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Luo D, Li Y, Yu X, Ji L, Gong X. Early onset pancreatic cancer: A review. Transl Oncol 2025; 52:102239. [PMID: 39672003 PMCID: PMC11699111 DOI: 10.1016/j.tranon.2024.102239] [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: 07/18/2024] [Revised: 11/17/2024] [Accepted: 12/07/2024] [Indexed: 12/15/2024] Open
Abstract
Early-onset pancreatic cancer (EOPC) is usually defined as patients with pancreatic cancer before the age of 50 years, which is relatively rare. However, the research on EOPC is somewhat obscure, and the specific clinical and molecular characteristics of this condition are debated. In this review, we discussed the differences between EOPC and late-onset pancreatic cancer (LOPC) or average-onset pancreatic cancer (AOPC) with a focus on clinical and molecular characteristics, survival outcomes and treatment to promote the diagnosis and treatment of EOPC.
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Affiliation(s)
- Dong Luo
- Department of Pancreatic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, China; Department of General, Visceral and Transplant Surgery, European Pancreas Centre, Heidelberg. University Hospital, Heidelberg, Germany
| | - Yixiong Li
- Department of Pancreatic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, China
| | - Xiao Yu
- Department of Hepatopancreatobiliary Surgery Ⅱ, Third Xiangya Hospital, Central South University, Changsha, 410013, China
| | - Liandong Ji
- Department of Pancreatic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, China.
| | - Xuejun Gong
- Department of Pancreatic Surgery, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, China; National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, China.
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Tschaidse T, Hofmann FO, Renz B, Hungbauer M, Klinger C, Buhr HJ, Uhl W, Mees ST, Keck T, Reissfelder C, Ghadimi M, D'Haese JG, Werner J, Ilmer M. Perioperative outcomes in an age-adapted analysis of the German StuDoQ|Pancreas registry for PDAC. BMC Surg 2025; 25:4. [PMID: 39755601 DOI: 10.1186/s12893-024-02647-1] [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: 04/22/2024] [Accepted: 10/28/2024] [Indexed: 01/06/2025] Open
Abstract
BACKGROUND Pancreatic ductal adenocarcinoma (PDAC) typically occurs in an older patient population. Yet, early-onset pancreatic cancer (EOPC) has one of the fastest growing incidence rates. This study investigated the influence of age and tumor location on postoperative morbidity and mortality in a large, real-world dataset. METHODS Patients with confirmed PDAC undergoing pancreatic surgery between 01/01/2014 and 31/12/2019 were identified from the German StuDoQ|Pancreas registry. After categorization into early- (EOPC; < 50 years), middle- (MOPC; 50 -70 years), and late-onset (LOPC; > 70 years), and stratification into pancreaticoduodenectomy (PD) or distal pancreatectomy (DP), differences in morbidity and mortality as well as clinicopathologic parameters were analyzed. RESULTS In total, 3011 patients were identified. No difference in the occurrence of postoperative pancreatic fistula (POPF), postpancreatectomy hemorrhage (PPH) or delayed gastric emptying (DGE) between different age groups and resection techniques was detected. However, in patients undergoing PD, major complications (Clavien-Dindo ≥ 3a) were observed more frequently in LOPC (30,7%) than in MOPC (26,2%) and EOPC (16,9%; p < 0,01). Mortality almost tripled from EOPC (2,4%) to MOPC (3,6%) to LOPC (6,6%, p < 0,01) and significantly higher failure to rescue (FTR) rates could be observed (EOPC 14,3%, MOPC 13,6%; LOPC 21,6%; p < 0,05). In centers with DGAV certification for pancreatic surgery, the risk of complications was significantly decreased in PD (OR 0,79; 95% CI 0,65-0,94; p = 0,010). CONCLUSION Age has a pronounced impact on the perioperative outcomes after pancreatic resections of PDAC. This effect is more prevalent in PD compared to DP. Pancreatic surgery-specific complications, such as POPF, DGE or PPH do not occur more frequently in the elderly. Overall, the risk of major complications and mortality increases in elderly patients mainly secondary to higher FTR rates.
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Affiliation(s)
- Tengis Tschaidse
- Department of General, Visceral and Transplantation Surgery, LMU University Hospital Munich, LMU Munich, Munich, Germany
| | - Felix O Hofmann
- Department of General, Visceral and Transplantation Surgery, LMU University Hospital Munich, LMU Munich, Munich, Germany
- German Cancer Consortium (DKTK), Partner Site Munich; and German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Bernhard Renz
- Department of General, Visceral and Transplantation Surgery, LMU University Hospital Munich, LMU Munich, Munich, Germany
- German Cancer Consortium (DKTK), Partner Site Munich; and German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Maximilian Hungbauer
- Department of General, Visceral and Transplantation Surgery, LMU University Hospital Munich, LMU Munich, Munich, Germany
| | - Carsten Klinger
- German Society of General and Visceral Surgery (DGAV), Berlin, Germany
| | - Heinz J Buhr
- German Society of General and Visceral Surgery (DGAV), Berlin, Germany
| | - Waldemar Uhl
- Department of General and Visceral Surgery, St. Josef-Hospital Bochum, Ruhr-University Bochum, Bochum, Germany
| | - Sören Torge Mees
- Department of General and Visceral Surgery, Dresden-Friedrichstadt General Hospital, Teaching Hospital of the Technical University Dresden, Dresden, Germany
| | - Tobias Keck
- Department of Surgery, University Medical Center Schleswig-Holstein, Campus Lübeck, Lübeck, Germany
| | - Christoph Reissfelder
- Department of Surgery, Universitätsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Michael Ghadimi
- Department of General, Visceral, and Paediatric Surgery, University Medical Center, Göttingen, Germany
| | - Jan G D'Haese
- Department for General, Visceral, Endocrine and Vascular Surgery, Krankenhaus Agatharied GmbH, Hausham, Germany
| | - Jens Werner
- Department of General, Visceral and Transplantation Surgery, LMU University Hospital Munich, LMU Munich, Munich, Germany
- German Cancer Consortium (DKTK), Partner Site Munich; and German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Matthias Ilmer
- Department of General, Visceral and Transplantation Surgery, LMU University Hospital Munich, LMU Munich, Munich, Germany.
- German Cancer Consortium (DKTK), Partner Site Munich; and German Cancer Research Center (DKFZ), Heidelberg, Germany.
- Department of General, Visceral, and Transplantation Surgery, Hospital of the University of Munich, Ludwig-Maximilians-University (LMU) Munich (Germany), Marchioninistr, 15, München, 81377, Germany.
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Chen X, Gong R, Wang L, Lei K, Liu X, Wang J, Sun M, Saluja AK, Yu Q, Ren H. hnRNPLL regulates MYOF alternative splicing and correlates with early metastasis in pancreatic ductal adenocarcinoma. Cancer Lett 2024; 611:217436. [PMID: 39742990 DOI: 10.1016/j.canlet.2024.217436] [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: 10/01/2024] [Revised: 11/30/2024] [Accepted: 12/29/2024] [Indexed: 01/04/2025]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer known for its high rate of early metastasis, necessitating the discovery of the underlying mechanisms. Herein, we report that heterogeneous nuclear ribonucleoprotein L-like (hnRNPLL) expression significantly increases at the invasion forefront in PDAC and is associated with early metastasis and poor prognosis. Our findings revealed that hnRNPLL knockdown resulted in extensive exon skipping (ES) events. In particular, we identified myoferlin (MYOF), a member of the ferlin family involved in membrane processes, as a functional splicing target of hnRNPLL. hnRNPLL depletion stimulates MYOF exon 17 retention to reduce the short isoform of MYOF (MYOFb) and inhibit metastasis. In contrast, hnRNPLL or MYOFb overexpression promoted pancreatic cancer cell migration and invasion. These results suggest that hnRNPLL is a critical factor for early PDAC metastasis. hnRNPLL and MYOFb may be potential therapeutic targets for PDAC.
