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21 "Pancreatic neoplasms"
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Original Articles
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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Gemcitabine Inhibits the Progression of Pancreatic Cancer by Restraining the WTAP/MYC Chain in an m6A-Dependent Manner
Pei Cao, Weigang Zhang, Junyi Qiu, Zuxiong Tang, Xiaofeng Xue, Tingting Feng
Cancer Res Treat. 2024;56(1):259-271.   Published online August 16, 2023
DOI: https://doi.org/10.4143/crt.2022.1600
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Pancreatic cancer (PC) is a common malignant tumor of the digestive system, and its 5-year survival rate is only 4%. N6-methyladenosine (m6A) RNA methylation is the most common post-transcriptional modification and dynamically regulates cancer development, while its role in PC treatment remains unclear.
Materials and Methods
We treated PC cells with gemcitabine and quantified the overall m6A level with m6A methylation quantification. Real-time quantitative reverse transcription polymerase chain reaction and Western blot analyses were used to detect expression changes of m6A regulators. We verified the m6A modification on the target genes through m6A-immunoprecipitation (IP), and further in vivo experiments and immunofluorescence (IF) assays were applied to verify regulation of gemcitabine on Wilms’ tumor 1–associated protein (WTAP) and MYC.
Results
Gemcitabine inhibited the proliferation and migration of PC cells and reduced the overall level of m6A modification. Additionally, the expression of the “writer” WTAP was significantly downregulated after gemcitabine treatment. We knocked down WTAP in cells and found target gene MYC expression was significantly downregulated, m6A-IP also confirmed the m6A modification on MYC. Our experiments showed that m6A-MYC may be recognized by the “reader” IGF2BP1. In vivo experiments revealed gemcitabine inhibited the tumorigenic ability of PC cells. IF analysis also showed that gemcitabine inhibited the expression of WTAP and MYC, which displayed a significant trend of co-expression.
Conclusion
Our study confirmed that gemcitabine interferes with WTAP protein expression in PC, reduces m6A modification on MYC and RNA stability, thereby inhibiting the downstream pathway of MYC, and inhibits the progression of PC.

Citations

Citations to this article as recorded by  
  • WTAP-mediated N6-methyladenosine modification promotes the inflammation, mitochondrial damage and ferroptosis of kidney tubular epithelial cells in acute kidney injury by regulating LMNB1 expression and activating NF-κB and JAK2/STAT3 pathways
    Fan Huang, Yuchen Wang, XiaoLi Lv, Chenda Huang
    Journal of Bioenergetics and Biomembranes.2024; 56(3): 285.     CrossRef
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General
Establishment of Patient-Derived Organoids Using Ascitic or Pleural Fluid from Cancer Patients
Wonyoung Choi, Yun-Hee Kim, Sang Myung Woo, Yebeen Yu, Mi Rim Lee, Woo Jin Lee, Jung Won Chun, Sung Hoon Sim, Heejung Chae, Hyoeun Shim, Keun Seok Lee, Sun-Young Kong
Cancer Res Treat. 2023;55(4):1077-1086.   Published online June 12, 2023
DOI: https://doi.org/10.4143/crt.2022.1630
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
Patient-derived tumor cells can be a powerful resource for studying pathophysiological mechanisms and developing robust strategies for precision medicine. However, establishing organoids from patient-derived cells is challenging because of limited access to tissue specimens. Therefore, we aimed to establish organoids from malignant ascites and pleural effusions.
Materials and Methods
Ascitic or pleural fluid from pancreatic, gastric, and breast cancer patients was collected and concentrated to culture tumor cells ex vivo. Organoids were considered to be successfully cultured when maintained for five or more passages. Immunohistochemical staining was performed to compare the molecular features, and drug sensitivity was assayed to analyze the clinical responses of original patients.
Results
We collected 70 fluid samples from 58 patients (pancreatic cancer, n=39; gastric cancer, n=21; and breast cancer, n=10). The overall success rate was 40%; however, it differed with types of malignancy, with pancreatic, gastric, and breast cancers showing 48.7%, 33.3%, and 20%, respectively. Cytopathological results significantly differed between successful and failed cases (p=0.014). Immunohistochemical staining of breast cancer organoids showed molecular features identical to those of tumor tissues. In drug sensitivity assays, pancreatic cancer organoids recapitulated the clinical responses of the original patients.
Conclusion
Tumor organoids established from malignant ascites or pleural effusion of pancreatic, gastric, and breast cancers reflect the molecular characteristics and drug sensitivity profiles. Our organoid platform could be used as a testbed for patients with pleural and peritoneal metastases to guide precision oncology and drug discovery.

Citations

Citations to this article as recorded by  
  • PRMT1 promotes pancreatic cancer development and resistance to chemotherapy
    Bomin Ku, David Eisenbarth, Seonguk Baek, Tae-Keun Jeong, Ju-Gyeong Kang, Daehee Hwang, Myung-Giun Noh, Chan Choi, Sungwoo Choi, Taejun Seol, Hail Kim, Yun-Hee Kim, Sang Myung Woo, Sun-Young Kong, Dae-Sik Lim
    Cell Reports Medicine.2024; 5(3): 101461.     CrossRef
  • Establishment and Advancement of Pancreatic Organoids
    Dong Hyeon Lee
    Keimyung Medical Journal.2024; 43(1): 3.     CrossRef
  • Organoid as a promising tool for primary liver cancer research: a comprehensive review
    Xuekai Hu, Jiayun Wei, Pinyan Liu, Qiuxia Zheng, Yue Zhang, Qichen Zhang, Jia Yao, Jingman Ni
    Cell & Bioscience.2024;[Epub]     CrossRef
  • The use of organoids in creating immune microenvironments and treating gynecological tumors
    Ling-Feng Zhou, Hui-Yan Liao, Yang Han, Yang Zhao
    Journal of Translational Medicine.2024;[Epub]     CrossRef
  • Organoid: Bridging the gap between basic research and clinical practice
    Guihu Weng, Jinxin Tao, Yueze Liu, Jiangdong Qiu, Dan Su, Ruobing Wang, Wenhao Luo, Taiping Zhang
    Cancer Letters.2023; 572: 216353.     CrossRef
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Gastrointestinal cancer
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

