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Background Oxaliplatin as part of XELOX regimen has a more favorable toxicity profile than cisplatin for patients with advanced gastric cancer (GC). However, oxaliplatin can induce sensory neuropathy, a cumulative, dose-related toxicity. Thus, capecitabine maintenance regimen might achieve maximum treatment effect while reducing cumulative neurotoxicity of oxaliplatin. The aim of this study was to compare survivals of AGC patients between capecitabine maintenance and observation after 1st line XELOX chemotherapy. Methods Sixty-three patients treated with six cycles of XELOX for AGC in six hospitals of the Catholic University of Korea were randomized 1:1 to capecitabine maintenance or observation. The primary end point was PFS (PFS) analyzed using a two-sided log-rank test stratified at 5% significance level. Results Between 2015 and 2020, 32 and 31 patients were randomized to maintenance and observation groups, respectively. After randomization, the median number of cycles for maintenance capecitabine was 6. PFS was significantly higher for the maintenance group (6.3 months vs. 4.1 months, P = 0.010). OS (OS) was not significantly different between the two groups (18.2 months vs. 16.5 months, P = 0.624). Toxicity such as hand-foot syndrome was reported in some cases of the maintenance group. Maintenance treatment was a significant factor associated with PFS in multivariate analysis (HR: 0.472, 95% CI: 0.250-0.890, P = 0.020). Conclusions After six cycles of XELOX chemotherapy, capecitabine maintenance significantly prolonged PFS than observation and toxicity was manageable. Maintenance treatment was a significant prognostic factor associated with PFS.

Introduction: There are similar and different properties between the epidermal growth factor receptor mutations (mEGFR), which are classified into common, uncommon, and compound mutation subtypes depending on their location and pattern on the EGFR gene. We investigated the RWD and RNA expression profile of non-common mutations (uncommon and compound mutations) in the mEGFR+ NSCLC patients. Method: We analyzed the NGS data extracted from the Foundation Medicine (FMI) SRC. And, we collected the medical information for stage I-IIIA mEGFR+ NSCLC patients receiving curative surgical resection. In Böehringer Ingelheim (BI) open data access (ODA), we analyzed treatment results in stage IV mEGFR+ NSCLC patients treated with EGFR TKI. We explored the RNA expression profile by High-Plex Digital Spatial Profiling. A total of 18,676 DEG libraries were constructed, and 419 significance genes with > 2-fold changes, 3-log 2 normalized read counts, and p-value = 0.05 (up and down) were identified. Result: In FMI-SRC cohort, 10,059 mEGFR+ cases of total 78,656 cases consist of common, 6,994 (69.5%), uncommon, 1,966 (19.6%), and compound, 1,099 (10.9%). In hospital cohort, 941 mEGFR+ cases consist of common, 860 (91.4%), uncommon, 60 (7.4%), and compound, 21 (2.2%). Median relapse-free survival (mRFS) in non-common mutations (31.4M and 33.7M) was shorter than common mutations (40.1M, p=0.877). CNS recurrence in the non-common mutations (40.0% and 35.3%) tended to be higher than that of common mutations (27.4%, p=0.361). In BI-ODA, median time on treatment (mTOT) in 163 uncommon mutations (10.0M) and 139 compound mutations (11.5M) were shorter than historical data of common mutations (17.3M). Spatial RNA-seq data of the ratio of deconvolution individual cells showed that genes involved in inflammatory and immune response were relatively lower in non-common mutations. Gene ontology string analysis revealed RNA expression of genes in compound mutations was functionally associated with chemokine production (23.4%), electron transfer activity (14.9%) and T cell selection (8.5%), and, in uncommon mutations, was associated with regulation of oligopeptide transport (26.1%), hypermethylation of CpG island (21.7%), and CD4+ CD25+ regulatory T cell lineage commitment (13.0%), compared to common mutations. Based on the GSEA, relatively highly clustered genes in compound mutations were the protein modification process, G-protein coupled receptor, regulation of cytosolic calcium ion concentration, and IL-5 production pathways, and lower ES levels in oxidative phosphorylation and RNA processing pathways, when compared to common mutations. Conclusion: Taken together, our results suggest that uncommon and compound mEGFR subtypes exhibiting shorter mRFS and mTOT, and distinguishing RNA expression profile of functional signaling pathways be not same disease entity as common mEGFR subtype Citation Format: Seoree Kim, Yeoun Eun Sung, Joo Ri Kim, Chan Kwon Jung, Jeong-Oh Kim, Jeong-yeon Shin, Guk Jin Lee, Sang hoon Chun, Young Ho Lee, Jin Hyoung Kang. Real world data and multi-genomic analysis of non-common mutations in the EGFR mutation-positive non-small cell lung cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4391.

