Sook Ryun Park

National Cancer Institute (USA), Maryland, United States

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Publications (68)357.93 Total impact

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    ABSTRACT: The CLASSIC trial was done to compare adjuvant capecitabine plus oxaliplatin versus observation after D2 gastrectomy for patients with stage II or III gastric cancer. The planned interim analysis of CLASSIC (median follow-up 34 months) showed that adjuvant capecitabine plus oxaliplatin significantly improved disease-free survival, the primary endpoint, compared with observation after D2 gastrectomy. We report the 5-year follow-up data from the trial. CLASSIC was a phase 3, randomised, open-label study done at 35 cancer centres, medical centres, and hospitals in China, South Korea, and Taiwan. Patients with stage II-IIIB gastric cancer who underwent curative D2 gastrectomy were randomly assigned (1:1) after surgery to receive adjuvant chemotherapy with capecitabine and oxaliplatin (eight 3-week cycles of oral capecitabine 1000 mg/m(2) twice daily on days 1-14 plus intravenous oxaliplatin 130 mg/m(2) on day 1) for 6 months or observation alone. Randomisation was stratified by country and disease stage with a permuted block (size four) design. Neither patients nor investigators were masked to treatment assignment. The primary outcome was 3-year disease-free survival in the intention-to-treat population. This analysis presents the final preplanned assessment of outcomes after 5 years. The study is registered with, NCT00411229. We enrolled 1035 patients: 520 were randomly assigned to adjuvant capecitabine and oxaliplatin, and 515 to observation. Median follow-up for this analysis in the intention-to-treat population was 62·4 months (IQR 54-70). 139 (27%) patients had disease-free survival events in the adjuvant capecitabine and oxaliplatin group versus 203 (39%) patients in the observation group (stratified hazard ratio [HR] 0·58, 95% CI 0·47-0·72; p<0·0001). Estimated 5-year disease-free survival was 68% (95% CI 63-73) in the adjuvant capecitabine and oxaliplatin group versus 53% (47-58) in the observation alone group. By the clinical cutoff date, 103 patients (20%) had died in the adjuvant capecitabine and oxaliplatin group versus 141 patients (27%) in the observation group (stratified HR 0·66, 95% CI 0·51-0·85; p=0·0015). Estimated 5-year overall survival was 78% (95% CI 74-82) in the adjuvant capecitabine and oxaliplatin group versus 69% (64-73) in the observation group. Adverse event data were not collected after the primary analysis. Adjuvant treatment with capecitabine plus oxaliplatin after D2 gastrectomy should be considered for patients with operable stage II or III gastric cancer. F Hoffmann La-Roche and Sanofi. Copyright © 2014 Elsevier Ltd. All rights reserved.
    The Lancet Oncology 11/2014; 15(12):1389-96. · 25.12 Impact Factor
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    ABSTRACT: Objective: This study examined changes in health-related quality of life (HRQoL) and quality of care (QoC) as perceived by terminally ill cancer patients and a stratified set of HRQoL or QoC factors that are most likely to influence survival at the end of life (EoL). Method: We administered questionnaires to 619 consecutive patients immediately after they were diagnosed with terminal cancer by physicians at 11 university hospitals and at the National Cancer Center in Korea. Subjects were followed up over 161.2 person-years until their deaths. We measured HRQoL using the core 30-item European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, and QoC using the Quality Care Questionnaire-End of Life (QCQ-EoL). We evaluated changes in HRQoL and QoC issues during the first three months after enrollment, performing sensitivity analysis by using data generated via four methods (complete case analysis, available case analysis, the last observation carried forward, and multiple imputation). Results: Emotional and cognitive functioning decreased significantly over time, while dyspnea, constipation, and pain increased significantly. Dignity-conserving care, care by healthcare professionals, family relationships, and QCQ-EoL total score decreased significantly. Global QoL, appetite loss, and Eastern Cooperative Oncology Group Performance Status (ECOG-PS) scores were significantly associated with survival. Significance of results: Future standardization of palliative care should be focused on assessment of these deteriorated types of quality. Accurate estimates of the length of life remaining for terminally ill cancer patients by such EoL-enhancing factors as global QoL, appetite loss, and ECOG-PS are needed to help patients experience a dignified and comfortable death.
