153 results on '"Heung-Moon Chang"'
Search Results
2. Adjuvant
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Margaret A, Tempero, Uwe, Pelzer, Eileen M, O'Reilly, Jordan, Winter, Do-Youn, Oh, Chung-Pin, Li, Giampaolo, Tortora, Heung-Moon, Chang, Charles D, Lopez, Tanios, Bekaii-Saab, Andrew H, Ko, Armando, Santoro, Joon Oh, Park, Marcus S, Noel, Giovanni Luca, Frassineti, Yan-Shen, Shan, Andrew, Dean, Hanno, Riess, Eric, Van Cutsem, Jordan, Berlin, Philip, Philip, Malcolm, Moore, David, Goldstein, Josep, Tabernero, Mingyu, Li, Stefano, Ferrara, Yvan, Le Bruchec, George, Zhang, Brian, Lu, Andrew V, Biankin, and Michele, Reni
- Abstract
This randomized, open-label trial compared the efficacy and safety of adjuvantWe assigned 866 treatment-naive patients with pancreatic ductal adenocarcinoma toTwo hundred eighty-seven of 432 patients and 310 of 434 patients completedThe primary end point (independently assessed DFS) was not met despite favorable OS seen with
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- 2022
3. Abstract 4333: Spatial analysis of tumor-infiltrating lymphocytes in tumor microenvironment as biomarker for immune checkpoint inhibition in biliary tract cancer
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Yeong Hak Bang, Kyunghye Bang, Jin Ho Shin, Hyunseok Yoon, Kyu-Pyo Kim, Inkeun Park, Jae Ho Jeong, Heung-Moon Chang, Baek-Yeol Ryoo, Chiyoon Oum, Seulki Kim, Yoojoo Lim, Gahee Park, Chan-Young Ock, and Changhoon Yoo
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Cancer Research ,Oncology - Abstract
Background: Recently, anti-PD-L1 in combination with cytotoxic chemotherapy has shown significant survival benefit in a randomized phase 3 trial for unresectable or metastatic biliary tract cancer (BTC). However, no biomarker including PD-L1 expression has been established to predict clinical outcomes, and there is an unmet need for a novel predictive biomarker for anti-PD-1 or PD-L1 therapy. Here, we assessed TILs using artificial intelligence (AI)-powered spatial analysis in advanced BTC treated with anti-PD-1 beyond 1st line treatment. Methods: An AI-powered whole-slide image (WSI) analyzer (Lunit SCOPE IO, Lunit, Seoul, Korea) was used to segment tumor epithelium and stroma, and identification of intratumor TIL (iTIL) and stromal TIL (sTIL). H&E stained WSI from pre-treatment samples was acquired from Asan Medical Center (n =166), and a total of 154 samples (92.8%) after quality control were used for the final analysis. Immune phenotypes (IP) were defined as follow: inflamed as high iTIL and sTIL; immune-excluded as low iTIL and high sTIL; immune-desert as low TIL overall. Among them, 20 patients were available for multi-color flow cytometry analysis (FACS) using peripheral blood mononuclear cells, collected at baseline, C1D8, and C2D1. Results: All patients (n=154) were treated with anti-PD-1 (pembrolizumab or nivolumab) monotherapy, and 72 of 154 patients (46.8%) were treated as 2nd line. Gemcitabine plus cisplatin (GemCis) was used prior to anti-PD-1 as first-line therapy in all patients. Overall, 15 (9.7%) patients showed inflamed IP. With median follow-up duration of 15.4 months, the inflamed IP group showed better overall survival (17.2 vs. 6.6 months, P=0.03), and progression-free survival (PFS; 4.5 vs. 2.6 months, P=0.09) along with higher PFS rate at 12 months (33.3% vs. 11.5%, P=0.035), and overall response rate (26. 7% vs. 8.6%, P=0.053) than other phenotype groups. There was no significant difference in median PFS with GemCis among IP groups (P=0.74). In the FACS available subgroup, inflamed IP showed higher baseline central memory T (Tcm)+effector memory T (Tem)/Tnaive ratio than other IPs. With the administration of anti-PD-1, Tcm+Tem/Tnaive ratio was increased, while the proportion of PD1+CD8+T, CD39+CD8+T, CD103+CD8+T and Treg were decreased in the inflamed IP group than other phenotype groups. Conclusions: Immune phenotypes classified by AI-powered spatial TIL analysis was effective to predict the clinical outcomes of patients with advanced BTC treated with anti-PD-1 therapy. Citation Format: Yeong Hak Bang, Kyunghye Bang, Jin Ho Shin, Hyunseok Yoon, Kyu-Pyo Kim, Inkeun Park, Jae Ho Jeong, Heung-Moon Chang, Baek-Yeol Ryoo, Chiyoon Oum, Seulki Kim, Yoojoo Lim, Gahee Park, Chan-Young Ock, Changhoon Yoo. Spatial analysis of tumor-infiltrating lymphocytes in tumor microenvironment as biomarker for immune checkpoint inhibition in biliary tract 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 4333.
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- 2023
4. Therapeutic relevance of targeted sequencing in management of patients with advanced biliary tract cancer: DNA damage repair gene mutations as a predictive biomarker
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Ki-Hun Kim, Seung-Mo Hong, Tae Jun Song, Heung-Moon Chang, Jae Hoon Lee, Changhoon Yoo, Sang Soo Lee, Song Cheol Kim, Se Jin Jang, Gi-Won Song, Deokhoon Kim, Chul Soo Ahn, Jae Ho Jeong, Baek-Yeol Ryoo, Kyu-Pyo Kim, Tae Won Kim, Do Hyun Park, Shin Hwang, Dae Wook Hwang, and Heejung Chae
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Adult ,Male ,0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Gene mutation ,medicine.disease_cause ,Targeted therapy ,Cholangiocarcinoma ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Exome Sequencing ,Biomarkers, Tumor ,medicine ,Humans ,Gallbladder cancer ,Exome sequencing ,Survival analysis ,Aged ,Platinum ,Retrospective Studies ,Aged, 80 and over ,Chemotherapy ,Predictive marker ,business.industry ,High-Throughput Nucleotide Sequencing ,Middle Aged ,Prognosis ,medicine.disease ,Combined Modality Therapy ,Gene Expression Regulation, Neoplastic ,Survival Rate ,Biliary Tract Surgical Procedures ,Bile Ducts, Intrahepatic ,Biliary Tract Neoplasms ,DNA Repair Enzymes ,030104 developmental biology ,Bile Duct Neoplasms ,030220 oncology & carcinogenesis ,Mutation ,Female ,KRAS ,business ,DNA Damage ,Follow-Up Studies - Abstract
Purpose In biliary tract cancer (BTC), standard chemotherapy has limited benefit and no molecular targeted agents have been approved. This study investigated the genetic profile of BTC to identify potential new therapeutic targets and predictive biomarkers. Methods Targeted exome sequencing was performed for 124 patients with BTC [gallbladder cancer (GBC), 25; intrahepatic cholangiocarcinoma (ICC), 55; extrahepatic cholangiocarcinoma (ECC), 44]. Survival analysis was performed in 112 patients who received palliative chemotherapy for locally unresectable or metastatic disease. Results Genetic alterations were observed in 104 patients (83.8%); the most commonly mutated genes were TP53 (44.4%), KRAS (29.0%), ARID1A (12.1%) and IDH1 (9.7%). IDH1/2 mutations appeared more frequently in ICC (23.6%, P = 0.0002) than in GBC (4.0%) or ECC (2.3%), while ERBB2/3 mutations were found only in GBC (20.0%) and ECC (11.4%). Patients harbouring TP53 mutations had shorter overall survival (OS; median 15.2 vs. 37.8 months, P = 0.018), while IDH1 mutations showed a tendency for longer progression-free survival (PFS; 10.6 vs. 6.1 months, P = 0.124). Potentially actionable genetic alterations were found in 54.8%, and 7.1% received appropriate molecular targeted therapy in the clinical trial setting. Germline or somatic mutations in DNA damage repair (DDR) genes were found in 63.5% of patients and were significantly associated with longer PFS (6.9 vs. 5.7 months, P = 0.013) and OS (21.0 vs. 13.3 months, P = 0.009) in patients who received first-line platinum-containing chemotherapies (n = 88). Conclusions A subgroup of patients with BTC may benefit from targeted therapy by the aid of genetic information. In particular, DDR alterations may be a predictive biomarker for response to platinum-containing chemotherapy in patients with BTC.
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- 2019
5. Epithelial–Mesenchymal Transition Phenotype and Peritumoral Immune Cell Infiltration in Advanced Biliary Tract Cancer
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Chung Ryul Oh, Heung-Moon Chang, Changhoon Yoo, Hyung-Don Kim, Kyu-Pyo Kim, Yeon-Mi Ryu, Jae Ho Jeong, Danbee Kim, Da Sol Lee, Baek-Yeol Ryoo, Seonmin Lee, Sang-Yeob Kim, and Miyeon Kim
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Cancer Research ,Biliary tract cancer ,Oncology ,business.industry ,Cancer research ,Medicine ,Epithelial–mesenchymal transition ,General Medicine ,business ,Immune cell infiltration ,Phenotype - Abstract
BackgroundWe evaluated the clinical implications of epithelial–mesenchymal transition (EMT) markers and peritumoral immune cell infiltration in patients with biliary tract cancer (BTC) treated with gemcitabine plus cisplatin (GemCis).MethodsForty-five patients with advanced BTC who received GemCis were included as the study population. We conducted multiplex immunohistochemistry and examined EMT markers and their correlations with immune cell infiltrate at the invasive tumor margin. Study population was subdivided into two groups: twenty-four patients with overall survival (OS) less than 10 months (short-term survivor group, SS) and 21 with OS of 20 months or longer (long-term survivor group, LS).ResultsThe density of tumor cells expressing epithelial marker E-cadherin (E-cadherin+ CK+) at the invasive tumor margin tended to be higher in the LS group than in the SS group (p = 0.065). The density of tumor cells expressing mesenchymal marker vimentin (vimentin+ CK+) was significantly higher in the SS group than in the LS group (p = 0.021). Accordingly, the density of E-cadherin- vimentin+ CK+ cells was also significantly higher in the SS group (p = 0.020). The density of OX40 expressing cells (OX40+) was significantly higher in the SS group than in the LS group (p = 0.006). The density of vimentin+ CK+ cells was positively correlated with FoxP3+ CD4+ regulatory T-cells (r = 0.29, p = 0.047) and OX40+ cells (r = 0.48, p < 0.001).ConclusionsEMT-related features were enriched in BTC patients with poor survival outcomes and were associated with the immunosuppressive tumor microenvironment.
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- 2021
6. Real-world outcomes of adjuvant gemcitabine
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Sora, Kang, Changhoon, Yoo, So Heun, Lee, Dongwook, Oh, Tae Jun, Song, Sang Soo, Lee, Jae Ho, Jeong, Do Hyun, Park, Dong Wan, Seo, Jin-Hong, Park, Dae Wook, Hwang, Ki Byung, Song, Jae Hoon, Lee, Woohyung, Lee, Bong Jun, Kwak, Sarang, Hong, Heung-Moon, Chang, Baek-Yeol, Ryoo, Kyu-Pyo, Kim, and Song Cheol, Kim
- Abstract
Adjuvant chemotherapy is the standard treatment after curative-intent surgery for pancreatic ductal adenocarcinoma (PDAC). The phase-3 ESPAC-4 trial demonstrated significantly improved overall survival (OS) with Gemcitabine plus capecitabine (GemCap) over Gemcitabine (Gem) in Europe. We conducted a retrospective efficacy and safety evaluation of GemCapThis retrospective analysis included 292 patients with PDAC who received adjuvant Gem or GemCap after curative resection between January 2017 and December 2020 at Asan Medical Center, Seoul, Korea.Adjuvant Gem and GemCap were administered to 161 (55.1%) and 131 (44.8%) patients, respectively. The Gem group had significantly older patients (median 66Adjuvant GemCap showed the consistent clinical outcomes with the ESPAC-4 trial. As mFOLFIRINOX is the new standard treatment for medically fit patients with resected PDAC, further evaluation of optimal adjuvant chemotherapy in daily practice is warranted.
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- 2021
7. MO6-5 Clinical relevance of adjuvant chemotherapy in patients who underwent surgery following neoadjuvant modified FOLFIRINOX
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So Heun Lee, Changhoon Yoo, Sora Kang, Heung-Moon Chang, Jae Ho Jeong, Kyu-Pyo Kim, and Baek-Yeol Ryoo
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Oncology ,Hematology - Published
- 2022
8. Clinical Benefit of Maintenance Therapy for Advanced Biliary Tract Cancer Patients Showing No Progression after First-Line Gemcitabine Plus Cisplatin
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Heung-Moon Chang, Jae Ho Jeong, Kyo-Pyo Kim, Bum Jun Kim, Baek-Yeol Ryoo, Changhoon Yoo, and Jaewon Hyung
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Male ,0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Deoxycytidine ,Gastroenterology ,Maintenance Chemotherapy ,Cholangiocarcinoma ,03 medical and health sciences ,0302 clinical medicine ,Maintenance therapy ,Internal medicine ,medicine ,Clinical endpoint ,Humans ,Watchful Waiting ,Aged ,Retrospective Studies ,Cisplatin ,Chemotherapy ,Biliary tract neoplasm ,Biliary tract cancer ,business.industry ,Middle Aged ,Gemcitabine ,Survival Analysis ,Progression-Free Survival ,Confidence interval ,Biliary Tract Neoplasms ,Treatment Outcome ,030104 developmental biology ,Oncology ,Case-Control Studies ,030220 oncology & carcinogenesis ,Original Article ,Female ,business ,medicine.drug - Abstract
Purpose Gemcitabine plus cisplatin (GemCis) is the standard first-line chemotherapy for patients with advanced biliary tract cancer (BTC). In ABC-02 study, the BTC patients received up to 6-8 cycles of 3-weekly GemCis; however, those without progression often receive more than 6-8 cycles. The clinical benefit of maintenance treatment in patients without progression is uncertain. Materials and methods Advanced BTC patients treated with GemCis between April 2010 and February 2015 at Asan Medical Center, Seoul, Korea, were retrospectively analysed. The patients without progression after 6-8 cycles were stratified according to further treatment i.e., with or without further cycles of GemCis (maintenance vs. observation groups). The primary endpoint was overall survival (OS) and progression-free survival (PFS). Results Among the 740 BTC patients in the initial screen, 231 cases (31.2%) were eligible for analysis (111 in the observation group, 120 in the maintenance group). The median OS from the GemCis initiation was 20.5 months (95% confidence interval [CI], 15.4 to 25.6) and 22.4 months (95% CI, 17.0 to 27.8) in the observation and maintenance groups, respectively (p=0.162). The median PFS was 10.4 months (95% CI, 7.0 to 13.8) and 13.2 months (95% CI, 11.3 to 15.2), respectively (p=0.320). Conclusions GemCis maintenance is not associated with an improved survival outcome.
