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Purpose This study aimed to evaluate the survivals of patients with metastatic or recurrent gastric cancer (MRGC) over a period of 16 years and to investigate the recent changes in chemotherapy patterns. Materials and Methods A total of 5,384 patients who received chemotherapy for MRGC between 2000 and 2015 were analyzed. The analysis focused on a comparison of the first-line chemotherapy between four periods: 2000–2003 (period 1), 2004–2007 (period 2), 2008–2011 (period 3), and 2012–2015 (period 4). Results There were 880 patients (16%) in period 1, 1,573 (29%) in period 2, 1,435 (27%) in period 3, and 1,496 (28%) in period 4. Cytotoxic doublet-based therapy was the most commonly used (78%) first-line chemotherapy, and the combination of trastuzumab and doublet chemotherapy was provided to 288 patients. The overall survival (OS) rates at 12 and 24 months were steadily improved as follows: 39.2% and 14.6% in period 1, 43.5% and 17.6% in period 2, 50.3% and 20.6% in period 3, and 51.7% and 24.1% in period 4, respectively (p < 0.001). Among the patients who received the doublet-based chemotherapy, the median OS of those who received trastuzumab was 18.0 months (95% confidence interval [CI], 15.5 to 20.6), while that of those who received other doublet therapies was 11.2 months (95% CI, 10.8 to 11.6). Conclusion The OS was improved over time with advancements in chemotherapy, particularly the introduction of the anti-HER2–targeted agent, which contributed to the increase in the number of long-term survivors and established the superiority of OS for the treatment of MRGC.

Before developing a national screening program for pancreatic cancer, more detailed and reliable estimation of pancreatic cancer incidence rate is needed according to sex, age, and diabetes mellitus status. Among populations who underwent a biennial or annual evaluation provided by the National Health Insurance Service Database of Claims between 2006 and 2015, data were evaluated from the medical records of 34.2 million individuals aged 30 years and over. The annual incidence rate (IR; per 100,000) of pancreatic cancer in 2006 was 5.96, and the IR in 2015 increased to 8.92. The IRs increased consistently and significantly with age (p for trend

Context It has been unclear whether the risk of pancreatic cancer is different according to glucose levels. Objective To determine the association between fasting glucose levels and pancreatic cancer risk using prospectively collected nationwide population-based cohort data in Korea. Design The National Health Insurance Service database of claims and preventive health check-up data recorded was used between 2009 and 2015. Setting and Participants A total of 25.4 million patients who had participated in a preventive health check-up between 2009 and 2013 were evaluated for pancreatic cancer incidence rates according to fasting glucose level. Main Outcomes Measures The cumulative incidence rate for pancreatic cancer was calculated after grouping according to fasting glucose levels as follows: (i) low normal ( Results The 5-year cumulative incidence rates (per 100,000) were as follows: (i) low normal = 32; (ii) high normal = 41; (iii) prediabetes level 1 = 50; (iv) prediabetes level 2 = 64; (v) diabetes = 75; and (vi) on anti-diabetic medications = 121. The risk of pancreatic cancer increased continuously with elevating fasting glucose levels (P < 0.0001). The incidence of pancreatic cancer increased significantly with increasing fasting blood glucose levels even after adjusting for age, sex, smoking, drinking, exercise, body mass index, and diabetes duration (P < 0.0001). Conclusions The cumulative incidence rate of pancreatic cancer significantly increased as the fasting glucose level elevated, even in populations with a normal glucose level range.

BACKGROUND/AIM Lymph node metastasis is an important prognostic factor in gastric cancer patients. In node-negative (N0) gastric cancer patients, additional prognostic factors are needed to reinforce TNM staging. PATIENTS AND METHODS We semi-quantitatively recorded the presence of lymphatic, venous, and perineural invasion and evaluated the possibility that they could be used as upstaging factors in N0 gastric cancer by comparing N0 gastric cancer cases with N1 cases. RESULTS Venous (p

This study sought to adapt the existing value framework (VF) to produce a reliable and valid Korean oncology VF. Two VFs developed by The American Society of Clinical Oncology (ASCO) and the European Society for Medical Oncology (ESMO) were selected for examination in the present study. Forward and backward translations were conducted for six high-priced drugs indicated for non-small-cell lung cancer and multiple myeloma. Inter-rater reliability was measured based on the intraclass correlation coefficient (ICC) and variation was described using the coefficient of variation. The relative weights of factors critically considered by Korean oncologists were derived following the analytic hierarchy process (AHP), and focus group interviews (FGIs) were used to obtain qualitative data regarding the applications of these two VFs in the Korean setting. The ICCs of the Korean VFs were 0.895 (0.654–0.983) for ASCO and 0.726 (0–0.982) for ESMO translations, suggesting excellent reliability for ASCO and good reliability for ESMO. AHP demonstrated that clinical benefit has the highest priority, which is consistent with the ASCO VF. The FGIs suggested that the result for AHP is acceptable and that both ESMO and ASCO VFs should be used complementarily. Although further evaluation with a larger sample size is needed, the Korean versions of ESMO/ASCO VFs are valid and reliable tools and are acceptable to Korean stakeholders, yet they should be applied with caution.

Background & aims Progranulin (PGRN) is known to promote tumorigenesis and proliferation of several types of cancer cells. However, little is known about the clinicopathological features of patients with gastrointestinal stromal tumors (GISTs) with regard to PGRN expression. Methods A retrospective analysis was performed on patients with GISTs who underwent curative surgical resection between 2007 and 2017. PGRN expression was evaluated by immunohistochemical (IHC) analysis and semi-quantitatively categorized (no expression, 0; weak, 1+; moderate, 2+; strong, 3+). Tumors with a staining intensity of 2+ or 3+ were considered high PGRN expression. Results Fifty-four patients were analyzed; 31 patients (57%) were male. The median age at surgery was 60 years (range, 33–79), and the most common primary site was the stomach (67%). Thirty-five patients (65%) had spindle histology; 42 patients (78%) were separated as a high-risk group according to the modified National Institutes of Health (NIH) classification. High PGRN-expressing tumors were observed in 27 patients (50%), had more epithelioid/mixed histology (68% vs. 32%; p = 0.046), and KIT exon 11 mutations (76% vs. 24%; p = 0.037). Patients with high PGRN-expressing tumors had a worse recurrence-free survival (RFS) (36% of 5-year RFS) compared to those with low PGRN-expressing tumors (96%; p60 years) were independent prognostic factors for poor RFS. Conclusions High PGRN-expressing GISTs showed more epithelioid/mixed histology and KIT exon 11 mutations. PGRN overexpression was significantly associated with poor RFS in patients with GISTs who underwent curative resection.

Old age alone does not reflect an intolerability to chemotherapy. However, upfront dose reduction (UDR) of the first cycle of first-line palliative chemotherapy has sometimes been chosen by physicians for older adults with metastatic cancer due to concerns regarding adverse events. The development of predictive factors for UDR of palliative chemotherapy would be helpful for treatment planning among older adults. This was a secondary analysis of a study on predicting adverse events of first-line palliative chemotherapy in 296 patients (&ge, 70 years) with solid cancer. We assessed the prevalence of UDR of the first cycle of first-line chemotherapy and the association of UDR with the variables of geriatric assessment (GA) and chemotherapy compliance. Among the 296 patients, 177 (59.8%) patients were treated with UDR. The mean percentage of UDR for the total patient group was 19.2% (range: 4&ndash, 47%) of the standard dose. In a multivariate analysis, poor performance status (PS) and living without a spouse were independent predictive factors of UDR of first-line palliative chemotherapy in older adults. Patients with UDR showed fewer grade 3&ndash, 5 adverse events versus the standard dose group. Study completion as planned was significantly higher in the UDR group versus the standard dose group. Older adults with UDR better tolerated chemotherapy than patients with a standard dose.

Purpose The purpose of this study was to evaluate chemotherapy patterns and changes in quality of life (QOL) during first-line palliative chemotherapy for Korean patients with unresectable or metastatic/recurrent gastric cancer (GC). Materials and Methods Thiswas a non-interventional, multi-center, prospective, observational study of 527 patients in Korea. QOL assessments were conducted using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires (QLQ)-C30 and QLQ-STO22 every 3 months over a 12-month period during first-line palliative chemotherapy. The specific chemotherapy regimens were selected by individual clinicians. Results Most patients (93.2%) received combination chemotherapy (mainly fluoropyrimidine plus platinum) as their first-line palliative chemotherapy. The median progression-free survival and overall survival were 8.2 and 14.8 months, respectively. Overall, “a little” changes (differences of 5-10 points from baseline)were observed in some of the functioning or symptom scales; none of the QOL scales showed either “moderate” or “very much” change (i.e., ≥ 11 point difference from baseline). When examining the best change in each QOL domain from baseline, scales related to some aspects of functioning, global health status/QOL, and most symptoms revealed significant improvements (p < 0.05). Throughout the course of first-line palliative chemotherapy, most patients’ QOL was maintained to a similar degree, regardless of their actual response to chemotherapy. Conclusion This observational study provides important information on the chemotherapy patterns and QOL changes in Korean patientswith advanced GC. Overall, first-line palliative chemotherapy was found to maintain QOL, and most parameters showed an improvement compared with the baseline at some point during the course.

Progranulin (PGRN) has been characterized as an autocrine growth and survival factor and is known to stimulate tumorigenesis and proliferation of several types of cancer cell. However, little is known about the prognostic role of PGRN in colorectal cancer (CRC). A retrospective analysis was performed for patients with colorectal cancer who underwent curative resection between May 2013 and June 2015. PGRN expression in tumor cells was semi-quantitatively categorized (no expression, 0; weak/focal, 1+; moderate/focal or diffuse, 2+; strong/diffuse, 3+), and high expression was considered for tumors graded ≥2+ staining intensity. A total of 109 patients (28 stage I, 32 stage II, and 49 stage III) were analyzed. Thirty-eight patients (35%) had tumors with high PGRN expression, and there was a trend of elevated pre-operative CEA and CA19–9 levels in patients with high PGRN-expressing tumors compared to those with low PGRN-expressing tumors (CEA, 49% vs. 21%; CA19–9, 21% vs. 7%). The 3–year recurrence-free survival (3Y–RFS) and overall survival rates were 83.7% (95% CI, 76.8–90.6) and 96.0% (95% CI, 92.3–99.7), respectively. Patients with high PGRN-expressing tumors had a worse rate of 3Y–RFS (66.8%) compared to those with low PGRN-expressing tumors (92.4%; p = 0.010). Multivariate analysis showed that high PGRN expression, age (>66 years), stage (III), and perineural invasion (+) were independent prognostic factors associated with poor RFS after adjusting for confounding factors including sex, MSI, tumor location, KRAS, and lympho-vascular invasion. PGRN overexpression was significantly associated with poor RFS in patients with CRC who have undergone curative resection.