    Palliative & supportive care. 09/2014;
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    ABSTRACT: Hypoxia-inducible factor-1 alpha (HIF-1α) is an important marker of hypoxia in human tumors and has been implicated in tumor progression. Drugs targeting HIF-1α are being developed, but the ability to measure drug-induced changes in HIF-1α is limited by the lability of the protein in normoxia. Our goal was to devise methods for specimen collection and processing that preserve HIF-1α in solid tumor tissues and to develop and validate a two-site chemiluminescent quantitative ELISA for HIF-1α. We tested various strategies for HIF-1α stabilization in solid tumors including nitrogen gas-purged lysis buffer, addition of proteasome inhibitors, or the prolyl hydroxylase inhibitor 2-hydroxyglutarate, and bead homogenization. Degassing and addition of 2-hydroxyglutarate to the collection buffer significantly increased HIF-1α recovery, while bead-homogenization in sealed tubes improved HIF-1α recovery and reduced sample variability. Validation of the ELISA demonstrated intra- and inter-assay variability of less than 15% and accuracy of 99.8% ± 8.3% as assessed by spike recovery. Inter-laboratory reproducibility was also demonstrated (R2 = 0.999). Careful sample handling techniques allow us to quantitatively detect HIF-1α in samples as small as 2.5 μg of total protein extract, and this method is currently being applied to analyze tumor biopsy specimens in early-phase clinical trials.
    Analytical Biochemistry 01/2014; · 2.58 Impact Factor
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    ABSTRACT: Hypoxia-inducible factor-1 (HIF-1) facilitates the adaptation of normal and tumor tissues to oxygen deprivation. HIF-1 is frequently overexpressed in cancer cells, where it is involved in the upregulation of many genes necessary for survival. EZN-2968 is an antisense oligodeoxynucleotide that specifically targets HIF-1α, one of the subunits of HIF-1. We conducted a trial of EZN-2968 in patients with refractory solid tumors to evaluate antitumor response and to measure modulation of HIF-1α mRNA and protein levels as well as HIF-1 target genes. Adult patients with refractory advanced solid tumors were administered EZN-2968 as a 2-h IV infusion at a dose of 18 mg/kg once a week for three consecutive weeks followed by 3-week off; in a 6-week cycle. Tumor biopsies and dynamic contrast enhanced MRI (DCE-MRI) were performed at baseline and after the third dose. Ten patients were enrolled, of whom all were evaluable for response; one patient with a duodenal neuroendocrine tumor had prolonged stabilization of disease (24 weeks). Reduction in HIF-1α mRNA levels compared to baseline was demonstrated in 4 of 6 patients with paired tumor biopsies. Reductions in levels of HIF-1α protein and mRNA levels of some target genes were observed in two patients. Quantitative analysis of DCE-MRI from two patients revealed changes in K (trans) and k ep. The trial was closed prematurely when the sponsor suspended development of this agent. This trial provides preliminary proof of concept for modulation of HIF-1α mRNA and protein expression and target genes in tumor biopsies following the administration of EZN-2968.
