Cancer Research and Treatment

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

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.

Citations

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Clinical outcomes of completing total pancreatectomy for isolated recurrence of pancreatic ductal adenocarcinoma in the remnant pancreas after initial pancreatectomy
Yejong Park, Dae Wook Hwang, Jae Hoon Lee, Ki Byung Song, Eunsung Jun, Woohyung Lee, Song Cheol Kim
Surgery.2026; 192: 110088. CrossRef
Systematic Review and Meta-Analysis of Current and Novel Approaches in the Management of Borderline Resectable and Locally Advanced Pancreatic Cancer
Kelvin Le, Khang Duy Ricky Le, Wei Hong, Peter Gibbs, Osamu Yoshino, Belinda Lee
Cancers.2026; 18(7): 1139. CrossRef
Comparative survival outcomes of surgical resection versus radiotherapy after FOLFIRINOX in borderline resectable and locally advanced pancreatic cancer
Jiwon Yu, Jeong Ha Lee, Hyunju Shin, Hee Chul Park, Joon Oh Park, Jung Yong Hong, Minsuk Kwon, Ji Eun Shin, Kyu Taek Lee, Kwang Hyuck Lee, Jong Kyun Lee, Joo Kyung Park, Young Hoon Choi, Jin Seok Heo, In Woong Han, Sang Hyun Shin, Hongbeom Kim, Ji Hye Min
Precision and Future Medicine.2026; 10(1): 39. CrossRef
Statistical cure fraction in patients with borderline resectable pancreatic ductal adenocarcinoma undergoing neoadjuvant therapy followed by radical resection: a secondary analysis of reconstructed individual patient data
Yong Hyun Jang, Ru Ri Lee, Yongkeun Park
Annals of Surgical Treatment and Research.2025; 109(3): 162. CrossRef
Outcomes of conversion surgery following chemotherapy for initially unresectable metastatic pancreatic ductal adenocarcinoma: a retrospective cohort study in Taiwan
Ping-Jui Su, Wei-Hsun Lu, Ting-Kai Liao, Chih-Jung Wang, Ying-Jui Chao, Yan-Shen Shan
Journal of Cancer Research and Clinical Oncology.2025;[Epub] CrossRef

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Analysis of Plasma Circulating Tumor DNA in Borderline Resectable Pancreatic Cancer Treated with Neoadjuvant Modified FOLFIRINOX: Clinical Relevance of DNA Damage Repair Gene Alteration Detection: Dong-Hoon Lim, Hyunseok Yoon, Kyu-pyo Kim, Baek-Yeol Ryoo, Sang Soo Lee, Do Hyun Park, Tae Jun Song, Dae Wook Hwang, Jae Hoon Lee, Ki Byung Song, Song Cheol Kim, Seung-Mo Hong, Jaewon Hyung, Changhoon Yoo; Cancer Res Treat. 2023;55(4):1313-1320. Published online May 4, 2023; DOI: https://doi.org/10.4143/crt.2023.452

Abstract PDF Supplementary Material PubReader ePub

Purpose
There are no reliable biomarkers to guide treatment for patients with borderline resectable pancreatic cancer (BRPC) in the neoadjuvant setting. We used plasma circulating tumor DNA (ctDNA) sequencing to search biomarkers for patients with BRPC receiving neoadjuvant mFOLFIRINOX in our phase 2 clinical trial (NCT02749136).
Materials and Methods
Among the 44 patients enrolled in the trial, patients with plasma ctDNA sequencing at baseline or post-operation were included in this analysis. Plasma cell-free DNA isolation and sequencing were performed using the Guardant 360 assay. Detection of genomic alterations, including DNA damage repair (DDR) genes, were examined for correlations with survival.
Results
Among the 44 patients, 28 patients had ctDNA sequencing data qualified for the analysis and were included in this study. Among the 25 patients with baseline plasma ctDNA data, 10 patients (40%) had alterations of DDR genes detected at baseline, inclu-ding ATM, BRCA1, BRCA2 and MLH1, and showed significantly better progression-free survival than those without such DDR gene alterations detected (median, 26.6 vs. 13.5 months; log-rank p=0.004). Patients with somatic KRAS mutations detected at baseline (n=6) had significantly worse overall survival (median, 8.5 months vs. not applicable; log-rank p=0.003) than those without. Among 13 patients with post-operative plasma ctDNA data, eight patients (61.5%) had detectable somatic alterations.
Conclusion
Detection of DDR gene mutations from plasma ctDNA at baseline was associated with better survival outcomes of pati-ents with borderline resectable pancreatic ductal adenocarcinoma treated with neoadjuvant mFOLFIRINOX and may be a prognostic biomarker.

