|
1
|
Wnuk J, Hudy D, Strzelczyk JK, Michalecki Ł, Dybek K, Gisterek-Grocholska I. Serum hsa-miR-22-3p, hsa-miR-885-5p, Lipase-to-Amylase Ratio, C-Reactive Protein, CA19-9, and Neutrophil-to-Lymphocyte Ratio as Prognostic Factors in Advanced Pancreatic Ductal Adenocarcinoma. Curr Issues Mol Biol 2025; 47:27. [PMID: 39852142 PMCID: PMC11763715 DOI: 10.3390/cimb47010027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2024] [Revised: 12/28/2024] [Accepted: 01/01/2025] [Indexed: 01/26/2025] Open
Abstract
Pancreatic cancer (PC) is the seventh most common cause of cancer-related death worldwide. The low survival rate may be due to late diagnosis and asymptomatic early-stage disease. Most patients are diagnosed at an advanced stage of the disease. The search for novel prognostic factors is still needed. Two miRNAs, miR-22-3p and miR-885-5p, which show increased expression in PC, were selected for this study. The aim of this study was to evaluate the utility of these miRNAs in the prognosis of PC. Other prognostic factors such as lipase-to-amylase ratio (LAR), neutrophil-to-lymphocyte ratio (NLR), and carbohydrate antigen 19-9 (CA19-9) were also evaluated in this study. This study was conducted in 50 patients previously diagnosed with pancreatic ductal adenocarcinoma in clinical stage (CS) III and IV. All patients underwent a complete medical history, physical examination, and routine laboratory tests including a complete blood count, C-reactive protein (CRP), CA19-9, lipase, and amylase. Two additional blood samples were taken from each patient to separate plasma and serum. Isolation of miRNA was performed using TRI reagent with cel-miR-39-3p as a spike-in control. Reverse transcription of miRNA was performed using a TaqMan Advanced miRNA cDNA Synthesis Kit. The relative expression levels of miR-22-3p and miR-885-5p were measured using RT-qPCR. Serum hsa-miR-22-3p was detected in 22 cases (44%), while hsa-miR-885-5p was detected in 33 cases (66%). There were no statistically significant differences in serum or plasma miRNA expression levels between patient groups based on clinical stage, gender, or BMI. There were no statistically significant differences in LAR between patients with different CS. For NLR, CRP and CA19-9 thresholds were determined using ROC analysis (6.63, 24.7 mg/L and 4691 U/mL, respectively). Cox's F test for overall survival showed statistically significant differences between groups (p = 0.002 for NLR, p = 0.007 for CRP and p = 0.007 for CA19-9). Utility as prognostic biomarkers was confirmed in univariate and multivariate analysis for CA19-9, CRP, and NLR. The selected miRNAs and LAR were not confirmed as reliable prognostic markers in PC.
Collapse
Affiliation(s)
- Jakub Wnuk
- Department of Oncology and Radiotherapy, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, 35 Ceglana St., 40-515 Katowice, Poland; (J.W.)
| | - Dorota Hudy
- Department of Medical and Molecular Biology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, 19 Jordana St., 41-808 Zabrze, Poland; (D.H.); (J.K.S.)
| | - Joanna Katarzyna Strzelczyk
- Department of Medical and Molecular Biology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, 19 Jordana St., 41-808 Zabrze, Poland; (D.H.); (J.K.S.)
| | - Łukasz Michalecki
- Department of Oncology and Radiotherapy, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, 35 Ceglana St., 40-515 Katowice, Poland; (J.W.)
| | - Kamil Dybek
- Central Laboratory, University Clinical Center, Medical University of Silesia in Katowice, 14 Medyków St., 40-752 Katowice, Poland
| | - Iwona Gisterek-Grocholska
- Department of Oncology and Radiotherapy, Faculty of Medical Sciences in Zabrze, Medical University of Silesia in Katowice, 35 Ceglana St., 40-515 Katowice, Poland; (J.W.)
| |
Collapse
|
|
2
|
Nam H, Lee W, Lee YJ, Kim JM, Jung KH, Hong SS, Kim SC, Park S. Taurine Synthesis by 2-Aminoethanethiol Dioxygenase as a Vulnerable Metabolic Alteration in Pancreatic Cancer. Biomol Ther (Seoul) 2025; 33:143-154. [PMID: 39637922 PMCID: PMC11704412 DOI: 10.4062/biomolther.2024.086] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2024] [Revised: 06/24/2024] [Accepted: 06/26/2024] [Indexed: 12/07/2024] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) exhibits an altered metabolic profile compared to normal pancreatic tissue. However, studies on actual pancreatic tissues are limited. Untargeted metabolomics analysis was conducted on 54 pairs of tumor and matched normal tissues. Taurine levels were validated via immunohistochemistry (IHC) on separate PDAC and normal tissues. Bioinformatics analysis of transcriptomics and proteomics data evaluated genes associated with taurine metabolism. Identified taurine-associated gene was validated through gene modulation. Clinical implications were evaluated using patient data. Metabolomics analysis showed a 2.51-fold increase in taurine in PDAC compared to normal tissues (n=54). IHC confirmed this in independent samples (n=99 PDAC, 19 normal). Bioinformatics identified 2-aminoethanethiol dioxygenase (ADO) as a key gene modulating taurine metabolism. IHC on a tissue microarray (39 PDAC, 10 normal) confirmed elevated ADO in PDAC. The ADO-Taurine axis correlated with PDAC recurrence and disease-free survival. ADO knockdown reduced cancer cell proliferation and tumor growth in a mouse xenograft model. The MEK-related signaling pathway is suggested to be modulated by ADO-Taurine metabolism. Our multi-omics investigation revealed elevated taurine synthesis mediated by ADO upregulation in PDAC. The ADO-Taurine axis may serve as a biomarker for PDAC prognosis and a therapeutic target.
Collapse
Affiliation(s)
- Hoonsik Nam
- Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea
| | - Woohyung Lee
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Republic of Korea
| | - Yun Ji Lee
- Department of Biomedical Sciences, College of Medicine, and Program in Biomedical Science & Engineering, Inha University, Incheon 22332, Republic of Korea
| | - Jin-Mo Kim
- Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea
| | - Kyung Hee Jung
- Department of Biomedical Sciences, College of Medicine, and Program in Biomedical Science & Engineering, Inha University, Incheon 22332, Republic of Korea
| | - Soon-Sun Hong
- Department of Biomedical Sciences, College of Medicine, and Program in Biomedical Science & Engineering, Inha University, Incheon 22332, Republic of Korea
| | - Song Cheol Kim
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul 05505, Republic of Korea
| | - Sunghyouk Park
- Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 08826, Republic of Korea
| |
Collapse
|
|
3
|
Jang JK, Byun JH, Choi SJ, Kim JH, Lee SS, Kim HJ, Yoo C, Kim KP, Hong SM, Seo DW, Hwang DW, Kim SC. Survival Outcomes According to NCCN Criteria for Resection Following Neoadjuvant Therapy for Patients with Localized Pancreatic Cancer. Ann Surg Oncol 2024:10.1245/s10434-024-16437-9. [PMID: 39485615 DOI: 10.1245/s10434-024-16437-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Accepted: 10/18/2024] [Indexed: 11/03/2024]
Abstract
BACKGROUND This study aimed to assess the prognostic value of the National Comprehensive Cancer Network (NCCN) criteria for resection following neoadjuvant therapy for patients with localized pancreatic ductal adenocarcinoma (PDAC). METHODS This retrospective single-center study assessed 193 consecutive patients with localized PDAC (104 males and 89 females; mean age, 61.1 ± 9.4 years) who underwent neoadjuvant therapy followed by surgery between January 2010 and March 2021. Combined resectability and carbohydrate antigen (CA) 19-9 evaluation before and after neoadjuvant therapy was used to determine whether patients were eligible for resection according to the NCCN criteria. Post-surgical overall survival (OS), recurrence free survival (RFS), and pathologic results were evaluated and compared between patients considered eligible according to the NCCN criteria and those considered ineligible. Preoperative factors associated with better OS and RFS also were investigated. RESULTS Of the 193 patients, 168 (87.0 %) were eligible for resection according to the NCCN criteria. The patients eligible according to the NCCN criteria showed marginally longer OS than those considered ineligible (p = 0.056). After adjustment of variables, meeting the NCCN criteria for resection was an independent predictor of better OS (hazard ratio, 0.57; 95 % confidence interval, 0.34-0.96; p = 0.034). The two groups had similar RFS. Lower T-staging (T2 or less) and less lympho-vascular invasion and peri-neural invasion were noted in the patients who met the NCCN criteria (p ≤ 0.045). CONCLUSIONS The patients eligible for resection according to the NCCN criteria showed a trend toward longer OS and better pathologic results than the patients considered ineligible.
Collapse
Affiliation(s)
- Jong Keon Jang
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Jae Ho Byun
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.
| | - Se Jin Choi
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Jin Hee Kim
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Seung Soo Lee
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Hyoung Jung Kim
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Changhoon Yoo
- Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Kyu-Pyo Kim
- Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Seung-Mo Hong
- Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Dong-Wan Seo
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Dae Wook Hwang
- Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Song Cheol Kim
- Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| |
Collapse
|
|
4
|
Li X, Yu R, Shi B, Chawla A, Feng X, Zhang K, Liang L. Liquid-liquid phase separation-related features of PYGB/ACTR3/CCNA2/ITGB1/ATP8A1/RAP1GAP2 predict the prognosis of pancreatic cancer. J Gastrointest Oncol 2024; 15:1723-1745. [PMID: 39279964 PMCID: PMC11399862 DOI: 10.21037/jgo-24-426] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Accepted: 08/06/2024] [Indexed: 09/18/2024] Open
Abstract
Background The growth and metastasis of pancreatic cancer (PC) has been found to be closely associated with liquid-liquid phase separation (LLPS). This study sought to identify LLPS-related biomarkers in PC to construct a robust prognostic model. Methods Transcriptomic data and clinical information related to PC were retrieved from publicly accessible databases. The PC-related data set was subjected to differential expression, Mendelian randomization (MR), univariate Cox, and least absolute selection and shrinkage operator analyses to identify biomarkers. Using the biomarkers, we subsequently constructed a risk model, identified the independent prognostic factors of PC, established a nomogram, and conducted an immune analysis. Results The study identified four genes linked with an increased risk of PC; that is, PYGB, ACTR3, CCNA2, and ITGB1. Conversely, ATP8A1, and RAP1GAP2 were found to provide protection against PC. These findings contributed significantly to the development of a highly precise risk model in which risk, age, and pathology N stage were categorized as independent factors in predicting the prognosis of PC patients. Using these factors, a nomogram was established to predict survival outcomes accurately. An immune analysis revealed varying levels of eosinophils, gamma delta T cells, and other immune cells between the distinct risk groups. The high-risk patients exhibited increased potential for immune escape, while the low-risk patients showed a higher response to immunotherapy. Conclusions Six genes were identified as having potential causal relationships with PC. These genes were integrated into a prognostic risk model, thereby serving as unique prognostic signatures. Our findings provide novel insights into predicting the prognosis of PC patients.
Collapse
Affiliation(s)
- Xiaofeng Li
- Department of Hepatobiliary Surgery, Shandong Provincial Third Hospital, Shandong University, Jinan, China
| | - Ranran Yu
- Department of Pathology, The Second Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Baochang Shi
- Department of Hepatobiliary Surgery, Shandong Provincial Third Hospital, Shandong University, Jinan, China
| | - Akhil Chawla
- Department of Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
- Division of Surgical Oncology, Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA
| | - Xianguang Feng
- Department of Hepatobiliary Surgery, Shandong Provincial Third Hospital, Shandong University, Jinan, China
| | - Kai Zhang
- Department of Hepatobiliary Surgery, Shandong Provincial Third Hospital, Shandong University, Jinan, China
| | - Li Liang
- Department of Hepatobiliary Surgery, Shandong Provincial Third Hospital, Shandong University, Jinan, China
| |
Collapse
|
|
5
|
Shibuki T, Otsuka T, Shimokawa M, Nakazawa J, Arima S, Fukahori M, Miwa K, Okabe Y, Koga F, Ueda Y, Kubotsu Y, Makiyama A, Shimokawa H, Takeshita S, Nishikawa K, Komori A, Otsu S, Hosokawa A, Sakai T, Oda H, Kawahira M, Arita S, Honda T, Taguchi H, Tsuneyoshi K, Kawaguchi Y, Fujita T, Sakae T, Nio K, Ide Y, Ureshino N, Shirakawa T, Mizuta T, Mitsugi K. Nanoliposomal irinotecan with fluorouracil and folinic acid, FOLFIRINOX, and S-1 as second-line treatment for unresectable pancreatic cancer after gemcitabine/nab-paclitaxel. Sci Rep 2024; 14:16906. [PMID: 39043707 PMCID: PMC11266600 DOI: 10.1038/s41598-024-65689-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Accepted: 06/24/2024] [Indexed: 07/25/2024] Open
Abstract
This study aimed to compare second-line treatment outcomes for patients with unresectable pancreatic cancer previously treated with gemcitabine plus nab-paclitaxel (GnP) therapy. We conducted an integrated analysis of two retrospective studies included 318 patients receiving nanoliposomal irinotecan + 5-fluorouracil/folinic acid (NFF) (n = 102), S-1 (n = 57), or FOLFIRINOX (n = 14) as second-line treatment. Median overall survival (OS) in the NFF group was 9.08 months, significantly better than S-1 (4.90 months, P = 0.002). FOLFIRINOX had a median OS of 4.77 months, not statistically different from NFF. Subgroup analyses of OS indicated NFF was generally superior, however, a statistical interaction was observed between the treatment regimen in serum Alb < 3.5 g/dL (P = 0.042) and serum CRP ≥ 0.3 mg/dL (P = 0.006). Median progression-free survival (PFS) was 2.93 months for NFF, significantly better than S-1 (2.53 months, P = 0.024), while FOLFIRINOX had a comparable PFS (3.04 months, P = 0.948). Multivariate analysis identified the serum CRP, serum CA19-9, duration of first-line GnP therapy, and use (yes/no) of S-1 for second-line treatment as independent predictors for OS. This study concludes that second-line NFF therapy demonstrated a more favorable OS compared to S-1 therapy, however, it is still important to consider the patient background characteristics while selecting the most appropriate treatment.
Collapse
Affiliation(s)
- Taro Shibuki
- Division of Drug and Diagnostic Development Promotion, Department for the Promotion of Drug and Diagnostic Development, Translational Research Support Office, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa-shi, Chiba, 277-8577, Japan
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa-shi, Chiba, 277-8577, Japan
| | - Taiga Otsuka
- Department of Medical Oncology, Saga-Ken Medical Center Koseikan, 400 Kase-machi, Saga-shi, Saga, 840-8571, Japan.
- Department of Internal Medicine, Minato Medical Clinic, 3-11-3 Nagahama, Chuo-ku, Fukuoka-shi, Fukuoka, 810-0072, Japan.
| | - Mototsugu Shimokawa
- Clinical Research Institute, National Kyushu Cancer Center, 3-1-1 Notame, Minami-ku, Fukuoka-shi, Fukuoka, 811-1395, Japan
- Department of Biostatistics, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube-shi, Yamaguchi, 755-8505, Japan
| | - Junichi Nakazawa
- Department of Gastroenterology, Kagoshima City Hospital, 37-1 Uearata-cho, Kagoshima-shi, Kagoshima, 890-8760, Japan
| | - Shiho Arima
- Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima-shi, Kagoshima, 890-8520, Japan
| | - Masaru Fukahori
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume-shi, Fukuoka, 830-0011, Japan.