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- 2019
9. Updated results of the FOENIX-CCA2 trial: Efficacy and safety of futibatinib in intrahepatic cholangiocarcinoma (iCCA) harboring FGFR2 fusions/rearrangements
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Lipika Goyal, Funda Meric-Bernstam, Antoine Hollebecque, Chigusa Morizane, Juan W. Valle, Thomas Benjamin Karasic, Thomas Adam Abrams, Robin Kate Kelley, Philippe Alexandre Cassier, Junji Furuse, Heinz-Josef Klümpen, Heung-Moon Chang, Li-Tzong Chen, Yoshito Komatsu, Kunihiro Masuda, Daniel H. Ahn, Kate Li, Karim A. Benhadji, Volker Wacheck, and John A. Bridgewater
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Cancer Research ,Oncology - Abstract
4009 Background: Survival outcomes are historically poor in patients (pts) with advanced/metastatic iCCA, with median overall survival (mOS) times of approximately 1 year with first-line gemcitabine plus cisplatin and approximately 6 months with second-line chemotherapy. Futibatinib, a highly selective, irreversible FGFR1–4 inhibitor, demonstrated efficacy with durable responses in pts with iCCA harboring FGFR2 fusion/rearrangements in the pivotal FOENIX-CCA2 phase 2 study (NCT02052778). At the primary analysis of this trial (data cutoff: October 1, 2020), an objective response rate (ORR) of 41.7% was observed, with a median duration of response (mDOR) of 9.7 mo. Here, we report updated efficacy (including mature OS data) and safety data from the final analysis with an additional 8 mo of follow-up. Methods: FOENIX-CCA2 was a single-arm phase 2 study that enrolled pts with advanced/metastatic iCCA with FGFR2 fusion/rearrangement and progressive disease (PD) after ≥1 prior treatment (tx; including gemcitabine plus platinum-based chemotherapy). Pts received futibatinib 20 mg once daily until PD/intolerability. The primary endpoint was ORR per RECIST v1.1 by independent central review. Secondary endpoints were DOR, disease control rate (DCR), progression-free survival (PFS), OS, safety, and patient-reported outcomes. Results: At the time of the final data cutoff (May 29, 2021), median follow-up was 25.0 mo, and 96/103 pts (93%) had discontinued tx. The median number of tx cycles was 13.0 for a median tx duration of 9.1 mo. The confirmed ORR was 41.7% (43/103) and thereby the same as of the primary analysis, as was the DCR (at 82.5%). The ORR was consistent across pt subgroups. The mDOR was 9.5 mo, and 74% of responses lasted ≥6 mo. mPFS was 8.9 mo, with a 12-mo PFS rate of 35.4%. Mature mOS was 20.0 mo, with a 12-mo OS rate of 73.1% . No new safety signals were identified. Common tx-related adverse events (TRAEs) included hyperphosphatemia (85%), alopecia (33%), dry mouth (30%), diarrhea (28%), dry skin (27%), and fatigue (25%). TRAEs resulted in tx discontinuation in 4 pts (4%). No tx-related deaths occurred. Quality of life was maintained from baseline to tx cycle 13. Conclusions: Findings from the final analysis of FOENIX-CCA2 confirm the results of the primary analysis and reinforce the durable efficacy and continued tolerability of futibatinib in previously treated pts with advanced/metastatic iCCA harboring FGFR2 fusion/rearrangements. Mature OS data were consistent with data from the primary analysis and far exceed historical data in this patient population. Clinical trial information: NCT02052778.
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- 2022
10. Clinical relevance of adjuvant chemotherapy in patients with pancreatic ductal adenocarcinoma who underwent surgery following neoadjuvant modified FOLFIRINOX
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So Heun Lee, Changhoon Yoo, Sora Kang, Heung-Moon Chang, Jae Ho Jeong, Kyu-Pyo Kim, and Baek-Yeol Ryoo
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Cancer Research ,Oncology ,Surgery ,General Medicine - Abstract
546 Background: The benefit of adjuvant chemotherapy (ACT) following curative-intent surgery in pancreatic ductal adenocarcinoma (PDAC) patients who had received neoadjuvant modified FOLFIRINOX (mFOLFIRINOX) remains unidentified. This retrospective analysis aimed to assess the clinical relevance of ACT in patients who underwent surgery following neoadjuvant mFOLFIRINOX. Methods: Between January 2017 and December 2020, 220 patients received neoadjuvant mFOLFIRINOX and underwent pancreatectomy for localized PDAC at the Asan Medical Center, Seoul, Korea. Patients unable to undergo curative-intent surgical resection (R0 or R1) and those with histological types other than ductal adenocarcinoma were excluded. Survival outcomes were compared according to ACT administration. Disease-free survival (DFS) was defined as the duration between surgery and recurrence or death of any etiology, whichever occurred first; and overall survival (OS) was that between surgery and death from any etiology. Results: ACT was administered to 150 (68.2%) patients. ACT recipients were significantly younger (median age, 61 vs. 64, p = 0.035) and they received significantly fewer cycles of neoadjuvant chemotherapy (median, 7 vs. 9, p = 0.0001) compared to non-recipients. As ACT, mFOLFIRINOX (n = 98, 65.3%), gemcitabine monotherapy (n = 39, 26.0%), and gemcitabine-capecitabine (n = 4, 2.7%) were administered. ACT recipients showed significantly better survival outcomes compared to non-recipients; median DFS 13.4 months (95% CI, 10.7–18.8) vs. 8.3 months (95% CI, 4.9–16.0), respectively (p = 0.0042); and median OS 33.4 months (95% CI, 29.9–NA) vs. 23.8 months (95% CI, 17.9–NA), respectively (p = 0.0021). DFS and OS were significantly better in ACT recipients regardless of the lymph node (LN) status during surgery (p = 0.033 for DFS and p = 0.027 for OS in negative LN; and p = 0.032 for DFS and p = 0.012 for OS in positive LN). There was no significant difference in DFS (p = 0.79) and OS (p = 0.49) between mFOLFIRINOX and gemcitabine-based regimens. In multivariate analysis, ACT remained significant as a favorable prognostic factor (DFS, hazard ratio [HR] 0.43 (95%CI, 0.26–0.71, p = 0.001); OS, HR 0.33 (95%CI, 0.17–0.64, p = 0.001). Conclusions: In PDAC patients who underwent surgery following neoadjuvant mFOLFIRINOX, ACT may be associated with improved survival outcomes. Its benefit was not affected by the LN status and ACT regimens.
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- 2022
11. Prognostic factors in patients with metastatic or recurrent pancreatic cancer treated with first-line nab-paclitaxel plus gemcitabine: implication of inflammation-based scores
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Jae Ho Jeong, Kyu-Pyo Kim, Inhwan Hwang, Changhoon Yoo, Heung-Moon Chang, Jihoon Kang, Hei Nga Natalie Ip, and Baek-Yeol Ryoo
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Male ,0301 basic medicine ,Oncology ,Multivariate analysis ,Neutrophils ,medicine.medical_treatment ,Deoxycytidine ,Metastasis ,0302 clinical medicine ,Antineoplastic Combined Chemotherapy Protocols ,Pharmacology (medical) ,Lymphocytes ,Aged, 80 and over ,Liver Neoplasms ,Middle Aged ,Prognosis ,Survival Rate ,Lymphatic Metastasis ,030220 oncology & carcinogenesis ,Distant Lymph Node ,Female ,medicine.symptom ,medicine.drug ,Adult ,Blood Platelets ,medicine.medical_specialty ,Paclitaxel ,Inflammation ,03 medical and health sciences ,Albumins ,Internal medicine ,Pancreatic cancer ,Biomarkers, Tumor ,medicine ,Humans ,Neoplasm Invasiveness ,In patient ,Aged ,Retrospective Studies ,Pharmacology ,Chemotherapy ,business.industry ,medicine.disease ,Gemcitabine ,Pancreatic Neoplasms ,030104 developmental biology ,Neoplasm Recurrence, Local ,business ,Follow-Up Studies - Abstract
Background Nab-paclitaxel plus gemcitabine (AG) is standard first-line chemotherapy for patients with metastatic pancreatic cancer (mPC). However, prognostic factors for patients with mPC treated with AG, are largely unknown. We retrospectively identified prognostic factors, including inflammation-based prognostic scores, in patients with mPC, and recurrent pancreatic cancer treated with AG as first-line treatment. Method A total of 203 patients with histologically-confirmed recurrent or metastatic pancreatic cancer who were treated with first-line AG in Asan Medical Center, Seoul, Korea, between February 2016 and December 2016 were included in this analysis. As inflammation-based scores, baseline neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and modified Glasgow prognostic scores (mGPS) were tested. Result Median age was 62 years and 116 patients (57%) were male. With median follow-up duration of 21.5 months, median progression-free survival (PFS) was 7.1 (95% CI 6.2-7.9) months, and overall survival (OS) was 15.1 (95% CI 12.6-17.6) months. In the multivariate analysis, PFS was significantly associated with liver metastasis (HR 1.43), distant lymph node metastasis (HR 1.48), and elevated CA19-9 (HR 1.56). In multivariate analysis for OS, elevated CA19-9 (HR 1.75), liver metastasis (HR 1.76), distant lymph node metastasis (HR 1.41), and high mGPS (mGPS ≥1 vs.0: HR 1.64) were independent prognostic factors. NLR and PLR were not significantly associated with PFS and OS. Conclusion Among the inflammation based prognostic scores, mGPS was a reliable prognostic indicator that could stratify survival outcomes in patients with recurrent or mPC who received AG as first-line chemotherapy.
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- 2018
12. Stereotactic Body Radiation Therapy versus Concurrent Chemoradiotherapy for Locally Advanced Pancreatic Cancer: A Propensity Score-Matched Analysis
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Young Seob Shin, Hee Hyun Park, Jin-hong Park, Dong-Wan Seo, Sang Soo Lee, Changhoon Yoo, Seonok Kim, Sang Min Yoon, Jinhong Jung, Myung-Hwan Kim, Sung Koo Lee, Do Hyun Park, Tae Jun Song, Dongwook Oh, Baek-Yeol Ryoo, Heung-Moon Chang, Kyu-pyo Kim, Jae Ho Jeong, and Jong Hoon Kim
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Cancer Research ,pancreatic neoplasms ,radiosurgery ,chemoradiotherapy ,treatment outcome ,Oncology - Abstract
In locally advanced pancreatic cancer (LAPC), stereotactic body radiation therapy (SBRT) has been applied as an alternative to concurrent chemoradiotherapy (CCRT); however, direct comparative evidence between these two modalities is scarce. The aim of this study was to compare the clinical outcomes of SBRT with CCRT for LAPC. We retrospectively reviewed the medical records of patients with LAPC who received SBRT (n = 95) or CCRT (n = 66) with a concurrent 5-FU-based regimen between January 2008 and July 2016. The clinical outcomes of freedom from local progression (FFLP), progression-free survival (PFS), overall survival (OS), and toxicities were analyzed before and after propensity score (PS) matching. After a median follow-up duration of 15.5 months (range, 2.3–64.5), the median OS, PFS, and FFLP of the unmatched patients were 17.3 months, 11 months, and 19.6 months, respectively. After PS matching, there were no significant differences between the SBRT and CCRT groups in terms of the 1-year rates of OS (66.7% vs. 80%, p = 0.455), PFS (40.0% vs. 54.2%, p = 0.123), and FFLP (77.2% and 87.1%, p = 0.691). Our results suggest SBRT could be a feasible alternative to CCRT in treating patients with LAPC.
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- 2022
13. Adjuvant gemcitabine (GEM) versus gemcitabine plus capecitabine (GEMCAP) in resected pancreatic adenocarcinoma: A retrospective analysis
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Sora Kang, Changhoon Yoo, So Heun Lee, Heung-Moon Chang, Jae Ho Jeong, Kyu-Pyo Kim, and Baek-Yeol Ryoo
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Cancer Research ,Oncology - Abstract
547 Background: For patients who underwent curative-intent upfront surgery, adjuvant chemotherapy is the current standard of care. The previous, randomized phase 3 ESPAC-4 study showed significantly improved overall survival (OS) with GEMCAP compared to GEM. However, this study was conducted in European countries and its implication in Asian patients has not been explored yet. We conducted a retrospective analysis to evaluate the efficacy and safety of GEMCAP compared to GEM regimen. Methods: Between January 2017 and December 2020, a total of 292 patients who received adjuvant GEM or GEMCAP after curative-intent surgery in Asan Medical Center, Seoul, Korea, were included in this retrospective analysis. Results: Adjuvant GEM and GEMCAP were administered in 161 patients (55.1%) and 131 patients (44.8 %), respectively. Compared the GEMCAP group, age of patients were significantly older in the GEM group (median 66 vs 63 yo, p = 0.025); otherwise, there was no significant difference in baseline characteristics between two groups. With the median follow-up duration of 39.4 months (95% CI 36.9 - 45.0 months) in GEM group and 39.4 months (95% CI 34.7-41.6 months) in GEMCAP group, the median OS was 36.8 months (95% CI 29.7-43.5 months) and 46.1 months (95% CI 31.5 months – not reached) in the GEM group and GEMCAP group, respectively (unadjusted HR 0.72, 95% CI 0.51-1.02, p = 0.065). The median recurrence-free survival was 14.3 months (95% CI, 12.9-17.7 months) and 17.0 months (95% CI, 13.3-28.8 months) in the GEM group and GEMCAP group, respectively (p = 0.52). In the GEMCAP group, hand-foot skin reaction (any grade, 15.27 % vs 0.62 %, p < 0.001), neutropenia (78.6% vs 67.7%, p=0.037) and thrombocytopenia (30.53% vs 20.5%, p=0.035) were more common in the GEMCAP group compared to the GEM group. In multivariate analysis, adjuvant GEMCAP was significantly associated with better OS compared to adjuvant GEM (adjusted HR 0.64, 95% CI, 0.44-0.91, p = 0.014). Otherwise, moderate or poor histologic grade, lymph node positive, positive resection margin, and elevated CA 19-9 levels (> median) were significantly associated with poorer OS. Conclusions: In this retrospective analysis for Korean patients, adjuvant GEMCAP showed consistent clinical outcomes shown in the ESPAC-4 trial. As mFOLFIRINOX is the new standard of care for medically fit patients with resected pancreatic adenocarcinoma, further evaluation of optimal adjuvant chemotherapy in daily practice is warranted.
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- 2022
14. Real-world outcomes of adjuvant gemcitabine versus gemcitabine plus capecitabine for resected pancreatic ductal adenocarcinoma
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Sora Kang, Changhoon Yoo, So Heun Lee, Dongwook Oh, Tae Jun Song, Sang Soo Lee, Jae Ho Jeong, Do Hyun Park, Dong Wan Seo, Jin-hong Park, Dae Wook Hwang, Ki Byung Song, Jae Hoon Lee, Woohyung Lee, Bong Jun Kwak, Sarang Hong, Heung-Moon Chang, Baek-Yeol Ryoo, Kyu-pyo Kim, and Song Cheol Kim
- Subjects
Oncology - Abstract
Background: Adjuvant chemotherapy is the standard treatment after curative-intent surgery for pancreatic ductal adenocarcinoma (PDAC). The phase-3 ESPAC-4 trial demonstrated significantly improved overall survival (OS) with Gemcitabine plus capecitabine (GemCap) over Gemcitabine (Gem) in Europe. We conducted a retrospective efficacy and safety evaluation of GemCap versus Gem in an Asian population. Methods: This retrospective analysis included 292 patients with PDAC who received adjuvant Gem or GemCap after curative resection between January 2017 and December 2020 at Asan Medical Center, Seoul, Korea. Results: Adjuvant Gem and GemCap were administered to 161 (55.1%) and 131 (44.8%) patients, respectively. The Gem group had significantly older patients (median 66 versus 63 years, p = 0.001); otherwise, the groups had similar baseline characteristics. With median follow-up durations of 39.4 [95% confidence interval (CI), 36.9–45.0] and 39.4 (95% CI, 34.7–41.6) months in the Gem and GemCap groups, the median OS was 36.8 (95% CI, 29.7–43.5) and 46.1 (95% CI, 31.5–not reached) months in the Gem and GemCap groups, respectively [unadjusted hazard ratio (HR) = 0.7; 95% CI, 0.5–1.0; p = 0.07). The median recurrence-free survival was 14.3 (95% CI, 12.9–17.7) and 17.0 (95% CI, 13.3–28.2) months, respectively ( p = 0.5). Hand-foot skin reactions (any grade, 15.3% versus 0.6%; p median) were significantly associated with worse OS. Conclusions: Adjuvant GemCap showed the consistent clinical outcomes with the ESPAC-4 trial. As mFOLFIRINOX is the new standard treatment for medically fit patients with resected PDAC, further evaluation of optimal adjuvant chemotherapy in daily practice is warranted.