Citations

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Personalized tumor-informed circulating tumor DNA monitoring for early detection of recurrence in postoperative pancreatic cancer
Jingjing Chen, Lu Zou, Xinyuan Bai, Fan Tong, Jiayao Ni, Haochen Tang, Yaru Liu, Xiang Kong, Jiani Yin, Fufeng Wang, Huizi Sha, Fanyan Meng, Juan Du
Frontiers in Oncology.2026;[Epub] CrossRef
A Review of Circulating Tumor DNA (ctDNA) in Pancreatic Cancer: Ready for the Clinic?
Purvi Jonnalagadda, Virginia Arnold, Benjamin A. Weinberg
Journal of Gastrointestinal Cancer.2025;[Epub] CrossRef
Blood-based biomarkers in pancreatic ductal adenocarcinoma: developments over the last decade and what holds for the future- a review
Ronit Juthani, Ashish Manne
Frontiers in Oncology.2025;[Epub] CrossRef
Therapeutic pancreatic cancer biomarkers and pharmacogenetics
Ales Langer, Pavel Soucek, Veronika Vymetalkova, Cosmeri Rizzato, Stefania Bunduc, Ilias P. Nikas, Viktor Hlavac, Michal Kroupa, Riccardo Farinella, Daniele Campa, Beatrice Mohelnikova-Duchonova
Seminars in Cancer Biology.2025; 116: 31. CrossRef
A Practical Approach to Interpreting Circulating Tumor DNA in the Management of Gastrointestinal Cancers
Zexi Allan, David S Liu, Margaret M Lee, Jeanne Tie, Nicholas J Clemons
Clinical Chemistry.2024; 70(1): 49. CrossRef
High somatic mutations in circulating tumor DNA predict response of metastatic pancreatic ductal adenocarcinoma to first-line nab-paclitaxel plus S-1: prospective study
Lei Huang, Yao Lv, Shasha Guan, Huan Yan, Lu Han, Zhikuan Wang, Quanli Han, Guanghai Dai, Yan Shi
Journal of Translational Medicine.2024;[Epub] CrossRef
Decoding the Dynamics of Circulating Tumor DNA in Liquid Biopsies
Khadija Turabi, Kelsey Klute, Prakash Radhakrishnan
Cancers.2024; 16(13): 2432. CrossRef
Building on the clinical applicability of ctDNA analysis in non-metastatic pancreatic ductal adenocarcinoma
Ibone Labiano, Ana E. Huerta, Maria Alsina, Hugo Arasanz, Natalia Castro, Saioa Mendaza, Arturo Lecumberri, Iranzu Gonzalez-Borja, David Guerrero-Setas, Ana Patiño-Garcia, Gorka Alkorta-Aranburu, Irene Hernández-Garcia, Virginia Arrazubi, Elena Mata, Davi
Scientific Reports.2024;[Epub] CrossRef
Liquid biopsy analysis of lipometabolic exosomes in pancreatic cancer
Wei Guo, Peiyao Ying, Ruiyang Ma, Zuoqian Jing, Gang Ma, Jin Long, Guichen Li, Zhe Liu
Cytokine & Growth Factor Reviews.2023; 73: 69. CrossRef

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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

