Cancer Research and Treatment

Special Article

Clinical Practice Recommendations for the Use of Next-Generation Sequencing in Patients with Solid Cancer: A Joint Report from KSMO and KSP: Miso Kim, Hyo Sup Shim, Sheehyun Kim, In Hee Lee, Jihun Kim, Shinkyo Yoon, Hyung-Don Kim, Inkeun Park, Jae Ho Jeong, Changhoon Yoo, Jaekyung Cheon, In-Ho Kim, Jieun Lee, Sook Hee Hong, Sehhoon Park, Hyun Ae Jung, Jin Won Kim, Han Jo Kim, Yongjun Cha, Sun Min Lim, Han Sang Kim, Choong-kun Lee, Jee Hung Kim, Sang Hoon Chun, Jina Yun, So Yeon Park, Hye Seung Lee, Yong Mee Cho, Soo Jeong Nam, Kiyong Na, Sun Och Yoon, Ahwon Lee, Kee-Taek Jang, Hongseok Yun, Sungyoung Lee, Jee Hyun Kim, Wan-Seop Kim; Cancer Res Treat. 2024;56(3):721-742. Published online November 29, 2023; DOI: https://doi.org/10.4143/crt.2023.1043

Abstract PDF PubReader ePub: In recent years, next-generation sequencing (NGS)–based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.

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Erratum

ERRATUM: Recommendations for the Use of Next-Generation Sequencing and the Molecular Tumor Board for Patients with Advanced Cancer: A Report from KSMO and KCSG Precision Medicine Networking Group: Shinkyo Yoon, Miso Kim, Yong Sang Hong, Han Sang Kim, Seung Tae Kim, Jihun Kim, Hongseok Yun, Changhoon Yoo, Hee Kyung Ahn, Hyo Song Kim, In Hee Lee, In-Ho Kim, Inkeun Park, Jae Ho Jeong, Jaekyung Cheon, Jin Won Kim, Jina Yun, Sun Min Lim, Yongjun Cha, Se Jin Jang, Dae Young Zang, Tae Won Kim, Jin Hyoung Kang, Jee Hyun Kim; Cancer Res Treat. 2023;55(3):1061-1061. Published online April 21, 2023; DOI: https://doi.org/10.4143/crt.2021.1115.E; Corrects: Cancer Res Treat 2022;54(1):1

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Original Article

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

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.

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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
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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
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Frontiers in Oncology.2024;[Epub] CrossRef

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Special Article

Recommendations for the Use of Next-Generation Sequencing and the Molecular Tumor Board for Patients with Advanced Cancer: A Report from KSMO and KCSG Precision Medicine Networking Group: Shinkyo Yoon, Miso Kim, Yong Sang Hong, Han Sang Kim, Seung Tae Kim, Jihun Kim, Hongseok Yun, Changhoon Yoo, Hee Kyung Ahn, Hyo Song Kim, In Hee Lee, In-Ho Kim, Inkeun Park, Jae Ho Jeong, Jaekyung Cheon, Jin Won Kim, Jina Yun, Sun Min Lim, Yongjun Cha, Se Jin Jang, Dae Young Zang, Tae Won Kim, Jin Hyoung Kang, Jee Hyun Kim; Cancer Res Treat. 2022;54(1):1-9. Published online December 13, 2021; DOI: https://doi.org/10.4143/crt.2021.1115; Correction in: Cancer Res Treat 2023;55(3):1061

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Next-generation sequencing (NGS) is becoming essential in the fields of precision oncology. With implementation of NGS in daily clinic, the needs for continued education, facilitated interpretation of NGS results and optimal treatment delivery based on NGS results have been addressed. Molecular tumor board (MTB) is multidisciplinary approach to keep pace with the growing knowledge of complex molecular alterations in patients with advanced solid cancer. Although guidelines for NGS use and MTB have been developed in western countries, there is limitation for reflection of Korea’s public health environment and daily clinical practice. These recommendations provide a critical guidance from NGS panel testing to final treatment decision based on MTB discussion.

