Sun Young Rha

Yonsei University, Sŏul, Seoul, South Korea

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Publications (331)1522.51 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: While the ToGA trial demonstrated the efficacy and safety of trastuzumab-based chemotherapy in HER2 (+) metastatic gastric cancer, the OS benefit was not found in Asian and diffuse-type cancer patients. The aim of the study is to investigate predictive markers for trastuzumab-based chemotherapy. Materials and methods Data of patients with HER2 (+) gastric cancer treated with trastuzumab-based chemotherapy were analyzed retrospectively. A total of 168 Asian patients were included. The median age was 60 (range 27-85) and the male:female ratio was 118 (70.2%):50 (29.8%). Fourteen (8.3%), 63 (37.5%), 75 (44.6%), and 11 (6.5%) patients had well, moderately, poorly differentiated tubular adenocarcinoma and signet ring cell carcinoma, respectively. With 14 complete responses and 73 partial responses, the response rate was 50.6%. The median PFS was 10.2 months (95% CI 8.7 - 11.7), and the median OS was 18.5 months (95% CI 16.4 - 50.6). Next, we investigated the effect of PDH (poorly differentiated histology, poorly differentiated tubular adenocarcinoma + signet ring cell carcinoma) on clinical outcomes. The median PFS (8.9 months vs. 11.5 months, p = 0.16) was slightly inferior in PDH patients, and the median OS was significantly shorter in PDH patients (14.6 months vs. 19.0 months, p = 0.025). While subset analysis of the ToGA trial demonstrated that trastuzumab-based chemotherapy may not be beneficial for Asians and patients with PDH, our data may suggest that even in Asian patients and patients with PDH, trastuzumab-based chemotherapy could be associated with improved clinical outcomes in patients with HER2 (+) gastric cancer.
    Cancer Research and Treatment 08/2015; DOI:10.4143/crt.2015.155 · 3.32 Impact Factor
  • Cancer Research 08/2015; 75(15 Supplement):1454-1454. DOI:10.1158/1538-7445.AM2015-1454 · 9.33 Impact Factor
  • Cancer Research 08/2015; 75(15 Supplement):661-661. DOI:10.1158/1538-7445.AM2015-661 · 9.33 Impact Factor
  • Cancer Research 08/2015; 75(15 Supplement):591-591. DOI:10.1158/1538-7445.AM2015-591 · 9.33 Impact Factor
  • Cancer Research 08/2015; 75(15 Supplement):391-391. DOI:10.1158/1538-7445.AM2015-391 · 9.33 Impact Factor
  • Cancer Research 08/2015; 75(15 Supplement):4055-4055. DOI:10.1158/1538-7445.AM2015-4055 · 9.33 Impact Factor
  • Cancer Research 08/2015; 75(15 Supplement):4694-4694. DOI:10.1158/1538-7445.AM2015-4694 · 9.33 Impact Factor
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    ABSTRACT: Presently, there is no scientific evidence supporting a definite role for follow-up after gastrectomy for cancer, and clinical practices are quite different around the globe. The aim of this consensus conference was to present an ideal prototype of follow-up after gastrectomy for cancer, based on shared experiences and taking into account the need to rationalize the diagnostic course without losing the possibility of detecting local recurrence at a potentially curable stage. On June 19-22, 2013 in Verona (Italy), during the 10th International Gastric Cancer Congress (IGCC) of the International Gastric Cancer Association, a consensus meeting was held, concluding a 6-month, Web-based, consensus conference entitled "Rationale of oncological follow-up after gastrectomy for cancer." Forty-eight experts, with a geographical distribution reflecting different health cultures worldwide, participated in the consensus conference, and 39 attended the consensus meeting. Six statements were finally approved, displayed in a plenary session and signed by the vast majority of the 10th IGCC participants. These statements are attached as an annex to the Charter Scaligero on Gastric Cancer. After gastrectomy for cancer, oncological follow-up should be offered to patients; it should be tailored to the stage of the disease, mainly based on cross-sectional imaging, and should be discontinued after 5 years.
