype. With a median follow-up period of 32.1 months, median progression-free survival (PFS) was 53.5 months (95% CI 0.0–122.5), and overall survival was not reached. 14 patients (48.2%) underwent subsequent treatment after the first relapse, but the response rate was 20% with a PFS of 2.2 months (95% CI 0.3–4.0). Six patients received autologous stem cell transplantation (auto-SCT). However, auto-SCT did not result in better outcomes. Additional studies are needed on standard care treatment of advanced or refractory and relapsed CTCLs.

ObjectivesTo investigate the associations between heavy metal exposure and serum ferritin levels, physical measurements and type 2 diabetes mellitus (DM).DesignA retrospective cohort study.SettingChangwon, the location of this study, is a Korean representative industrial city. Data were obtained from medical check-ups between 2002 and 2018.ParticipantsA total of 34 814 male subjects were included. Of them, 1035 subjects with lead exposure, 200 subjects with cadmium exposure and the 33 579 remaining were assigned to cohort A, cohort B and the control cohort, respectively. Data including personal history of alcohol and smoking, age, height, weight, the follow-up duration, haemoglobin A1c (HbA1c), fasting blood sugar (FBS), ferritin levels, and lead and cadmium levels within 1 year after exposure were collected.Primary outcome measureIn subjects without diabetes, changes in FBS and HbA1c were analysed through repeated tests at intervals of 1 year or longer after the occupational exposure to heavy metals.ResultsIn Cohort A, DM was diagnosed in 33 subjects. There was a significant difference in lead concentrations between the subjects diagnosed with DM and those without DM during the follow-up period (3.94±2.92 mg/dL vs 2.81±2.03 mg/dL, p=0.002). Simple exposure to heavy metals (lead and cadmium) was not associated with DM in Cox regression models (lead exposure (HR) 1.01, 95% CI: 0.58 to 1.77, p 0.971; cadmium exposure HR 1.48, 95% CI: 0.61 to 3.55, p=0.385). Annual changes in FBS according to lead concentration at the beginning of exposure showed a positive correlation (r=0.072, p=0.032).ConclusionOur findings demonstrated that simple occupational exposure to heavy metals lead and cadmium was not associated with the incidence of DM. However, lead concentrations at the beginning of the exposure might be an indicator of DM and glucose elevations.

Background Gastric cancer (GC) is a heterogenous disease consisted of several subtypes with distinct molecular traits. The clinical implication of molecular classification has been limited especially in association with treatment efficacy of ramucirumab or various targeted agents. Methods We conducted a prospective non-randomized phase II single-arm trial of ramucirumab plus paclitaxel as second-line chemotherapy in 62 patients with metastatic GC who failed to respond to first-line fluoropyrimidine plus platinum treatment. For integrative molecular characterization, all patients underwent pre-ramucirumab treatment tissue biopsy for whole-exome/whole-transcriptome sequencing to categorize patients based on molecular subtypes. We also systematically performed integrative analysis, combining genomic, transcriptomic, and clinical features, to identify potential molecular predictors of sensitivity and resistance to ramucirumab treatment. Results Sixty-two patients were enrolled in this study between May 2016 and October 2017. Survival follow-up in all patients was completed as of the date of cut-off on January 2, 2019. No patient attained complete response (CR), while 22 patients achieved confirmed partial response (PR), resulting in a response rate (RR) of 35.5% (95% CI, 23.6–47.4). According to TCGA molecular classification, there were 30 GS, 18 CIN, 3 EBV, and 0 MSI tumors. The RR was 33% in GS (10/30), 33% in CIN (6/18), and 100% in EBV-positive GC patients with significant statistical difference for EBV(+) against EBV(−) tumors (P = 0.016; chi-squared test). Moreover, responsive patients were marked by activation of angiogenesis, VEGF, and TCR-associated pathways, while non-responder patients demonstrated enrichments of sonic hedgehog signaling pathway and metabolism activity. Integrative multi-layer data analysis further identified molecular determinants, including EBV status, and somatic mutation in GNAQ to ramucirumab activity. Conclusions Prospective molecular characterization identified a subset of GC patients with distinct clinical response to ramucirumab therapy, and our results demonstrate the feasibility of personalized therapeutic opportunities in gastric cancer. Trial registration The study was registered on ClinicalTrial.gov (NCT02628951) on June 12, 2015.

Background We investigated whether distancemax, that is, the degree of distance between the upper aerodigestive tract (UAT) mass and the farthest pathologic lymph node, was significantly associated with survival in patients with limited-stage UAT natural killer/T cell lymphoma (NKTCL). Methods A total of 157 patients who received chemotherapy (CTx) with/without radiotherapy (RTx) were enrolled. Results In the survival analysis, an elevated lactate dehydrogenase level [progression-free survival (PFS): hazard ratio (HR), 2.948; 95% confidence interval (CI), 1.606‒5.404; P

Background: Peripheral T-cell lymphomas (PTCLs) are uncommon and their incidence is regionally heterogeneous. Several studies have been conducted to evaluate the clinical features and treatment outcomes of this disease entity, but the majority of these were conducted in limited areas, making it difficult to comprehensively analyze their relative incidence and clinical features. Furthermore, no consensus treatment for PTCLs has been established. Therefore, we conducted an Asia-specific study to understand the relative incidence of PTCLs and assess treatments and their outcomes in Asian patients. Methods: We performed a multinational, multicenter, prospective registry of adult patients with PTCLs that was named as the International Cooperative non-Hodgkin T-cell lymphoma prospective registry study where thirty-two institutes from six Asian countries and territories (Korea, China, Taiwan, Singapore, Malaysia, and Indonesia) participated. Findings: A total of 486 patients were registered between April 2016 and February 2019, and more than a half of patients (57.4%) had stage III or IV. Extranodal natural killer (NK)/T- cell lymphoma was the most common subtype (n=139, 28.6%), followed by angioimmunoblastic T-cell lymphoma (AITL, n=120, 24.7%), PTCL-not otherwise specified (PTCL-NOS, n=101, 20.8%), ALK-positive anaplastic large cell lymphoma (ALCL, n=34, 6.9%), and ALK-negative ALCL (n=30, 6.2%) in decreasing order of frequency. The median progression-free survival (PFS) and overall survival (OS) were 21.1 months (95% CI,10.6–31.6) and 83.6 months (95% CI, 56.7–110.5), respectively. Upfront use of combined treatment with chemotherapy and radiotherapy showed better PFS than chemotherapy alone in localized ENKTL whereas consolidation with upfront autologous stem cell transplantation (SCT) provided longer PFS in advance stage ENKTL. In patients with PTCLs other than ENKTL, anthracycline-containing chemotherapies were widely used, but the outcome of those regimens was not satisfactory, and upfront autologous SCT was not significantly associated with survival benefit, either. The treatment outcome of salvage chemotherapy was disappointing, and none of the salvage strategies showed superiority to any other. Interpretation: This multinational, multicenter study identified the relative incidence of each subtype of PTCLs across Asian countries, and the survival outcomes according to the therapeutic strategies currently in use. Funding Statement: This study was supported by a grant from the Samsung Biomedical Research Institute (GFO1150161). Declaration of Interests: We declare no competing interests. Ethics Approval Statement: This registry was approved by the Institutional Review Boards or Scientific Review Committees as required by the policies of individual institutions. Written informed consent was obtained from each patient before study enrollment.