- Published
- 2022
15. Supplementary_Table – Supplemental material for FOLFIRINOX in borderline resectable and locally advanced unresectable pancreatic adenocarcinoma
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Changhoon Yoo, Inhwan Hwang, Song, Tae Jun, Lee, Sang Soo, Jeong, Jae Ho, Park, Do Hyun, Seo, Dong Wan, Lee, Sung Koo, Myung-Hwan Kim, Byun, Jae Ho, Park, Jin-Hong, Hwang, Dae Wook, Song, Ki Byung, Lee, Jae Hoon, Woohyung Lee, Heung-Moon Chang, Kyu-Pyo Kim, Kim, Song Cheol, and Baek-Yeol Ryoo
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110203 Respiratory Diseases ,FOS: Clinical medicine ,111702 Aged Health Care ,FOS: Health sciences ,111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified ,111299 Oncology and Carcinogenesis not elsewhere classified - Abstract
Supplemental material, Supplementary_Table for FOLFIRINOX in borderline resectable and locally advanced unresectable pancreatic adenocarcinoma by Changhoon Yoo, Inhwan Hwang, Tae Jun Song, Sang Soo Lee, Jae Ho Jeong, Do Hyun Park, Dong Wan Seo, Sung Koo Lee, Myung-Hwan Kim, Jae Ho Byun, Jin-hong Park, Dae Wook Hwang, Ki Byung Song, Jae Hoon Lee, Woohyung Lee, Heung-Moon Chang, Kyu-pyo Kim, Song Cheol Kim and Baek-Yeol Ryoo in Therapeutic Advances in Medical Oncology
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- 2020
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16. Rivaroxaban
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Jwa Hoon, Kim, Seyoung, Seo, Kyu-Pyo, Kim, Heung-Moon, Chang, Baek-Yeol, Ryoo, Changhoon, Yoo, Jae Ho, Jeong, Jae-Lyun, Lee, Hyeon-Su, Im, Hyehyun, Jeong, Yeonghak, Bang, and Sook Ryun, Park
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Aged, 80 and over ,Male ,Hemorrhage ,Kaplan-Meier Estimate ,Venous Thromboembolism ,Heparin, Low-Molecular-Weight ,Middle Aged ,Digestive System Neoplasms ,Prognosis ,Treatment Outcome ,Rivaroxaban ,Humans ,Female ,Aged ,Neoplasm Staging ,Research Article - Abstract
Background/Aim: The aim of this study was to examine the efficacy and safety of direct oral anticoagulants for cancer-associated venous thromboembolism (VTE) in patients with active cancer. Patients and Methods: This study included patients with advanced unresectable/metastatic upper gastrointestinal (GI) or hepatopancreatobiliary (HPB) cancers with high risks of VTE and bleeding. Results: No significant differences were noted in potential bleeding factors between the rivaroxaban (n=105) and low-molecular-weight heparin (LMWH) (n=69) groups. Rivaroxaban exhibited similar risk of recurrent/aggravated VTE compared with LMWH (p=0.625) but increased risk of major bleeding (17.4% vs. 7.6%; p=0.072), clinically relevant bleeding (31.9% vs. 14.3%; p=0.019), and total bleeding (40.6% vs. 19%; p=0.010). The multivariate analysis regarded rivaroxaban as a significant factor for major bleeding (p=0.043) and clinically relevant bleeding (p=0.043). Conclusion: Rivaroxaban exhibits comparable efficacy but increases bleeding risks compared with LMWH in patients with active unresectable/metastatic upper GI tract or HPB cancers, requiring extra caution of higher major bleeding risks.
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- 2019
17. Prognostic Implication of Inflammation-based Prognostic Scores in Patients with Intrahepatic Cholangiocarcinoma Treated with First-line Gemcitabine plus Cisplatin
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Gi-Won Song, Changhoon Yoo, Jae Hoon Lee, Kang Mo Kim, Kyu-Pyo Kim, Heung-Moon Chang, Hyungwoo Cho, Deok-Bog Moon, Ju Hyun Shim, Sung Koo Lee, Han Chu Lee, Myung-Hwan Kim, Young-Suk Lim, Young-Joo Lee, Sang Soo Lee, Tae Jun Song, Jae Ho Jeong, Baek-Yeol Ryoo, Shin Hwang, Jihoon Kang, and Do Hyun Park
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Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,Multivariate analysis ,First line ,Inflammation ,Deoxycytidine ,Gastroenterology ,Cholangiocarcinoma ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Pharmacology (medical) ,In patient ,Intrahepatic Cholangiocarcinoma ,Aged ,Pharmacology ,Cisplatin ,Univariate analysis ,business.industry ,Middle Aged ,Prognosis ,Gemcitabine ,Progression-Free Survival ,Treatment Outcome ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Multivariate Analysis ,Female ,medicine.symptom ,business ,medicine.drug - Abstract
Background We aimed to comprehensively evaluate the prognostic value of inflammation-based prognostic scores, including the modified Glasgow Prognostic Score (mGPS), neutrophil–lymphocyte ratio (NLR), and platelet–lymphocyte ratio (PLR), exclusively in patients with advanced intrahepatic cholangiocarcinoma (iCCA). Methods Between May 2010 and April 2015, 305 patients with histologically documented unresectable or metastatic iCCA were treated with first-line gemcitabine plus cisplatin (GemCis). Among these, 257 patients had complete data for inflammation-based prognostic scores and were included. Results Median age was 59 (range: 27–78) years, and 158 patients (61.5%) were males. High mGPS was independently associated with poor progression-free survival (PFS; mGPS ≥1 vs. 0: median, 3.9 vs. 5.5 months; P = 0.001) and overall survival (OS; mGPS ≥1 vs. 0; median, 6.9 vs. 14.1 months; P = 0.002) in the multivariate analysis. Regarding high NLR (> median) and PLR (> median), although a potential association existed with poor PFS or OS in the univariate analysis, these did not remain as significant in the multivariate analyses. Conclusion The current study suggests that mGPS might be the relevant prognostic index that could stratify the survival outcomes of patients with unresectable or metastatic iCCA who received first-line GemCis.
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- 2017
18. Abstract CT010: Primary results of phase 2 FOENIX-CCA2: The irreversible FGFR1-4 inhibitor futibatinib in intrahepatic cholangiocarcinoma (iCCA) with FGFR2 fusions/rearrangements
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Thomas A. Abrams, Li-Tzong Chen, Kunihiro Masuda, Juan W. Valle, Karim A. Benhadji, Daniel H. Ahn, Nital Soni, Philippe A. Cassier, Yaohua He, Antoine Hollebecque, Junji Furuse, Yoshito Komatsu, John Bridgewater, Heung-Moon Chang, Thomas Benjamin Karasic, Lipika Goyal, Robin Kate Kelley, Heinz-Josef Klümpen, Chigusa Morizane, and Funda Meric-Bernstam
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Cancer Research ,medicine.medical_specialty ,education.field_of_study ,business.industry ,Population ,Cancer ,medicine.disease ,Gastroenterology ,Hyperphosphatemia ,Oncology ,Internal medicine ,medicine ,Clinical endpoint ,Biomarker (medicine) ,Dosing ,business ,education ,Intrahepatic Cholangiocarcinoma ,Progressive disease - Abstract
Background FGFR2 fusions occur in ~15% of patients (pts) with iCCA, a rare cancer with a poor prognosis. Futibatinib, a highly selective, irreversible FGFR1-4 inhibitor, has shown activity across tumor types, including iCCA, in a phase 1 study. The pivotal phase 2 FOENIX-CCA2 trial (NCT02052778) is evaluating futibatinib in iCCA harboring FGFR2 fusions/rearrangements. Here, we report the first efficacy, safety, and quality of life (QoL) data for the complete FOENIX-CCA2 population. Methods Eligible pts had unresectable/metastatic iCCA with an FGFR2 fusion/rearrangement and progressive disease (PD) after ≥1 prior treatment (tx; excluding FGFR inhibitors). Pts received futibatinib 20 mg QD until PD/intolerability. The primary endpoint was objective response rate (ORR) per RECIST v1.1 by independent central review (target ORR: 20%). Secondary endpoints included duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), safety, and patient-reported outcomes (PROs). Subgroup analyses were performed by pt characteristic and molecular alteration. Results Among 103 pts (56% female), 53% had received ≥2 prior tx. FGFR2 fusions were present in 78% (23% had FGFR2-BICC1 fusions) and FGFR2 rearrangements in 22%. At data cutoff (Oct 1, 2020), 72 pts (70%) had discontinued tx. The study met its primary objective with a confirmed ORR of 41.7% (43/103). Responses were durable, with a median (m) DOR of 9.7 mo and 72% of responses ≥6 mo. DCR was 82.5%. mPFS was 9.0 mo; mOS was 21.7 mo, with a 12-mo OS rate of 72%. ORR was consistent across pt demographic subgroups (≥65 y: 65.2%; 2 prior tx: 38.7%). Common tx-related AEs (TRAEs) were hyperphosphatemia (85%), alopecia (33%), and dry mouth (30%). The most frequent grade 3 TRAE, hyperphosphatemia (30%), resolved with adequate management (median 7 d). Retinal disorders (all grade 1-2) were reported in 8% of pts. TRAEs were managed with dosing interruptions (50%)/reductions (54%); 2 pts discontinued tx due to TRAEs. No tx-related deaths occurred. ORRs were consistent in pts with dosing interruptions (40.2%) or reductions (46.8%). PROs were stable through 11.0 mo of tx. In exploratory biomarker analyses, ORR was consistent in pts with FGFR2 fusions (43.8%) and other FGFR2 rearrangements (34.8%) and in pts with BICC1 (41.7%) and non-BICC1 (44.6%) fusion partners. Notably, no obvious differences in ORR were observed in pts with co-occurring genetic alterations, including TP53 comutations (ORR, 38.5% [5/13]). Additional biomarker data will be presented. Conclusions Futibatinib resulted in frequent, durable objective responses in pts with iCCA harboring FGFR2 fusion/rearrangements, regardless of pt baseline characteristic, molecular alteration, or comutation. AEs were manageable with dosing modifications that did not impact response. QoL was maintained. Citation Format: Lipika Goyal, Funda Meric-Bernstam, Antoine Hollebecque, Chigusa Morizane, Juan W. Valle, Thomas B. Karasic, Thomas A. Abrams, Robin Kate Kelley, Philippe Cassier, Junji Furuse, Heinz-Josef Klümpen, Heung-Moon Chang, Li-Tzong Chen, Yoshito Komatsu, Kunihiro Masuda, Daniel Ahn, Yaohua He, Nital Soni, Karim A. Benhadji, John A. Bridgewater. Primary results of phase 2 FOENIX-CCA2: The irreversible FGFR1-4 inhibitor futibatinib in intrahepatic cholangiocarcinoma (iCCA) with FGFR2 fusions/rearrangements [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT010.
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- 2021
19. Germline BRCA mutations in Asian patients with pancreatic adenocarcinoma: a prospective study evaluating risk category for genetic testing
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Kyoung-Jin Park, Myung-Hwan Kim, Tae Jun Song, Dong Wan Seo, Jae Hoon Lee, Sang Hyun Shin, Do Hyun Park, Dae Wook Hwang, Sung Koo Lee, Song Cheol Kim, Heung-Moon Chang, Woochang Lee, Kyu-Pyo Kim, Sang Soo Lee, Tae Won Kim, Kyoungmin Lee, Changhoon Yoo, Ki Byung Song, Baek-Yeol Ryoo, and Jae-Lyun Lee
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Male ,Oncology ,medicine.medical_specialty ,endocrine system diseases ,Population ,Breast Neoplasms ,Adenocarcinoma ,Germline ,03 medical and health sciences ,0302 clinical medicine ,Asian People ,Risk Factors ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Pharmacology (medical) ,Medical history ,Genetic Testing ,030212 general & internal medicine ,Family history ,Medical History Taking ,skin and connective tissue diseases ,education ,Prospective cohort study ,Germ-Line Mutation ,Aged ,Genetic testing ,BRCA2 Protein ,Ovarian Neoplasms ,Pharmacology ,education.field_of_study ,medicine.diagnostic_test ,BRCA1 Protein ,business.industry ,Middle Aged ,medicine.disease ,Progression-Free Survival ,Pancreatic Neoplasms ,030220 oncology & carcinogenesis ,Female ,Ovarian cancer ,business - Abstract
Introduction Germline BRCA mutations may have therapeutic implications as surrogate markers of DNA-damage repair status in pancreatic ductal adenocarcinoma (PDAC). We performed a prospective study to evaluate the efficiency of risk criteria based on personal or family history of breast and ovarian cancer for determining germline BRCA mutations in PDAC patients with Asian ethnicity. Methods Between November 2015 and May 2016, we screened consecutive PDAC patients with locally advanced unresectable or metastatic disease who were referred for systemic chemotherapy. Analyses for germline BRCA mutations were performed if patients had one or more first-degree or second-degree relatives with breast or ovarian cancers or had a personal medical history of these diseases. DNA was extracted from whole blood, and all coding exons and their flanking intron regions of BRCA1 and BRCA2 were sequenced. Results A total of 175 patients were screened for personal and family history and 10 (5.7%) met the inclusion criteria for genetic sequencing. Pathogenic germline BRCA2 mutation [c.7480C>T (p.Arg2494*)] was identified in one male patient, resulting in a frequency of 10% for the risk-stratified patients and 0.6% for the unselected PDAC population. Two patients had germline BRCA2 variants of uncertain significance [c.1744A>C (p.Thr582Pro) and c.68-7T>A]. Conclusion Personal or family history of breast or ovarian cancers is a feasible, cost-effective risk categorization for screening germline BRCA mutations in Asian PDAC patients as 10% of this population had the pathogenic mutation herein. Future validation from a large, prospective cohort is needed.
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- 2017
20. Clinical outcomes of patients with resectable pancreatic acinar cell carcinoma
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Song Cheol Kim, Ki-Hun Kim, Shin Hwang, Seyoung Seo, Seung-Mo Hong, Jae Hoon Lee, Kyu-poy Kim, Dae Wook Hwang, Heung-Moon Chang, Baek-Yeol Ryoo, Changhoon Yoo, and Ki Byung Song
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Oncology ,Cisplatin ,medicine.medical_specialty ,business.industry ,Gastroenterology ,Clinical course ,Disease ,Neuroendocrine tumors ,medicine.disease ,Gemcitabine ,03 medical and health sciences ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Carcinoma ,030211 gastroenterology & hepatology ,business ,Etoposide ,medicine.drug ,Pancreatic Acinar Cell Carcinoma - Abstract
OBJECTIVE Given the rarity of the disease, the post-resection clinical course of localized pancreatic acinar cell carcinoma (ACC) is largely unknown. Therefore, we aimed to analyze the outcomes of patients with localized pancreatic ACC who underwent curative surgical resection. METHODS We retrospectively analyzed the outcomes of 20 patients with resectable pancreatic ACC who underwent surgery. RESULTS Altogether 20 patients were included in the study, with a median age of 57 years and a male predominance. There were eight pure ACC, 10 mixed acinar–neuroendocrine carcinomas and two mixed acinar–ductal adenocarcinomas. Among the 15 patients who were staged histologically, 3, 8 and 4 were at stages IB, IIA and IIB, respectively. Eleven patients received adjuvant chemotherapy (5-fluorouracil-based [n = 9]; gemcitabine [n = 1]; etoposide plus cisplatin [n = 1]). In a median follow-up period of 27.1 months, disease recurred in 10 patients, most commonly in the liver (90%). Median recurrence-free survival and overall survival were 16.9 months and 75.0 months, respectively. Elevation of cancer antigen 19-9 (CA19-9), lymph node metastasis and neural invasion were significantly associated with poor overall survival (P = 0.007, P = 0.027 and P = 0.016, respectively). CONCLUSIONS Compared with ductal adenocarcinoma, resectable pancreatic ACC has a favorable prognosis after surgery. Considering that distant metastasis is the most common pattern of recurrence, further studies are necessary to define the role of adjuvant chemotherapy for improving survival outcomes.