- Kyoto Innovation Center for Next Generation Clinical Trials and iPS Cell Therapy, Kyoto University Hospital, 54 Kawaharacho, Shogoin, Sakyo-ku, Kyoto, 606-8507, Japan.
| | - Keisuke Miwa
- Multidisciplinary Treatment Cancer Center, Kurume University Hospital, 67 Asahi-machi, Kurume-shi, Fukuoka, 830-0011, Japan
| | - Yoshinobu Okabe
- Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, 67 Asahi-machi, Kurume-shi, Fukuoka, 830-0011, Japan
| | - Futa Koga
- Department of Hepatobiliary and Pancreatology, Saga Medical Center Koseikan, 400 Kase-machi, Saga-shi, Saga, 840-8571, Japan
| | - Yujiro Ueda
- Department of Hematology and Oncology, Japanese Red Cross Kumamoto Hospital, 2-1-1 Nagamine-Minami, Higashi-ku, Kumamoto-shi, Kumamoto, 861-8520, Japan
| | - Yoshihito Kubotsu
- Department of Internal Medicine, Karatsu Red Cross Hospital, 2430 Watada,Karatsu-shi, Saga, 847-8588, Japan
| | - Akitaka Makiyama
- Department of Hematology Oncology, Japan Community Healthcare Organization Kyushu Hospital, 1-8-1 Kishinoura, Yahatanishi-ku, Kitakyushu-shi, Fukuoka, 806-8501, Japan
- Cancer Center, Gifu University Hospital, 1-1 Yanagido, Gifu-shi, Gifu, 501-1194, Japan
| | - Hozumi Shimokawa
- Department of Hematology Oncology, Japan Community Healthcare Organization Kyushu Hospital, 1-8-1 Kishinoura, Yahatanishi-ku, Kitakyushu-shi, Fukuoka, 806-8501, Japan
| | - Shigeyuki Takeshita
- Department of Gastroenterology, Japanese Red Cross Nagasaki Genbaku Hospital, 3-15, Morimachi, Nagasaki-shi, Nagasaki, 852-8511, Japan
| | - Kazuo Nishikawa
- Department of Medical Oncology and Hematology, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu-shi, Oita, 879-5593, Japan
| | - Azusa Komori
- Department of Medical Oncology and Hematology, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu-shi, Oita, 879-5593, Japan
- Department of Gastrointestinal Medical Oncology, National Hospital Organization Shikoku Cancer Center, 160 Minamiumemoto-cho, Matsuyama-shi, Ehime, 791-0280, Japan
| | - Satoshi Otsu
- Department of Medical Oncology and Hematology, Oita University Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Yufu-shi, Oita, 879-5593, Japan
| | - Ayumu Hosokawa
- Department of Clinical Oncology, University of Miyazaki Hospital, 5200, Kiyotakechoukihara, Miyazaki-shi, Miyazaki, 889-1692, Japan
| | - Tatsunori Sakai
- Department of Medical Oncology, National Hospital Organization Kumamoto Medical Center, 1-5, Ninomaru, Chuo-ku, Kumamoto-shi, Kumamoto, 860-0008, Japan
| | - Hisanobu Oda
- Division of Integrative Medical Oncology, Saiseikai Kumamoto Hospital, 5-3-1,Oumi, Minami-ku, Kmamoto-shi, Kumamoto, 861-4193, Japan
| | - Machiko Kawahira
- Department of Gastroenterology, Kagoshima Kouseiren Hospital, 1-13-1, Yojirou,Kagoshima-shi, Kagoshima, 890-0062, Japan
| | - Shuji Arita
- Department of Chemotherapy, Miyazaki Prefectural Miyazaki Hospital, Miyazaki, Japan
| | - Takuya Honda
- Department of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki-shi, Nagasaki, 852-8501, Japan
| | - Hiroki Taguchi
- Department of Gastroenterology, Kagoshima City Hospital, 37-1 Uearata-cho, Kagoshima-shi, Kagoshima, 890-8760, Japan
- Department of Gastroenterology, Saiseikai Sendai Hospital, 2-46 Harada-cho, Satsumasendai-shi, Kagoshima, 895-0074, Japan
| | - Kengo Tsuneyoshi
- Department of Gastroenterology, Izumi General Medical Center, 520, Myoujin-cho, Izumi-shi, Kagoshima, 899-0131, Japan
| | - Yasunori Kawaguchi
- Department of Gastroenterology, Asakura Medical Association Hospital, 422-1, Raiha, Asakura-shi, Fukuoka, 838-0069, Japan
| | - Toshihiro Fujita
- Department of Gastroenterology, Saiseikai Sendai Hospital, 2-46 Harada-cho, Satsumasendai-shi, Kagoshima, 895-0074, Japan
| | - Takahiro Sakae
- Department of Gastroenterology, Saiseikai Sendai Hospital, 2-46 Harada-cho, Satsumasendai-shi, Kagoshima, 895-0074, Japan
| | - Kenta Nio
- Department of Medical Oncology, Sasebo Kyosai Hospital, 10-17 Shimanji-cho, Sasebo-shi, Nagasaki, 857-8575, Japan
- Department of Medical Oncology, Hamanomachi Hospital, 3-3-1 Nagahama, Chuo-ku, Fukuoka-shi, Fukuoka, 810-8539, Japan
| | - Yasushi Ide
- Department of Internal Medicine, Karatsu Red Cross Hospital, 2430 Watada,Karatsu-shi, Saga, 847-8588, Japan
- Department of Internal Medicine, National Hospital Organization Saga Hospital, 1-20-1 Hinode, Saga-shi, Saga, 849-8577, Japan
| | - Norio Ureshino
- Department of Medical Oncology, Saga-Ken Medical Center Koseikan, 400 Kase-machi, Saga-shi, Saga, 840-8571, Japan
- Department of Medical Oncology, Kimitsu Chuo Hospital, 1010 Sakurai, Kisarazu-shi, Chiba, 292-8535, Japan
| | - Tsuyoshi Shirakawa
- Eikoh Hospital, 3-8-15 Befu-nishi, Shime-machi, Kasuya-gun, Fukuoka, 811-2232, Japan
- Clinical Hematology Oncology Treatment Study Group, 1-14-6 Muromi-gaoka, Nishi-ku, Fukuoka-shi, Fukuoka, 819-0030, Japan
| | - Toshihiko Mizuta
- Department of Internal Medicine, Fujikawa Hospital, 1-2-6 Matsubara, Saga-shi, Saga, 840-0831, Japan
| | - Kenji Mitsugi
- Department of Medical Oncology, Sasebo Kyosai Hospital, 10-17 Shimanji-cho, Sasebo-shi, Nagasaki, 857-8575, Japan
- Department of Medical Oncology, Hamanomachi Hospital, 3-3-1 Nagahama, Chuo-ku, Fukuoka-shi, Fukuoka, 810-8539, Japan
| |
Collapse
|
|
6
|
Cai W, Zhu Y, Teng Z, Li D, Cong R, Chen Z, Ma X, Zhao X. Extracellular volume-based scoring system for tracking tumor progression in pancreatic cancer patients receiving intraoperative radiotherapy. Insights Imaging 2024; 15:116. [PMID: 38735009 PMCID: PMC11089023 DOI: 10.1186/s13244-024-01689-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2023] [Accepted: 04/03/2024] [Indexed: 05/13/2024] Open
Abstract
OBJECTIVES To investigate the value of extracellular volume (ECV) derived from portal-venous phase (PVP) in predicting prognosis in locally advanced pancreatic cancer (LAPC) patients receiving intraoperative radiotherapy (IORT) with initial stable disease (SD) and to construct a risk-scoring system based on ECV and clinical-radiological features. MATERIALS AND METHODS One hundred and three patients with LAPC who received IORT demonstrating SD were enrolled and underwent multiphasic contrast-enhanced CT (CECT) before and after IORT. ECV maps were generated from unenhanced and PVP CT images. Clinical and CT imaging features were analyzed. The independent predictors of progression-free survival (PFS) determined by multivariate Cox regression model were used to construct the risk-scoring system. Time-dependent receiver operating characteristic (ROC) curve analysis and the Kaplan-Meier method were used to evaluate the predictive performance of the scoring system. RESULTS Multivariable analysis revealed that ECV, rim-enhancement, peripancreatic fat infiltration, and carbohydrate antigen 19-9 (CA19-9) response were significant predictors of PFS (all p < 0.05). Time-dependent ROC of the risk-scoring system showed a satisfactory predictive performance for disease progression with area under the curve (AUC) all above 0.70. High-risk patients (risk score ≥ 2) progress significantly faster than low-risk patients (risk score < 2) (p < 0.001). CONCLUSION ECV derived from PVP of conventional CECT was an independent predictor for progression in LAPC patients assessed as SD after IORT. The scoring system integrating ECV, radiological features, and CA19-9 response can be used as a practical tool for stratifying prognosis in these patients, assisting clinicians in developing an appropriate treatment approach. CRITICAL RELEVANCE STATEMENT The scoring system integrating ECV fraction, radiological features, and CA19-9 response can track tumor progression in patients with LAPC receiving IORT, aiding clinicians in choosing individual treatment strategies and improving their prognosis. KEY POINTS Predicting the progression of LAPC in patients receiving IORT is important. Our ECV-based scoring system can risk stratifying patients with initial SD. Appropriate prognostication can assist clinicians in developing appropriate treatment approaches.
Collapse
Affiliation(s)
- Wei Cai
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yongjian Zhu
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ze Teng
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Dengfeng Li
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Rong Cong
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhaowei Chen
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiaohong Ma
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
| | - Xinming Zhao
- Department of Diagnostic Radiology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
| |
Collapse
|
|
7
|
Kikuchi Y, Shimada H, Yamasaki F, Yamashita T, Araki K, Horimoto K, Yajima S, Yashiro M, Yokoi K, Cho H, Ehira T, Nakahara K, Yasuda H, Isobe K, Hayashida T, Hatakeyama S, Akakura K, Aoki D, Nomura H, Tada Y, Yoshimatsu Y, Miyachi H, Takebayashi C, Hanamura I, Takahashi H. Clinical practice guidelines for molecular tumor marker, 2nd edition review part 2. Int J Clin Oncol 2024; 29:512-534. [PMID: 38493447 DOI: 10.1007/s10147-024-02497-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2024] [Accepted: 02/21/2024] [Indexed: 03/19/2024]
Abstract
In recent years, rapid advancement in gene/protein analysis technology has resulted in target molecule identification that may be useful in cancer treatment. Therefore, "Clinical Practice Guidelines for Molecular Tumor Marker, Second Edition" was published in Japan in September 2021. These guidelines were established to align the clinical usefulness of external diagnostic products with the evaluation criteria of the Pharmaceuticals and Medical Devices Agency. The guidelines were scoped for each tumor, and a clinical questionnaire was developed based on a serious clinical problem. This guideline was based on a careful review of the evidence obtained through a literature search, and recommendations were identified following the recommended grades of the Medical Information Network Distribution Services (Minds). Therefore, this guideline can be a tool for cancer treatment in clinical practice. We have already reported the review portion of "Clinical Practice Guidelines for Molecular Tumor Marker, Second Edition" as Part 1. Here, we present the English version of each part of the Clinical Practice Guidelines for Molecular Tumor Marker, Second Edition.
Collapse
Affiliation(s)
| | - Hideaki Shimada
- Department of Clinical Oncology, Toho University, Tokyo, Japan.
- Department of Surgery, Toho University, Tokyo, Japan.
| | - Fumiyuki Yamasaki
- Department of Neurosurgery, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
| | - Taku Yamashita
- Department of Otorhinolaryngology-Head and Neck Surgery, Kitasato University School of Medicine, Kanagawa, Japan
| | - Koji Araki
- Department of Otorhinolaryngology-Head and Neck Surgery, National Defense Medical College, Saitama, Japan
| | - Kohei Horimoto
- Department of Dermatology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | | | - Masakazu Yashiro
- Department of Molecular Oncology and Therapeutics, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Keigo Yokoi
- Department of Lower Gastrointestinal Surgery, Kitasato University School of Medicine, Kanagawa, Japan
| | - Haruhiko Cho
- Department of Surgery, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan
| | - Takuya Ehira
- Department of Gastroenterology, St. Marianna University School of Medicine, Kanagawa, Japan
| | - Kazunari Nakahara
- Department of Gastroenterology, St. Marianna University School of Medicine, Kanagawa, Japan
| | - Hiroshi Yasuda
- Department of Gastroenterology, St. Marianna University School of Medicine, Kanagawa, Japan
| | - Kazutoshi Isobe
- Division of Respiratory Medicine, Department of Internal Medicine (Omori), Toho University, Tokyo, Japan
| | - Tetsu Hayashida
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Shingo Hatakeyama
- Department of Urology, Hirosaki University Graduate School of Medicine, Aomori, Japan
| | | | - Daisuke Aoki
- International University of Health and Welfare Graduate School, Tokyo, Japan
| | - Hiroyuki Nomura
- Department of Obstetrics and Gynecology, School of Medicine, Fujita Health University, Aichi, Japan
| | - Yuji Tada
- Department of Pulmonology, School of Medicine, International University of Health and Welfare, Chiba, Japan
| | - Yuki Yoshimatsu
- Department of Patient-Derived Cancer Model, Tochigi Cancer Center Research Institute, Tochigi, Japan
| | - Hayato Miyachi
- Faculty of Clinical Laboratory Sciences, Nitobe Bunka College, Tokyo, Japan
| | - Chiaki Takebayashi
- Division of Hematology and Oncology, Department of Internal Medicine (Omori), Toho University, Tokyo, Japan
| | - Ichiro Hanamura
- Division of Hematology, Department of Internal Medicine, Aichi Medical University, Aichi, Japan
| | | |
Collapse
|
|
8
|
Pacheco-Barcia V, Custodio-Cabello S, Carrasco-Valero F, Palka-Kotlowska M, Mariño-Mendez A, Carmona-Bayonas A, Gallego J, Martín AJM, Jimenez-Fonseca P, Cabezon-Gutierrez L. Systemic Inflammation Response Index and weight loss as prognostic factors in metastatic pancreatic cancer: A concept study from the PANTHEIA-SEOM trial. World J Gastrointest Oncol 2024; 16:386-397. [PMID: 38425396 PMCID: PMC10900150 DOI: 10.4251/wjgo.v16.i2.386] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2023] [Revised: 12/14/2023] [Accepted: 01/10/2024] [Indexed: 02/02/2024] Open
Abstract
BACKGROUND The prognostic value of the Systemic Inflammation Response Index (SIRI) in advanced pancreatic cancer is recognized, but its correlation with patients´ nutritional status and outcomes remains unexplored. AIM To study the prognostic significance of SIRI and weight loss in metastatic pancreatic cancer. METHODS The PANTHEIA-Spanish Society of Medical Oncology (SEOM) study is a multicentric (16 Spanish hospitals), observational, longitudinal, non-interventional initiative, promoted by the SEOM Real World-Evidence work group. This pilot study sought to analyze the association between weight loss and inflammatory status as defined by SIRI. The cohort stems from a proof-of-concept pilot study conducted at one of the coordinating centers. Patients with pathologically confirmed metastatic pancreatic adenocarcinoma, treated from January 2020 to January 2023, were included. The index was calculated using the product of neutrophil and monocyte counts, divided by lymphocyte counts, obtained within 15 days before initiation chemotherapy. This study evaluated associations between overall survival (OS), SIRI and weight loss. RESULTS A total of 50 patients were included. 66% of these patients were male and the median age was 66 years. Metastasis sites: 36% liver, 12% peritoneal carcinomatosis, 10% lung, and 42% multiple locations. Regarding the first line palliative chemotherapy treatments: 50% received gemcitabine plus nab-paclitaxel; 28%, modified fluorouracil, leucovorin, irinotecan and oxaliplatin, and 16% were administered gemcitabine. 42% had a weight loss > 5% in the three months (mo) preceding diagnosis. 21 patients with a SIRI ≥ 2.3 × 103/L exhibited a trend towards a lower median OS compared to those with a SIRI < 2.3 × 103/L (4 vs 18 mo; P < 0.000). Among 21 patients with > 5% weight loss before diagnosis, the median OS was 6 mo, in contrast to 19 mo for those who did not experience such weight loss (P = 0.003). Patients with a weight loss > 5% showed higher SIRI levels. This difference was statistically significant (P < 0.000). For patients with a SIRI < 2.3 × 103/L, those who did not lose > 5% of their weight had an OS of 20 mo, compared to 11 mo for those who did (P < 0.001). No association was found between carbohydrate antigen 19-9 levels ≥ 1000 U/mL and weight loss. CONCLUSION A higher SIRI was correlated with decreased survival rates in patients with metastatic pancreatic cancer and associated with weight loss. An elevated SIRI is suggested as a predictor of survival, emphasizing the need for prospective validation in the upcoming PANTHEIA-SEOM study.
Collapse
Affiliation(s)
- Vilma Pacheco-Barcia
- Department of Medical Oncology, Hospital Universitario de Torrejon, Madrid 28850, Spain
| | - Sara Custodio-Cabello
- Department of Medical Oncology, Hospital Universitario de Torrejon, Madrid 28850, Spain
| | - Fatima Carrasco-Valero
- Department of Internal Medicine, Hospital Universitario de Torrejon, Madrid 28850, Spain
| | - Magda Palka-Kotlowska
- Department of Medical Oncology, Hospital Universitario de Torrejon, Madrid 28850, Spain
| | - Axel Mariño-Mendez
- Department of Medical Oncology, Hospital Universitario Central de Asturias, Oviedo 33011, Spain
| | - Alberto Carmona-Bayonas
- Department of Medical Oncology, Hospital Universitario Morales Meseguer, University of Murcia, Murcia 30001, Spain
| | - Javier Gallego
- Department of Medical Oncology, Hospital General Universitario de Elche, Elche 03202, Spain
| | - A J Muñoz Martín
- Department of Medical Oncology, Hospital General Universitario Gregorio Marañón, Universidad Complutense Madrid, Madrid 28007, Spain
| | - Paula Jimenez-Fonseca
- Department of Medical Oncology, Hospital Universitario Central de Asturias, Oviedo 33011, Spain
| | - Luis Cabezon-Gutierrez
- Department of Medical Oncology, Hospital Universitario de Torrejon, Madrid 28850, Spain
- Universidad Francisco de Vitoria, Madrid 28223, Spain
| |
Collapse
|
|
9
|
García-Ortiz MV, Cano-Ramírez P, Toledano-Fonseca M, Aranda E, Rodríguez-Ariza A. Diagnosing and monitoring pancreatic cancer through cell-free DNA methylation: progress and prospects. Biomark Res 2023; 11:88. [PMID: 37798621 PMCID: PMC10552233 DOI: 10.1186/s40364-023-00528-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2023] [Accepted: 09/21/2023] [Indexed: 10/07/2023] Open
Abstract
Pancreatic cancer is one of the most challenging cancers due to its high mortality rates. Considering the late diagnosis and the limited survival benefit with current treatment options, it becomes imperative to optimize early detection, prognosis and prediction of treatment response. To address these challenges, significant research efforts have been undertaken in recent years to develop liquid-biopsy-based biomarkers for pancreatic cancer. In particular, an increasing number of studies point to cell-free DNA (cfDNA) methylation analysis as a promising non-invasive approach for the discovery and validation of epigenetic biomarkers with diagnostic or prognostic potential. In this review we provide an update on recent advancements in the field of cfDNA methylation analysis in pancreatic cancer. We discuss the relevance of DNA methylation in the context of pancreatic cancer, recent cfDNA methylation research, its clinical utility, and future directions for integrating cfDNA methylation analysis into routine clinical practice.
Collapse
Affiliation(s)
- María Victoria García-Ortiz
- Maimónides Biomedical Research Institute of Córdoba (IMIBIC), Córdoba, Spain.
- Andalusia-Roche Network Mixed Alliance in Precision Medical Oncology, Sevilla, Spain.