Citations to this article as recorded by  
  • 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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Daily Vigorous Intensity Physical Activity and Its Preventive Effect on Pancreatic Cancer
Sung Keun Park, Ju Young Jung, Chang-Mo Oh, Min-Ho Kim, Eunhee Ha, Yeji Kim, Do Jin Nam, Jae-Hong Ryoo
Cancer Res Treat. 2022;54(3):873-881.   Published online September 27, 2021
DOI: https://doi.org/10.4143/crt.2021.400
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
There has been accumulating evidence for the preventive effect of high physical activity on cancer. However, it is still unclear which level of physical activity is associated with the decreased risk of pancreatic cancer. The purpose of current study is to assess the association between the frequency of vigorous intensity physical activity and the risk of pancreatic cancer.
Materials and Methods
The nationwide retrospective cohort study was conducted using the National Health Information Database. Study participants were 220,357 Koreans who received health check-up in 2009. They were divided into four groups by the weekly frequency of vigorous intensity physical activity longer than 20 minutes (group 1, no vigorous intensity physical activity (reference); group 2, 1-3 days; group 3, 4-5 days and group 4, 6-7 days). Cox proportional hazard model was used to calculate the adjusted hazard ratios (HRs) and 95% confidence interval (CI) for incident pancreatic cancer (adjusted HRs [95% CI]) according to the weekly frequency of vigorous intensity physical activity.
Results
For 4.38 years’ follow-up on average, 377 cases of pancreatic cancer developed. Subjects without incident pancreatic cancer had more favorable metabolic condition and higher physical activity than subjects with incident pancreatic cancer. Adjusted HRs and 95% CI indicated that only group 4 was significantly associated with the decreased risk of pancreatic cancer (group 1, reference; group 2, 1.10 [0.86-1.40]; group 3, 0.75 [0.45-1.25] and group 4, 0.47 [0.25-0.89]).
Conclusion
In this nationwide representative cohort study, near daily vigorous intensity physical activity showed the preventive effect on pancreatic cancer.

Citations

Citations to this article as recorded by  
  • Association between waist circumference change after smoking cessation and incidence of hypertension in Korean adults
    H.J. Lee, J.W. Choi
    Public Health.2024; 229: 73.     CrossRef
  • Physical Activity Decreases Inflammation and Delays the Development of Obesity-Associated Pancreatic Ductal Adenocarcinoma
    Valentina Pita-Grisanti, Ericka Velez-Bonet, Kaylin Chasser, Zachary Hurst, Alexus Liette, Grace Vulic, Kelly Dubay, Ali Lahooti, Niharika Badi, Olivia Ueltschi, Kristyn Gumpper-Fedus, Hsiang-Yin Hsueh, Ila Lahooti, Myrriah Chavez-Tomar, Samantha Terhorst
    Cancer Research.2024; 84(18): 3058.     CrossRef
  • The role of exercise in obesity-related cancers: Current evidence and biological mechanisms
    Elisabeth A. Larson, Maria Dalamaga, Faidon Magkos
    Seminars in Cancer Biology.2023; 91: 16.     CrossRef
  • Effect of physical activity on incidence and mortality in patients with gastric cancer: evidence from real-world studies
    Shaodi Ma, Haixia Liu, Chenyu Sun, Muzi Meng, Guangbo Qu, Yuemeng Jiang, Birong Wu, Juan Gao, Linya Feng, Peng Xie, Weihang Xia, Yehuan Sun
    Cancer Causes & Control.2023; 34(12): 1095.     CrossRef
  • Integrated procedures for accelerating, deepening, and leading genetic inquiry: A first application on human muscle secretome
    Danilo Bondi, Michele Bevere, Rosanna Piccirillo, Guglielmo Sorci, Valentina Di Felice, Andrea David Re Cecconi, Daniela D'Amico, Tiziana Pietrangelo, Stefania Fulle
    Molecular Genetics and Metabolism.2023; 140(3): 107705.     CrossRef
  • 6,373 View
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  • 5 Web of Science
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First Course of treatment and Prognosis of Exocrine Pancreatic Cancer in Korea from 2006 to 2017
Mee Joo Kang, Jiwon Lim, Sung-Sik Han, Hyeong Min Park, Sang-Jae Park, Young-Joo Won, Sun-Whe Kim
Cancer Res Treat. 2022;54(1):208-217.   Published online May 21, 2021
DOI: https://doi.org/10.4143/crt.2021.421
AbstractAbstract PDFPubReaderePub
Purpose
Hospital-based clinical studies have limitations in holistic assessment of cancer treatment and prognosis, as they omit out-of-hospital patients including elderly individuals. This study aimed to investigate trends in initial treatment and corresponding prognosis of patients with exocrine pancreatic cancer (EPC) in Korea.
Materials and Methods
The Korea Central Cancer Registry data of patients with EPC from 2006 to 2017 were retrospectively reviewed. We defined the first course of treatment (FT) as the cancer-directed treatment administered within four months after cancer diagnosis according to Surveillance, Epidemiology, and End Results (SEER) program.
Results
Among 62,209 patients with EPC, localized and regional (LR) SEER stage; patients over 70 years old; and ductal adenocarcinoma excluding cystic or mucinous (DAC) accounted for 40.6%, 50.1%, and 95.9%, respectively. “No active treatment” (NT, 46.5%) was the most frequent, followed by non-surgical FT (28.7%) and surgical FT (22.0%). Among 25,198 patients with LR EPC, surgical FT increased (35.9% to 46.3%) and NT decreased (45.0% to 29.5%) from 2006 to 2017. The rate of surgical FT was inversely related to age (55.1% [< 70 years], 37.3% [70-79 years], 10.9% [≥ 80 years]). Five-year relative survival rates of LR DAC were higher after surgical FT than after NT in localized (46.1% vs. 12.9%) and regional stage (23.6% vs. 4.9%) from 2012 to 2017.
Conclusion
Less than half of overall patients with LR EPC underwent surgical FT, and this proportion decreased significantly in elderly individuals. Clinicians should focus attention on elderly patients with EPC to provide appropriate medical advice.