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- 2017
21. Efficacy of Chemotherapy in Patients with Unresectable or Metastatic Pancreatic Acinar Cell Carcinoma: Potentially Improved Efficacy with Oxaliplatin-Containing Regimen
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Tae Won Kim, Jae-Lyun Lee, Changhoon Yoo, Kyu-Pyo Kim, Heung-Moon Chang, Baek-Yeol Ryoo, and Bum Jun Kim
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Adult ,Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,Organoplatinum Compounds ,Pancreatic neoplasms ,medicine.medical_treatment ,Capecitabine ,03 medical and health sciences ,0302 clinical medicine ,Maintenance therapy ,FOLFOX ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Antineoplastic agents ,Humans ,Medicine ,Neoplasm Metastasis ,Acinar cell carcinoma ,Aged ,Neoplasm Staging ,Retrospective Studies ,Chemotherapy ,Carcinoma, Acinar Cell ,business.industry ,Middle Aged ,Gemcitabine ,Oxaliplatin ,Regimen ,Treatment Outcome ,030220 oncology & carcinogenesis ,Female ,Original Article ,030211 gastroenterology & hepatology ,business ,medicine.drug ,Pancreatic Acinar Cell Carcinoma - Abstract
Purpose Pancreatic acinar cell carcinoma (ACC) is a rare cancer of the exocrine pancreas. Because of its rare incidence, the efficacy of chemotherapy in this patient population has been largely unknown. Therefore, we retrospectively analyzed the outcomes of patients with advanced pancreatic ACC who received chemotherapy. Materials and methods Between January 1997 and March 2015, 15 patients with unresectable or metastatic pancreatic ACC who received systemic chemotherapy were identified in Asan Medical Center, Korea. Results The median age was 58 years. Eleven and four patients had recurrent/metastatic and locally advanced unresectable disease. The median overall survival in all patients was 20.9 months (95% confidence interval [CI], 15.7 to 26.1). As first-line therapy, intravenous 5-fluorouracil were administered in four patients (27%), gemcitabine in five (33%), gemcitabine plus capecitabine in two (13%), oxaliplatin plus 5-fluorouracil/leucovorin (FOLFOX) in two (13%), and concurrent chemoradiotherapy followed by capecitabine maintenance therapy in two (13%). The objective response rate (ORR) to chemotherapy alone was 23% and the median progression-free survival (PFS) was 5.6 months (95% CI, 2.8 to 8.4). After progression, second-line chemotherapy was administered in eight patients, while four patients received FOLFOX and the other four patients received gemcitabine. The ORR was 38%, and patients administered FOLFOX had significantly better PFS than those administered gemcitabine (median, 6.5 months vs. 1.4 months; p=0.007). The ratio of time to tumor progression (TTP) during first-line chemotherapy to TTP at second-line chemotherapy was significantly higher in patients administered FOLFOX (4.07; range, 0.87 to 8.30) than in those administered gemcitabine (0.12; range, 0.08 to 0.25; p=0.029). Conclusion Our results suggest that oxaliplatin-containing regimens may have improved activity against pancreatic ACC.
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- 2017
22. Efficacy and safety of neoadjuvant FOLFIRINOX for borderline resectable pancreatic adenocarcinoma: improved efficacy compared with gemcitabine-based regimen
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Dong Wan Seo, Tae Jun Song, Jae Hoon Lee, Dae Wook Hwang, Sang Soo Lee, Jihoon Kang, Jin-Hong Park, Do Hyun Park, Sung Koo Lee, Baek-Yeol Ryoo, Kyu-Pyo Kim, Myung-Hwan Kim, Jae-Lyun Lee, Song Cheol Kim, Changhoon Yoo, Ki Byung Song, and Heung-Moon Chang
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Adult ,Male ,medicine.medical_specialty ,FOLFIRINOX ,medicine.medical_treatment ,pancreatic cancer ,Phases of clinical research ,Adenocarcinoma ,chemotherapy ,Gastroenterology ,Capecitabine ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Pancreatic cancer ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Neoplasm Metastasis ,Survival analysis ,Aged ,Neoplasm Staging ,Chemotherapy ,business.industry ,neoadjuvant ,Middle Aged ,medicine.disease ,Combined Modality Therapy ,Survival Analysis ,Gemcitabine ,Surgery ,Pancreatic Neoplasms ,Regimen ,Treatment Outcome ,Oncology ,030220 oncology & carcinogenesis ,Female ,030211 gastroenterology & hepatology ,business ,Research Paper ,medicine.drug - Abstract
Borderline resectable pancreatic cancer (BRPC) is a potentially resectable disease but is associated with poorer survival compared to primary resectable disease. There has been no prospective trial that compare the efficacy of FOLFIRNOX and gemcitabine-based regimen for BRPC. Between February 2013 and December 2014, 18 patients with BRPC receiving FOLFIRINOX were reviewed retrospectively. For comparative analysis, data for all BRPC patients (n=18) in our previous phase 2 study of neoadjuvant fixed-dose rate-gemcitabine plus capecitabine were pooled. Patients received a median 6 cycles (range, 3-13) of FOLFIRINOX. Surgical resection was performed in 12 patients (67%) and R0 resection in 9 patients. Median progression-free survival (PFS) and overall survival (OS) were 16.8 (95% confidence interval [CI], 9.4-24.2) and 21.2 (95% CI, 14.2-28.2) months, respectively. Patients who underwent surgical resection showed significantly better PFS (p=0.01) and OS (p=0.003) than those unresected. In the exploratory analysis, patients receiving FOLFIRINOX showed significantly longer PFS compared to those receiving fixed-dose rate-gemcitabine plus capecitabine (median 16.8 months [95% CI, 9.4-24.2] vs. 6.5 months [1.6-11.3]; p = 0.04). There was a trend toward improved OS in patients who received FOLFIRINOX (median 21.2 months [95% CI, 14.2-28.2]) compared to those who received fixed-dose rate-gemcitabine plus capecitabine (13.6 months [11.8-15.4]; p=0.12). FOLFIRINOX was feasible and effective as neoadjuvant chemotherapy for patients with BRPC and may have improved efficacy compared to a gemcitabine-based regimen.
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- 2017
23. Bilateral lung metastasectomy in carcinoma of the ampulla of Vater
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Gyu Young Pih, Dong Kwan Kim, Kwang-Min Park, and Heung-Moon Chang
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Colorectal cancer ,medicine.medical_treatment ,digestive system ,03 medical and health sciences ,0302 clinical medicine ,Carcinoma ,medicine ,Pathological ,Lung ,business.industry ,General surgery ,Ampulla of Vater ,Cancer ,General Medicine ,respiratory system ,medicine.disease ,Pancreaticoduodenectomy ,digestive system diseases ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,030211 gastroenterology & hepatology ,Radiology ,Metastasectomy ,business - Abstract
The efficacy of lung metastasectomy is well established in several cancers, including colorectal cancer. However, little is known about the result of lung metastasectomy in carcinoma of the ampulla of Vater. Only two case reports have reported the efficacy of metastasectomy in ampullary cancer patients with pulmonary metastasis. We report the result of bilateral lung metastasectomy in a patient with ampullary cancer. A 63-year-old woman underwent pylorus-preserving pancreaticoduodenectomy for carcinoma of the ampulla of Vater. About three years after the surgery, two non-calcified lung nodules in the right lower and left upper lobes had developed. Wedge resections of both lung nodules were performed and the pathological examination showed that the lung nodules were pulmonary metastases from the ampullary cancer. Ten years after the lung surgery, the patient is well and there is no evidence of recurrence. Surgical resection could be considered in patients with pulmonary metastasis from ampulla of Vater cancer, even when the metastases are bilateral.
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- 2017
24. Comparison of gemcitabine plus cisplatin versus capecitabine plus cisplatin as first-line chemotherapy for advanced biliary tract cancer
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Seong Joon Park, Kwonoh Park, Heung-Moon Chang, and Kyu-Pyo Kim
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0301 basic medicine ,Oncology ,Cisplatin ,medicine.medical_specialty ,Chemotherapy ,Biliary tract cancer ,business.industry ,medicine.medical_treatment ,Hazard ratio ,General Medicine ,Gemcitabine ,Capecitabine ,03 medical and health sciences ,Regimen ,030104 developmental biology ,0302 clinical medicine ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,First line chemotherapy ,business ,medicine.drug - Abstract
Aim: It remains unclear whether capecitabine combined with cisplatin would show similar effects compared with standard therapy using gemcitabine and cisplatin in advanced biliary tract cancer (BTC). Methods: Patients with advanced BTC who were treated with first-line chemotherapy at Asan Medical Center were retrospectively analyzed. All patients received either cisplatin followed by gemcitabine on days 1 and 8 every 3 weeks (GP group), or capecitabine on days 1–14 with cisplatin on day 1 every 3 weeks (XP group). Results: Of the 134 patients who met the inclusion criteria, 78 received XP and 56 were treated with GP. After a median follow-up of 26.2 months, the progression-free survival was 5.7 months for XP versus 4.1 months for GP (hazard ratio [HR] = 0.81, P = 0.31). The overall survival (OS) was 11.0 months for XP versus 9.8 months for GP (HR = 0.84, P = 0.36). In the multivariate analysis, there were no significant differences in PFS and OS between the two groups. Conclusion: XP seems to be as effective as GP in patients with advanced BTC. The XP regimen is feasible and might offer increased convenience regarding the schedule of drug administration.
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- 2016
25. Clinical Outcomes of Second-Line Chemotherapy after Progression on Nab-Paclitaxel Plus Gemcitabine in Patients with Metastatic Pancreatic Adenocarcinoma
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Tae Jun Song, Changhoon Yoo, Kyu-Pyo Kim, Baek-Yeol Ryoo, Kyunghye Bang, Sung Koo Lee, Sang Soo Lee, Heung-Moon Chang, Jin-Hong Park, Jae Ho Jeong, Kyoungmin Lee, Inhwan Hwang, Do Hyun Park, Dongwook Oh, and Myung-Hwan Kim
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0301 basic medicine ,Oncology ,Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Paclitaxel ,Pancreatic neoplasms ,medicine.medical_treatment ,Kaplan-Meier Estimate ,Second-line ,Adenocarcinoma ,Nab-paclitaxel ,Second line chemotherapy ,Deoxycytidine ,03 medical and health sciences ,0302 clinical medicine ,FOLFOX ,Internal medicine ,Albumins ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Neoplasm Metastasis ,Aged ,Neoplasm Staging ,Retrospective Studies ,Chemotherapy ,business.industry ,Metastatic Pancreatic Adenocarcinoma ,Middle Aged ,Prognosis ,Gemcitabine ,Oxaliplatin ,030104 developmental biology ,Fluorouracil ,030220 oncology & carcinogenesis ,Retreatment ,Female ,Original Article ,business ,medicine.drug - Abstract
PURPOSE Since the introduction of nab-paclitaxel plus gemcitabine (nab-P+GEM) as first-line (1L) treatment for metastatic pancreatic adenocarcinoma (mPDAC), optimal second-line (2L) chemotherapy after progression is unclear. We assessed clinical outcomes of 2L chemotherapy for disease that progressed on 1L nab-P+GEM. Materials and Methods Among the 203 patients previously treated with 1L nab-P+GEM for mPDAC at Asan Medical Center, between February and December 2016, records of 120 patients receiving 2L chemotherapy after progression on nab-P+GEM were retrospectively reviewed. The response rate and survival were evaluated along with analysis of prognostic factors. RESULTS Fluoropyrimidine-oxaliplatin doublets (FOLFOX or XELOX) were used in 78 patients (65.0%), fluoropyrimidine monotherapy in 37 (30.8%), and liposomal irinotecan plus fluorouracil in two (1.7%). The median progression-free survival (PFS) and overall survival (OS) were 3.29 months and 7.33 months from the start of 2L therapy. Fluoropyrimidine-oxaliplatin regimens and fluoropyrimidine monotherapy did not yield significantly different median PFS (2.89 months vs. 3.81 months, p=0.40) or OS (7.04 months vs. 7.43 months, p=0.86). A high neutrophil-lymphocyte ratio (> 2.2) and a short time to progression with 1L nab-P+GEM (< 6.4 months) were independent prognostic factors of poor OS with 2L therapy. CONCLUSION 2L fluoropyrimidine-oxaliplatin doublets and fluoropyrimidine monotherapy after failure of 1L nab-P+GEM had modest efficacy, with no differences in treatment outcomes between them. Further investigation is warranted for the optimal 2L chemo-regimens and sequencing of systemic chemotherapy for patients with mPDAC.
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- 2019
26. Stereotactic body radiation therapy for locally advanced pancreatic cancer
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Sang Min Yoon, Jinhong Jung, Heung-Moon Chang, Baek-Yeol Ryoo, Jong Hoon Kim, Jae Hoon Lee, Dae Wook Hwang, Kyu-Pyo Kim, Yoon Young Jo, Jin-Hong Park, Tae Jun Song, Sung Koo Lee, Dong Wan Seo, Do Hyun Park, Song Cheol Kim, Jongmoo Park, Jae Ho Jeong, Sang Soo Lee, Myung-Hwan Kim, Changhoon Yoo, and Ki Byung Song
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0301 basic medicine ,Endoscopic ultrasound ,Adult ,Male ,medicine.medical_specialty ,Nausea ,Science ,medicine.medical_treatment ,Radiosurgery ,Disease-Free Survival ,03 medical and health sciences ,0302 clinical medicine ,Medicine ,Humans ,Four-Dimensional Computed Tomography ,Survival rate ,Pancreas ,Aged ,Retrospective Studies ,Aged, 80 and over ,Chemotherapy ,Multidisciplinary ,medicine.diagnostic_test ,business.industry ,Retrospective cohort study ,Cone-Beam Computed Tomography ,Middle Aged ,Gemcitabine ,Pancreatic Neoplasms ,Survival Rate ,030104 developmental biology ,030220 oncology & carcinogenesis ,Vomiting ,Female ,Radiology ,medicine.symptom ,business ,medicine.drug ,Follow-Up Studies - Abstract
PurposeStereotactic body radiation therapy (SBRT) is a promising treatment modality for locally advanced pancreatic cancer (LAPC). We evaluated the clinical outcomes of SBRT in patients with LAPC.Patients and methodsWe retrospectively analyzed the medical records of patients with LAPC who underwent SBRT at our institution between April 2011 and July 2016. Fiducial markers were implanted using endoscopic ultrasound guidance one week prior to 4-dimensional computed tomography (CT) simulation and daily cone beam CT was used for image guidance. Patients received volumetric modulated arc therapy or intensity modulated radiotherapy using respiratory gating technique. A median dose of 28 Gy (range, 24-36 Gy) was given over four consecutive fractions delivered within one week. Survival outcomes including freedom from local disease progression (FFLP), progression-free survival (PFS), and overall survival (OS) were analyzed. Acute and late toxicities related to SBRT were assessed.ResultsA total of 95 patients with LAPC were analyzed, 52 of which (54.7%) had pancreatic head cancers. Most (94.7%) had received gemcitabine-based chemotherapy. The 1-year FFLP rate was 80.1%. Median OS and PFS were 16.7 months and 10.2 months, respectively; the 1-year OS and PFS rates were 67.4% and 42.9%, respectively. Among 79 patients who experienced failure, the sites of first failures were isolated local progressions in 12 patients (15.2%), distant metastasis in 55 patients (69.6%), and both in 12 patients (15.2%). Seven patients (7.4%) were able to undergo surgical resection after SBRT and four had margin-negative resections. Three patients (3.2%) had grade 3 nausea/vomiting during SBRT, and late grade 3 toxicity was observed in another three patients.ConclusionsLAPC patients who received chemotherapy and SBRT had favorable FFLP and OS with minimal treatment-related toxicity. The most common pattern of failure was distant metastasis, which warrants further studies on the optimal scheme of chemotherapy and SBRT.