Purpose The treatment of male breast cancer (MBC) has been extrapolated from female breast cancer (FBC) because of its rarity despite their different clinicopathologic characteristics. We aimed to investigate the distribution of intrinsic subtypes based on immunohistochemistry, their clinical impact, and treatment pattern in clinical practice through a multicenter study in Korea.Materials and Methods We retrospectively analyzed clinical data of 248 MBC patients from 18 institutions across the country from January 1995 to July 2016.Results The median age of MBC patients was 63 years (range, 25 to 102 years). Among 148 intrinsic subtype classified patients, 61 (41.2%), 44 (29.7%), 29 (19.5%), and 14 (9.5%) were luminal A, luminal B, human epidermal growth factor receptor 2, and triple-negative breast cancer, respectively. Luminal A subtype showed trends for superior survival compared to other subtypes. Most hormone receptor-positive patients (166 patients, 82.6%) received adjuvant endocrine treatment. Five-year completion of adjuvant endocrine treatment was associated with superior disease-free survival (DFS) in patients classified with an intrinsic subtype (hazard ratio [HR], 0.15; 95% confidence interval [CI], 0.04 to 0.49; p=0.002) and in all patients (HR, 0.16; 95% CI, 0.05 to 0.54; p=0.003).Conclusion Distribution of subtypes of MBC was similar to FBC and luminal type A was most common. Overall survival tended to be improved for luminal A subtype, although there was no statistical significance. Completion of adjuvant endocrine treatment was associated with prolonged DFS in intrinsic subtype classified patients. MBC patients tended to receive less treatment. MBC patients should receive standard treatment according to guidelines as FBC patients.

Purpose The purpose of this study was to evaluate clinical characteristics and treatment pattern of ovarian clear cell carcinoma (OCCC) in Korea and the role of adjuvant chemotherapy in early-stage. Materials and Methods Medical records of 308 cases of from 21 institutions were reviewed and data including age, performance status, endometriosis, thromboembolism, stage, cancer antigen 125, treatment, recurrence, and death were collected. Results Regarding stage of OCCC, it was stage I in 194 (63.6%), stage II in 34 (11.1%), stage III in 66 (21.6%), and stage IV in 11 (3.6%) patients. All patients underwent surgery. Optimal surgery (residual disease ≤ 1 cm) was achieved in 89.3%. Majority of patients (80.5%) received postoperative chemotherapy. The most common regimen was taxane-platinum combination (96%). Median relapse-free survival (RFS) was 138.5 months for stage I, 33.4 for stage II, 19.3 for stage III, and 9.7 for stage IV. Median overall survival (OS) were not reached, 112.4, 48.7, and 18.3 months for stage I, II, III, and IV, respectively. Early-stage (stage I), endometriosis, and optimal debulking were identified as favorable prognostic factors for RFS. Early-stage and optimal debulking were also favorable prognostic factors for OS. Majority of patients with early-stage received adjuvant chemotherapy. However, additional survival benefit was not found in terms of recurrence. Conclusion Majority of patients had early-stage and received postoperative chemotherapy regardless of stage. Early-stage and optimal debulking were identified as favorable prognostic factors. In stage IA or IB, adding adjuvant chemotherapy did not show difference in survival. Further study focusing on OCCC is required.

ObjectiveThe accurate estimation of expected survival in terminal cancer patients is important. The palliative performance scale (PPS) is an important factor in predicting survival of hospice patients. The purpose of this study was to examine how initial status of PPS and changes in PPS affect the survival of hospice patients in Korea.MethodWe retrospectively examined 315 patients who were admitted to our hospice unit between January 2017 and December 2018. The patients were divided based on the PPS of ≥50% (group A) and ≤40% (group B). We performed survival analysis for factors associated with the length of survival (LOS) in group A. Based on the hospice team's weekly evaluation of PPS, we examined the effect of initial levels and changes in group A on the prognosis of patients who survived for 2 weeks or more.ResultsAt the time of admission to hospice, 265 (84.1%) patients were PPS ≥50%, and 50 (15.9%) were PPS ≤40%. The median LOS of PPS ≥50% and PPS ≤40% were 15 (2–158 days) and 9 (2–43 days), respectively. Male, gastrointestinal cancer, and lower initial PPS all predicted poor prognosis in group A. Male, gastrointestinal cancer, and a PPS change of 10% or greater, compared with initial status 1 week and 2 weeks of hospitalization, were all predictors of poor prognosis in group A patients who survived for 2 weeks or longer.Significance of resultsOur research demonstrates the significance of PPS change at 1 week and 2 weeks, suggesting the importance of evaluating not only initial PPS but also change in PPS.

Background/aims Colorectal cancer (CRC) rate increases with aging. Aging-related proteins, such as sirtuins (SIRTs) may be a potential therapeutic target in the elderly patients with CRC. The clinical implications of SIRT1 and SIRT2 have not been reported for elderly patients with cancer. The aim of this study was to evaluate the impact of expression of SIRT1 and SIRT2 on clinical outcome in two extreme age groups of patients with CRC. Methods The expression of SIRT1 and SIRT2 were evaluated in CRC tissues of 101 patients aged ≥ 80 years and 29 patients aged ≤ 40 years by immunohistochemistry. We defined the patients aged ≥ 80 years as the very elderly and patients aged ≤ 40 years as the young patients. Correlations between the expression of these proteins and clinicopathological features were analyzed. Results The prognosis for the very elderly patients with high expressions of SIRT1 was significantly worse than that for patients showing low expression (median survival, 24.9 months vs. 38.6 months, p = 0.027) whereas high expression of SIRT2 better prognosis (median survival, 37.9 months vs. 17.3 months, p = 0.006). However, the young patients did not show any difference in prognosis according to expression of SIRT1 and SIRT2. In multivariate analysis, high SIRT1 expression retained statistical significance as a poor prognostic factor in the very elderly patients with CRC. Conclusion The results suggest that high SIRT1 expression could be predictive of a poor outcome for very elderly patients with CRC.