- Cancer Network Biomedical Research Center (CIBERONC), Madrid, Spain.
| | - Pablo Cano-Ramírez
- Maimónides Biomedical Research Institute of Córdoba (IMIBIC), Córdoba, Spain
- Andalusia-Roche Network Mixed Alliance in Precision Medical Oncology, Sevilla, Spain
| | - Marta Toledano-Fonseca
- Maimónides Biomedical Research Institute of Córdoba (IMIBIC), Córdoba, Spain
- Andalusia-Roche Network Mixed Alliance in Precision Medical Oncology, Sevilla, Spain
- Cancer Network Biomedical Research Center (CIBERONC), Madrid, Spain
| | - Enrique Aranda
- Maimónides Biomedical Research Institute of Córdoba (IMIBIC), Córdoba, Spain
- Andalusia-Roche Network Mixed Alliance in Precision Medical Oncology, Sevilla, Spain
- Cancer Network Biomedical Research Center (CIBERONC), Madrid, Spain
- Medical Oncology Department, Reina Sofía University Hospital, Córdoba, Spain
- Department of Medicine, Faculty of Medicine, University of Córdoba, Córdoba, Spain
| | - Antonio Rodríguez-Ariza
- Maimónides Biomedical Research Institute of Córdoba (IMIBIC), Córdoba, Spain
- Andalusia-Roche Network Mixed Alliance in Precision Medical Oncology, Sevilla, Spain
- Cancer Network Biomedical Research Center (CIBERONC), Madrid, Spain
- Medical Oncology Department, Reina Sofía University Hospital, Córdoba, Spain
| |
Collapse
|
|
10
|
Chiu YF, Liu TW, Shan YS, Chen JS, Li CP, Ho CL, Hsieh RK, Hwang TL, Chen LT, Ch'ang HJ. Carbohydrate Antigen 19-9 Response to Initial Adjuvant Chemotherapy Predicts Survival and Failure Pattern of Resected Pancreatic Adenocarcinoma but Not Which Patients Are Suited for Additional Adjuvant Chemoradiation Therapy: From a Prospective Randomized Study. Int J Radiat Oncol Biol Phys 2023; 117:74-86. [PMID: 37055279 DOI: 10.1016/j.ijrobp.2023.02.061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Revised: 02/19/2023] [Accepted: 02/25/2023] [Indexed: 04/15/2023]
Abstract
PURPOSE The predictive value of carbohydrate antigen 19-9 (CA19-9) for adjuvant chemo(radiation) therapy of resected pancreatic adenocarcinoma (PDAC) is undefined. METHODS AND MATERIALS We analyzed CA19-9 levels in patients with resected PDAC in a prospective randomized trial of adjuvant chemotherapy with or without additional chemoradiation therapy (CRT). Patients with postoperative CA19-9 ≤92.5 U/mL and serum bilirubin ≤2 mg/dL were randomized to 2 arms: patients in 1 arm received 6 cycles of gemcitabine, whereas those in the other received 3 cycles of gemcitabine followed by CRT and another 3 cycles of gemcitabine. Serum CA19-9 was measured every 12 weeks. Those who had CA19-9 levels always <3 U/mL were excluded from the exploratory analysis. RESULTS One hundred forty-seven patients were enrolled in this randomized trial. Twenty-two patients with CA19-9 levels always ≤3 U/mL were excluded from the analysis. For the 125 participants, median overall survival (OS) and recurrence-free survival were 23.1 and 12.1 months, respectively, with no significant differences between the study arms. Postresection CA19-9 levels and, to a lesser extent, CA19-9 change predicted OS (P = .040 and .077, respectively). For the 89 patients who completed the initial 3 cycles of adjuvant gemcitabine, the CA19-9 response was significantly correlated with initial failure over the distant site (P = .023) and OS (P = .0022). Despite a trend of less initial failure over the locoregional area (P = .031), neither postoperative CA19-9 level nor CA19-9 response helped to select patients who might have a survival benefit from additional adjuvant CRT. CONCLUSIONS CA19-9 response to initial adjuvant gemcitabine predicts survival and distant failure of PDAC after resection; however, it cannot select patients suited for additional adjuvant CRT. Monitoring CA19-9 levels during adjuvant therapy for postoperative patients with PDAC may guide therapeutic decisions to prevent distant failure.
Collapse
Affiliation(s)
- Yen-Feng Chiu
- Institute of Public Health Sciences, National Health Research Institutes, Miaoli, Taiwan
| | - Tsang-Wu Liu
- National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan
| | - Yan-Shen Shan
- Department of Surgery, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan
| | - Jen-Shi Chen
- Department of Hematology-Oncology, Linkou Chang-Gung Memorial Hospital, Tao-Yuan, Taiwan
| | - Chung-Pin Li
- Divisions of Clinical Skills Training, Department of Medical Education, Taipei, Taiwan; Divisions of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Ching-Liang Ho
- Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Ruey-Kuen Hsieh
- Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan
| | - Tsann-Long Hwang
- Department of Surgery, Linkou Chang-Gung Memorial Hospital, Tao-Yuan, Taiwan
| | - Li-Tzong Chen
- National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan; Department of Internal Medicine, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan; Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Hui-Ju Ch'ang
- National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan; Department of Radiation Oncology, National Cheng Kung University Hospital, National Cheng Kung University, Tainan, Taiwan; Taipei Cancer Center, Taipei Medical University, Taipei, Taiwan.
| |
Collapse
|
|
11
|
Stubbe BE, Madsen PH, Larsen AC, Krarup HB, Pedersen IS, Hansen CP, Johansen JS, Henriksen SD, Thorlacius-Ussing O. Promoter hypermethylation of SFRP1 as a prognostic and potentially predictive blood-based biomarker in patients with stage III or IV pancreatic ductal adenocarcinoma. Pancreatology 2023; 23:512-521. [PMID: 37230892 DOI: 10.1016/j.pan.2023.05.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2023] [Revised: 05/09/2023] [Accepted: 05/10/2023] [Indexed: 05/27/2023]
Abstract
BACKGROUND Pancreatic ductal adenocarcinoma remains one of the major causes of cancer-related mortality globally. Unfortunately, current prognostic biomarkers are limited, and no predictive biomarkers exist. This study examined promoter hypermethylation of secreted frizzled-related protein 1 (phSFRP1) in cfDNA as a prognostic biomarker and predictor of treatment effect in patients with metastatic FOLFIRINOX-treated PDAC and locally advanced PDAC. METHODS We performed methylation-specific PCR of the SFRP1 genes' promoter region, based on bisulfite treatment. Survival was assessed as time-to-event data using the pseudo-observation method and analyzed with Kaplan-Meier curves and generalized linear regressions. RESULTS The study included 52 patients with FOLFIRINOX-treated metastatic PDAC. Patients with unmethylated (um) SFRP1 (n = 29) had a longer median overall survival (15.7 months) than those with phSFRP1 (6.8 months). In crude regression, phSFRP1 was associated with an increased risk of death of 36.9% (95% CI 12.0%-61.7%) and 19.8% (95% CI 1.9-37.6) at 12 and 24-months, respectively. In supplementary regression analysis, interaction terms between SFRP1 methylation status and treatment were significant, indicating reduced benefit of chemotherapy. Forty-four patients with locally advanced PDAC were included. phSFRP1 was associated with an increased risk of death at 24-months CONCLUSIONS: This indicates that phSFRP1 is a clinically useful prognostic biomarker in metastatic PDAC and possibly in locally advanced PDAC. Together with existing literature, results could indicate the value of cfDNA-measured phSFRP1 as a predictive biomarker of standard palliative chemotherapy in patients with metastatic PDAC. This could facilitate personalized treatment of patients with metastatic PDAC.
Collapse
Affiliation(s)
- Benjamin E Stubbe
- Department of Gastrointestinal Surgery, Aalborg University Hospital, Denmark; Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Denmark.
| | - Poul H Madsen
- Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark; Department of Molecular Diagnostics, Aalborg University Hospital, Denmark
| | - Anders C Larsen
- Department of Gastrointestinal Surgery, Aalborg University Hospital, Denmark; Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Denmark
| | - Henrik B Krarup
- Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark; Department of Molecular Diagnostics, Aalborg University Hospital, Denmark
| | - Inge S Pedersen
- Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark; Department of Molecular Diagnostics, Aalborg University Hospital, Denmark; Department of Clinical Medicine, Aalborg University, Denmark
| | - Carsten P Hansen
- Department of Surgery, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
| | - Julia S Johansen
- Department of Medicine, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Oncology, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark
| | - Stine D Henriksen
- Department of Gastrointestinal Surgery, Aalborg University Hospital, Denmark; Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Denmark
| | - Ole Thorlacius-Ussing
- Department of Gastrointestinal Surgery, Aalborg University Hospital, Denmark; Clinical Cancer Research Center, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Denmark
| |
Collapse
|
|
12
|
García-Ortiz MV, Cano-Ramírez P, Toledano-Fonseca M, Cano MT, Inga-Saavedra E, Rodríguez-Alonso RM, Guil-Luna S, Gómez-España MA, Rodríguez-Ariza A, Aranda E. Circulating NPTX2 methylation as a non-invasive biomarker for prognosis and monitoring of metastatic pancreatic cancer. Clin Epigenetics 2023; 15:118. [PMID: 37481552 PMCID: PMC10362605 DOI: 10.1186/s13148-023-01535-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Accepted: 07/16/2023] [Indexed: 07/24/2023] Open
Abstract
BACKGROUND Pancreatic cancer is the most lethal cancer with a dismal prognosis mainly due to diagnosis at advanced stage and ineffective treatments. CA19-9 levels and computed tomography (CT) imaging are the main standard criteria for evaluating disease progression and treatment response. In this study we explored liquid biopsy-based epigenetic biomarkers for prognosis and monitoring disease in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC). METHODS Plasma samples were collected from 44 mPDAC patients at the time of diagnosis, and in 15 of them, additional samples were obtained during follow-up of the disease. After cell-free DNA (cfDNA), isolation circulating levels of methylated NPTX2, SPARC, BMP3, SFRP1 and TFPI2 genes were measured using digital droplet PCR (ddPCR). BEAMing technique was performed for quantitation of RAS mutations in cfDNA, and CA19-9 was measured using standard techniques. RESULTS NPTX2 was the most highly and frequently methylated gene in cfDNA samples from mPDAC patients. Higher circulating NPTX2 methylation levels at diagnosis were associated with poor prognosis and efficiently stratified patients for prediction of overall survival (6.06% cut-off, p = 0.0067). Dynamics of circulating NPTX2 methylation levels correlated with disease progression and response to therapy and predicted better than CA19-9 the evolution of disease in mPDAC patients. Remarkably, in many cases the disease progression detected by CT scan was anticipated by an increase in circulating NPTX2 methylation levels. CONCLUSIONS Our study supports circulating NPTX2 methylation levels as a promising liquid biopsy-based clinical tool for non-invasive prognosis, monitoring disease evolution and response to treatment in mPDAC patients.
Collapse
Affiliation(s)
- María Victoria García-Ortiz
- Maimónides Biomedical Research Institute of Córdoba (IMIBIC), Córdoba, Spain
- Andalusia-Roche Network Mixed Alliance in Precision Medical Oncology, Seville, Spain
- Cancer Network Biomedical Research Center (CIBERONC), Madrid, Spain
| | - Pablo Cano-Ramírez
- Maimónides Biomedical Research Institute of Córdoba (IMIBIC), Córdoba, Spain
- Andalusia-Roche Network Mixed Alliance in Precision Medical Oncology, Seville, Spain
| | - Marta Toledano-Fonseca
- Maimónides Biomedical Research Institute of Córdoba (IMIBIC), Córdoba, Spain
- Andalusia-Roche Network Mixed Alliance in Precision Medical Oncology, Seville, Spain
- Cancer Network Biomedical Research Center (CIBERONC), Madrid, Spain
| | - María Teresa Cano
- Maimónides Biomedical Research Institute of Córdoba (IMIBIC), Córdoba, Spain
- Andalusia-Roche Network Mixed Alliance in Precision Medical Oncology, Seville, Spain
- Medical Oncology Department, Reina Sofía University Hospital, Córdoba, Spain
| | - Elizabeth Inga-Saavedra
- Maimónides Biomedical Research Institute of Córdoba (IMIBIC), Córdoba, Spain
- Andalusia-Roche Network Mixed Alliance in Precision Medical Oncology, Seville, Spain
- Medical Oncology Department, Reina Sofía University Hospital, Córdoba, Spain
| | | | - Silvia Guil-Luna
- Maimónides Biomedical Research Institute of Córdoba (IMIBIC), Córdoba, Spain
- Andalusia-Roche Network Mixed Alliance in Precision Medical Oncology, Seville, Spain
- Cancer Network Biomedical Research Center (CIBERONC), Madrid, Spain
- Department of Anatomy and Comparative Pathology, University of Córdoba, Córdoba, Spain
| | - María Auxiliadora Gómez-España
- Maimónides Biomedical Research Institute of Córdoba (IMIBIC), Córdoba, Spain
- Andalusia-Roche Network Mixed Alliance in Precision Medical Oncology, Seville, Spain
- Cancer Network Biomedical Research Center (CIBERONC), Madrid, Spain
- Medical Oncology Department, Reina Sofía University Hospital, Córdoba, Spain
| | - Antonio Rodríguez-Ariza
- Maimónides Biomedical Research Institute of Córdoba (IMIBIC), Córdoba, Spain
- Andalusia-Roche Network Mixed Alliance in Precision Medical Oncology, Seville, Spain
- Cancer Network Biomedical Research Center (CIBERONC), Madrid, Spain
- Medical Oncology Department, Reina Sofía University Hospital, Córdoba, Spain
| | - Enrique Aranda
- Maimónides Biomedical Research Institute of Córdoba (IMIBIC), Córdoba, Spain
- Andalusia-Roche Network Mixed Alliance in Precision Medical Oncology, Seville, Spain
- Cancer Network Biomedical Research Center (CIBERONC), Madrid, Spain
- Medical Oncology Department, Reina Sofía University Hospital, Córdoba, Spain
- Department of Medicine, Faculty of Medicine, University of Córdoba, Córdoba, Spain
| |
Collapse
|
|
13
|
Ghabi EM, Shoucair S, Ding D, Javed AA, Thompson ED, Zheng L, Cameron JL, Wolfgang CL, Shubert CR, Lafaro KJ, Burkhart RA, Burns WR, He J. Tailoring Adjuvant Chemotherapy to Biologic Response Following Neoadjuvant Chemotherapy Impacts Overall Survival in Pancreatic Cancer. J Gastrointest Surg 2023; 27:691-700. [PMID: 36280632 PMCID: PMC10079604 DOI: 10.1007/s11605-022-05476-w] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Accepted: 09/16/2022] [Indexed: 01/31/2023]
Abstract
BACKGROUND The role of postoperative chemotherapy in patients with resected pancreatic cancer who receive neoadjuvant treatment is unknown. Clinicians use changes in CA19-9 and histopathologic scores to assess treatment response. We sought to investigate if CA19-9 normalization in response to NAT can help guide the need for postoperative treatment. METHODS Patients with elevated baseline CA19-9 (CA19-9 > 37U/mL) who received NAT followed by surgery between 2011 and 2019 were retrospectively reviewed. Treatment response was determined by CA19-9 normalization following NAT and histopathologic scoring. The role of postoperative chemotherapy was analyzed in light of CA19-9 normalization and histopathologic response. RESULTS We identified and included 345 patients. Following NAT, CA19-9 normalization was observed in 125 patients (36.2%). CA19-9 normalization was associated with a favorable histopathologic response (41.6% vs 23.2%, p < 0.001) and a lower ypT (p < 0.001) and ypN stage (p = 0.003). Receipt of adjuvant chemotherapy was associated with improved overall survival in patients in whom CA19-9 did not normalize following NAT (26.8 vs 16.4 months, p = 0.008). In patients who received 5FU-based NAT and in whom CA19-9 did not normalize, receipt of 5FU-based adjuvant chemotherapy was associated with improved OS (p = 0.014). CONCLUSION CA19-9 normalization in response to NAT was associated with favorable outcomes and can serve as a biomarker for treatment response. In patients where CA19-9 did not normalize, receipt of postoperative chemotherapy was associated with improved OS. These patients also benefited from additional 5FU-based postoperative chemotherapy following 5FU-based NAT.
Collapse
Affiliation(s)
- Elie M Ghabi
- Department of Surgery, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Blalock 685, Baltimore, MD, 21287, USA
| | - Sami Shoucair
- Department of Surgery, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Blalock 685, Baltimore, MD, 21287, USA
| | - Ding Ding
- Department of Surgery, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Blalock 685, Baltimore, MD, 21287, USA
| | - Ammar A Javed
- Department of Surgery, NYU Langone Health, New York, NY, USA
| | - Elizabeth D Thompson
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Lei Zheng
- Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - John L Cameron
- Department of Surgery, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Blalock 685, Baltimore, MD, 21287, USA
| | | | - Christopher R Shubert
- Department of Surgery, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Blalock 685, Baltimore, MD, 21287, USA
| | - Kelly J Lafaro
- Department of Surgery, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Blalock 685, Baltimore, MD, 21287, USA
| | - Richard A Burkhart
- Department of Surgery, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Blalock 685, Baltimore, MD, 21287, USA
| | - William R Burns
- Department of Surgery, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Blalock 685, Baltimore, MD, 21287, USA
| | - Jin He
- Department of Surgery, Johns Hopkins University School of Medicine, 600 N. Wolfe Street, Blalock 685, Baltimore, MD, 21287, USA.
| |
Collapse
|
|
14
|
Law NC, Lomma C. Pancreatic adenocarcinoma with brain metastases. BMJ Case Rep 2023; 16:e253557. [PMID: 36941017 PMCID: PMC10030487 DOI: 10.1136/bcr-2022-253557] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/09/2023] [Indexed: 03/22/2023] Open
Abstract
Brain metastases are rare for patients with pancreatic adenocarcinoma. The incidence of brain metastasis may increase as improved systemic treatment regimens improve overall survival. Given the low incidence of brain metastasis, recognition of disease and management remain a challenge. We report three cases of metastatic pancreatic adenocarcinoma with brain metastases, review the literature and discuss its management principles.