Manifestations of malignant pleural effusions (MPEs) are alleviated by local therapies as well as by systemic treatment. After 2009, when commercial use of talc was discontinued in Korea, we have used Helixor-M, which is derived from the European mistletoe (Viscum album), as an alternative sclerosing agent for pleurodesis. We aimed to evaluate the efficacy and safety of Helixor-M for controlling MPE. Between 2009 and 2015, we consecutively enrolled 52 patients with lung cancer, who underwent pleurodesis to treat MPE and were analyzed retrospectively. On day 1, 100 mg of Helixor-M was instilled via pleural catheter. If the procedure was not effective, it was repeated every other day up to five times, and the dose increased each time by 100 mg. The primary study outcome was reappearance of pleural effusion at 1 month after the last pleurodesis procedure. The median age of patient was 63 years, and 77% of the 52 patients were male. About 85% of pleural effusions were found to be malignant by cytogenetic analysis. Forty-two (81%) patients were evaluable for recurrence of MPE. The 1-month recurrence rate was 48% (20/42). Among the 20 patients who developed recurrent MPE, 6 required therapeutic thoracentesis. Thirteen (25%) patients experienced procedure-related pain requiring medication. Eight (15%) had fever > 38 °C. Our results suggest that a pleurodesis with Helixor-M was an effective and tolerable procedure for controlling MPE in lung cancer patients.

Background Older patients have increased risk of toxicity from chemotherapy. Current prediction tools do not provide information on cumulative risk. Methods Patients aged ≥ 70 years with solid cancer were prospectively enrolled. A prediction model was developed for adverse events (AEs) ≥ Grade 3 (G3), based on geriatric assessment (GA), laboratory, and clinical variables. Results 301 patients were enrolled (median age, 75 years). Median number of chemotherapy cycles was 4. During first-line chemotherapy, 53.8% of patients experienced AEs ≥ G3. Serum protein < 6.7 g/dL, initial full-dose chemotherapy, psychological stress or acute disease in the past 3 months, water consumption < 3 cups/day, unable to obey a simple command, and self-perception of poor health were significantly related with AEs ≥ G3. A predicting model with these six variables ranging 0–8 points was selected with the highest discriminatory ability (c-statistic= 0.646), which could classify patients into four risk groups. Predicted cumulative incidence of AEs ≥ G3 was discriminated according to risk groups. Conclusions This prediction tool could identify the risk of AEs ≥ G3 after chemotherapy and provide information on the cumulative incidence of AEs in each cycle. Clinical Trial Id WHO ICTRP number, KCT0001071

Ubiquitin-specific proteases (USPs) play an important role in fundamental cellular processes. Among these, USP10 is known for its association with tumor development and progression of multiple cancers. We aimed to investigate the clinical significance of USP10 expression in colorectal cancer and examined the potential link between USP10 and p14ARF in patients with colorectal cancer. USP10 and p14ARF protein expression was assessed via immunohistochemistry (IHC) on a tissue microarray from 280 colorectal cancer cases. IHC scores were evaluated by digital image analysis and compared with patients' outcomes. In addition, we examined DNA hypermethylation in colorectal cancer cell lines and tissues, which were matched with adjacent normal colon samples. USP10 expression was lost (USP10loss) in 18.6% of samples (52/280 cases), which was linked to lymphovascular invasion (p = 0.019) and distant metastases (p < 0.001). Similarly, loss of p14ARF expression (p14ARFloss) was associated with more advanced tumors. USP10 expression correlated positively with p14ARF expression (r = 0.617, p < 0.001). USP10loss, p14ARFloss, and dual loss of USP10 and p14ARF were significantly associated with shorter disease-free survival and overall survival in comparison to USP10intact, p14ARFintact, and dual loss of USP10 and p14ARF, respectively. Multivariate analysis revealed that USP10loss (p = 0.030) and dual loss of USP10 and p14ARF (p = 0.014) are independent prognostic factors for poor disease-free survival in colorectal cancer patients. Furthermore, aberrant hypermethylation of the USP10 promoter region was found in colorectal cancer cell lines and tissues. The present results suggest that USP10loss is a potential prognostic marker for colorectal cancer.

PurposeThe purpose of this study was to compare ramosetron (RAM), aprepitant (APR), and dexamethasone (DEX) [RAD] with palonosetron (PAL), APR, and DEX [PAD] in controlling highly-emetogenic chemotherapy (HEC)–induced nausea and vomiting. Materials and MethodsPatients were randomly assigned (1:1) to receive RAD or PAD:RAM (0.3 mg intravenously) or PAL (0.25 mg intravenously) D1, combined with APR (125 mg orally, D1 and 80 mg orally, D2-3) and DEX (12 mg orally or intravenously, D1 and 8 mg orally, D2-4). Patients were stratified by gender, cisplatin-based chemotherapy, and administration schedule. The primary endpoint was overall complete response (CR), defined as no emesis and no rescue regimen during 5 days of HEC. Secondary endpoints were overall complete protection (CP; CR+nausea score < 25 mm) and total control (TC; CR+nausea score < 5 mm). Quality of life was assessed by Functional Living Index Emesis (FLIE) questionnaire on D0 and D6.ResultsA total of 279 patients receiving RAD (n=137) or PAD (n=142) were evaluated. Overall CR rates in RAD and PAD recipients were 81.8% and 79.6% (risk difference [RD], 2.2%; 95% confidence interval [CI], −7.1 to 11.4), respectively. Overall CP and TC rates for RAD and PAD were 56.2% and 58.5% (RD, −2.3%; 95% CI, −13.9 to 9.4) and 47.5% vs. 43.7% (RD, 3.8%; 95% CI, −7.9 to 15.5), respectively. FLIE total score ≥ 108 (no impact on daily life) was comparable between RAD and PAD (73.9% vs. 73.4%, respectively). Adverse events were similar between the two groups.ConclusionIn all aspects of efficacy, safety and QOL, RAD is non-inferior to PAD for the control of CINV in cancer patients receiving HEC.

Neutrophil-to-lymphocyte ratio (NLR) is associated with poor prognosis in patients with lung cancer, but the predictive role of NLR on the risk of developing lung cancer is unknown. We investigated the association between NLR and lung cancer mortality in lung cancer-free adults. A cohort study was performed with 527,124 Korean adults who were free of lung cancer and were followed for up to 16 years. Vital status and lung cancer-related deaths were ascertained through national death records. Hazard ratios (HRs) and 95% confidence intervals (CIs) for lung cancer mortality were estimated using a Cox proportional hazards model. During 4,567,495.8 person-years of follow-up, 574 lung cancer deaths were identified. A higher NLR was positively associated with lung cancer mortality. The multivariable-adjusted HR (95% CI) for lung cancer mortality comparing quintiles 2, 3, 4 and 5 of NLR to the lowest quintile were 1.26 (0.96-1.67), 1.23 (0.93-1.63), 1.33 (1.01-1.75) and 1.47 (1.13-1.92), respectively. The highest risk of lung cancer mortality was also observed in the highest NLR quintile among never-smokers and low-risk individuals after adjusting for lung function and other possible confounders. Platelet-to-lymphocyte ratio showed an inverse J-shaped association with lung cancer mortality in men but the trends in women, low-risk individuals or never-smokers were neither linear nor U-shaped. In this large cohort of young and middle-aged individuals, NLR was independently associated with increased risk of lung cancer mortality in low-risk individuals, indicating a role of systemic inflammation in lung cancer mortality in our study population.

Background: Pembrolizumab monotherapy did not improve overall survival compared with paclitaxel in second-line treatment for AGC in Keynote-061. Here, we report the results of patients (pts) with evaluable lesions treated with combination of nivolumab (Nivo) and paclitaxel (PTX) in AGC who progressed on first-line chemotherapy with a platinum and fluoropyrimidine. Methods: This open label, single arm, phase 1b/2 study is part of biomarker-integrated umbrella study conducted at multi-centers in South Korea. Phase 1b included 6 all-comer pts irrespective of biomarkers in a 3+3 design. In phase 2, 47 pts with either EBV-related, deficient mismatch repair (dMMR)/MSI-H or PD-L1 positive were enrolled. PD-L1 was defined as combined positive score (CPS) of >1. The primary endpoints were determining maximum tolerated dose (MTD) and recommended phase II dose (RP2D) for phase 1b, and progression-free survival (PFS) for phase 2. Secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), PFS rate at 6 months and toxicity. Results: In phase 1b, dose limiting toxicities were not observed, and the RP2D was Nivo (3 mg/kg on days 1 and 15) combined with PTX (80 mg/m2 on days 1, 8 and 15) every 28 days. Phase 2 pts included CPS >1 (n=41), EBV positive (n=2), and 4 patients showed more than one biomarkers: CPS >1, EBV positive (n=2), CPS >1, dMMR/MSI-H (n=1), and CPS >1, EBV positive, dMMR/MSI-H (n=1). With a median follow-up period of 12.1 months, 7 pts remain on treatment (treatment duration: 1.1 to 23.1 months) as of August, 2020. In patients with measurable lesions (n=33), ORR was 24% (CR 9%, PR 15%) and DCR was 39%. Median duration of response was 18.4 months (95% CI, 3.2-19.8). Median PFS was 3.9 months (95% CI, 2.9-4.9) and PFS rate at 6 months was 32%. Median OS was 18.9 months (95% CI, 8.8-28.9). There was no statistical difference in PFS or OS by all biomarkers, including CPS cutoff for 1, 5, and 10. Of the 40 pts who had disease progression, 23 pts (49%) were treated with subsequent therapy. Treatment-related AEs (≥G3) occurred in 22 pts (47%), and immune-related AE (>G3) was observed in 3 pts (6%), including pneumonitis (G3) (n=1, 2%). Exploratory analysis of 13 cytokines from plasma at baseline showed an increase of interleukin-1 receptor antagonist (IL-1ra) (p=0.05), and increasing tendency of IL-8 and IL-12 in non-responders (PFS 8 mo.). Conclusion: Combination of Nivo and PTX demonstrated antitumor activity with manageable toxicity profiles as second-line treatment for AGC. Genomic analysis of tumor tissues by targeted next-generation sequencing are awaiting. Clinical trial information: NCT02951091 Citation Format: Rha Sun Young, Jii Bum Lee, Hyo Song Kim, Minkyu Jung, Choong-kun Lee, Sook Ryun Park, Dong-Hoe Koo, Hyun Woo Lee, Woo Kyun Bae, Hei Cheul Jeung, Hyun Cheol Chung. Open label, single-arm, multi-center phase Ib/II study to evaluate the safety and efficacy of nivolumab in combination with paclitaxel in Epstein-Barr virus (EBV)-related, or microsatellite instability-high (MSI-H), or programmed cell death ligand 1 (PD-L1) positive advanced gastric cancer (AGC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT159.