Citations

Citations to this article as recorded by  
  • Conditional Relative Survival of Exocrine Pancreatic Cancer: A Population-Based Study
    Mee Joo Kang, Johyun Ha, Hyeong Min Park, Sang-Jae Park, Kyu-Won Jung, Sung-Sik Han
    Annals of Surgical Oncology.2024; 31(2): 1178.     CrossRef
  • Potential role of Fibrosis‐4 score in hepatocellular carcinoma screening: The Kangbuk Samsung Health Study
    Sujeong Shin, Won Sohn, Yoosoo Chang, Yoosun Cho, Min‐Jung Kwon, Sarah H. Wild, Christopher D. Byrne, Seungho Ryu
    Hepatology Research.2024; 54(6): 551.     CrossRef
  • Three-year follow-up study reveals improved survival rate in NSCLC patients underwent guideline-concordant diagnosis and treatment
    Huijuan Mu, Xing Yang, Yanxia Li, Bingzheng Zhou, Li Liu, Minmin Zhang, Qihao Wang, Qian Chen, Lingjun Yan, Wei Sun, Guowei Pan
    Frontiers in Oncology.2024;[Epub]     CrossRef
  • Epidemiological trends and factors associated with survival in patients with medulloblastoma: A 45-year population-based retrospective study
    Dongjie He, Yahui Yang, Peiwen Wu, Siying Zhu, Hao Chang, Chao Zhang, Qiuju Shao, Zongyan Yu
    Journal of Clinical Neuroscience.2024; 126: 154.     CrossRef
  • Surgical management for elderly patients with pancreatic cancer
    Sun-Whe Kim
    Annals of Surgical Treatment and Research.2023; 105(2): 63.     CrossRef
  • Exocrine pancreatic cancer as a second primary malignancy: A population-based study
    Mee Joo Kang, Jiwon Lim, Sung-Sik Han, Hyeong Min Park, Sung Chun Cho, Sang-Jae Park, Sun-Whe Kim, Young-Joo Won
    Annals of Hepato-Biliary-Pancreatic Surgery.2023; 27(4): 415.     CrossRef
  • Distinct prognosis of biliary tract cancer according to tumor location, stage, and treatment: a population-based study
    Mee Joo Kang, Jiwon Lim, Sung-Sik Han, Hyeong Min Park, Sun-Whe Kim, Woo Jin Lee, Sang Myung Woo, Tae Hyun Kim, Young-Joo Won, Sang-Jae Park
    Scientific Reports.2022;[Epub]     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
  • Epidemiology of Gastric Cancer in Korea: Trends in Incidence and Survival Based on Korea Central Cancer Registry Data (1999–2019)
    Sin Hye Park, Mee Joo Kang, E Hwa Yun, Kyu-Won Jung
    Journal of Gastric Cancer.2022; 22(3): 160.     CrossRef
  • Incidence, mortality and survival of gallbladder, extrahepatic bile duct, and pancreatic cancer using Korea central cancer registry database: 1999-2019
    Mee Joo Kang, E Hwa Yun, Kyu-Won Jung, Sang-Jae Park
    Annals of Hepato-Biliary-Pancreatic Surgery.2022; 26(3): 220.     CrossRef
  • Incidence, mortality, and survival of liver cancer using Korea central cancer registry database: 1999-2019
    Sung Yeon Hong, Mee Joo Kang, Taegyu Kim, Kyu-Won Jung, Bong-Wan Kim
    Annals of Hepato-Biliary-Pancreatic Surgery.2022; 26(3): 211.     CrossRef
  • 5,780 View
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  • 11 Web of Science
  • 11 Crossref
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Gastrointestinal Cancer
Phase II Trial of Postoperative Adjuvant Gemcitabine and Cisplatin Chemotherapy Followed by Chemoradiotherapy with Gemcitabine in Patients with Resected Pancreatic Cancer
Kyung-Hun Lee, Eui Kyu Chie, Seock-Ah Im, Jee Hyun Kim, Jihyun Kwon, Sae-Won Han, Do-Youn Oh, Jin-Young Jang, Jae-Sung Kim, Tae-You Kim, Yung-Jue Bang, Sun Whe Kim, Sung W. Ha
Cancer Res Treat. 2021;53(4):1096-1103.   Published online December 30, 2020
DOI: https://doi.org/10.4143/crt.2020.928
AbstractAbstract PDFPubReaderePub
Purpose
Despite curative resection, the 5-year survival for patients with resectable pancreatic cancer is less than 20%. Recurrence occurs both locally and at distant sites and effective multimodality adjuvant treatment is needed.
Materials and Methods
Patients with curatively resected stage IB-IIB pancreatic adenocarcinoma were eligible. Treatment consisted of chemotherapy with gemcitabine 1,000 mg/m2 on days 1 and 8 and cisplatin 60 mg/m2 on day 1 every 3 weeks for two cycles, followed by chemoradiotherapy (50.4 Gy/28 fx) with weekly gemcitabine (300 mg/m2/wk), and then gemcitabine 1,000 mg/m2 on days 1 and 8 every 3 weeks for four cycles. The primary endpoint was 1-year disease-free survival rate. The secondary endpoints were disease-free survival, overall survival, and safety.
Results
Seventy-four patients were enrolled. One-year disease-free survival rate was 57.9%. Median disease-free and overall survival were 15.0 months (95% confidence interval [CI], 11.6 to 18.4) and 33.0 months (95% CI, 21.8 to 44.2), respectively. At the median follow-up of 32 months, 57 patients (77.0%) had recurrence including 11 patients whose recurrence was during the adjuvant treatment. Most of the recurrences were systemic (52 patients). Stage at the time of diagnosis (70.0% in IIA, 51.2% in IIB, p=0.006) were significantly related with 1-year disease-free survival rate. Toxicities were generally tolerable, with 53 events of grade 3 or 4 hematologic toxicity and four patients with febrile neutropenia.
Conclusion
Adjuvant gemcitabine and cisplatin chemotherapy followed by chemoradiotherapy with gemcitabine and maintenance gemcitabine showed efficacy and good tolerability in curatively resected pancreatic cancer.