    Cancer Chemotherapy and Pharmacology 11/2013; · 2.80 Impact Factor
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    ABSTRACT: Background Anti-angiogenic therapies such as bevacizumab upregulate hypoxia-inducible factor-1α (HIF-1α), a possible mechanism of drug resistance. Camptothecin analogues, including SN-38, have been shown to reduce the expression and transcriptional activity of HIF-1α in preclinical models. We hypothesized that co-administration of pegylated SN-38 (EZN-2208) may offset the induction of HIF-1α following bevacizumab treatment, resulting in synergistic antitumor effects. Patients and Methods Patients with refractory solid tumors were enrolled. Objectives were to evaluate the modulation of HIF-1α protein and target genes in tumor biopsies following administration of the combination of EZN-2208 administered weekly × 3 (days 1, 8, 15) and bevacizumab administered every 2 weeks, in 28-day cycles, and to establish the safety and tolerability of the combination. Tumor biopsies and dynamic contrast enhanced MRI (DCE-MRI) were obtained following bevacizumab alone (before EZN-2208) and after administration of both study drugs. Results Twelve patients were enrolled; ten were evaluable for response. Prolonged stable disease was observed in 2 patients, one with HCC (16 cycles) and another with desmoplastic round cell tumor (7 cycles). Reduction in HIF-1α protein levels in tumor biopsies compared to baseline was observed in 5 of 7 patients. Quantitative analysis of DCE-MRI from 2 patients revealed changes in K(trans) and kep. The study closed prematurely as further clinical development of EZN-2208 was suspended by the pharmaceutical sponsor. Conclusion Preliminary proof-of-concept for modulation of HIF-1α protein in tumor biopsies following administration of EZN-2208 was observed. Two of 10 patients had prolonged disease stabilization following treatment with the EZN-2208 and bevacizumab combination.
    Investigational New Drugs 11/2013; · 3.50 Impact Factor
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    ABSTRACT: Gastric cancer is the fourth most common cancer globally, and is the second most common cause of death from cancer worldwide. About three-quarters of newly diagnosed cases in 2008 were from Asian countries. With a high mortality-to-incidence ratio, management of gastric cancer is challenging. We discuss evidence for optimum management of gastric cancer in aspects of screening and early detection, diagnosis, and staging; endoscopic and surgical intervention; and the concepts of perioperative, postoperative, and palliative chemotherapy and use of molecularly targeted therapy. Recommendations are formulated on the basis of the framework provided by the Breast Health Global Initiative, using the categories of basic, limited, enhanced, and maximum level. We aim to provide a stepwise strategy for management of gastric cancer applicable to different levels of health-care resources in Asian countries.
    The Lancet Oncology 11/2013; 14(12):e535-47. · 25.12 Impact Factor
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    ABSTRACT: The prognosis of patients with positive surgical resection margins is dismal in gastric cancer. However, the influence of positive margin itself on prognosis is still uncertain, especially in advanced gastric cancer (AGC). The aims of the present study were to evaluate the prognostic impact of microscopic tumor involved resection margins in stage III-IV AGC after gastric resection in comparison with other well-known factors. Among 1,536 consecutive gastric cancer patients who received intentional curative resection for stage III-IV AGC between April 2001 and December 2011 at the National Cancer Center, 35 patients (2.28 %) had positive resection margins on their final histology. A comparison of clinicopathologic characteristics, recurrence pattern, overall survival (OS), and disease-free survival (DFS) was made between positive margin (PM) patients and negative margin (NM) patients. Among the 35 PM patients, 15 (42.9 %) had proximal involved margins, 21 (60.0 %) had distal involved margins, and one (2.9 %) had both involved margins. Twenty-eight PM patients (80.0 %) were stage III, and 7 (20.0 %) were stage IV. Recurrence was significantly higher in PM than NM (63.6 % vs. 39.7 %, respectively; p = 0.005). The OS and DFS rates were significantly lower in the PM group than in the NM group (14.9 vs. 36.3 months, p < 0.001 and 11.6 vs. 27.1 months, p = 0.005, respectively). The presence of PM was an independent risk factor for both OS and DFS. The presence of PM is an independent risk factor for OS and DFS. Considering the prognostic impact of PM, a sufficient resection margin should be ensured when determining the resection line in gastrectomy with curative intent. The reoperation to secure clear resection margins should be considered as a treatment of choice in the case of PM.