Collapse
Affiliation(s)
- Ngie Chang Law
- Medical Oncology Department, Fiona Stanley Hospital, Murdoch, Western Australia, Australia
| | - Christopher Lomma
- Medical Oncology Department, Fiona Stanley Hospital, Murdoch, Western Australia, Australia
| |
Collapse
|
|
15
|
INPP5A/HLA-G1/IL-10/MMP-21 Axis in Progression of Esophageal Squamous Cell Carcinoma. IRANIAN BIOMEDICAL JOURNAL 2022; 26:440-53. [PMID: 36437782 PMCID: PMC9841225 DOI: 10.52547/ibj.3716] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Background Background: Type I inositol polyphosphate-5-phosphatase A (INPP5A) is involved in different cellular events, including cell proliferation. Since INPP5A, HLAG1, IL-10, and matrix metalloproteinases (MMP)-21 genes play fundamental roles in esophageal squamous cell carcinoma (ESCC) tumorigenesis, we aimed in this study to clarify the possible interplay of these genes and explore the potential of these chemistries as a predictor marker for diagnosis in ESCC disease. Methods Methods: Gene expression analysis of INPP5A, HLAG-1, IL-10, and MMP-21 was performed using relative comparative real-time PCR in 56 ESCCs compared to their margin normal tissues. Immunohistochemical staining was accomplished for INPP5A in ESCCs. Analysis of ROC curves and the AUC were applied to evaluate the diagnostic capability of the candidate genes. Results Results: High levels of HLA-G1, MMP-21, and IL-10 were detected in nearly 23.2%, 62.5%, and 53.5% of ESCCs compared to the normal tissues, respectively, whereas INPP5A underexpression was detected in 19.6% of ESCCs, which all tested genes indicated significant correlations with each other. The protein expression level of INPP5A in ESCC tissues was significantly lower than that of the non-tumor esophageal tissues (p = 0.001). Interestingly, the concomitant expression of the INPP5A/HLA-G1, INPP5A/MMP-21, INPP5A/IL-10, HLA-G1/MMP-21, HLA-G1/IL-10, and MMP-21/IL-10 was significantly correlated with several clinicopathological variables. INPP5A, HLA-G1, MMP-21, and IL-10 showed to be the most appropriate candidates to discriminate tumor/non-tumor groups due to the total AUCs of all combinations (>60%). Conclusion Conclusion: Our results represent a new regulatory axis containing INPP5A/HLAG-1/IL-10/MMP-21 markers in ESCC development and may provide novel insight into the mechanism of immune evasion mediated
by the INPP5A/HLAG-1/IL-10/MMP-21 regulatory network in the disease.
Collapse
|
|
16
|
Li M, Duan X, Xiao Y, Yuan M, Zhao Z, Cui X, Wu D, Shi J. BUB1 Is Identified as a Potential Therapeutic Target for Pancreatic Cancer Treatment. Front Public Health 2022; 10:900853. [PMID: 35769782 PMCID: PMC9235519 DOI: 10.3389/fpubh.2022.900853] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2022] [Accepted: 05/03/2022] [Indexed: 11/17/2022] Open
Abstract
Pancreatic cancer is one of the most challenging cancer types in clinical treatment worldwide. This study aimed to understand the tumorigenesis mechanism and explore potential therapeutic targets for patients with pancreatic cancer. Single-cell data and expression profiles of pancreatic cancer samples and normal tissues from multiple databases were included. Comprehensive bioinformatics analyses were applied to clarify tumor microenvironment and identify key genes involved in cancer development. Immense difference of cell types was shown between tumor and normal samples. Four cell types (B cell_1, B cell_2, cancer cell_3, and CD1C+_B dendritic cell_3) were screened to be significantly associated with prognosis. Three ligand-receptor pairs, including CD74-MIF, CD74-COPA, and CD74-APP, greatly contributed to tumorigenesis. High expression of BUB1 (BUB1 Mitotic Checkpoint Serine/Threonine Kinase) was closely correlated with worse prognosis. CD1C+_B dendritic cell_3 played a key role in tumorigenesis and cancer progression possibly through CD74-MIF. BUB1 can serve as a prognostic biomarker and a therapeutic target for patients with pancreatic cancer. The study provided a novel insight into studying the molecular mechanism of pancreatic cancer development and proposed a potential strategy for exploiting new drugs.
Collapse
Affiliation(s)
- Ming Li
- Department of General Surgery, Shijiazhuang People's Hospital, Shijiazhuang, China
| | - Xiaoyang Duan
- Department of Medical Oncology, The Fourth Hospital of Hebei Medical University, Hebei Tumor Hospital, Shijiazhuang, China
| | - Yajie Xiao
- Translational Medicine, YuceBio Technology Co., Ltd., Shenzhen, China
| | - Meng Yuan
- Internal Medical, University of Occupational and Environmental Health, Fukuoka, Japan
| | - Zhikun Zhao
- Translational Medicine, YuceBio Technology Co., Ltd., Shenzhen, China
| | - Xiaoli Cui
- Translational Medicine, YuceBio Technology Co., Ltd., Shenzhen, China
| | - Dongfang Wu
- Translational Medicine, YuceBio Technology Co., Ltd., Shenzhen, China
| | - Jian Shi
- Department of Medical Oncology, The Fourth Hospital of Hebei Medical University, Hebei Tumor Hospital, Shijiazhuang, China
| |
Collapse
|
|
17
|
Jang JK, Choi SJ, Byun JH, Kim JH, Lee SS, Kim HJ, Yoo C, Kim KP, Hong SM, Seo DW, Hwang DW, Kim SC. Prediction of Margin-Negative Resection of Pancreatic Ductal Adenocarcinoma Following Neoadjuvant Therapy: Diagnostic Performance of NCCN Criteria for Resection vs. CT-Determined Resectability. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2022; 29:1025-1034. [PMID: 35658103 DOI: 10.1002/jhbp.1192] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Revised: 04/12/2022] [Accepted: 04/17/2022] [Indexed: 11/12/2022]
Abstract
BACKGROUND Accurate assessment of pancreatic ductal adenocarcinoma (PDAC) resectability after neoadjuvant therapy (NAT) is crucial. Recently, the NCCN introduced criteria for resection of PDAC following NAT. METHODS We analyzed 127 patients who underwent NAT and pancreatectomy for PDAC between January 2010 and March 2020. CT-determined resectability according to the NCCN guideline, and CA 19-9 level was evaluated before and after NAT. Diagnostic performance of the NCCN criteria for margin-negative (R0) resection was investigated and compared with CT alone. RESULTS R0 resection was achieved in 104 (81.9%) patients. After NAT, there were 30 (23.6%) resectable, 90 (70.9%) borderline resectable, and seven (5.5%) locally advanced tumors. Significantly decreased or stable CA 19-9 levels were noted in 114 (89.8%) patients. The sensitivity and specificity of the NCCN criteria were 87.5% (91/104) and 21.7% (5/23), respectively, which were significantly different from CT including only resectable PDAC (26.9% [28/104] and 91.3% [21/23]; p<0.001), but less prominently different from CT including resectable and borderline resectable PDAC (95.2% [99/104]; p=0.022 and 8.7% [2/23]; p=0.375). CONCLUSIONS The NCCN criteria for resection following NAT showed high sensitivity and low specificity for predicting R0 resection. It had supplementary benefit over CT alone, mainly in preventing underestimation of R0 resection.
Collapse
Affiliation(s)
- Jong Keon Jang
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Se Jin Choi
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Jae Ho Byun
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Jin Hee Kim
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Seung Soo Lee
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Hyoung Jung Kim
- Department of Radiology and Research Institute of Radiology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Changhoon Yoo
- Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Kyu-Pyo Kim
- Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Seung-Mo Hong
- Department of Pathology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Dong-Wan Seo
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Dae Wook Hwang
- Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| | - Song Cheol Kim
- Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 05505, Republic of Korea
| |
Collapse
|
|
18
|
Simpson G, Jin W, Spieler B, Portelance L, Mellon E, Kwon D, Ford JC, Dogan N. Predictive Value of Delta-Radiomics Texture Features in 0.35 Tesla Magnetic Resonance Setup Images Acquired During Stereotactic Ablative Radiotherapy of Pancreatic Cancer. Front Oncol 2022; 12:807725. [PMID: 35515129 PMCID: PMC9063004 DOI: 10.3389/fonc.2022.807725] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Accepted: 03/21/2022] [Indexed: 11/22/2022] Open
Abstract
Purpose The purpose of this work is to explore delta-radiomics texture features for predicting response using setup images of pancreatic cancer patients treated with magnetic resonance image guided (MRI-guided) stereotactic ablative radiotherapy (SBRT). Methods The total biological effective dose (BED) was calculated for 30 patients treated with MRI-guided SBRT that delivered physical doses of 30–60 Gy in three to five fractions. Texture features were then binned into groups based upon BED per fraction by dividing BED by the number of fractions. Delta-radiomics texture features were calculated after delivery of 20 Gy BED (BED20 features) and 40 Gy BED (BED40 features). A random forest (RF) model was constructed using BED20 and then BED40 features to predict binary outcome. During model training, the Gini Index, a measure of a variable’s importance for accurate prediction, was calculated for all features, and the two features that ranked the highest were selected for internal validation. The two features selected from each bin were used in a bootstrapped logistic regression model to predict response and performance quantified using the area under the receiver operating characteristic curve (AUC). This process was an internal validation analysis. Results After RF model training, the Gini Index was highest for gray-level co-occurrence matrix-based (GLCM) sum average, and neighborhood gray tone difference matrix-based (NGTDM) busyness for BED20 features and gray-level size zone matrix-based (GLSZM) large zones low gray-level emphasis and gray-level run length matrix-based (GLRLM) run percentage was selected from the BED40-based features. The mean AUC obtained using the two BED20 features was AUC = 0.845 with the 2.5 percentile and 97.5 percentile values ranging from 0.794 to 0.856. Internal validation of the BED40 delta-radiomics features resulted in a mean AUC = 0.567 with a 2.5 and 97.5 percentile range of 0.502–0.675. Conclusion Early changes in treatment quantified with the BED20 delta-radiomics texture features in low field images acquired during MRI-guided SBRT demonstrated better performance in internal validation than features calculated later in treatment. Further analysis of delta-radiomics texture analysis in low field MRI is warranted.
Collapse
Affiliation(s)
- Garrett Simpson
- Radiation Oncology, Miller School of Medicine, University of Miami, Miami, FL, United States
| | - William Jin
- Radiation Oncology, Miller School of Medicine, University of Miami, Miami, FL, United States
| | - Benjamin Spieler
- Radiation Oncology, Miller School of Medicine, University of Miami, Miami, FL, United States
| | - Lorraine Portelance
- Radiation Oncology, Miller School of Medicine, University of Miami, Miami, FL, United States
| | - Eric Mellon
- Radiation Oncology, Miller School of Medicine, University of Miami, Miami, FL, United States
| | - Deukwoo Kwon
- Radiation Oncology, Miller School of Medicine, University of Miami, Miami, FL, United States
| | - John C Ford
- Radiation Oncology, Miller School of Medicine, University of Miami, Miami, FL, United States
| | - Nesrin Dogan
- Radiation Oncology, Miller School of Medicine, University of Miami, Miami, FL, United States
| |
Collapse
|
|
19
|
Wei K, Zhu H, Qin G, Zhu Z, Tu D. Multiply robust subgroup analysis based on a single-index threshold linear marginal model for longitudinal data with dropouts. Stat Med 2022; 41:2822-2839. [PMID: 35347738 DOI: 10.1002/sim.9386] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Revised: 02/21/2022] [Accepted: 03/02/2022] [Indexed: 11/08/2022]
Abstract
Identifying subpopulations that may be sensitive to the specific treatment is an important step toward precision medicine. On the other hand, longitudinal data with dropouts is common in medical research, and subgroup analysis for this data type is still limited. In this paper, we consider a single-index threshold linear marginal model, which can be used simultaneously to identify subgroups with differential treatment effects based on linear combination of the selected biomarkers, estimate the treatment effects in different subgroups based on regression coefficients, and test the significance of the difference in treatment effects based on treatment-subgroup interaction. The regression parameters are estimated by solving a penalized smoothed generalized estimating equation and the selection bias caused by missingness is corrected by a multiply robust weighting matrix, which allows multiple missingness models to be taken account into estimation. The proposed estimator remains consistent when any model for missingness is correctly specified. Under regularity conditions, the asymptotic normality of the estimator is established. Simulation studies confirm the desirable finite-sample performance of the proposed method. As an application, we analyze the data from a clinical trial on pancreatic cancer.
Collapse
Affiliation(s)
- Kecheng Wei
- Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China
| | - Huichen Zhu
- Department of Statistics, The Chinese University of Hong Kong, Hong Kong, China
| | - Guoyou Qin
- Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China
| | - Zhongyi Zhu
- Department of Statistics, School of Management, Fudan University, Shanghai, China
| | - Dongsheng Tu
- Canadian Cancer Trials Group, Queen's University, Kingston, Ontario, Canada
| |
Collapse
|
|
20
|
Yang Y, Su X, Shen K, Zhang C, Dai H, Ma H, Jiang Y, Shuai L, Liu Z, You J, Min K, Chen Z. PUM1 is upregulated by DNA methylation to suppress antitumor immunity and results in poor prognosis in pancreatic cancer. Transl Cancer Res 2022; 10:2153-2168. [PMID: 35116535 PMCID: PMC8798770 DOI: 10.21037/tcr-20-3295] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Accepted: 02/26/2021] [Indexed: 12/24/2022]
Abstract
Background Pancreatic carcinoma (PAAD) is a highly malignant cancer with a poor prognosis and high mortality rate. Pumilio homologous protein 1 (PUM1) promotes cell growth, invasion, and metastasis and suppresses apoptosis in many different kinds of cancers, such as non-small-cell lung carcinoma (NSCLC), ovarian cancer and lymphocyte leukemia. However, the underlying mechanism and potential role of PUM1 in PAAD have not been investigated. Methods Bioinformatics analysis was performed using multiple databases [The Cancer Genome Atlas (TCGA), Gene Expression Profiling Interactive Analysis (GEPIA), BBCancer, Human Protein Atlas (HPA), MethSurv, cBioPortal, The Cancer Imaging Archive (TCIA), xCell, Gene Expression Omnibus (GEO)] to explore the diagnostic and prognostic role of PUM1, and the relationship between expression of PUM1 and prognosis of patients with PAAD. The analysis was further validated using the Kaplan-Meier plotter. Results PUM1 plays a role in both diagnostic and prognostic prediction. The PUM1 mRNA expression level correlates with both the prognosis and incidence of pancreatic cancer. PUM1 can serve as a potential diagnostic indicator for pancreatic cancer. Furthermore, the DNA methylation levels of PUM1 affects its oncogene function in pancreatic cancer. PUM1 can also inhibit the immune microenvironment by altering immune cell infiltration, which affects immunotherapy response in pancreatic cancer. Conclusions PUM1 takes a crucial part in the immune microenvironment and immunotherapy response of PAAD and is potentially useful for the development of novel diagnostic and treatment strategies.
Collapse
Affiliation(s)
- Yishi Yang
- Department of Hepatobiliary Surgery, Southwest Hospital, First Affiliated Hospital of the Army Medical University, Chongqing, China
| | - Xingxing Su
- Department of Hepatobiliary Surgery, Southwest Hospital, First Affiliated Hospital of the Army Medical University, Chongqing, China
| | - Kaicheng Shen
- Department of Hepatobiliary Surgery, Southwest Hospital, First Affiliated Hospital of the Army Medical University, Chongqing, China
| | - Chengcheng Zhang
- Department of Hepatobiliary Surgery, Southwest Hospital, First Affiliated Hospital of the Army Medical University, Chongqing, China
| | - Haisu Dai
- Department of Hepatobiliary Surgery, Southwest Hospital, First Affiliated Hospital of the Army Medical University, Chongqing, China
| | - Hongbo Ma
- Department of Oncology, The Fuling Central Hospital of Chongqing City, Chongqing, China
| | - Yan Jiang
- Department of Hepatobiliary Surgery, Southwest Hospital, First Affiliated Hospital of the Army Medical University, Chongqing, China
| | - Ling Shuai
- Department of Hepatobiliary Surgery, Southwest Hospital, First Affiliated Hospital of the Army Medical University, Chongqing, China
| | - Zhipeng Liu
- Department of Hepatobiliary Surgery, Southwest Hospital, First Affiliated Hospital of the Army Medical University, Chongqing, China
| | - Jinshan You
- Department of Hepatobiliary Surgery, Southwest Hospital, First Affiliated Hospital of the Army Medical University, Chongqing, China
| | - Ke Min
- Department of Hepatobiliary Surgery, Southwest Hospital, First Affiliated Hospital of the Army Medical University, Chongqing, China
| | - Zhiyu Chen
- Department of Hepatobiliary Surgery, Southwest Hospital, First Affiliated Hospital of the Army Medical University, Chongqing, China
| |
Collapse
|
|
21
|
Vanek P, Eid M, Psar R, Zoundjiekpon V, Urban O, Kunovský L. Current trends in the diagnosis of pancreatic cancer. VNITRNI LEKARSTVI 2022; 68:363-370. [PMID: 36316197 DOI: 10.36290/vnl.2022.076] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/16/2023]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a dreaded malignancy with a dismal 5-year survival rate despite maximal efforts on optimizing treatment strategies. Currently, early detection is considered to be the most effective way to improve survival as radical resection is the only potential cure. PDAC is often divided into four categories based on the extent of disease: resectable, borderline resectable, locally advanced, and metastatic. Unfortunately, the majority of patients are diagnosed with locally advanced or metastatic disease, which renders them ineligible for curative resection. This is mainly due to the lack of or vague symptoms while the disease is still localized, although appropriate utilization and prompt availability of adequate diagnostic tools is also critical given the aggressive nature of the disease. A cost-effective biomarker with high specificity and sensitivity allowing early detection of PDAC without the need for advanced or invasive methods is still not available. This leaves the diagnosis dependent on radiodiagnostic methods or endoscopic ultrasound. Here we summarize the latest epidemiological data, risk factors, clinical manifestation, and current diagnostic trends and implications of PDAC focusing on serum biomarkers and imaging modalities. Additionally, up-to-date management and therapeutic algorithms are outlined.
Collapse
|
|
22
|
Nam H, Kang S, Park MS, Kang S, Kim HS, Mai VH, Kim J, Lee H, Lee W, Suh YJ, Lim JH, Kim SY, Kim SC, Kim SH, Jung KH, Hong SS, Park S. A Serum Marker for Early Pancreatic Cancer with a Possible Link to Diabetes. J Natl Cancer Inst 2021; 114:228-234. [PMID: 34613397 DOI: 10.1093/jnci/djab191] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Revised: 07/23/2021] [Accepted: 09/16/2021] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND Pancreatic cancer (PC) has a grim prognosis, and an early diagnostic biomarker has been highly desired. The molecular link between diabetes and PC has not been well-established. METHODS Bioinformatics screening was performed for a serum PC marker. Experiments in cell lines (5 PC and 1 normal cell lines), mouse models, and human tissue staining (37 PC and 10 normal cases) were performed to test asprosin production from PC. Asprosin's diagnostic performance was tested with serums from multi-center cohorts (347 PC, 209 normal, and 55 additional diabetic subjects) and evaluated according to PC status, stages, and diabetic status, which was compared with that of CA19-9. RESULTS Asprosin, a diabetes-related hormone, was found from the bioinformatics screening, and its production from PC was confirmed. Serum asprosin levels from multi-center cohorts yielded an age-adjusted diagnostic AUC of 0.987 (95% confidence interval [CI] = 0.961 to 0.997), superior to that of CA19-9 (AUC = 0.876, 95% CI = 0.847 to 0.905), and a cut-off of 7.18 ng/mL, at which the validation set exhibited a sensitivity of 0.957 and a specificity of 0.924. Importantly, the performance was maintained in early-stage and non-metastatic PC, consistent with the tissue staining. A slightly lower performance against additional diabetic patients (n = 55) was restored by combining asprosin and CA19-9 (AUC = 0.985, 95% CI = 0.975 to 0.995). CONCLUSION Asprosin is presented as an early-stage PC serum marker that may provide clues for PC-induced diabetes. Larger prospective clinical studies are warranted to solidify its utility.