Citations

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  • NUDT21 interacts with NDUFS2 to activate the PI3K/AKT pathway and promotes pancreatic cancer pathogenesis
    Xiao-Dong Huang, Yong-Wei Chen, Lv Tian, Li Du, Xiao-Chen Cheng, Yu-Xin Lu, Dong-Dong Lin, Feng-Jun Xiao
    Journal of Cancer Research and Clinical Oncology.2024;[Epub]     CrossRef
  • Efficacy of Cisplatin-Containing Chemotherapy Regimens in Patients of Pancreatic Ductal Adenocarcinoma: A Systematic Review and Meta-analysis
    Obaid Ur Rehman, Eeshal Fatima, Zain Ali Nadeem, Arish Azeem, Jatin Motwani, Habiba Imran, Hadia Mehboob, Alishba Khan, Omer Usman
    Journal of Gastrointestinal Cancer.2024; 55(2): 559.     CrossRef
  • OTUB1/NDUFS2 axis promotes pancreatic tumorigenesis through protecting against mitochondrial cell death
    Xiao-Dong Huang, Li Du, Xiao-Chen Cheng, Yu-Xin Lu, Qiao-Wei Liu, Yi-Wu Wang, Ya-Jin Liao, Dong-Dong Lin, Feng-Jun Xiao
    Cell Death Discovery.2024;[Epub]     CrossRef
  • Impact of obesity on pathological complete remission in early stage breast cancer patients after neoadjuvant chemotherapy: a retrospective study from a German University breast center
    Johannes Felix Englisch, Alexander Englisch, Dominik Dannehl, Kenneth Eissler, Christian Martin Tegeler, Sabine Matovina, Léa Louise Volmer, Diethelm Wallwiener, Sara Y. Brucker, Andreas Hartkopf, Tobias Engler
    Archives of Gynecology and Obstetrics.2024;[Epub]     CrossRef
  • A Photothermal Therapy Study Based on Electrospinning Nanofibers Blended and Coated with Polydopamine Nanoparticles
    Chunhong Sui, Yijia Luo, Xiao Xiao, Jiaxue Liu, Xiaotong Shao, Yingxue Xue, Cheng Wang, Wenliang Li
    ChemistrySelect.2023;[Epub]     CrossRef
  • Ivermectin and gemcitabine combination treatment induces apoptosis of pancreatic cancer cells via mitochondrial dysfunction
    Da Eun Lee, Hyeon Woong Kang, So Yi Kim, Myeong Jin Kim, Jae Woong Jeong, Woosol Chris Hong, Sungsoon Fang, Hyung Sun Kim, Yun Sun Lee, Hyo Jung Kim, Joon Seong Park
    Frontiers in Pharmacology.2022;[Epub]     CrossRef
  • CircLMTK2 Silencing Attenuates Gemcitabine Resistance in Pancreatic Cancer by Sponging miR-485-5p and to Target PAK1
    Yeting Lu, Shuping Zhou, Gong Cheng, Yi Ruan, Yuan Tian, Kaiji Lv, Shuo Han, Xinhua Zhou, Xiangya Ding
    Journal of Oncology.2022; 2022: 1.     CrossRef
  • Effects of Radiotherapy and Chemotherapy on Postoperative Prognosis of Patients Undergoing Radical Surgery for Pancreatic Cancer—Based on SEER Database Analysis
    媛媛 苏
    Advances in Clinical Medicine.2022; 12(10): 9540.     CrossRef
  • Zebrafish Patient-Derived Xenografts Identify Chemo-Response in Pancreatic Ductal Adenocarcinoma Patients
    Alice Usai, Gregorio Di Franco, Margherita Piccardi, Perla Cateni, Luca Emanuele Pollina, Caterina Vivaldi, Enrico Vasile, Niccola Funel, Matteo Palmeri, Luciana Dente, Alfredo Falcone, Dimitri Giunchi, Alessandro Massolo, Vittoria Raffa, Luca Morelli
    Cancers.2021; 13(16): 4131.     CrossRef
  • Hypoxia-Induced ZWINT Mediates Pancreatic Cancer Proliferation by Interacting With p53/p21
    Peng Chen, Zhiwei He, Jie Wang, Jian Xu, Xueyi Jiang, Yankun Chen, Xinyuan Liu, Jianxin Jiang
    Frontiers in Cell and Developmental Biology.2021;[Epub]     CrossRef
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Gastrointestinal cancer
Systemic Inflammatory Biomarkers, Especially Fibrinogen to Albumin Ratio, Predict Prognosis in Patients with Pancreatic Cancer
Lin Fang, Fei-Hu Yan, Chao Liu, Jing Chen, Dan Wang, Chun-Hui Zhang, Chang-Jie Lou, Jie Lian, Yang Yao, Bo-Jun Wang, Rui-Yang Li, Shu-Ling Han, Yi-Bing Bai, Jia-Ni Yang, Zhi-Wei Li, Yan-Qiao Zhang
Cancer Res Treat. 2021;53(1):131-139.   Published online August 24, 2020
DOI: https://doi.org/10.4143/crt.2020.330
AbstractAbstract PDFSupplementary MaterialPubReader
Purpose
Systemic inflammatory response is a critical factor that promotes the initiation and metastasis of malignancies including pancreatic cancer (PC). This study was designed to determine and compare the prognostic value of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and fibrinogen-to-albumin ratio (FAR) in resectable PC and locally advanced or metastatic PC.
Materials and Methods
Three hundred fifty-three patients with resectable PC and 807 patients with locally advan-ced or metastatic PC were recruited in this study. These patients were classified into a training set (n=758) and a validation set (n=402). Kaplan-Meier survival plots and Cox proportional hazards regression models were used to analyze prognosis.
Results
Overall survival (OS) was significantly better for patients with resectable PC with low preoperative PLR (p=0.048) and MLR (p=0.027). Low FAR, MLR, NLR (p < 0.001), and PLR (p=0.003) were significantly associated with decreased risk of death for locally advanced or metastatic PC patients. FAR (hazard ratio [HR], 1.522; 95% confidential interval [CI], 1.261 to 1.837; p < 0.001) and MLR (HR, 1.248; 95% CI, 1.017 to 1.532; p=0.034) were independent prognostic factors for locally advanced or metastatic PC.
Conclusion
The prognostic roles of FAR, MLR, NLR, and PLR in resectable PC and locally advanced or metastatic PC were different. FAR showed the most prognostic power in locally advanced or metastatic PC. Low FAR was positively correlated with OS in locally advanced or metastatic PC, which could be used to predict the prognosis.

