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  • American Society of Clinical Oncology (ASCO)  (12)
  • Im, Seock-Ah  (12)
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  • American Society of Clinical Oncology (ASCO)  (12)
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  • 1
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 4_suppl ( 2012-02-01), p. 623-623
    Abstract: 623 Background: Ethnic diversity of genetic polymorphism can result in individual differences in the efficacy and toxicity of cancer chemotherapy. Methods: A total of 292 Korean patients (183 men and 109 women) from six hospitals in Korea were prospectively enrolled. Patients had resected stage III or high-risk stage II colon cancer and were treated with 12 cycles of adjuvant oxaliplatin plus leucovorin plus 5-fluorouracil (FOLFOX) chemotherapy. 20 germline polymorphisms in 10 genes (TS, MTHFR, ERCC1, XPD, XRCC1, ABCC2, AGXT, GSTP1, GSTT1 and GSTM1) were analyzed from peripheral blood. TS genotype in 5’UTR was classified as ‘high’ (2R/3G, 3C/3G, and 3G/3G) or ‘low’ (2R/2R, 2R/3C, and 3C/3C). Results: Most patients (86.3%) received 12 complete cycles of FOLFOX chemotherapy. In contrast to previous studies in Caucasians, neutropenia (grade 3–4, 60.5%) was frequently observed in our Korean patients, whereas only 16.4% experienced grade 2 or more sensory neuropathy. Neutropenia was more frequent in MTHFR 677TT [adjusted odds ratio (OR) 2.32, 95% confidence interval (CI) 1.19–4.55] and ERCC1 19007TT (adjusted OR 4.58, 95% CI 1.20–17.40) genotypes. Patients harboring XRCC1 23885GG had lower risk of neuropathy (adjusted hazard ratio 0.56, 95% CI 0.32-0.99) and longer time to the onset of grade 2-4 neuropathy. MTHFR 677TT and XRCC1 23885GG genotype was also more prevalent in Koreans compared to Caucasians, and the difference of genotypic frequency could partly explain the ethnically different toxicity profile. After median 49.4 months of follow-up, there were 58 (19.9%) relapses and 19 (6.5%) deaths. TS ‘low’ genotype [adjusted hazard ratio (OR) 1.83, 95% CI 1.003–3.34] was significantly related to shorter disease-free survival. Overall survival was not significantly different according to the polymorphisms. Conclusions: Polymorphisms in MTHFR, XRCC1 and TS are related to toxicities and disease-free survival in patients with colon cancer. These polymorphisms may explain the ethnic difference in toxicity profile following adjuvant FOLFOX chemotherapy.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
    detail.hit.zdb_id: 2005181-5
    detail.hit.zdb_id: 604914-X
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  • 2
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. 3550-3550
    Abstract: 3550 Background: There have been controversies in prognostic impact of mucinous histology in colorectal cancer (CRC) and its implication in pts treated with adjuvant FOLFOX is unclear. This study aimed at elucidating the molecular characteristics and prognostic implication of mucinous histology in pts treated with adjuvant FOLFOX. Methods: Stage II and III CRC pts who received adjuvant FOLFOX were analyzed. Pts were grouped according to the mucinous content: 〉 50%, mucinous adenocarcinoma (MAC); 〈 50%, adenocarcinoma with intermediated mucinous component (AIM); and without any mucinous component, nonmucinous adenocarcinoma (NMA). Clinicopathologic features, MSI status (N = 518), CpG island methylator phenotype (CIMP) (N = 322) BRAF mutation (N = 269) and disease-free survival (DFS) were compared. Results: Among a total of 521 pts, 27 (5.2%) had MAC, 41 (7.9%) AIM, and 453 (86.9%) NMA. MAC and AIM had higher frequency of proximal location and lower angiolymphatic invasion. MAC had higher proportion of T4 tumors. AIM had higher frequency of age ≥65 years and female. In terms of molecular characteristics, MAC and AIM showed similarly higher proportion of MSI-high and CIMP-high compared to NMA. BRAF mutation also showed similar trend. In contrast to the similarities between MAC and AIM, DFS was significantly different. MAC showed significantly worse DFS compared with AIM and NMA, whereas AIM and NMA showed similar DFS. Multivariate analysis revealed MAC as an independent negative prognostic factor of DFS (adjusted HR 7.96, 95% CI 3.76-16.8). Conclusions: AIM and MAC has distinct clinico-pathologic features and molecular characteristics compared with NMA. Only MAC but not AIM has an adverse prognostic impact on stage II or III CRC treated with adjuvant FOLFOX compared with NMA. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