    World Journal of Surgery 10/2013; · 2.23 Impact Factor
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    ABSTRACT: Self-expandable metallic stents are used widely to relieve malignant gastric outlet obstruction (GOO). However, restenosis or migration of first stents is a frequent complication. The purpose of this retrospective cohort study was to evaluate the effectiveness of second stents as an approach to manage failure of first stents in patients with malignant GOO. A total of 222 patients with gastric cancer received first stents due to inoperable GOO at National Cancer Center in Korea between January 2008 and June 2011. Monthly follow-up interviews were performed, and second stents (stent-in-stent or stent-after-migration) were inserted in 59 patients by June 2012. Technical and clinical successes and long-term complications were evaluated. The technical and immediate clinical success rates were 98.3 % (58/59) and 91.5 % (54/59), respectively. Patients who received a second stent due to late complications involving the first stent (migration, restenosis, and fracture) showed a higher clinical success rate (95.8 % [46/48]) than patients who received a second stent due to immediate clinical failure of the first stent (72.7 % [8/11], p = 0.04). The immediate clinical success rate of stent-after-migration (100 % [11/11]) was not different from that of stent-in-stent (89.6 % [43/48], p = 1.0). The stent dysfunction rate of stent-after-migration (27.3 % [3/11]) also was similar to that of stent-in-stent (29.2 % [14/48], p = 1.0). The median patencies of stent-in-stent and stent-after-migration were 27.4 and 58.4 weeks, respectively (p = 0.177). There were no significant prognostic factors for patency of second stents. Insertion of a second stent is effective for treating the first-stent failure in gastric cancer patients with GOO, especially if the immediate outcome of the first stent was successful.
    Surgical Endoscopy 09/2013; · 3.43 Impact Factor
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    ABSTRACT: We conducted a phase I study of S-1 combined with irinotecan and oxaliplatin (TIROX) to determine the maximum-tolerated dose (MTD) and recommended dose (RD) and to assess its safety, pharmacokinetics, pharmacogenetics, and preliminary efficacy in patients with metastatic colorectal cancer (MCRC) or metastatic gastric cancer (MGC). Patients received escalating doses of S-1 (30-40 mg/m(2) b.i.d.) orally on days 1-14, an escalating dose of intravenous irinotecan (120-150 mg/m(2)) on day 1, and a fixed dose of intravenous oxaliplatin (85 mg/m(2)) on day 1 every 3 weeks. Twenty-three patients (10 MCRC, 13 MGC; 13 chemonaive, 10 previously treated for metastatic disease) were treated across six dose levels. Because only one patient experienced a dose-limiting toxicity of grade 3 anorexia at the highest dose level (S-1 40 mg/m(2) b.i.d., irinotecan 150 mg/m(2), and oxaliplatin 85 mg/m(2)) (n = 8), the MTD was not obtained, and this level was established as the RD. With a median of 10 cycles per patient, the most common grade 3 or 4 adverse events included neutropenia (43 %), diarrhea (13 %), and nausea (13 %). In 22 efficacy-evaluable patients, the objective tumor response rate was 59.1 % (75 % for both MCRC and MGC in the first-line setting) and the disease control rate was 100 %. The exploratory pharmacokinetic/pharmacogenetic study showed that CYP2A6 variants (*4, *7, *9) are associated with a lower metabolic ratio of S-1 (exposure ratio of 5-fluorouracil to tegafur). The new triplet TIROX regimen has shown promising antitumor activity and a favorable toxicity profile in patients with MCRC and MGC.