Collapse
Affiliation(s)
- Hoonsik Nam
- Natural Product Research Institute, College of Pharmacy, Seoul National University, Seoul, Korea
| | - Sunmi Kang
- Natural Product Research Institute, College of Pharmacy, Seoul National University, Seoul, Korea
| | - Min Seok Park
- Department of Biomedical Sciences, College of Medicine, and Program in Biomedical Science & Engineering, Inha University, Incheon, Korea
| | - Suyeon Kang
- Department of Statistics, College of Natural Sciences, Inha University, Incheon, Korea
| | - Han Sun Kim
- Natural Product Research Institute, College of Pharmacy, Seoul National University, Seoul, Korea
| | - Van-Hieu Mai
- Natural Product Research Institute, College of Pharmacy, Seoul National University, Seoul, Korea
| | - Juyoung Kim
- Department of Biomedical Sciences, College of Medicine, and Program in Biomedical Science & Engineering, Inha University, Incheon, Korea
| | - Ho Lee
- Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea
| | - Woohyung Lee
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - Young Ju Suh
- Department of Biomedical Sciences, College of Medicine, and Program in Biomedical Science & Engineering, Inha University, Incheon, Korea
| | - Joo Han Lim
- Division of Hematology and Oncology, Department of Internal Medicine, Inha University Hospital, Inha University, Incheon, Korea
| | - Soo-Youl Kim
- Division of Cancer Biology, Research Institute, National Cancer Center, Goyang, Korea
| | - Song Cheol Kim
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea
| | - So Hun Kim
- Department of Endocrinology and Metabolism, Department of Internal Medicine, Inha University Hospital, Inha University, Incheon, Korea
| | - Kyung Hee Jung
- Department of Biomedical Sciences, College of Medicine, and Program in Biomedical Science & Engineering, Inha University, Incheon, Korea
| | - Soon-Sun Hong
- Department of Biomedical Sciences, College of Medicine, and Program in Biomedical Science & Engineering, Inha University, Incheon, Korea
| | - Sunghyouk Park
- Natural Product Research Institute, College of Pharmacy, Seoul National University, Seoul, Korea
| |
Collapse
|
|
23
|
Shin K, Jung EK, Park SJ, Jeong S, Kim IH, Lee MA. Neutrophil-to-lymphocyte ratio and carbohydrate antigen 19-9 as prognostic markers for advanced pancreatic cancer patients receiving first-line chemotherapy. World J Gastrointest Oncol 2021; 13:915-928. [PMID: 34457195 PMCID: PMC8371515 DOI: 10.4251/wjgo.v13.i8.915] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/24/2021] [Revised: 05/03/2021] [Accepted: 07/09/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND A decline in serum carbohydrate antigen 19-9 (CA19-9) levels during systemic chemotherapy is considered as a prognostic marker for patients with advanced pancreatic cancer. Neutrophil-to-lymphocyte ratio (NLR) has been extensively studied as a simple and useful indicator of prognosis in various cancers including pancreatic cancer.
AIM To assess the prognostic significance of NLR and CA19-9 in patients with advanced pancreatic adenocarcinoma received first-line chemotherapy according to CA19-9 positivity.
METHODS We retrospectively analyzed patients diagnosed with advanced pancreatic cancer who received first-line chemotherapy between January 2010 and July 2017 at the Catholic University of Seoul St. Mary’s Hospital. Patients were divided according to CA19-9 positivity (CA19-9-positive vs -negative groups) and pre-and post-treatment NLR levels. To determine cut-off value of NLR and CA19-9 reduction, time-dependent receiver operating characteristic curve was applied. We evaluated overall survival (OS) and progression-free survival (PFS) for each group using Kaplan-Meier method, and we performed multivariate analyses on the entire cohort.
RESULTS We included 271 patients in this study. Cut-off value of NLR and CA19-9 reduction was determined as 2.62 and 18%. Multivariate analysis showed that post-treatment NLR < 2.62 and reduction of ≥ 18% of baseline CA19-9 were significantly associated with OS and PFS. Post-treatment NLR ≥ 2.62 showed hazard ratio (HR) of 2.47 [95% confidence interval (CI): 1.84-3.32, P < 0.001] and CA19-9 decline (≥ 18%) showed HR of 0.51 (95%CI: 0.39-0.67, P < 0.001) for OS. When CA19-9-positive patients were divided into groups according to CA19-9 response (responder vs non-responder) and post-treatment NLR (< 2.62 vs ≥ 2.62), CA19-9 responder and post-treatment NLR < 2.62 group showed better survival than CA19-9 non-responder and post-treatment NLR ≥ 2.62 group (OS 11.0 mo vs 3.9 mo, P < 0.001; PFS 6.3 mo vs 2.0 mo, P < 0.001). The combination of CA19-9 decline and post-treatment NLR showed a significant correlation with clinical response in CA 19-9 positive group. Within the CA19-9-negative group, the post-treatment NLR < 2.62 group showed better survival than the post-treatment NLR ≥ 2.62 group (OS 12.7 mo vs 7.7 mo, P < 0.001; PFS 6.7 mo vs 2.1 mo, P < 0.001), and post-treatment NLR showed correlation with clinical response.
CONCLUSION In advanced pancreatic cancer patients positive for CA19-9 and treated with systemic chemotherapy, the combination of post-treatment NLR < 2.62 and 18% decline of CA19-9 at the first response evaluation is a good prognostic marker. Post-treatment NLR < 2.62 alone could be used as a prognostic marker and an adjunctive tool for response evaluation in CA19-9-negative patients.
Collapse
Affiliation(s)
- Kabsoo Shin
- Division of Medical Oncology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea
- Catholic Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea
| | - Eun-Kyo Jung
- Division of Medical Oncology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea
- Catholic Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea
| | - Se Jun Park
- Division of Medical Oncology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea
- Catholic Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea
| | - Sangwoon Jeong
- Division of Medical Oncology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea
- Catholic Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea
| | - In-Ho Kim
- Division of Medical Oncology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea
- Catholic Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea
| | - Myung-ah Lee
- Division of Medical Oncology, Department of Internal Medicine, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea
- Catholic Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul 06591, South Korea
| |
Collapse
|
|
24
|
Hayuka K, Okuyama H, Murakami A, Okita Y, Nishiuchi T, Okano K, Suzuki Y, Tsuji A. Gemcitabine Plus Nab-Paclitaxel as Second-Line Chemotherapy following FOLFIRINOX in Patients with Unresectable Pancreatic Cancer: A Single-Institution, Retrospective Analysis. Chemotherapy 2021; 66:58-64. [PMID: 34284397 DOI: 10.1159/000517244] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Accepted: 05/09/2021] [Indexed: 11/19/2022]
Abstract
INTRODUCTION Patients with advanced pancreatic cancer have a poor prognosis. FOLFIRINOX (FFX) and gemcitabine plus nab-paclitaxel (GnP) have been established as first-line treatment, but they have not been confirmed as second-line treatment after FFX. The aim of this study was to evaluate the safety and efficacy of GnP as second-line therapy after FFX in patients with unresectable pancreatic cancer. METHODS Twenty-five patients with unresectable pancreatic cancer were enrolled. The patients were treated with GnP after FFX between September 2015 and September 2019. Tumor response, progression-free survival (PFS), overall survival (OS), and incidence of adverse events were evaluated. RESULTS The response rate, disease control rate, median PFS, and median OS were 12%, 96%, 5.3 months, and 15.6 months, respectively. The common grade 3 or 4 adverse events were neutropenia (76%) and anemia (16%). CONCLUSIONS GnP after FOLFIRINOX is expected to be one of the second-line recommendations for patients with unresectable pancreatic cancer.
Collapse
Affiliation(s)
- Kotone Hayuka
- Department of Clinical Oncology, Faculty of Medicine, Kagawa University, Takamatsu, Japan,
| | - Hiroyuki Okuyama
- Department of Clinical Oncology, Faculty of Medicine, Kagawa University, Takamatsu, Japan
| | - Akitsu Murakami
- Department of Clinical Oncology, Faculty of Medicine, Kagawa University, Takamatsu, Japan
| | - Yoshihiro Okita
- Department of Clinical Oncology, Faculty of Medicine, Kagawa University, Takamatsu, Japan
| | - Takamasa Nishiuchi
- Department of Clinical Oncology, Faculty of Medicine, Kagawa University, Takamatsu, Japan
| | - Keiichi Okano
- Department of Gastroenterological Surgery, Kagawa University, Takamatsu, Japan
| | - Yasuyuki Suzuki
- Department of Gastroenterological Surgery, Kagawa University, Takamatsu, Japan
| | - Akihito Tsuji
- Department of Clinical Oncology, Faculty of Medicine, Kagawa University, Takamatsu, Japan
| |
Collapse
|
|
25
|
Understanding the Clinical Impact of MUC5AC Expression on Pancreatic Ductal Adenocarcinoma. Cancers (Basel) 2021; 13:cancers13123059. [PMID: 34205412 PMCID: PMC8235261 DOI: 10.3390/cancers13123059] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Revised: 06/15/2021] [Accepted: 06/17/2021] [Indexed: 12/27/2022] Open
Abstract
Simple Summary Management of pancreatic cancer is challenging as there are limited treatment options, and most cases are diagnosed at advanced stages. In addition, there are no dependable tests available to predict bad outcomes or treatment responses in current clinical practice. Here, we shed light on the available evidence on mucin, MUC5AC in predicting the outcome of pancreatic cancers. We also discuss variants of MUC5AC believed to have a role in the malignant transformation of pancreatic tissues. Abstract Mucin-5AC (MUC5AC) is a heavily glycosylated gel-forming secreted mucin with a reliable prognostic value when detected in multiple malignancies. It is highly prevalent (70%) in PDA and is nonexistent in normal pancreatic tissues. Retrospective studies on PDA tumor tissue (detected by immunohistochemistry or IHC)) have investigated the prognostic value of MUC5AC expression but were equivocal. Some studies associated it with poor outcomes (survival or pathological features such as lymph node disease, vascular/neural invasion in resected tumors), while others have concluded that it is a good prognostic marker. The examination of expression level threshold (5%, 10%, or 25%) and the detected region (apical vs. cytoplasmic) were variable among the studies. The maturation stage and glycoform of MUC5AC detected also differed with the Monoclonal antibody (Mab) employed for IHC. CLH2 detects less mature/less glycosylated versions while 45M1 or 21-1 detect mature/more glycosylated forms. Interestingly, aberrantly glycosylated variants of MUC5AC were detected using lectin assays (Wheat Germ Agglutinin-MUC5AC), and Mabs such as NPC-1C and PAM4 have are more specific to malignant pancreatic tissues. NPC-1C and PAM4 antibody reactive epitopes on MUC5AC are immunogenic and could represent specific changes on the native MUC5AC glycoprotein linked to carcinogenesis. It was never studied to predict treatment response.
Collapse
|
|
26
|
Review of clinical and emerging biomarkers for early diagnosis and treatment management of pancreatic cancer: towards personalised medicine. JOURNAL OF RADIOTHERAPY IN PRACTICE 2021. [DOI: 10.1017/s1460396921000182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
Abstract
Abstract
Background:
Pancreatic cancer is the 12th most commonly diagnosed cancer and the 3rd leading cause of cancer mortality and accounts for approximately 2·7% of all newly diagnosed cancer cases and 6·4% of all cancer mortalities in Canada. It has a very poor survival rate mainly due to the difficulty of detecting the disease at an early stage. Consequently, in the advancement of disease management towards the concept of precision medicine that takes individual patient variabilities into account, several investigators have focused on the identification of effective clinical biomarkers with high specificity and sensitivity, capable of early diagnosis of symptomatic patients and early detection of the disease in asymptomatic individuals at high risk for developing pancreatic cancer.
Materials and methods:
We searched several databases from August to December 2020 for relevant studies published in English between 2000 and 2020 and reporting on biomarkers for the management of pancreatic cancer. In this narrative review paper, we describe 13 clinical and emerging biomarkers for pancreatic cancers used in screening for early detection and diagnosis, to identify patients’ risk for metastatic disease and subsequent relapse, to monitor patient response to specific treatment and to provide clinicians the possibility of prospectively identifying groups of patients who will benefit from a particular treatment.
Conclusions:
Current and emerging biomarkers for pancreatic cancer with high specificity and sensitivity has the potential to account for individual patient variabilities, for early detection of disease before the onset of metastasis to improve treatment outcome and patients’ survival, help screen high-risk populations, predict prognosis, provide accurate information of patient response to specific treatment and improve patients monitoring during treatment. Thus, the future holds promise for the use of effective clinical biomarkers or a panel of biomarkers for personalised patient-specific targeted medicine for pancreatic cancer.
Collapse
|
|
27
|
Shusterman M, Jou E, Kaubisch A, Chuy JW, Rajdev L, Aparo S, Tang J, Ohri N, Negassa A, Goel S. The Neutrophil-to-Lymphocyte Ratio is a Prognostic Biomarker in An Ethnically Diverse Patient Population with Advanced Pancreatic Cancer. J Gastrointest Cancer 2021; 51:868-876. [PMID: 31677056 DOI: 10.1007/s12029-019-00316-8] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
PURPOSE The neutrophil-to-lymphocyte ratio (NLR) is associated with decreased overall survival in patients with pancreatic adenocarcinoma (PAC) in studies including few minority patients. We investigated the association between NLR and survival in patients with advanced PAC in an ethnically diverse population. METHODS We retrospectively evaluated 226 patients with advanced PAC treated at Montefiore Medical Center between 2006 and 2015. Adjusted Cox proportion hazard regression models were utilized to derive effect estimates for survival duration. RESULTS Patients with a NLR ≤ 5 (126 patients, median age 66 years) were more likely to be non-Hispanic Black (30.8% vs. 20%), while patients with a NLR > 5 (70 patients, median age 66 years) were more likely to be non-Hispanic White (21.4% vs. 12.2%) or Hispanic (44.3% vs. 34%). A NLR > 5 compared with a NLR ≤ 5 was significantly associated with a worse overall survival when adjusted for a priori and exploratory variables from the univariate analysis (median survival 7.4 vs. 12 months, HR 1.650, 95% CI 1.139, 2.390). CONCLUSIONS In an ethnically diverse population, elevated NLR is an independent marker of poor prognosis and a potentially valuable factor in driving therapeutic decisions and defining prognosis for patients in the locally advanced or metastatic for PAC setting, meriting investigation in prospective clinical trials.
Collapse
Affiliation(s)
- Michael Shusterman
- Department of Medical Oncology, Montefiore Medical Center, 1695 Eastchester Road, Bronx, NY, USA
| | - Erin Jou
- Department of Medical Oncology, Montefiore Medical Center, 1695 Eastchester Road, Bronx, NY, USA
| | - Andreas Kaubisch
- Department of Medical Oncology, Montefiore Medical Center, 1695 Eastchester Road, Bronx, NY, USA.,Albert Einstein College of Medicine, Bronx, NY, 10461, USA
| | - Jennifer W Chuy
- Department of Medical Oncology, Montefiore Medical Center, 1695 Eastchester Road, Bronx, NY, USA.,Albert Einstein College of Medicine, Bronx, NY, 10461, USA
| | - Lakshmi Rajdev
- Department of Medical Oncology, Montefiore Medical Center, 1695 Eastchester Road, Bronx, NY, USA.,Albert Einstein College of Medicine, Bronx, NY, 10461, USA
| | - Santiago Aparo
- Department of Medical Oncology, Montefiore Medical Center, 1695 Eastchester Road, Bronx, NY, USA.,Albert Einstein College of Medicine, Bronx, NY, 10461, USA
| | - Justin Tang
- Department of Radiation Oncology, Montefiore Medical Center, Bronx, NY, USA
| | - Nitin Ohri
- Department of Radiation Oncology, Montefiore Medical Center, Bronx, NY, USA.,Albert Einstein College of Medicine, Bronx, NY, 10461, USA
| | - Abdissa Negassa
- Department of Epidemiology and Population Health, Bronx, USA.,Albert Einstein College of Medicine, Bronx, NY, 10461, USA
| | - Sanjay Goel
- Department of Medical Oncology, Montefiore Medical Center, 1695 Eastchester Road, Bronx, NY, USA. .,Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
| |
Collapse
|
|
28
|
Real World First-Line Treatments and Outcomes of Nab-Paclitaxel Plus Gemcitabine, mFOLFIRINOX and GEMOX in Unresectable Pancreatic Cancer from a Chinese Single Institution. ACTA ACUST UNITED AC 2020; 28:209-219. [PMID: 33704188 PMCID: PMC7816170 DOI: 10.3390/curroncol28010023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Revised: 12/16/2020] [Accepted: 12/24/2020] [Indexed: 12/24/2022]
Abstract
Background: There have not been any head-to-head prospective studies to compare the effects of different chemotherapy regimens as first-line treatments for unresectable pancreatic cancer (UPC). We aimed to compare the effectiveness of nab-paclitaxel plus gemcitabine, mFOLFIRINOX and gemcitabine plus oxaliplatin (GEMOX) as first-line treatments by using real-world data from Chinese patients. Methods: We retrospectively included patients with UPC treated with nab-paclitaxel plus gemcitabine, mFOLFIRINOX or GEMOX as a first-line treatment at Sun Yat-sen University Cancer Center. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR) were assessed. Results: A total of 117 patients were administered nab-paclitaxel plus gemcitabine (n = 62), mFOLFIRINOX (n = 30) or GEMOX (n = 25) as first-line chemotherapy. The median OS was 11.1, 10.1 and 10.2 months (p = 0.75) in the nab-paclitaxel plus gemcitabine, mFOLFIRINOX and GEMOX, respectively. The ORR was similar among the three groups (24%, 23% and 32%, p = 0.76) and the DCR was higher in the nab-paclitaxel-gemcitabine group (82%) than the other two groups (60% and 64%, p = 0.04). The most common adverse events of grade 3 or 4 were neutropenia (32%, 28% and 5%), peripheral neuropathy (13%, 16% and 0) and fatigue (9%, 16% and 5%). Febrile neutropenia occurred in 2%, 4% and 5% of the patients in the three groups. Conclusion: In the first line treatment of UPC, our results suggest that nab-paclitaxel plus gemcitabine was associated with a higher DCR than mFOLFIRINOX or GEMOX, while all groups demonstrated similar OS, PFS and ORR.