e21504 Background: The immune checkpoint inhibitors (ICIs), have improved survival with durable response for advanced malignant melanomas, but, only a minority of patients has achieved. To stay sway failure of triage patients, considerable side effects and costs of ICB therapies, the development of robust signatures predictive of response to ICB therapies is warranted. Methods: Clinical data were collected at Seoul St. Mary’s Hospitals. Among them, we examined RNA expression profile by QuantSeq 3’ mRNA-Sequencing and the composition, and spatial distance of immune cells by multiplex immunofluorescent staining. Results: The gene sets with relatively higher RNA expression in the good response group, were as follows; hematopoietic cell dedifferentiation gene, T-cell related adaptive immunity gene, IFN-related cytokine gene, and macrophage (TAM), NK cell, innate immunity gene set. Meanwhile, in the poor response group, inflammatory response, fibrosis response genes was increased.The cell densities of T cells, cytotoxic T cells, Treg cells, CD8+Treg cells, and exhausted T cells in the good response group tended to be higher, which was clearer in the peritumoral (PT) area than the intratumoral (IT) area. For the good response group, M1/M2 ratio in the IT area was significantly higher compared to that of poor response group (p = 0.045). According to the nearest neighbor analysis for % of melanoma cells within 15um distance present a close distance from M1, M2, and NK cells tended to be higher in the IT area than PT area. For the cases with higher spatial distribution from M1 in the IT area, PFS and OS was significantly extended (PFS, p = 0.0021; OS, p = 0.036). The gene sets with relatively higher mRNA expression in high neighborhood macrophage group, were cell death, apoptosis process gene set. In low neighboring M1 macrophage group, relatively higher mRNA expressions of extracellular component inflammation and fibrosis gene, cell migration, and cell de-differentiation gene set were observed. Conclusions: Taken together, our results suggest 4 key points. First, good and poor responder groups for ICB show marked differences from mRNA profiling to protein expression according to central dogma. Second, immune cells can be distributed sporadically in many places, but the actionable ground of the adaptive immune cells of the T cell family is the PT, and the playground of innate immune cells such as TAM and NK cells is the IT. In particular, the anti-tumor response of M1 macrophage and M2 macrophage was oppositely in IT. Third, high TAMs in IT are interpreted to have a tumoricidal effect because they show a stationery state while coding the killing effect gene set. In addition, topologically, spatial analysis as well as bulk genomics are important for predicting tumor response for ICIs.

e12528 Background: The treatment of male breast cancer (MBC) has been extrapolated from female breast cancer (FBC) because of its rarity despite their different clinicopathologic characteristics. We aimed to investigate the distribution of intrinsic subtypes based on immunohistochemistry (IHC), their clinical impact, and treatment pattern in clinical practice through a multicenter study in Korea. Methods: We retrospectively analyzed clinical data of 248 MBC patients 18 institutions across the country from January 1995 to July 2016. Results: The median age of MBC patients was 63 years (range: 25–102 years). Among the 148 patients that underwent intrinsic subtype classification, 61 (41.2%), 44 (29.7%), 29 (19.5%), and 14 (9.5%) were luminal A, luminal B, HER2, and triple-negative breast cancer (TNBC), respectively. TNBC patients showed inferior survival compared with those with other subtypes. Of the 221 patients with operable breast cancer, 108 (48.6%) received adjuvant chemotherapy and 52 (23.5%) received adjuvant radiation therapy. Most hormone receptor-positive patients (166 patients, 82.6%) received adjuvant endocrine treatment. Five-year completion of adjuvant endocrine treatment was associated with superior disease-free survival (DFS) in patients classified with an intrinsic subtype (hazard ratio [HR] = 0.19, 95% confidence interval [CI] 0.005–0.65, P = 0.008) and in all patients (HR = 0.16, 95% CI 0.05–0.54, P = 0.003). Conclusions: Distribution of subtypes of MBC was similar to FBC and luminal type A was most common. Overall survival tended to be improved for luminal A subtype although there was no statistical significance. Completion of adjuvant endocrine treatment was associated with prolonged DFS in intrinsic subtype classified patients. MBC patients have tended to receive les treatment. MBC patients should be treated with standard guideline as FBC patients receive.

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.

Purpose Breast cancer treatment has progressed significantly over the past 20 years. However, knowledge regarding male breast cancer (MBC) is sparse because of its rarity. This study is an investigation of the clinicopathologic features, treatments, and clinical outcomes of MBC. Materials and methods Clinical records of 59 MBC patients diagnosed during 1995-2014 from seven institutions in Korea were reviewed retrospectively. Results Over a 20-year period, MBC patients accounted for 0.98% among total breast cancer patients, and increased every 5 years. The median age of MBC patientswas 66 years (range, 24 to 87 years). Forty-three patients (73%) complained of a palpable breast mass initially. The median symptom duration was 5 months (range, 1 to 36 months). Mastectomy was performed in 96% of the patients. The most frequent histology was infiltrating ductal carcinoma (75%). Ninety-one percent of tumors (38/43) were estrogen receptor-positive, and 28% (11/40) showed epidermal growth factor receptor 2 (HER-2) overexpression. After curative surgery, 42% of patients (19/45) received adjuvant chemotherapy; 77% (27/35) received hormone therapy. Five out of ten patients with HER-2 overexpressing tumors did not receive adjuvant anti-HER-2 therapy, while two out of four patients with HER-2 overexpressing tumors received palliative trastuzumab for recurrent and metastatic disease. Letrozole was used for one patient in the palliative setting. The median overall survival durations were 7.2 years (range, 0.6 to 17.0 years) in patients with localized disease and 2.9 years (range, 0.6 to 4.3 years) in those with recurrent or metastatic disease. Conclusion Anti-HER-2 and hormonal therapy, except tamoxifen, have been underutilized in Korean MBC patients compared to female breast cancer patients. With the development of precision medicine, active treatment with targeted agents should be applied. Further investigation of the unique pathobiology of MBC is clinically warranted.