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Affiliation(s)
- Xianghan Chen
- Shandong Provincial Key Laboratory of Clinical Research for Pancreatic Diseases, Tumor Immunology and Cytotherapy, Medical Research Center, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China; State Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical University (Air Force Medical University), Xi'an, 710032, China
| | - Ruining Gong
- Shandong Provincial Key Laboratory of Clinical Research for Pancreatic Diseases, Tumor Immunology and Cytotherapy, Medical Research Center, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China; Gastrointestinal Cancer Institute/Pancreatic Disease Institute, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China
| | - Lili Wang
- Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China
| | - Ke Lei
- Shandong Provincial Key Laboratory of Clinical Research for Pancreatic Diseases, Tumor Immunology and Cytotherapy, Medical Research Center, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China
| | - Xiaolan Liu
- Shandong Provincial Key Laboratory of Clinical Research for Pancreatic Diseases, Tumor Immunology and Cytotherapy, Medical Research Center, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China
| | - Jigang Wang
- Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China
| | - Mingyue Sun
- Shandong Provincial Key Laboratory of Clinical Research for Pancreatic Diseases, Tumor Immunology and Cytotherapy, Medical Research Center, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China
| | - Ashok Kumar Saluja
- Department of Surgery, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, 33136, USA
| | - Qian Yu
- Shandong Provincial Key Laboratory of Clinical Research for Pancreatic Diseases, Tumor Immunology and Cytotherapy, Medical Research Center, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China.
| | - He Ren
- Shandong Provincial Key Laboratory of Clinical Research for Pancreatic Diseases, Tumor Immunology and Cytotherapy, Medical Research Center, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China; Gastrointestinal Cancer Institute/Pancreatic Disease Institute, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China.
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Rashad N, Gouda A, Sabra E, Youssef MA, Alshazly H, Samir S. Early Onset Pancreatic Adenocarcinoma (EOPAC): presentation, clinical course and treatment outcomes in comparison to Average Onset Pancreatic Adenocarcinoma (AOPAC): a retrospective cohort study. BMC Cancer 2024; 24:1289. [PMID: 39425084 PMCID: PMC11487769 DOI: 10.1186/s12885-024-12955-7] [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: 07/26/2024] [Accepted: 09/16/2024] [Indexed: 10/21/2024] Open
Abstract
BACKGROUND Pancreatic adenocarcinoma (PAC) is a disease of decimal prognosis, with around 50% of patients presenting with metastatic disease. Previous trials reported a high incidence of early onset pancreatic cancer (EOPAC) in Egypt, presenting about 25% of patients with PAC. The clinic-pathological features and prognosis of EOPAC needs more study. PATIENTS AND METHODS A retrospective analysis of patients' records at Shefa Al-Orman comprehensive cancer center database. Patients with histo-pathologically confirmed diagnosis of PAC. We categorized patients according to the age at diagnosis into EOPAC (≤ 50 years) and average onset PAC (AOPAC). Data on risk factors, family history, presenting symptoms, clinic-pathological features, treatment, and prognosis were extracted. Patients with histopathologically confirmed diagnosis of pancreatic cancer diagnosed between December 2016-December 2022 were included. RESULTS The study cohort consisted of 412 patients. EOPAC represented 20.3% of patients, with no significant differences in risk factors and family history compared to AOPAC. Duration of symptoms before diagnosis is longer in EOPAC, with the majority of EOPAC presenting with localized disease (23.8%) and locally advanced tumors (28.5%) compared to AOPAC. AOPAC presented more with metastatic disease (64% vs. 45.2%, p = 0.003). EOPAC are usually submitted to more aggressive treatment including radical surgery, neoadjuvant therapy, and aggressive chemotherapy regimens in metastatic disease. Disease free survival (DFS) of EOPAC was shorter than AOPAC (11 months vs. 17 months, p = 0.889), but overall survival OS was significantly longer in EOPAC (10 months vs. 6 months, p = 0.013). CONCLUSION Patients with EOPAC in Egypt represent around 25% of cases. EOPAC tend to have a shorter disease free survival (DFS) in patients presenting with localized disease. The overall survival (OS) is longer in EOPAC compared to AOPAC. Further studies are mandatory to identify the epidemiological and risk factors of EOPAC in Egypt.
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Affiliation(s)
- Noha Rashad
- Medical Oncology Department, Shefaa Al-Orman Oncology Hospital, Luxor, Egypt.
- Department OF clinical oncology, Faculty of medicine, Suez University, PO Box 43221, Suez, Egypt.
| | - Abdelrahman Gouda
- Medical Oncology Department, Shefaa Al-Orman Oncology Hospital, Luxor, Egypt
- Clinical oncology department, Aswan University, Aswan, Egypt
| | - Esraa Sabra
- Medical Oncology Department, Shefaa Al-Orman Oncology Hospital, Luxor, Egypt
| | - Mohamed A Youssef
- Department of internal medicine, Medical branch, University of Texas medical branch, USA, Galveston
| | - Hossam Alshazly
- Clinical pharmacy Department, Shefaa Al-Orman Oncology Hospital, Luxor, Egypt
| | - Sandra Samir
- Medical Oncology Department, Shefaa Al-Orman Oncology Hospital, Luxor, Egypt
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Chen DS, Chen ZP, Zhu DZ, Guan LX, Zhu Q, Lou YC, He ZP, Chen HN, Sun HC. Burden landscape of hepatobiliary and pancreatic cancers in Chinese young adults: 30 years’ overview and forecasted trends. World J Gastrointest Oncol 2024; 16:4177-4193. [DOI: 10.4251/wjgo.v16.i10.4177] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2024] [Revised: 08/18/2024] [Accepted: 08/28/2024] [Indexed: 09/26/2024] Open
Abstract
BACKGROUND Hepatobiliary and pancreatic (HBP) cancers impose a considerable burden on young populations (aged 15 to 49 years), resulting in a substantial number of new cases and fatalities each year. In young populations, the HBP cancers shows extensive variance worldwide and the updated data in China is lacking.
AIM To investigate the current status, trends, projections, and underlying risk factors of HBP cancers among young populations in China.
METHODS The Global Burden of Disease Study 2019 provided data on the annual incidence, mortality, disability-adjusted life years (DALYs), age-standardized incidence rate (ASIR), mortality rate (ASMR), and DALYs rate (ASDR) of HBP cancers in young Chinese adults between 1990 and 2019. Temporal trends were assessed using estimated annual percentage change and hierarchical clustering. Sex-specific mortality and DALYs caused by various risks were analyzed across China and other regions, with future trends until 2035 projected using the Bayesian age-period-cohort model.
RESULTS From 1990 to 2019, incident cases, deaths, DALYs, ASIR, ASMR, and ASDR for liver cancer (LC) in young Chinese individuals decreased, classified into 'significant decrease' group. Conversely, cases of gallbladder and biliary tract cancer and pancreatic cancer rose, categorized as either 'significant increase' or 'minor increase' groups. The contribution of risk factors to mortality and DALYs for HBP tumors increased to varying degrees. Healthy lifestyle behaviors, such as tobacco control, weight management, alcohol moderation, and drug avoidance, could lower HBP cancers incidence. Moreover, except for LC in females, which is likely to initially decline slightly and then rise, the forecasting model predicted that the ASIR and ASMR for all HPB cancers subtypes by gender will increase among young adults.
CONCLUSION HBP cancers burden among young adults in China is expected to increase until 2035, necessitating lifestyle interventions and targeted treatment strategies to mitigate the public health impact of these cancers.