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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.

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The Role of Consolidation Chemoradiotherapy in Locally Advanced Pancreatic Cancer Receiving Chemotherapy: An Updated Systematic Review and Meta-Analysis
Jeffrey S. Chang, Yen-Feng Chiu, Jih-Chang Yu, Li-Tzong Chen, Hui-Ju Ch’ang
Cancer Res Treat. 2018;50(2):562-574.   Published online June 9, 2017
DOI: https://doi.org/10.4143/crt.2017.105
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
The role of consolidation chemoradiation (CCRT) after systemic chemotherapy in locally advanced pancreatic cancer (LAPC) is still controversial. We aim to evaluate the effectiveness of CCRT in LAPC using systematic review and meta-analysis of prospective studies.
Materials and Methods
Prospective clinical trials of LAPC receiving chemotherapy with or without subsequent CCRT were included in the analysis. We systematically searched in PubMed, MEDLINE, Embase, and Web of Science. The primary outcome of interest was 1-year survival. Secondary endpoints were median overall survival, progression-free survival, toxicity, and resection rate.
Results
Forty-one studies with 49 study arms were included with a total of 1,018 patients receiving CCRT after induction chemotherapy (ICT) and 954 patients receiving chemotherapy alone. CCRT after ICT did not improve 1-year survival significantly in LAPC patients compared with chemotherapy alone (58% vs. 52%). ICT lasted for at least 3 months revealed significantly improved survival of additional CCRT to LAPC patients compared to chemotherapy alone (65% vs. 52%). A marginal survival benefit of consolidation CCRT was noted in studies using maintenance chemotherapy (59% vs. 52%), and fluorouracil-based CCRT (64% vs. 52%), as well as in studies conducted after the 2010 (64% vs. 55%).
Conclusion
The survival benefit of ICT+CCRT over chemotherapy alone in treating LAPC was noted when ICT lasted for at least 3 months. Fluorouracil-based CCRT, and maintenance chemotherapy were associated with improved clinical outcomes.

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Induction Chemotherapy with Gemcitabine and Cisplatin Followed by Simultaneous Integrated Boost–Intensity Modulated Radiotherapy with Concurrent Gemcitabine for Locally Advanced Unresectable Pancreatic Cancer: Results from a Feasibility Study
Sang Myung Woo, Min Kyeong Kim, Jungnam Joo, Kyong-Ah Yoon, Boram Park, Sang-Jae Park, Sung-Sik Han, Ju Hee Lee, Eun Kyung Hong, Yun-Hee Kim, Hae Moon, Sun-Young Kong, Tae Hyun Kim, Woo Jin Lee
Cancer Res Treat. 2017;49(4):1022-1032.   Published online January 19, 2017
DOI: https://doi.org/10.4143/crt.2016.495
AbstractAbstract PDFSupplementary MaterialPubReaderePub
Purpose
This study assessed the feasibility and compliance of induction chemotherapy with gemcitabine and cisplatin followed by simultaneous integrated boost–intensity modulated radiotherapy (SIB-IMRT) with concurrent gemcitabine in patients with locally advanced unresectable pancreatic cancer.
Materials and Methods
In this trial, patients received induction chemotherapy consisting of gemcitabine (1,000 mg/m2) and cisplatin (25 mg/m2) on days 1, 8, and 15 of each treatment cycle. Patients were subsequently treated with gemcitabine (300 mg/m2/wk) during SIB-IMRT. The patients received total doses of 55 and 44 Gy in 22 fractions to planning target volume 1 and 2, respectively. As an ancillary study, digital polymerase chain reaction was performed to screen for the seven most common mutations in codons 12 and 13 of the KRAS oncogene of circulating cell free DNA (cfDNA).
Results
Forty-four patients were enrolled between 2012 and 2015. Of these, 33 (75%) completed the treatment. The most common toxicities during induction chemotherapy were grades 3 and 4 neutropenia (18.2%), grade 3 nausea (6.8%) and vomiting (6.8%). The most common toxicities during SIB-IMRT were grade 3 neutropenia (24.2%) and grade 3 anemia (12.1%). Ten patients (23%) underwent a curative resection after therapy. Median overall survival was significantly longer in patients who underwent curative resection (16.8 months vs. 11 months, p < 0.01). The median cfDNA concentration was significantly lower after treatment (108.5 ng/mL vs. 18.4 ng/mL, p < 0.001).
Conclusion
Induction chemotherapy with gemcitabine and cisplatin followed by concurrent SIB-IMRT was well tolerated and active.

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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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Meta-Analysis
Impact of Resection Margin Distance on Survival of Pancreatic Cancer: A Systematic Review and Meta-Analysis
Kyung Su Kim, Jeanny Kwon, Kyubo Kim, Eui Kyu Chie
Cancer Res Treat. 2017;49(3):824-833.   Published online August 26, 2016
DOI: https://doi.org/10.4143/crt.2016.336
AbstractAbstract PDFPubReaderePub
Purpose
While curative resection is the only chance of cure in pancreatic cancer, controversies exist about the impact of surgical margin status on survival. Non-standardized pathologic report and different criteria on the R1 status made it difficult to implicate adjuvant therapy after resection based on the margin status. We evaluated the influence of resection margins on survival by meta-analysis.
Materials and Methods
We thoroughly searched electronic databases of PubMed, EMBASE, and Cochrane Library. We included studies reporting survival outcomeswith different margin status: involved margin (R0 mm), margin clearance with ≤ 1 mm (R0-1 mm), and margin with > 1 mm (R>1 mm). Hazard ratio (HR) for overall survival was extracted, and a random-effects model was used for pooled analysis.
Results
A total of eight retrospective studies involving 1,932 patients were included. Pooled HR for overall survival showed that patients with R>1 mm had reduced risk of death than those with R0-1 mm (HR, 0.74; 95% confidence interval [CI], 0.61 to 0.88; p=0.001). In addition, patients with R0-1 mm had reduced risk of death than those with R0 mm (HR, 0.81; 95% CI, 0.72 to 0.91; p < 0.001). There was no heterogeneity between the included studies (I 2 index, 42% and 0%; p=0.10 and p=0.82, respectively).
Conclusion
Our results suggest that stratification of the patients based on margin status is warranted in the clinical trials assessing the role of adjuvant treatment for pancreatic cancer.