Thymic epithelial tumors (TET) are heterogenous tumors which are composed of thymoma (TM) and thymic carcinoma (TC). We attempted to determine differences in gene expression between TM and TC, and to determine the effect of such genes on the prognosis of patients with TET.Gene expression profiles of SOX2, OCT-4, IGF-1, IGF-1R and IR mRNA transcripts in tumor tissues of TM and TC were determined using real-time PCR (RT-PCR). We constructed tissue microarray with 140 paraffin-embedded tumor tissues and performed immunohistochemistry (IHC) for IGF-1R-related signaling molecules, including SOX2, IGF-1, IGF-1R and pAKT.SOX2 mRNA expression was notably higher (216-fold) in TCs than in TMs. However, there was no significant difference in expression of IGF-1, IGF-1R, OCT-4 or IR between the two tumor types. In IHC results, SOX2 (HR: 7.57, P = 0.001) and IGF-1 (HR: 9.43, P = 0.001) expression levels in TC were significantly higher than those in TM. There was a significant correlation in expression of SOX2 with IGF-1 (P = 0.021) and pAKT (P = 0.026). In univariate analysis, clinical TNM stage, WHO classification, serum LDH, expression of SOX2, IGF-1R, IGF-1 and pAKT, were significantly correlated with overall survival (OS). Multivariate analysis using a forward-selection procedure revealed that clinical N stage (HR: 4.08, P 0.001), M stage (HR: 3.37, P = 0.001) and SOX2 expression (HR: 4.53, P = 0.010) were significantly associated with OS.SOX2 is expressed significantly higher in TC than in TM. SOX2 expression is also closely related to IGF-1 and pAKT expression. The higher expression of SOX2 is significantly associated with shorter survival in patients with TET.

(Received: June 16, 2015; Revised: June 24, 2015; Accepted: June 29, 2015)Abstract : The number of wild animal species is gradually decreasing due to poaching, hunting and habitat loss. Whileseveral endangered animal species have been successfully preserved at the zoo, assisted reproductive technology (ART)must be applied to restore wild animals. In the case of critically endangered animals, somatic cell cloning is consideredthe most appropriate method of ART. Somatic cell cloning can be beneficial for the reproduction of endangered specieswith limited female populations. However, gene and cell banks, and understanding of reproductive physiology andoptimization of ART for wild animals are urgently required for further activation of artificial reproduction of endangeredspecies, which enlarges its application and maintains biodiversity. Care should also be taken to consider ethical andlegal issues associated with somatic cell cloning for conservation of endangered animals.Keywords : artificial reproduction, conservation, endangered species, ethical and legal issue, somatic cell cloning

A 56-year-old female was referred to our hospital due to a mass measuring 5 cm in size in the left pelvic cavity, which was found incidentally during a health examination by ultrasonography. Exploratory laparotomy was performed and the mass was located at the left retroperitoneal parametrium without invasion of the uterus and ovary. The pathology report confirmed squamous cell carcinoma. Even after further studies, we did not find any other primary lesion. Human papillomavirus (HPV) DNA chip test (HPV 9G DNA Membrane Kit, Biometrixtechnology Inc.) showed that the surgical specimen was positive for HPV 18. She received adjuvant chemotherapy and would receive radiation therapy for the possibility of occult gynecologic cancer. Retroperitoneal squamous cell carcinoma of unknown primary is extremely rare and little is known about it. It is reported that HPV may be associated with the disease. Hence, the result of HPV test could have an impact on finding a suspicious primary lesion and treatment modality in this case.

Purpose This study investigated setup error and effectiveness of weekly image-guided radiotherapy (IGRT) of TomoDirect for early breast cancer. Materials and Methods One hundred and fifty-one breasts of 147 consecutive patients who underwent breast conserving surgery followed by whole breast irradiation using TomoDirect in 2012 and 2013 were evaluated. All patients received weekly IGRT. The weekly setup errors from simulation to each treatment in reference to chest wall and surgical clips were measured. Random, systemic, and 3-dimensional setup errors were assessed. Extensive setup error was defined as 5 mm above the margin in any directions. Results All mean errors were within 3 mm of all directions. The mean angle of gantry shifts was 0.6°. The mean value of absolute 3-dimensional setup error was 4.67 mm. In multivariate analysis, breast size (odds ratio, 2.82; 95% confidence interval, 1.00 to 7.90) was a significant factor for extensive error. The largest significant deviation of setup error was observed in the first week of radiotherapy (p < 0.001) and the deviations gradually decreased with time. The deviation of setup error was 5.68 mm in the first week and within 5 mm after the second week. Conclusion In this study, there was a significant association between breast size and significant setup error in breast cancer patients who received TomoDirect. The largest deviation occurred in the first week of treatment. Therefore, patients with large breasts should be closely observed on every fraction and fastidious attention is required in the first fraction of IGRT.