    Cancer Chemotherapy and Pharmacology 08/2013; · 2.80 Impact Factor
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    ABSTRACT: PURPOSE: A multi-cohort phase II study of fostamatinib, an oral multi-kinase inhibitor, was conducted to determine the response rate in patients with advanced colorectal (CRC), thyroid, non-small cell lung, head and neck, and renal cell carcinomas, and pheochromocytomas. METHODS: Patients received 200 mg fostamatinib BID in 4-week cycles with response assessed every 2 cycles. Blood was collected for pharmacokinetic analysis and measurements of circulating tumor cells and circulating endothelial (progenitor) cells (CE(P)Cs). RESULTS: A total of 37 patients (22 CRC), median of 4 prior therapies, were enrolled. Due to toxicities in four of the first five patients, the study was amended to incorporate a dose escalation phase for each histology. The maximum-tolerated dose was established at 50 mg BID in CRC but was not established for the other cancers. Common grade 3/4 toxicities included transaminitis, hyperbilirubinemia, and hypertension. Pharmacokinetic profile was similar to previous reports. Seventy-three percent of CRC patients had liver involvement and 91 % had prior anti-angiogenic therapy. Patients with abnormal liver tests at baseline were more likely to experience grade ≥2 hepatotoxicity than those with normal tests (44 vs. 0 %). No responses were observed; disease stabilization rate was 27 % in CRC. Reduction in CECs following treatment was associated with a better disease stabilization rate (75 vs. 0 %) in CRC. CONCLUSION: Fostamatinib had limited anti-tumor activity in this first clinical trial in patients with advanced refractory solid tumors; reduction in CECs and CEPs was indicative of anti-angiogenic effects. Abnormal liver testing at baseline appeared to influence drug tolerability.
    Cancer Chemotherapy and Pharmacology 02/2013; · 2.80 Impact Factor
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    ABSTRACT: Background: Although caregiving to patients with terminal illness is known to be a stressful burden to family members, little attention has been focused on work-related problems. We aimed to investigate employment status and work-related difficulties of family caregivers of terminal cancer patients, comparing with the general population. Methods: Using structured questionnaires, we assessed family caregivers of 481 cancer patients determined by physicians to be terminally ill, from 11 university hospitals and the National Cancer Center in Korea. Results: Among 381 family caregivers of terminal cancer patients (response rate, 87.6%), 169 (43.9%) were not working before cancer diagnosis, but currently 233 (63.7%) were not working. Compared with the general population (36.5%), the percentage of not working among the family caregivers was higher (OR = 2.39; 95% CI= 1.73-3.29). A major reason for not working was to provide assistance to the patients (71.6%). 40.6% of those who continued working and 32.3% of those who not working family members reported extreme fatigue. Caregivers of old age, those who were female, those with a lower household income, and those caring for patients with a low performance status were not working at a more significant rate. Conclusion: Family caregivers of terminal cancer patients suffer job loss and severe work-related difficulties, probably due to caregiving itself and to fatigue. We need to develop supportive programs to overcome the burden of caregivers of the terminally ill.
    Asian Pacific journal of cancer prevention: APJCP 01/2013; 14(1):373-380. · 1.50 Impact Factor
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    ABSTRACT: Objectives: Terminal cancer patients and their caregivers often experience traumatic stress and need many types of assistance. In the present study we interviewed terminally ill cancer patients and caregivers to determine how much burden they experienced and to find out what factors are most important for satisfaction. Design: We constructed a questionnaire including overall care burden and needs experienced, and administered it to 659 terminal cancer patients and 659 important caregivers at 11 university hospitals and 1 national cancer center in Korea. Results: Finally, 481 terminal cancer patients and 381 caregivers completed the questionnaire. Care burden was not insubstantial in both and the caregiver group felt more burden than the patient group (P <0.001). While the patient group needed financial support most (39.0%), the caregiver group placed greatest emphasis on discussion about further treatment plans (44.8%). Stepwise multiple logistic regression analyses showed that in the patient group, patient's health status (OR, 2.03; 95% CI, 1.16-3.56) and burden (OR, 2.82; 95% CI, 1.76-4.50) influenced satisfaction about overall care, while in the caregiver group, high education level`(OR, 1.84; 95% CI, 1.76-4.50), burden (OR, 2.94; 95% CI, 1.75-4.93) and good family function (OR, 1.94; 95% CI, 1.24-3.04) were important. Conclusions: Our study showed that burden was great in both terminal cancer patients and their caregivers and was perceived to be more severe by caregivers. Our study also showed that burden was the factor most predicting satisfaction about overall care in both groups.