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Original Articles
Prognostic Factors for Risk Stratification of Patients with Recurrent or Metastatic Pancreatic Adenocarcinoma Who Were Treated with Gemcitabine-Based Chemotherapy
Inkeun Park, Seung Joon Choi, Young Saing Kim, Hee Kyung Ahn, Junshik Hong, Sun Jin Sym, Jinny Park, Eun Kyung Cho, Jae Hoon Lee, Yong Ju Shin, Dong Bok Shin
Cancer Res Treat. 2016;48(4):1264-1273.   Published online March 23, 2016
DOI: https://doi.org/10.4143/crt.2015.250
AbstractAbstract PDFPubReaderePub
Purpose
The aim of this study was to verify prognostic factors including sarcopenia in patients with recurrent or metastatic pancreatic cancer receiving gemcitabine-based chemotherapy. Materials and Methods Medical records and computed tomography scan of consecutive patients treated with palliative gemcitabine-based chemotherapy from 2008 to 2014 were reviewed. The lumbar skeletal muscle index at third lumbar spine level was computed, and together with clinicolaboratory factors, univariate and multivariable analyses for overall survival (OS) were performed.
Results
A total of 88 patients were found. Median age was 65 years, and male patients were predominant (67.0%). Most patients had initially metastatic disease (72.7%), and gemcitabine monotherapy was administered in 29 patients (33.0%) while gemcitabine plus erlotinib was administered in 59 patients (67.0%). Seventy-six patients (86.3%) had sarcopenia. With a median follow-up period of 44.3 months (range, 0.6 to 44.3 months), median OS was 5.35 months (95% confidence interval [CI], 4.11 to 6.59). In univariate and multivariable analysis, high carcinoembryonic antigen level (hazard ratio [HR], 4.18; 95% CI, 1.95 to 8.97; p < 0.001), initially metastatic disease (HR, 3.37; 95% CI, 1.55 to 7.32; p=0.002), sarcopenia (HR, 2.97; 95% CI, 1.20 to 7.36; p=0.019), neutrophilia (HR, 2.94; 95% CI, 1.27 to 6.79; p=0.012), and high lactate dehydrogenase level (HR, 1.96; 95% CI, 1.07 to 3.58; p=0.029) were identified as independent prognostic factors for OS. Conclusion Five independent prognostic factors in patients with recurrent or metastatic pancreatic cancer who received gemcitabine-based chemotherapy were identified. These findings may be helpful in prediction of prognosis in clinical practice and can be used as a stratification factor for clinical trials.

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    Pancreatology.2019; 19(5): 722.     CrossRef
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    James Bundred, Sivesh K. Kamarajah, Keith J. Roberts
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    Sachiyo Onishi, Masahiro Tajika, Tsutomu Tanaka, Yutaka Hirayama, Kazuo Hara, Nobumasa Mizuno, Takamichi Kuwahara, Nozomi Okuno, Yoshitaka Inaba, Takeshi Kodaira, Tetsuya Abe, Kei Muro, Masahito Shimizu, Yasumasa Niwa
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Prognostic Scoring Index for Patients with Metastatic Pancreatic Adenocarcinoma
Hyung Soon Park, Hye Sun Lee, Ji Soo Park, Joon Seong Park, Dong Ki Lee, Se-Joon Lee, Dong Sup Yoon, Min Goo Lee, Hei-Cheul Jeung
Cancer Res Treat. 2016;48(4):1253-1263.   Published online February 3, 2016
DOI: https://doi.org/10.4143/crt.2015.400
AbstractAbstract PDFPubReaderePub
Purpose
This study focused on implementation of a prognostic scoring index based on clinico-laboratory parameters measured routinely on admission in metastatic pancreatic cancer patients.
Materials and Methods
Records from 403 patients of metastatic disease were analyzed retrospectively. Continuous variables were dichotomized according to the normal range or the best cut-off values statistically determined by Contal and O’Quigley method, and then analyzed in association with prognosis—overall survival (OS), using Cox’s proportional hazard model. Scores were calculated by summing the rounded chi-square scores for the factors that emerged in the multivariate analysis.
Results
Performance status, hemoglobin, leucocyte count, neutrophil-lymphocyte ratio, and carcinoembryonic antigen were independent factors for OS. When patients were divided into three risk groups according to these factors, median survival was 11.7, 6.2, and 1.3 months for the low, intermediate, and high-risk groups, respectively (p < 0.001). Palliative chemotherapy has a significant survival benefit for low and intermediate-risk patients (median OS; 12.5 months vs. 5.9 months, p < 0.001 and 8.0 months vs. 2.0 months, p < 0.001, respectively).
Conclusion
We advocate the use of a multivariable approach with continuous variables for prognostic modeling. Our index is helpful in accurate patient risk stratification and may aid in treatment selection.