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Affiliation(s)
- De-Sheng Chen
- Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
| | - Ze-Ping Chen
- Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
| | - Dong-Zi Zhu
- Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China
| | - Lv-Xin Guan
- Shenzhen Institute of Translational Medicine, The First Affiliated Hospital of Shenzhen University, Shenzhen 518035, Guangdong Province, China
| | - Qi Zhu
- Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
| | - Yi-Chao Lou
- Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
| | - Ze-Ping He
- Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
| | - Hao-Nan Chen
- Department of General Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, Zhejiang Province, China
| | - Hong-Cheng Sun
- Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China
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Danpanichkul P, Aboona MB, Sukphutanan B, Kongarin S, Duangsonk K, Ng CH, Muthiah MD, Huang DQ, Seko Y, Díaz LA, Arab JP, Yang JD, Chen VL, Kim D, Noureddin M, Liangpunsakul S, Wijarnpreecha K. Incidence of liver cancer in young adults according to the Global Burden of Disease database 2019. Hepatology 2024; 80:828-843. [PMID: 38598364 DOI: 10.1097/hep.0000000000000872] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/18/2024] [Accepted: 02/19/2024] [Indexed: 04/12/2024]
Abstract
BACKGROUND AND AIMS The worldwide burden of cancer is increasing in younger populations. However, the epidemiology of primary liver cancer remains understudied in young adults compared to other cancer forms. APPROACH AND RESULTS This study analyzed data from the Global Burden of Disease study between 2010 and 2019 to assess the age-standardized incidence, mortality, and disability-adjusted life years associated with primary liver cancer in the young (15-49 y), stratified by region, nation, sociodemographic index, and sex. The study found a global estimate of 78,299 primary liver cancer cases, 60,602 deaths, and 2.90 million disability-adjusted life years in the young population. The Western Pacific region exhibited the highest burden in 2019, showing the most significant increase compared to other regions between 2010 and 2019. More than half of the countries worldwide have undergone an increase in primary liver cancer incidence rates in young adults. Around 12.51% of deaths due to primary liver cancer occur in young individuals. Throughout the study period, there was a significant decline in primary liver cancer mortality due to most etiologies, except for metabolic dysfunction-associated steatotic liver disease-attributable primary liver cancer (annual percentage change + 0.87%, 95% CI: 0.70%-1.05%) and alcohol-attributable primary liver cancer (annual percentage change + 0.21%, 95% CI: 0.01%-0.42%). The limitations of the Global Burden of Disease database include reliance on the quality of primary data and possible underestimation of alcohol consumption. CONCLUSIONS Over the past decade, there has been a marked increase in the burden of primary liver cancer, especially that originating from steatotic liver disease. This trend calls for the development of urgent and comprehensive strategies to mitigate this rising burden globally.
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Affiliation(s)
- Pojsakorn Danpanichkul
- Immunology Unit, Department of Microbiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
- Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas, USA
| | - Majd B Aboona
- Department of Internal Medicine, University of Arizona College of Medicine, Phoenix, Arizona, USA
| | | | | | - Kwanjit Duangsonk
- Department of Microbiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Cheng Han Ng
- Department of Medicine, Division of Gastroenterology and Hepatology, National University Health System, Singapore
- Department of Medicine, Division of Gastroenterology, Kurume University School of Medicine, Kurume, Japan
| | - Mark D Muthiah
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Daniel Q Huang
- Department of Medicine, Division of Gastroenterology and Hepatology, National University Health System, Singapore
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- MASLD Research Center, Division of Gastroenterology, University of California, San Diego, La Jolla, California, USA
| | - Yuya Seko
- Department of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyou-ku, Kyoto, Japan
| | - Luis Antonio Díaz
- Departamento de Gastroenterologia, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile
- Observatorio Multicéntrico de Enfermedades Gastrointestinales, OMEGA, Santiago, Chile
| | - Juan Pablo Arab
- Departamento de Gastroenterologia, Escuela de Medicina, Pontificia Universidad Catolica de Chile, Santiago, Chile
- Department of Medicine, Division of Gastroenterology, Schulich School of Medicine, Western University & London Health Sciences Centre, London, Ontario, Canada
- Department of Epidemiology and Biostatistics, Schulich School of Medicine, Western University, London, Ontario, Canada
| | - Ju Dong Yang
- Karsh Division of Gastroenterology and Hepatology, Comprehensive Transplant Center, and Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Vincent L Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
| | - Donghee Kim
- Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, California, USA
| | - Mazen Noureddin
- Houston Research Institute and Houston Methodist Hospital, Houston, Texas, USA
| | - Suthat Liangpunsakul
- Department of Medicine, Division of Gastroenterology and Hepatology, Indiana University School of Medicine, Indianapolis, Indiana, USA
- Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana, USA
- Roudebush Veterans Administration Medical Center, Indianapolis, Indiana, USA
| | - Karn Wijarnpreecha
- Department of Medicine, Division of Gastroenterology and Hepatology, University of Arizona College of Medicine, Phoenix, Arizona, USA
- Department of Internal Medicine, Banner University Medical Center, Phoenix, Arizona, USA
- BIO5 Institute, University of Arizona College of Medicine-Phoenix, Phoenix, Arizona, USA
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Renaldi K, William A. The Association between Early-Onset Pancreatic Ductal Adenocarcinoma and Patients Survival: A Systematic Review and Meta-Analysis. F1000Res 2024; 13:976. [PMID: 39355802 PMCID: PMC11443187 DOI: 10.12688/f1000research.153743.1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/20/2024] [Indexed: 10/03/2024] Open
Abstract
Background In recent years, the incidence of early-onset pancreatic cancer (EOPC) has increased. Several studies comparing the survival of patients with EOPC to those with average-onset pancreatic cancer (AOPC) have reported mixed results. We aimed, therefore, to perform a meta-analysis summarizing the current evidence. Methods We searched the MEDLINE and EMBASE databases for relevant articles published through March 2024. Articles comparing the survival of patients with EOPC - defined as pancreatic ductal adenocarcinoma (PDAC) diagnosed at ≤ 50 years of age - and AOPC were included in the present meta-analysis. The primary outcome was the pooled adjusted hazard ratio (aHR), and the risk of bias analysis was performed using the Quality in Prognostic Factor Studies tool. The meta-analysis was performed using a random-effects model. Results A total of 17 studies were eligible for the primary analysis, the results of which indicated that patients with EOPC had a longer overall survival than those with AOPC (aHR = 0.80; 95% confidence interval [CI], 0.74-0.86; P < 0.001). The rate of distant metastasis was higher in EOPC than AOPC; however, patients with EOPC also received more treatments than those with AOPC. Conclusions Patients with EOPC had a better prognosis than those with AOPC. Clinicians must ensure that patients with PDAC receive early and appropriate treatment to improve their survival.