4063 Background: We evaluated the safety and efficacy of adding trastuzumab to ramucirumab and paclitaxel (TRP) as a second line treatment in human epidermal growth factor receptor 2 (HER-2)-positive advanced gastric or gastroesophageal junction (G/GEJ) cancer progressed from trastuzumab containing chemotherapy. Methods: Patients with HER-2-positive advanced G/GEJ cancer who progressed after first-line chemotherapy with trastuzumab in combination with fluoropyrimidine and platinum were eligible. Trastuzumab (Herzuma[CT-P6], Celltrion Inc.) 4mg/kg on day 1 followed by 2mg/kg on days 8, 15, and 22, ramucirumab 8mg/kg on days 1 and 15, and paclitaxel (dose level 1: 80mg/m2, dose level -1: 70 mg/m2) on days 1, 8, and 15 of a 28-day cycle was tested. After safety analysis of lead-in safety cohort (phase 1b), phase 2 part was conducted to evaluate the primary endpoint of progression-free survival (PFS). Secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Results: At the phase 1b part, as there was no dose limiting toxicity in 3 patients at the dose level 1, dose level 1 with full dose combination was determined as recommended phase 2 dose. At the time of data lock on Jan. 31, 2021, 45 patients among enrolled 50 patients were evaluable for response and safety including 3 patients from phase 1b part. Median age was 59 years old (range 30-82) and most patients were male (37/45). At baseline, 33 patients had tumors with HER-2 3+ by immunohistochemistry (IHC) and 12 had those with HER-2 2+ by IHC with ERBB2 amplification by in situ hybridization. With median follow-up duration of 11.6 months, median PFS and OS were 7.2 months (95% confidence interval [CI]: 6.0-8.5 months) and 13.6 months (95% CI: 10.3-16.9 months), respectively. ORR was 55.6% (25/45, complete response = 1, partial response = 24) and DCR was 95.6% (43/45), respectively. Most common hematologic adverse event (AE) was neutropenia (all grade: 64.4%, grade 3/4: 51.1%) with 1 case of febrile neutropenia (2.2%). Most common non-hematologic AE was peripheral sensory neuropathy (all grade: 33.3%, grade 3: 2.2%). Gastrointestinal (GI) bleeding occurred in 4 patients (grade 3 upper GI bleeding: 6.7%, grade 1 lower GI bleeding: 2.2%), whereas GI perforation was not observed. Hypertension occurred in 3 patients (all grade: 6.7%, grade 3: 4.4%). No new or unexpected AEs resulting in treatment cessation were observed with this combination regimen. Conclusions: The continuous use of trastuzumab beyond progression in combination with ramucirumab and paclitaxel showed promising activity and manageable safety profile in HER2 positive G/GEJ cancer patients who progressed after trastuzumab containing chemotherapy. Updated outcomes for ongoing patients will be presented.

PURPOSE This study was conducted to explore the process and operation of a cancer multidisciplinary team (MDT) after the reimbursement decision in Korea, and to identify ways to overcome the major barriers to effective and sustainable MDTs. MATERIALS AND METHODS Approximately 1,000 cancer specialists, including medical oncologists, surgical oncologists, radiation oncologists, pathologists, and radiologists in general hospitals in Koreawere invited to complete the survey. The questionnaire covered the following topics: organizational structure of MDTs, candidates for consulting, the clinical decision-making initiative, and responsibility for dealing with legal disputes. RESULTS We collected a total of 179 responses (18%) from physicians at institutions where an MDT approach was active. A surgical oncologist (91%), internist (90%),radiologist (89%),radiation oncologist (86%), pathologist (71%), and trainees (20%) regularly participated in MDT operations. Approximately 55% of respondents stated that MDTs met regularly. In cases of a split opinion, the physician in charge (69%) or chairperson (17%) made the final decision, and most (86%) stated they followed the final decision. About 15% and 32% of respondents were "very satisfied" and "satisfied," respectively, with the current MDT's operations. Among 38 institutional representatives, 34% responded that the MDT operation became more active and 18% stated an MDT was newly implemented after the reimbursement decision. CONCLUSION The reimbursement decision invigorated MDT operations in almost half of eligible hospitals. Dissatisfaction regarding current MDTs was over 50%, and the high discordance rates regarding risk sharing suggest that it is necessary to revise the current system of MDTs.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors originating in the gastrointestinal tract. With the introduction of molecular-targeted therapy for GISTs which has yielded remarkable outcomes, these tumors have become a model of multidisciplinary oncological treatment. Although Western clinical guidelines are available for GISTs, such as those published by the National Comprehensive Cancer Network (NCCN) and the European Society of Medical Oncology (ESMO), the clinical situations in Asian countries are different from those in Western countries in terms of diagnostic methods, surgical approach, and availability of new targeted agents. Accordingly, we have reviewed current versions of several GIST guidelines published by Asian countries (Japan, Korea, China, and Taiwan) and the NCCN and ESMO and discussed the areas of dissensus. We here present the first version of the Asian GIST consensus guidelines that were prepared through a series of meetings involving multidisciplinary experts in the four countries. These guidelines provide an optimal approach to the diagnosis and management of GIST patients in Asian countries.

218 Background: We report the updated clinical data and molecular profiling results of a multi-institutional phase Ib/II trial of triple combination (pembrolizumab, trastuzumab, and chempotherapy) as first line therapy for HER2 positive advanced gastric and gastroesophageal junction (AGC/GEJ) cancer. (PANTHERA trial; NCT02901301). Methods: Pembrolizumab 200mg IV D1, Trastuzumab 6mg/kg (after 8mg/kg load) D1, Capecitabine 1000mg/m2 bid D1-14, and Cisplatin 80mg/m2 D1 every 3 weeks was selected as recommended phase II dose. The primary endpoint for phase II was ORR per RECIST v1.1. Secondary endpoints included PFS, OS, DOR, safety, and predictive biomarker analysis by targeted NGS. Results: At the time of data lock on Aug 31, 2020, total of 43 patients were treated with median follow up of 18.2 months, and 3 patients remained on the treatment, and 6 patients finished 2-year treatment without progression. ORR was 76.7% (CR 16.3%, PR 60.5%, conversion surgery 4.6%) with 26 pts (56.6%) showing more than 50% of tumor burden reduction. Median PFS was 8.6 months (95% CI 7.2-16.5) and median OS was 19.3 months (95% CI 16.5-NR). There were no MSI-H/dMMR or EBV-positive pts. No patient discontinued pembrolizumab because of immune-related adverse events. Clinical features including PD-L1 status (55.3% of pts ≥ CPS 1 and 13.2% of pts ≥ CPS 10 among available 38 pts), metastatic organ or baseline tumor burden was not related to the survival. Ninety-eight tumor tissues from 39 pts (paired tumor tissues from 22 pts) were analyzed with targeted NGS. Although every pts were HER2 IHC-positive, baseline HER2 amplification by NGS was related to the survival ( HER2 amp (n=8) vs HER2 non-amp (n=23); mPFS, not reached vs 7.7 months, P=0.0178; mOS, not reached vs 17.9 months, P=0.044) but no other signaling pathways predicted pts’ survival. HER2 mutations including L869R or D769H were related to the acquired resistance. High TMB showed a tendency toward better survival (mPFS; High (n=7) vs Low (n=24) TMB, 22.0 vs 8.2, P=0.2835) due to small number of patients. Updated immune markers and serial NGS analyses will be presented. Conclusions: First-line triplet regimen (Pembrolizumab, Trastuzumab, and Chemotherapy) showed promising efficacy based on HER2 amplification by NGS regardless of PD-L1 status in AGC/GEJ cancer. Correlative biomarkers found from NGS study need to be validated through on-going phase III Keynote-811 study. Clinical trial information: NCT02901301. [Table: see text]

e19391 Background: Emerging oncology drugs such as targeted agents and immune checkpoint inhibitors (ICIs) have brought dramatic advances in cancer treatment, while rapid rise in the drug cost. In Korea, the policy of expansion of health insurance coverage has improved accessibility to high-priced oncology drugs through their registrations in reimbursement list. However, this made a considerable impact on the financial burden of national health insurance. The objective of this study was to assess the awareness and perceptions of medical oncologists about the value frameworks of cancer drugs in Korea. Methods: We collected the data from survey for 102 medical oncologists at cancer conference. They were asked about prioritization among multiple considerations when they prescribe cancer drugs, The second question was awareness of value frameworks such as American Society of Clinical Oncology (ASCO) value framework and European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). Additionally, potential application of value framework to the decision on reimbursement coverage was included. Results: The majority of respondents (90%) chose clinical efficacy as the most important factor when they selected oncology drug for cancer patients. Safety/tolerability and drug cost were followed as 5.9% and 1%, respectively. Meanwhile, the order of priority of considerations for ICIs treatment was as follows: clinical efficacy (74.5%), drug costs (13.7%), and safety/tolerability (9%). More than half of those questioned (53.9%) were already aware of ASCO value framework and ESMO-MCBS, while 26.5% did not recognize them at all. Over 90% of respondents agreed with the need for development of new value framework tool which can be complementary to current valuation system for oncology drugs. Oncologists responded positively to the necessity of the assessment tool as a criterion for reimbursement registration (84.3%) as well as post-reimbursement re-evaluation (89.2%). Conclusions: Our results suggest that value assessment tool of oncology drug be necessary for providing medical evidences for clinical decision and for determination to health insurance reimbursement in Korea.