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Expert Consensus on Molecular Tumor Boards in Taiwan: Joint Position Paper by the Taiwan Oncology Society and the Taiwan Society of Pathology
Ming-Huang Chen, Wan-Shan Li, Bin-Chi Liao, Chiao-En Wu, Chien-Feng Li, Chia-Hsun Hsieh, Feng-Che Kuan, Huey-En Tzeng, Jen-Fan Hang, Nai-Jung Chiang, Tse-Ching Chen, Tom Wei-Wu Chen, John Wen-Cheng Chang, Yao-Yu Hsieh, Yen-Lin Chen, Yi-Chen Yeh, Yi-Hsin L
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Pragmatic nationwide master observational trial based on genomic alterations in advanced solid tumors: KOrean Precision Medicine Networking Group Study of MOlecular profiling guided therapy based on genomic alterations in advanced Solid tumors (KOSMOS)-II
Sun Young Kim, Jee Hyun Kim, Tae-Yong Kim, Sook Ryun Park, Shinkyo Yoon, Soohyeon Lee, Se-Hoon Lee, Tae Min Kim, Sae-Won Han, Hye Ryun Kim, Hongseok Yun, Sejoon Lee, Jihun Kim, Yoon-La Choi, Kui Son Choi, Heejung Chae, Hyewon Ryu, Gyeong-Won Lee, Dae Youn
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Journal of Translational Medicine.2024;[Epub] CrossRef
Clinical practice recommendations for the use of next-generation sequencing in patients with solid cancer: a joint report from KSMO and KSP
Miso Kim, Hyo Sup Shim, Sheehyun Kim, In Hee Lee, Jihun Kim, Shinkyo Yoon, Hyung-Don Kim, Inkeun Park, Jae Ho Jeong, Changhoon Yoo, Jaekyung Cheon, In-Ho Kim, Jieun Lee, Sook Hee Hong, Sehhoon Park, Hyun Ae Jung, Jin Won Kim, Han Jo Kim, Yongjun Cha, Sun
Journal of Pathology and Translational Medicine.2024; 58(4): 147. CrossRef
Clinical Practice Recommendations for the Use of Next-Generation Sequencing in Patients with Solid Cancer: A Joint Report from KSMO and KSP
Miso Kim, Hyo Sup Shim, Sheehyun Kim, In Hee Lee, Jihun Kim, Shinkyo Yoon, Hyung-Don Kim, Inkeun Park, Jae Ho Jeong, Changhoon Yoo, Jaekyung Cheon, In-Ho Kim, Jieun Lee, Sook Hee Hong, Sehhoon Park, Hyun Ae Jung, Jin Won Kim, Han Jo Kim, Yongjun Cha, Sun
Cancer Research and Treatment.2024; 56(3): 721. CrossRef
Nationwide precision oncology pilot study: KOrean Precision Medicine Networking Group Study of MOlecular profiling-guided therapy based on genomic alterations in advanced solid tumors (KOSMOS) KCSG AL-20-05
T.-Y. Kim, S.Y. Kim, J.H. Kim, H.A. Jung, Y.J. Choi, I.G. Hwang, Y. Cha, G.-W. Lee, Y.-G. Lee, T.M. Kim, S.-H. Lee, S. Lee, H. Yun, Y.L. Choi, S. Yoon, S.W. Han, T.-Y. Kim, T.W. Kim, D.Y. Zang, J.H. Kang
ESMO Open.2024; 9(10): 103709. CrossRef
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Yongjun Cha, Sheehyun Kim, Sae-Won Han
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Mutational evolution after chemotherapy‐progression in metastatic colorectal cancer revealed by circulating tumor DNA analysis
Sheehyun Kim, Yongjun Cha, Yoojoo Lim, Hanseong Roh, Jun‐Kyu Kang, Kyung‐Hun Lee, Min Jung Kim, Ji Won Park, Seung‐Bum Ryoo, Hwang‐Phill Kim, Seung‐Yong Jeong, Kyu Joo Park, Sae‐Won Han, Tae‐You Kim
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Yuji SHIMODA, Takeshi NAGASHIMA, Kenichi URAKAMI, Fukumi KAMADA, Sou NAKATANI, Maki MIZUGUCHI, Masakuni SERIZAWA, Keiichi HATAKEYAMA, Keiichi OHSHIMA, Tohru MOCHIZUKI, Sumiko OHNAMI, Shumpei OHNAMI, Takeshi KAWAKAMI, Kentaro YAMAZAKI, Haruyasu MURAKAMI, H
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Somatic Mutations of TP53 Identified by Targeted Next-Generation Sequencing Are Poor Prognostic Factors for Primary Operable Breast Cancer: A Single-Center Study
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Original Articles