    Asian Pacific journal of cancer prevention: APJCP 01/2013; 14(1):209-216. · 1.50 Impact Factor
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    ABSTRACT: The plethora of novel molecular-targeted agents (MTAs) has provided an opportunity to selectively target pathways involved in carcinogenesis and tumour progression. Combination strategies of MTAs are being used to inhibit multiple aberrant pathways in the hope of optimizing antitumour efficacy and to prevent development of resistance. While the selection of specific agents in a given combination has been based on biological considerations (including the role of the putative targets in cancer) and the interactions of the agents used in combination, there has been little exploration of the possible enhanced toxicity of combinations resulting from alterations in multiple signalling pathways in normal cell biology. Owing to the complex networks and crosstalk that govern normal and tumour cell proliferation, inhibiting multiple pathways with MTA combinations can result in unpredictable disturbances in normal physiology. This Review focuses on the main toxicities and the lack of tolerability of some common MTA combinations, particularly where evidence of enhanced toxicity compared to either agent alone is documented or there is development of unexpected toxicity. Toxicities caused by MTA combinations highlight the need to introduce new preclinical testing paradigms early in the drug development process for the assessment of chronic toxicities resulting from such combinations.
    Nature Reviews Clinical Oncology 01/2013; · 15.03 Impact Factor
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    ABSTRACT: BACKGROUND AND AIMS: The best therapeutic modality has not been established for gastric low-grade adenomas or dysplasia (LGD), which can progress to invasive carcinoma despite a low risk. This study aims to investigate the clinical efficacy, safety, and local recurrence after argon plasma coagulation (APC) treatment of gastric LGD compared with endoscopic submucosal dissection (ESD). PATIENTS AND METHODS: A total of 320 patients with gastric LGD ≤2.0 cm treated with APC or ESD between 2004 and 2011 were retrospectively analyzed. We compared local recurrence rate, complication rate, procedure time, and admission to hospital between APC and ESD groups. RESULTS: Of the 320 patients, 116 patients were treated with APC and 204 with ESD. During follow-up, local recurrence was more common in the APC group (3.8 %, 4/106) than the ESD group (0.5 %, 1/188; log-rank test P = 0.036). However, all patients with local recurrence (n = 5) were treated by additional APC, and followed up without further recurrences. ESD was complicated by two perforations (1.0 %, 2/204) compared with no perforations in the APC group (0 %, 0/116). Bleeding complications were not different between the APC (1.7 %, 2/116) and ESD (2.0 %, 4/204) groups. Procedure time was shorter in the APC (7.8 ± 5.1 min) than the ESD (53.1 ± 38.1 min) group (P < 0.001). The proportion of hospitalization was less in the APC group (31.0 %, 36/116) than the ESD group (100.0 %, 204/204) (P < 0.001). CONCLUSIONS: APC can be a good treatment option for patients with LGD ≤2.0 cm.
    Surgical Endoscopy 10/2012; · 3.43 Impact Factor
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    ABSTRACT: PURPOSE: To evaluate the efficacy and safety of 2-year adjuvant imatinib for patients at high risk of recurrence after complete resection of localized gastrointestinal stromal tumor with KIT exon 11 mutation. METHODS: Imatinib 400 mg/d was administered until disease recurrence, intolerable toxicities, or for 2 years. The primary end point was recurrence-free survival. RESULTS: Patients (n = 47) from 4 centers in Korea were enrolled. Treatment was well tolerated. Grade 3-4 toxicities included neutropenia (27.7 %), skin rash (8.5 %), anorexia (4.3 %), and constipation (2.1 %). At a median follow-up of 56.7 months, 19 patients had recurrences. Median recurrence-free survival was 58.9 months, which was significantly longer than 22.7 months from historical data of 27 patients in the pre-imatinib era (P < 0.0001). Imatinib was rechallenged for 15 patients with recurrence after completion of adjuvant imatinib. Thirteen patients had partial response, and two had stable disease. There was only one death so far. CONCLUSIONS: Postoperative adjuvant imatinib for 2 years was safe and could prolong the recurrence-free survival in patients with a high risk of recurrence after complete resection of localized KIT exon 11 mutated gastrointestinal stromal tumor. Reintroduction of imatinib after recurrence appears to be effective if the recurrence develops after completion of adjuvant imatinib.