Background Hodgkin's lymphoma (HL) constitutes 10%–20% of all malignant lymphomas and has a high cure rate (5-year survival, around 90%). Recently, interest has increased concerning preventing secondary complications (secondary cancer, endocrine disorders) in long-term survivors. We aimed to study the epidemiologic features and therapeutic outcomes of HL in children, adolescents, and young adults in Korea. Methods We performed a multicenter, retrospective study of 224 patients aged < 25 years diagnosed with HL at 22 participating institutes in Korea from January 2007 to August 2016. Results A higher percentage of males was diagnosed at a younger age. Nodular sclerosis histopathological HL subtype was most common, followed by mixed cellularity subtype. Eighty-one (36.2%), 101 (45.1%), and 42 (18.8%) patients were classified into low, intermediate, and high-risk groups, respectively. Doxorubicin, bleomycin, vinblastine, dacarbazine was the most common protocol (n = 102, 45.5%). Event-free survival rate was 86.0% ± 2.4%, while five-year overall survival (OS) rate was 96.1% ± 1.4%: 98.7% ± 1.3%, 97.7% ± 1.6%, and 86.5% ± 5.6% in the low, intermediate, and high-risk groups, respectively (P = 0.021). Five-year OS was worse in patients with B-symptoms, stage IV disease, high-risk, splenic involvement, extra-nodal lymphoma, and elevated lactate dehydrogenase level. In multivariate analysis, B-symptoms and extra-nodal involvement were prognostic factors for poor OS. Late complications of endocrine disorders and secondary malignancy were observed in 17 and 6 patients, respectively. Conclusion This is the first study on the epidemiology and treatment outcomes of HL in children, adolescents, and young adults in Korea. Future prospective studies are indicated to develop therapies that minimize treatment toxicity while maximizing cure rates in children, adolescents, and young adults with HL., Graphical Abstract

The mucosa-associated lymphoid tissue (MALT) International Prognostic Index (IPI) was recently proposed as a prognostic index for patients with MALT lymphoma. We aimed to investigate the prognostic value of the serum β2-microglobulin level in the context of MALT-IPI, and we proposed a new prognostic index. Survival outcomes were analysed with regard to β2-microglobulin level, MALT-IPI, and the new prognostic index in MALT lymphoma patients (n = 571). The validity of the new prognostic index was assessed using an independent cohort (n = 216). Patients with high β2-microglobulin levels had significantly worse progression-free survival (PFS) and overall survival (OS) outcomes. A high β2-microglobulin level was independently associated with poor PFS and OS. β2-microglobulin levels further stratified patients in the MALT-IPI intermediate-risk group in terms of PFS and OS. A new prognostic index based on the MALT-IPI and the β2-microglobulin level, MALT-IPI-B, was proposed. The MALT-IPI-B was able to stratify patients into subgroups having distinct PFS and OS outcomes in both the training and validation cohorts. MALT-IPI-B enabled the identification of patients with poor survival outcomes who were classified into the intermediate-risk group by the MALT-IPI. In conclusion, this new β2-microglobulin-based prognostic index may have the specific advantage of identifying high-risk patients who may require systemic treatment.

There are still controversies about the use of interim positron emission tomography/computed tomography (PET/CT) in indolent non-Hodgkin lymphoma due to the variable fluorodeoxyglucose (FDG) avidity. Therefore, this study aimed to evaluate the roles of interim PET/CT in marginal zone lymphoma (MZL), a representative indolent lymphoma. We analyzed the data of 146 MZL patients. All were treated with rituximab-containing immunochemotherapy. Interim PET/CT scan was performed after 2–3 cycles of therapy, and the response was assessed using the Deauville 5-point scales (5-PS) and a semi-quantitative assessment using the SUVmax reduction rate (ΔSUVmax). Progression-free survival (PFS) was well stratified according to a visual assessment of interim PET/CT using 5-PS (p p = 0.031). The interim PET/CT response based on the 5-PS is useful for predicting PFS of patients with MZL in the post-rituximab era.

Background/Aims: Febrile neutropenia (FN) interferes with the proper chemotherapy dose density or intensity in non-Hodgkin’s lymphoma (NHL) patients. Chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) ± rituximab has an intermediate FN risk. Prophylactic granulocyte colony-stimulating factor (G-CSF) support is recommended for patients with other host-related risk factors.Methods: We evaluated the risk factors for FN-related admission in NHL patients who have received primary G-CSF (lenograstim) prophylaxis.Results: Data from 148 patients were analyzed. The incidence of neutropenic fever was 96 events (12.2%), and the median period was 3.85 days (range, 0 to 5.9); the median duration of neutropenia was 4.21 days (range, 3.3 to 5.07). Eighty-three FN-related admissions were reported. Advanced age (> 60 years), female sex, a low albumin level, and prednisone use were associated with FN-related admission in multivariable analysis (p = 0.010, p < 0.001, and p = 0.010, respectively). A comparison between diffuse large B-cell lymphoma patients treated with R-CHOP and pegylated G-CSF and those treated with R-CHOP and lenograstim did not reveal significant differences in the FN-related admission rate between the two groups, although the lenograstim-treated group had a higher incidence of severe neutropenia.Conclusions: Elderly patients, female patients, and patients with low albumin levels need to be actively followed-up for FN even when primary prophylaxis with G-CSF has been used.

Purpose Although chemotherapy is recommended by various guidelines for advanced biliary tract cancer (BTC), the evidence supporting its use over best supportive care (BSC) is limited. The aim of this study was to investigate the survival benefit of chemotherapy over that of BSC in advanced BTC patients. Materials and Methods Advanced BTC patientswith a good performance status (Eastern CooperativeOncologyGroup [ECOG] 0-2) were eligible for the study. Data were retrospectively collected from four tertiary cancer centers and analyzed using propensity score matching (PSM). Of the 604 patients enrolled, 206 received BSC and 398 received chemotherapy. PSM analysis was performed using the following variables: age, ECOG status, carcinoembryonic antigen (CEA) level, white blood cell level, albumin level, total bilirubin level, and aspartate aminotransferase level. The sample size of each group was 164 patients after PSM. Median survival was compared between the two groups by using the Kaplan-Meier method, and prognostic factors were investigated using Cox proportional regression analysis. Results In post-PSM analysis, the respective median survival for the chemotherapy and BSC groups was dependent on the following prognostic factors: total population, 12.0 months vs. 7.5 months (p=0.001); locally advanced disease, 16.7 months vs. 13.4 months (p=0.490); cancer antigen 19-9 ≤ 100 IU/mL, 12.7 months vs. 10.6 months (p=0.330); and CEA ≤ 3.4 ng/mL, 17.1 months vs. 10.6 months (p=0.052). Conclusion Chemotherapy improved overall survival of patients with advanced BTC who had a good performance status. However, this survival benefit was not observed in BTC patients with locally advanced disease or with lower tumor marker. Individualized approach is needed for initiation of palliative chemotherapy in advanced BTC.