Collapse
|
|
29
|
Yu S, Zhang C, Xie KP. Therapeutic resistance of pancreatic cancer: Roadmap to its reversal. Biochim Biophys Acta Rev Cancer 2020; 1875:188461. [PMID: 33157162 DOI: 10.1016/j.bbcan.2020.188461] [Citation(s) in RCA: 67] [Impact Index Per Article: 13.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2020] [Revised: 10/20/2020] [Accepted: 10/24/2020] [Indexed: 02/07/2023]
Abstract
Pancreatic cancer is a lethal disease with limited opportunity for resectable surgery as the first choice for cure due to its late diagnosis and early metastasis. The desmoplastic stroma and cellular genetic or epigenetic alterations of pancreatic cancer impose physical and biological barriers to effective therapies, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy. Here, we review the current therapeutic options for pancreatic cancer, and underlying mechanisms and potential reversal of therapeutic resistance, a hallmark of this deadly disease.
Collapse
Affiliation(s)
- Sen Yu
- Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital Affiliated to the South China University of Technology, School of Medicine, Guangzhou, Guangdong, People's Republic of China
| | - Chunyu Zhang
- Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital Affiliated to the South China University of Technology, School of Medicine, Guangzhou, Guangdong, People's Republic of China
| | - Ke-Ping Xie
- Department of Gastroenterology and Hepatology, Guangzhou First People's Hospital Affiliated to the South China University of Technology, School of Medicine, Guangzhou, Guangdong, People's Republic of China.
| |
Collapse
|
|
30
|
Colloca GA, Venturino A, Guarneri D. Tumor growth kinetics by CA 19-9 in patients with unresectable pancreatic cancer receiving chemotherapy: A retrospective analysis. Pancreatology 2020; 20:1189-1194. [PMID: 32747196 DOI: 10.1016/j.pan.2020.07.397] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2019] [Revised: 07/19/2020] [Accepted: 07/21/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Recently, measures of tumor growth kinetics calculated by carbohydrate antigen 19-9 (CA 19-9) determinations after cytotoxic chemotherapy (CHT) have been reported as effective prognostic indicators in locally-advanced unresectable and metastatic pancreatic adenocarcinoma (mPDAC). The study aims to evaluate the prognostic role of tumor kinetics measured by CA 19-9 in patients with mPDAC, measuring it by three different ways. METHODS Patients with mPDAC receiving a first-line CHT between 2009 and 2017 were identified, and those for whom CA 19-9 data were available were enrolled. Three CA 19-9-related variables were calculated: CA 19-9 related reduction rate (RR) and tumor growth rate (G), after 8 weeks of CHT, tumor growth and inflammation index (TGII), after 90 days of CHT. The relationships with the outcome were analysed, and a Cox model has been build with each of the three variables. RESULTS Of 118 patients only 48 were eligible for the analysis. RR, G, or TGII appear as significant prognostic factors, and, after multivariate analysis, a reduction rate of 20% the baseline or more was associated with good survival (HR 0.321; CIs 0.156-0.661) as well as a G > -0.4%/day (HR 2.114; CIs 1.034-4.321), whereas TGII >190 was not correlated with the outcome (HR 1.788; CIs 0.789-4.055). CONCLUSIONS In patients with mPDAC, after 8 weeks of first-line CHT, CA 19-9-related tumor reduction or growth rate appear as valuable prognostic factors.
Collapse
|
|
31
|
Kan M, Imaoka H, Watanabe K, Sasaki M, Takahashi H, Hashimoto Y, Ohno I, Mitsunaga S, Umemoto K, Kimura G, Suzuki Y, Eguchi H, Otsuru T, Goda K, Ikeda M. Chemotherapy-induced neutropenia as a prognostic factor in patients with pancreatic cancer treated with gemcitabine plus nab-paclitaxel: a retrospective cohort study. Cancer Chemother Pharmacol 2020; 86:203-210. [PMID: 32632515 DOI: 10.1007/s00280-020-04110-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Accepted: 06/30/2020] [Indexed: 10/23/2022]
Abstract
OBJECTIVES Chemotherapy-induced neutropenia (CIN) is a common adverse event of chemotherapy. Several reports have suggested that CIN could be an important prognostic factor in chemotherapy of various cancers. However, whether CIN is a prognostic factor in unresectable pancreatic cancer (PC) treated with gemcitabine plus nab-paclitaxel (GnP) is unknown. The primary endpoint of this study was to compare overall survival (OS) between patients with severe CIN (grade ≥ 3) and those with absent/mild CIN (grade ≤ 2) in unresectable PC cases treated with GnP as first-line chemotherapy. METHODS A retrospective, cohort study was conducted using data from a computerized database. A total of 290 patients with pathologically confirmed PC treated with GnP as first-line chemotherapy were analyzed (severe CIN: ≥ grade 3, n = 174; absent/mild CIN: ≤ grade 2, n = 116). RESULTS The median OS was longer in the severe CIN group than in the absent/mild CIN group (19.2 months vs 11.3 months, respectively; P < 0.001). After adjustment, severe CIN was an independent predictive factor for OS (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.38-0.74; P < 0.001). After adjustment by time-varying covariates, severe CIN was still a significant prognostic factor for OS (HR, 0.79; 95% CI 0.69-0.91, P = 0.001). CONCLUSION The present results show that severe CIN is an independent and useful prognostic factor in PC patients treated with GnP.
Collapse
Affiliation(s)
- Motoyasu Kan
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, 277-8577, Japan
| | - Hiroshi Imaoka
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, 277-8577, Japan.
| | - Kazuo Watanabe
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, 277-8577, Japan
| | - Mitsuhito Sasaki
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, 277-8577, Japan
| | - Hideaki Takahashi
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, 277-8577, Japan
| | - Yusuke Hashimoto
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, 277-8577, Japan
| | - Izumi Ohno
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, 277-8577, Japan
| | - Shuichi Mitsunaga
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, 277-8577, Japan
| | - Kumiko Umemoto
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, 277-8577, Japan
| | - Gen Kimura
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, 277-8577, Japan
| | - Yuko Suzuki
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, 277-8577, Japan
| | - Hiroki Eguchi
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, 277-8577, Japan
| | - Toru Otsuru
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, 277-8577, Japan
| | - Kyosuke Goda
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, 277-8577, Japan
| | - Masafumi Ikeda
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital East, 6-5-1, Kashiwanoha, Kashiwa, 277-8577, Japan
| |
Collapse
|
|
32
|
Toledano-Fonseca M, Cano MT, Inga E, Rodríguez-Alonso R, Gómez-España MA, Guil-Luna S, Mena-Osuna R, de la Haba-Rodríguez JR, Rodríguez-Ariza A, Aranda E. Circulating Cell-Free DNA-Based Liquid Biopsy Markers for the Non-Invasive Prognosis and Monitoring of Metastatic Pancreatic Cancer. Cancers (Basel) 2020; 12:cancers12071754. [PMID: 32630266 PMCID: PMC7409337 DOI: 10.3390/cancers12071754] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Revised: 06/26/2020] [Accepted: 06/29/2020] [Indexed: 12/20/2022] Open
Abstract
Liquid biopsy may assist in the management of cancer patients, which can be particularly applicable in pancreatic ductal adenocarcinoma (PDAC). In this study, we investigated the utility of circulating cell-free DNA (cfDNA)-based markers as prognostic tools in metastatic PDAC. Plasma was obtained from 61 metastatic PDAC patients, and cfDNA levels and fragmentation were determined. BEAMing technique was used for quantitative determination of RAS mutation allele fraction (MAF) in cfDNA. We found that the prognosis was more accurately predicted by RAS mutation detection in plasma than in tissue. RAS mutation status in plasma was a strong independent prognostic factor for both overall survival (OS) and progression-free survival (PFS). Moreover, RAS MAF in cfDNA was also an independent risk factor for poor OS, and was strongly associated with primary tumours in the body/tail of the pancreas and liver metastases. Higher cfDNA levels and fragmentation were also associated with poorer OS and shorter PFS, body/tail tumors, and hepatic metastases, whereas cfDNA fragmentation positively correlated with RAS MAF. Remarkably, the combination of CA19-9 with MAF, cfDNA levels and fragmentation improved the prognostic stratification of patients. Furthermore, dynamics of RAS MAF better correlated with patients’ outcome than standard CA19-9 marker. In conclusion, our study supports the use of cfDNA-based liquid biopsy markers as clinical tools for the non-invasive prognosis and monitoring of metastatic PDAC patients.
Collapse
Affiliation(s)
- Marta Toledano-Fonseca
- Maimónides Biomedical Research Institute of Córdoba (IMIBIC), E14004 Córdoba, Spain; (M.T.-F.); (S.G.-L.); (R.M.-O.); (J.R.d.l.H.-R.); (E.A.)
- Cancer Network Biomedical Research Center (CIBERONC), E28029 Madrid, Spain;
| | - M. Teresa Cano
- Medical Oncology Department, Reina Sofía University Hospital, E14004 Córdoba, Spain; (M.T.C.); (E.I.); (R.R.-A.)
| | - Elizabeth Inga
- Medical Oncology Department, Reina Sofía University Hospital, E14004 Córdoba, Spain; (M.T.C.); (E.I.); (R.R.-A.)
| | - Rosa Rodríguez-Alonso
- Medical Oncology Department, Reina Sofía University Hospital, E14004 Córdoba, Spain; (M.T.C.); (E.I.); (R.R.-A.)
| | - M. Auxiliadora Gómez-España
- Cancer Network Biomedical Research Center (CIBERONC), E28029 Madrid, Spain;
- Medical Oncology Department, Reina Sofía University Hospital, E14004 Córdoba, Spain; (M.T.C.); (E.I.); (R.R.-A.)
| | - Silvia Guil-Luna
- Maimónides Biomedical Research Institute of Córdoba (IMIBIC), E14004 Córdoba, Spain; (M.T.-F.); (S.G.-L.); (R.M.-O.); (J.R.d.l.H.-R.); (E.A.)
- Cancer Network Biomedical Research Center (CIBERONC), E28029 Madrid, Spain;
| | - Rafael Mena-Osuna
- Maimónides Biomedical Research Institute of Córdoba (IMIBIC), E14004 Córdoba, Spain; (M.T.-F.); (S.G.-L.); (R.M.-O.); (J.R.d.l.H.-R.); (E.A.)
| | - Juan R. de la Haba-Rodríguez
- Maimónides Biomedical Research Institute of Córdoba (IMIBIC), E14004 Córdoba, Spain; (M.T.-F.); (S.G.-L.); (R.M.-O.); (J.R.d.l.H.-R.); (E.A.)
- Cancer Network Biomedical Research Center (CIBERONC), E28029 Madrid, Spain;
- Medical Oncology Department, Reina Sofía University Hospital, E14004 Córdoba, Spain; (M.T.C.); (E.I.); (R.R.-A.)
| | - Antonio Rodríguez-Ariza
- Maimónides Biomedical Research Institute of Córdoba (IMIBIC), E14004 Córdoba, Spain; (M.T.-F.); (S.G.-L.); (R.M.-O.); (J.R.d.l.H.-R.); (E.A.)
- Cancer Network Biomedical Research Center (CIBERONC), E28029 Madrid, Spain;
- Medical Oncology Department, Reina Sofía University Hospital, E14004 Córdoba, Spain; (M.T.C.); (E.I.); (R.R.-A.)
- Correspondence:
| | - Enrique Aranda
- Maimónides Biomedical Research Institute of Córdoba (IMIBIC), E14004 Córdoba, Spain; (M.T.-F.); (S.G.-L.); (R.M.-O.); (J.R.d.l.H.-R.); (E.A.)
- Cancer Network Biomedical Research Center (CIBERONC), E28029 Madrid, Spain;
- Medical Oncology Department, Reina Sofía University Hospital, E14004 Córdoba, Spain; (M.T.C.); (E.I.); (R.R.-A.)
- Department of Medicine, Faculty of Medicine, University of Córdoba, E14004 Córdoba, Spain
| |
Collapse
|
|
33
|
Abstract
OBJECTIVES This analysis investigated nomogram use to evaluate metastatic pancreatic cancer prognosis. METHODS Thirty-four baseline factors were examined in the Metastatic Pancreatic Adenocarcinoma Clinical Trial (MPACT) (nab-paclitaxel plus gemcitabine vs gemcitabine) data set. Factors significantly (P < 0.1) associated with overall survival (OS) in a univariable model or with known clinical relevance were tested further. In a multivariable model, factors associated with OS (P < 0.1) were selected to generate the primary nomogram, which was internally validated using bootstrapping, a concordance index, and calibration plots. RESULTS Using data from 861 patients, 6 factors were retained (multivariable analysis): neutrophil-lymphocyte ratio, albumin level, Karnofsky performance status, sum of longest diameter of target lesions, presence of liver metastases, and previous Whipple procedure. The nomogram distinguished low-, medium-, and high-risk groups (concordance index, 0.67; 95% confidence interval, 0.65-0.69; median OS, 11.7, 8.0, and 3.3 months, respectively). CONCLUSIONS This nomogram may guide estimates of the range of OS outcomes and contribute to patient stratification in future prospective metastatic pancreatic cancer trials; however, external validation is required to improve estimate reliability and applicability to a general patient population. Caution should be exercised in interpreting these results for treatment decisions: patient characteristics could differ from those included in the nomogram development.
Collapse
|
|
34
|
Mizrahi JD, Surana R, Valle JW, Shroff RT. Pancreatic cancer. Lancet 2020; 395:2008-2020. [PMID: 32593337 DOI: 10.1016/s0140-6736(20)30974-0] [Citation(s) in RCA: 1570] [Impact Index Per Article: 314.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2020] [Revised: 04/06/2020] [Accepted: 04/17/2020] [Indexed: 02/07/2023]
Abstract
Pancreatic cancer is a highly fatal disease with a 5-year survival rate of approximately 10% in the USA, and it is becoming an increasingly common cause of cancer mortality. Risk factors for developing pancreatic cancer include family history, obesity, type 2 diabetes, and tobacco use. Patients typically present with advanced disease due to lack of or vague symptoms when the cancer is still localised. High quality computed tomography with intravenous contrast using a dual phase pancreatic protocol is typically the best method to detect a pancreatic tumour and to determine surgical resectability. Endoscopic ultrasound is an increasingly used complementary staging modality which also allows for diagnostic confirmation when combined with fine needle aspiration. Patients with pancreatic cancer are often divided into one of four categories based on extent of disease: resectable, borderline resectable, locally advanced, and metastatic; patient condition is also an important consideration. Surgical resection represents the only chance for cure, and advancements in adjuvant chemotherapy have improved long-term outcomes in these patients. Systemic chemotherapy combinations including FOLFIRINOX (5-fluorouracil, folinic acid [leucovorin], irinotecan, and oxaliplatin) and gemcitabine plus nab-paclitaxel remain the mainstay of treatment for patients with advanced disease. Data on the benefit of PARP inhibition as maintenance therapy in patients with germline BRCA1 or BRACA2 mutations might prove to be a harbinger of advancement in targeted therapy. Additional research efforts are focusing on modulating the pancreatic tumour microenvironment to enhance the efficacy of the immunotherapeutic strategies.
Collapse
Affiliation(s)
- Jonathan D Mizrahi
- Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Rishi Surana
- Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Juan W Valle
- Division of Cancer Sciences, University of Manchester, Department of Medical Oncology, Christie NHS Foundation Trust, Manchester, UK
| | - Rachna T Shroff
- Division of Hematology and Oncology, Department of Medicine, University of Arizona Cancer Center, Tucson, AZ, USA.
| |
Collapse
|
|
35
|
Zeh HJ, Bahary N, Boone BA, Singhi AD, Miller-Ocuin JL, Normolle DP, Zureikat AH, Hogg ME, Bartlett DL, Lee KK, Tsung A, Marsh JW, Murthy P, Tang D, Seiser N, Amaravadi RK, Espina V, Liotta L, Lotze MT. A Randomized Phase II Preoperative Study of Autophagy Inhibition with High-Dose Hydroxychloroquine and Gemcitabine/Nab-Paclitaxel in Pancreatic Cancer Patients. Clin Cancer Res 2020; 26:3126-3134. [PMID: 32156749 DOI: 10.1158/1078-0432.ccr-19-4042] [Citation(s) in RCA: 147] [Impact Index Per Article: 29.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2019] [Revised: 02/05/2020] [Accepted: 03/06/2020] [Indexed: 12/19/2022]
Abstract
PURPOSE We hypothesized that autophagy inhibition would increase response to chemotherapy in the preoperative setting for patients with pancreatic adenocarcinoma. We performed a randomized controlled trial to assess the autophagy inhibitor hydroxychloroquine in combination with gemcitabine and nab-paclitaxel. PATIENTS AND METHODS Participants with potentially resectable tumors were randomized to two cycles of nab-paclitaxel and gemcitabine (PG) alone or with hydroxychloroquine (PGH), followed by resection. The primary endpoint was histopathologic response in the resected specimen. Secondary clinical endpoints included serum CA 19-9 biomarker response and margin negative R0 resection. Exploratory endpoints included markers of autophagy, immune infiltrate, and serum cytokines. RESULTS Thirty-four patients in the PGH arm and 30 in the PG arm were evaluable for the primary endpoint. The PGH arm demonstrated statistically improved Evans grade histopathologic responses (P = 0.00016), compared with control. In patients with elevated CA 19-9, a return to normal was associated with improved overall and recurrence-free survival (P < 0.0001). There were no differences in serious adverse events between arms and chemotherapy dose number was equivalent. The PGH arm had greater evidence of autophagy inhibition in their resected specimens (increased SQSTM1, P = 0.027, as well as increased immune cell tumor infiltration, P = 0.033). Overall survival (P = 0.59) and relapse-free survival (P = 0.55) did not differ between the two arms. CONCLUSIONS The addition of hydroxychloroquine to preoperative gemcitabine and nab-paclitaxel chemotherapy in patients with resectable pancreatic adenocarcinoma resulted in greater pathologic tumor response, improved serum biomarker response, and evidence of autophagy inhibition and immune activity.