    detail.hit.zdb_id: 2005181-5
    detail.hit.zdb_id: 604914-X
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  • 3
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 4_suppl ( 2012-02-01), p. 626-626
    Abstract: 626 Background: Systemic chemotherapy is still mainstay of treatment of metastatic colorectal cancer (mCRC), while the role of palliative resection is not convincing. We intended to find out the role of palliative resection in mCRC. Methods: A total of 1,015 patients were diagnosed with mCRC at Seoul National University Hospital between 2000 and 2009. Except 169 patients who received curative metastectomy of liver and/or lung, 847 patients were retrospectively analyzed. Results: Out of 847 patients, 556 (65.6%) had metastasis at the time of diagnosis and 291 (34.4%) had recurrence after surgery. The median age was 61 (range, 16-88) and 491 (58.0%) were male. The median number of metastatic site was 1 (range, 1-6) and 738 (87.1%) had limited metastasis (number of metastatic site ≤2). The liver was most frequently involved site (451, 53.2%). Surgery was done in 527 (62.2%). One hundred three patients received resection of both primary and metastatic sites (group 1), while 347 and 78 received resection of primary (group 2) and metastatic sties (group 3), respectively. R0 resection was done in 95 patients (G1: 53, G3: 42), while R1/2 was done 431 in patients (G1: 56, G2: 336, G3:39). Of 95 patients with R0 resection, 93 (97.8%) had limited metastasis (number of metastatic organ ≤2) in the peritoneum, lymph nodes, liver, or lung. The median overall survival (OS) was 19.0 months (95% CI, 17.8-20.1) and resected patients had prolonged median OS compared with patients never resected (21.3 vs 14.1 months, p 〈 0.001). In multivariate analysis, R0 resection was associated with superior OS compared to R2 resection (51.3 vs 18.7 months; HR, 3.0; 95% CI, 1.86 to 4.85, P 〈 0.001), and no resection (51.3 vs 14.1 months; HR, 2.93; 95% CI, 1.73 to 4.96, P 〈 0.001). Palliative chemotherapy was administered in 746 (88.1%), while chemotherapy was not performed in 101 (11.9%) due to patient’s refusal and poor performance status. In multivariate analysis, chemotherapy was also independent prognostic factor for OS (20.4 vs 5.4 months, HR, 3.47; 95% CI, 2.25 to 5.35, P 〈 0.001). Conclusions: Palliative resection with curative intent and chemotherapy confer long-term survival on subsets of mCRC with limited metastasis.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
    detail.hit.zdb_id: 2005181-5
    detail.hit.zdb_id: 604914-X
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  • 4
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 5 ( 2020-02-10), p. 434-443
    Abstract: The addition of ovarian function suppression (OFS) for 5 years to tamoxifen (TAM) for treatment of premenopausal patients with breast cancer after completion of chemotherapy has beneficial effects on disease-free survival (DFS). This study evaluated the efficacy of adding 2 years of OFS to TAM in patients with hormone receptor–positive breast cancer who remain in a premenopausal state or resume ovarian function after chemotherapy. PATIENTS AND METHODS We enrolled 1,483 premenopausal women (age ≤ 45 years) with estrogen receptor–positive breast cancer treated with definitive surgery after completing adjuvant or neoadjuvant chemotherapy. Ovarian function was assessed every 6 months for 2 years since enrollment on the basis of follicular-stimulating hormone levels and vaginal bleeding history. If ovarian function was confirmed to be premenopausal at each visit, the patient was randomly assigned to complete 5 years of TAM alone (TAM-only) group or 5 years of TAM with OFS for 2 years that involved monthly goserelin