Breast cancer

Comparison of the Effectiveness and Clinical Outcome of Everolimus Followed by CDK4/6 Inhibitors with the Opposite Treatment Sequence in Hormone Receptor-Positive, HER2-Negative Metastatic Breast Cancer: Hyehyun Jeong, Jae Ho Jeong, Jeong Eun Kim, Jin-Hee Ahn, Kyung Hae Jung, Sung-Bae Kim; Cancer Res Treat. 2022;54(2):469-477. Published online June 23, 2021; DOI: https://doi.org/10.4143/crt.2021.205

Abstract PDF Supplementary Material PubReader ePub

Purpose
In hormone receptor-positive, human epidermal growth factor receptor 2–negative metastatic breast cancer (HR+ HER2–MBC), the mainstay treatment options include cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) and everolimus (EVE) in combination with endocrine treatment. This study aims to compare the outcomes of the following treatment sequences: CDK4/6i followed by EVE and EVE followed by CDK4/6i.
Materials and Methods
Data from HR+ HER2– MBC patients treated between January 2014 and November 2020 with both CDK4/6i and EVE were retrospectively analyzed.
Results
Among the 88 patients included in the study, 51 received CDK4/6i before EVE (C→E group), and 37 received EVE before CDK4/6i (E→C group) with endocrine treatment. More patients in the E→C group had endocrine resistance (13.7% vs. 40.5%), experienced palliative chemotherapy (7.8% vs. 40.5%), and were heavily treated (treated as ≥ 3rd line, 5.9% vs. 40.5%). Median overall survival was 46.8 months in the C→E group and 38.9 months in the E→C group (p=0.151). Median composite progression-free survival (PFS), defined as the time from the start of the preceding regimen to disease progression on the following regimen or death, was 24.8 months in the C→E group vs. 21.8 months in the E→C group (p=0.681). Median PFS2/PFS1 ratio did not differ significantly between groups (0.5 in the C→E group, 0.6 in the E→C group; p=0.775). Ten patients (11.4%) discontinued EVE, and two patients (2.3%) discontinued CDK4/6i during treatment.
Conclusion
Although the CDK4/6i-based regimen should be considered as an earlier line of treatment, CDK4/6i- and EVE-based treatments can be valid options in circumstances where the other treatment had been already given.

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The different sequences of CDK4/6 inhibitor and mTOR inhibitor in HR+/HER2-advanced breast cancer: A multicenter real-world study
Yuqian Liao, Yujing Tan, Yipeng Li, Fei Ma, Jiayu Wang, Pin Zhang, Qing Li, Qiao Li, Yang Luo, Bo Lan, Shanshan Chen, Binghe Xu, Hanfang Jiang, Weihong Zhao, Ying Fan
Heliyon.2024; 10(19): e38147. CrossRef
Long-Term Results with Everolimus in Advanced Hormone Receptor Positive Breast Cancer in a Multicenter National Real-World Observational Study
Hélène François-Martin, Audrey Lardy-Cléaud, Barbara Pistilli, Christelle Levy, Véronique Diéras, Jean-Sébastien Frenel, Séverine Guiu, Marie-Ange Mouret-Reynier, Audrey Mailliez, Jean-Christophe Eymard, Thierry Petit, Mony Ung, Isabelle Desmoulins, Paule
Cancers.2023; 15(4): 1191. CrossRef
Selective protection of normal cells from chemotherapy, while killing drug-resistant cancer cells
Mikhail V. Blagosklonny
Oncotarget.2023; 14(1): 193. CrossRef
A systematic review of computational approaches to understand cancer biology for informed drug repurposing
Faheem Ahmed, Anupama Samantasinghar, Afaque Manzoor Soomro, Sejong Kim, Kyung Hyun Choi
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Tetraspanin 1 (TSPAN1) promotes growth and transferation of breast cancer cells via mediating PI3K/Akt pathway
Yange Wu, Wenxiu Chen, Yufeng Gong, Hongxia Liu, Bo Zhang
Bioengineered.2021; 12(2): 10761. CrossRef