    Gastric Cancer 07/2015; DOI:10.1007/s10120-015-0513-0 · 3.72 Impact Factor
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    ABSTRACT: The growing volume and the diversity of clinical research has led to related laws and regulations as well as the Institutional Review Board (IRB) approval process becoming more stringent. To conduct clinical research efficiently and while following regulations, information about the IRB approval process and feedback is important for investigators. This has yet to be studied. We included 381 gastrointestinal disease research proposals (79 with inflammatory bowel disease [IBD], and 302 with non-IBD) reviewed by the IRB of Severance Hospital between January 2009 and December 2013. We retrospectively analyzed research characteristics including research risk levels, results of initial reviews, frequencies of continuing review, numbers of IRB comments, frequencies of IRB comments, and durations from submission to approval. Investigators' decisions on risk level were higher in the IBD group than in the non-IBD group (P<0.05). Results of initial reviews, frequencies of continuing reviews, the numbers of IRB review comments, and durations from submission to approval were not different between the two groups, but IRB decisions on risk level were higher in the IBD group (P<0.05). In subgroup analysis, the number of IRB comments from initial review on informed consent forms and procedures as well were quest of more information were significantly higher in the IBD group than in the non-IBD group (P<0.001 and 0.01, respectively). In Korea, rare diseases such as IBD require more information for the IRB process due to their distinct characteristics. IBD researchers should develop research protocols more carefully and make their research as subject-friendly as possible.
    07/2015; 13(3):274-81. DOI:10.5217/ir.2015.13.3.274
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    ABSTRACT: We performed this study to define distinctive clinical features of leiomyosarcoma by assessing prognostic factors. Between 1988 and 2011, 129 leiomyosarcoma patients who underwent surgical resection with curative intent were retrospectively reviewed. Of the 129 leiomyosarcoma patients, the distribution of anatomic locations was: extremity (n = 25), pelvis (n = 40), thoracic cavity (n = 11), intra-abdomen (n = 19), retroperitoneum (n = 23), and head/neck (n = 11). We classified the anatomic locations into two categories as abdominal (intra-abdomen and retroperitoneum, n = 42) and extra-abdominal (extremity, pelvis, thoracic cavity, and head/neck, n = 87). Prognosis was worse for the abdominal group than for the extra-abdominal group (median DFS 2.9 9.0 years, P = 0.04). Similarly, overall survival (OS) was also significantly worse for abdominal group (P = 0.027). Independent prognostic factors for survival were primary site (P = 0.041, hazard ratio (HR) 1.7; 95 % CI 1.2-2.8), tumor size (P = 0.038, HR 1.9; 95 % CI 1.13-3.38), margin status (P = 0.019, HR 2.1; 95 % CI 1.13-3.88), and histology grade (P = 0.01, HR 3.59; 95 % CI 1.64-7.87). We identified four different risk groups with different survival outcome: group 1 (n = 8), no adverse factors; groups 2 (n = 37) and 3 (n = 61) with one and two adverse factors, and group 4 (n = 23) with 3 or 4 adverse factors. Primary site, tumor size, resection margin, and histology subtype were independently associated with survival outcome. A prognostic model for leiomyosarcoma patients revealed four distinct groups of patients with good prognostic discrimination.