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p21-Activated Kinase 4 (PAK4) as a Predictive Marker of Gemcitabine Sensitivity in Pancreatic Cancer Cell Lines
Sung-Ung Moon, Jin Won Kim, Ji Hea Sung, Mi Hyun Kang, Se-Hyun Kim, Hyun Chang, Jeong-Ok Lee, Yu Jung Kim, Keun-Wook Lee, Jee Hyun Kim, Soo-Mee Bang, Jong Seok Lee
Cancer Res Treat. 2015;47(3):501-508.   Published online November 24, 2014
DOI: https://doi.org/10.4143/crt.2014.054
AbstractAbstract PDFPubReaderePub
Purpose
p21-activated kinases (PAKs) are involved in cytoskeletal reorganization, gene transcription, cell proliferation and survival, and oncogenic transformation. Therefore, we hypothesized that PAK expression levels could predict the sensitivity of pancreatic cancer cells to gemcitabine treatment, and PAKs could be therapeutic targets.
Materials and Methods
Cell viability inhibition by gemcitabine was evaluated in human pancreatic cancer cell lines (Capan-1, Capan-2, MIA PaCa-2, PANC-1, Aspc-1, SNU-213, and SNU-410). Protein expression and mRNA of molecules was detected by immunoblot analysis and reverse transcription polymerase chain reaction. To define the function of PAK4, PAK4 was controlled using PAK4 siRNA.
Results
Capan-2, PANC-1, and SNU-410 cells were resistant to gemcitabine treatment. Immunoblot analysis of signaling molecules reported to indicate gemcitabine sensitivity showed higher expression of PAK4 and lower expression of human equilibrative nucleoside transporter 1 (hENT1), a well-known predictive marker for gemcitabine activity, in the resistant cell lines. Knockdown of PAK4 using siRNA induced the upregulation of hENT1. In resistant cell lines (Capan-2, PANC-1, and SNU-410), knockdown of PAK4 by siRNA resulted in restoration of sensitivity to gemcitabine.
Conclusion
PAK4 could be a predictive marker of gemcitabine sensitivity and a potential therapeutic target to increase gemcitabine sensitivity in pancreatic cancer.

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Prognostic Value of Splenic Artery Invasion in Patients Undergoing Adjuvant Chemoradiotherapy after Distal Pancreatectomy for Pancreatic Adenocarcinoma
Byoung Hyuck Kim, Kyubo Kim, Eui Kyu Chie, Jin-Young Jang, Sun Whe Kim, Sae-Won Han, Do-Youn Oh, Seock-Ah Im, Tae-You Kim, Yung-Jue Bang, Ijin Joo, Sung W. Ha
Cancer Res Treat. 2015;47(2):274-281.   Published online September 12, 2014
DOI: https://doi.org/10.4143/crt.2014.025
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study was to evaluate the outcome of adjuvant chemoradiotherapy (CRT) after distal pancreatectomy (DP) in patients with pancreatic adenocarcinoma, and to identify the prognostic factors for these patients.
Materials and Methods
We performed a retrospective review of 62 consecutive patients who underwent curative DP followed by adjuvant CRT between 2000 and 2011. There were 31 men and 31 women, and the median age was 64 years (range, 38 to 80 years). Adjuvant radiotherapy was delivered to the tumor bed and regional lymph nodes with a median dose of 50.4 Gy (range, 40 to 55.8 Gy). All patients received concomitant chemotherapy, and 53 patients (85.5%) also received maintenance chemotherapy. The median follow-up period was 24 months.
Results
Forty patients (64.5%) experienced relapse. Isolated locoregional recurrence developed in 5 patients (8.1%) and distant metastasis in 35 patients (56.5%), of whom 13 had both locoregional recurrence and distant metastasis. The median overall survival (OS) and disease-free survival (DFS) were 37.5 months and 15.4 months, respectively. On multivariate analysis, splenic artery (SA) invasion (p=0.0186) and resection margin (RM) involvement (p=0.0004) were identified as significant adverse prognosticators for DFS. Also, male gender (p=0.0325) and RM involvement (p=0.0007) were associated with a significantly poor OS. Grade 3 or higher hematologic and gastrointestinal toxicities occurred in 22.6% and 4.8% of patients, respectively.
Conclusion
Adjuvant CRT may improve survival after DP for pancreatic body or tail adenocarcinoma. Our results indicated that SA invasion was a significant factor predicting inferior DFS, as was RM involvement. When SA invasion is identified preoperatively, neoadjuvant treatment may be considered.

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Gemcitabine Combined with Capecitabine Compared to Gemcitabine with or without Erlotinib as First-Line Chemotherapy in Patients with Advanced Pancreatic Cancer
Jae Yun Lim, Jang Ho Cho, Se Joon Lee, Dong Ki Lee, Dong Sup Yoon, Jae Yong Cho
Cancer Res Treat. 2015;47(2):266-273.   Published online August 29, 2014
DOI: https://doi.org/10.4143/crt.2013.158
AbstractAbstract PDFPubReaderePub
Purpose
The purpose of this study is to retrospectively compare the efficacy and tolerability between three regimens for first-line chemotherapy—gemcitabine plus capecitabine (GEM-X), gemcitabine plus erlotinib (GEM-T), and gemcitabine monotherapy (GEM)—in patients with advanced pancreatic cancer. Materials and Methods There was a total of 127 patients who underwent chemotherapy for pancreatic cancer between January 2007 and November 2011 at our institution. Patients were treated with either GEM (gemcitabine 1,000 mg/m2 on days 1, 8, and 15 every 4 weeks), GEM-T (gemcitabine 1,000 mg/m2 on days 1 and 8 every 3 weeks and erlotinib 100 mg daily), or GEM-X (gemcitabine 1,000 mg/m2 on days 1 and 8 every 3 weeks and capecitabine 850 mg/m2 twice daily for 2 weeks followed by 1 week’s rest) as the first-line treatment. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and toxicity were evaluated. Results The patient population was divided into groups depending on their first-line treatment: GEM (n=47), GEM-T (n=44), and GEM-X (n=36). GEM-X significantly improved ORR (21.2% vs. 12.7% and 15.9%), PFS (8.9 vs. 5.2 and 3.9 months; p < 0.001), and OS (12.1 vs. 10.4 and 9.9 months; p = 0.03) compared to GEM and GEM-T, respectively. There were higher incidences of some non-hematologic adverse events with GEM-X and GEM-T compared to GEM, but most were grade 1 or 2. Conclusion GEM-X presented better clinical efficacy and acceptable tolerability than GEM-T and GEM in advanced pancreatic cancers. It is worthy to further investigate which agent has a clinical advantage as a combination drug with gemcitabine in pancreatic cancer and to explore the predictive markers leading to personalize anti-cancer treatment.