Collapse
Affiliation(s)
- Herbert J Zeh
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Nathan Bahary
- Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
| | - Brian A Boone
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Aatur D Singhi
- Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania
| | | | - Daniel P Normolle
- Department of Biostatistics, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Amer H Zureikat
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Melissa E Hogg
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - David L Bartlett
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Kenneth K Lee
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Allan Tsung
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - J Wallis Marsh
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Pranav Murthy
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Daolin Tang
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Natalie Seiser
- HPB and Transplant Institute at St. Vincent's Medical Center, Los Angeles, California
| | - Ravi K Amaravadi
- Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Virginia Espina
- Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, Virginia
| | - Lance Liotta
- Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, Virginia
| | - Michael T Lotze
- Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania.,Department of Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania.,Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania
| |
Collapse
|
|
36
|
Sun Q, Zhang Y, Liu M, Ye Z, Yu X, Xu X, Qin Y. Prognostic and diagnostic significance of galectins in pancreatic cancer: a systematic review and meta-analysis. Cancer Cell Int 2019; 19:309. [PMID: 31832021 PMCID: PMC6873495 DOI: 10.1186/s12935-019-1025-5] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2019] [Accepted: 11/11/2019] [Indexed: 02/06/2023] Open
Abstract
Background Galectins constitute a family of β-galactoside-binding proteins, which influence various hallmarks of pancreatic cancer, including cell proliferation, invasion and migration; immune escape; and angiogenesis. Although many studies have concentrated on the role of galectins in pancreatic cancer, the results remain controversial. Hence, we performed a comprehensive meta-analysis to clarify the precise diagnostic and prognostic value of galectins in pancreatic cancer. Methods PubMed/MEDLINE, EMBASE and Web of Science were used to search related published literature up to July 2019. Pooled hazard ratios (HRs), diagnostic accuracy variables and related 95% confidence intervals (CIs) were calculated using STATA 14.0 software. Results Eleven studies including 1227 participants met our inclusion criteria. High expression of galectin family was not correlated with overall survival (OS) in pancreatic cancer (HR, 1.19; 95% CI 0.67-2.11). According to subgroup analysis, high levels of galectin-1 were significantly correlated with worse OS in pancreatic cancer (HR, 4.77; 95% CI 2.47-9.21), while high levels of tandem-repeat galectins (galectin-4 or galectin-9) predicted both better OS (HR, 0.63; 95% CI 0.46-0.86) and disease-free survival (DFS) (HR, 0.63; 95% CI 0.48-0.83). The expression levels of galectin-3 did not directly correlate with prognosis (HR, 0.99; 95% CI 0.40-2.46). The pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratios of galectin-3 were 0.64 (95% CI 0.41-0.82), 0.76 (95% CI 0.59-0.88), 2.70 (95% CI 1.21-6.1), and 0.47 (95% CI 0.23-0.98), respectively. The area under the curve (AUC) of galectin-3 was 0.77. Conclusion Taken together, our results suggest that high expression of galectin-1 and low levels of galectin-4 or galectin-9 are predictors of worse prognosis in pancreatic cancer patients. The expression of galectin-3 was not directly related to OS and other clinical characteristics. Although galectin-3 exhibited some diagnostic value in patients with pancreatic cancer in this meta-analysis, clinical application prospects remain to be validated. Further studies are warranted to confirm and strengthen these findings.
Collapse
Affiliation(s)
- Qiqing Sun
- 1Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032 China.,2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032 China.,3Pancreatic Cancer Institute, Fudan University, Shanghai, 200032 China.,4Shanghai Pancreatic Cancer Institute, Shanghai, 200032 China
| | - Yiyin Zhang
- 1Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032 China.,2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032 China.,3Pancreatic Cancer Institute, Fudan University, Shanghai, 200032 China.,4Shanghai Pancreatic Cancer Institute, Shanghai, 200032 China
| | - Mengqi Liu
- 1Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032 China.,2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032 China.,3Pancreatic Cancer Institute, Fudan University, Shanghai, 200032 China.,4Shanghai Pancreatic Cancer Institute, Shanghai, 200032 China
| | - Zeng Ye
- 1Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032 China.,2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032 China.,3Pancreatic Cancer Institute, Fudan University, Shanghai, 200032 China.,4Shanghai Pancreatic Cancer Institute, Shanghai, 200032 China
| | - Xianjun Yu
- 1Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032 China.,2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032 China.,3Pancreatic Cancer Institute, Fudan University, Shanghai, 200032 China.,4Shanghai Pancreatic Cancer Institute, Shanghai, 200032 China
| | - Xiaowu Xu
- 1Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032 China.,2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032 China.,3Pancreatic Cancer Institute, Fudan University, Shanghai, 200032 China.,4Shanghai Pancreatic Cancer Institute, Shanghai, 200032 China
| | - Yi Qin
- 1Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, 200032 China.,2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032 China.,3Pancreatic Cancer Institute, Fudan University, Shanghai, 200032 China.,4Shanghai Pancreatic Cancer Institute, Shanghai, 200032 China
| |
Collapse
|
|
37
|
Chen Y, Wang YR, Deng GC, Dai GH. CA19-9 decrease and survival according to platelet level in patients with advanced pancreatic cancer. BMC Cancer 2019; 19:860. [PMID: 31470818 PMCID: PMC6716806 DOI: 10.1186/s12885-019-6078-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2018] [Accepted: 08/22/2019] [Indexed: 12/16/2022] Open
Abstract
Background CA19–9 decrease during treatment has been associated with superior survival of pancreatic cancer in several studies. The evidence to show the correlation of high platelet level with inferior survival is insufficient in pancreatic cancer. It also remains unclear whether the association between CA19–9 decrease and survival was corresponded to different levels of platelet in metastatic pancreatic cancer. Methods We measured CA19–9 serum concentration and platelet level at baseline and after the second cycle of chemotherapy for 200 advanced pancreatic cancer patients. A Cox proportional hazards model was used to compute mortality hazard ratios (HRs) for CA19–9 decrease, adjusting for potential confounders, including age, sex, KPS, prediagnosis body mass index, Diabetes Mellitus, tumor location, first-line chemotherapy regimen, and radiotherapy. Results We found that the association of CA19–9 decrease with superior overall survival was stronger in advanced pancreatic cancer with a low level of platelet (Pinteraction < 0.001) compared with intermediate and high level of platelet. Multivariable-adjusted hazard ratios per unit decrease of CA19–9 change was 0.45 [95% confidence interval (CI), 0.33 to 0.62] in cases with low platelet level, 0.74 (95% CI, 0.50 to 1.09) in cases with intermediate platelet level, and 0.94 (95% CI, 0.74 to 1.10) in cases with high platelet level. A similar differential association was found between CA19–9 decrease and progression-free survival in strata of platelet level (Pinteraction = 0.034). Conclusion The association of CA19–9 decrease with superior pancreatic cancer survival appeared to be pronounced in patients with a low platelet level. This finding could provide supports for the underlying mechanisms of CA19–9 involved in platelet / tumor cell interaction. Electronic supplementary material The online version of this article (10.1186/s12885-019-6078-2) contains supplementary material, which is available to authorized users.
Collapse
Affiliation(s)
- Y Chen
- Department of Medical Oncology, Chinese People's Liberation Army (PLA) General Hospital and Chinese PLA Medical School, Beijing, 100853, China.,Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital and Institute, 52 Fucheng Road, Haidian District, Beijing, 100142, China
| | - Y R Wang
- Department of Medical Oncology, Chinese People's Liberation Army (PLA) General Hospital and Chinese PLA Medical School, Beijing, 100853, China
| | - G C Deng
- Department of Medical Oncology, Chinese People's Liberation Army (PLA) General Hospital and Chinese PLA Medical School, Beijing, 100853, China
| | - G H Dai
- Department of Medical Oncology, Chinese People's Liberation Army (PLA) General Hospital and Chinese PLA Medical School, Beijing, 100853, China.
| |
Collapse
|
|
38
|
Bonnet E, Mastier C, Lardy-Cléaud A, Rochefort P, Sarabi M, Guibert P, Cattey-Javouhey A, Desseigne F, de La Fouchardière C. FOLFIRINOX in patients with peritoneal carcinomatosis from pancreatic adenocarcinoma: a retrospective study. ACTA ACUST UNITED AC 2019; 26:e466-e472. [PMID: 31548814 DOI: 10.3747/co.26.4903] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Background Peritoneal carcinomatosis (pcm) in metastatic pancreatic ductal adenocarcinomas (mpdac) is frequently encountered in day-to-day practice, but rarely addressed in the literature. The objective of the present study was to describe the management and outcome of patients diagnosed with pcm. Methods Data for all consecutive patients with mpdac treated in our centre between 1 January 2014 and 31 August 2015 were analyzed retrospectively. Computed tomography imaging was centrally reviewed by a dedicated radiologist to determine the date of pcm diagnosis. Results The analysis included 48 patients. Median age in the group was 61 years, and 41 patients had an Eastern Cooperative Oncology Group performance status (ecog ps) of 0-1. All patients presented with pcm either synchronously (group 1) or metachronously (group 2). Those groups differed significantly by baseline ecog ps and neutrophil-to-lymphocyte ratio (nlr), with ecog ps being poorer and nlr being higher in group 1. In addition to pcm, the main sites of metastasis were liver (62.5%) and lungs (31.3%). First-line chemotherapy in 36 patients (75%) was folfirinox (fluorouracil-irinotecan-leucovorin-oxaliplatin). The median overall survival for the entire population was 10.81 months [95% confidence interval (ci): 7.16 months to 14.16 months]; it was 13.17 months (95% ci: 5.9 months to 15.4 months) for patients treated with folfirinox. Median overall survival was 7.13 months (95% ci: 4.24 months to 10.41 months) for patients in group 1 and 14.34 months (95% ci: 9.79 months to 19.91 months) for patients in group 2, p = 0.1296. Conclusions Compared with other metastatic sites, synchronous pcm seems to be a poor prognostic factor. It could be more frequently associated with a poor ecog ps and a nlr greater than 5 in this group of patients. In patients with mpdac and pcm, either synchronous or metachronous, folfirinox remains an efficient regimen.
Collapse
Affiliation(s)
- E Bonnet
- Medical Oncology Department, Centre Léon Bérard, Lyon, France
| | - C Mastier
- Radiology Department, Centre Léon Bérard, Lyon, France
| | - A Lardy-Cléaud
- Clinical Research and Innovation Department, Centre Léon Bérard, Lyon, France
| | - P Rochefort
- Medical Oncology Department, Centre Léon Bérard, Lyon, France
| | - M Sarabi
- Medical Oncology Department, Centre Léon Bérard, Lyon, France
| | - P Guibert
- Medical Oncology Department, Centre Léon Bérard, Lyon, France
| | | | - F Desseigne
- Medical Oncology Department, Centre Léon Bérard, Lyon, France
| | | |
Collapse
|
|
39
|
Nebot-Villacampa MJ, Zafra-Morales R, Alfaro-Olea A, Marín-Gorricho R, Casajús-Navasal A, Uriarte-Pinto M. Effectiveness and safety of nab-paclitaxel/gemcitabine in locally advanced or metastatic pancreatic adenocarcinoma. J Oncol Pharm Pract 2019; 26:603-611. [PMID: 31315550 DOI: 10.1177/1078155219862035] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Treatment based on nab-paclitaxel plus gemcitabine is one of the standard treatments for locally advanced or metastatic pancreatic adenocarcinoma. Not much information is available about its use in clinical practice. Looking for prognostic markers may aid in improving treatment plans for patients. OBJECTIVE To describe the effectiveness and safety profile of nab-paclitaxel/gemcitabine in locally advanced or metastatic pancreatic adenocarcinoma. We also tried to evaluate prognostic markers of response to treatment. SETTING Retrospective descriptive study carried out in a tertiary hospital of Spain. METHOD Patients with locally advanced or metastatic pancreatic adenocarcinoma treated with nab-paclitaxel/gemcitabina between January 2014 and December 2017 were included in the analyses. MAIN OUTCOME MEASURE Effectiveness was measured in terms of overall survival, progression-free survival and response rate. To evaluate the safety profile, every adverse event from the start of the treatment and up to 10 days after its completion was registered. RESULTS Fifty patients were included. Thirty-three (66%) had metastatic disease. Median overall survival was 8.8 months (95%CI: 5.1-12.5) and the median progression-free survival was 5.6 months (95%CI: 4.3-6.9). Relevance of carbohydrate antigen 19-9 baseline levels as prognostic response marker was confirmed, while neutrophil-to-lymphocyte ratio did not show conclusive results for overall survival. Safety profile was similar to that observed in clinical trials, with a single case of treatment discontinuation due to grade 3 neuropathy. CONCLUSION The studied schedule for locally advanced or metastatic pancreatic adenocarcinoma seems to be an effective therapeutic option, with an easy to manage toxicity profile, similar to other schedules used in pancreatic adenocarcinoma.
Collapse
|
|
40
|
The efficacy and safety of nab paclitaxel plus gemcitabine in elderly patients over 75 years with unresectable pancreatic cancer compared with younger patients. Cancer Chemother Pharmacol 2019; 84:647-654. [DOI: 10.1007/s00280-019-03895-2] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2019] [Accepted: 06/14/2019] [Indexed: 02/06/2023]
|
|
41
|
Yang Y, Huang X, Zhou L, Deng T, Ning T, Liu R, Zhang L, Bai M, Zhang H, Li H, Ba Y. Clinical use of tumor biomarkers in prediction for prognosis and chemotherapeutic effect in esophageal squamous cell carcinoma. BMC Cancer 2019; 19:526. [PMID: 31151431 PMCID: PMC6544972 DOI: 10.1186/s12885-019-5755-5] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2018] [Accepted: 05/27/2019] [Indexed: 11/21/2022] Open
Abstract
BACKGROUND Growing evidence has indicated that tumor biomarkers, including cytokeratin 19 fragment antigen 21-1 (Cyfra21-1), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 72-4 (CA72-4), carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCC-Ag) were reported to be commonly used in diagnosis and prognosis in esophageal squamous cell carcinoma (ESCC). However, which is the best marker for predicting prognosis remains unknown. Few papers focused on the relationship between tumor biomarkers and postoperative treatment in ESCC. METHODS A total of 416 ESCC patients were enrolled in this study. The association between tumor markers and overall survival (OS) was analyzed using Kaplan-Meier method with log-rank test, followed by multivariate Cox regression models. RESULTS The results of Cox multivariate analysis indicated that among these tumor biomarkers, CA19-9 (≥ 37 vs. < 37) [hazard ratio (HR) = 2.130, 95% confidence interval (CI) = 1.138-3.986, p = 0.018] and CEA (≥ 5 vs. < 5) (HR = 1.827, 95% CI = 1.089-3.064, p = 0.022) were the independent prognostic factors of poor OS. For the ESCC patients with CA19-9 < 37, CEA < 5 or SCC-Ag < 1.5, the surgery plus postoperative chemotherapy group had a significantly longer OS than the surgery group alone (p < 0.05), but this significant difference of OS between these two groups cannot be found in patients with CA19-9 ≥ 37, CEA ≥ 5 or SCC-Ag ≥ 1.5 (p > 0.05). CONCLUSIONS CEA and CA19-9 maybe are superior to other tumor biomarkers as prognostic indicators in ESCC. CA19-9, CEA, SCC-Ag may be useful in predicting the therapeutic effect of postoperative chemotherapy in ESCC.
Collapse
Affiliation(s)
- Yuchong Yang
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University, Huanhuxi Road, Tiyuanbei, Hexi District, Tianjin, 300060 People’s Republic of China
| | - Xuanzhang Huang
- 0000 0004 1764 2632grid.417384.dDepartment of Chemotherapy and Radiotherapy, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou City, 325027 People’s Republic of China
| | - Likun Zhou
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University, Huanhuxi Road, Tiyuanbei, Hexi District, Tianjin, 300060 People’s Republic of China
| | - Ting Deng
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University, Huanhuxi Road, Tiyuanbei, Hexi District, Tianjin, 300060 People’s Republic of China
| | - Tao Ning
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University, Huanhuxi Road, Tiyuanbei, Hexi District, Tianjin, 300060 People’s Republic of China
| | - Rui Liu
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University, Huanhuxi Road, Tiyuanbei, Hexi District, Tianjin, 300060 People’s Republic of China
| | - Le Zhang
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University, Huanhuxi Road, Tiyuanbei, Hexi District, Tianjin, 300060 People’s Republic of China
| | - Ming Bai
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University, Huanhuxi Road, Tiyuanbei, Hexi District, Tianjin, 300060 People’s Republic of China
| | - Haiyang Zhang
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University, Huanhuxi Road, Tiyuanbei, Hexi District, Tianjin, 300060 People’s Republic of China
| | - Hongli Li
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University, Huanhuxi Road, Tiyuanbei, Hexi District, Tianjin, 300060 People’s Republic of China
| | - Yi Ba
- Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University, Huanhuxi Road, Tiyuanbei, Hexi District, Tianjin, 300060 People’s Republic of China
| |
Collapse
|
|
42
|
Laurent L, Sefrioui D, Bignon AL, Parzy A, Sidali S, Hassine M, Gangloff A, Galais MP, Bouhier-Leporrier K, Michel P, Di Fiore F. CA19.9 decrease >15% is a predictor of favourable outcome in patients treated for advanced pancreatic carcinoma: analysis of two independent cohorts. HPB (Oxford) 2019; 21:582-588. [PMID: 30466797 DOI: 10.1016/j.hpb.2018.09.006] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/11/2018] [Revised: 08/19/2018] [Accepted: 09/06/2018] [Indexed: 12/12/2022]
Abstract
BACKGROUND Although carbohydrate antigen 19.9 (CA19.9) is widely used in pancreatic adenocarcinoma (PA), no consensual cut-off value of CA19.9 decrease has been established for treatment monitoring. METHODS This was a retrospective study including patients with a baseline CA19.9 ≥ 37 UI/ml and with locally advanced or metastatic PA from two French centers. CA19.9 measurements were performed at baseline and first CT-scan evaluation. The aim was to use a training set to determine the best cut-off of CA19.9 decrease for predicting progressive disease (PD) and to analyze its performance in an independent validation cohort. RESULTS A total of 95 and 93 patients were included in the training and validation sets, respectively. A ≤15% CA19.9 decrease was the best cut-off for predicting PD with a sensitivity (Se) = 68% and a specificity (Sp) = 90%. In the validation set, this threshold was associated with Se = 76% and Sp = 83%. A >15% CA19.9 decrease was significantly associated with improved PFS (median 8.3 versus 3.1 months, p < 0.0001) and OS (median 14 versus 7.2 months, p < 0.0001). A >15% CA19.9 decrease was also identified as a factor independently associated with OS (HRa = 0.25, 95% CI:0.14-0.44). CONCLUSIONS A CA 19.9 decrease >15% is a favourable predictor of outcome in patients treated for advanced PA.