    International Journal of Clinical Oncology 06/2015; DOI:10.1007/s10147-015-0847-y · 2.13 Impact Factor
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    ABSTRACT: The use of trastuzumab, a monoclonal antibody targeting the HER2 protein, in combination with 5-fluorouracil/platinum-based chemotherapy improves survival in patients with HER2-positive advanced gastric cancer. In addition, TS-one (S-1)/platinum is also used as a standard of care in Asian countries. However, little is known about the combination of S-1/cisplatin chemotherapy and trastuzumab in patients with HER2-positive advanced gastric/gastroesophageal junction (GEJ) cancer. We conducted a single-arm, two-stage, open-label, multicenter phase II study. Trastuzumab was administered intravenously on day 1 of the first cycle at 8 mg/kg and 6 mg/kg on day 1 of subsequent cycles. Cisplatin was administered intravenously at 60 mg/m(2) on day 1 of each cycle after trastuzumab. S-1 was administered orally [based on body surface area (BSA)] twice a day for 14 days in a 3-weekly cycle. Patients with BSA of <1.25 received a total of 80 mg of S-1, those with BSA ≥1.5 received 120 mg, and the remaining received 100 mg daily in two divided doses. All evaluable patients experienced tumor reduction during the trial. The primary end point (overall survival rate) was 59.3 %, with a clinical benefit rate of 66.7 %. Median progression-free survival was 7.4 months; 62.6 % patients were free from disease progression at 6 months. Median overall survival was 14.6 months, and the median time to treatment failure was 6.0 months. The combination of trastuzumab with S-1 and cisplatin demonstrated good activity, was generally well tolerated, and is a feasible treatment option in the first-line treatment of HER2-positive advanced gastric/GEJ cancers.
    Cancer Chemotherapy and Pharmacology 06/2015; 76(2). DOI:10.1007/s00280-015-2811-y · 2.77 Impact Factor
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    ABSTRACT: Cutaneous squamous cell carcinomas and keratoacanthomas commonly occur in patients treated with BRAF inhibitors. We investigated the effect of the BRAF inhibitor vemurafenib on normal immortalized human HaCaT keratinocytes to explore the mechanism of hyperproliferative cutaneous neoplasia associated with the use of BRAF inhibitors. Vemurafenib induced an increase in viable cell number in BRAF wild-type cell lines (SK-MEL-2 and HaCaT) but not in BRAF mutant cell lines (SK-MEL-24 and G361). In HaCaT keratinocytes, a low concentration (2 μmol/L) of vemurafenib increased cell proliferation and activated mitogen-activated protein kinase kinase/extracellular signal-regulated kinase in a CRAF-dependent manner. Invasiveness of HaCaT cells in a Matrigel assay significantly increased upon cultivation of cells with 2 μmol/L vemurafenib for 24 h. Gelatin zymography, reverse transcription polymerase chain reaction and western blot results revealed that 2 μmol/L vemurafenib treatment increased matrix metalloproteinase (MMP)-2 and MMP-9 expressions and activities in HaCaT cells. These results offer additional insight into the complex mechanism of paradoxical mitogen-activated protein kinase signaling involved in hyperproliferative cutaneous neoplasias that arise after BRAF inhibition and suggest a possible role for MMP in tumor progression and invasion. © 2015 Japanese Dermatological Association.
    The Journal of Dermatology 06/2015; 42(9). DOI:10.1111/1346-8138.12950 · 2.25 Impact Factor
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    Annals of Oncology 06/2015; 26(suppl 4). DOI:10.1093/annonc/mdv233.57 · 7.04 Impact Factor
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    ABSTRACT: RAS gene activation and its association with human papillomavirus (HPV) infection have been extensively studied in various cancers. However, the correlation between RAS mutations and HPV in keratoacanthoma (KA) has not yet been investigated. Detection of HPV DNA was performed by nested polymerase chain reaction in 28 KA specimens. Molecular analysis was also performed to identify oncogenic mutations (HRAS, KRAS, NRAS). Statistical analyses were performed using the Fisher's exact tests. HPV DNA was detected in eight (28.6%) of the 28 samples, and RAS mutations were detected in eight (28.6%). Six samples had an HRAS mutation, and two showed the NRAS mutation. The presence of an RAS mutation was significantly correlated with a history of chronic sun damage (P = 0.005). However, no significant correlation was observed between HPV infection and RAS mutation. Our findings suggest that mutational activation of the RAS gene is a common event in KA. However, RAS oncogene activation and HPV infection seem to represent two independent factors in the development of KA. © 2015 The International Society of Dermatology.