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  • Clinical efficacy and safety of erlotinib combined with chemotherapy in the treatment of advanced pancreatic cancer: A meta-analysis
    Xiao-Yan Liu, Hong-Nian Pan, Yue Yu
    World Journal of Gastrointestinal Surgery.2024; 16(3): 921.     CrossRef
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    Umme Hani, Riyaz Ali M. Osmani, Ayesha Siddiqua, Shadma Wahab, Sadia Batool, Hissana Ather, Norhan Shereba, Ali Alqahtani
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    Kunxi Bao, Xiaobing Li, Xiaojing He, Lingyan Jian
    Clinical Therapeutics.2021; 43(6): 1107.     CrossRef
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    Andrada Seicean
    World Journal of Gastroenterology.2015; 21(20): 6127.     CrossRef
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  • 13 Web of Science
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A Phase II Trial of Gemcitabine plus Capecitabine for Patients with Advanced Pancreatic Cancer
Jong Gwon Choi, Jae Hong Seo, Sang Cheul Oh, Chul Won Choi, Jun Suk Kim
Cancer Res Treat. 2012;44(2):127-132.   Published online June 30, 2012
DOI: https://doi.org/10.4143/crt.2012.44.2.127
AbstractAbstract PDFPubReaderePub
PURPOSE
The purpose of this study was to determine the efficacy and safety of treatment using gemcitabine and capecitabine for patients with advanced pancreatic cancer.
MATERIALS AND METHODS
Patients with advanced unresectable pancreatic adenocarcinoma were enrolled in the study. Inclusion criteria included no prior systemic chemotherapy or radiation therapy, at least one radiographically documented and measurable tumor lesion, and adequate patient organ functions. The patients received 1,000 mg/m2 gemcitabine intravenously on days 1, 8 and 15, and 830 mg/m2 of oral capecitabine twice a day on days 1-21 of a 28-day cycle.
RESULTS
Fifty patients with a median age of 53 years (range, 39 to 76 years) were enrolled in the study. The median follow-up was 10.0 months. The objective response rate of the 50 patients was 48.0% (95% CI, 22.5 to 57.1%). The median time to progression and overall survival were 6.5 months (95% CI, 2.3 to 8.7 months) and 10.0 months (95% CI, 5.7 to 16.7 months), respectively. Grade 3-4 toxicities associated with chemotherapy included neutropenia (22%), anemia (8%), thrombocytopenia (6%), and hand-foot syndrome (10%).
CONCLUSION
Combination chemotherapy using gemcitabine and capecitabine was well tolerated and demonstrated promising efficacy in the treatment of advanced pancreatic cancer.

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Review Article
Tumor Angiogenesis: Initiation and Targeting - Therapeutic Targeting of an FGF-Binding Protein, an Angiogenic Switch Molecule, and Indicator of Early Stages of Gastrointestinal Adenocarcinomas -
Elena Tassi, Anton Wellstein
Cancer Res Treat. 2006;38(4):189-197.   Published online December 31, 2006
DOI: https://doi.org/10.4143/crt.2006.38.4.189
AbstractAbstract PDFPubReaderePub

Tumor angiogenesis has been related to the initiation as well as progression toward more aggressive behavior of human tumors. In particular, the activity of angiogenic factors is crucial for tumor progression. We previously characterized a secreted fibroblast growth factor-binding protein (FGF-BP) as a chaperone molecule, which binds to various FGFs, enhances FGF-mediated biochemical and biologic events and importantly is a crucial rate-limiting factor for tumor-dependent angiogenesis. We generated monoclonal antibodies that target FGF-BP protein and used them as a tool to evaluate frequency and pattern of FGF-BP expression during the malignant progression of pancreas and colorectal carcinoma in archival tissue samples. We found that FGF-BP is dramatically upregulated during the initiation of colorectal and pancreatic adenocarcinoma. Crucial genetic events underlying the initiation and progression of colorectal and pancreatic adenocarcinoma with a particular focus on the modulation of angiogenesis and antiangiogenic therapies are discussed. We propose that the upregulation of the secreted FGF-BP protein during early phases of pancreas and colon cancer could make this protein a possible serum marker indicating the presence of high-risk premalignant lesions. Furthermore, the biological activity of FGF-BP is neutralized by monoclonal antibodies suggesting the potential for antibody-based therapeutic targeting.

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Original Article
Identification of CLP36 as a Tumor Antigen that Induces an Antibody Response in Pancreatic Cancer
Su-Hyung Hong
Cancer Res Treat. 2005;37(1):71-77.   Published online February 28, 2005
DOI: https://doi.org/10.4143/crt.2005.37.1.71
AbstractAbstract PDFPubReaderePub
Purpose

Pancreatic cancer has a poor prognosis, due in part to the lack of an effective approach for its early detection. The identification of tumor antigens potentially provides a means for the early diagnosis. The purpose of this study was to use a proteomic approach for the identification of proteins that commonly induce a humoral response in patients with pancreatic cancer.

Materials and Methods

Proteins from the pancreatic adenocarcinoma cell line, BxPC3, were subjected to two-dimensional polyacrylamide gel electrophoresis, followed by Western blot analysis, where individual sera were tested for autoantibodies. Sera from 36 patients with pancreatic adenocarcinoma, and 68 from control groups (14 from lung adenocarcinoma, 19 from colon adenocarcinoma and 35 from healthy subjects) were analyzed. CLP36 expression was evaluated by immunohistochemical analysis and real-time PCR. The cellular localization of CLP36 as an autoantigen was investigated by Western blot analysis.

Results

The autoantibody was detected against a protein, identified by mass spectrometry as CLP36, in 14 of the 36 sera (38.9%) from patients with a pancreatic adenocarcinoma, and 3 of the 68 controls (4.4%). Immunohistochemical analysis of CLP36 in a tissue array demonstrated diffuse and consistent immunoreactivity in the pancreatic adenocarcinomas. The levels of CLP36 mRNA were highest in the pancreatic cancer cell lines of the different cells analyzed. The molecular weight of the protein displayed in the membrane-rich fraction was larger than that in the cytosolic fraction, which is likely attributable to a post-translational modification.

Conclusion

CLP36 was identified as a tumor autoantigen inducing a humoral immune response in pancreatic adenocarcinomas. More detailed studies need to be undertaken to understand whether the humoral response by CLP36 is tumor-specific.

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    Mona Motwani, Da-Qiang Li, Anelia Horvath, Rakesh Kumar, Wei-Guo Zhu
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