    Cancer Chemotherapy and Pharmacology 10/2012; · 2.80 Impact Factor
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    ABSTRACT: PURPOSE: To compare chemotherapy alone with chemoradiation therapy in stage III-IV(M0) gastric cancer treated with R0 gastrectomy and D2 lymph node dissection. METHODS AND MATERIALS: The chemotherapy arm received 5 cycles of fluorouracil and leucovorin (FL), and the chemoradiation therapy arm received 1 cycle of FL, then radiation therapy of 45 Gy concurrently with 2 cycles of FL, followed by 2 cycles of FL. Intent-to-treat analysis and per-protocol analyses were performed. RESULTS: Between May 6, 2002 and June 29, 2006, a total of 90 patients were enrolled. Forty-four were randomly assigned to the chemotherapy arm and 46 to the chemoradiation therapy arm. Treatment was completed as planned by 93.2% of patients in the chemotherapy arm and 87.0% in the chemoradiation therapy arm. Overall intent-to-treat analysis showed that addition of radiation therapy to chemotherapy significantly improved locoregional recurrence-free survival (LRRFS) but not disease-free survival. In subgroup analysis for stage III, chemoradiation therapy significantly prolonged the 5-year LRRFS and disease-free survival rates compared with chemotherapy (93.2% vs 66.8%, P=.014; 73.5% vs 54.6%, P=.056, respectively). CONCLUSIONS: Addition of radiation therapy to chemotherapy could improve the LRRFS in stage III gastric cancer treated with R0 gastrectomy and D2 lymph node dissection.
    International journal of radiation oncology, biology, physics 09/2012; · 4.59 Impact Factor
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    Sook Ryun Park, Alice Chen
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    ABSTRACT: Recently, the development of poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors as a synthetic lethality approach has brought a major breakthrough in the treatment of breast cancer susceptibility gene (BRCA)-mutant cancers. Because sporadic cancers have also been found to commonly have other defects in DNA repair, PARP inhibitors are under active clinical investigation in combination with DNA-damaging therapeutics in a wide range of sporadic cancers. In this review, the authors discuss DNA repair mechanisms and PARP as a therapeutic target and summarize an update on clinical trials of available PARP inhibitors and predictive biomarkers for their efficacy.
    Hematology/oncology clinics of North America 06/2012; 26(3):649-70, ix. · 2.05 Impact Factor
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    ABSTRACT: The aim of the present study was to assess the association between the pre-operative plasma fibrinogen level and the adjacent organ involvement in advanced gastric cancer. A total of 923 pre-operative plasma samples were obtained from 923 patients diagnosed clinically as having advanced gastric cancer, and fibrinogen levels were measured by immunoassay. Associations between fibrinogen levels and clinicopathologic findings (depth of tumor, adjacent organ involvement, and lymph node metastasis), along with survival were examined by univariate and multivariate analyses. Tumor size, tumor depth, and the presence of lymph node metastasis were found to be positively correlated with the preoperative plasma fibrinogen levels (P<0.001). Fifty (5.4%) patients had adjacent organ involvement. Lymphatic invasion (P<0.001), tumor size (P<0.001), clinical T (depth of invasion) stage (P<0.001), and clinical nodal stage (P=0.018) were found to be associated with adjacent organ involvement. Univariate and multivariate regression analyses showed that a preoperatively elevated plasma fibrinogen level was associated with adjacent organ involvement (P<0.001, 0.028), and Kaplan-Meier analysis showed that it was associated with poorer survival (P<0.001). Plasma fibrinogen was found to be a clinically useful marker of adjacent organ involvement and overall survival. When a high fibrinogen level is encountered, preoperatively, adjacent organ involvement should be suspected in clinically advanced gastric cancer.
    Journal of gastric cancer. 06/2012; 12(2):81-7.