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Affiliation(s)
- Kaka Renaldi
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine University of Indonesia/Cipto Mangunkusumo National General Hospital, Central Jakarta, Jakarta, 10430, Indonesia
| | - Andy William
- Faculty of Medicine, University of Indonesia, Jakarta, Indonesia
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Heervä E, Väliaho V, Nurmi H, Lietzen E, Ålgars A, Kauhanen S. Outcomes After Multimodality Treatment of Pancreatic Cancer in an Unselected Single-Center Cohort. Cancer Manag Res 2024; 16:1065-1076. [PMID: 39220815 PMCID: PMC11363961 DOI: 10.2147/cmar.s465512] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2024] [Accepted: 08/02/2024] [Indexed: 09/04/2024] Open
Abstract
Background Pancreatic ductal adenocarcinoma (PDAC) remains a lethal and rarely resectable malignancy. Here we explore the outcomes of surgery, as compared to definitive radiotherapy (dRT) or systemic therapy only in PDAC. Methods Pancreatic surgery and radiotherapy in Southwest Finland have been centralized to Turku University Hospital. Previously validated population-based electronic health records database was searched for all unselected PDAC patients from the years 2009-2019. Main outcome was median overall survival (mOS). Demographics, pathology, surgery, and oncological treatment data were collected. Results We identified 1006 patients with PDAC, 49% male, median age 71 years and 77% presenting with metastatic disease. In total, 405 patients were treated; 92 resected, 26 dRT without resection and 287 systemic therapy only. mOS was 34.6 months for resected, 26.7 months for dRT, and 7.5 months for systemic therapy patients. Among the 88 patients with locally advanced inoperable PDAC, dRT was independently associated with longer mOS (26.7 months) as compared to systemic therapy only (mOS 10.6 months). Among the 287 patients treated with systemic therapy only, combination chemotherapy was independently associated with longer mOS (11.6 months) as compared to gemcitabine-monotherapy (6.8 months). In patients progressing to second-line systemic treatment after gemcitabine failure, mOS was the same (5.0 months) with single or combination regimens. Conclusion Surgery remains the only curative approach for PDAC. In locally advanced PDAC, dRT was associated with longer survival as compared to systemic therapy only. Concerning first-line systemic therapy, our results support the use of combination chemotherapy over single-agent therapy.
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Affiliation(s)
- Eetu Heervä
- Department of Oncology, Turku University Hospital and University of Turku, Turku, Finland
| | - Vesa Väliaho
- Department of Oncology, Turku University Hospital and University of Turku, Turku, Finland
| | - Heidi Nurmi
- Department of Oncology, Turku University Hospital and University of Turku, Turku, Finland
| | - Elina Lietzen
- Department of Digestive Surgery, Turku University Hospital and University of Turku, Turku, Finland
| | - Annika Ålgars
- Department of Oncology, Turku University Hospital and University of Turku, Turku, Finland
| | - Saila Kauhanen
- Department of Digestive Surgery, Turku University Hospital and University of Turku, Turku, Finland
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Grigorescu RR, Husar-Sburlan IA, Gheorghe C. Pancreatic Cancer: A Review of Risk Factors. Life (Basel) 2024; 14:980. [PMID: 39202722 PMCID: PMC11355429 DOI: 10.3390/life14080980] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2024] [Revised: 07/28/2024] [Accepted: 08/01/2024] [Indexed: 09/03/2024] Open
Abstract
Pancreatic adenocarcinoma is one of the most lethal types of gastrointestinal cancer despite the latest medical advances. Its incidence has continuously increased in recent years in developed countries. The location of the pancreas can result in the initial symptoms of neoplasia being overlooked, which can lead to a delayed diagnosis and a subsequent reduction in the spectrum of available therapeutic options. The role of modifiable risk factors in pancreatic cancer has been extensively studied in recent years, with smoking and alcohol consumption identified as key contributors. However, the few screening programs that have been developed focus exclusively on genetic factors, without considering the potential impact of modifiable factors on disease occurrence. Thus, fully understanding and detecting the risk factors for pancreatic cancer represents an important step in the prevention and early diagnosis of this type of neoplasia. This review reports the available evidence on different risk factors and identifies the areas that could benefit the most from additional studies.
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Affiliation(s)
- Raluca Roxana Grigorescu
- Gastroenterology Department, “Sfanta Maria” Hospital, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania
| | | | - Cristian Gheorghe
- Center for Digestive Disease and Liver Transplantation, Fundeni Clinical Institute, “Carol Davila” University of Medicine and Pharmacy, 020021 Bucharest, Romania
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10
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Zheng B, Ding G, Lu G, Li L. Development and external validation of a prognostic nomogram to predict survival in patients aged ≥60 years with pancreatic ductal adenocarcinoma. Transl Cancer Res 2024; 13:2751-2766. [PMID: 38988930 PMCID: PMC11231776 DOI: 10.21037/tcr-24-5] [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: 01/02/2024] [Accepted: 05/07/2024] [Indexed: 07/12/2024]
Abstract
Background Pancreatic ductal adenocarcinoma (PDAC), which accounts for the vast majority of pancreatic cancer (PC), is a highly aggressive malignancy with a dismal prognosis. Age is shown to be an independent factor affecting survival outcomes in patients with PDAC. Our study aimed to identify prognostic factors and construct a nomogram to predict survival in PDAC patients aged ≥60 years. Methods Data of PDAC patients aged ≥60 years were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Multivariate Cox regression analysis was used to determined prognostic factors of overall survival (OS) and cancer-specific survival (CSS), and two nomograms were constructed and validated by calibration plots, concordance index (C-index) and decision curve analysis (DCA). Additionally, 432 patients from the First Affiliated Hospital of Wenzhou Medical University were included as an external cohort. Kaplan-Meier curves were applied to further verify the clinical validity of the nomograms. Results Ten independent prognostic factors were identified to establish the nomograms. The C-indexes of the training and validation groups based on the OS nomogram were 0.759 and 0.760, higher than those of the tumor-node-metastasis (TNM) staging system (0.638 and 0.636, respectively). Calibration curves showed high consistency between predictions and observations. Better area under the receiver operator characteristic (ROC) curve (AUC) values and DCA were also obtained compared to the TNM system. The risk stratification based on the nomogram could distinguish patients with different survival risks. Conclusions We constructed and externally validated a population-based survival-predicting nomogram for PDAC patients aged ≥60 years. The new model could help clinicians personalize survival prediction and risk assessment.
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Affiliation(s)
- Binjiao Zheng
- School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China
| | - Gangfeng Ding
- The First Clinical Medical College of Wenzhou Medical University, Wenzhou, China
| | - Guangrong Lu
- Department of Gastroenterology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China
| | - Lili Li
- Department of Medical Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
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11
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Chen L, Jin T, Fang Y, Wu G, Yuan Y. Comparison of postoperative survival between early-onset and late-onset adenocarcinoma of esophagogastric junction: a population-based study. J Gastroenterol Hepatol 2024; 39:1073-1081. [PMID: 38353050 DOI: 10.1111/jgh.16514] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2023] [Revised: 01/07/2024] [Accepted: 01/28/2024] [Indexed: 06/19/2024]
Abstract
BACKGROUND AND AIM The prognosis of early-onset adenocarcinoma of esophagogastric junction (AEG) remains unclear. This research aimed at comparing the prognosis between early-onset and late-onset AEGs. METHODS We extracted eligible patients with surgically resected, pathologically confirmed, nonmetastatic AEG from the Surveillance, Epidemiology, and End Results database from 2004 to 2015. The cutoff age of early-onset AEG was set at ≤50 years old. Univariate and multivariate Cox analysis as well as competing risk model were adopted for comparing overall survival (OS) and cancer-specific survival (CSS) between early-onset and late-onset AEGs. In addition, multiple imputation and propensity score matching (PSM) were also carried out for sensitivity analysis. RESULTS In total, 4610 eligible AEG patients were collected in this study, including 610 early-onset AEGs and 4000 late-onset AEGs. Kaplan-Meier curves revealed significantly better survival in early-onset AEGs than late-onset AEGs. After interpolating missing data by multiple imputation, multivariate Cox regression analysis similarly showed better OS and CSS in early-onset AEGs. By using PSM analysis at a ratio of 1:1, we matched 610 early-onset AEG patients with 610 late-onset AEG patients. After PSM, univariate Cox regression model still revealed favorable prognosis in early-onset AEGs. Similar results were confirmed by performing PSM analysis at a ratio of 1:2 and 1:3. In addition, competing risk model demonstrated significantly lower cancer-specific death in early-onset AEGs compared to late-onset AEGs before and after matching. CONCLUSION By applying several effective sensitivity analyses, we reported significantly favorable OS and CSS in early-onset AEGs compared to late-onset AEGs.