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- 2019
27. Efficacy and safety of mFOLFIRINOX in patients with borderline resectable and locally advanced unresectable pancreatic cancer: Intention-to-treat population analysis
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Jae Ho Byun, Kyu-Pyo Kim, Inhwan Hwang, Heung-Moon Chang, Changhoon Yoo, Baek-Yeol Ryoo, and Jae Ho Jeong
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Oncology ,Unresectable Pancreatic Cancer ,Cancer Research ,medicine.medical_specialty ,education.field_of_study ,Disease entity ,Intention-to-treat analysis ,business.industry ,Population ,Locally advanced ,medicine.disease ,Borderline resectable ,Internal medicine ,Pancreatic cancer ,medicine ,In patient ,education ,business - Abstract
720 Background: Borderline resectable pancreatic cancer (BRPC) and locally advanced unresectable pancreatic cancer (LAUPC) are heterogeneous disease entity with various prognosis. Based on the phase III PRODIGE trial, (m)FOLFIRINOX has been widely used for the management of patients with BRPC and LAUPC. Considering the lack of large phase 3 trial of (m)FOLFIRINOX for BRPC and LAUPC, real-life evidences of (m)FOLFIRINOX are needed. Methods: In this retrospective analysis, 199 patients who received at least one dose of (m)FOLFIRINOX between February 2013 and January 2017 were included. Endpoints of this study were objective response rates (ORR), surgical resection rate, progression-free survival (PFS) and overall survival (OS). Results: Median age was 60 years (range, 33-79) and 62.3% of patients were male. Pancreas head (n=112, 56.3%) was the most common primary tumor site, followed by body (n=42, 21.1%) and multifocal (n=34, 17.1%). By an independent radiology review, patients were classified to BRPC (n=75, 37.7%) and LAUPC (n=124, 62.3%). With median 40.3 months (95% CI, 36.7-43.8) of follow-up duration in surviving patients, ORR was 26.6% (n=53), median PFS and OS were 10.6 months (95% CI, 9.5-11.7) and 17.1 months (95% CI, 13.2-20.9), respectively. There was no difference in PFS and OS between BRPC and LAUPC (median PFS, 11.1 months [95% CI, 8.8-13.5] vs. 10.1 months [95% CI, 8.4-11.8], p=0.47); (median OS, 18.4 months [95% CI, 16.1-20.8] vs. 17.1 months [95% CI, 13.2-20.9], p=0.50). Curative-intent surgery (R0 and R1) was done in 63 patients (33.2%, 49 for R0 and 14 for R1) after treatment with (m)FOLFIRINOX. Resection rates were 58.2% in BRPC patients and 19.4% in LAUPC patients (p
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- 2020
28. TAS-118 (S-1 plus leucovorin) versus S-1 in patients with gemcitabine-refractory advanced pancreatic cancer: a randomised, open-label, phase 3 study (GRAPE trial)
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Hideki Ueno, Ichinosuke Hyodo, Yasushi Omuro, Junji Furuse, Makoto Ueno, Hiroki Hara, Takuji Okusaka, Hiroyuki Maguchi, Masashi Kanai, Seigo Yukisawa, Nobumasa Mizuno, Taketo Yamaguchi, Joon Oh Park, Narikazu Boku, Naoki Sasahira, Kazuya Sugimori, Masafumi Ikeda, Kengo Fukuzawa, Shoji Nakamori, Ik Joo Chung, Masahiro Takeuchi, Jun Suk Kim, Masayuki Furukawa, Heung Moon Chang, and Tatsuya Ioka
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0301 basic medicine ,Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Antimetabolites, Antineoplastic ,Time Factors ,medicine.medical_treatment ,Leucovorin ,Phases of clinical research ,Adenocarcinoma ,Gastroenterology ,Deoxycytidine ,03 medical and health sciences ,Carcinoma, Adenosquamous ,0302 clinical medicine ,Japan ,Internal medicine ,Pancreatic cancer ,Antineoplastic Combined Chemotherapy Protocols ,Republic of Korea ,Medicine ,Humans ,Adverse effect ,Aged ,Tegafur ,Chemotherapy ,business.industry ,Incidence (epidemiology) ,Hazard ratio ,Middle Aged ,medicine.disease ,Gemcitabine ,Confidence interval ,Progression-Free Survival ,Pancreatic Neoplasms ,Drug Combinations ,Oxonic Acid ,030104 developmental biology ,Oncology ,Drug Resistance, Neoplasm ,030220 oncology & carcinogenesis ,Disease Progression ,Female ,business ,medicine.drug - Abstract
Background In our previous randomised phase 2 study for patients with gemcitabine-refractory advanced pancreatic cancer, S-1 plus leucovorin improved progression-free survival compared with S-1 alone. Here, we evaluated the efficacy of TAS-118 (S-1 plus leucovorin) versus S-1 in overall survival (OS). Patients and methods This randomised, open-label, phase 3 study was conducted at 58 centres in Japan and Korea. Patients with metastatic pancreatic cancer that progressed during first-line gemcitabine-based chemotherapy or recurred during or after post-operative gemcitabine-based adjuvant treatment were randomly assigned (1:1) to receive either S-1 (40–60 mg, twice daily for 4 weeks in a 6-week cycle) or TAS-118 (S-1 40–60 mg plus leucovorin 25 mg, twice daily for 1 week in a 2-week cycle). The primary end-point was OS. Results A total of 603 patients were randomised, and 300 and 301 patients received TAS-118 and S-1, respectively. There was no difference in OS between groups (median OS for TAS-118 versus S-1, 7.6 months versus 7.9 months; hazard ratio [HR], 0.98 [95% confidence interval (CI), 0.82–1.16]; P = 0.756). Progression-free survival was significantly longer with TAS-118 than S-1 (median, 3.9 months versus 2.8 months; HR, 0.80 [95% CI, 0.67–0.95]; P = 0.009). There were interactions between Japan and Korea (P = 0.004) and between unresectable and recurrent disease (P = 0.025) in OS. Incidence, profile and severity of adverse events were similar between groups. Conclusion TAS-118 did not improve OS in patients with gemcitabine-refractory advanced pancreatic cancer compared to S-1. Further studies are needed to find patients who have benefit from adding leucovorin to S-1.
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- 2018
29. Prognostic implications of hepatitis B virus infection in intrahepatic cholangiocarcinoma treated with first-line gemcitabine plus cisplatin
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Kang Mo Kim, Do Hyun Park, Kyu-Pyo Kim, Jae Hoon Lee, Changhoon Yoo, Deok-Bog Moon, Sang Soo Lee, Heung-Moon Chang, Jihoon Kang, Ju Hyun Shim, Shin Hwang, Heejung Chae, Gi-Won Song, Jae Ho Jeong, Young-Joo Lee, Han Chu Lee, Young-Suk Lim, Baek-Yeol Ryoo, Hyungwoo Cho, and Tae Jun Song
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Oncology ,Adult ,Male ,Cancer Research ,medicine.medical_specialty ,First line ,Clinical Biochemistry ,medicine.disease_cause ,Deoxycytidine ,Pathology and Forensic Medicine ,Cholangiocarcinoma ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Risk factor ,Intrahepatic Cholangiocarcinoma ,Aged ,Retrospective Studies ,Hepatitis B virus ,Cisplatin ,business.industry ,Bilirubin ,Middle Aged ,Hepatitis B ,Prognosis ,Gemcitabine ,Bile Duct Neoplasms ,030220 oncology & carcinogenesis ,030211 gastroenterology & hepatology ,Female ,business ,medicine.drug - Abstract
Purpose: Hepatitis B virus infection is a well-known risk factor for intrahepatic cholangiocarcinoma. However, its prognostic impact has rarely been investigated in advanced intrahepatic cholangiocarcinoma. Methods: Between April 2010 and May 2015, 296 patients with unresectable or metastatic intrahepatic cholangiocarcinoma who received gemcitabine plus cisplatin (GemCis) were categorized into a hepatitis B virus group (n=62; 21%) and a non-hepatitis B virus group (n=234; 79%). Clinicopathological features and survival outcomes were retrospectively reviewed and analyzed. Results: The median age of patients was 59 years (range, 27–78). The median overall survival with first-line GemCis was 9.4 months (95% CI 8.4, 10.4). Compared to the non-hepatitis B virus group, the hepatitis B virus group was younger (median age, 57 vs. 61 years, P = 0.001), mainly male (74% vs. 57%, P = 0.02), and had lower frequency of elevated cancer antigen (CA) 19-9 (34% vs. 59%, P = 0.001) and alkaline phosphatase (43% vs. 61%, P = 0.01). In a univariate analysis, the hepatitis B virus infection showed a marginal relationship with poor overall survival compared to the non-hepatitis B virus infection (median, 8.3 vs. 10.0 months; P=0.13). A multivariate analysis of potential prognostic factors revealed a significant association with poor overall survival in the hepatitis B virus group (hazard ratio (HR) =1.50, P = 0.02). Initial metastatic disease (vs. recurrent/unresectable disease; HR=1.50), metastatic sites ⩾ 2 (vs. 0–1; HR=1.51), Eastern Cooperative Oncology Group performance status ⩾ 2 (vs. 0–1; HR=1.93), elevated total bilirubin (vs. normal; HR=1.83), and low albumin (vs. normal; HR=1.52) were significantly related to an unfavorable overall survival. Conclusions: This study suggests that the hepatitis B virus infection may be associated with distinctive clinicopathological characteristics and poor outcome in advanced intrahepatic cholangiocarcinoma treated with GemCis.
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- 2018
30. Nab-paclitaxel plus gemcitabine versus FOLFIRINOX as the first-line chemotherapy for patients with metastatic pancreatic cancer: retrospective analysis
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Sang Soo Lee, Jae Ho Jeong, Kyu-Pyo Kim, Sang Hyun Shin, Dong Wan Seo, Myung-Hwan Kim, Sung Koo Lee, Inhwan Hwang, Jihoon Kang, Seung-Mo Hong, Jae Hoon Lee, Heung-Moon Chang, Baek-Yeol Ryoo, Do Hyun Park, Changhoon Yoo, Ki Byung Song, Tae Jun Song, Dae Wook Hwang, and Song Cheol Kim
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0301 basic medicine ,Oncology ,Male ,medicine.medical_specialty ,Paclitaxel ,FOLFIRINOX ,medicine.medical_treatment ,Leucovorin ,Irinotecan ,Deoxycytidine ,Disease-Free Survival ,Metastasis ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Pancreatic cancer ,Albumins ,Metastatic pancreatic cancer ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Retrospective analysis ,Organometallic Compounds ,Humans ,Pharmacology (medical) ,Nab-paclitaxel ,Aged ,Retrospective Studies ,Pharmacology ,Chemotherapy ,business.industry ,medicine.disease ,Gemcitabine ,Oxaliplatin ,Pancreatic Neoplasms ,Drug Combinations ,030104 developmental biology ,030220 oncology & carcinogenesis ,Female ,Fluorouracil ,business ,medicine.drug - Abstract
Purpose nab-paclitaxel plus gemcitabine (AG) and FOLFIRINOX have been established as standard first-line treatment in metastatic pancreatic cancer (mPC). We performed retrospective analysis comparing the efficacies of AG and FOLFIRINOX in daily practice setting. Materials and Methods We analyzed 308 patients who presented initially as mPC and received AG (n = 149) or FOLFIRINOX (n = 159) as first-line treatment between 2013 and 2016. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Result There were no significant differences between the two groups in terms of baseline characteristics, except older age and higher Charlson Comorbidity Index (CCI) score in AG group. The response rates (34% vs 34%) and median PFS (6.8 vs 5.1 months) were comparable between two groups (p = 0.88 and p = 0.19, respectively), while median OS was significantly better with AG than FOLFIRINOX (11.4 vs 9.6 months; p = 0.002). Elevated baseline CA19–9 level and liver metastasis were independent adverse prognostic factors for PFS and OS. In subgroup analyses, PFS with AG was better in patients with age ≥ 65 years, peritoneal metastasis, and higher CCI than that with FOLFIRINOX. Conclusion Both AG and FOLFIRINOX showed comparable efficacy outcomes in daily practice setting. AG might be preferentially considered in patients with peritoneal metastasis, comorbid medical conditions or old age.
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- 2018
31. Clinical outcomes of patients with resectable pancreatic acinar cell carcinoma
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Seyoung, Seo, Changhoon, Yoo, Kyu-Poy, Kim, Baek-Yeol, Ryoo, Heung-Moon, Chang, Seung-Mo, Hong, Jae Hoon, Lee, Ki Byung, Song, Dae Wook, Hwang, Ki-Hun, Kim, Shin, Hwang, and Song Cheol, Kim
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Adult ,Male ,Carcinoma, Acinar Cell ,Kaplan-Meier Estimate ,Middle Aged ,Prognosis ,Pancreatic Neoplasms ,Pancreatectomy ,Treatment Outcome ,Chemotherapy, Adjuvant ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Female ,Neoplasm Recurrence, Local ,Aged ,Follow-Up Studies ,Neoplasm Staging ,Retrospective Studies - Abstract
Given the rarity of the disease, the post-resection clinical course of localized pancreatic acinar cell carcinoma (ACC) is largely unknown. Therefore, we aimed to analyze the outcomes of patients with localized pancreatic ACC who underwent curative surgical resection.We retrospectively analyzed the outcomes of 20 patients with resectable pancreatic ACC who underwent surgery.Altogether 20 patients were included in the study, with a median age of 57 years and a male predominance. There were eight pure ACC, 10 mixed acinar-neuroendocrine carcinomas and two mixed acinar-ductal adenocarcinomas. Among the 15 patients who were staged histologically, 3, 8 and 4 were at stages IB, IIA and IIB, respectively. Eleven patients received adjuvant chemotherapy (5-fluorouracil-based [n = 9]; gemcitabine [n = 1]; etoposide plus cisplatin [n = 1]). In a median follow-up period of 27.1 months, disease recurred in 10 patients, most commonly in the liver (90%). Median recurrence-free survival and overall survival were 16.9 months and 75.0 months, respectively. Elevation of cancer antigen 19-9 (CA19-9), lymph node metastasis and neural invasion were significantly associated with poor overall survival (P = 0.007, P = 0.027 and P = 0.016, respectively).Compared with ductal adenocarcinoma, resectable pancreatic ACC has a favorable prognosis after surgery. Considering that distant metastasis is the most common pattern of recurrence, further studies are necessary to define the role of adjuvant chemotherapy for improving survival outcomes.
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- 2017
32. Prognostic factors in patients with advanced biliary tract cancer treated with first-line gemcitabine plus cisplatin: retrospective analysis of 740 patients
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Kyu-Pyo Kim, Myung-Hwan Kim, Bum Jun Kim, Sang Soo Lee, Baek-Yeol Ryoo, Dong Wan Seo, Jaewon Hyung, Seong Joon Park, Sung Koo Lee, Changhoon Yoo, Jin-Hong Park, Do Hyun Park, Heung-Moon Chang, Hyungwoo Cho, and Tae Jun Song
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0301 basic medicine ,Oncology ,Adult ,Male ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Disease ,Toxicology ,Gastroenterology ,Deoxycytidine ,Disease-Free Survival ,Cholangiocarcinoma ,03 medical and health sciences ,0302 clinical medicine ,Sex Factors ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Republic of Korea ,medicine ,Humans ,Pharmacology (medical) ,Gallbladder cancer ,Aged ,Retrospective Studies ,Pharmacology ,Cisplatin ,Aged, 80 and over ,Chemotherapy ,business.industry ,Hazard ratio ,Middle Aged ,medicine.disease ,Prognosis ,Primary tumor ,Gemcitabine ,Clinical trial ,030104 developmental biology ,Treatment Outcome ,030220 oncology & carcinogenesis ,Multivariate Analysis ,Female ,Gallbladder Neoplasms ,business ,medicine.drug ,Follow-Up Studies - Abstract
Biliary tract cancer (BTC) is a heterogeneous group of diseases comprising intrahepatic and extrahepatic cholangiocarcinoma and gallbladder cancer. Although gemcitabine plus cisplatin (GEMCIS) was established as the standard first-line chemotherapy based on the ABC-02 trial, more data are needed to define the clinical course of BTC and its prognostic factors with the standard GEMCIS treatment. Between April 2010 and June 2016, 740 patients with histologically documented cholangiocarcinoma and gallbladder cancer were treated with first-line GEMCIS in Asan Medical Center, Seoul, Korea. In 389 patients with measurable disease (53%), the objective response rate was 13% (n = 50) and there was no significant difference between primary tumor sites (p = 0.45). With a median follow-up duration of 27.3 months (95% CI 24.2–30.5), the median PFS and OS were 5.2 months (95% CI 4.7–5.6) and 10.4 months (95% CI 9.6–11.2), respectively. In multivariate analysis, male gender (female versus male, hazard ratio [HR] 0.83), baseline CA 19-9 level (elevated versus normal, HR 1.31), initially metastatic disease (versus locally advanced disease, HR 1.92), poor performance status (2 versus 0–1, HR 1.45), and measurable disease by RECIST criteria (versus non-measurable, HR 1.40) were significantly associated with a poorer OS (all p
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- 2017
33. Efficacy and safety of everolimus and sunitinib in patients with gastroenteropancreatic neuroendocrine tumor
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Baek-Yeol Ryoo, Min-Hee Ryu, Hyungwoo Cho, Yong Sang Hong, Seung-Mo Hong, Min Jeong Song, Song Cheol Kim, Kyu-Pyo Kim, Changhoon Yoo, Heejung Chae, Yoon-Koo Kang, Tae Won Kim, and Heung-Moon Chang
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Oncology ,Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Indoles ,Rectum ,Antineoplastic Agents ,Neuroendocrine tumors ,Toxicology ,Disease-Free Survival ,03 medical and health sciences ,0302 clinical medicine ,Stomach Neoplasms ,Internal medicine ,Intestinal Neoplasms ,medicine ,Sunitinib ,Humans ,Pharmacology (medical) ,In patient ,Pyrroles ,030212 general & internal medicine ,Everolimus ,Aged ,Retrospective Studies ,Pharmacology ,Aged, 80 and over ,business.industry ,Stomach ,Retrospective cohort study ,Middle Aged ,medicine.disease ,Pancreatic Neoplasms ,Neuroendocrine Tumors ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Female ,business ,Pancreas ,medicine.drug - Abstract
Efficacy of targeted agents, such as everolimus and sunitinib, has been demonstrated in prospective trials on patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Considering the heterogeneous clinicopathological characteristics of neuroendocrine tumors (NETs), evaluation of treatment outcomes in a real-world setting is necessary. Clinical records of 44 patients with GEP-NET who were treated with everolimus or sunitinib between March 2007 and October 2014 were retrospectively reviewed. Considering the distinct characteristics of pancreatic NETs (pNETs) and non-pancreatic gastrointestinal NETs (GI-NETs), efficacy analysis was performed separately. Pancreas was the most common primary site (n = 28, 64%), followed by rectum (n = 10, 23%) and stomach (n = 3, 7%). Sunitinib and everolimus were administered in 27 (61%) and 17 (39%) patients, respectively. In patients with pNET, median progression-free survival (PFS) with everolimus and sunitinib was 16.6 months (95% CI 8.0–25.1) and 8.0 months (95% CI 0.0–17.4), respectively (p = 0.51). Among non-pancreatic GI-NET patients, median PFS with everolimus and sunitinib was 14.7 months (95% CI 2.4–27.0) and 1.7 months (95% CI 0.5–3.0), respectively (p = 0.001). Compared to patients treated with everolimus, tumor grade 3 (30 vs. 0%) and history of prior cytotoxic chemotherapy (70 vs. 50%) were more common in patients treated with sunitinib. Both everolimus and sunitinib were effective in GEP-NET patients. Outcomes of everolimus therapy in GEP-NETs were consistent with those reported elsewhere. Poor efficacy of sunitinib in non-pancreatic GI-NETs may be attributable to the baseline characteristics associated with poor clinical outcomes.