3081 Background: Combining anti-PD-1 agent and trastuzumab has shown synergy in HER2 positive preclinical cancer models. We first report the result of a multi-institutional phase Ib/II trial of triple combination (pembrolizumab, trastuzumab, and chempotherapy) as first line therapy for HER2 positive AGC. (PANTHERA trial; NCT02901301). Methods: Pembrolizumab 200mg IV D1, Trastuzumab 6mg/kg (after 8mg/kg load) D1, Capecitabine 1000mg/m2 bid D1-14, and Cisplatin 80mg/m2 D1 every 3 weeks was selected as recommended phase II dose. The primary endpoint for phase II was ORR per RECIST v1.1. Secondary endpoints included PFS, OS, DoR, safety, and molecular analysis by targeted NGS. Results: Total of 43 patients were treated with median follow up of 16.1 months, and 11 pts remained on the treatment (treatment duration range: 1.4 to 24 months). There was significant tumor shrinkage of 95.3% with 54.6% median depth of response, with 76.7% ORR (CR 16.3%, PR 60.5%, conversion surgery 4.6%), and 97.7% DCR. Median PFS was 8.6 months (95% CI 7.2-22.0) and median OS was 18.4 months (95% CI 17.9-NA). Subsequent chemotherapy was given to 83.3% of 30 progressed pts. There were no MSI-H/dMMR or EBV-positive pts. PD-L1 status (57.1% of pts ≥ CPS 1 and 14.3% of pts ≥ CPS 10 among 35 pts), metastatic organ or baseline tumor burden was not related to the survival. Treatment-related AE (≥G3) occurred in 32 pts (74.4%) including 17 pts (39.5%) with neutropenia G3-4. Immune-related AEs (≥G3) occurred in 4 pts (10%). Ninety-six tumor tissues from 32 pts (paired tumor tissues from 25 pts) were analyzed with targeted NGS. TMB (median 12.7 mut/MB with range of 9.45-16.71) was not related to the PD-L1 expression or survival. Conclusions: First-line triplet regimen (Pembrolizumab, Trastuzumab, and Chemotherapy) confers a significant tumor shrinkage for HER2 positive AGC, regardless of PD-L1 status. Phase III Keynote-811 study (NCT03615326) is ongoing based on the protocol of this study. Clinical trial information: NCT02901301 . [Table: see text]

e16586 Background: Approximately 75% of GC cases occur in Asian persons. Pembrolizumab has shown antitumor activity in global studies of GC. KEYNOTE-063 (NCT03019588) is a randomized, open-label, phase 3 trial in Asian patients with advanced PD-L1–positive (combined positive score [CPS] ≥1) GC that progressed after platinum + fluoropyrimidine chemotherapy. After the KEYNOTE-063 study began, results of the global KEYNOTE-061 study (NCT02370498) showed that pembrolizumab did not prolong overall survival (OS) vs paclitaxel in patients previously treated for advanced GC (median OS, 9.1 months vs 8.3 months; hazard ratio [HR], 0.82; 95% CI, 0.66-1.03; 1-sided P= 0.0421 [significance threshold for OS was 1-sided P= 0.0135]). Methods: Eligible patients were randomly assigned in a 1:1 ratio to receive pembrolizumab 200 mg Q3W for up to 35 cycles (~2 years) or standard-dose paclitaxel. The primary efficacy end points were OS and progression-free survival (PFS). Planned enrollment was ~360 patients. Results: Because pembrolizumab did not significantly prolong OS in KEYNOTE-061, enrollment in KEYNOTE-063 was discontinued after 94 patients were enrolled (47 patients in each treatment group). In these Asian patients, median OS was 8.4 months in the pembrolizumab group and 7.7 months in the paclitaxel group; median PFS was 1.9 months and 4.0 months, respectively (Table). Objective response rate (ORR) and median duration of response (DOR) are shown in the Table. Drug-related adverse events (AEs) occurred in 59.6% of patients receiving pembrolizumab and in 95.5% of patients receiving paclitaxel (Table). Conclusions: In this small sample of Asian patients with PD-L1–positive advanced GC, definitive conclusions are limited; however, second-line pembrolizumab monotherapy seems to be well tolerated in this patient population. Because this study was terminated early, there was insufficient power for comparisons between groups; therefore, these data should be viewed with caution. Clinical trial information: NCT03019588 . [Table: see text]

The purpose of the current study was to evaluate the clinical outcomes of patients with metastatic renal cell carcinoma (mRCC) who interrupted vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI) therapy.A retrospective analysis of medical records was performed on all patients with mRCC treated with VEGFR-TKIs between January 2008 and July 2014 (n = 505). Patients who achieved stable disease (SD) or a better response under TKI and later discontinued TKI treatment for any reason with the exception of disease progression were included in the analysis.We identified 32 patients (sunitinib = 20, sorafenib = 7, and pazopanib = 5). The responses to VEGFR-TKIs were complete response (CR, n = 4), partial response (PR, n = 11), SD (n = 15), and controlled but nonmeasurable response (n = 2). Median time to TKI discontinuation from the initiation of VEGFR-TKI therapy was 16.6 months (95 % CI 12.8-20.3), and the main cause of VEGFR-TKI discontinuation was toxicity (n = 19, 59.4 %). At the time of analysis, 16 patients had disease progression and one patient died. With a median follow-up duration of 51.7 months (range 11.5-87.6), median progression-free survival (PFS) after TKI discontinuation was 20.2 months (95 % CI 6.4-34.0). In multivariate analysis, the duration of TKI therapy (1 year) before TKI discontinuation was an independent significant prognostic factor of poor PFS (p = 0.045). Among 11 patients who were retreated with the same TKI, two patients (18.2 %) achieved PR and nine achieved SD (81.8 %).VEGFR-TKI could be interrupted at least temporarily when clinically warranted in patients with mRCC sufficiently controlled by TKIs.

Purpose: Although a Do-Not-Resuscitate (DNR) order is widely in use, it is one of the challenging issues in end-of-life care. This study was conducted to investigate attit udes toward DNR according to education and clinical experience. Methods: Data were collected using a structured questionnaire comprisin g 30 items in a tertiary hospital in Seoul, Korea. Results: Participants were 238 nurses and 72 physicians. Most participants (99%) agreed to the necessity of DNR for reasons such as dignified death (52%), irreversible medical condition (23%) and patients' autonomy in decision making (19%). Among all, 33% participants had received education about DNR and 87% had DNR experience. According to participants' clinical DNR experience, their attitudes toward DNR significantly differed in terms of the necessity of DNR, timing of the DNR consent and post-DNR treatments including anti- biotics. However, when participants were grouped by the level of DNR education, no significant difference was observed except in the timing of the DNR consent. Conclusion: This study suggests that the attitudes toward DNR were more affected by clinical experience of DNR rather than education. Therefore, DNR education programs should involve clinical settings.

Trastuzumab (H)-based chemotherapy has been an active treatment in patients with HER2-positive breast cancer; however, primary and secondary resistance has occurred in patients treated with H alone or in combination with chemotherapy. Biomarkers were searched using tissue microarrays (TMA) in HER2-positive advanced breast cancer patients treated with H and paclitaxel (P) combination chemotherapy between October 2004 and August 2010. Tumor blocks were analyzed for Tau-protein, beta-III tubulin, PTEN, p27, IGF-1R, c-Met, CD44, and MUC4 by immunohistochemical (IHC) analysis. The correlation between IHC status and clinical outcomes, including response rate (RR), progression free survival (PFS), and overall survival (OS), was investigated. With a median follow-up duration of 54.1 months (range, 42.3-72.7 months), 65 patients received H + P chemotherapy. The overall RR was 63 % (95 % CI, 51-75 %), and seven patients (11 %) with high Tau/low PTEN expression showed a significantly lower RR (14 % vs. 69 %; p = 0.008). The odds ratio for a poor response was 13.3 (95 % CI, 1.5-119.0; p = 0.020). In addition, patients with high Tau/low PTEN showed a trend of poor survival in terms of PFS (6.6 months vs. 9.6 months, p = 0.052). Subsequent multivariate analysis showed that high Tau/low PTEN (hazard ratio [HR] 2.40, 95 % CI, 1.06-5.47; p = 0.037) was the poor prognostic factor independently associated with PFS after adjusting for possible confounding factors such as recurrence/metastasis, age, performance status, visceral metastasis, and hormone receptor status. High Tau-protein and low PTEN expression showed a significant association with poor response to H + P chemotherapy in patients with HER2-positive advanced breast cancer.