Purpose To date, the risk factors for central venous port-related bloodstream infection (CVPBSI) in solid cancer patients have not been fully elucidated. We conducted this study in order to determine the risk factors for CVP-BSI in patients with solid cancer. Materials and Methods A total of 1,642 patients with solid cancer received an implantable central venous port for delivery of chemotherapy between October 2008 and December 2011 in a single center. CVP-BSI was diagnosed in 66 patients (4%). We selected a control group of 130 patients, who were individually matched with respect to age, sex, and catheter insertion time. Results CVP-BSI occurred most frequently between September and November (37.9%). The most common pathogen was gram-positive cocci (n=35, 53.0%), followed by fungus (n=14, 21.2%). Multivariate analysis identified monthly catheter-stay as a risk factor for CVP-BSI (p=0.000), however, its risk was lower in primary gastrointestinal cancer than in other cancer (p=0.002). Initial metastatic disease and long catheter-stay were statistically significant factors affecting catheter life span (p=0.005 and p=0.000). Results of multivariate analysis showed that recent transfusion was a risk factor for mortality in patients with CVP-BSI (p=0.047). Conclusion In analysis of the results with respect to risk factors, prolonged catheter-stay should be avoided as much as possible. It is necessary to be cautious of CVP-BSI in metastatic solid cancer, especially non-gastrointestinal cancer. In addition, avoidance of unnecessary transfusion is essential in order to reduce the mortality of CVP-BSI. Finally, considering the fact that confounding factors may have affected the results, conduct of a well-designed prospective controlled study is warranted.

Background/Objective: The oragnotypic tumor slice culture model resembles the in vivo situation of tumor. It may serve as a proper ex vivo platform for response to anti-tumor therapies. We aimed to evaluate the response of pancreatic ductal adenocarcinoma (PDA) cells and helper, cytotoxic, and regulatory T cells to gemcitabine using human PDA slice culture model. Methods: PDA tissues were obtained from patients who were operated on for pancreatic resection. The tumors were sliced by a vibratome, and the tumor slices were then cultured until 5 days with 0.1 μM, 1 μM, and 10 μM gemcitabine for 1 or 2 days. Tumor responses were evaluated by number of tumor cells and proportion of Ki-67 or caspase-3 positively expressed cells in the tumor. CD4+, CD8+, and FOXP3+ cells were analyzed by immunohistochemistry staining. Results: Gemcitabine treatment to PDA slices exerted proportional cytotoxic effects in terms of tumor cell number, and Ki-67 and cleaved caspase-3 expression. Mean Ki-67 positive cells in PDA cells tended to decrease according to increase of gemcitabine concentration (case 1, 48 hr treatment; 65.7% in control vs. 27.9% in 0.1 μM, p=0.025). Mean caspase-3 positive cells in PDA cells tended to increase according to increase of gemcitabine concentration (case 1, 48 hr treatment; 8.6% in control vs. 18.6% in 0.1 μM, p=0.042). Mean PDA cells per x200 tended to decrease according to increase of gemcitabine concentration (case 2, 48 hr treatment; 78.3 in 1.0 μM vs. 27.3 in 10 μM, p=0.042). Mean CD4+, CD8+, and FOXP3+ cells/total cells tended to decrease according to increase of gemcitabine concentration; in case 3 (24hr treatment), mean CD4+ cells/total cells decreased as 2.6%, 1.6%, 1.5%, and 0.5%, mean CD8+ cells/total cells decreased as 2.6%, 1.5%, 1.4%, and 1.1%, and mean FOXP3+ cells/total cells were 0.2%, 0.3%, 0.2%, and 0.1% in control, 0.1 μM, 1 μM, and 10 μM gemcitabine, respectively. However, mean CD8+/FOXP3+ cell ratio did not significantly decrease, and even increase from 4.4 in 0.1 μM to 8.6 in 1 μM (p=0.039). Conclusions: Tumoricidal effect of gemcitabine could be demonstrated using organotypic slice culture model. T cells in the tumor decreased according to increase of gemcitabine concentration; however CD8+/FOXP3+ cell ratio relatively maintained. Citation Format: Jae Hyuck Chang, Chae Yoon Lim, Weon Sun Lee, Guk Jin Lee. Response of pancreatic ductal adenocarcinoma to gemcitabine using human organotypic slice cultures [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1096.