Abstract PDF Supplementary Material PubReader ePub

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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Prognostic factors in localized pancreatic ductal adenocarcinoma after neoadjuvant therapy and resection: a systematic review and meta-analysis
Ammar A Javed, Alyssar Habib, Omar Mahmud, Asad Saulat Fatimi, Mahip Grewal, Nabiha Mughal, Jin He, Christopher L Wolfgang, Lois Daamen, Marc G Besselink
JNCI: Journal of the National Cancer Institute.2025; 117(5): 840. CrossRef
Chemotherapy hypersensitivity: Current insights and novel desensitization strategies
Gordon K.H. Chu, Andy K.C. Kan, James K.Y. Hooi, Hye-Ryun Kang, Philip H. Li
Journal of Allergy and Hypersensitivity Diseases.2025; 6: 100042. CrossRef
Radiotherapy of pancreatic cancer patients. Past and present: a review
M. A. Ilin, S. D. Trotsenko, M. V. Podolskaya
Diagnostic radiology and radiotherapy.2025; 16(2): 20. CrossRef
Neoadjuvant Therapy for Resectable and Borderline Resectable Pancreatic Cancer
Julia Groszewska, Michał Romaniuk, Ewa Małecka-Wojciesko
International Journal of Translational Medicine.2025; 5(4): 55. CrossRef
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

Abstract PDF Supplementary Material PubReader ePub

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

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FOLFIRINOX: The Best Adjuvant Treatment for Ampullary Adenocarcinoma? A Multicenter Study by the Turkish Oncology Group (TOG)
Ali Kalem, Tulay Kus, Taha Koray Sahin, Omer Dizdar, Safa Can Efil, Mehmet Ali Nahit Sendur, Talat Aykut, Murat Araz, Hatice Bolek, Yuksel Urun, Nadiye Sever, Ibrahim Vedat Bayoglu, Eyyup Cavdar, Muhammed Fatih Sagıroglu, Tugce Kubra Gunes, Melike Ozcelik
Cancers.2025; 17(17): 2730. CrossRef
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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Spatial Distribution and Prognostic Implications of Tumor-Infiltrating FoxP3^- CD4⁺ T Cells in Biliary Tract Cancer: Hyung-Don Kim, Jwa Hoon Kim, Yeon-Mi Ryu, Danbee Kim, Sunmin Lee, Jaehoon Shin, Seung-Mo Hong, Ki-Hun Kim, Dong‐Hwan Jung, Gi‐Won Song, Dae Wook Hwang, Jae Hoon Lee, Ki Byung Song, Baek-Yeol Ryoo, Jae Ho Jeong, Kyu-pyo Kim, Sang-Yeob Kim, Changhoon Yoo; Cancer Res Treat. 2021;53(1):162-171. Published online August 31, 2020; DOI: https://doi.org/10.4143/crt.2020.704

Abstract PDF Supplementary Material PubReader ePub

Purpose
The clinical implications of tumor-infiltrating T cell subsets and their spatial distribution in biliary tract cancer (BTC) patients treated with gemcitabine plus cisplatin were investigated.
Materials and Methods
A total of 52 BTC patients treated with palliative gemcitabine plus cisplatin were included. Multiplexed immunohistochemistry was performed on tumor tissues, and immune infiltrates were separately analyzed for the stroma, tumor margin, and tumor core.
Results
The density of CD8⁺ T cells, FoxP3^- CD4⁺ helper T cells, and FoxP3⁺ CD4⁺ regulatory T cells was significantly higher in the tumor margin than in the stroma and tumor core. The density of LAG3- or TIM3-expressing CD8⁺ T cell and FoxP3^- CD4⁺ helper T cell infiltrates was also higher in the tumor margin. In extrahepatic cholangiocarcinoma, there was a higher density of T cell subsets in the tumor core and regulatory T cells in all regions. A high density of FoxP3^-CD4⁺ helper T cells in the tumor margin showed a trend toward better progression-free survival (PFS) (p=0.092) and significantly better overall survival (OS) (p=0.012). In multivariate analyses, a high density of FoxP3^- CD4⁺ helper T cells in the tumor margin was independently associated with favorable PFS and OS.
Conclusion
The tumor margin is the major site for the active infiltration of T cell subsets with higher levels of LAG3 and TIM3 expression in BTC. The density of tumor margin-infiltrating FoxP3^-CD4⁺ helper T cells may be associated with clinical outcomes in BTC patients treated with gemcitabine plus cisplatin.