Purpose: The goals of this study were to investigate the clinical activity, safety, and biomarkers of dacomitinib, an irreversible tyrosine kinase inhibitor of EGFR, HER2, and HER4, in recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M-SCCHN). Experimental Design: Patients were eligible if the diseases were not amenable to curative treatment and had progressed on platinum-based chemotherapy, and were treated with dacomitinib 45 mg/day. The primary endpoint was objective response rate by RECISTv1.1. Exploratory analysis included the characterization of somatic mutation, gene copy number, gene expression, p16INK4A expression by IHC, and investigation of their relationship with clinical outcomes. Results: Forty-eight patients were evaluable for efficacy and toxicity. Ten patients (20.8%) had partial responses and 31 patients (65%) had stable diseases. The median progression-free survival (PFS) and overall survival (OS) were 3.9 months [95% confidence interval (CI), 2.9–5.0] and 6.6 months (95% CI, 5.4–10.3). Adverse events were mostly grade 1–2. Mutations in the PI3K pathway (PIK3CA, PTEN) and high expression of inflammatory cytokines (IL6, IL8, IL1A, IL1B, IL4, and TNF) were significantly associated with shorter PFS (2.9 vs. 4.9 months without mutations, P = 0.013; 2.8 vs. 9.9 months with low expression, P = 0.004). Those harboring PI3K pathway mutations or high inflammatory cytokine expression had shorter median OS (6.1 vs. 12.5 months lacking PI3K pathway mutations and with low inflammatory cytokine expression, P = 0.005). Conclusions: Dacomitinib demonstrated clinical efficacy with manageable toxicity in platinum-failed R/M-SCCHN patients. Screening of PI3K pathway mutation and inflammatory cytokine expression may help identify which R/M-SCCHN patients are likely to gain benefit from dacomitinib. Clin Cancer Res; 21(3); 544–52. ©2014 AACR.

Ramucirumab improves survival in gastric cancer patients. The efficacy and safety of ramucirumab outside of a clinical trial were evaluated using an expanded access program (EAP). Advanced gastric cancer patients treated with ramucirumab in combination with paclitaxel or with ramucirumab monotherapy in a Korean EAP were evaluated. Baseline characteristics were assessed for progression-free survival (PFS) and overall survival (OS), and adverse events were evaluated according to the treatment regimen. Of 265 patients, 228 received ramucirumab plus paclitaxel, and 37 received ramucirumab monotherapy. Grade 3 or 4 neutropenia was more common with ramucirumab plus paclitaxel than with ramucirumab monotherapy (46.7 vs. 8.1%). Gastrointestinal (GI) perforation developed in seven patients (3.1%) in the ramucirumab plus paclitaxel group. The overall response and disease control rates were 16.6 and 66.3% in the ramucirumab plus paclitaxel group, and 5.4 and 37.8% in the ramucirumab monotherapy group, respectively. PFS and OS were 3.8 and 8.6 months in the ramucirumab plus paclitaxel group, and 1.8 and 6.4 months in the ramucirumab monotherapy group, respectively. In multivariate analysis, alkaline phosphatase, albumin, and neutrophil-to-lymphocyte ratio (NLR) were the independent prognostic factors for PFS, while albumin, NLR, number of metastatic sites, and large amount of ascites were independent prognostic factors for OS. In the Korean EAP cohort, ramucirumab showed similar efficacy to the results of the previous trials for gastric cancer. However, the level of GI perforation was slightly increased in the ramucirumab plus paclitaxel group.

141 Background: Radiofrequency ablation (RFA) has been increasingly used for the treatment of pulmonary metastases from several types of malignancies. Methods: A retrospective analysis was performed for the safety and efficacy of percutaneous RFA in patients with metastatic colorectal cancer between October 2016 and June 2019 as well as assessing prognostic factors of local tumor control. Results: RFA was carried out for 48 lung metastases in 31 consecutive colorectal cancer patients. Male was 17 patients (55%), and the median age at RFA was 61 years (range, 42-81). The mean diameter of metastases targeted for RFA was 12 mm (range, 4-32), and 17 tumors (35%) were located in a sub-pleural or deep position. Although five cases (10%) were failed due to immediate complications, there was no procedure-related death. In terms of immediate complication, a total of 12 cases (25%) had events including nine pneumothorax (percutaneous drain in four), one pleural effusion, and two hemoptysis (ICU care in one). Delayed complications were lung abscess and diaphragm injury in each one patient, respectively. At the time of analysis, the median follow-up duration from RFA was 12.0 months (interquartile range, 6.5-23.1). Only two patients (6%) died of disease progression, and 3-year overall survival rate was 85.5% (95% CI, 75.5-95.5). RFA site progression was observed in 11 patients (23%), and 1-year and 2-year progression-free survival rates were 71.5% (95% CI, 58.7-84.3) and 56.6% (95% CI, 42.6-70.6), respectively. Multivariate analysis showed that extra-pulmonary progression (hazard ratio 17.49; p = 0.023) was only one independent prognostic factor associated with RFA site progression after adjusting for confounding factors including sex, age, performance, tumor size, location, contact with the vessel, last chemotherapy response, and duration. Conclusions: RFA is a comparatively safe and effective option for the treatment of small-sized lung metastases; however, the control of extra-pulmonary metastases should be accompanied for effective local control.

This study was designed to evaluate the prevalence of chromosomal abnormalities and to identify the specific abnormalities associated with poor prognosis. A total of 2,474 patients whose conventional cytogenetics were available at the time of diagnosis were evaluated via a nationwide registry. Normal metaphase cytogenetics was observed in 2,012 patients (81.3%). Among the 462 patients with chromosomal abnormalities, there were 161 (34.8%) patients with hyperdiploidy, 197 (42.6%) with pseudodiploidy, 79 (17.1%) with hypodiploidy, and 25 (5.5%) with near-tetraploidy. Deletion 13 (Δ13) in metaphase was observed in 167 patients (6.8%). Fluorescent in situ hybridization (FISH) was carried out in 967 patients (39.1%), and 66 (13.7%) out of 482 and 63 (10.3%) out of 611 patients were positive for t(4;14) and del(17p), respectively. With a median follow-up duration of 25.1 months, the median overall survival (OS) was 51.2 months (95% confidence interval, 46.5-55.9 months). In univariate analysis, the following four chromosomal abnormalities were significantly associated with a poor survival outcome: Δ13, hypodiploidy, del(13q) in FISH, and del(17p) in FISH. In the subsequent multivariate analysis, in which del(13q) and del(17p) in FISH were excluded due to a relatively low number of patients, Δ13 and hypodiploid status were independently associated with a poor survival outcome after adjusting for important clinical factors, including age, sex, performance, beta2-microglobulin, albumin, and lactate dehydrogenase (LDH). Using conventional metaphase cytogenetics, we confirmed that both Δ13 and hypodiploid status were robust poor prognostic factors. The metaphase karyotyping should remain the primary cytogenetic tool and an essential investigation for risk stratification in newly diagnosed multiple myeloma patients.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematological malignancy with a clinically aggressive phenotype arising from CD4/CD56-expressing plasmacytoid dendritic cell precursors [1]. BPDCN was categorized under "AML and related precursor neoplasms" by the 2008 WHO classification, with most cases having been previously classified as blastic natural killer (NK)-cell lymphoma/leukemia or agranular CD4+, CD56+ hematodermic neoplasm [2]. BPDCN cells generally express CD4, CD56, CD123, and TCL-1 but are negative for other T-, B-, NK-cell, or myeloid markers [3]. Clinically, patients with this disease typically present with a high incidence of cutaneous involvement described as generalized, localized, or solitary macules, plaques, and/or tumors, as the first manifestation, followed by involvement of bone marrow (BM), peripheral blood (PB), and lymph nodes (LNs). BM involvement usually occurs with leukemic progression of advanced or relapsed disease and is associated with a poor prognosis [4]. Diagnosis of leukemic BPDCN without cutaneous manifestation is rare. Here, we report a 41-yr-old man who was diagnosed with BPDCN in the absence of skin manifestation. This patient was admitted for evaluation and management of palpable multiple neck lymphadenopathies that had developed a week previously. No improvement was noted despite antibiotic therapy, and the lymphadenopathies spread to the left axillary and inguinal LNs. The initial blood analysis revealed a white blood cell (WBC) count of 6.1×109/L (reference range, 4.1-10.2×109/L), an Hb level of 12.7 g/dL (reference range, 13.7-16.8 g/dL), and a platelet count of 329×109/L (reference range, 158-332×109/L). Approximately 25% of cells appeared atypical on PB smear. Other laboratory findings were not significant except for an increased lactate dehydrogenase (LDH) level of 719 IU/L (reference range, 252-458 IU/L). Computed tomography (CT) imaging revealed multiple enlargements of the supraclavicular, right interlobar, inguinal, and iliac LNs, with no evidence of hepatosplenomegaly. Right supraclavicular LN biopsy and BM examination were also performed to characterize the atypical cells in the PB. Microscopic examination of the LN biopsies revealed diffuse infiltration by uniform, medium-sized cells together with effacement of the normal LN architecture. The tumor cells exhibited round or polygonal nuclei, coarse chromatin, and prominent nucleoli. Analysis of the BM aspirate revealed that blastoid cells accounted for up to 61% of all nucleated cells and had a similar morphology to those tumor cells that had infiltrated the LN in the BM study (Fig. 1). Fig. 1 (A) Peripheral blood smear (Wright-Giemsa stain, ×1,000): large atypical cells with high nuclear cytoplasmic (N/C) ratios, basophilic cytoplasm, and prominent nucleoli accounted for up to 25% of the leukocyte population. (B) In the bone marrow ... Flow cytometric analysis of the BM aspirate revealed 48% CD45dim positive cells within the blast gate, which were positive for CD33, CD7, CD56, CD117, HLA-DR, CD13 weak (w), CD11cw, and negative for myeloperoxidase (MPO), CD14, CD64, CD2, CD3, CD5, cytoplasmic CD3, CD10, CD19, CD20, CD22, CD79a, kappa and lambda light chain, terminal deoxynucleotidyl transferase (TdT), and CD34 (Fig. 2). Immunohistochemical staining of the BM section revealed it to be negative for MPO, non-specific esterase (NSE), and Periodic acid-Schiff (PAS) stain. The acute leukemic presentation and expression of myeloid lineage-associated markers with the exception of MPO was suggestive of AML with minimal differentiation. Fig. 2 Flow cytometric analysis of the bone marrow aspirate. CD45dim cells within the blast gated cells were negative for CD34 and positive for CD56, CD33, and CD7 (red circles). The neoplastic BPDCN cells are characterized as medium-sized cells with round nuclei and finely dispersed chromatin with absent or indistinct nucleoli, which thus resemble blasts. In addition, the cytoplasm is scant and has no granules [1]. Likewise, in this case, it could be confused with acute leukemia and the BPDCN could consequently be missed because the neoplastic BPDCN cells are similar to blasts that lack lineage-specific markers. Further evaluation is necessary for an accurate diagnosis. Therefore, we performed immunohistochemical staining of the LN biopsy and found that the tumor cells were positive for leukocyte common antigen (LCA), CD4, CD56 and bcl-2 (Fig. 3); negative for MPO, CD3, CD5, CD8, CD10, CD20, CD21, CD15, CD30, CD1a, CD34, TdT, multiple myeloma oncogene 1 (MUM1), anaplastic lymphoma kinase (ALK), and bcl-6; and had a ki-67 labeling index of 60%. Based on these findings, the initial differential diagnosis included leukemic infiltration of acute leukemia, T cell lymphoma, myeloid leukemia/sarcoma, or acute leukemia presenting as BPDCN. We examined the whole body for skin involvement, but found no skin lesions in this patient. Nonetheless, the leukemic presentation with strong positivity for CD4 and CD56, combined with the absence of lineage-specific markers in blastoid cells were indicative of BPDCN. We additionally confirmed immunohistochemical positivity for CD4 and CD123 in BM and CD123 in the LN biopsy. Taken together, the diagnosis was most consistent with the current WHO category of BPDCN within the "AML and related precursor neoplasms" group of malignancies. Fig. 3 Immunohistochemical staining of the right supraclavicular lymph nodes biopsy. (A) CD4+, (B) CD56+, (C) leukocyte common antigen (LCA)+, and (D) CD123+. In a cytogenetic study, complex structural abnormalities were observed and the karyotype was found to be 45,XY,der(3;7)(q10;q10),t(6;19)(p21.1;p13.3),t(8;18)(q24.1;q21.1) in 16 out of 20 analyzed metaphase cells. Leroux et al. [5] reported that chromosomal alterations in BPDCN seemed to occur most frequently at 6 chromosomal sites: 5q (72%), 12p and 13q (each 64%), 6q (50%), 15q (43%), and 9 (28%). However, the malignant cells in this case did not show aberrations at any of these chromosomal sites. BPDCN might be linked to genetic disorders that involve CDKN1B, CDKN2A, ARF, CDKN2, RB1, and MLL-ENL rearrangement, although the etiology and prognosis of BPDCN remains unclear [6-8]. BPDCN is initially highly sensitive to chemotherapy, with complete response rates ranging from 47% to 86%. However, the prognosis is poor even for patients who achieve a complete response, with a median survival period of 14 months (range, 10-18 months), and 2- and 5-yr overall survival rates of 33% and 6%, respectively [9, 10]. In leukemic BPDCN patients without cutaneous manifestations, the median survival was even lower at only 10 months. However, this survival data should be interpreted with caution because the therapeutic management of the patients was inhomogeneous and often not optimal [11]. It was recently suggested that patients with BPDCN should be treated with chemotherapy similar to that used for AML, followed by allogeneic stem cell transplantation (SCT) on complete response [12]. We performed further molecular studies of prognostic markers such as NPM1, cKIT, and FLT3-ITD, but detected no mutations. Induction chemotherapy with cytarabine and daunorubicin was administered, and a follow-up BM biopsy at day 14 after the start of chemotherapy revealed a marrow hypocellularity of 15% with no residual leukemic cells. The patient was transferred to another hospital for allogenic stem cell transplantation. Although a few case reports and literature reviews of BPDCN without cutaneous lesion have been reported worldwide [9, 11], there has been no report in Korea. We describe, to our knowledge, the first Korean case of acute leukemic presentation of BPDCN without cutaneous lesion. Even in the absence of characteristic cutaneous manifestations of BPDCN, patients with leukemic presentation and an absence of lineage-specific markers should undergo immunophenotyping including CD4, CD56, and CD123 to exclude this malignancy. Cytogenetic molecular analysis is necessary to further investigate the pathogenesis and genetic background of BPDCN.