administration (TAM + OFS) group. DFS was defined from the time of enrollment to the time of the first event. RESULTS A total of 1,293 patients were randomly assigned, and 1,282 patients were eligible for analysis. The estimated 5-year DFS rate was 91.1% in the TAM + OFS group and 87.5% in the TAM-only group (hazard ratio, 0.69; 95% CI, 0.48 to 0.97; P = .033). The estimated 5-year overall survival rate was 99.4% in the TAM + OFS group and 97.8% in the TAM-only group (hazard ratio, 0.31; 95% CI, 0.10 to 0.94; P = .029). CONCLUSION The addition of 2 years of OFS to TAM significantly improved DFS compared with TAM alone in patients who remained premenopausal or resumed ovarian function after chemotherapy.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
    detail.hit.zdb_id: 604914-X
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  • 5
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. 3076-3076
    Abstract: 3076 Background: HM781-36B is a pan-HER tyrosine kinase inhibitor, which showed a potent activity against the gefitinib- or erlotinib-resistant, EGFR L858R/T790M double mutant cells. A phase I study was conducted to determine the MTD, pharmacokinetics, and antitumor activity. Methods: Eligible pts had advanced malignancies refractory to standard therapies. Standard 3+3 scheme was used in the dose escalation part, and additional 12 pts were enrolled in the expansion cohort of molecular enrichment. Results: In dose-escalation part, 43 pts (median age: 55 yrs (range 25-82), M:F=25:18, ECOG PS 0/1/2/3: 23/17/2/1, median prior chemotherapy: 4) were treated. DLTs were G3 diarrheas in 5 pts, one at 12 mg, 16 mg, 24 mg, and two at 32 mg. The MTD was determined as 24mg. The most common drug-related adverse events were diarrhea, stomatitis, rash, pruritus, and anorexia. Among 41 evaluable pts, 4 pts achieved PR (1 unconfirmed, duration of response: 11.9 mo, 7.07 mo+, 4.5 mo+), and 19 pts had SD. Two of 4 PR pts were Her2-positive breast cancer pts. The median duration of treatment in pts with PR or SD was 3.87 (2.47- 15.17) months. In the dose range of 0.5 to 24 mg, it showed linear pharmacokinetics proportional to dose-escalation, relatively short half-life, and little accumulation. Additional 12 pts in the expansion cohort are under treatment at 24 mg (6 pts: EGFR-mutant NSCLC, 3 pts: Her2-positive gastric cancer, 2 pts: Her2-positive breast cancer, 1 pt: rectal cancer). Conclusions: HM781-36B was safe and well tolerable in advanced solid tumors. Preliminary evidence of anticancer activity has been observed. Updated data will be presented at the meeting.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
    detail.hit.zdb_id: 2005181-5
    detail.hit.zdb_id: 604914-X
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  • 6
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 4_suppl ( 2017-02-01), p. 416-416
    Abstract: 416 Background: Systemic inflammation is known to promote carcinogenesis in biliary tract cancer (BTC). Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are indicative of systemic inflammation. We evaluated the clinical significance of systemic inflammation measured by NLR and PLR in patients with advanced BTC. Additionally, we also co-analyzed the dynamics of NLR and PLR during chemotherapy. Methods: We reviewed 554 patients with advanced BTC receiving palliative chemotherapy. NLR and PLR were obtained before initiation of palliative chemotherapy. Changes in NLR, PLR were obtained by subtracting the initial value from the value obtained after progression of chemotherapy. Results: Higher systemic inflammation status also had relation with a primary tumor site ( p = 0.044) and higher levels of CEA ( p = 0.041). The ROC cut-off values of NLR and PLR for predicting overall survival (OS) were 3.8 and 121, respectively. Patients with a high NLR or PLR had worse OS independently in multivariate analysis (7.10 vs. 10.23 months, p 〈 0.001; 8.43 vs. 11.87 months, p = 0.001, respectively). High NLR with increased NLR after chemotherapy is associated with worse OS and progression-free survival (PFS) ( p = 0.014, p= 0.020 respectively). Results are similar for PLR. Conclusions: Systemic inflammation represented by NLR and PLR, predicts the OS of patients with advanced BTC who are receiving palliative chemotherapy. In addition, considering NLR/PLR with a dynamic change of NLR/PLR during chemotherapy might help to predict a more accurate prognosis.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