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Affiliation(s)
- Liubo Chen
- Department of Medical Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Tian Jin
- Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Yimin Fang
- Department of Colorectal Surgery and Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Gaoqi Wu
- Institute of Immunology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
| | - Ying Yuan
- Department of Medical Oncology, Key Laboratory of Cancer Prevention and Intervention, Ministry of Education, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China
- Cancer Center, Zhejiang University, Hangzhou, Zhejiang, China
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12
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Mendis S, Lipton L, To YH, Ananda S, Michael M, McLachlan SA, Thomson B, Loveday B, Knowles B, Fox A, Nikfarjam M, Usatoff V, Shapiro J, Clarke K, Pattison S, Chee CE, Zielinski R, Wong R, Gibbs P, Lee B. Early onset pancreatic cancer-exploring contemporary treatment and outcomes using real-world data. Br J Cancer 2024; 130:1477-1484. [PMID: 38448752 PMCID: PMC11058801 DOI: 10.1038/s41416-024-02619-5] [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: 01/26/2023] [Revised: 02/01/2024] [Accepted: 02/09/2024] [Indexed: 03/08/2024] Open
Abstract
BACKGROUND Pancreatic cancer incidence is increasing in younger populations. Differences between early onset pancreatic cancer (EOPC) and later onset pancreatic cancer (LOPC), and how these should inform management warrant exploration in the contemporary setting. METHODS A prospectively collected multi-site dataset on consecutive pancreatic adenocarcinoma patients was interrogated. Patient, tumour, treatment, and outcome data were extracted for EOPC (≤50 years old) vs LOPC (>50 years old). RESULTS Of 1683 patients diagnosed between 2016 and 2022, 112 (6.7%) were EOPC. EOPC more frequently had the tail of pancreas tumours, earlier stage disease, surgical resection, and trended towards increased receipt of chemotherapy in the curative setting compared to LOPC. EOPC more frequently received 1st line chemotherapy, 2nd line chemotherapy, and chemoradiotherapy than LOPC in the palliative setting. Recurrence-free survival was improved for the tail of pancreas EOPC vs LOPC in the resected setting; overall survival was superior for EOPC compared to LOPC across the resected, locally advanced unresectable and metastatic settings. CONCLUSIONS EOPC remains a small proportion of pancreatic cancer diagnoses. The more favourable outcomes in EOPC suggest these younger patients are overall deriving benefits from increased treatment in the curative setting and increased therapy in the palliative setting.
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Affiliation(s)
- Shehara Mendis
- Walter & Eliza Hall Institute of Medical Research, Parkville, VIC, Australia.
| | | | - Yat Hang To
- Walter & Eliza Hall Institute of Medical Research, Parkville, VIC, Australia
- University of Melbourne, Parkville, VIC, Australia
- Department of Medical Oncology, Peter MacCallum Cancer Centre, Parkville, VIC, Australia
| | - Sumitra Ananda
- University of Melbourne, Parkville, VIC, Australia
- Department of Medical Oncology, Peter MacCallum Cancer Centre, Parkville, VIC, Australia
| | - Michael Michael
- Department of Medical Oncology, Peter MacCallum Cancer Centre, Parkville, VIC, Australia
| | - Sue-Anne McLachlan
- University of Melbourne, Parkville, VIC, Australia
- Department of Medical Oncology, St Vincent's Hospital, Fitzroy, VIC, Australia
| | - Benjamin Thomson
- Department of Surgery, Royal Melbourne Hospital, Parkville, VIC, Australia
- Department of Surgical Oncology, Peter MacCallum Cancer Centre, Parkville, VIC, Australia
| | - Benjamin Loveday
- Department of Surgery, Royal Melbourne Hospital, Parkville, VIC, Australia
- Department of Surgical Oncology, Peter MacCallum Cancer Centre, Parkville, VIC, Australia
| | - Brett Knowles
- Department of Surgery, Royal Melbourne Hospital, Parkville, VIC, Australia
- Department of Surgical Oncology, Peter MacCallum Cancer Centre, Parkville, VIC, Australia
- Epworth Healthcare, Melbourne, VIC, Australia
| | - Adrian Fox
- Department of Hepatobiliary Surgery, St Vincent's Hospital, Fitzroy, VIC, Australia
| | - Mehrdad Nikfarjam
- University of Melbourne, Parkville, VIC, Australia
- Department of Hepatobiliary Surgery, Austin Health, Heidelberg, VIC, Australia
| | | | - Julia Shapiro
- Department of Medicine, Alfred Hospital, Prahran, VIC, Australia
| | - Kate Clarke
- Department of Medical Oncology, Wellington Hospital, Wellington, New Zealand
| | - Sharon Pattison
- Department of Medicine, Dunedin School of Medicine, University of Otago, Otago, New Zealand
| | - Cheng Ean Chee
- Department of Hematology-Oncology, National University Cancer Institute, Singapore, Singapore
| | - Rob Zielinski
- Department of Medical Oncology, Orange Hospital, Orange, NSW, Australia
- Department of Medical Oncology, Dubbo Base Hospital, Dubbo, NSW, Australia
- Department of Medical Oncology, Bathurst Base Hospital, West Bathurst, NSW, Australia
| | - Rachel Wong
- Epworth Healthcare, Melbourne, VIC, Australia
- Eastern Health Clinical School, Monash University, Box Hill, VIC, Australia
- Department of Medical Oncology, Eastern Health, Box Hill, VIC, Australia
| | - Peter Gibbs
- Walter & Eliza Hall Institute of Medical Research, Parkville, VIC, Australia
- University of Melbourne, Parkville, VIC, Australia
| | - Belinda Lee
- Walter & Eliza Hall Institute of Medical Research, Parkville, VIC, Australia
- University of Melbourne, Parkville, VIC, Australia
- Department of Medical Oncology, Peter MacCallum Cancer Centre, Parkville, VIC, Australia
- Department of Medical Oncology, Northern Hospital, Epping, VIC, Australia
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13
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Danpanichkul P, Suparan K, Jaroenlapnopparat A, Polpichai N, Fangsaard P, Detboon A, Moolkaew P, Sripusanapan A, Srisurapanont K, Kanjanakot Y, Duangsonk K, Wallace MB, Wijarnpreecha K. The Global Burden of Early-Onset Pancreatic Cancer and Its Risk Factors: A Perspective From Global Burden of Disease Study 2019. Pancreas 2024; 53:e434-e444. [PMID: 38530945 DOI: 10.1097/mpa.0000000000002331] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/28/2024]
Abstract
OBJECTIVES Despite evidence of increased incidence of early-onset pancreatic cancer (EOPC), defined as pancreatic cancer diagnosed in patients below 50 years old, and its risk factors in the Western region, global epidemiological data addressing this issue is still lacking. MATERIALS AND METHODS Utilizing data from the Global Burden of Disease Study 2019, we aimed to conduct a comprehensive analysis of the incidence, deaths, and disability-adjusted life years (DALYs) associated with EOPC and its risk factors, including smoking, obesity, and diabetes. The analysis examined the annual percentage change (APC) over the period. RESULTS In 2019, the incidence of EOPC surpassed 35,000 cases worldwide. This burden of EOPC tends to be more prevalent in males, as well as in Europe and high SDI countries. However, there is a noticeable upward trend in the burden of EOPC in the Eastern Mediterranean. While there is a global decline in EOPC mortality attributed to smoking (APC -0.33%), there is a concerning increase in mortality associated with diabetes (APC +2.84%) and obesity (APC +2.12%). CONCLUSIONS The burden of EOPC has been increasing. The mortality is rising mainly from metabolic factors. There is an urgent need for national policy development for reducing the burden of this disease.
