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7 "Heung-Moon Chang"
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Gastrointestinal cancer
Clinical Outcomes of Surgery after Neoadjuvant Chemotherapy in Locally Advanced Pancreatic Ductal Adenocarcinoma
Yoo Na Lee, Min Kyu Sung, Dae Wook Hwang, Yejong Park, Bong Jun Kwak, Woohyung Lee, Ki Byung Song, Jae Hoon Lee, Changhoon Yoo, Kyu-Pyo Kim, Heung-Moon Chang, Baek-Yeol Ryoo, Song Cheol Kim
Cancer Res Treat. 2024;56(4):1240-1251.   Published online June 19, 2024
DOI: https://doi.org/10.4143/crt.2023.977
AbstractAbstract PDFPubReaderePub
Purpose
Clinical outcomes of surgery after neoadjuvant chemotherapy have not been investigated for locally advanced pancreatic cancer (LAPC), despite well-established outcomes in borderline resectable pancreatic cancer (BRPC). This study aimed to investigate the clinical outcomes of patients with LAPC who underwent curative resection following neoadjuvant chemotherapy.
Materials and Methods
We retrospectively reviewed the records of patients diagnosed with pancreatic adenocarcinoma between January 2017 and December 2020.
Results
Among 1,358 patients, 260 underwent surgery following neoadjuvant chemotherapy. Among 356 LAPC patients, 98 (27.5%) and 147 (35.1%) of 418 BRPC patients underwent surgery after neoadjuvant chemotherapy. Compared to resectable pancreatic cancer (resectable PC) with upfront surgery, both LAPC and BRPC exhibited higher rates of venous resection (28.6% vs. 49.0% vs. 4.0%), arterial resection (30.6% vs. 6.8% vs. 0.5%) and greater estimated blood loss (260.5 vs. 213.1 vs. 70.4 mL). However, hospital stay, readmission rates, and postoperative pancreatic fistula rates (grade B or C) did not differ significantly between LAPC, BRPC, and resectable PC. Overall and relapse-free survival did not differ significantly between LAPC and BRPC patients. The median overall survival was 37.3 months for LAPC and 37.0 months for BRPC. The median relapse-free survival was 22.7 months for LAPC and 26.0 months for BRPC.
Conclusion
Overall survival time and postoperative complications in LAPC patients who underwent curative resection following neoadjuvant chemotherapy showed similar results to those of BRPC patients. Further research is needed to identify specific sub-populations of LAPC patients who benefit most from conversion surgery and to minimize postoperative complications.
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Survival Benefit of Adjuvant Chemotherapy in Patients with Pancreatic Ductal Adenocarcinoma Who Underwent Surgery Following Neoadjuvant FOLFIRINOX
So Heun Lee, Dae Wook Hwang, Changhoon Yoo, Kyu-pyo Kim, Sora Kang, Jae Ho Jeong, Dongwook Oh, Tae Jun Song, Sang Soo Lee, Do Hyun Park, Dong Wan Seo, Jin-hong Park, Ki Byung Song, Jae Hoon Lee, Woohyung Lee, Yejong Park, Bong Jun Kwak, Heung-Moon Chang, Baek-Yeol Ryoo, Song Cheol Kim
Cancer Res Treat. 2023;55(3):956-968.   Published online February 27, 2023
DOI: https://doi.org/10.4143/crt.2022.409
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The benefit of adjuvant chemotherapy following curative-intent surgery in pancreatic ductal adenocarcinoma (PDAC) patients who had received neoadjuvant FOLFIRINOX is unclear. This study aimed to assess the survival benefit of adjuvant chemotherapy in this patient population.
Materials and Methods
This retrospective study included 218 patients with localized non-metastatic PDAC who received neoadjuvant FOLFIRINOX and underwent curative-intent surgery (R0 or R1) between January 2017 and December 2020. The association of adjuvant chemotherapy with disease-free survival (DFS) and overall survival (OS) was evaluated in overall patients and in the propensity score matched (PSM) cohort. Subgroup analysis was conducted according to the pathology-proven lymph node status.
Results
Adjuvant chemotherapy was administered to 149 patients (68.3%). In the overall cohort, the adjuvant chemotherapy group had significantly improved DFS and OS compared to the observation group (DFS: median, 13.8 months [95% confidence interval (CI), 11.0 to 19.1] vs. 8.2 months [95% CI, 6.5 to 12.0]; p < 0.001; and OS: median, 38.0 months [95% CI, 32.2 to not assessable] vs. 25.7 months [95% CI, 18.3 to not assessable]; p=0.005). In the PSM cohort of 57 matched pairs of patients, DFS and OS were better in the adjuvant chemotherapy group than in the observation group (p < 0.001 and p=0.038, respectively). In the multivariate analysis, adjuvant chemotherapy was a significant favorable prognostic factor (vs. observation; DFS: hazard ratio [HR], 0.51 [95% CI, 0.36 to 0.71; p < 0.001]; OS: HR, 0.45 [95% CI, 0.29 to 0.71; p < 0.001]).
Conclusion
Among PDAC patients who underwent surgery following neoadjuvant FOLFIRINOX, adjuvant chemotherapy may be associated with improved survival. Randomized studies should be conducted to validate this finding.