ObjectiveAnemia of chronic disease (ACD) refers to hypoproliferative anemia in the context of acute or chronic activation of the immune system. There is a paucity of prospective data addressing the risk factors for ACD development. An association between common chronic diseases and ACD was examined cross-sectionally and longitudinally.MethodA cohort of 265,459 healthy participants without ACD at baseline were prospectively followed annually or biennially.ResultsDuring average follow-up period of 62 months, 4,906 participants developed ACD (incidence rate 3.58 per 1000 person-years). Multivariable-adjusted hazard ratio (HR) [95% confidence interval (CI)] for incident ACD comparing estimated glomerular filtration rate 30-60 and < 30 vs. ≥ 60 ml/min/1.73 m2 were 3.93 [3.18-4.85] and 39.11 [18.50-82.69]; HRs [95% CI] for ACD comparing prediabetes and diabetes vs. normal were 1.19 [1.12-1.27] and 2.46 [2.14-2.84], respectively. HRs [95% CI] for incident ACD comparing body-mass-index (BMI) of < 18.5, 23-24.9 and ≥ 25 vs. 18.5-22.9 kg/m2 were 0.89 [0.78-1.00], 0.89 [0.80-0.99] and 0.78 [0.66-0.91], respectively. HRs [95% CI] for incident ACD comparing prehypertension and hypertension vs. normal were 0.79 [0.73-0.86] and 1.10 [0.99-1.23], respectively. Metabolic syndrome, hypertension, chronic liver disease, and chronic obstructive pulmonary disease were not associated with incident ACD.ConclusionsThe severity of chronic kidney disease and diabetic status were independently associated with an increased incidence of ACD, whereas prehypertension and an increasing BMI were significantly associated with decreased risk of ACD.

A phase I trial of first-line vorinostat, an orally bio-available histone deacetylase inhibitor, in combination with capecitabine plus cisplatin (XP) was performed to assess recommend phase II trial dose in patients with advanced gastric cancer. Five dose levels of three-weekly vorinostat-XP were tested; vorinostat was dosed at 300-400 mg once daily on Days 1-14, capecitabine at 800-1,000 mg/m(2) twice daily on Days 1-14, and cisplatin at 60-80 mg/m(2) on Day 1. To assess the pharmacodynamics of vorinostat, histone H3 acetylation was assessed in peripheral blood mononuclear cells before the study treatment and at Day 8 of cycle 1. In total, 30 patients with unresectable or metastatic gastric adenocarcinoma were included. Dose-limiting toxicities were thrombocytopenia, fatigue, stomatitis, and anorexia. The following doses were recommended for phase II trial: 400 mg of vorinostat once daily, 1,000 mg/m(2) of capecitabine twice daily, and 60 mg/m(2) of cisplatin. The most common grade 3-4 toxicities were neutropenia (47 %), anorexia (20 %), thrombocytopenia (17 %), and fatigue (13 %). In overall, response rate was 56 % (95 % confidence interval [CI]: 32-81). With a median follow-up of 14.1 months, the median progression-free survival and overall survival were 7.1 months (95 % CI: 3.8-10.3) and 18.0 months (95 % CI: 4.8-31.1), respectively. The change in H3 acetylation after treatment with vorinostat correlated significantly with the vorinostat dose (300 vs. 400 mg/day) and the baseline level of H3 acetylation before treatment. Three-weekly vorinostat-XP regimen is feasible and recommended for further development in advanced gastric cancer.

Although recent studies have suggested that cessation of imatinib (IM) in chronic myeloid leukemia patients can be associated with sustained response, further validation is needed to explore predictive factors. In a prospective, multicenter study, chronic phase patients were eligible for cessation of IM therapy after more than 3 years if they had no detectable BCR-ABL1 transcript for at least 2 years. A total of 48 patients with a median age of 47 years (19-74 years) were enrolled. Twenty patients received IM for post-transplant relapse. After a median follow-up of 15.8 months (1.4-28.2 months) after IM discontinuation, nine of the non-transplant group lost undetectable molecular residual disease (UMRD) and major molecular response (MMR), whereas none of the 20 patients in the transplant group experienced UMRD loss. Probabilities for sustained MMR and UMRD were 64.4% and 66.3% in the non-transplant group, respectively. Of nine patients re-treated with IM, eight patients re-achieved MMR at a median of 1.7 months (0.9-2.8 months). Seven of these patients re-achieved UMRD at a median of 5.6 months (2.8-12.1 months). Previous transplantation, IM duration, and UMRD duration were significantly associated with sustained molecular responses. Our data strongly suggest that immunological control contributes to sustained suppression of residual leukemia cell expansion and that IM can be safely discontinued in patients with post-transplant relapse.

This study aims to comprehensively assess the publication of clinical trial results and factors associated with their publication.Phase II and III trials of advanced breast cancer registered on ClinicalTrials.gov between October 1, 2000, and September 30, 2012, were identified. Publications were searched by using PubMed and reviewing those listed on the registry site. The main outcomes were publication rate, public availability of results, and time to publication.Of 352 phase II and 74 phase III trials, 12.5% and 31.1% were published, whereas 46.9% and 58.1% had publicly available results, respectively. Compared to those with significant results, studies with nonsignificant results had delays in time to publication (P 0.001). Even after adjusting for funding source and phase type, the significance of study outcomes was a significant factor that affected time to publication (hazard ratio = 6.02; 95% confidence interval: 3.59, 10.07; P 0.001), with trials with significant outcomes taking less time to publish than those with nonsignificant outcomes.Underreporting of results and nonpublication or delays in the publication of negative results were identified in registered trials of advanced breast cancer. Thus, further initiatives appear necessary to urgently address such publication bias.