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Frontiers in Immunology.2025;[Epub] CrossRef
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Prognostic Predictability of American Joint Committee on Cancer 8th Staging System for Perihilar Cholangiocarcinoma: Limited Improvement Compared with the 7th Staging System: Jong Woo Lee, Jae Hoon Lee, Yejong Park, Woohyung Lee, Jaewoo Kwon, Ki Byung Song, Dae Wook Hwang, Song Cheol Kim; Cancer Res Treat. 2020;52(3):886-895. Published online March 12, 2020; DOI: https://doi.org/10.4143/crt.2020.023

Abstract PDF PubReader ePub

Purpose
This study was conducted to evaluate the prognostic values of the 7th and 8th American Joint Committee on Cancer (AJCC) staging systems for patients with resected perihilar cholangiocarcinoma (PHCC).
Materials and Methods
A total of 348 patients who underwent major hepatectomy for PHCC between 2008 and 2015 were identified from a single center. Overall survival (OS) was estimated using the Kaplan-Meier method and compared across stage groups with the log-rank test. The concordance index was used to evaluate the prognostic predictability of the 8th AJCC staging system compared with that of the 7th.
Results
In the 8th edition, the stratification of each group of T classification improved compared to that in the 7th, as the survival rate of T4 decreased (T2, 31.2%; T3, 13.9%; T4, 15.1%; T1- T2, p=0.260; T2-T3, p=0.001; T3-T4, p=0.996). Both editions showed significant survival differences between each N category, except between N1 and N2 (p=0.063) in 7th edition. Differences of point estimates between the 8th and 7th T and N classification and overall stages were +0.028, +0.006, and +0.039, respectively (T, p=0.005; N, p=0.115; overall stage, p=0.005). In multivariable analysis, posthepatectomy liver failure, T category, N category, distant metastasis, histologic differentiation, intraoperative transfusion, and resection margin status were associated with OS.
Conclusion
The prognostic predictability of 8th AJCC staging for PHCC improved slightly, with statistical significance, compared to the 7th edition, but its overall performance is still unsatisfactory.

Citations

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Tao Wei, Jian Zhang, Odysseas P. Chatzipanagiotou, Shouliang Guo, Alfredo Guglielmi, Hugo P. Marques, Federico Aucejo, Shishir K. Maithel, Carlo Pulitano, George A. Poultsides, Xu-Feng Zhang, Bas Groot Koerkamp, Endo Itaru, Tingbo Liang, Timothy M. Pawlik
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Efficacy and Safety of Pembrolizumab in Patients with Refractory Advanced Biliary Tract Cancer: Tumor Proportion Score as a Potential Biomarker for Response: Junho Kang, Jae Ho Jeong, Hee-Sang Hwang, Sang Soo Lee, Do Hyun Park, Dong Wook Oh, Tae Jun Song, Ki-Hun Kim, Shin Hwang, Dae Wook Hwang, Song Cheol Kim, Jin-hong Park, Seung-Mo Hong, Kyu-pyo Kim, Baek-Yeol Ryoo, Changhoon Yoo; Cancer Res Treat. 2020;52(2):594-603. Published online December 18, 2019; DOI: https://doi.org/10.4143/crt.2019.493

Abstract PDF PubReader ePub

Purpose
The current standard chemotherapy for advanced biliary tract cancer (BTC) has limited benefit, and novel therapies need to be investigated.
Materials and Methods
In this prospective cohort study, programmed death ligand-1 (PD-L1)–positive BTC patients who progressed on first-line gemcitabine plus cisplatin were enrolled. Pembrolizumab 200 mg was administered intravenously every 3 weeks.
Results
Between May 2018 and February 2019, 40 patients were enrolled. Pembrolizumab was given as second-line (47.5%) or ≥ third-line therapy (52.5%). The objective response rate was 10% and 12.5% by Response Evaluation Criteria in Solid Tumor (RECIST) v1.1 and immune- modified RECIST (imRECIST) and median duration of response was 6.3 months. Among patients with progressive disease as best response, one patient (1/20, 5.0%) achieved complete response subsequently. The median progression-free survival (PFS) and overall survival (OS) were 1.5 months (95% confidence interval [CI], 0.0 to 3.0) and 4.3 months (95% CI, 3.5 to 5.1), respectively, and objective response per imRECIST was significantly associated with PFS (p < 0.001) and OS (p=0.001). Tumor proportion score ≥ 50% was significantly associated with higher response rates including the response after pseudoprogression (vs. < 50%; 37.5% vs. 6.5%; p=0.049).
Conclusion
Pembrolizumab showed modest anti-tumor activity in heavily pretreated PD-L1–positive BTC patients. In patients who showed objective response, durable response could be achieved.