Collapse
Affiliation(s)
- Lucie Laurent
- Rouen University Hospital, Department of Hepato-Gastroenterology, Digestive Oncology Unit, F 76000, Rouen, France
| | - David Sefrioui
- Normandie Univ, UNIROUEN, Inserm U1245, IRON Group, Rouen University Hospital, Department of Hepato-Gastroenterology, Digestive Oncology Unit, F 76000, Rouen, France
| | - Anne-Laure Bignon
- Caen University Hospital, Department of Hepato-Gastroenterology and Nutrition, F 14000, Caen, France
| | - Aurélie Parzy
- Centre Régional François Baclesse, Digestive Oncology Unit, F 14000, Caen, France
| | - Sabrina Sidali
- Rouen University Hospital, Department of Hepato-Gastroenterology, Digestive Oncology Unit, F 76000, Rouen, France
| | - Mélanie Hassine
- Rouen University Hospital, Department of Hepato-Gastroenterology, Digestive Oncology Unit, F 76000, Rouen, France
| | - Alice Gangloff
- Rouen University Hospital, Department of Hepato-Gastroenterology, Digestive Oncology Unit, F 76000, Rouen, France
| | - Marie-Pierre Galais
- Centre Régional François Baclesse, Digestive Oncology Unit, F 14000, Caen, France
| | - Karine Bouhier-Leporrier
- Caen University Hospital, Department of Hepato-Gastroenterology and Nutrition, F 14000, Caen, France
| | - Pierre Michel
- Normandie Univ, UNIROUEN, Inserm U1245, IRON Group, Rouen University Hospital, Department of Hepato-Gastroenterology, Digestive Oncology Unit, F 76000, Rouen, France
| | - Frédéric Di Fiore
- Normandie Univ, UNIROUEN, Inserm U1245, IRON Group, Rouen University Hospital, Digestive Oncology Unit and Department of Medical Oncology, Henri Becquerel Centre, Rouen, F 76000, Rouen, France.
| |
Collapse
|
|
43
|
Jin KT, Lan HR, Chen XY, Wang SB, Ying XJ, Lin Y, Mou XZ. Recent advances in carbohydrate-based cancer vaccines. Biotechnol Lett 2019; 41:641-650. [DOI: 10.1007/s10529-019-02675-5] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Accepted: 04/11/2019] [Indexed: 12/22/2022]
|
|
44
|
Xian J, Zhang Q, Guo X, Liang X, Liu X, Feng Y. A prognostic signature based on three non-coding RNAs for prediction of the overall survival of glioma patients. FEBS Open Bio 2019; 9:682-692. [PMID: 30984542 PMCID: PMC6443874 DOI: 10.1002/2211-5463.12602] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2018] [Revised: 01/21/2019] [Accepted: 01/24/2019] [Indexed: 12/11/2022] Open
Abstract
Recent studies have identified certain non‐coding RNAs (ncRNAs) as biomarkers of disease progression. Glioma is the most common primary intracranial cancer, with high mortality. Here, we developed a prognostic signature for prediction of overall survival (OS) of glioma patients by analyzing ncRNA expression profiles. We downloaded gene expression profiles of glioma patients along with their clinical information from the Gene Expression Omnibus and extracted ncRNA expression profiles via a microarray annotation file. Correlations between ncRNAs and glioma patients’ OS were first evaluated through univariate Cox regression analysis and a permutation test, followed by random survival forest analysis for further screening of valuable ncRNA signatures. Prognostic signatures could be established as a risk score formula by including ncRNA signature expression values weighted by their estimated regression coefficients. Patients could be divided into high risk and low risk subgroups by using the median risk score as cutoff. As a result, glioma patients with a high risk score tended to have shorter OS than those with low risk scores, which was confirmed by analyzing another set of glioma patients in an independent dataset. Additionally, gene set enrichment analysis showed significant enrichment of cancer development‐related biological processes and pathways. Our study may provide further insights into the evaluation of glioma patients’ prognosis.
Collapse
Affiliation(s)
- Junmin Xian
- Department of Neurosurgery The Affiliated Hospital of Qingdao University China.,Department of Neurosurgery Heze Municipal Hospital China
| | | | - Xiwen Guo
- Department of Neurosurgery Heze Municipal Hospital China
| | - Xiankun Liang
- Department of Neurosurgery Heze Municipal Hospital China
| | - Xinhua Liu
- School of Biomedical Engineering Tianjin Medical University China
| | - Yugong Feng
- Department of Neurosurgery The Affiliated Hospital of Qingdao University China
| |
Collapse
|
|
45
|
Li J, Li Z, Kan H, Sun Z, Xing J, Cheng Y, Bai C. CA19-9 elevation as an indication to start salvage treatment in surveillance after pancreatic cancer resection. Pancreatology 2019; 19:302-306. [PMID: 30737189 DOI: 10.1016/j.pan.2019.01.023] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2018] [Revised: 01/25/2019] [Accepted: 01/31/2019] [Indexed: 12/24/2022]
Abstract
BACKGROUND CA19-9 is the most commonly used tumor marker in the diagnosis, prognosis and surveillance of pancreatic cancer. We hypothesized that CA19-9 elevation can be taken as an indication to start salvage treatment in surveillance after resection. METHODS From January 2014 and July 2017, 80 pancreatic cancer patients who underwent R0 surgical resection and received adjuvant chemotherapy were included. RESULTS Twenty-six (32.5%) patients started salvage treatment at the time of CA19-9 elevation without radiological evidence of recurrence. Fifty-four (67.5%) patients treated conventionally before recurrence was confirmed by radiological examinations. Sixty (75%) patients had CA19-9 elevation that preceded radiographic recurrence by about 3 months. In the intervention group, the median DFS (23.6 months vs. 12.1 months, P < 0.001) and OS (28.1 months vs. 20.7 months, P = 0.049) were significantly longer than those in the control group. CONCLUSIONS CA19-9 elevation could preceded recurrence confirmed by radiographic examinations in most patients. Tumor marker-guided salvage treatment can significantly prolong disease-free survival and overall survival in patients under surveillance after pancreatic cancer resection.
Collapse
Affiliation(s)
- Jiarui Li
- Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100032, China.
| | - Zhe Li
- Department of Gynecologic Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
| | - Haoxuan Kan
- Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100032, China.
| | - Zhao Sun
- Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100032, China.
| | - Jiazhang Xing
- Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100032, China.
| | - Yuejuan Cheng
- Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100032, China.
| | - Chunmei Bai
- Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, 100032, China.
| |
Collapse
|
|
46
|
Zhang K, Hua YQ, Wang D, Chen LY, Wu CJ, Chen Z, Liu LM, Chen H. Systemic immune-inflammation index predicts prognosis of patients with advanced pancreatic cancer. J Transl Med 2019; 17:30. [PMID: 30658662 PMCID: PMC6339361 DOI: 10.1186/s12967-019-1782-x] [Citation(s) in RCA: 66] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/07/2018] [Accepted: 01/11/2019] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Systemic inflammation and immune dysfunction have been proved to be associated with cancer progression and metastasis in various malignancies. The aim of this retrospective study was to evaluate the prognostic significance of pre-treatment systemic immune-inflammation index (SII) in patients with advanced pancreatic cancer. METHODS In total, 419 patients diagnosed with advanced pancreatic cancer, between January 2011 and December 2015, were retrospectively enrolled. The SII was developed based on a training set of 197 patients from 2011 to 2013 and validated in an independent cohort of 222 patients from 2014 to 2015. Data on baseline clinicopathologic characteristics; pre-treatment laboratory variables such as absolute neutrophil, lymphocyte, and platelet counts; and carbohydrate antigen 19-9 (CA19-9), total bilirubin (TBIL), albumin (ALB), alkaline phosphatase (ALP), alanine transaminase (ALT), and aspartate transaminase (AST) levels were collected. The association between clinicopathologic characteristics and SII was assessed. The overall survival was calculated using the Kaplan-Meier survival curves and compared using the log-rank test. Univariate and multivariate Cox proportional hazard regression models were used to analyze the prognostic value of the SII. RESULT An optimal cutoff point for the SII of 440 stratified the patients with advanced pancreatic cancer into high (> 440) and low (≤ 440) SII groups in the training cohort. Univariate and multivariate analyses revealed that the SII was an independent predictor for overall survival. The prognostic significance of the SII was confirmed in both normal and elevated CA19-9 levels. CONCLUSION The baseline SII serves as an independent prognostic marker for patients with advanced pancreatic cancer and can be used in patients with both normal and elevated CA19-9 levels.
Collapse
Affiliation(s)
- Ke Zhang
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Yong-Qiang Hua
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Dan Wang
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Lian-Yu Chen
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Cai-Jun Wu
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Zhen Chen
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Lu-Ming Liu
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Hao Chen
- Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China. .,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
| |
Collapse
|
|
47
|
Shi S, Yu X. Selecting chemotherapy for pancreatic cancer: Far away or so close? Semin Oncol 2018; 46:39-47. [PMID: 30611527 DOI: 10.1053/j.seminoncol.2018.12.004] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2017] [Revised: 01/26/2018] [Accepted: 12/19/2018] [Indexed: 02/06/2023]
Abstract
Pancreatic cancer is a lethal disease with a very poor prognosis. In contrast to treatments for many other tumor types, cytotoxic agents are still the first-line drugs for pancreatic cancer in both the palliative and adjuvant settings. Some progress has been made in recent years, but most large phase 3 studies have not shown significant improvements in survival. Because the available drugs and regimens are limited in both type and effect, the selection of chemotherapy based on clinicopathologic characteristics may be consequential for pancreatic cancer. In the present report, we focused on 7 landmark clinical trials for pancreatic cancer. We observed that FOLFIRINOX (oxaliplatin, irinotecan, fluorouracil, and leucovorin) and NG (nab-paclitaxel and gemcitabine), 2 first-line regimens, exerted opposite effects on metastatic pancreatic cancer patients with different baseline carbohydrate antigen 19-9 (CA19-9) levels. This suggested that not only the performance status but possibly also CA19-9 levels should be considered when making a therapeutic choice for patients with advanced pancreatic cancer. Moreover, we found that patients with a diagnosis of pancreatic cancer who have undergone a surgical resection with a negative margin (R0) may benefit more from fluorouracil and/or oral prodrugs of fluorouracil-based adjuvant therapy than from gemcitabine. Conversely, gemcitabine or gemcitabine-based regimens may be more effective for patients with a positive resection margin (R1). Based on these findings, we propose flowcharts for selecting chemotherapy for both advanced and resected pancreatic cancer. Furthermore, we present possible mechanisms and interpretations underlying the selection of chemotherapy for pancreatic cancer and propose the tumor burden as a key variable in this process. Regardless of the possible bias and exact treatment selection process, this study offers an opportunity to improve patient outcomes by using agents currently used in the therapy of pancreatic cancer. Although these conclusions are based on indirect evidence, we provide insights and possibilities to drive the selection of chemotherapy for pancreatic cancer.
Collapse
Affiliation(s)
- Si Shi
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Pancreatic Cancer Institute, Fudan University, Shanghai, China
| | - Xianjun Yu
- Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Pancreatic Cancer Institute, Fudan University, Shanghai, China.
| |
Collapse
|
|
48
|
Lin YK, Hsieh MC, Chang CL, Chow JM, Yuan KSP, Wu ATH, Wu SY. Intensity-modulated radiotherapy with systemic chemotherapy improves survival in patients with nonmetastatic unresectable pancreatic adenocarcinoma: A propensity score-matched, nationwide, population-based cohort study. Radiother Oncol 2018; 129:326-332. [PMID: 30082144 DOI: 10.1016/j.radonc.2018.07.012] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2018] [Revised: 06/29/2018] [Accepted: 07/15/2018] [Indexed: 12/25/2022]
Abstract
PURPOSE In the era of intensity-modulation radiation therapy (IMRT), no prospective randomized trial has evaluated the efficacy of IMRT exclusively, such as concurrent chemoradiotherapy (CCRT), sequential induction chemotherapy followed by radiotherapy (CT-RT), and systemic chemotherapy (CT) alone, for treating unresectable pancreatic adenocarcinomas (PAs) without metastasis. Through propensity score matching, we designed a nationwide, population-based, head-to-head cohort study to determine the effects of various treatments on unresectable PAs. PATIENTS AND METHODS We minimized the confounding effects of various treatment outcomes in patients with unresectable PAs from the Taiwan Cancer Registry database by dividing them as follows: group 1, CCRT; group 2, sequential CT-RT; group 3, nontreatment; and group 4, CT alone. RESULTS The matching process yielded a final cohort of 2960 patients (740 patients each in groups 1, 2, 3, and 4). In both univariate and multivariate Cox regression analyses, the adjusted hazard ratios (95% confidence interval) derived for the definitive CCRT and sequential CT-RT groups compared with the CT alone group were 0.443 (0.397-0.495) and 0.633 (0.568-0.705), respectively. CONCLUSIONS A combination of IMRT and systemic CT for the treatment of unresectable PAs might increase survival compared with CT alone.
Collapse
Affiliation(s)
- Yen-Kuang Lin
- Biostatistics Center and School of Public Health, Taipei Medical University, Taiwan
| | - Mao-Chih Hsieh
- Department of General Surgery, Wan Fang Hospital, Taipei Medical University, Taiwan
| | - Chia-Lun Chang
- Department of Hemato-Oncology, Wan Fang Hospital, Taipei Medical University, Taiwan
| | - Jyh-Ming Chow
- Department of Hemato-Oncology, Wan Fang Hospital, Taipei Medical University, Taiwan
| | - Kevin Sheng-Po Yuan
- Department of Otorhinolaryngology, Wan Fang Hospital, Taipei Medical University, Taiwan
| | - Alexander T H Wu
- Ph.D. Program for Translational Medicine, Taipei Medical University, Taiwan
| | - Szu-Yuan Wu
- Department of Radiation Oncology, Wanfang Hospital, Taipei Medical University, Taipei, Taiwan; Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Institute of Clinical Science, Zhongshan Hospital, Fudan University, Shanghai, China.
| |
Collapse
|
|
49
|
He Y, Lin H, Tu D. A single-index threshold Cox proportional hazard model for identifying a treatment-sensitive subset based on multiple biomarkers. Stat Med 2018; 37:3267-3279. [PMID: 29869381 DOI: 10.1002/sim.7837] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2017] [Revised: 04/18/2018] [Accepted: 05/07/2018] [Indexed: 01/18/2023]
Abstract
In this paper, we introduce a single-index threshold Cox proportional hazard model to select and combine biomarkers to identify patients who may be sensitive to a specific treatment. A penalized smoothed partial likelihood is proposed to estimate the parameters in the model. A simple, efficient, and unified algorithm is presented to maximize this likelihood function. The estimators based on this likelihood function are shown to be consistent and asymptotically normal. Under mild conditions, the proposed estimators also achieve the oracle property. The proposed approach is evaluated through simulation analyses and application to the analysis of data from two clinical trials, one involving patients with locally advanced or metastatic pancreatic cancer and one involving patients with resectable lung cancer.
Collapse
Affiliation(s)
- Ye He
- Center of Statistical Research, School of Statistics, Southwestern University of Finance and Economics, Chengdu, China
| | - Huazhen Lin
- Center of Statistical Research, School of Statistics, Southwestern University of Finance and Economics, Chengdu, China
| | - Dongsheng Tu
- Department of Public Health Sciences, Canadian Cancer Trials Group, Queen's University, Kingston, Ontario, Canada
| |
Collapse
|
|
50
|
Luo Y, Zhu H, Tan T, He J. Current Standards and Recent Advances in Biomarkers of Major Endocrine Tumors. Front Pharmacol 2018; 9:963. [PMID: 30250431 PMCID: PMC6139354 DOI: 10.3389/fphar.2018.00963] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2018] [Accepted: 08/03/2018] [Indexed: 12/18/2022] Open
Abstract
The complexity of endocrine tumor diagnosis stems from its variable symptoms and presentation that may mimic many other disease states, or display asymptomatic properties for a prolonged amount of time. Early and accurate disease identification is needed for better patient prognosis. The key to this may be in using validated biomarkers with enhanced sensitivity and specificity. Several biomarkers are consistently used across various endocrine tumor types, possibly indicating a deeper pathophysiological mechanism behind endocrine cancer genesis and development. For example, carbohydrate antigen (CA) is measured in both pancreatic adenocarcinoma as well as ovarian cancer for diagnosis, surveillance, and risk stratification. The discovery of measuring miRNAs that are highly expressed in malignant tumors is also a novel strategy across multiple endocrine tumor types, and is propelling the future advancement of biomarker development. This review introduces currently utilized biomarkers in some of the commonly known endocrine tumors, including thyroid, adrenal, pituitary, pancreatic, and gonadal carcinoma, as well as future research directions.
Collapse
Affiliation(s)
- Yanhong Luo
- Children’s Hospital of Chongqing Medical University, Chongqing, China
| | - Hua Zhu
- Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH, United States
| | - Tao Tan
- Department of Surgery, Davis Heart and Lung Research Institute, The Ohio State University Wexner Medical Center, Columbus, OH, United States
| | - Jianfeng He
- Children’s Hospital of Chongqing Medical University, Chongqing, China
| |
Collapse
|