Citations

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  • The survival effect of neoadjuvant therapy and neoadjuvant plus adjuvant therapy on pancreatic ductal adenocarcinoma patients with different TNM stages: a propensity score matching analysis based on the SEER database
    Hao Hu, Yang Xu, Qiang Zhang, Yuan Gao, Zhenyu Wu
    Expert Review of Anticancer Therapy.2024; 24(6): 467.     CrossRef
  • Neoadjuvant treatment of pancreatic ductal adenocarcinoma: Whom, when and how
    Nebojsa Manojlovic, Goran Savic, Stevan Manojlovic
    World Journal of Gastrointestinal Surgery.2024; 16(5): 1223.     CrossRef
  • Case Study on Analysing the Early Disease Detection of Pancreatic Ductal Adenocarcinoma in Korean Association for Clinical Oncology
    Sijithra Ponnarassery Chandran, N. Santhi
    American Journal of Clinical Oncology.2024; 47(10): 475.     CrossRef
  • Evaluating the benefits of adjuvant chemotherapy in patients with pancreatic cancer undergoing radical pancreatectomy after neoadjuvant therapy—a systematic review and meta-analysis
    Jiahao Wu, Yike Zhang, Haodong Wang, Wenyi Guo, Chengqing Li, Yichen Yu, Han Liu, Feng Li, Lei Wang, Jianwei Xu
    Frontiers in Oncology.2024;[Epub]     CrossRef
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Adjuvant Chemotherapy for Resected Ampulla of Vater Carcinoma: Retrospective Analysis of 646 Patients
Jwa Hoon Kim, Jae Ho Jeong, Baek-Yeol Ryoo, Kyu-pyo Kim, Heung-Moon Chang, Dongwook Oh, Tae Jun Song, Sang Soo Lee, Dong Wan Seo, Sung Koo Lee, Myung-Hwan Kim, Yejong Park, Jae Woo Kwon, Dae Wook Hwang, Jae Hoon Lee, Woohyung Lee, Song Cheol Kim, Changhoon Yoo, Ki Byung Song
Cancer Res Treat. 2021;53(2):424-435.   Published online November 9, 2020
DOI: https://doi.org/10.4143/crt.2020.953
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study evaluated the efficacy of adjuvant chemotherapy (AC) in patients with resected ampulla of Vater (AoV) carcinoma.
Materials and Methods
Data from 646 patients who underwent surgical resection at Asan Medical Center between 2000 and 2017 were retrospectively reviewed.
Results
The median age of the patients was 62 years, and 54.2% were male. Patients were classified into AC group (n=165, 25.5%) and no AC group (n=481, 74.5%). With a median follow-up duration of 88 months, in patients with stage I, II, III, median recurrence-free survival (RFS) was not reached, 44 months, and 15 months, respectively, and the median overall survival (OS) were not reached, 88 months and 35 months, respectively. Despite no statistical significance, RFS and OS were better in stage II patients with AC than in those without AC (median RFS, 151 months vs. 38 months; p=0.156 and median OS, 153 months vs. 74 months; p=0.299). In multivariate analysis for RFS and OS, TNM stage, R1 resection status, presence of lymphovascular invasion, and perineural invasion remained significant factors, whereas AC (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.54 to 1.00; p=0.052) was marginally related with RFS. After propensity score matching in only stage II/III patients, RFS and OS with AC were numerically longer than those without AC (HR, 0.80; 95% CI, 0.60 to 1.06; p=0.116 and HR, 0.77; 95% CI, 0.56 to 1.06; p=0.111).
Conclusion
AC with fluoropyrimidine did not improve survival of patients with resected AoV carcinoma. However, multivariate analysis with prognostic factors showed a marginally significant survival benefit with AC.