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- 2016
34. Efficacy of fluoropyrimidine-based chemotherapy in patients with advanced biliary tract cancer after failure of gemcitabine plus cisplatin: retrospective analysis of 321 patients
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Baek-Yeol Ryoo, Seong Joon Park, Jaewon Hyung, Kyu-Pyo Kim, Changhoon Yoo, Bum Jun Kim, and Heung-Moon Chang
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0301 basic medicine ,Oncology ,Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Combination therapy ,medicine.medical_treatment ,efficacy ,Leucovorin ,Disease-Free Survival ,Capecitabine ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,biliary tract cancer ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,platinum ,Survival rate ,Aged ,Retrospective Studies ,Cisplatin ,Aged, 80 and over ,Chemotherapy ,fluoropyrimidine ,second-line chemotherapy ,business.industry ,Retrospective cohort study ,Middle Aged ,Gemcitabine ,Survival Rate ,030104 developmental biology ,Biliary Tract Neoplasms ,Pyrimidines ,Treatment Outcome ,Fluorouracil ,030220 oncology & carcinogenesis ,Clinical Study ,Female ,business ,cholangiocarcinoma ,medicine.drug - Abstract
Background: We aimed to assess the efficacy of second-line fluoropyrimidine-based chemotherapy in patients with advanced biliary tract cancer (BTC) after failure of gemcitabine plus cisplatin (GEMCIS). Methods: We retrospectively examined patients with histologically documented advanced BTC who received first-line GEMCIS between December 2010 and June 2015. Among 748 patients treated with first-line GEMCIS, 321 (43%) subsequently received fluoropyrimidine-based second-line systemic chemotherapy. Results: Fluoropyrimidine monotherapy and fluoropyrimidine–platinum combination were used in 255 and 66 patients, respectively. In patients with measurable disease, the overall response rate (ORR) was 3% and disease control rate was 47%. After a median follow-up of 27.6 months (range, 0.9–70.4 months), the median progression-free survival (PFS) and overall survival (OS) were 1.9 months (95% confidence interval (CI), 1.6–2.2) and 6.5 months (95% CI, 5.9–7.0), respectively. The ORR was significantly higher in patients who received fluoropyrimidine–platinum combination compared with those who received fluoropyrimidine alone (8 vs 1%, P=0.009), although the PFS (P=0.43) and OS (P=0.88) did not significantly differ between these groups. Conclusions: Fluoropyrimidine-based chemotherapy was modestly effective as a second-line chemotherapy for advanced BTC patients after failure of GEMCIS. Fluoropyrimidine–platinum combination therapy was not associated with improved survival outcomes, as compared with fluoropyrimidine monotherapy.
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- 2016
35. APACT: phase III, multicenter, international, open-label, randomized trial of adjuvant nab-paclitaxel plus gemcitabine (nab-P/G) vs gemcitabine (G) for surgically resected pancreatic adenocarcinoma
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Andrew V. Biankin, Do-Youn Oh, Eric Van Cutsem, Hanno Riess, Charles D. Lopez, Giampaolo Tortora, Eileen M. O'Reilly, Mingyu Li, Josep Tabernero, Brian Lu, Jordan M. Winter, Chung-Pin Li, Margaret A. Tempero, Jordan Berlin, Stefano Ferrara, Heung-Moon Chang, Michele Reni, Philip A. Philip, Uwe Pelzer, and David Goldstein
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Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,medicine.disease ,Gemcitabine ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Randomized controlled trial ,law ,030220 oncology & carcinogenesis ,Internal medicine ,Metastatic pancreatic cancer ,medicine ,Overall survival ,Adenocarcinoma ,Open label ,business ,Adjuvant ,030215 immunology ,Nab-paclitaxel ,medicine.drug - Abstract
4000 Background: In metastatic pancreatic cancer (PC), nab-P/G demonstrated significantly longer overall survival (OS) vs G. APACT assessed efficacy & safety of nab-P/G vs G in surgically resected PC. Methods: Treatment (tx)-naive patients (pts) with histologically confirmed PC, macroscopic complete resection, ECOG PS 0/1, & CA19-9 < 100 U/mL were eligible. Stratification factors: resection status (R0/R1), lymph node status (LN+/−), & geographic region. Tx was initiated ≤ 12 wks postsurgery. Pts received nab-P 125 mg/m2 + G 1000 mg/m2 or G 1000 mg/m2 on days 1, 8, 15 of six 28-day cycles. Primary endpoint was disease-free survival (DFS) by independent reviewer (IR); IRs received baseline clinical data & scans. Secondary endpoints were OS & safety. ≈438 DFS events were needed for 90% power to detect an HR for disease recurrence or death of 0.73 with nab-P/G vs G at a 2-sided significance level of 0.05. Results: 866 pts were randomized. Median age was 64 y (range, 34 - 86); most pts had ECOG PS 0 (60%), LN+ (72%), & R0 (76%). 69% of pts completed 6 tx cycles ( nab-P/G, 66%; G, 71%). Median follow up for OS was 38.5 mo. Median IR-assessed DFS (439 events) was 19.4 mo ( nab-P/G) vs 18.8 mo (G) (HR, 0.88; 95% CI, 0.729 - 1.063; stratified log-rank P = 0.1824). Investigator-assessed DFS (571 events) was 16.6 mo ( nab-P/G) vs 13.7 mo (G) (HR, 0.82; 95% CI, 0.694 - 0.965; nominal P = 0.0168). Interim OS (427 events) was 40.5 mo ( nab-P/G) vs 36.2 mo (G) (HR, 0.82; 95% CI, 0.680 - 0.996; nominal P = 0.045). Grade ≥ 3 TEAEs were reported in 86% vs 68% of pts with nab-P/G vs G. The most common grade ≥ 3 hematologic & nonhematologic TEAEs with nab-P/G vs G were neutropenia (49% vs 43%) & fatigue (10% vs 3%). TEAEs led to death in 2 pts in each arm. Conclusions: IR DFS with nab-P/G was not significantly longer vs G; median DFS with G was longer than historical data. DFS by investigator (sensitivity analysis) and interim OS were improved with nab-P/G vs G (HR 0.82 for both). Adjuvant nab-P/G may be an option for pts who are ineligible for FOLFIRINOX. Additional OS follow-up may better support nab-P/G as an option in the adjuvant setting. Clinical trial information: NCT01964430.
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- 2019
36. DNA damage repair (DDR) gene alterations as a predictive biomarker for response to platinum-containing chemotherapy in advanced biliary tract cancer (BTC)
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Jae Ho Jeong, Deokhoon Kim, Kyu-Pyo Kim, Baek-Yeol Ryoo, Changhoon Yoo, H. Chae, and Heung-Moon Chang
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Cancer Research ,Chemotherapy ,Biliary tract cancer ,Oncology ,business.industry ,medicine.medical_treatment ,medicine ,Cancer research ,Molecular Profile ,DNA Damage Repair ,business ,Gene ,Predictive biomarker - Abstract
4078 Background: Although many studies using whole-exome sequencing or targeted sequencing have reported the molecular profile of BTC, its clinical implications remains unclear. In this study, we assessed a predictive role of DDR gene mutations in advanced BTC patients treated with platinum-containing regimen. Methods: Eighty-eight patients with pathologically-confirmed BTC who received first-line gemcitabine-cisplatin combination (n = 69) or fluoropyrimidine-oxaliplatin combination (n = 19) were included in this analysis. Targeted exome sequencing was performed using Foundation Medicine T7 assay or in-house OncoPanel AMC. Germline or somatic mutations in ATM, ATR, BAP1, BARD1, BRCA1, BRCA2, BRIP1, CHEK2, FAM175A, GEN1, MLH1, MSH2, MSH6, MRE11A, NBN, PALB2, PMS2, RAD50, RAD51, RAD51C, RAD51D, and XRCC2 were classified as DDR gene mutations. Data regarding baseline characteristics and treatment outcomes were retrospectively obtained from medical records. Results: The median age was 62 years (range, 25-78), with male comprising 64.8% (n = 57). By primary tumor site, 21 patients with GBC (23.9%), 44 with ICC (50.0%) and 23 with ECC (26.1%) were included. Most patients received palliative chemotherapy for their initially metastatic (50.0%) or recurred (44.3%) disease; the rest 5.7% had locally advanced disease. The median PFS and OS of overall patients were 7.1 and 16.1 months, respectively with median follow-up duration of 20.2 months. DDR gene mutations were found in 63.5% of patients. BRCA2 (18.2%) was most frequently mutated, followed by ATM (13.6%), and ATR (8.0%). DDR gene mutations were significantly associated with prolonged PFS (presence vs. absence; median, 6.9 vs. 5.7 months; P = 0.013) and OS (median, 21.0 vs. 13.3 months, P = 0.009). The impact of DDR gene mutations remained significant in multivariate analyses for PFS that included other prognostic factors (hazard ratio, 0.51; P = 0.009), but not for OS. Conclusions: The presence of DDR gene mutations might be a promising predictive biomarker for response to platinum-based chemotherapies in advanced BTC. Future investigation using novel agents targeting DDR gene alteration in BTC are warranted.
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- 2019
37. Clinical Outcomes of Conversion Surgery after Neoadjuvant Chemotherapy in Patients with Borderline Resectable and Locally Advanced Unresectable Pancreatic Cancer: A Single-Center, Retrospective Analysis
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Dae Wook Hwang, Do Hyun Park, Jun Ho Kang, Changhoon Yoo, Ki Byung Song, Sang Soo Lee, Baek-Yeol Ryoo, Heung-Moon Chang, Sang Hyun Shin, Sung Koo Lee, Jae Ho Jeong, Kyu-Pyo Kim, Myung-Hwan Kim, Jae Hoon Lee, Tae Jun Song, Jin-Hong Park, Dong Wan Seo, and Song Cheol Kim
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0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,FOLFIRINOX ,medicine.medical_treatment ,pancreatic cancer ,Single Center ,lcsh:RC254-282 ,Article ,03 medical and health sciences ,0302 clinical medicine ,Borderline resectable ,Pancreatic cancer ,medicine ,Prospective cohort study ,Chemotherapy ,business.industry ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,locally advanced pancreatic cancer ,Gemcitabine ,Surgery ,Clinical trial ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,business ,borderline resectable pancreatic cancer ,neoadjuvant chemotherapy ,medicine.drug - Abstract
The clinical benefit and potential risks of conversion surgery after neoadjuvant chemotherapy (NACT) have not been fully investigated in patients with borderline resectable pancreatic cancer (BRPC) and locally advanced unresectable pancreatic cancer (LAPC). Therefore, this has been evaluated in a retrospective, prospective cohort-based analysis. Between October 2005 and April 2017, 135 patients (65 with BRPC and 70 with LAPC) received conversion surgery after NACT. Exploratory analysis to assess clinical outcomes in comparison with patients who underwent upfront surgery in the same time period (n = 359) was also conducted. NACT with gemcitabine-based regimens (including gemcitabine monotherapy, gemcitabine-capecitabine combination, and gemcitabine-erlotinib combination) was used in 69 patients (51%) and FOLFIRINOX in 66 patients (49%). The median overall survival (OS) and disease-free survival (DFS) from the time of surgery was 25.4 months (95% CI, 18.6&ndash, 32.2 months) and 9.0 months (95% CI, 6.8&ndash, 11.2 months), respectively. The median OS and progression-free survival from the initiation of NACT was 29.7 months (95% CI, 22.5&ndash, 36.8 months) and 13.4 months (95% CI, 12.5&ndash, 14.4 months), respectively. In the exploratory analysis, conversion surgery after NACT was associated with a better median OS and DFS than upfront surgery (vs. 17.1 months, 95% CI, 15.5&ndash, 18.7 months, p = 0.001 and vs. 7.1 months, 95% CI, 6.4&ndash, 7.8 months, p = 0.005, respectively). There was no difference in length of hospital stay between the two groups, and conversion surgery after NACT showed a significantly lower incidence of postoperative complications than upfront surgery (38% vs. 27%, p = 0.03). Conversion surgery after NACT is a feasible and effective therapeutic strategy for the treatment of patients with BRPC and LAPC. Further clinical trials investigating optimal therapeutic strategies for BRPC and LAPC are warranted.
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- 2019
38. Neoadjuvant chemotherapy followed by surgery versus upfront surgery in patients with borderline resectable and locally advanced unresectable pancreatic adenocarcinoma
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Dong Wan Seo, Myung-Hwan Kim, Dae Wook Hwang, Sang Soo Lee, Sung Koo Lee, Jae Hoon Lee, Heung-Moon Chang, Song Cheol Kim, J. H. Kang, Jae Ho Jeong, Kyu-Pyo Kim, Tae Jun Song, Jin-Hong Park, Sang Hyun Shin, Do Hyun Park, Changhoon Yoo, Ki Byung Song, and Baek-Yeol Ryoo
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Cancer Research ,Chemotherapy ,medicine.medical_specialty ,business.industry ,Potential risk ,medicine.medical_treatment ,Locally advanced ,medicine.disease ,Surgery ,Oncology ,Borderline resectable ,medicine ,Adenocarcinoma ,In patient ,business - Abstract
312 Background: Although neoadjuvant chemotherapy (NACT) has been widely investigated, the magnitude of the clinical benefit and the potential risk of NACT followed by surgery compared with upfront surgery remains unclear for patients with locally advanced pancreatic cancer (LAPC). Methods: This retrospective, prospective cohort-based analysis included 135 patients who underwent NACT followed by surgery and 359 patients who received upfront surgery for LAPC between October 2005 and April 2017. Disease-free survival (DFS) and overall survival (OS) from surgery were compared between the two groups. Results: There were no significant differences in gender (male, 53% vs 56%) and age (median 60 vs 61 years) between the NACT followed by surgery group and upfront surgery group. As NACT, gemcitabine-based regimens and FOLFIRINOX were used in 69 (51%) and 66 (49%) patients, respectively. The NACT followed by surgery group showed significantly less advanced T stage (T3–4, 93% vs 99%, p = 0.001) and N stage (N+, 49% vs 71%, p < 0.001) than the upfront surgery group. NACT followed by surgery was significantly associated with better OS (median, 25.4 [18.6–32.2] vs 17.1 [15.5–18.7] months, p = 0.001) and DFS (median, 9.0 [95% CI, 6.8–11.2] vs 7.1 [6.4–7.8] months, p = 0.005) than upfront surgery. These results were consistent in the multivariate analysis for OS (adjusted hazard ratio [aHR], 0.73 [95% CI, 0.56–0.96], p = 0.02) and DFS (aHR, 0.72 [95% CI, 0.56–0.93], p = 0.01). There was no difference in length of hospital stay (median 13 vs 17 days, p = 0.14) for surgery between the two groups, and the NACT followed by surgery group showed a significantly lower incidence of postoperative complication than the upfront surgery group (38% vs 27%, p = 0.03). Conclusions: The present study revealed that NACT followed by surgery may provide survival benefit compared with upfront surgery in LAPC without causing significant safety issues.