    International journal of dermatology 05/2015; DOI:10.1111/ijd.12669 · 1.31 Impact Factor
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    ABSTRACT: Hypermethylation of the CpG island of p16 (INK4a) occurs in a significant proportion of colorectal cancer (CRC). We aimed to investigate its predictive role in CRC patients treated with 5-fluorouracil, leucovorin, irinotecan (FOLFIRI), and cetuximab. Pyrosequencing was used to identify KRAS mutation and hypermethylation of 6 CpG island loci (p16, p14, MINT1, MINT2, MINT31, and hMLH1) in DNA extracted from formalin-fixed paraffin-embedded specimens. Logistic regression and Cox regression were performed for analysis of the relation between methylation status of CIMP markers including p16 and clinical outcome. Hypermethylation of the p16 gene was detected in 14 of 49 patients (28.6%) and showed significant association with KRAS mutation (Fisher`s exact, P=0.01) and CIMP positivity (Fisher`s exact, P=0.002). Patients with p16-unmethylated tumors had significantly longer time to progression (TTP, median 9.0 vs 3.5 months; log-rank, P=0.001) and overall survival (OS, median 44.9 vs 16.4 months; log-rank, P=0.008) than those with p16-methylated tumors. Patients with both KRAS and p16 aberrancy (n=6) had markedly shortened TTP (median 2.8 months) compared to those with either KRAS or p16 aberrancy (n=11; median 8.6 months, P=0.021) or those with neither (n=32; median 9.0 months, P <0.0001). In multivariate analysis, KRAS mutation and p16 methylation showed independent association with shorter TTP (KRAS mutation HR=3.21, P=0.017; p16 methylation HR=2.97, P=0.027). Hypermethylation of p16 was predictive of clinical outcome in mCRC patients treated with cetuximab and FOLFIRI, irrespective of KRAS mutation.
    Cancer Research and Treatment 04/2015; DOI:10.4143/crt.2014.314 · 3.32 Impact Factor
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    ABSTRACT: We retrospectively reviewed outcomes of treatment with pazopanib, an oral multi-tyrosine kinase angiogenesis inhibitor, in patients with advanced soft tissue sarcoma, a rare and heterogeneous tumor group with limited treatment options. Between 2009 and 2013, 43 patients with metastatic soft tissue sarcoma received pazopanib as salvage chemotherapy after one or more cytotoxic regimens. Response rate, progression-free survival, and overall survival were analyzed according to histological subtype, Eastern Cooperative Oncology Group performance status, and metastatic site. Common histological subtypes included leiomyosarcoma (n = 9), angiosarcoma (n = 6), malignant fibrous histiocytoma/undifferentiated pleomorphic sarcoma (MFH/UPS, n = 5), malignant peripheral nerve sheath tumor (MPNST, n = 5), and synovial sarcoma (n = 4). Nineteen patients (44.2%) received more than two chemotherapy regimens before pazopanib. At the time of analysis, 208 treatment cycles of pazopanib had been administered (median, 4.8 cycles per patient), and no treatment-related mortality occurred. The disease control rate was 61.0% (95% confidence interval [CI], 46.1-75.9%), and the overall response rate was 17.1% (partial response, n = 7; complete response, n = 0). Partial response was achieved in two patients with synovial sarcoma, two with MFH/UPS, one with MPNST, one with leiomyosarcoma, and one with angiosarcoma. The median lengths of progression-free survival and overall survival were 5.0 months (95% CI, 3.6-6.4 months) and 8.2 months (95% CI, 5.8-10.6 months), respectively. Progression-free survival was shorter in the patients with liposarcoma and rhabdomyosarcoma (1.3 and 0.9 months, respectively) than in those with leiomyosarcoma, MPNST, MFH/UPS, and synovial sarcoma (5.6, 6.5, 7.1, and 7.7 months, respectively). Pazopanib demonstrated acceptable antitumor activity in the Asian patients who had been heavily pretreated for sarcoma, with seemingly more favorable results in the patients with leiomyosarcoma, MPNST, MFH/UPS, and synovial sarcoma than in those with liposarcoma and rhabdomyosarcoma.