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Affiliation(s)
- Pojsakorn Danpanichkul
- From the Immunology Unit, Department of Microbiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Kanokphong Suparan
- From the Immunology Unit, Department of Microbiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | | | | | - Panisara Fangsaard
- Department of Internal Medicine, Bassett Medical Center, Cooperstown, NY
| | | | | | | | | | - Yatawee Kanjanakot
- Department of Surgery, School of Medicine, Mae Fah Luang University, Chiang Rai
| | - Kwanjit Duangsonk
- Department of Microbiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
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Debernardi S, Liszka L, Ntala C, Steiger K, Esposito I, Carlotti E, Baker A, McDonald S, Graham T, Dmitrovic B, Feakins RM, Crnogorac‐Jurcevic T. Molecular characteristics of early-onset pancreatic ductal adenocarcinoma. Mol Oncol 2024; 18:677-690. [PMID: 38145461 PMCID: PMC10920080 DOI: 10.1002/1878-0261.13576] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2023] [Revised: 12/01/2023] [Accepted: 12/22/2023] [Indexed: 12/26/2023] Open
Abstract
The median age of patients with pancreatic ductal adenocarcinoma (PDAC) at diagnosis is 71 years; however, around 10% present with early-onset pancreatic cancer (EOPC), i.e., before age 50. The molecular mechanisms underlying such an early onset are unknown. We assessed the role of common PDAC drivers (KRAS, TP53, CDKN2A and SMAD4) and determined their mutational status and protein expression in 90 formalin-fixed, paraffin-embedded tissues, including multiple primary and matched metastases, from 37 EOPC patients. KRAS was mutated in 88% of patients; p53 was altered in 94%, and p16 and SMAD4 were lost in 86% and 71% of patients, respectively. Meta-synthesis showed a higher rate of p53 alterations in EOPC than in late-onset PDAC (94% vs. 69%, P = 0.0009) and significantly higher loss of SMAD4 (71% vs. 44%, P = 0.0025). The majority of EOPC patients accumulated aberrations in all four drivers; in addition, high tumour heterogeneity was observed across all tissues. The cumulative effect of an exceptionally high rate of alterations in all common PDAC driver genes combined with high tumour heterogeneity suggests an important mechanism underlying the early onset of PDAC.
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Affiliation(s)
- Silvana Debernardi
- Centre for Cancer Biomarkers and Biotherapeutics, Barts Cancer InstituteQueen Mary University of LondonUK
| | - Lukasz Liszka
- Department of Pathomorphology and Molecular DiagnosticsMedical University of SilesiaKatowicePoland
| | | | - Katja Steiger
- Institute of Pathology, School of Medicine and HealthTechnical University of MunichGermany
| | - Irene Esposito
- Institute of PathologyHeinrich‐Heine University and University Hospital of DusseldorfGermany
| | - Emanuela Carlotti
- Centre for Tumour Biology, Barts Cancer InstituteQueen Mary University of LondonUK
| | - Ann‐Marie Baker
- Centre for Tumour Biology, Barts Cancer InstituteQueen Mary University of LondonUK
| | - Stuart McDonald
- Centre for Tumour Biology, Barts Cancer InstituteQueen Mary University of LondonUK
| | - Trevor Graham
- Centre for Tumour Biology, Barts Cancer InstituteQueen Mary University of LondonUK
| | - Branko Dmitrovic
- Department of Pathology and Forensic MedicineClinical Hospital Center OsijekCroatia
| | - Roger M. Feakins
- Department of Cellular PathologyRoyal Free London NHS Foundation TrustUK
| | - Tatjana Crnogorac‐Jurcevic
- Centre for Cancer Biomarkers and Biotherapeutics, Barts Cancer InstituteQueen Mary University of LondonUK
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15
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Gueiderikh A, Tarabay A, Abdelouahab M, Smolenschi C, Tanguy ML, Valery M, Malka D, Pudlarz T, Fuerea A, Boige V, Hollebecque A, Ducreux M, Boilève A. Pancreatic adenocarcinoma third line systemic treatments: a retrospective cohort study. BMC Cancer 2024; 24:272. [PMID: 38408958 PMCID: PMC10898186 DOI: 10.1186/s12885-024-12016-z] [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: 11/02/2023] [Accepted: 02/16/2024] [Indexed: 02/28/2024] Open
Abstract
BACKGROUND Chemotherapy for metastatic pancreatic adenocarcinoma (PDAC) primarily relies on FOLFIRINOX (LV5FU- irinotecan - Oxaliplatine) and Gemcitabine - Nab-Paclitaxel in the first-line setting. However, second-lines remain less well-defined and there is limited data regarding third-line treatments. The objective of our study was to determine the proportion of patients advancing to third line chemotherapy, to outline the various third-line chemotherapy regimens used in routine practice and to evaluate their respective efficacy. METHODS A retrospective single-center cohort from 2010-2022 compiled baseline characteristics, treatment outcomes and survival of PDAC patients who received at least one chemotherapy line in a French tertiary-center. Overall survivals (OS) were analyzed using a Cox multivariable model. RESULTS In total, 676 patients were included, with a median follow-up time of 69.4 months, (Interquartile Range (IQR) = 72.1). Of these, 251 patients (37%) that proceeded to 3rd-line chemotherapy. The median PFS in 3rd line was 2.03 months, [CI95%: 1.83, 2.36]. The median 3rd line overall survival was 5.5 months, [CI95%: 4.8, 6.3]. In multivariable analysis erlotinib-based chemotherapy was found to be deleterious (HR=2.38, [CI95%: 1.30, 4.34], p=0.005) compared to fluoropyrimidine-based chemotherapy in terms of 3rd line overall survival while gemcitabine monotherapy showed a tendency towards negative outcomes. First and 2nd line chemotherapies sequence didn't influence 3rd line outcome. CONCLUSION In our cohort, one-third of treated patients proceeded to 3rd line chemotherapy resulting in a 5.5 months median 3rd line OS, consistent with treatments at advanced stage. Our results argue against the use of erlotinib and gemcitabine monotherapy.
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Affiliation(s)
- A Gueiderikh
- Département de médecine oncologique, Gustave Roussy, 94800, Villejuif, France
- Université Paris Saclay, 91471, Orsay, France
| | - A Tarabay
- Département de médecine oncologique, Gustave Roussy, 94800, Villejuif, France
| | - M Abdelouahab
- Département de statistiques, Gustave Roussy, 94800, Villejuif, France
| | - C Smolenschi
- Département de médecine oncologique, Gustave Roussy, 94800, Villejuif, France
- Gustave Roussy, DITEP, 94800, Villejuif, France
| | - M L Tanguy
- Département de statistiques, Gustave Roussy, 94800, Villejuif, France
| | - M Valery
- Département de médecine oncologique, Gustave Roussy, 94800, Villejuif, France
| | - D Malka
- Département d'oncologie médicale, Institut Mutualiste Montsouris, 75014, Paris, France
| | - T Pudlarz
- Département de médecine oncologique, Gustave Roussy, 94800, Villejuif, France
| | - A Fuerea
- Département de médecine oncologique, Gustave Roussy, 94800, Villejuif, France
| | - V Boige
- Département de médecine oncologique, Gustave Roussy, 94800, Villejuif, France
| | - A Hollebecque
- Département de médecine oncologique, Gustave Roussy, 94800, Villejuif, France
- Gustave Roussy, DITEP, 94800, Villejuif, France
| | - M Ducreux
- Département de médecine oncologique, Gustave Roussy, 94800, Villejuif, France
- Université Paris Saclay, 91471, Orsay, France
| | - A Boilève
- Département de médecine oncologique, Gustave Roussy, 94800, Villejuif, France.