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- 2019
39. FOENIX-101: A phase II trial of TAS-120 in patients with intrahepatic cholangiocarcinoma harboring FGFR2 gene rearrangements
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Do-Youn Oh, Rastilav Bahleda, Juan W. Valle, Jerry Huang, Junji Furuse, Milind Javle, Nataliya Volodymyrivna Uboha, Li-Tzong Chen, Mitesh J. Borad, Lipika Goyal, Heinz-Josef Klümpen, Heung-Moon Chang, Chigusa Morizane, Peter J. O'Dwyer, John Bridgewater, Markus Moehler, Daneng Li, and Robin Kate Kelley
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Cancer Research ,business.industry ,Standard treatment ,Intrahepatic bile ducts ,Cancer ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,Oncology ,030220 oncology & carcinogenesis ,Cancer research ,medicine ,Cytotoxic T cell ,In patient ,business ,Gene ,Intrahepatic Cholangiocarcinoma ,030215 immunology - Abstract
TPS468 Background: Intrahepatic cholangiocarcinoma (iCCA) is a cancer arising from the intrahepatic bile duct. Standard treatment of unresectable, recurrent, or metastatic iCCA is with cytotoxic chemotherapy. FGFR2 gene fusions have been identified as oncogenic drivers in 10–20% of iCCA tumors, but no targeted agents have been established to date. TAS-120 is an investigational irreversible FGFR1–4 inhibitor in development as a once-daily oral treatment for iCCA. Based on initial studies in multiple tumor types expressing FGFR abnormalities, iCCA was identified as a tumor type with potential susceptibility to FGFR inhibition and high unmet need. A phase I portion of the trial with an iCCA expansion cohort demonstrated tolerability and preliminary evidence of clinical efficacy with TAS-120 as a continuous, once-daily oral treatment in patients with iCCA. The most common AEs in the phase I portion of the trial were hyperphosphatemia, a mechanism-based on-target side effect, cutaneous AEs, and gastrointestinal AEs. The phase I portion of the study is continuing to enroll, and final results are anticipated in early 2019. Based on preliminary findings, a phase II portion of the study (FOENIX-101; clinicaltrials.gov registration NCT02052778) has been initiated. Methods: The phase II portion of the trial is a global, single-arm study of TAS-120 in patients with iCCA harboring FGFR2 gene rearrangements. The study will enroll approximately 100 adult patients with locally advanced or metastatic iCCA that progressed after ≥ 1 systemic therapies and with an ECOG PS of 0 or 1. Prior systemic therapy must include gemcitabine plus platinum-based chemotherapy. Screening for FGFR2 gene rearrangements will be performed at a central laboratory. The primary endpoint is objective response rate based on RECIST v1.1. Secondary endpoints include duration of response, disease control rate, overall survival, progression-free survival, safety, and health-related quality of life. Clinical trial information: NCT02052778.
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- 2019
40. A UGT1A1*28 and *6 genotype-directed phase I dose-escalation trial of irinotecan with fixed-dose capecitabine in Korean patients with metastatic colorectal cancer
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Kyu-Pyo Kim, Jae-Gook Shin, Tae Won Kim, Jae-Lyun Lee, Ho-Sook Kim, Jung Shin Lee, Sun Jin Sym, Yong Sang Hong, Yoon-Koo Kang, Kyun-Seop Bae, and Heung-Moon Chang
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Male ,Oncology ,Cancer Research ,Colorectal cancer ,Kaplan-Meier Estimate ,Toxicology ,Deoxycytidine ,Antineoplastic Combined Chemotherapy Protocols ,Genotype ,Dose escalation ,Pharmacology (medical) ,Glucuronosyltransferase ,Neoplasm Metastasis ,Young adult ,Infusions, Intravenous ,Middle Aged ,Tolerability ,Female ,Fluorouracil ,Colorectal Neoplasms ,therapeutics ,medicine.drug ,Adult ,medicine.medical_specialty ,Adolescent ,Maximum Tolerated Dose ,Irinotecan ,digestive system ,Fixed dose ,Disease-Free Survival ,Drug Administration Schedule ,Capecitabine ,Young Adult ,Internal medicine ,Republic of Korea ,medicine ,Humans ,neoplasms ,Aged ,Pharmacology ,Dose-Response Relationship, Drug ,business.industry ,medicine.disease ,digestive system diseases ,stomatognathic diseases ,Camptothecin ,business - Abstract
UGT1A1 genotypes are important when considering treatment with irinotecan-containing regimens. In this study, we determined the dose, efficacy, and tolerability of irinotecan according to UGT1A1 genotypes when combined with capecitabine in patients with metastatic colorectal cancer.Patients with histologically confirmed metastatic adenocarcinoma of the colon or rectum were enrolled into a UGT1A1 genotype-directed dose-escalation trial of irinotecan plus fixed-dose capecitabine (2,000 mg/m(2)/day). The starting dose of irinotecan was different for each genotype group and ranged from 200 to 280 mg/m(2). Pharmacokinetic concentrations of irinotecan and metabolites were determined by LC/MS/MS.Fifty patients were genotyped for UGT1A1 *28 and *6, and grouped according to the numbers of defective alleles (DA): 0, 1, and 2. Plasma concentrations of irinotecan, SN-38, and SN-38G were measured. The maximum tolerated dose of irinotecan was 350 mg/m(2) for the 0 and 1 DA groups, and 200 mg/m(2) for the 2 DA group. For the 0, 1, and 2 DA groups, mean AUClast ratios of SN-38G to SN-38 were 7.72, 5.71, and 2.72 (P = 0.0023) and relative dose intensities at recommended dose were 85, 83, and 97 %.Irinotecan dosing based on UGT1A1*28 and *6 is feasible, and higher doses of irinotecan can be safely administered in patients with 0 or 1 DA, compared to those with 2 DA.
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- 2013
41. Two-year adjuvant imatinib mesylate after complete resection of localized, high-risk GIST with KIT exon 11 mutation
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Seock-Ah Im, Min-Hee Ryu, Sook Ryun Park, Tae Won Kim, Won Ki Kang, Kyung Hae Jung, Yoon-Koo Kang, Jae-Lyun Lee, Do-Youn Oh, Byung Woog Kang, and Heung Moon Chang
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Adult ,Male ,Cancer Research ,Gastrointestinal Stromal Tumors ,medicine.medical_treatment ,Antineoplastic Agents ,Toxicology ,Disease-Free Survival ,Piperazines ,Exon ,Republic of Korea ,medicine ,Humans ,Pharmacology (medical) ,Prospective Studies ,Stromal tumor ,Prospective cohort study ,Aged ,Gastrointestinal Neoplasms ,Pharmacology ,GiST ,business.industry ,Imatinib ,Exons ,Middle Aged ,Proto-Oncogene Proteins c-kit ,Pyrimidines ,Treatment Outcome ,Imatinib mesylate ,Oncology ,Chemotherapy, Adjuvant ,Benzamides ,Mutation ,Mutation (genetic algorithm) ,Imatinib Mesylate ,Cancer research ,Female ,Neoplasm Recurrence, Local ,business ,Adjuvant ,Follow-Up Studies ,medicine.drug - Abstract
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.Imatinib 400 mg/d was administered until disease recurrence, intolerable toxicities, or for 2 years. The primary end point was recurrence-free survival.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 (P0.0001). 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.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.
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- 2012
42. A phase I study of DHP107, a mucoadhesive lipid form of oral paclitaxel, in patients with advanced solid tumors: Crossover comparisons with intravenous paclitaxel
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Hyeong-Seok Lim, Tae Won Kim, Kyu-Pyo Kim, Yong Sang Hong, Jae-Lyun Lee, Min-Hee Ryu, Yoon-Koo Kang, Kyun-Seop Bae, Heung Moon Chang, and Hyeyoun Kim
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Adult ,Male ,medicine.medical_specialty ,Maximum Tolerated Dose ,Paclitaxel ,Administration, Oral ,Pharmacology ,Neutropenia ,Gastroenterology ,Young Adult ,chemistry.chemical_compound ,Refractory ,Pharmacokinetics ,Neoplasms ,Internal medicine ,Humans ,Medicine ,Pharmacology (medical) ,Aged ,Cross-Over Studies ,business.industry ,Middle Aged ,medicine.disease ,Antineoplastic Agents, Phytogenic ,Crossover study ,Clinical trial ,Diarrhea ,Oncology ,chemistry ,Toxicity ,Administration, Intravenous ,Female ,medicine.symptom ,business - Abstract
Purpose This study investigated the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), and pharmacokinetic (PK) profiles of DHP107, a novel oral paclitaxel containing neither Cremophor EL nor P-glycoprotein (P-gp) inhibitor. Patients and methods Patients with advanced solid tumors refractory to all standard treatments were administered a single oral dose of DHP107 on a dose-escalating schedule (60–600 mg/m2) during the first chemotherapy cycle, and intravenous paclitaxel 175 mg/m2 during subsequent cycles. Cohorts of 3 patients were treated at each dose level provided no DLTs were observed. The pharmacokinetics of paclitaxel and its metabolites were investigated for oral DHP107 and intravenous paclitaxel. Results Thirty-four patients were enrolled. Dose-limiting toxicities were not observed, even at the highest dose level (600 mg/m2). Further dose escalation was not performed because pharmacokinetics did not increase proportionally at doses above 250 mg/m2. The coefficient of variance of AUClast DHP107 ranged from 11.8 % to 34.0 %, comparable to 24.4 % of intravenous paclitaxel 175 mg/m2. There were no grade 4 toxicities, whereas grade 3 toxicities included diarrhea (12.1 %), neutropenia (6.1 %) and fatigue (3.0 %). While no objective responses were observed, 11 patients (33.3 %) showed stable disease. Conclusions DHP107 was safe and feasible in patients with advanced malignancies. As exposure of paclitaxel plateau among patients receiving more than 250 mg/m2 of DHP107, the dose escalation of DHP107 may be limited to 250 mg/m2 in further clinical trials.
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- 2012
43. Comprehensive analysis of HER2 expression and gene amplification in gastric cancers using immunohistochemistry and in situ hybridization: which scoring system should we use?
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Hye Jin Park, Hee Sang Hwang, Se Jin Jang, Byung Sik Kim, Jeong Hwan Yook, Heung Moon Chang, Young Su Park, Yoon-Koo Kang, and Min Hee Ryu
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Adult ,Male ,Receptor, ErbB-2 ,medicine.drug_class ,Gene Expression ,Adenocarcinoma ,Biology ,Monoclonal antibody ,HercepTest ,Pathology and Forensic Medicine ,Young Adult ,Predictive Value of Tests ,Stomach Neoplasms ,Trastuzumab ,Biomarkers, Tumor ,medicine ,Humans ,skin and connective tissue diseases ,In Situ Hybridization, Fluorescence ,Aged ,Neoplasm Staging ,Retrospective Studies ,Tissue microarray ,medicine.diagnostic_test ,Gene Amplification ,Cancer ,Middle Aged ,medicine.disease ,Immunohistochemistry ,Molecular biology ,Tissue Array Analysis ,Monoclonal ,Female ,medicine.drug ,Fluorescence in situ hybridization - Abstract
It has been reported that HER2 expression is different in gastric and breast cancers, and a gastric cancer scoring system (GCSS) has recently been suggested. We investigated HER2 protein expression using GCSS and a breast cancer scoring system (BCSS) and correlated it with HER2 gene amplification. HER2 status was evaluated in 1091 cases by analyzing tissue microarrays constructed using 2 different cores from each case. Polyclonal (HercepTest) and monoclonal (Pathway) antibodies were used for immunohistochemistry (IHC), and results were scored by BCSS and GCSS. Gene amplification was evaluated by automated dual-color silver-enhanced in situ hybridization (SISH) in all cases and correlated with the results from fluorescence in situ hybridization (FISH) in 590 cases. The concordance between the IHC results using polyclonal and monoclonal antibodies was high (κ = 0.785). The results of dual-color SISH and FISH showed very high concordance as well (κ = 0.918). GCSS was significantly more sensitive for detecting SISH positivity than was BCSS in both antibodies (polyclonal, P = .003; monoclonal, P < .001), but specificity was higher in BCSS than GCSS (polyclonal, P = .004; monoclonal, P < .001). It has been recently shown that HER2-overexpressing patients with unresectable gastric cancer benefited from trastuzumab therapy. Because IHC is recommended before gene amplification studies in HER2 testing, GCSS should be used for evaluating HER2 expression in gastric cancers.
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- 2012
44. Gemcitabine and oxaliplatin with or without erlotinib in advanced biliary-tract cancer: a multicentre, open-label, randomised, phase 3 study
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Jeeyun, Lee, Se Hoon, Park, Heung-Moon, Chang, Jun Suk, Kim, Hye Jin, Choi, Myung Ah, Lee, Joung Soon, Jang, Joung Soon, Chang, Hei Cheul, Jeung, Jung Hun, Kang, Hyun Woo, Lee, Dong Bok, Shin, Hye Jin, Kang, Jong-Mu, Sun, Joon Oh, Park, Young Suk, Park, Won Ki, Kang, and Ho Yeong, Lim
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Male ,Oncology ,medicine.medical_specialty ,Organoplatinum Compounds ,medicine.medical_treatment ,GemOx ,Deoxycytidine ,Disease-Free Survival ,Cholangiocarcinoma ,Erlotinib Hydrochloride ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Medicine ,Neoplasm Metastasis ,neoplasms ,Aged ,Neoplasm Staging ,Chemotherapy ,business.industry ,Standard treatment ,Combination chemotherapy ,Middle Aged ,medicine.disease ,Gemcitabine ,Oxaliplatin ,Biliary Tract Neoplasms ,Disease Progression ,Quinazolines ,Female ,Gallbladder Neoplasms ,Erlotinib ,business ,Febrile neutropenia ,medicine.drug - Abstract
Summary Background Combination chemotherapy with gemcitabine and a platinum-based agent is regarded as a standard treatment for patients with advanced biliary-tract cancer. Results of phase 2 trials of single-agent erlotinib in biliary-tract cancer and of gemcitabine plus erlotinib in pancreatic cancer have shown modest benefits. Therefore, we aimed to investigate the efficacy of gemcitabine and oxaliplatin plus erlotinib versus chemotherapy alone for advanced biliary-tract cancer. Methods In this open label, randomised, phase 3 trial, we randomly assigned patients (in a 1:1 ratio) with metastatic biliary-tract cancer (cholangiocarcinoma, gallbladder cancer, or ampulla of Vater cancer) to receive either first-line treatment with chemotherapy alone (gemcitabine 1000 mg/m 2 on day 1 and oxaliplatin 100 mg/m 2 on day 2) or chemotherapy plus erlotinib (100 mg daily). Treatment was repeated every 2 weeks until disease progression or unacceptable toxic effects. Randomisation was done centrally (stratified by participating centre and presence of measurable lesion). The primary endpoint was progression-free survival. Analyses were by intention-to-treat. This study is registered with ClinicalTrials.gov, number NCT01149122. Findings 133 patients were randomly assigned to the chemotherapy alone group and 135 to the chemotherapy plus erlotinib group. The groups were balanced except for a higher proportion of patients with cholangiocarcinoma in the group given erlotinib than in the chemotherapy alone group (96 [71%] patients vs 84 [63%]). Median progression-free survival was 4·2 months (95% CI 2·7–5·7) in the chemotherapy alone group and 5·8 months (95% CI 4·6–7·0) in the chemotherapy plus erlotinib group (hazard ratio [HR] 0·80, 95% CI 0·61–1·03; p=0·087). Significantly more patients had an objective response in the chemotherapy plus erlotinib group than in the chemotherapy alone group (40 patients vs 21 patients; p=0·005), but median overall survival was the same in both groups (9·5 months [95% CI 7·5–11·5] in the chemotherapy alone group and 9·5 months [7·6–11·4] in the chemotherapy plus erlotinib group; HR 0·93, 0·69–1·25; p=0·611). All-cause deaths within 30 days of random assignment occurred in one (1%) of the patients in the chemotherapy alone group and in four (3%) of those in the chemotherapy plus erlotinib group. The most common grade 3–4 adverse event was febrile neutropenia (eight [6%] patients in the chemotherapy alone group and six [4%] in the chemotherapy plus erlotinib group). No patient died of treatment-related causes during the study. Subgroup analyses by primary site of disease showed that for patients with cholangiocarcinoma, the addition of erlotinib to chemotherapy significantly prolonged median progression-free survival (5·9 months [95% CI 4·7–7·1] for chemotherapy plus erlotinib vs 3·0 months [1·1–4·9] for chemotherapy alone; HR 0·73, 95% CI 0·53–1·00; p=0·049). Interpretation Although no significant difference in progression-free survival was noted between groups, the addition of erlotinib to gemcitabine and oxaliplatin showed antitumour activity and might be a treatment option for patients with cholangiocarcinoma. Funding None.