e17062 Background: Clear cell ovarian cancer is rare, accounts for about 3-10% of epithelial ovarian carcinoma, and is known to be associated with endometriosis. This tumor type has poor prognosis due to inherent chemoresistance. We investigated clinical characteristics and prognostic factors of clear cell ovarian cancer in South Korea. Methods: We reviewed the medical records of 308 patients with clear cell histology ovarian cancer who underwent debulking surgery from 21 institutions in South Korea between 1995 and 2015. Results: Mean age was 51 years (range, 25-81) and 194 patients (63.7%) had stage I disease, 34 (11.1%) had stage II, 66 (21.6%) had stage III, and 11 (3.6%) had stage IV. 107 patients (34.9%) had endometriosis. 9 patients (2.9%) received neoadjuvant chemotherapy, 248 (80.5%) received postoperative chemotherapy, and among them, 238 (96%) received taxane-platinum chemotherapy. 275 patients (89.3%) achieved optimal debulking. 112 patients (37%) had recurrence, 182 (59.1%) was disease-free, and 12 (3.9%) lost follow up. Median value of CA-125 was 72.34 U/ml (range, 1.9-8930), 45.7 in stage I, 98.9 in stage II, 192.1 in stage III, and 634.8 in stage IV. 1-year, and 3-year rate of disease-free survival (DFS) was 70%, and 63%, respectively. 1-yr DFS rate was 90% in stage Ia and Ib, 88% in stage Ic and II, and 60% in stage III and IV. According to the same stage grouping, 3-year DFS rate was 82%, 70%, and 40%, respectively. Overall survival (OS) rate at 1 year was 97%, 99%, and 90%, and 97%, 96%, and 88% at 3 year. Multivariate analysis revealed optimal debulking (HR 6.62, p < 0.001) as a significant prognostic factor for DFS. Among the 94 patients with early stage (Ia and Ib), 17 patients (18.1%) received adjuvant chemotherapy, and there was no significant difference in DFS according to adjuvant chemotherapy (log rank p = 0.57). Conclusions: In patients with clear cell ovarian cancer, optimal debulking surgery was associated with improved DFS. And the role of adjuvant chemotherapy in early stage clear cell ovarian cancer is elusive and needs further study.

344 Background: Nal-IRI plus 5-FU/LV has demonstrated efficacy in mPDAC pts who previously received gemcitabine-based therapy in the pivotal NAPOLI-1 trial. Real-world data are helpful to measure the clinical outcomes and safety profile of this regimen in daily practice setting. Methods: Between January 2017 and April 2018, a Named Patient Program (NPP) was activated to provide controlled, pre-approval access of nal-IRI in Korea. This analysis is multicenter retrospective study for patients who received nal-IRI plus 5-FU/LV under the NPP. Results: A total of 86 patients entered into this NPP among 10 Korean institutions. Median age was 61 years (range, 37-79) and 52 pts (60%) were male. Liver (n=49, 57%), peritoneum (30, 35%), and lung (27, n=31%) were the most common metastatic sites. All patients had ECOG performance status 0-1 and previously received gemcitabine-based therapy. Prior to nal-IRI plus 5-FU/LV, 35 (41%) and 51 (59%) patients received

The efficacy of second-line chemotherapy for relapsed primary peritoneal serous carcinoma has been numerously reported, but reports on durable response after second-line therapy have been rare. We report the case of a 66-year-old woman with relapsed primary peritoneal serous carcinoma who showed durable response after just one cycle of second-line belotecan-based therapy. The response might be a complete pathologic remission. Considering the fact that our patient suffered from neutropenic sepsis during her treatment, we concluded that belotecan-based chemotherapy could be a good option for second-line chemotherapy in some selected patients, so patient selection should be carefully performed due to the toxicity of belotecan.

8578Background: Thymic epithelial tumors (TET) are consisted of thymoma(TM) and thymic carcinoma(TC). They are rare heterogeneous tumors with a broad spectrum of clinical characteristics. Although ...

486 Background: There is no estabilished consensus about chemoradiation therapy for resected cholangiocarcinoma, and many studies are ongoing. We tried to cofirm the effectiveness and side effects of chemoradiation after operation of cholangiocarcinoma and find the prognostic factors. Methods: We found the patients with cholangiocarcinoma who receieved chemoradiation after surgery between 2002 and 2015 from two hospitals in South Korea. We checked the baseline chareacteristics, efficacy and toxicities. And we tried to identify the prognostic factors for recurrence by statistical anaylsis. Results: We retrospectivally studied 51 cholangiocarcinoma patients. Median age was 64 (range 48-83), and Men was 30 patients (58.8%) of them. By location, there were 10 (19,6%) intrahepatic cholangiocarcinomas, 13 (25.5%) hilar cholangiocarcinoma, and 28 (54.9%) extrahepatic cholangiocarcinomas. All patient received 5-FU chemoradiation after surgery. R0 resections were 31 (60.8%), R1 resections were 20 (39.2%) There was recurrence with 35 (68.6%) patients. Median relapse free survival was 292 (range 86-1769) days. Locoregional recurrence were 16 (31.4%), and distant recurrences were 26 (51.0%). For hematological toxicity, the patients showed grade 3 toxicities, as leukopenia 5 (9.8%), anemia 1 (2.0%) , thrombocytopenia 1 (2.0%). For non-hematological toxicities, there were G3 toxicities as Infection 2 (4.0%), nausea/vomiting 1 (2.0%), Adhesive ileus 1 (2.0%), bleeding 1 (2.0%). For multivariate analysis, Tumor site (HR 1.88 (95% CI 1.09-3.23). P = 0.022) and modality of radiation therapy (HR 13.27 (95% CI, 3.56-49.50)), P < 0.001) were statistically meaningful factors. Conclusions: Although this is a retrospective study, we found that the result of chemoradiation therapy for some patients showed good efficacy and tolerable toxicity. We could consider chemoradiation for adjuvant therapy in cholangiocarcinoma, especially for extrahepatic cholangiocarcinoma. And intensity-modulated radiation therapy should be performed than three-dimensional radiation therapy in cholangiocarcinoma.