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Gastrointestinal cancer

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

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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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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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Deciphering the tumor immune microenvironment from a multidimensional omics perspective: insight into next-generation CAR-T cell immunotherapy and beyond
Zhaokai Zhou, Jiahui Wang, Jiaojiao Wang, Shuai Yang, Ruizhi Wang, Ge Zhang, Zhengrui Li, Run Shi, Zhan Wang, Qiong Lu
Molecular Cancer.2024;[Epub] CrossRef
Tumor-infiltrating T lymphocytes: A promising immunotherapeutic target for preventing immune escape in cholangiocarcinoma
Sijia Hua, Xinyi Gu, Hangbin Jin, Xiaofeng Zhang, Qiang Liu, Jianfeng Yang
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Focusing on the Immune Cells: Recent Advances in Immunotherapy for Biliary Tract Cancer
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Prognostic value of tumor-infiltrating lymphocytes in distal extrahepatic bile duct carcinoma
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Siqi Yang, Ruiqi Zou, Yushi Dai, Yafei Hu, Fuyu Li, Haijie Hu
International Journal of Oncology.2023;[Epub] CrossRef
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Chaoqun Li, Lei Bie, Muhua Chen, Jieer Ying
Exploration of Targeted Anti-tumor Therapy.2023; 4(6): 1310. CrossRef
Dynamic increase of M2 macrophages is associated with disease progression of colorectal cancers following cetuximab-based treatment
Hyung-Don Kim, Sun Young Kim, Jihun Kim, Jeong Eun Kim, Yong Sang Hong, Buhm Han, Eunyoung Tak, Yeon-Mi Ryu, Sang-Yeob Kim, Tae Won Kim
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Taek Chung, Young Nyun Park
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The role of tumor-infiltrating lymphocytes in cholangiocarcinoma
Dong Liu, Lara Rosaline Heij, Zoltan Czigany, Edgar Dahl, Sven Arke Lang, Tom Florian Ulmer, Tom Luedde, Ulf Peter Neumann, Jan Bednarsch
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Clinical implications of the tumor microenvironment using multiplexed immunohistochemistry in patients with advanced or metastatic renal cell carcinoma treated with nivolumab plus ipilimumab
Jwa Hoon Kim, Gi Hwan Kim, Yeon-Mi Ryu, Sang-Yeob Kim, Hyung-Don Kim, Shin Kyo Yoon, Yong Mee Cho, Jae Lyun Lee
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Spatial architecture of the immune microenvironment orchestrates tumor immunity and therapeutic response
Tong Fu, Lei-Jie Dai, Song-Yang Wu, Yi Xiao, Ding Ma, Yi-Zhou Jiang, Zhi-Ming Shao
Journal of Hematology & Oncology.2021;[Epub] CrossRef

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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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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

Abstract PDF Supplementary Material PubReader ePub

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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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
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Liposomal irinotecan plus fluorouracil/leucovorin versus FOLFIRINOX as the second-line chemotherapy for patients with metastatic pancreatic cancer: a multicenter retrospective study of the Korean Cancer Study Group (KCSG)
H.S. Park, B. Kang, H.J. Chon, H.-S. Im, C.-K. Lee, I. Kim, M.J. Kang, J.E. Hwang, W.K. Bae, J. Cheon, J.O. Park, J.Y. Hong, J.H. Kang, J.H. Kim, S.H. Lim, J.W. Kim, J.-W. Kim, C. Yoo, H.J. Choi
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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

Abstract PDF Supplementary Material PubReader ePub

Purpose
Gemcitabine plus cisplatin (GemCis) is the standard first-line chemotherapy for patients with advanced biliary tract cancer (BTC). In ABC-02 study, the BTC patients received up to 6-8 cycles of 3-weekly GemCis; however, those without progression often receive more than 6-8 cycles. The clinical benefit of maintenance treatment in patients without progression is uncertain.
Materials and Methods
Advanced BTC patients treated with GemCis between April 2010 and February 2015 at Asan Medical Center, Seoul, Korea, were retrospectively analysed. The patients without progression after 6-8 cycles were stratified according to further treatment i.e., with or without further cycles of GemCis (maintenance vs. observation groups). The primary endpoint was overall survival (OS) and progression-free survival (PFS).
Results
Among the 740 BTC patients in the initial screen, 231 cases (31.2%) were eligible for analysis (111 in the observation group, 120 in the maintenance group). The median OS from the GemCis initiation was 20.5 months (95% confidence interval [CI], 15.4 to 25.6) and 22.4 months (95% CI, 17.0 to 27.8) in the observation and maintenance groups, respectively (p=0.162). The median PFS was 10.4 months (95% CI, 7.0 to 13.8) and 13.2 months (95% CI, 11.3 to 15.2), respectively (p=0.320).
Conclusions
GemCis maintenance is not associated with an improved survival outcome.

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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

Abstract PDF Supplementary Material PubReader ePub

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.

Citations

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