Background: In stage I/II natural killer (NK)/T-cell lymphoma, concurrent chemoradiotherapy (CCRT) had previously been shown to result in superior outcome compared with anthracycline-containing regimens, which have since been considered ineffective. The role of CCRT in comparison with approaches employing nonanthracycline-containing chemotherapy (CT) and sequential radiotherapy (RT) in such patients remains to be defined. Patients and methods: Three hundred and three untreated patients (207 men, 96 women; median age: 51, 18-86 years) with stage I/II NK/T-cell lymphoma who had received nonanthracycline-containing regimens were collected from an international consortium and retrospectively analyzed. Treatment included single modality (CT and RT), sequential modalities (CT+RT; RT+CT) and concurrent modalities (CCRT; CCRT+CT). The impact of clinicopathologic parameters and types of treatment on complete response (CR) rate, progression-free-survival (PFS) and overall-survival (OS) was evaluated. Results: For CR, stage (P=0.027), prognostic index for NK/T-cell lymphoma (PINK) (P=0.026) and types of initial treatment (P=0.011) were significant prognostic factors on multivariate analysis. On Cox regression analysis, ECOG performance score (P=0.021) and PINK-EBV DNA (PINK-E) (P=0.002) significantly impacted on PFS; whereas ECOG performance score (P=0.008) and stage (P

After introducing a rituximab-containing chemoimmunotherapy (R-CHOP) for diffuse large B cell lymphoma (DLBCL), a partial response (PR) which is regarded as treatment failure is still observed. To investigate the prognostic factors for the DLBCL patients with a PR to R-CHOP, we retrospectively evaluated 758 newly diagnosed DLBCL patients. After R-CHOP, 88 (11.6%) achieved a PR. Three-year progression-free and overall survival rates measured from the date of PR achievement (PFS2 and OS2) were 57.4 and 67.8%, respectively. The secondary International Prognostic Index (IPI2) scores after R-CHOP were low (0-1) in 68.2% and high (2-3) in 31.8% of the patients. The Deauville scores from 18-fluorodeoxyglucose positron emission tomography after R-CHOP showed low (2-3) in 58.0% and high (4) in 42.0% of the patients. High IPI2 and high Deauville scores were associated with worse PFS2 (P 0.001 and P = 0.009) and OS2 (P = 0.013 and P = 0.067). The high-risk group defined by the IPI2 and Deauville scores, whose scores were both high, showed significantly lower 3-year PFS2 (P 0.001) and OS2 (P = 0.006) rates compared with those of the other groups. In multivariate analyses, the IPI score of ≥ 3 at diagnosis and bone marrow involvement at diagnosis were independent prognostic factors. In addition, high IPI2-Deauville score after R-CHOP was significantly associated with poor PFS2 (P = 0.009) and demonstrated a trend toward inferior OS2. In conclusion, DLBCL patients who partially responded to R-CHOP are still a heterogeneous group, for which IPI2 and Deauville scores should be evaluated for prediction of prognosis.

// Sung-Yong Kim 1 , Suk-Woo Yang 2 , Won-Sik Lee 3 , Jae Wook Yang 4 , Sung Yong Oh 5 , Hee Bae Ahn 6 , Deok-Hwan Yang 7 , Seong Kyu Park 8 , Jee Ho Chang 9 , Hyo Jung Kim 10 , Min Joung Lee 11 and Seok-Goo Cho 12 1 Department of Hematology-Oncology, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea 2 Department of Ophthalmology and Visual Science, Seoul St. Mary’s Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea 3 Department of Hematology and Oncology, Inje University College of Medicine, Busan Paik Hospital, Busan, Korea 4 Department of Ophthalmology, Busan Paik Hospital, Inje University, Busan, Korea 5 Department of Internal Medicine, Dong-A University College of Medicine, Busan, Korea 6 Department of Ophthalmology, Dong-A University College of Medicine, Busan, Korea 7 Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Jeollanamdo, Korea 8 Department of Internal Medicine, Soonchunhyang University Bucheon Hospital, Soonchunhyang University, Bucheon, Korea 9 Department of Ophthalmology, Soonchunhyang University Bucheon Hospital, Soonchunhyang University, Bucheon, Korea 10 Division of Hematology-Oncology, Department of Internal Medicine, College of Medicine, Hallym University, Hallym University Sacred Heart Hospital, Anyang, Korea 11 Department of Ophthalmology, College of Medicine, Hallym University, Hallym University Sacred Heart Hospital, Anyang, Korea 12 Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Korea Correspondence to: Seok-Goo Cho, email: chosg@catholic.ac.kr Keywords: lymphoma, ocular, mucosa associated lymphoid tissue, rituximab, chemoimmunotherapy Received: March 09, 2017 Accepted: June 24, 2017 Published: August 02, 2017 ABSTRACT Background: Radiotherapy is a commonly used treatment for limited-stage ocular adnexal mucosa-associated lymphoid tissue lymphoma (OAML) but showed a substantial relapse risk if the disease involves beyond-conjunctiva or bilateral conjunctivae. Systemic chemoimmunotherapy may be an alternative frontline therapy for the limited disease with those adverse prognostic factors. Patients and methods: We designed a multicenter, phase II study of the chemoimmunotherapy, rituximab, cyclophosphamide, vincristine, and prednisolone (R-CVP) for the treatment of patients with limited-stage OAML with bilateral or beyond-conjunctival involvement. Thirty-three patients with Ann Arbor stage I OAML with the adverse factors were enrolled. Patients received six cycles of R-CVP followed by two cycles of rituximab therapy. Results: At the end of treatment, all the enrolled patients had responded. The cumulative complete response achievement was 93.9% at 2 years. At a median follow-up of 50.6 months, three patients had progressed. Progression-free survival and overall survival at 4 years was 90.3±5.3% and 100%, respectively. Conclusions: This phase II study demonstrated durable efficacy of R-CVP chemoimmunotherapy, which has promise as an alternative frontline therapy for the limited-stage OAML patients with adverse prognostic factors. Clinical trial registration: NCT01427114.