Background: Because many physicians seem reluctant to recommend splenectomy for elderly patients with immune thrombocytopenia (ITP), we investigated the safety and efficacy of splenectomy and the predictive factors for response in these patients. Methods: 184 patients with primary ITP were retrospectively analyzed based on age at splenectomy: an elderly group (≥60 years, n = 52) and a younger group (Results: There was no difference in the response rate of elderly versus younger patients (80.7 vs. 80.3%, p = 0.466). Relapse (45.2 vs. 22.6%, p = 0.006), complications, and median postoperative stay (9.5 vs. 7 days, p = 0.019) were significantly higher in the elderly group. The 5-year relapse-free survival of responders was 51.8% in the elderly group and 76.3% in the younger group (p = 0.002). Response to any treatment before splenectomy (HR 2.9, 95% CI: 1.24-6.80, p = 0.014) and platelet count on postoperative day 14 ≥200 × 109/l (HR 31.43, 95% CI: 4.15-238.28, p = 0.001) were independent factors for a favorable response. Conclusions: Age ≥60 years did not influence the response to splenectomy but was associated with increased relapse and postoperative complications. Splenectomy could provide a durable long-term response for elderly ITP patients.

Bans on TBT based antifouling paints have been drafted since 1998 by meetings 42, 43, 45 and 46 for the MEPC (Marine Environmental Protection Committee) of the International Marine Organization, and decided finally at a Diplomatic Conference of IMO in October 2001. It was a key issue that there should be a global prohibition on the application of organo-tin compounds as biocides in Anti-fouling systems by Jan. 2003, and a complete prohibition on the presence of organo-tin compounds on ships by 1 Jan. 2008. This paper suggests a method to design International Anti-fouling system cretificate, Record of anti-fouling system, Endorsement of the Records, Declaration on Anti-fouling System, Port State Control and reform(legislative) associated a law.

The efficacy of second-line chemotherapy for relapsed primary peritoneal serous carcinoma has been numerously reported, but reports on durable response after second-line therapy have been rare. We report the case of a 66-year-old woman with relapsed primary peritoneal serous carcinoma who showed durable response after just one cycle of second-line belotecan-based therapy. The response might be a complete pathologic remission. Considering the fact that our patient suffered from neutropenic sepsis during her treatment, we concluded that belotecan-based chemotherapy could be a good option for second-line chemotherapy in some selected patients, so patient selection should be carefully performed due to the toxicity of belotecan.

We evaluate the correlation of clinical staging on positron emission tomography-computed tomography (PET-CT) and pathologic staging and the prognostic value of PET-CT after induction chemotherapy in patients with locally advanced nonsmall cell lung cancer (NSCLC). We analyzed 42 cases of clinical stage IIIA-N2 NSCLC who receive 2 to 4 cycles of preoperative chemotherapy with or without radiation followed by curative resection. The maximum standard uptake value (SUVmax) of the suspected lesion on PET-CT was recorded. PET-CT findings after induction chemotherapy were compared with those of initial PET-CT and pathology after surgery. The accuracy of PET-CT in restaging of the primary tumor after induction chemotherapy was 50.0%. Eighteen (42.8%) of 42 patients were underestimated ycT stage, and 3 (7.1%) of 42 patients was overestimated ycT stage by PET-CT scan. The accuracy of PET-CT in restaging of the nodal disease was 71.4%. Six (14.3%) of 42 patients were underestimated ycN stage, and 6 (14.3%) of 42 patients were overestimated ycN stage as compared with pathologic staging. The 2-year overall survival (OS) and relapse-free survival (RFS) rate were 68.5% and 40.9%, respectively. Complete responders (ycT0N0M0) on PET-CT after induction chemotherapy had a significantly longer RFS time than did incomplete responders (28.3 vs 9.1 months, P = 0.021). Complete response on PET-CT after induction chemotherapy with or without radiation was a good prognosticator for RFS in stage IIIA-N2 NSCLC patients who received surgery. However, response evaluation on PET-CT after induction chemotherapy should be interpreted with caution due to its unacceptable accuracy.

A 67-year-old male presented with left temporal hemianopsia and left hemiparesis. A contrast-enhanced magnetic resonance image revealed a 4.5×3.5×5.0 cm rim-enhancing mass with central necrosis and associated edema located in the left occipital lobe. Of positron emission tomography and abdominal computed tomography, a 9–cm mass with poor enhancement was found in the right hepatic lobe. Craniotomy and right hemihepatectomy was performed. The resected specimen showed histological features and immunochemical staining consistent with a metastatic neuroendocrine tumor (NET). Four months later, the tumors recurred in the brain, liverand spinal cord. Palliative chemotherapy with etoposide and cisplatin led to complete remission of recurred lesions, but the patient died for pneumonia. This is the first case of a metastatic brain NET originating from the liver. If the metastatic NET of brain is suspicious, investigation for primary lesion should be considered including liver.