Citations

Citations to this article as recorded by  
  • Survival benefit of concurrent chemoradiotherapy for advanced ampulla of Vater cancer
    Chae Hwa Kwon, Hyung Il Seo, Dong Uk Kim, Sung Yong Han, Suk Kim, Nam Kyung Lee, Seung Baek Hong, Ji Hyun Ahn, Young Mok Park, Byeong Gwan Noh
    World Journal of Clinical Cases.2024; 12(2): 267.     CrossRef
  • Prognostic efficacy of lymph node parameters in resected ampullary adenocarcinoma based on long-term follow-up data after adjuvant treatment
    Namyoung Park, In Rae Cho, Sang Hyub Lee, Joo Seong Kim, Jin Ho Choi, Min Woo Lee, Woo Hyun Paik, Kwang Ro Joo, Ji Kon Ryu, Yong-Tae Kim
    World Journal of Surgical Oncology.2024;[Epub]     CrossRef
  • Adjuvant Chemotherapy and Effect on Long-Term Survival in Ampullary Adenocarcinoma: A Multicenter Cohort Study
    Dong Woo Shin, Jae Min Lee, Jong-chan Lee, Hee Seung Lee, Seung Bae Yoon, Dong Kee Jang, Joo Kyung Park, Min Kyu Jung, Yoon Suk Lee, Jin-Hyeok Hwang
    Journal of the American College of Surgeons.2023; 237(3): 501.     CrossRef
  • Role of adjuvant chemotherapy on recurrence and survival in patients with resected ampulla of Vater carcinoma
    Se Jun Park, Kabsoo Shin, In-Ho Kim, Tae Ho Hong, Younghoon Kim, Myung-ah Lee
    World Journal of Gastrointestinal Oncology.2023; 15(4): 677.     CrossRef
  • Remission from the 5-Fu-Based Chemotherapy to Gemcitabine-Based Chemotherapy-Based on the Pathological Classification of Periampullary Carcinoma: A Case Report and Literature Review
    Wei Hu, Zhiqing Duan, Yinuo Zhang, Jing Liu, Jing Bao, Ruqing Gao, Yajie Tang, Tiande Liu, Hu Xiong, Wen Li, Xiaowei Fu, Shousheng Liao, Lu Fang, Bo Liang
    OncoTargets and Therapy.2022; Volume 15: 891.     CrossRef
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Clinical Outcomes of Second-Line Chemotherapy after Progression on Nab-Paclitaxel Plus Gemcitabine in Patients with Metastatic Pancreatic Adenocarcinoma
Kyoungmin Lee, Kyunghye Bang, Changhoon Yoo, Inhwan Hwang, Jae Ho Jeong, Heung-Moon Chang, Dongwook Oh, Tae Jun Song, Do Hyun Park, Sang Soo Lee, Sung Koo Lee, Myung-Hwan Kim, Jin-hong Park, Kyu-pyo Kim, Baek-Yeol Ryoo
Cancer Res Treat. 2020;52(1):254-262.   Published online July 9, 2019
DOI: https://doi.org/10.4143/crt.2019.190
AbstractAbstract PDFSupplementary MaterialPubReaderePub
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.