- Université Paris Saclay, 91471, Orsay, France.
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16
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Chandana SR, Woods LM, Maxwell F, Gandolfo R, Bekaii-Saab T. Risk factors for early-onset pancreatic ductal adenocarcinoma: A systematic literature review. Eur J Cancer 2024; 198:113471. [PMID: 38154392 DOI: 10.1016/j.ejca.2023.113471] [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: 09/11/2023] [Revised: 11/27/2023] [Accepted: 11/30/2023] [Indexed: 12/30/2023]
Abstract
BACKGROUND Emerging cancer trends suggest an increase in pancreatic cancer incidence in individuals younger than its typical age of onset, potentially reflecting changes in population exposures and lifestyles. PATIENTS AND METHODS We conducted a PRISMA-standard systematic literature review to identify non-heritable risk factors for early-onset pancreatic ductal adenocarcinoma (PDAC) (PROSPERO number: CRD42022299397). Systematic searches of MEDLINE and Embase bibliographic databases were performed (January 2022), and publications were screened against predetermined eligibility criteria; data were extracted using standardised data fields. The STROBE checklist was used to assess the completeness of reporting as a proxy for publication quality. Data were categorised by risk factor and analysed descriptively. RESULTS In total, 24 publications were included. All publications reported observational study data; thresholds for age group comparisons ranged between 40 and 65 years. Lifestyle factors investigated included smoking, alcohol consumption, obesity, physical inactivity, meat intake, socioeconomic status and geographical residence. Clinical factors investigated included pancreatitis, diabetes/insulin resistance, prior cancer and cancer stage at diagnosis, hepatitis B infection, metabolic syndrome and long-term proton pump inhibitor exposure. Publication STROBE scores were 6-21 (maximum, 22). Eight studies reported results adjusted for confounders. Potential non-heritable risk factors for early-onset PDAC that warrant further investigation included smoking, alcohol consumption, pancreatitis and hepatitis B infection. CONCLUSION Evidence for non-heritable risk factors for early-onset PDAC is heterogeneous, but four factors were identified that might aid the identification of at-risk individuals who may benefit from screening and risk reduction strategies.
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Affiliation(s)
- Sreenivasa R Chandana
- Department of Gastrointestinal Medical Oncology, The Cancer and Hematology Centers, Grand Rapids, MI, USA.
| | - Laura M Woods
- Population Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle, UK
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17
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Flecchia C, Auclin E, Alouani E, Mercier M, Hollebecque A, Turpin A, Mazard T, Pernot S, Dutherage M, Cohen R, Borg C, Hautefeuille V, Sclafani F, Ben-Abdelghani M, Aparicio T, De La Fouchardière C, Herve C, Perkins G, Heinrich K, Kunzmann V, Gallois C, Guimbaud R, Tougeron D, Taieb J. Primary resistance to immunotherapy in patients with a dMMR/MSI metastatic gastrointestinal cancer: who is at risk? An AGEO real-world study. Br J Cancer 2024; 130:442-449. [PMID: 38102227 PMCID: PMC10844357 DOI: 10.1038/s41416-023-02524-3] [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: 07/10/2023] [Revised: 11/09/2023] [Accepted: 11/24/2023] [Indexed: 12/17/2023] Open
Abstract
BACKGROUND The outstanding efficacy of immunotherapy in metastatic dMMR/MSI gastro-intestinal (GI) cancers has led to a rapid increase in the number of patients treated. However, 20-30% of patients experience primary resistance to immune checkpoint inhibitors (ICIPR) and need better characterization. METHODS This AGEO real-world study retrospectively analyzed the efficacy and safety of ICIs and identified clinical variables associated with ICIPR in patients with metastatic dMMR/MSI GI cancers treated with immunotherapy between 2015 and 2022. RESULTS 399 patients were included, 284 with colorectal cancer (CRC) and 115 with non-CRC, mostly treated by an anti-PD(L)1 (88.0%). PFS at 24 months was 55.8% (95CI [50.8-61.2]) and OS at 48 months was 59.1% (95CI [53.0-65.9]). ORR was 51.0%, and 25.1% of patients were ICIPR. There was no statistical difference in ORR, DCR, PFS, or OS between CRC and non-CRC groups. In multivariable analysis, ICIPR was associated with ECOG-PS ≥ 2 (OR = 3.36), liver metastases (OR = 2.19), peritoneal metastases (OR = 2.00), ≥1 previous line of treatment (OR = 1.83), and age≤50 years old (OR = 1.76). CONCLUSION These five clinical factors associated with primary resistance to ICIs should be considered by physicians to guide treatment choice in GI dMMR/MSI metastatic cancer patients.
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Affiliation(s)
- Clémence Flecchia
- Department of Digestive Oncology, Georges Pompidou European Hospital, Assistance Publique des Hôpitaux de Paris (AP-HP), Université Paris Cité, Paris, France
| | - Edouard Auclin
- CARPEM, SIRIC, Université Paris Cité, Georges Pompidou European Hospital, Paris, France
| | - Emily Alouani
- Digestive Oncology Department, Rangueil Hospital, University Hospital of Toulouse, Toulouse, France
| | - Mathilde Mercier
- Gastroenterology and Hepatology Department, Poitiers University Hospital, Poitiers, France
| | - Antoine Hollebecque
- Drug Development Department (DITEP), Gustave Roussy Institute, Saclay University, 94800, Villejuif, France
| | - Anthony Turpin
- Department of Medical Oncology, CNRS UMR9020, Inserm UMR-S 1277-Canther-Cancer Heterogeneity, Plasticity and Resistance to Therapies, University of Lille, CHU Lille, Lille, France
| | - Thibault Mazard
- Department of Medical Oncology, Institut de Recherche en Cancérologie de Montpellier, INSERM, University of Montpellier, ICM, Montpellier, France
| | - Simon Pernot
- Department of Digestive Oncology, Institut Bergonié, Bordeaux, France
| | - Marie Dutherage
- Department of Medical Oncology, Henri Becquerel Centre, Rouen, France
| | - Romain Cohen
- Department of Medical Oncology, Sorbonne University, Hôpital Saint-Antoine, AP-HP, and INSERM UMRS 938, Équipe Instabilité des Microsatellites et Cancer, Équipe Labellisée par la Ligue Nationale Contre le Cancer, SIRIC CURAMUS, Centre de recherche Saint Antoine, Paris, France
| | - Christophe Borg
- Department of Medical Oncology, University Hospital of Besançon, Besançon, France
| | - Vincent Hautefeuille
- Department of Hepato-Gastroenterology and Digestive Oncology, CHU Amiens Picardie, Amiens, France
| | - Francesco Sclafani
- Department of Digestive Oncology, Institut Jules Bordet, The Brussels University Hospital, Université Libre de Bruxelles, 1070, Anderlecht, Belgium
| | | | - Thomas Aparicio
- Gastroenterology Department, Saint Louis Hospital, APHP, Paris, France
| | | | - Camille Herve
- Department of Medical Oncology, GHM, Grenoble, France
| | | | - Kathrin Heinrich
- Department of Medicine III and Comprehensive Cancer Center (CCC Munich LMU), University Hospital, LMU Munich, Marchioninistraße 15, 81377, Munich, Germany; German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany
| | - Volker Kunzmann
- Department of Internal Medicine II, University Hospital Würzburg, Germany on behalf of the WERA Comprehensive Cancer Center Alliance, Würzburg, Germany
| | - Claire Gallois
- CARPEM, SIRIC, Université Paris Cité, Georges Pompidou European Hospital, Paris, France
| | - Rosine Guimbaud
- Digestive Oncology Department, Rangueil Hospital, University Hospital of Toulouse, Toulouse, France
| | - David Tougeron
- Gastroenterology and Hepatology Department, Poitiers University Hospital, Poitiers, France
| | - Julien Taieb
- Department of Digestive Oncology, Georges Pompidou European Hospital, Assistance Publique des Hôpitaux de Paris (AP-HP), Université Paris Cité, Paris, France.