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- 2012
45. Genetic Polymorphisms of FcγRIIa and FcγRIIIa Are Not Predictive of Clinical Outcomes after Cetuximab plus Irinotecan Chemotherapy in Patients with Metastatic Colorectal Cancer
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Kyu-Pyo Kim, Min-Hee Ryu, Seong Joon Park, Heung Moon Chang, Yoon-Koo Kang, Yong Sang Hong, Jae-Lyun Lee, Young-Soon Na, Chang Sik Yu, Tae-Won Kim, Dong-Hoon Jin, Jin Cheon Kim, and Yong Chel Ahn
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Oncology ,Cancer Research ,medicine.medical_specialty ,genetic structures ,medicine.drug_class ,Colorectal cancer ,medicine.medical_treatment ,medicine.disease_cause ,Monoclonal antibody ,Growth factor receptor ,Internal medicine ,medicine ,neoplasms ,Chemotherapy ,integumentary system ,Cetuximab ,business.industry ,General Medicine ,medicine.disease ,digestive system diseases ,Irinotecan ,Monoclonal ,Cancer research ,KRAS ,business ,medicine.drug - Abstract
Objective: The anti-epidermal growth factor receptor monoclonal antibody cetuximab has been shown to be effective in patients with wild-type KRAS metastatic colorectal cancer (mCRC). Fragment C γ receptor (FcγR) polymorphisms may predict the effectiveness of cetuximab, but this has not been established. This study investigated the clinical relevance of FcγR gene polymorphisms and KRAS status in iri-notecan-refractory mCRC patients treated with cetuximab. Methods: The total number of irinotecan-refractory mCRC patients studied was 118. Among them, 117 and 107 patients were screened for KRAS mutations and genetic polymorphisms of FcγRIIa-131H/R and FcγRIIIa-158V/F, respectively. The association of FcγR polymorphisms and KRAS mutations with clinical outcome was analyzed. Results:KRAS mutations were found in 33 patients (27.1%). Wild-type KRAS was associated with a better response rate (p < 0.001), longer progression-free survival (p < 0.001) and longer overall survival (p < 0.001). FcγRIIa H/H, H/R and R/R polymorphisms were observed in 54, 49 and 4 patients, respectively, and FcγRIIIa V/V, V/F and F/F polymorphisms were observed in 6, 65, and 36 patients, respectively. Clinical outcomes were not significantly associated with either FcγRIIa or FcγRIIIa polymorphisms or with combinations of KRAS status and FcγR polymorphisms. Conclusion: The FcγRIIa and FcγRIIIa polymorphisms may not be useful molecular biomarkers for the activity of cetuximab in patients with mCRC.
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- 2012
46. A Phase II Study of Clinical Outcomes of 3-Week Cycles of Irinotecan and S-1 in Patients with Previously Untreated Metastatic Colorectal Cancer: Influence of the UGT1A1 and CYP2A6 Polymorphisms on Clinical Activity
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Heung Moon Chang, Sung Sook Lee, Ho-Sook Kim, Yoon Choi, Yong Sang Hong, Baek-Yeol Ryoo, Jae-Gook Shin, Tae-Won Kim, Yoon-Koo Kang, Kyu-Pyo Kim, Min-Hee Ryu, and Jae-Lyun Lee
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,urogenital system ,business.industry ,Colorectal cancer ,Phases of clinical research ,General Medicine ,urologic and male genital diseases ,medicine.disease ,Tegafur ,digestive system diseases ,Irinotecan ,Regimen ,Internal medicine ,medicine ,heterocyclic compounds ,In patient ,CYP2A6 ,business ,neoplasms ,Camptothecin ,medicine.drug - Abstract
Objectives: We investigated the efficacy and safety of the combination of irinotecan (CPT-11) and S-1 (IRIS regimen) as a first-line treatment in patients with metastatic colorectal cancer. We also evaluated the association between UGT1A1 and CYP2A6 polymorphisms and clinical phenotypes. Methods: The patients received CPT-11 (225 mg/m2) on day 1 and S-1 (80 mg/m2) on days 1–14 every 3 weeks. The association of the UGT1A1 (*6 and *28) and CYP2A6(*4, *7, *9, and *10) polymorphisms with toxicities and efficacy were analyzed. Results: Thirty patients were treated. The overall response rate was 66.7% (95% CI 48.7–84.6). The median time to progression was 7.6 months (95% CI 5.8–9.5). The most common grade 3/4 hematologic and non-hematologic toxicity were neutropenia (53.4%) and diarrhea (16.7%), respectively. The allele frequencies of UGT1A1*6 and *28 were 15.5 and 10.3%, respectively. The frequencies of CYP2A6*4, *7, *9, and *10 were 15.5, 8.6, 29.3, and 3.5%, respectively. Stratification of patients according to the number of UGT1A1*28 and *6 alleles showed a significant correlation between the number of defective alleles and the incidence of grade 3/4 neutropenia. Conclusions: Our results indicate that IRIS is a promising first-line regimen in patients with metastatic colorectal cancer. Severe neutropenia may be associated with interindividual variations in UGT1A1 polymorphisms.
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- 2012
47. Combination Chemotherapy of Oxaliplatin, 5-Fluorouracil, and Leucovorin in 5-Fluorouracil-Pretreated Patients with Metastatic Colorectal Cancer
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Young Suk Park, Eun Kyung Cho, Jae Hoon Lee, Jin Seok Ahn, Young Iee Park, Myung Jue Ahn, Dong Bok Shin, Jae Hwan Oh, Heung Moon Chang, Soo Mee Bang, and Jung Ae Lee
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Cancer Research ,medicine.medical_specialty ,Chemotherapy ,business.industry ,Colorectal cancer ,medicine.medical_treatment ,Combination chemotherapy ,medicine.disease ,Gastroenterology ,Oxaliplatin ,Surgery ,Regimen ,Oncology ,Fluorouracil ,Internal medicine ,Toxicity ,medicine ,Progression-free survival ,business ,medicine.drug - Abstract
PURPOSE To evaluate the efficacy and toxicity of oxaliplatin in combination with 5-fluorouracil (5-FU) and leucovorin (LV) in patients with metastatic colorectal cancer who previously treated with 5-FU-based chemotherapy. MATERIALS AND METHODS Between April 1999 and January 2001, thirty-two patients were enrolled in this study. Oxaliplatin 130 mg/m2 was given intravenously (IV) on day 1 as was 5-FU 500 mg/m2 IV followed by continuous infusion of 5-FU 3,000 mg/m2 and LV 100 mg/m2 for 48 hours administered every 3 weeks. Six patients had received 5-FU as an adjuvant setting and 26 patients as a palliative regimen. RESULTS The median age of the patients was 50 years (range; 19-69) and the dominant sites of metastasis were the liver, lung or both in 9, 5 and 2 patients respectively. In 30 evaluable patients, the overall response rate was 27% including 1 complete response and 7 partial responses. The median response duration was 28 weeks (95% confidence interval; 22~34 weeks) and the median progression free survival of all patients was 24 weeks (95% confidence interval; 15~33 weeks). A median 5 cycles (range; 2~9) and total 155 cycles were performed in 32 patients. 150 cycles were evaluable for toxicity. The most common hematologic toxicity was grade 1~2 anemia in 78 cycles (52%). Leukopenia (39%) and thrombocytopenia (23%) were fully reversible. The most common non-hematologic toxicity was nausea/vomiting (43/30%) followed by diarrhea (23%), hepatotoxicity (21%) and neurotoxicity (21%). One patient ceased therapy due to grade 4 diarrhea. No other severe toxicity interrupted this treatment. CONCLUSION Oxaliplatin, 5-FU and LV in combination showed significant activity in previously treated metastatic colorectal cancer with favorable toxicity.
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- 2015
48. Association between deficient mismatch repair system and efficacy to irinotecan-containing chemotherapy in metastatic colon cancer
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Yoon-Koo Kang, Jin Cheon Kim, Tae-Won Kim, Seok-Byung Lim, Chang Sik Yu, Mi-Jung Kim, Heung Moon Chang, Jeong Eun Kim, Yong Sang Hong, Jong Hoon Kim, Jae-Lyun Lee, Se-Jin Jang, and Min-Hee Ryu
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Adult ,Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,Colorectal cancer ,medicine.medical_treatment ,Irinotecan ,MLH1 ,DNA Mismatch Repair ,Disease-Free Survival ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Adaptor Proteins, Signal Transducing ,Aged ,Chemotherapy ,Predictive marker ,business.industry ,Nuclear Proteins ,Microsatellite instability ,General Medicine ,Middle Aged ,Prognosis ,medicine.disease ,digestive system diseases ,Regimen ,MutS Homolog 2 Protein ,Treatment Outcome ,MSH2 ,Colonic Neoplasms ,Camptothecin ,Female ,Microsatellite Instability ,MutL Protein Homolog 1 ,business ,medicine.drug - Abstract
The present study investigated the association between deficient mismatch repair (dMMR) and efficacy outcomes of irinotecan-based first-line chemotherapy in patients with metastatic colorectal cancer (mCRC). Among 297 patients with sporadic mCRC receiving an irinotecan-containing regimen as first-line chemotherapy, 197 with available paraffin-embedded tissues were included in the current analysis. Tumors displaying loss of MMR protein (MLH1 or MSH2) and/or a microsatellite instability-high (MSI-H) genotype by PCR were classified as dMMR. Deficient mismatch repair was found in 23 evaluable tumors, among which eight displayed negativity for MLH1 expression, 11 for MSH2 expression, and four for both. The overall response rate was 47.2% (46.0% in proficient MMR (pMMR) and 56.5% in dMMR), with no significant difference between the two groups (P = 0.569). Median progression-free survival was 8.85 months in patients with dMMR tumors and 6.82 months in patients with pMMR tumors, but this difference did not reach statistical significance (P = 0.089). Median overall survival was not different between the two groups (P = 0.413). Efficacy outcomes of first-line irinotecan-based chemotherapy did not differ significantly between mCRC patients with pMMR and those with dMMR. Our data collectively indicate that MMR status is not effective as a single predictive marker for response to irinotecan-based chemotherapy in mCRC patients.
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- 2011
49. Postoperative Chemoradiotherapy for Extrahepatic Bile Duct Cancer
- Author
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Jin-Hong Park, Young-Joo Lee, Young Seok Kim, Shin Hwang, Heung Moon Chang, Kwang-Min Park, Si Yeol Song, Eun Kyung Choi, Jae-Lyun Lee, Sung-Gyu Lee, Tae Won Kim, Seung Do Ahn, Sang-wook Lee, Yu Sun Lee, Jong Hoon Kim, and Sang Min Yoon
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Adult ,Male ,Antimetabolites, Antineoplastic ,Cancer Research ,medicine.medical_specialty ,Neoplasm, Residual ,CA-19-9 Antigen ,Postoperative chemoradiotherapy ,medicine.medical_treatment ,Extrahepatic bile duct cancer ,Gastroenterology ,Bile Ducts, Extrahepatic ,Internal medicine ,Republic of Korea ,medicine ,Adjuvant therapy ,Humans ,Radiology, Nuclear Medicine and imaging ,Survival analysis ,Aged ,Retrospective Studies ,Chemotherapy ,Radiation ,business.industry ,Radiotherapy Dosage ,Middle Aged ,Combined Modality Therapy ,Survival Analysis ,Surgery ,Radiation therapy ,Bile Duct Neoplasms ,Oncology ,Biliary tract ,Female ,Fluorouracil ,Neoplasm Recurrence, Local ,Radiotherapy, Conformal ,business ,Adjuvant - Abstract
Purpose To evaluate the effect of postoperative concurrent chemoradiotherapy using three-dimensional conformal radiotherapy and to identify the prognostic factors that influence survival in patients with extrahepatic bile duct cancer. Methods and Materials We retrospectively analyzed the data from 101 patients with extrahepatic bile duct cancer who had undergone postoperative concurrent chemoradiotherapy using three-dimensional conformal radiotherapy. Of the 101 patients, 52 (51%) had undergone complete resection (R0 resection) and 49 (49%) had microscopic or macroscopic residual tumors (R1 or R2 resection). The median radiation dose was 50 Gy. Also, 85 patients (84%) underwent concurrent chemotherapy with 5-fluorouracil. Results The median follow-up period was 47 months for the surviving patients. The 5-year overall survival rate was 34% for all patients. A comparison between patients with R0 and R1 resection indicated no significant difference in the 5-year overall survival (44% vs. 33%, p = .2779), progression-free survival (35% vs. 22%, p = .3107), or locoregional progression-free survival (75% vs. 63%, p = .2784) rates. An analysis of the first failure site in the 89 patients with R0 or R1 resection indicated isolated locoregional recurrence in 7 patients. Elevated postoperative carbohydrate antigen 19-9 level was an independent prognostic factor for overall survival ( p = .001) and progression-free survival ( p = .033). A total of 3 patients developed Grade 3 or greater late toxicity. Conclusion Adjuvant concurrent chemoradiotherapy using three-dimensional conformal radiotherapy appears to improve locoregional control and survival in extrahepatic bile duct cancer patients with R1 resection. The postoperative carbohydrate antigen 19-9 level might be a useful prognostic marker to select patients for more intensified adjuvant therapy.
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- 2011
50. A phase I study of combination therapy with S-1 and irinotecan in patients with previously untreated metastatic or recurrent colorectal cancer
- Author
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Min-Hee Ryu, Jae-Lyun Lee, Sung Sook Lee, Yoon Choi, Tae Won Kim, Heung Moon Chang, Yong Sang Hong, and Yoon-Koo Kang
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Adult ,Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,Maximum Tolerated Dose ,Combination therapy ,Ileus ,Colorectal cancer ,Neutropenia ,Irinotecan ,Toxicology ,Gastroenterology ,Enteritis ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Pharmacology (medical) ,Recurrent Colorectal Cancer ,Neoplasm Metastasis ,Aged ,Tegafur ,Pharmacology ,Dose-Response Relationship, Drug ,business.industry ,Middle Aged ,medicine.disease ,Drug Combinations ,Oxonic Acid ,Diarrhea ,Treatment Outcome ,Camptothecin ,Female ,Neoplasm Recurrence, Local ,medicine.symptom ,Colorectal Neoplasms ,business ,medicine.drug - Abstract
To investigate the combination of S-1 and irinotecan (CPT-11) as an alternative to infusional 5-fluorouracil/leucovorin plus CPT-11, we performed a phase I trial to determine the maximum tolerated dose, recommended dose (RD), and dose-limiting toxicities (DLTs) in patients with metastatic or recurrent colorectal cancer.S-1 and CPT-11 doses were escalated using a standard 3 + 3 design. S-1 was administered orally at 70 mg/m(2) (levels 1-3) or 80 mg/m(2) (levels 4 and 5) for 14 consecutive days followed by 1-week rest. CPT-11 was administered intravenously on day 1, at 175 mg/m(2) (level 1), 200 mg/m(2) (level 2), 225 mg/m(2) (levels 3 and 4), or 250 mg/m(2) (level 5). Treatment was repeated every 3 weeks, unless disease progression or severe toxicities were observed.Twenty-three patients were treated. One patient at each of levels 2 and 4 developed a DLT, grade 3 ileus, and grade 3 diarrhea, respectively. At both levels, an additional three patients did not experience DLTs. At level 5, two of five patients experienced DLTs, including grade 3 enteritis and grade 4 neutropenia for more than 5 days. The RD was determined at level 4 (80 mg/m(2) S-1 and 225 mg/m(2) CPT-11). An objective response was observed in 7 of 17 patients with measurable disease: 2 of 5 at level 2; 3 of 4 at level 4; and 2 of 4 at level 5.The RDs of CPT-11 and S-1 were determined as 225 and 80 mg/m(2), respectively, and further phase II trials are warranted.
- Published
- 2011
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