    BMC Cancer 03/2015; 15(1):154. DOI:10.1186/s12885-015-1160-x · 3.36 Impact Factor
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    ABSTRACT: Sinonasal mucosal melanoma (SMM) is an aggressive and rare type of melanoma. Although the classic RAS-RAF-MEK pathway is thought to be the main pathway involved in melanoma pathogenesis, genetic alterations in the PI3K-AKT pathway, including PTEN-regulated signaling, are also thought to contribute. So far, data regarding altered PTEN expression and epigenetic mechanism of PTEN silencing in development of SMM is extremely limited. Herein we report on a case of SMM with liver and bone metastases with an epigenetic alteration of PTEN. Results of mutation analysis for BRAF, NRAS, HRAS, KRAS, PIK3CA, C-kit, and PTEN were negative, however, methylation of PTEN CpG islands was observed. Our case not only supports PTEN as a major tumor suppressor involved in melanoma tumorigenesis, but also a potential epigenetic mechanism of PTEN silencing in development of SMM.
    Cancer Research and Treatment 03/2015; DOI:10.4143/crt.2014.356 · 3.32 Impact Factor
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    ABSTRACT: Family caregivers of cancer patients become responsible for many elements of cancer care, usually without preparation or training in provision of care. Their efforts of care generate caregiving burden, which could deteriorate caregivers' quality of life (QOL). A secondary data analysis of a cross-sectional descriptive study was conducted to describe the influence of caregiving burden on the QOL of family caregivers of cancer patients with consideration of correlates (N = 212). The Korean versions of Zarit Burden Interview and the World Health Organization QOL BREF were used. Multiple regression analyses were applied to analyze the relationship between the caregiving burden and QOL. Caregiving burden explained 30.3% of variance of the QOL (β = -0.534, p < 0.001). Caregivers caring for patients with functional deterioration experienced higher burden. Caregivers providing care for hospitalized patients demonstrated lower QOL. The caregiver's educational level was a positively contributing factor for the QOL. Caregiving burden was the influential, negatively affecting factor for the QOL. Assessment of caregiving burden with special attention being paid to caregivers caring for patients with functional decline would help to identify caregivers in need of support. Supportive care needs to be sought to alleviate caregiving burden and improve the QOL of caregivers, especially for the caregivers of hospitalized patients. Copyright © 2015 Elsevier Ltd. All rights reserved.
    European journal of oncology nursing: the official journal of European Oncology Nursing Society 03/2015; 19(4). DOI:10.1016/j.ejon.2015.01.004 · 1.43 Impact Factor
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    ABSTRACT: To investigate the efficacy of neoadjuvant chemoradiotherapy (NACRT) for resectability of locally advanced gastric cancer (LAGC). Between November 2007 and January 2014, 29 patients with LAGC (clinically T3 with distal esophagus invasion/T4 or bulky regional node metastasis) that were treated with NACRT followed by D2 gastrectomy were included in this study. Resectability was evaluated with radiologic and endoscopic exams before and after NACRT. Using three-dimensional conformal radiotherapy, patients received 45 Gy, with a daily dose of 1.8 Gy. The entire tumor extent and the regional metastatic lymph nodes were included in the gross tumor volume. Patients presenting with a resectable tumor after NACRT received a total or subtotal gastrectomy with D2 dissection. The pathologic tumor response was evaluated using Japanese Gastric Cancer Association histologic evaluation criteria. Postoperative morbidity was evaluated using the National Cancer Institute-Common Terminology Criteria for Adverse Events version 4.0. Overall survival (OS) and progression-free survival (PFS) rates were estimated using a Kaplan-Meier analysis and compared using the log-rank test. All patients were assessed as unresectable cases. Twenty-four patients (24/29; 82.8%) showed LAGC on positron emission tomography-computed tomography (CT) and contrast-enhanced CT, whereas four patients (4/29; 13.8%) with vague invasion or abutment to an adjacent organ underwent diagnostic laparoscopy. One patient (1/29; 3.4%), initially assessed as a resectable case, underwent an "open and closure" after the tumor was found to be unresectable. Abutment to an adjacent organ (34.5%) was the most common reason for NACRT. The clinical response rate one month after NACRT was 44.8%. After NACRT, 69% (20/29) of patients had a resectable tumor. Of the 20 patients with a resectable tumor, 18 patients (62.1%) underwent a D2 gastrectomy. The R0 resection rate was 94.4% and two patients (2/18; 11.1%) showed a complete response. The median follow-up duration was 13.5 mo. The one-year OS and PFS rates were 72.4 and 48.9%, respectively. The one-year OS, PFS, local failure-free survival, and distant metastasis-free survival were higher in patients with a resectable tumor after NACRT (P < 0.001, P < 0.001, P < 0.001, and P = 0.078, respectively). No grade 3-4 late treatment-related toxicities or postoperative mortalities were observed. NACRT with D2 gastrectomy showed a high rate of R0 resection and promising local control, which may increase the R0 resection opportunity resulting in survival benefit.