Background The clinical characteristics of elderly patients with AML differ from those of younger patients, resulting in poorer survival and treatment outcomes. We analyzed retrospectively the clinical data of AML patients 65 years old and above to describe patients' characteristics and treatment patterns, and to define meaningful prognostic factors of survival in the Korean population. Methods Basic patients' characteristics, clinical outcomes according to treatments, and prognostic factors associated with survival and treatment intensity were examined in a total of 168 patients diagnosed in 5 institutes between 1996 and 2012 as having AML. Results Herein, 84 patients (50.0%) received high-intensity regimens (HIR), 18 (10.7%) received low-intensity regimens (LIR), and 66 (39.3%) received supportive care (SC) only. The median survival of all patients was 4.5 months; and median survival times with HIR, LIR, and SC were 6.8 months, 10.2 months, and 1.6 months, respectively. Median survival times with HIR and LIR were significantly longer than that with SC (P

e14558 Background: Although many clinical trials of newly developed chemotherapeutic drugs have been conducted, limited studies have focused on gastric cancer patients specifically diagnosed with peritoneal carcinomatosis (PC) without measurable regions. In the current study, we characterized the outcomes of systemic chemotherapy and prognostic factors for patients with gastric cancer PC, particularly in cases without measurable disease. Methods: Clinical data from 211 gastric cancer PC patients (137 without and 74 with measurable disease) subjected to systemic chemotherapy between January 2000 and December 2010 at a single center were reviewed. Results: Median OS rates of gastric cancer PC patients with no measurable disease were significantly longer than those of patients with measurable disease (18.2 vs 12.0 months, p=0.011). In multivariate analysis, poor PS (Hazard ratio (HR) = 2.33, 95% CI, 1.42-3.8, P=0.001), presence of metastatic lymphadenopathy (LAP) (HR=2.23, 95% CI, 1.42-3.5, p=0.002) and high-grade PC (HR=1.82, 95% CI, 1.09-3.04, p=0.025) were associated with significantly decreased OS. Combined with clinical PC grade and measurability of disease, median OS of patients with low-grade PC without measurable disease was 19.6 months (95% CI, 15.5-23.7 months). Median OS rates of 12.6, 13.7 and 6.8 months were estimated in high-grade PC without measurable disease, low-grade PC with measurable disease, and high-grade PC with measurable disease, respectively. Median OS of low-grade PC patients with no measurable disease was significantly higher than that of patients in all other groups (p=0.001, p=0.029 and p

e19614 Background: There are some known risk factors for deep vein thrombosis in cancer patients, such as primary site of cancer, white blood cell count (WBC), hemoglobin (Hb), platelet count (PLT). We investigated the association between these factors and the overall survival as prognostic factor in gastrointestinal (GI) cancer patients. Methods: All the patients with gastrointestinal cancer, who developed deep vein thrombosis or pulmonary thromboembolism through the clinical course, were retrospectively reviewed between January 2009 and June 2011 at Seoul St. Mary’s Hospital. According to treatment, patients were classified into two groups; the chemotherapy group and the supportive care group. Results: Of the fifty-six patients, median age was sixty three year-old. Stomach cancer was most common 35% , pancreatic cancer 31%, colorectal cancer 19%, and biliary cancer was 15%. There were three pattern of thrombosis: 19 (34%) deep vein thrombosis (DVT) only, 12 (21%) pulmonary thromboembolism (PTE) only, 25 (45%) combined DVT with PTE. WBC count above 11,000/µ° showed the poor overall survival than other group (median survival 3.4 months vs. 1.7 months, respectively, p=0.015) However, other risk factor did not show any significant association (Hb: p=0.521, PLT: p=0.295) In chemotherapy group, twelve (55%) patients had progressive disease and ten (45%) patients had stable disease at the time of thrombotic event. There was no statistically significant association between thrombosis and tumor response. The chemotherapy group had tendency of better survival outcome than the supportive care group without statistical significance (median survival 2.4 months vs. 5.3months, p=0.07). Conclusions: In GI cancer patients, elevated white blood cell count above 11,000/µ° can be important prognostic and risk factor for thrombosis with poor survival outcome. And the response of chemotherapy seemed to have no influence on thrombotic event during chemotherapy. This is very limited study due to small sample size and retrospective analysis, and heterogenous type of cancer. Further large study should be warranted to define the thrombotic risk factor as prognostic marker.

Pituitary stalk interruption and ectopic neurohypophysis seen on magnetic resonance Imaging (MRI) are often associated with either isolated growth hormone (GH) deficiency or combined anterior pituitary hormone deficiency, but their pathogenesis is not clear and the clinical data regarding these anatomical defect is limited. We experienced a 23-year-old male with the absence of secondary sexual characteristics and this was accompanied with pituitary stalk dysgenesis and ectopic neurohypophysis. He received growth hormone for a year when he was 12 years old due to his short stature. Sella MRI showed no visible pituitary stalk with minimal high signal change, suggesting ectopic neurohypophysis. The combined pituitary stimulation test revealed blunted responses of growth hormone, follicle stimulating hormone and luteinizing hormone. For the hypogonadotropic hypogonadism, the patient was given testosterone intramuscularly and he gradually developed secondary sexual characteristics. We concluded that the hypogonadism and growth hormone deficiency in this patient was caused by hypopituitarism due to pituitary stalk dysgenesis and ecopic nuerohypophysis. (Endocrinol Metab 26:67-71, 2011)

Left ventricle-coronary sinus fistula and left ventricular pseudoaneurysm are unusual and frightening complications after mitral valve replacement. A 27-year-old female patient underwent mitral valve replacement 5 years previously and trans-thoracic echocardiography showed an outpouching lesion at the atrioventricular groove. It was difficult to differentiate whether the lesion was a left ventricle-coronary sinus fistula or a left ventricular pseudoaneurysm by two-dimensional echocardiography. Cardiac computed tomography confirmed a left ventricular pseudoaneurysm compressing the coronary sinus.