Aim To evaluate tumor markers as prognostic factors in patients with metastatic or recurrent gastric cancer receiving first-line chemotherapy. Methods Between January 2000 and December 2008, 1178 patients with metastatic or recurrent gastric cancer were assayed for expression of three serum tumor markers, CA 19-9, CA 72-4 and carcinoembryonic antigen (CEA), prior to the initiation of first-line chemotherapy. Results Elevated serum concentrations of carbohydrate antigen (CA) 19-9 (>37 U/mL), CA 72-4 (>4 U/mL) and carcinoembryonic antigen (CEA) (>6 ng/mL) were observed in 38, 56 and 33% of patients, respectively. Univariate analysis showed that elevated serum concentration of each of the three markers, CA 19-9 (P = 0.001), CA 72-4 (P = 0.001) and CEA (P = 0.030), was significantly associated with poor patient prognosis. However, multivariate analysis showed that an elevated CA 19-9 concentration only was significantly associated with shorter survival (hazard ratio [HR] 1.22; 95% CI, 1.08–1.37, P = 0.002). In the good risk and moderate risk groups, previously defined by clinical factors alone, survival was significantly lower in patients with elevated CA 19-9 (P

Backgrounds: Trastuzumab-based chemotherapy has been an active treatment in patients (pts) with HER2−positive breast cancer; however, primary and secondary resistance has occurred in pts treated with trastuzumab (H) alone or in combination with chemotherapy. Material and Methods: Biomarkers were searched using tissue microarrays (TMA) in the HER2−positive breast cancer pts treated with H and paclitaxel (P) combination chemotherapy between October 2004 and August 2010. Tumor blocks of 101 pts were analyzed for VEGF, IGF-1R, p-Akt, beta-III tubulin, CD44, Tau-protein, p27 and PTEN by immunohistochemical (IHC) analysis. Eight biomarkers were assessed to investigate the correlation with the clinical outcomes, including response rate (RR), progression free survival (PFS), and overall survival (OS). Results: With a median follow-up duration of 21.7 months (range, 9.1−55.2 months), 101 pts received H+P chemotherapy in neoadjuvant setting (n=36, 35.6%) and recurrent or metastatic setting (n=65, 64.4%). Median age was 48 (range, 19–83 years), and the majority of pts (n=95, 94.1%) had good performance status. Premenopausal pts and hormone receptor-negative pts were 48 (47.5%) and 52 (51.5%), respectively. The median cycle of H+P chemotherapy was six (range, H 1–43; P 1–21). Overall RR was 68.3% (n=69) including complete response with 7 pts, and PFS and OS were significantly longer in pts responsive to H+P chemotherapy compared with non-responsive patients (PFS, p=0.001; OS, p=0.015). Although VEGF, IGF-1R, p-Akt, beta-III tubulin, CD44, p27 and PTEN status by IHC were not significantly associated with response to H+P chemotherapy, Tau-protein showed a trend of association without statistical significance (RR, 46.2% vs. 71.6%, p=0.066). Among 13 pts with high Tau protein expression, 9 pts with both high Tau-protein and low PTEN level showed statistically significant lower RR compared with other 92 pts (22.2% vs. 72.8%; p=0.002). None of the biomarkers was related to PFS and OS in pts with recurrent or metastatic disease, and to pathologic complete response in pts after H+P chemotherapy as neoadjuvant therapy. Conclusion: Our data showed that both low PTEN level and high Tauprotein expression were significantly associated with poor response to H+P chemotherapy in patients with HER2−positive breast cancer. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-13-11.

Many predictive models have been proposed for better stratification of diffuse large B-cell lymphoma (DLBCL). Hans' algorithm has been widely used as standard to sub-classify DLBCL into germinal center B-cell (GCB) and non-GCB origins. However, there have been disagreements in the literature regarding its prognostic significance. Here, we retrospectively analyzed Hans' algorithm and the individual immunohistochemical biomarkers at different cut-off values (5%, 30%, 50% or 75%) in 94 Korean patients with DLBCL treated with combination chemotherapy with cyclophosphamide, daunorubicin, vincristine, and prednisone. No significant differences were observed between the GCB (18 patients, 19.1%) and non-GCB (76, 80.9%) groups. Among individual biomarkers, CD10 negativity (cut point: 30%) and bcl-6 positivity (cut point: 5%) were independent good prognostic markers in progression-free survival (PFS), whereas bcl-6 (cut point: 5%) positivity was an independent good prognostic marker in overall survival irrelevant of international prognostic index. The present study showed the lack of predictability of Hans' algorithm in DLBCL patients, and that CD10, Bcl-6 may have diverse prognostic significance at different cut-off values. Our results suggest that the proposed cut-off value may not be applied universally, and that the optimal cut-off value may need to be optimized for individual laboratory.

Objectives: We evaluated prognostic factors affecting relapse-free survival (RFS) and overall survival (OS), and investigated the role of adjuvant chemotherapy in patients with small bowel adenocarcinoma (SBA). Methods: Data from 52 patients with SBA who underwent curative surgery at the Asan Medical Center between January 1989 and December 2009 were retrospectively analyzed. Patients were divided into two groups: those who did (n = 23) and did not (n = 29) receive adjuvant chemotherapy. Results: At a median follow-up of 32.2 months (range, 5.5–212.2 months), relapses had occurred in 17 patients (32.7%), with a 5-year RFS rate of 52.9% (95% CI, 39.3–66.5%), and 19 patients (36.5%) had died, with a 5-year OS rate of 59.0% (95% CI, 45.6–72.4%). The most frequent sites of relapse were the peritoneum and liver. Multivariate analysis showed that lymph node involvement was the only factor independently associated with poor RFS and OS. After inverse probability of treatment weighting adjustment, adjuvant chemotherapy did not enhance RFS [hazard ratio (HR), 1.399; 95% CI, 0.498–3.933] or OS (HR 0.797; 95% CI, 0.307–2.068). Conclusions: Lymph node involvement is a predictor of poor prognosis in patients with SBA who undergo curative surgery.

Ifosfamide, a potent alkylating agent, is rarely incorporated into small cell lung cancer (SCLC) treatment. The aim of this study was to assess the efficacy and safety of ifosfamide in combination with carboplatin and etoposide (ICE) in previously untreated patients with SCLC.From January 2002 to January 2014, we consecutively enrolled 69 patients with SCLC who were treated with ICE as initial chemotherapy at Kangbuk Samsung Hospital. The modified ICE regimen consists of ifosfamide 1200 mg/m(2)/day on days 1, 2, and 3 with mesna, etoposide 80 mg/m(2)/day on days 1, 2, and 3, and carboplatin AUC 6 on day 1. Treatment was repeated every 3 weeks and continued for up to nine cycles. Response assessments were performed every three cycles with computed tomography.Among 69 patients with SCLC, the median age was 69 years (range 51-88 years). Sixteen (23 %) patients had limited disease (LD), and 53 (77 %) had extensive disease (ED). The overall response rate was 73 %. Stable disease rate was 20 %. The median overall survival was 11.3 months [95 % confidence interval (CI) 8.9-14.1] in the overall population, 20.6 months (95 % CI 14.2-21.2) for LD and 9.1 months (95 % CI 7.8-11.6) for ED. The median number of administered cycles was 6 (range 1-9). Grade ≥3 hematological toxicities included neutropenia (34 %), anemia (59 %), and thrombocytopenia (31 %). Grade ≥3 non-hematological toxicities included peripheral neuropathy in 2 %.In chemonaïve patients with SCLC, modified ICE is well tolerated and shows favorable efficacy.

The aim of this study was to investigate the changes in health-related profiles including quality-of-life (HRQoL) in the chronic myeloid leukemia (CML) patients who discontinued imatinib (IM). An HRQoL survey composed of 43 parameters about IM-related adverse events (AEs), physical health-related and mental health-related was provided at baseline and 6 months post-discontinuation. A total of 55 patients with a sustained UMRD over 6 months were analyzed. Although the majority of IM-related AEs were significantly improved, unexpectedly pruritus and musculoskeletal pain worsen or newly develop in 29.1% and 21.8% of patients, respectively. The improvements in physical and mental health condition were variable in individual patients. In addition, rapid restorations of the hematological and biochemical parameters were observed. The results showed the changes of HRQoL and laboratory tests in treatment-off patients and the necessity of continuing physical and mental support for some patients in tyrosine kinase inhibitor (TKI)-off studies.

83 Background: Progranulin (PGRN), characterized as an autocrine growth and survival factor, is known to stimulate the tumorigenesis and proliferation of several cancer cell types. However, little is known about the prognostic role of PGRN in metastatic or recurrent gastric cancers (MRGCs). Methods: A retrospective analysis was performed on patients with MRGCs who had received palliative chemotherapy between January 2010 and March 2014. PGRN expression in tumor cells by immunohistochemical staining was calculated as the product of proportion (0 = none; 1 ≤ 25%; 26% ≤ 2 ≤ 50%; 3 > 50%) and intensity score (0, no staining; 1, weak; 2, moderate; 3, strong), and categorized as high expression (Score ≥ 4) or low expression ( < 4). Results: A total of 101 patients were analyzed with the median age of 57 years (range, 24–79) at first-line chemotherapy, and 66 patients (65%) were male. Twenty-three patients (23%) had high PGRN expression tumors, and they were almost younger patients (≤ 65 years, 96%). In terms of metastatic sites, the patients with high PGRN tumors had more liver metastasis (30% vs. 17%), and the patients with low PGRN had more bone metastasis (10% vs. 4%). There were no significant differences in the proportion of patients with a response to chemotherapy (32% vs 38%) between patients with high or low PGRN tumors. The median follow-up duration of surviving patients was 54.8 months (range 34.5-81.4 months). Overall, 90 patients (89%) died, and a median overall survival (OS) and progression free survival (PFS) were 13.1 months (95% CI, 9.5–16.8 months) and 5.6 months (95% CI, 4.7-6.5), respectively. The PFS and OS were not statistically different between patients with high PGRN tumors and those that were low PGRN (median PFS 5.2 vs 5.9 and OS 14.9 vs 13.0 months, P = 0.471 and 0.927, respectively). In addition, multivariate analysis showed that PGRN expression was not a prognostic factor in both PFS and OS after adjusting for possible confounding factors including sex, age, performance, histopathology and number of metastasis. Conclusions: There was no relationship between PGRN expression and response to chemotherapy or prognosis in patients with MRGCs.