BACKGROUND To assess whether the rotation of dexamethasone to methylprednisolone decreases the intensity of dexamethasone-induced hiccup (DIH) in cancer patients treated with chemotherapy. MATERIALS AND METHODS Adult patients who experienced DIH within 3 days after the administration of dexamethasone as an antiemetic were screened. Eligible patients were randomly assigned to receive dexamethasone (n = 33) or methylprednisolone (n = 32) as an antiemetic (randomization phase). In the next cycle of chemotherapy, the dexamethasone group received methylprednisolone and vice versa in the methylprednisolone group (crossover phase). The primary endpoint was the difference in hiccup intensity as measured using the numeric rating scale (NRS) between two groups. RESULTS No female patients were enrolled, although the study did not exclude them. At the randomization phase, hiccup frequency was 28/33 (84.8%) in the dexamethasone group versus 20/32 (62.5%) in the methylprednisolone group (p = .04). Intensity of hiccup was significantly higher in the dexamethasone group than that in the methylprednisolone group (mean NRS, 3.5 vs. 1.4, p

The management of advanced prostate cancer has evolved rapidly. Androgen deprivation therapy, via surgical or medical castration, is the first-line therapy for hormone-naive metastatic prostate cancer. For approximately a decade, docetaxel-based chemotherapy was the only approved agent to show a survival benefit for castration-resistant prostate cancer. However, over the last 5 years, significant advances in the field have led to the approval of several new agents with different mechanisms of action, such as the new androgen pathway inhibitors abiraterone and enzalutamide, a new cytotoxic agent, cabazitaxel, and new bone-seeking agents such as radium-223, which have all been associated with improved quality of life and pain palliation and an increase in survival. However, there has been no Korean treatment guideline for metastatic prostate cancer which is developed based on thorough search for relevant articles, including recently developed agents, and adequate review and assessment of evidences, and thus, a guideline adequate for domestic circumstance is eagerly needed. Experts from the Genitourinary Oncology Committee of the Korea Cancer Study Group developed clinical recommendations for the treatment of metastatic prostate cancer based on 19 key questions. The Korean Association for Clinical Oncology, the Korean Prostate Society, the Korean Urological Oncology Society, and the Korean Society of Pathologists reviewed and endorsed the guidelines. These are the first Korean treatment guidelines developed specifically for metastatic prostate cancer. (Korean J Med 2017;92:124-141)

// Dok Hyun Yoon 1, * , Byeong Seok Sohn 2, * , Sung Yong Oh 3 , Won-Sik Lee 4 , Sang Min Lee 4 , Deok-Hwan Yang 5 , Jooryung Huh 6 , Cheolwon Suh 1 1 Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea 2 Department of Internal Medicine, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Korea 3 Department of Internal Medicine, Dong-A University Hospital, Busan, Korea 4 Department of Hemato-Oncology, Internal Medicine, Busan Paik Hospital, Inje University College of Medicine, Busan, Korea 5 Department of Hematology-Oncology, Chonnam National University Hwasun Hospital, Hwasun, Korea 6 Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea * These authors have contributed equally to this work Correspondence to: Cheolwon Suh, email: csuh@amc.seoul.kr Dok Hyun Yoon, email: dhyoon@amc.seoul.kr Keywords: diffuse large B-cell lymphoma, limited stage, complete resection, abbreviated cycles and R-CHOP chemotherapy Received: November 04, 2016 Accepted: December 28, 2016 Published: January 05, 2017 ABSTRACT Background: The appropriate number of chemotherapy cycles for limited stage diffuse large B-cell lymphoma (DLBCL) patients without gross residual lesions after complete resection, has not been specifically questioned. We performed a multicenter, single-arm, phase 2 study to investigate the feasibility of 3 cycles of abbreviated R-CHOP chemotherapy in low-risk patients with completely resected localized CD20+ DLBCL. Results: Between December 2010 and May 2013, we recruited 23 patients. One was excluded due to ineligibility, and hence, 22 were included in the final analysis. The primary sites comprised the intestine ( n = 15), cervical lymph nodes ( n = 4), stomach ( n = 1), tonsil ( n = 1), and spleen ( n = 1). All patients successfully completed the 3 cycles of planned R-CHOP chemotherapy. Over a median follow-up of 39.5 months (95% confidence interval, 29.9—47.1 months), both the estimated 2-year disease-free survival and overall survival rates was 95% confidence interval, 85.9–104.1%. Only one patient with an international prognostic index of 2 experienced relapse and died. The most common grade 3 or 4 toxicity condition included neutropenia ( n = 8, 36.4%). Three patients experienced grade 3 febrile neutropenia, but no grade 3 or 4 non-hematologic toxicity was observed. Materials and Methods: DLBCL patients without residual lesions after resection were enrolled and R-CHOP chemotherapy was repeated at 3-week-intervals over 3 cycles. The primary endpoint was 2-year disease-free survival. Conclusions: Three cycles of abbreviated R-CHOP immunochemotherapy is feasible for completely resected low risk localized DLBCL.

Background The upregulated expression of the JAK/STAT pathway promotes tumor growth in Hodgkin lymphoma (HL) and primary mediastinal large B-cell lymphoma (PMBCL). Based on the hypothesis that JAK2 is a therapeutic target, we performed a prospective pilot study using ruxolitinib. Methods Relapsed or refractory patients with HL or PMBCL were eligible for this study, and JAK2 amplification was assessed by fluorescence in situ hybridization. Ruxolitinib was administered orally at a dose of 20 mg twice daily for a 28-day cycle. Treatment was continued for up to 16 cycles or until progressive disease or intolerability. The primary objective was to assess the overall disease control rate comprising complete response (CR), partial response (PR), or stable disease (SD). Results We analyzed 13 HL patients and six PMBCL patients. All responders (one CR, five PR, and one SD) had HL whereas all cases of PMBCL progressed after first or second cycle. The disease control rate for HL was 54% (7/13) with median response duration of 5.6 months. JAK2 amplification was present in six of nine patients tested (four HL, two PMBCL), and three of these HL patients showed PR (n = 2) or SD (n = 1). None of the three HL patients shown to not have JAK2 amplification responded to ruxolitinib. Most treatment-related adverse events were grade 1 or 2 and manageable. Conclusions Ruxolitinib has single-agent activity against HL but does not act against PMBCL with or without JAK2 amplification. Trial registration The study population was patients who had relapsed or refractory HL or PMBCL, and patients were registered for our pilot study after providing written informed consent between November 2013 and November 2015 (CilinicalTrials.gov: NCT01965119).