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    ABSTRACT: Family history of gastric cancer is a major risk factor for the disease. In this study, we investigated the prognoses of patients with gastric cancer with a family history. We retrospectively reviewed data from 1,273 patients with gastric adenocarcinoma who had undergone gastrectomy between 2001 and 2005 at a tertiary cancer center hospital. A positive family history was defined as a self-reported history of cancer in first- or second-degree relatives. Patients were followed up until December 2009 for death or recurrence. Clinicopathologic characteristics were compared by family history. Kaplan-Meier plots and Cox proportional hazards regressions were applied for disease-free survival (DFS), recurrence-free survival (RFS), and overall survival (OS). Of 1,273 patients, 263 patients (20.6%) had first-degree relatives with a history of gastric cancer. First-degree family history of gastric cancer was associated with better DFS, RFS, and OS (P = .012, .006, and .005, respectively). In patients with stage I or II gastric cancer, first-degree family history was not associated with survival. However, it was associated with a reduced risk of recurrence or mortality in patients with stage III or IV gastric cancer. Compared with patients without a family history, the adjusted hazard ratios for those with a first-degree family history of gastric cancer were 0.49 (95% CI, 0.29 to 0.84) for DFS, 0.51 (95% CI, 0.30 to 0.87) for RFS, and 0.47 (95% CI, 0.26 to 0.84) for OS in patients with stage III or IV gastric cancer. A first-degree family history of gastric cancer is associated with improved survival after curative-intent surgery in patients with stage III or IV gastric cancer.
    Journal of Clinical Oncology 03/2012; 30(7):701-8. · 18.04 Impact Factor
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    ABSTRACT: The purpose of this study was to compare the clinical usefulness of the seventh Union Internationale Contre le Cancer/American Joint Committee on Cancer (AJCC/UICC) staging system vs the sixth AJCC/UICC staging system in patients with gastric cancer. Included were 1,799 patients who underwent surgery for gastric cancer between January 2001 and June 2005 at the National Cancer Center (South Korea). For the sixth and seventh AJCC/UICC staging systems, survival outcomes stratified by stage, by T classification, and by N classification were summarized using Kaplan-Meier curves and compared statistically using a log rank test; survival differences were quantified using hazard ratios estimated from a Cox regression model. The 2 systems were compared in terms of prognostic performances using the linear trend chi-square test, likelihood ratio chi-square test, and Akaike information criterion (AIC) in the Cox regression analysis. Significant survival differences between each stage were not found using the seventh staging system, especially for stages IB, IIA, and IIB (p = 0.14 and p = 0.11). The sixth staging system had higher linear trend chi-square score and likelihood ratio chi-square score, which means better discriminatory ability, monotonicity, and homogeneity, and had smaller AIC, which indicates better optimistic prognostic stratification, especially in the N classification. The modified staging system combining the T classification of the seventh AJCC/UICC system and the N classification of the sixth system showed better prognostic performance compared with each separate version (sixth or seventh) of the staging system. The seventh AJCC/UICC staging system is not more clinically useful than the sixth system in surgically treated patients with gastric cancer because of an inappropriate N classification. A new TNM system is required with a different N classification.
    Journal of the American College of Surgeons 01/2012; 214(1):88-96. · 4.50 Impact Factor

Publication Stats

912 Citations
357.93 Total Impact Points


  • 2012–2014
    • National Cancer Institute (USA)
      • Division of Cancer Treatment and Diagnosis
      Maryland, United States
  • 2005–2014
    • National Cancer Center Korea
      • Gastric Cancer Branch
      Kōyō, Gyeonggi Province, South Korea
  • 2013
    • National Institutes of Health
      • Division of Cancer Treatment and Diagnosis
      Bethesda, MD, United States
  • 2003–2013
    • Seoul National University Hospital
      • Department of Internal Medicine
      Sŏul, Seoul, South Korea
  • 2009–2012
    • Konyang University Hospital
      Gaigeturi, Jeju, South Korea