696 Background: Progranulin (PGRN), characterized as an autocrine growth and survival factor, is known to stimulate the tumorigenesis and proliferation of several cancer cell types. Evidence has emerged for a potential role of PGRN as biomarkers in some diseases, however, little is known about the prognostic role of PGRN in colorectal cancers (CRCs). Methods: A retrospective analysis was performed on patients with CRCs underwent curative resection between May 2013 and June 2015. PGRN expression in tumor cells was semiquantitatively categorized (no expression, 0; weak/focal, 1+; moderate/focal or diffuse, 2+; strong/diffuse, 3+). PGRN was considered positive when either tumor cells were shown with 2+ or 3+ staining intensity. Results: A total of 109 patients (28 stage I, 32 stage II, and 49 stage III) were analyzed. The median age was 67 years (range, 30–86) and 66 patients (61%) were male. Thirty-eight patients (35%) had high tumor PGRN expression (PGRN-positive), and there was a trend of elevated pre-operative CEA and CA19–9 in patients with PGRN–positive tumor compared to those with PGRN–negative tumor (CEA, 49% vs. 21%, P = 0.003; CA19–9, 21% vs. 7%; P = 0.077). The median follow-up duration for surviving patients was 28.9 months (interquartile range, 22.5–33.9). The 3–year RFS and OS were 83.7% (95% CI, 76.8–90.6) and 96.0% (95% CI, 92.3–99.7), respectively. Patients with PGRN–positive tumors had a worse recurrence free survival (RFS) with a 66.8% at 3–year (95% CI, 51.8–81.8) compared to PGRN–negative patients with a 92.4% at 3–year (95% CI, 86.2–98.6; P = 0.01). Multivariate analysis for RFS showed that PGRN–positive tumors (hazard ratio [HR] 4.61, 95% CI, 1.26–16.93; P = 0.021) and age ( > 66 years, HR 8.87, 95% CI, 1.94–40.53; P = 0.005), stage (III, HR 8.56, 95% CI, 2.02–36.27; P = 0.004) and perineural invasion (HR 4.64, 95% CI, 1.05–20.62; P = 0.043) were prognostic factors independently associated with poor RFS after adjusting for possible confounding factors including sex, MSI status, tumor location, KRAS status, and lympho-vascular invasion. Conclusions: PGRN overexpression was significantly associated with poor RFS in patients with CRCs underwent curative resection.

Although epidermal growth factor receptor–tyrosine kinase inhibitors (EGFR–TKIs) have become key therapeutic agents for non-small cell lung cancer (NSCLC) patients with EGFR mutation, little is known about the efficacy of EGFR–TKIs according to different treatment timings. A total of 1,250 patients with NSCLC were screened for EGFR mutations at a single institution between March 2006 and May 2010. The efficacy of EGFR–TKIs in terms of response rate (RR), progression-free survival (PFS), and overall survival (OS) were compared according to the treatment timing. Among the 437 patients (36.1 %) with EGFR mutation, we analyzed 222 patients who received EGFR–TKI treatment. With a median follow-up duration of 27.5 months (range 8.3–69.2), EGFR–TKI was given to 97 (43.7 %), 109 (49.1 %), and 16 (7.2 %) patients as first-line, second-line, and third-line therapy, respectively. All three groups showed similar RR (71.1, 72.5, and 75.0 %, respectively) to EGFR–TKI (p = 0.802). No significant difference was observed according to treatment timing of EGFR–TKI in terms of PFS (median 10.6, 13.0, and 10.4 months; p = 0.670) and OS (median 20.5, 26.2, and 17.1 months; p = 0.142). The treatment timing of EGFR–TKI still showed no association with PFS or OS after adjusting significant prognostic factors including performance, disease status, and EGFR mutation types. EGFR–TKIs showed similar efficacy in patients with EGFR mutation-positive adenocarcinoma in terms of RR, PFS, and OS irrespective of treatment timing. Although EGFR–TKIs are currently the treatment of choice of first-line treatment in patients with EGFR-positive tumors, the sequential treatment with EGFR–TKI could be a reasonable option when EGFR mutation status cannot be obtained in a short time.

The most common metastatic sites from gastric cancer are the liver, intra-abdominal lymph nodes, ovary and peritoneal cavity. Cutaneous metastasis of gastric cancer is rare, and most cutaneous metastases are typically solitary, nodular, have a firm consistency, and are red or hyperpigmented. Thus, cutaneous metastasis is easily distinguished from other skin disease. We report a case of a 60-year-old woman with cutaneous metastasis of gastric cancer, whose facial skin showed painless pruritic eczema, resembling acute dermatitis. She had earlier undergone a total gastrectomy for advanced gastric cancer in our hospital. After 14 months, she developed eczematous facial lesions; the presumptive diagnosis was acute dermatitis. However, skin biopsy unexpectedly revealed cutaneous metastasis of gastric cancer. After 6 months of systemic chemotherapy with capecitabine and cisplatin, the cutaneous metastasis was markedly improved and a clinically complete remission was accomplished.

In the version of this article initially published, the first affiliation (affiliation number 1) was incorrectly stated as "Division of Gastroentorology, Department of Internal Medicine." The correct affiliation is "Department of Internal Medicine."

Classical Kaposi’s sarcoma is an unusual multifocal neoplasm of vascular endothelial cell origin, and considered a less malignant, slowly-progressing tumor. Although visceral involvement is occasionally seen in HIV/AIDS patients with KS, tumor dissemination to visceral lymph nodes in classical KS is very rare. A 72-year-old woman without any other relevant past medical history presented with anorexia, weight loss, night sweats, and skin eruptions. As the rapid progression of cytopenias and lymphadenopathy were observed, bone marrow biopsy and imaging were performed. Positron emission tomography showed disseminated lymphadenopathy in the cervical, axillary, mediastinal, inguinal, and abdomino-pelvic nodal areas. Inguinal lymph node biopsy was compatible with KS, positive for CD31, CD34, and human herpesvirus-8 by immunohistochemical stain. We report a case of aggressive classical KS mimicking aggressive malignant lymphoma.

BackgroundProgranulin (PGRN) is considered to play an important role in breast cancer tumorigenesis and in inhibiting tamoxifen-induced apoptosis. We aimed to determine whether PGRN levels are associated with breast cancer recurrence after curative surgery.Methodology/principal findingsWe evaluated the associations between preoperative serum PGRN levels and breast cancer recurrence in a cohort of 697 newly diagnosed breast cancer patients who underwent curative surgery between April 2001 and December 2004. The mean age ± standard deviation (SD) was 46 ± 9.8 years, and all patients with hormone receptor (HR)-positive tumors received adjuvant tamoxifen therapy. At a median follow-up of 62.2 months (range, 2.9-98.2), 89 patients (12.8%) had experienced a recurrence and 51 patients (7.3%) had died. In the HR-positive group, serum PGRN levels were associated with recurrence according to the log-rank test for trend (p for trend = 0.049). There was no association between PGRN levels and recurrence in the HR-negative group (p for trend = 0.658). Adjusted hazard ratios, including possible confounders, revealed a linear relationship between serum PGRN levels and recurrence in the HR-positive group (p for trend = 0.049), and this association was further strengthened after excluding patients who had no lymph node metastasis (p for trend = 0.038).Conclusions/significanceSerum PGRN levels were clinically significant for predicting recurrence in patients with HR-positive breast cancer during adjuvant tamoxifen therapy.

This phase II study evaluated the feasibility and efficacy of one cycle of induction chemotherapy, followed by concurrent chemoradiotherapy (CRT) featuring capecitabine/cisplatin, followed in turn by surgery, in the treatment of patients with resectable esophageal squamous cell carcinoma.Between March 2003 and April 2005, 54 patients with stage II or III esophageal cancer were treated with induction chemotherapy (cisplatin 60 mg/m(2) on day 1; capecitabine 1,000 mg/m(2) bid on days 1-14) followed by concurrent radiotherapy (46 Gy in 23 fractions) and chemotherapy (cisplatin 30 mg/m(2) on days 1, 8, 15, and 22; capecitabine 800 mg/m(2) bid 5 days/week). Surgery was performed within 8 weeks of the end of radiotherapy.Median age of the patients was 64.5 years (range, 45-74 years). After CRT, 52 patients (96%) showed a clinical response, including 26 (48%) who exhibited a complete response (CR). Surgery was performed on 41 patients (76%), with 20 (37%) achieving pathologic CR and 3 (6%) dying of postoperative pneumonia. At a median follow-up time of 74.2 months (range, 64.3-84.8 months), 16 patients (30%) had experienced tumor recurrence and 36 (67%) had died. Of the 41 patients who underwent esophagectomy, 5 (12%) had exclusively locoregional disease and 7 (17%) had distant metastasis, whereas no one had both. The 5-year progression-free and overall survival rates were 30.2% (95% confidence interval [CI], 18.0-42.4%) and 37.0% (95% CI, 24.1-50.0%), respectively.A trimodal approach, consisting of a single cycle of induction chemotherapy, CRT containing capecitabine and cisplatin, and surgery, was feasible and effective in patients with resectable esophageal squamous cell carcinoma.

Doses and schedules of the combination of S-1 and cisplatin for the treatment of advanced gastric cancer (AGC) have not been standardized. We therefore evaluated the efficacy and feasibility of a 3-week schedule of S-1 and cisplatin in patients with AGC, as well as assessing factors prognostic of patient outcomes.A total of 159 patients with AGC were treated with S-1 (40 mg/m(2) bid on days 1-14) and cisplatin (60 mg/m(2) IV on day 1) between January 2004 and December 2008.Median follow-up duration was 20.0 months (range, 11.4-48.5 months), during which time 129 patients (81.1%) died. Patients received a median 6 cycles of chemotherapy (range, 1-19 cycles). Among the 59 patients with measurable disease, 1 achieved a complete response (1.7%) and 24 (40.7%) had partial responses, giving an overall response rate of 42.4% (95% CI, 23.0-61.8%). The median progression-free survival (PFS) was 5.8 months (95% CI, 4.8-6.9 months), and the median overall survival (OS) was 11.3 months (95% CI, 9.6-13.0 months). Multivariate analysis showed that initial metastasis, bone metastasis, and liver metastasis were independent prognostic factors for reduced PFS, whereas poor performance status, initial metastasis, and bone metastasis were prognostic for reduced OS. Application of a previous prognostic model showed that observed PFS and OS survival curves for patients in various risk groups differed significantly (P0.001 each).A 3-week regimen of S-1 plus cisplatin was active and well tolerated as first-line treatment in patients with AGC. Disease status and bone metastasis were the most important prognostic factors.