Background: Liposomal irinotecan (nal-IRI) plus 5-fluorouracil and leucovorin (5-FU/LV) was effective and well-tolerated in patients with metastatic pancreatic adenocarcinoma (mPAC) that progressed on gemcitabine-based therapy in the global NAPOLI-1 trial. Real-world data may further clarify the outcomes and safety profile of nal-IRI + 5-FU/LV in clinical practice. Methods: This retrospective analysis included patients with mPAC who received nal-IRI + 5-FU/LV following gemcitabine-based therapy under a Managed Access Program in Korea. Results: From January 2017 to April 2018, 86 patients across 10 institutions received nal-IRI + 5-FU/LV (median age, 61 years; 60% male; ECOG performance status, 0–1). A total of 35 (41%) and 51 (59%) patients had received less than two and two or more lines of chemotherapy before inclusion, respectively. At a median follow up of 6.4 months, median overall survival (OS) was 9.4 months (95% confidence interval [CI] 7.4–11.4) and median progression-free survival (PFS) was 3.5 months (95% CI 1.3–5.7). Six-month OS and PFS rates were 65.1% and 37.5%, respectively. Objective response and disease control rates were 10% and 55%, respectively. Most common grade 3–4 toxicities were neutropenia (37.2%), nausea (10.5%), vomiting (9.3%), anorexia (8.1%) and diarrhoea (4.7%). Conclusion: Real-life data for Korean patients indicate that, consistent with NAPOLI-1, nal-IRI + 5-FU/LV is effective and well-tolerated in patients with mPAC that progressed on gemcitabine-based therapy.

Background The response rate and survival improvement for rituximab, a CD20-targeting monoclonal antibody, have been demonstrated in marginal zone lymphoma (MZL) as monotherapy and in combination with chemotherapeutic regimens, yet relapses still occur despite treatment completion. Thus, extending the period of remission in MZL patients remains an essential goal. This multicenter, single-arm, open-label phase II study evaluated the survival efficacy of 2 years of rituximab-maintenance therapy in patients with stage III–IV CD20-positive MZL who had responded to first-line R–CVP (rituximab, cyclophosphamide, vincristine, and prednisolone). The objective of this study was to determine whether rituximab maintenance following R–CVP warrants further investigation. Methods Prior to rituximab-maintenance therapy, patients received 6–8 cycles of first-line R–CVP therapy for stage III–IV MZL. Rituximab (375 mg/m2), cyclophosphamide (750 mg/m2), and vincristine (1.4 mg/m2; maximum 2 mg) were administered via an intravenous infusion on day 1 of each 3-week cycle, while oral prednisolone (100 mg) was given on days 1–5 of each 3-week cycle. The patients who achieved complete response (CR), partial response (PR), or stable disease (SD) to R–CVP treatment, were prescribed rituximab-maintenance therapy which was administered intravenously at a dose of 375 mg/m2 every 8 weeks for up to 12 cycles. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS) and treatment safety. Results 47 patients were enrolled, of whom, 45 (96%) received rituximab-maintenance treatment. Fifteen (33%) patients had nodal MZL. Following R–CVP first-line therapy, 20 (44%), 22 (49%), and 3 (7%) patients achieved CR, PR, and SD, respectively. After a median follow-up of 38.2 months, their observed 3-year PFS rate was 81%. During the rituximab-maintenance, 6 PR and 1 SD patients achieved CR following the administration of R–CVP. Elevated LDH and the presence of B symptoms were found to be significant prognostic factors for PFS (P = 0.003) and demonstrated a 3-year OS rate of 90%. Rituximab-maintenance therapy was well tolerated, and the common treatment-emergent adverse events were sensory neuropathy (18%), myalgia (13%), fatigue (9%), and neutropenia (9%). Conclusion Rituximab-maintenance therapy following first-line R–CVP demonstrated good PFS in patients with stage III–IV MZL, in addition to a favorable toxicity profile. Trial registration clinicaltrials.gov: NCT01213095

Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a provisional entity in the 2017 World Health Organization classifications. To further elucidate the clinicopathologic features of this new disease, we carried out a retrospective, multicenter analysis of 42 patients with MEITL. The median age of the patients was 59 years (range, 20–84 years), and 27 patients (64 %) were male. Thirty-two patients (76 %) were Ann-Arbor stages I–II and 28 (67 %) were Lugano stages I–II1&2. The most frequent site of involvement was the jejunum (N = 21). Most cases expressed CD8 (79 %) and CD56 (95 %) and did not express CD30 (5 %) or EBER (0 %). The median progression-free survival was 6.9 months (95 % CI 4.3–9.6); the median OS was 14.8 months (2.4–27.2). Thirty-two patients (76 %) underwent surgery and 37 (88 %) received chemotherapy. A complete response (CR) rate was 38 %. Sixteen patients had undergone autologous stem cell transplantation (ASCT). Relapse or progression was documented in 24 cases, most frequently in the primary site (N = 23). Four cases showed central nervous system relapse. Age over 55 years, poor performance scale, advanced Lugano stage (IIE–IV), not achieving CR, and not receiving ASCT were associated with inferior OS. While the optimal management of MEITL remains undetermined, achieving CR and consolidative ASCT seem essential. As CHOP might be insufficient for achieving CR, more efficient combinations should be investigated. Additionally, considering the frequent local failure and CNS relapse, novel therapeutic approaches are required to improve survival.

Background The efficacy of epidermal growth factor (EGF) receptor (EGFR) inhibitors in patients with non‐small cell lung cancer (NSCLC), pancreatic cancer (PC), or colorectal cancer (CRC) has been demonstrated. However, dermatological reactions to these inhibitors can cause significant physical and psychosocial discomfort. The objective of the present study was to evaluate the efficacy of EGF ointment for EGFR inhibitor‐related skin adverse events (ERSEs). Materials and Methods This placebo‐controlled, double‐blind, multicenter, pilot phase III trial enrolled patients with NSCLC, PC, or CRC treated with EGFR inhibitors. Patients with grade ≥2 ERSEs were included. Patients were randomized to three treatment arms: arm 1, placebo; arm 2, 1 ppm of EGF ointment; and arm 3, 20 ppm of EGF ointment. Patients applied ointment to their skin lesions twice daily. Results Efficacy evaluation was available for 80 patients (9 for PC, 28 for NSCLC, and 43 for CRC). Responses were 44.4% in arm 1, 61.5% in arm 2, and 77.8% in arm 3. There was a linear correlation between EGF concentrations and responses (p = .012). Quality of life (QoL) was assessed for 74 patients. Maximum changes in composite scores by Skindex‐16 after treatment were significantly different among arms (mean ± SD: −5.2 ± 8.6 for arm 1, −11.7 ± 14.2 for arm 2, and − 18.6 ± 17.7 for arm 3; p = .008). EGF arms showed significant improvement in emotions (p = .005) and functioning (p = .044) scores over the placebo arm. Conclusion EGF ointment is effective for managing ERSEs. It can also improve patients’ QoL compared with placebo. Clinical trial identification number. NCT02284139 Implications for Practice Patients with non‐small cell lung cancer, pancreatic cancer, or colorectal cancer who are treated with epidermal growth factor (EGF) receptor (EGFR) inhibitors may experience dermatologic reactions to their treatment. This study investigated the benefit of an EGF ointment in the treatment of these adverse events and observed the ointment to be effective in managing EGFR inhibitor‐related skin adverse events., Epidermal growth factor (EGFR) is an important target for antitumor therapy. This article evaluates the efficacy of EGF ointment for EGFR inhibitor‐related adverse events of the skin.