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Validation of the 8th Edition of the American Joint Committee on Cancer Staging System for Gallbladder Cancer and Implications for the Follow-up of Patients without Node Dissection: You-Na Sung, Minjeong Song, Jae Hoon Lee, Ki Byung Song, Dae Wook Hwang, Chul-Soo Ahn, Shin Hwang, Seung-Mo Hong; Cancer Res Treat. 2020;52(2):455-468. Published online October 17, 2019; DOI: https://doi.org/10.4143/crt.2019.271

Abstract PDF PubReader ePub

Purpose
The 8th edition of gallbladder cancer staging in the American Joint Committee on Cancer (AJCC) staging system changed the T and N categories.
Materials and Methods
In order to validate the new staging system, a total of 348 surgically resected gallbladder cancers were grouped based on the 8th edition of the T and N categories and compared with patients’ survival.
Results
Significant differences were noted between T1b-T2a (p=0.003) and T2b-T3 (p < 0.001) tumors, but not between Tis-T1a, T1a-T1b, and T2a-T2b tumors. However, significant survival differences were observed both by the overall and pair-wise (T1-T2, T2-T3) comparisons (all, p < 0.001) without dividing T1/T2 subcategories. When cases with ≥ 6 examined lymph nodes were evaluated, significant survival differences were observed among the entire comparison (p < 0.001) and pair-wise comparisons of N0-N1 (p=0.001) and N1-N2 (p=0.039) lesions. When cases without nodal dissection (NX) were additionally compared, significant survival differences were observed between patients with N0-NX (p=0.001) and NX-N1 (p < 0.001) lesions.
Conclusion
The T category in the 8th edition of the AJCC staging system did not completely stratify the prognosis of patients with gallbladder cancer. Modification by eliminating T subcategories can better stratify the prognosis. In contrast, the N category clearly determines patients’ survival with ≥ 6 examined lymph nodes. The survival time in patients of gallbladder cancers without nodal dissection is between N0 and N1 cases. Therefore, close postoperative followed up is recommended for those patients.

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Prognosis of Pancreatic Cancer Patients with Synchronous or Metachronous Malignancies from Other Organs Is Better than Those with Pancreatic Cancer Only: Su-Jin Shin, Hosub Park, You-Na Sung, Changhoon Yoo, Dae Wook Hwang, Jin-hong Park, Kyu-pyo Kim, Sang Soo Lee, Baek-Yeol Ryoo, Dong-Wan Seo, Song Cheol Kim, Seung-Mo Hong; Cancer Res Treat. 2018;50(4):1175-1185. Published online December 20, 2017; DOI: https://doi.org/10.4143/crt.2017.494

Abstract PDF Supplementary Material PubReader ePub

Purpose
Pancreatic cancer associated double primary tumors are rare and their clinicopathologic characteristics are not well elucidated.
Materials and Methods
Clinicopathologic factors of 1,352 primary pancreatic cancers with or without associated double primary tumors were evaluated.
Results
Of resected primary pancreatic cancers, 113 (8.4%) had associated double primary tumors, including 26 stomach, 25 colorectal, 18 lung, and 13 thyroid cancers. The median interval between the diagnoses of pancreatic cancer and associated double primary tumors was 0.5 months. Overall survival (OS) of pancreatic cancer patients with associated double primary tumors was longer than those with pancreatic cancer only (median, 23.1 months vs. 17.0 months, p=0.002). Patients whose pancreatic cancers were resected before the diagnosis of metachronous tumors had a better OS than patients whose pancreatic cancer resected after the diagnosis of metachronous tumors (48.9 months and 13.5 months, p=0.001) or those whose pancreatic cancers were resected synchronously with non-pancreas tumors (19.1 months, p=0.043). The OS of pancreatic cancer patients with stomach (33.9 months, p=0.032) and thyroid (117.8 months, p=0.049) cancers was significantly better than those with pancreas cancer only (17.0 months).
Conclusion
About 8% of resected pancreatic cancers had associated double primary tumors, and those from the colorectum, stomach, lung, and thyroid were common. Patients whose pancreatic cancer was resected before the diagnosis of metachronous tumors had better OS than those resected after the diagnosis of metachronous tumors or those resected synchronously.

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