    detail.hit.zdb_id: 2005181-5
    detail.hit.zdb_id: 604914-X
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  • 7
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2016
    In:  Journal of Clinical Oncology Vol. 34, No. 4_suppl ( 2016-02-01), p. 411-411
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 4_suppl ( 2016-02-01), p. 411-411
    Abstract: 411 Background: Host antitumor immunity measured by neutrophil-lymphocyte ratio (NLR) is reported to be associated with prognosis of cancer patients. Standard uptake value (SUV)by 18 F-FDG PET represents the metabolic activity of tumor itself. The correlation of host immunity and tumor metabolic activity has not been studied. We investigate the association of these two factors and evaluate their roles in prediction of overall survival (OS) in metastatic pancreatic cancer (MPC) patients who receive palliative chemotherapy. Methods: We reviewed 396 MPC patients receivingpalliative chemotherapy. NLR was obtained before initiation of chemotherapy and after 1 st cycle of chemotherapy. In 118 patients who were evaluated with 18 F-FDG PET before initiation of chemotherapy (PET cohort), maximum SUV (SUVmax) was collected. Cut-offs for each variable were determined by ROC curve. Results: In multivariate analysis, higher NLR was associated with worse OS ( 〈 2.5, 9.0 m; 2.5-4.4, 7.2 m; ≥ 4.5, 3.9 m; p 〈 0.001). Reduction of NLR after 1 st cycle of chemotherapywas associated with betterOS (8.0 m vs 6.1 m; HR 0.653; p 〈 0.001). We made the risk scoring model considering both NLR (score 0, NLR 〈 2.5; score 1, 2.5 ≤ NLR 〈 4.5; score 2, NLR ≥ 4.5) and ΔNLR(score 0:ΔNLR 〈 0; score 1: ΔNLR ≥ 0), which identified 4 risk groups with different prognosis (group with risk score 0 vs 1 vs 2 vs 3: OS 9.7 vs 7.9 vs 5.7 vs 2.6 months; HR 1 vs 1.329 vs 2.137 vs 7.915, respectively; P 〈 0.001). In PET cohort (118 patients), NLR and SUVmax were independent prognostic factors for OS. The risk model considering both NLR (score 0, NLR 〈 2.5; score 1, 2.5 ≤ NLR 〈 4.5; score 2, NLR ≥ 4.5) and SUVmax (score 0:SUVmax 〈 4.5; score 1: SUVmax ≥ 4.5), which define 4 risk groups with different OS. (group with risk score 0 vs 1 vs 2 vs 3: OS 11.8 vs 9.8 vs 7.2 vs 4.6 months; HR 1 vs 1.536 vs 2.958 vs 5.336, respectively; P 〈 0.001). Conclusions: NLR and SUVmax as simple parameters of host antitumor immunity and tumor metabolic activity, respectively, have significant impacts on the survival of metastatic pancreatic cancer patients independently. Consideration of both aspects allows more precise prediction of patients’ prognosis.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2016
    detail.hit.zdb_id: 2005181-5
    detail.hit.zdb_id: 604914-X
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  • 8
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 15_suppl ( 2012-05-20), p. 3624-3624
    Abstract: 3624 Background: CpG island methylator phenotype (CIMP) is characterized by concurrent methylation of multiple CpG islands in tumor DNA, which can inactivate tumor suppressor genes or promote carcinogenesis. The prognostic impact of CIMP on treatment outcome of colon cancer patients receiving adjuvant 5-fluorouracil/leucovorin/oxaliplatin (FOLFOX) is unclear. We investigated CIMP markers in colorectal cancer patients treated with adjuvant FOLFOX. Methods: Sporadic colorectal cancer patients treated with curative resection followed by adjuvant FOLFOX were included. DNA was extracted from formalin-fixed paraffin-embedded surgical specimen. 