The Glasgow Prognostic Score (GPS) serves a prognostic role in several lymphomas. The objectives of the present study were to determine whether GPS predicts clinical outcomes and to compare the utility of four prognostic scores, including GPS, in patients diagnosed with peripheral T-cell lymphoma (PTCL). We selected for this retrospective study 96 patients consecutively diagnosed with PTCL according to the World Health Organization classification from January 2002 to February 2013 and followed up in five different institutions. Low GPS was a good prognostic biomarker of progression-free survival (PFS, P = 0.030) and overall survival (OS, P = 0.013). Estimated 3-year OS rates (low-risk vs. intermediate- or high-risk) by the International Prognostic Index (IPI), the Prognostic Index for T-cell lymphoma (PIT), the International Peripheral T-cell Lymphoma Project (IPTCLP) score, and GPS were 83% vs. 44% (P

We assessed the efficacy and toxicity of etoposide, methylprednisolone, high-dose cytarabine, and oxaliplatin (ESHAOx) combination chemotherapy in patients with refractory or relapsed Hodgkin’s lymphoma (HL). This was an open-label, non-randomized, multi-center phase II study. The ESHAOx regimen consisted of intravenous (i.v.) etoposide 40 mg/m2 on days 1 to 4, i.v. methylprednisolone 500 mg on days 1 to 5, i.v. cytarabine 2 g/m2 on day 5, and i.v. oxaliplatin 130 mg/m2 on day 1. Cycles (up to six) were repeated every 3 weeks. In an effort to identify prognostic markers, the serum levels of cytokines including tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and vascular endothelial growth factor (VEGF) were measured at the time of study entry. A total of 37 patients were enrolled, and 36 were available for evaluation of tumor response. The overall response rate was 72.2% (26/36) (complete response, 33.3% [12/36]; partial response, 38.9% [14/36]). The median time to progression was 34.9 months (95% confidence interval, 23.1–46.7 months). The most common grade 3 or 4 hematological adverse events were neutropenia (16/37, 43.2%), followed by thrombocytopenia (10/37, 27.0%). Grade 3 or 4 non-hematological adverse events were nausea (3/37, 8.1%), anorexia (2/37, 5.4%), mucositis (1/37, 2.7%), and skin rash (1/37, 2.7%). There were no treatment-related deaths. High levels of TNF-α and CRP were significantly associated with poorer overall survival (p = 0.00005 for TNF-α, p = 0.0004 for CRP, respectively). The ESHAOx regimen exhibited antitumor activity and an acceptable safety profile in patients with refractory or relapsed HL. Trial Registration: ClinicalTrials.gov. Registered February 21, 2011, https://clinicaltrials.gov/ct2/show/NCT01300156

4119 Background: Modified FOLFIRINOX (mFOLFIRINOX) consisting of 5-fluorouracil/leucovorin, irinotecan, and oxaliplatin has been assessed as second-line treatment of patients with advanced pancreatic cancer in retrospective and phase II studies. However, the result was not confirmed by randomized controlled trial. Methods: A randomized, open-label, phase III trial was conducted at 9 institutions in Korea. Patients with metastatic pancreatic adenocarcinoma (mPAC) and Eastern Cooperative Oncology Group performance status of 0-1 who failed to first-line gemcitabine-based chemotherapy were randomly assigned to receive mFOLFIRINOX or S-1. The primary endpoint was overall survival. Results: A total of 80 patients were enrolled from March 2017 to December 2019. The accrual of patients was early terminated due to clear difference of efficacy in the interim analysis and expectation of poor recruitment due to conflicting adjuvant regimens. Objective response and disease control rates were 15.4% vs. 2.4% ( p= 0.041) and 66.7% vs. 36.6% ( p= 0.007) in the mFOLFIRINOX and S-1 arms, respectively. The median progression-free survival was 5.2 and 2.2 months in the mFOLFIRINOX and S-1 arms, respectively ( p= 0.002). The median overall survival was 9.2 and 4.9 months in the mFOLFIRINOX and S-1 arms, respectively ( p= 0.048). The adjusted hazard ratio of the mFOLFIRINOX arm to the S-1 arm for overall survival was 0.402 (95% confidence interval 0.223-0.725, p= 0.002). All grade 3-4 adverse events occurred in 56.5% and 17.1% in the mFOLFIRINOX and S-1 arms, respectively ( p< 0.001). However, only one patient in each arm prematurely discontinued treatment due to toxicity and there was no treatment-related mortality in both arms. Minimally important differences in the health-related quality of life were not observed in both arms. Conclusions: mFOLFIRINOX as second-line treatment in mPAC patients failed to gemcitabine-based chemotherapy demonstrated a survival benefit versus S-1 alone with acceptable toxicities. Clinical trial information: KCT0003534.

Common carp is a major aquaculture species. Frequent feeding in aquaculture species resulted in improved growth parameters and feed conversion rate. Overfeeding cause water quality deterioration, increase labor cost, increase feed cost, and reduce profit. We examine the effect of feeding frequency on growth, feed conversion rate, and body composition of juvenile common carp. Feeding frequencies of one, three, five, six, seven, and eight meals daily were given to juvenile common carp for 60 days. Fish grew from an initial body weight of 2.4 g up to 15.2 g (one meal daily), 37.5 g (three meals daily), 50.4 g (five meals daily), 53.6 g (six meals daily), 55.4 g (seven meals daily), and 51.1 g (eight meals daily). Significantly higher final weight was exhibited by fish in groups fed six meals and seven meals daily compared to groups fed three meals and one meal daily. Lipid content of the group fed one meal daily was the lowest. No significant difference in final weight, specific growth rate, feed intake and, feed conversion rate between group fed six and seven meals daily. Feeding six meals daily is the optimum feeding frequency for juvenile common carp.