Citations

Citations to this article as recorded by  
  • Effect of a MUC5AC Antibody (NPC-1C) Administered With Second-Line Gemcitabine and Nab-Paclitaxel on the Survival of Patients With Advanced Pancreatic Ductal Adenocarcinoma
    Brandon M. Huffman, Atrayee Basu Mallick, Nora K. Horick, Andrea Wang-Gillam, Peter Joel Hosein, Michael A. Morse, Muhammad Shaalan Beg, Janet E. Murphy, Sharon Mavroukakis, Anjum Zaki, Benjamin L. Schlechter, Hanna Sanoff, Christopher Manz, Brian M. Wolp
    JAMA Network Open.2023; 6(1): e2249720.     CrossRef
  • Trend Analysis and Prediction of Hepatobiliary Pancreatic Cancer Incidence and Mortality in Korea
    Hyeong Min Park, Young-Joo Won, Mee Joo Kang, Sang-Jae Park, Sun-Whe Kim, Kyu-Won Jung, Sung-Sik Han
    Journal of Korean Medical Science.2022;[Epub]     CrossRef
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    World Journal of Gastroenterology.2021; 27(17): 1847.     CrossRef
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    Surgical Oncology Clinics of North America.2021; 30(4): 673.     CrossRef
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    International Journal of Oncology.2021;[Epub]     CrossRef
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Clinical Benefit of Maintenance Therapy for Advanced Biliary Tract Cancer Patients Showing No Progression after First-Line Gemcitabine Plus Cisplatin
Jaewon Hyung, Bumjun Kim, Changhoon Yoo, Kyo-pyo Kim, Jae Ho Jeong, Heung-Moon Chang, Baek-Yeol Ryoo
Cancer Res Treat. 2019;51(3):901-909.   Published online October 4, 2018
DOI: https://doi.org/10.4143/crt.2018.326
AbstractAbstract PDFSupplementary MaterialPubReaderePub
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.

Citations

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Multicenter Phase II Study of Oxaliplatin, Irinotecan, and S-1 as First-line Treatment for Patients with Recurrent or Metastatic Biliary Tract Cancer
Changhoon Yoo, Boram Han, Hyeong Su Kim, Kyu-pyo Kim, Deokhoon Kim, Jae Ho Jeong, Jae-Lyun Lee, Tae Won Kim, Jung Han Kim, Dae Ro Choi, Hong Il Ha, Jinwon Seo, Heung-Moon Chang, Baek-Yeol Ryoo, Dae Young Zang
Cancer Res Treat. 2018;50(4):1324-1330.   Published online January 8, 2018
DOI: https://doi.org/10.4143/crt.2017.526
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Although gemcitabine plus cisplatin has been established as the standard first-line chemotherapy for patients with advanced biliary tract cancer (BTC), overall prognosis remains poor. We investigated the efficacy of a novel triplet combination of oxaliplatin, irinotecan, and S-1 (OIS) for advanced BTC.
Materials and Methods
Chemotherapy-naive patientswith histologically documented unresectable or metastatic BTC were eligible for this multicenter, single-arm phase II study. Patients received 65 mg/m2 oxaliplatin (day 1), 135 mg/m2 irinotecan (day 1), and 40 mg/m2 S-1 (twice a day, days 1-7) every 2 weeks. Primary endpoint was objective response rate. Targeted exome sequencing for biomarker analysis was performed using archival tissue.
Results
In total, 32 patients were enrolled between October 2015 and June 2016. Median age was 64 years (range, 40 to 76 years), with 24 (75%) male patients; 97% patients had metastatic or recurrent disease. Response rate was 50%, and median progression-free survival and overall survival (OS) were 6.8 months (95% confidence interval [CI], 4.8 to 8.8) and 12.5 months (95% CI, 7.0 to 18.0), respectively. The most common grade 3-4 adverse events were neutropenia (32%), diarrhea (6%), and peripheral neuropathy (6%). TP53 and KRAS mutations were the most frequent genomic alterations (42% and 32%, respectively), and KRAS mutations showed a marginal relationship with worse OS (p=0.07).
Conclusion
OIS combination chemotherapy was feasible and associated with favorable efficacy outcomes as a first-line treatment in patients with advanced BTC. Randomized studies are needed to compare OIS with gemcitabine plus cisplatin.

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Efficacy of Chemotherapy in Patients with Unresectable or Metastatic Pancreatic Acinar Cell Carcinoma: Potentially Improved Efficacy with Oxaliplatin-Containing Regimen
Changhoon Yoo, Bum Jun Kim, Kyu-pyo Kim, Jae-Lyun Lee, Tae Won Kim, Baek-Yeol Ryoo, Heung-Moon Chang
Cancer Res Treat. 2017;49(3):759-765.   Published online November 9, 2016
DOI: https://doi.org/10.4143/crt.2016.371
AbstractAbstract PDFSupplementary MaterialPubReaderePub
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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