8 CpG island loci (CACNA1G, CRABP1, IGF2, MLH1, NEUROG1, P16, RUNX3 and SOCS1) were examined using MethyLight analysis. Disease-free survival (DFS) was evaluated according to each methylation loci. Results: A total of 322 patients were included. Methylation at 1 or more loci was observed in 150 patients (46.6%) and 6 or more loci in 15 (4.7%). During a median follow-up duration of 39.7 months, 55 recurrences were observed. Three year DFS in the patient cohort was 84%. CRABP1 (23.9%) was the most frequently methylated loci, followed by p16 (22.7%) and NEUROG1 (20.8%). Patients having methylation at NEUROG1 (3 year DFS 78% in (+) vs. 86% in (-), p = 0.014) and p16 (3 year DFS 78% in (+) vs. 86% in (-), p = 0.12) had worse DFS, whereas methylation at MLH1 had better DFS (3 year DFS 100% in (+) vs. 86% in (-), p = 0.19). In a combined analysis, patients with MLH1(-)/NEUROG1(+)/p16(+) had worst treatment outcome compared to MLH1(-)/NEUROG1(+) or p16(+), MLH1(-)/ NEUROG1(-) /p16(-), and MLH1(+) (3 year DFS 62%, 82%, 87%, and 100%, respectively; p = 0.002). In multivariate analysis, NEUROG1(+)/p16(+) was associated with significantly higher recurrence compared with other patients (adjusted hazard ratio (HR) 2.15 (95% confidence interval (CI) 1.08 - 4.27, p = 0.029). Conclusions: Methylation status of NEUROG1, p16, and MLH1 is associated with recurrence following adjuvant FOLFOX in stage II/III colorectal cancer. Further validation and translational studies to improve treatment outcome in the subset of patients are warranted in the future.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
    detail.hit.zdb_id: 2005181-5
    detail.hit.zdb_id: 604914-X
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  • 9
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. 551-551
    Abstract: 551 Background: Although young age breast cancer represents poor prognosis, no definitive explanation could have been made for the phenomenon. A tumor proliferation marker Ki67 is known to be a marker for both prognosis and prediction for chemotherapy responsiveness, and its level varies widely depending on the breast cancer subtype. This study was aimed to analyze Ki67 in relationship with age in hormone receptor positive breast cancer patients. Methods: We retrospectively reviewed 9061 consecutive cases of hormone receptor positive invasive breast cancer from data base at Seoul National University Hospital (SNUH) (between 2000 and 2012), Samsung Medical Center (SMC) (between 2004 and 2010), and National Cancer Center (NCC) (between 2001 and 2010) in Korea. Patients with estrogen receptor (ER) or progesterone receptor (PR) positive tumors were included irrespective of HER2 amplification. A multicenter data of Ki67 level identified by immunohistochemistry (IHC) and age at diagnosis were analyzed. Patients who underwent neoadjuvant systemic therapy were excluded. Results: Total 6222 cases from SNUH, 976 from SMC and 1863 from NCC were included. The three datasets were analyzed separately due to variable IHC methods in each institute. Mean ages were 49.30 years (range 20-86), 47.75 years (range 22-81) and 45.31 years (range 25-59), and mean Ki67 levels were 4.66% (range 1-100), 22.98% (range 1-97) and 14.58% (range 1-90), at SNUH, SMC, NCC respectively. Ki67 level was inversely proportional with age at diagnosis in all three datasets, and the level was significantly higher for patients 〈 40 years compared to ≥40 years (mean Ki67: 5.97 vs 4.41, p 〈 0.001; 28.60 vs 21.88, p 〈 0.001; 17.01 vs 14.03, p 〈 0.001, respectively). There was an inverse relation with age as well when Ki67 level was categorized into ‘ 〈 10% vs ≥10% (p 〈 0.001)’, ‘ 〈 20% vs ≥20% (p=0.03)’ and ‘ 〈 14% vs ≥14% (p 〈 0.001)’ respectively. Conclusions: Despite the variability of assessing Ki67 expression, Ki67 level was significantly higher in young age hormone receptor positive breast cancer from all three analyses. This could partly explain the poor prognosis and substantial responsiveness to chemotherapy in this age group of patients.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
    detail.hit.zdb_id: 2005181-5
    detail.hit.zdb_id: 604914-X
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  • 10
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 15_suppl ( 2016-05-20), p. e23268-e23268
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2016
    detail.hit.zdb_id: 2005181-5
    detail.hit.zdb_id: 604914-X
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