TPS185 Background: LIV-1 is a transmembrane protein expressed in a variety of cancer types. SGN-LIV1A, or ladiratuzumab vedotin (LV), is a novel investigational humanized IgG1 antibody-drug conjugate (ADC) directed against LIV-1. LV mediates delivery of monomethyl auristatin E (MMAE), which drives antitumor activity through cytotoxic cell killing and induces immunogenic cell death. In a phase 1 study, LV was tolerable and active in heavily pretreated patients with metastatic breast cancer (Modi 2017). This study is currently evaluating the safety and efficacy of LV in different advanced solid tumors with various LIV-1 expression, including metastatic castration-resistant prostate cancer (mCRPC), advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma, esophageal squamous cell carcinoma, small cell lung cancer (SCLC), non-small cell lung cancer (squamous and nonsquamous), head and neck squamous cell carcinoma, and melanoma. Methods: SGNLVA-005 (NCT04032704) is an open-label, phase 2 study evaluating LV monotherapy in patients with previously treated, locally advanced unresectable or metastatic advanced solid tumors, including mCRPC. Patients with mCRPC will receive LV administered as a 30 minute intravenous infusion (IV) at 1.25 mg/kg every 1 week. Up to 30 patients with mCRPC will be enrolled. Patients in the mCRPC cohort must have metastatic castration-resistant disease, have received no more than 1 prior line of androgen receptor-targeted therapy, have ≥28 days between androgen receptor-targeted therapy and start of study treatment, an Eastern Cooperative Oncology Group (ECOG) score of 0 or 1, and adequate organ function. In addition, mCRPC patients with measurable and non-measurable disease are eligible if the protocol-defined criteria are met. mCRPC patients must not have BRCA gene mutations, prior cytotoxic chemotherapy in the metastatic mCRPC setting, prior radioisotope therapy, or radiotherapy to ≥30% of bone marrow. Patients are not preselected based on tumor LIV-1 expression. Their tumor samples will be analyzed for correlation between LIV-1 expression and response. Safety and efficacy will be monitored throughout the study. Study objectives include objective tumor response rate per RECIST 1.1 and prostate-specific antigen (PSA) response rate per Prostate Cancer Clinical Trials Working Group 3 (both primary); safety and tolerability, disease control rate, duration of response, progression-free and overall survival, and pharmacokinetics and immunogenicity (all secondary); and pharmacodynamics. Study accrual is ongoing in the USA, Italy, South Korea, Taiwan, Australia, and the UK. Clinical trial information: NCT04032704.

TPS256 Background: LIV-1 is a transmembrane protein expressed in a variety of cancer types. SGN-LIV1A, or ladiratuzumab vedotin (LV), is a novel investigational humanized IgG1 antibody-drug conjugate (ADC) directed against LIV-1. LV mediates delivery of monomethyl auristatin E (MMAE), which drives antitumor activity through cytotoxic cell killing and induces immunogenic cell death. In a phase 1 study, LV was tolerable and active in heavily pretreated patients with metastatic breast cancer at a recommended dose of 2.5 mg/kg every 21 days (Modi 2017). More frequent, fractionated dosing has improved the activity and/or safety of other ADCs. Thus, this study is currently evaluating the safety and efficacy of weekly LV dosing (Days 1, 8, and 15 of every 3-week cycle) in different advanced solid tumors with various LIV-1 expression, including advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma, esophageal squamous cell carcinoma, small cell lung cancer (SCLC), non-small cell lung cancer (squamous and nonsquamous), head and neck squamous cell carcinoma, castration resistant prostate cancer, and melanoma. Methods: SGNLVA-005 (NCT04032704) is an open-label, phase 2 study evaluating LV monotherapy in patients with 8 different advanced solid tumors in two parts (administered as a 30 minute intravenous infusion [IV]: Part A LV 2.5 mg/kg IV every 3 weeks [up to n = 72 total]; Part B LV 1.0 or 1.25 mg/kg every 1 week [up to n = 252 total]). The study is enrolling previously treated patients with unresectable locally advanced or metastatic disease. Patients must have measurable disease per RECIST v1.1, an Eastern Cooperative Oncology Group (ECOG) score of 0 or 1, and adequate organ function. Cohort specific inclusion criteria require that patients in the gastric and GEJ adenocarcinoma and esophageal squamous cell carcinoma cohorts must have received and progressed during or after no more than 1 prior line of platinum based cytotoxic chemotherapy. Patients in the gastric and GEJ adenocarcinoma cohort may have received prior anti-programmed cell death (ligand) 1 (anti-PD[L]1) therapy (unless contraindicated), and patients with known human epidermal growth factor receptor 2 (HER2) overexpression must have received prior HER2-targeted therapy. Patients are not preselected based on tumor LIV-1 expression. Tumor samples will be analyzed for correlation between LIV-1 expression and tumor response. Safety and efficacy will be monitored throughout the study. Study objectives include objective response rate (primary); safety and tolerability, disease control rate, duration of response, progression-free and overall survival, and pharmacokinetics and immunogenicity (all secondary); and pharmacodynamics. Study accrual is ongoing in the USA, Italy, South Korea, Taiwan, Australia, and the UK. Clinical trial information: NCT04032704.

Purpose The purpose of this study is to assess the role of adjuvant therapy in stage I-III gallbladder cancer (GBC) patients who have undergone R0 resection. Materials and Methods Clinical data were collected on 441 consecutive patients who underwent R0 resection for stage I-III GBC. Eligible patients were classified into adjuvant therapy and surveillance only groups. Propensity score matching (PSM) between the two groups was performed, adjusting clinical factors. Results In total, 84 and 279 patients treated with adjuvant therapy and followed up with surveillance only, respectively, were included in the analysis. Before PSM, the 5-year relapse-free survival (RFS) rate was lower in the adjuvant therapy group than in the surveillance only group (50.8% vs. 74.8%, p < 0.001), although there was no statistically significant difference in the 5-year overall survival (OS) rate (66.2% vs. 79.5%, p=0.089). After the PSM, baseline characteristics became comparable and there were no differences in the 5-year RFS (50.8% vs. 64.8%, p=0.319) and OS (66.2% vs. 70.4%, p=0.703) rates between the two groups. Conclusion The results suggest that fluoropyrimidine-based adjuvant therapy is not indicated in stage I-III GBC patients who have undergone R0 resection.

// Sung Yong Oh 1 , Aesun Shin 2 , Seong-Geun Kim 3 , Jung-Ah Hwang 4 , Seung Hyun Hong 4 , Yeon-Su Lee 4 , Hyuk-Chan Kwon 5 1 Department of Internal Medicine, Dong-A University College of Medicine, Busan, Korea 2 Department of Preventive Medicine, Seoul National University, Korea 3 Department of Internal Medicine, Pusan National University Yangsan Hospital, Yangsan, Korea 4 Cancer Genomics Branch, Research Institute, National Cancer Center, Goyang, Gyeonggi-do, Korea 5 Sillajen Inc., Busan, Korea Correspondence to: Yeon-Su Lee, email: yslee2@ncc.re.kr Hyuk-Chan Kwon, email: hckwon@sillajen.com Keywords: insulin-like growth factor, polymorphism, gastric cancer Received: January 08, 2016 Accepted: April 11, 2016 Published: April 29, 2016 ABSTRACT The insulin-like growth factor (IGF) axis plays a crucial role in proliferation, differentiation, migration, angiogenesis, and apoptosis. The present study evaluated the associations between IGF axis single-nucleotide polymorphisms (SNPs) and clinical outcomes in advanced gastric cancer (AGC) patients treated with oxaliplatin, 5-fluorouracil, and leucovorin (FOLFOX). A total of 190 patients undergoing FOLFOX chemotherapy for AGC were considered eligible for this study. Forty-four SNPs of 10 IGF axis genes were genotyped. Levels of serum IGF1 were measured using enzyme-linked immunoassays. SNPs of the IGF1R (rs12423791), and IGF1 (rs2162679, rs5742612, rs35767) genes were significantly associated with tumor response to FOLFOX. SNPs of rs4619 and rs17847203 were significantly associated with PFS (hazard ratio [HR] 0.575, 95% CI 0.385–0.858, P = 0.007; and HR 2.530, 95% CI 1.289–4.966, P = 0.007; respectively). SNPs of rs2872060 were significantly associated with OS—OS was shorter in patients carrying the TT variant than in those with the GG/GT genotypes (HR, 1.708, 95% CI 1.024–2.850, P = 0.040). The GT genotype of rs12847203 was also identified as an independent prognostic factor (HR 2.087, 95% CI 1.070–4.069, P = 0.031). These results suggest that IGF axis-pathway SNPs could be used as prognostic biomarkers of the outcome of FOLFOX chemotherapy in AGC patients. This information may facilitate identification of population subgroups that could benefit from IGF1R-targeted agents.