    03/2015; 21(9):2711-8. DOI:10.3748/wjg.v21.i9.2711
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    ABSTRACT: Rearrangement of ALK is an established driver aberration in lung cancer. Accordingly, this study attempted to determine the frequency and prognostic impact of ALK alterations in patients with surgically resected gastric cancer. The study evaluated ALK alterations in whole tumor sections of 455 curatively resected gastric cancers via immunohistochemistry (IHC) and fluorescent in situ hybridization (FISH). Any expression of ALK protein (1+, 2+, 3+ by IHC) was considered as evidence of ALK positivity (ALK+), and the relationship between ALK positivity and clinicopathologic parameters, including survival outcome, was analyzed. Of the 455 tumors, 38 (8.4 %) were ALK positive, as measured by IHC. Among the ALK+ patients, two displayed break-apart signals of 5 and 11 % on FISH, respectively. The ALK+ patients were younger (57 vs. 61 years; P = 0.02) and more likely to exhibit a signet ring cell component. Moreover, as ALK intensity measured by IHC increased, so did the proportion of signet ring cells in tumors (defined as ≥10 % of tumor cells; P = 0.02). In terms of survival outcome, the ALK+ patients displayed worse disease-free survival (DFS) and overall survival (OS) than the ALK- patients (P = 0.010 for DFS; P = 0.023 for OS). Multivariate analysis demonstrated that ALK+ gastric cancer patients were at an increased risk of recurrence and death after adjustment for sex, age, tumor location, stage, adjuvant chemotherapy, histology, and epidermal growth factor receptor 2 (HER2) positivity (P = 0.04 for DFS; P = 0.02 for OS). The findings showed ALK positivity to be an independent negative prognostic factor in surgically resected gastric cancers associated with signet ring cell histology.
    Annals of Surgical Oncology 02/2015; DOI:10.1245/s10434-015-4376-8 · 3.93 Impact Factor

Publication Stats

4k Citations
1,522.51 Total Impact Points


  • 1998–2015
    • Yonsei University
      • • College of Medicine
      • • Department of Internal Medicine
      • • Division of Medical Oncology
      Sŏul, Seoul, South Korea
  • 2012–2014
    • Wonju Severance Christian Hospital
      Genshū, Gangwon-do, South Korea
    • Duke-NUS Graduate Medical School Singapore
      • PhD Program in Cancer and Stem Cell Biology
      Tumasik, Singapore
    • The Chinese University of Hong Kong
      • Department of Clinical Oncology
      Hong Kong, Hong Kong
  • 1996–2014
    • Yonsei University Hospital
      • Department of Internal Medicine
      Sŏul, Seoul, South Korea
  • 2013
    • Konkuk University
      Sŏul, Seoul, South Korea
  • 2000–2012
    • Seoul Medical Center
      Sŏul, Seoul, South Korea
  • 2006–2009
    • National Cancer Center Korea
      Kōyō, Gyeonggi-do, South Korea