Background/aims CD11c is a dendritic cell marker in humans, which potentially induces a cytotoxic effect on lymphoma cells. Forkhead boxP3 (FOXP3) is a regulator of T lymphocyte in the microenvironment of the lymphoma. The principal objective of this study was to determine whether the tumors' microenvironment expressions of CD11c and FOXP3 are predictive of clinical outcomes in diffuse large B-cell lymphoma (DLBCL) patients receiving treatment with rituximab, cyclophosphamide, anthracycline, vincristine, and prednisone (R-CHOP) combination chemotherapy. Methods The study population consisted of 100 patients with DLBCL. The CD11c and FOXP3 expression in primary tumors' microenvironment were evaluated using an immunohistochemistry (IHC). Results CD11c and FOXP3 expression positivity in microenvironment were 25% and 35%, respectively. Each one counted for 1 point. In CD11c and FOXP3 stain, positive was counted as 0 and negative was 1. The points were separated into low risk (0 to 1) and high risk (2) groups. Only the extranodal DLBCL patient group analysis conveyed significant differences of progression-free survival (p = 0.019) and overall survival (p = 0.039) between the two groups. Conclusions We can achieve possible clinical significance of lymphoma tumor microenvironments through CD11c and FOXP3 IHC stains in extranodal DLBCL patients receiving R-CHOP therapy.

Purpose The peroxisome proliferator-activated receptor γ (PPARγ) is a nuclear receptor that regulates expression of mediators of lipid metabolism and the inflammatory response. Thyroid hormone receptor-associated proteins 220 (TRAP220) is an essential component of the TRAP/Mediator complex. The objective of this study was to clarify whether PPARγ or TRAP220 are significant prognostic markers in resectable colorectal cancer (CRC). Materials and Methods A total of 399 patients who underwent curative resection for CRC were enrolled. We investigated the presence of PPARγ and TARP220 in CRC tissues and adjacent normal tissues by immunohistochemistry. Correlation between the expression of these factors and clinicopathologic features and survival was investigated. Results Median age of the patients was 63 years (range, 22 to 87 years), and median follow-up duration 61.1 months (range, 2 to 114 months). PPARγ and TRAP220 expression showed significant correlation with depth of invasion (p=0.013 and p=0.001, respectively). Expression of TRAP220 also showed association with lymph node metastasis and TNM stage (p=0.001). Compared with patients with TRAP220 negative tumors, patients with TRAP220 positive tumors had longer 5-year disease-free survival (DFS) tendency (p=0.051). Patients who were PPARγ positive combined with TRAP220 positive had a better 5-year DFS (64.8% vs. 79.3%, p=0.013). In multivariate analysis expression of both PPARγ and TRAP220 significantly affected DFS (hazard ratio, 0.620; 95% confidence interval, 0.379 to 0.997; p=0.048). Conclusion TRAP220 may be a valuable marker for nodal metastasis and TNM stage. Tumor co-expression of PPARγ and TRAP220 represents a biomarker for good prognosis in CRC patients.

Adenomyoepithelioma (AME) of the breast is an uncommon tumor characterized by its dual differentiation into luminal cells and myoepithelial cells. In most cases these tumors have a benign clinical course, but distant metastases have been reported. We present the case of a 51-year-old woman diagnosed with malignant AME. The patient underwent a right modified radical mastectomy, and pathological examination confirmed the diagnosis of malignant AME. Ten months after the operation, multiple hepatic, pleural, and abdominal wall metastases were detected. A number of palliative chemotherapeutic agents were tried, including anthracycline and taxanes. However, the disease continued to progress, and superior vena cava syndrome developed as a result of direct tumor invasion. The patient received salvage eribulin monotherapy. After two cycles of this treatment, her clinical symptoms were ameliorated, and a computed tomography scan showed a partial response. Eribulin chemotherapy was thus effective in treating malignant AME in this case.

The mechanisms of epidermal growth factor (EGF) affecting EGF receptor inhibitor (EGFRI)-related skin toxicities are as yet unknown. We investigated which mechanisms are involved in EGF&rsquo, s positive effects. Two types of EGFRIs, cetuximab and gefitinib, were used to treat the cells or 3d-cultured human skin tissue with recombinant human EGF (rhEGF). As a result, rhEGF increased EGFR and pEGFR expression. Furthermore, rhEGF induces EGFR signaling by pAKT and pPI3K expression in gefitinib and rhEGF co-treated cells. In addition, rhEGF bound to EGFR after than cetuximab, but cetuximab bound to EGFR more strongly than rhEGF. Moreover, expressions of proliferation and differentiation proteins, both ki-67 and filaggrin, were decreased in EGFRI-treated tissue. However, in rhEGF and EGFRI co-treated tissue, those expressions were increased. Expression of IL-1&alpha, IL-8, and TNF-&alpha, was increased by EGFRIs and down-regulated by rhEGF. Furthermore, hBD-2 and hBD-3 protein expressions were inhibited by cetuximab or gefitinib treatment, and those decrements were increased by rhEGF treatment. In patients&rsquo, tissue evaluation, compared with controls, patients&rsquo, Ki-67 and EGFR expression were decreased (p = 0.015, p = 0.001). Patients&rsquo, IL-17 and TNF-&alpha, expression intensity was higher than that of the control group (p = 0.038, p = 0.037). After treatment with EGF ointment, average values of Ki-67, EGFR, and Melan-A were changed to normal values. Oppositely, patients&rsquo, proportions of IL-17 and TNF-&alpha, were decreased to low stain level. In conclusion, treatment of rhEGF improved EGFRI-induced skin eruption via normalizing the proliferation and differentiation of keratinocytes, reducing inflammatory cytokines by the affected EGFRIs.