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18
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Dahia SS, Konduru L, Pandol SJ, Barreto SG. The burden of young-onset pancreatic cancer and its risk factors from 1990 to 2019: A systematic analysis of the global burden of disease study 2019. Pancreatology 2024; 24:119-129. [PMID: 38151359 DOI: 10.1016/j.pan.2023.12.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Revised: 11/13/2023] [Accepted: 12/18/2023] [Indexed: 12/29/2023]
Abstract
OBJECTIVE To investigate worldwide incidence, deaths, disability-adjusted life years (DALYs) and risk factors for young-onset pancreatic cancer (YOPC) using the Global Burden of Disease Study 2019-20 data. METHODS We queried the Global Health Data Exchange tool for "pancreatic cancer" and "incidence", "deaths" as the "measure", and "DALYs" as the "cause" for the age group of 15-49 years to determine global, regional, and national trends in the incidence, deaths, and DALYs of YOPC. Sociodemographic index (SDI) was used to evaluate the associations between socioeconomic development and YOPC. Risk factors including smoking, tobacco use, hi2gh body mass index (BMI), and high fasting plasma glucose (FPG) were evaluated, and their attributable burden was estimated. RESULTS Global incidence, death, and DALY rates of YOPC significantly increased from 1990 to 2019 ((0.30 (p = 0.001), 0.25 (p = 0.001), and 11.18 (p = 0.002), respectively). Regions with the highest and lowest incidence, death, and DALY rates of YOPC were Eastern Europe and Central Sub-Saharan Africa, respectively. Incidence, death, and DALY rates increased with increasing age and SDI. Leading risk factors for YOPC in 2019 were smoking and tobacco use. DALYs attributable to smoking and tobacco use decreased from 1990 to 2019, especially in females, while those attributable to high BMI and FPG increased during the same period. CONCLUSIONS The global incidence, death and DALY rates of YOPC have significantly increased over 3 decades. Certain regions and nations are witnessing a higher increase in this trend. There is an urgent need for global efforts targeting preventable causes of YOPC.
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Affiliation(s)
| | - Laalithya Konduru
- College of Medicine and Public Health, Flinders University, South Australia, Australia
| | - Stephen J Pandol
- Division of Digestive and Liver Diseases, Cedars-Sinai Medical Center, Los Angeles, CA, USA
| | - Savio George Barreto
- College of Medicine and Public Health, Flinders University, South Australia, Australia; Division of Surgery and Perioperative Medicine, Flinders Medical Center, Bedford Park, Adelaide, South Australia, Australia.
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Li Z, Zhang X, Sun C, Li Z, Fei H, Zhao D. Global, regional, and national burdens of early onset pancreatic cancer in adolescents and adults aged 15-49 years from 1990 to 2019 based on the Global Burden of disease study 2019: A cross-sectional study. Int J Surg 2024; 110:01279778-990000000-00947. [PMID: 38215264 PMCID: PMC11020133 DOI: 10.1097/js9.0000000000001054] [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: 10/26/2023] [Accepted: 12/21/2023] [Indexed: 01/14/2024]
Abstract
BACKGROUND Early-onset pancreatic cancer (EOPC) in younger populations (age≤50 y) is likely to be a more aggressive phenotype characterized by poor differentiation. The emerging analysis of the global burden of EOPC is limited and outdated. AIM To systematically investigate the burden and trend of EOPC based on global populations. METHODS In this systematic analysis based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we present the number of cases, age-standardized rates (ASRs) per 100,000 population, and risk factors for 204 countries and territories. The average annual percentage changes (AAPCs) for the incidence, mortality, and disability-adjusted life-years (DALYs) of EOPC were calculated using joinpoint regression analysis. RESULTS According to the GBD 2019 estimates, there were 36,852 new cases of EOPC and 32,004 related deaths. East Asia had the highest number of cases, with 11,401 incidences and 10,149 deaths. The ASRs were 0.94 per 100,000 individuals for incidence and 0.81 per 100,000 for mortality. From 1990 to 2019, the age-standardized incidence increased by 46.9%, mortality increased by 44.6%, and DALYs increased by 41.9% globally. In trend analysis, the global incidence (AAPC, 1.26), mortality (AAPC, 1.24), and DALYs (AAPC, 1.25) of EOPC showed an increasing pattern. The ASRs of incidence, mortality, and DALYs of EOPC in Africa, America, and Asia exhibited a continuous upward trend, while the trend in Europe was fluctuating. Asian males exhibited the fastest growth in incidence (AAPC, 2.15) and mortality (AAPC, 2.13), whereas males in the Americas experienced the slowest increase in new cases (AAPC, 0.72) and deaths (AAPC, 0.67). A certain proportion of EOPC DALYs were attributable to known risk factors: tobacco smoking (13.3%), high body-mass index (BMI, 5.6%), and high fasting plasma glucose (FPG, 3.2%). Integrating the socio-demographic index (SDI), ASRs of incidence and mortality initially increased with rising SDI, reaching a peak in central Europe (1.5 per 100,000 CONCLUSIONS The findings offer valuable insights into the global distribution and magnitude of the EOPC burden. The burden is increasing at a rapid pace worldwide, particularly in Asia, and is notably high in central and eastern Europe. This highlights the need for additional preventive control efforts targeting high-risk populations.
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Affiliation(s)
| | | | | | | | | | - Dongbing Zhao
- Department of Pancreatic and Gastric Surgical Oncology, National Cancer Center/National Clinical Research for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China
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20
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Zironda A, Zhang C, Day C, McWilliams RR, Starlinger P, Warner SG, Smoot RL, Cleary SP, Kendrick ML, Truty MJ, Thiels CA. Early vs conventional onset pancreatic ductal adenocarcinoma: analysis of surgical and oncologic outcomes in patients undergoing curative intent resection. HPB (Oxford) 2024; 26:145-153. [PMID: 37752029 DOI: 10.1016/j.hpb.2023.09.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/07/2023] [Revised: 08/21/2023] [Accepted: 09/06/2023] [Indexed: 09/28/2023]
Abstract
BACKGROUND Pancreatic ductal adenocarcinoma (PDAC) impacts patients in their 60s, but its incidence in younger patients is increasing. We hypothesize that younger patients may have worse oncologic outcomes. METHODS Patients who underwent curative pancreatic resection for PDAC between January 2011 and December 2021 at a single institution were analyzed. Early-onset pancreatic cancer (EOPC) was defined as pancreatic cancer diagnosed in patients ≤50 years. Clinical and survival outcomes were compared between EOPC and Conventional Onset Pancreas Cancer (COPC). RESULTS A total of 1133 patients were identified, 65 (5.7%) were EOPC. Preoperative patient characteristics including sex, smoking status, alcohol habitus, diabetes mellitus, CA 19-9, and neoadjuvant therapy were similar between EOPC and COPC (p > 0.05). EOPC patients were more likely non-white (p = 0.03), had lower ASA scores (p = 0.02) and larger median tumor size (33 vs 28 mm, p = 0.04), but had similar pathological stages and rate of R0 resections (p > 0.05). Postoperative outcomes were similar (p > 0.05). There was no statistically significant difference in overall (HR 0.93, CI 0.64, 1.33; p = 0.68) or recurrence free (HR 1.05, CI 0.75, 1.48; p = 0.77) survival between the EOPC and COPC after adjusting for significant factors. CONCLUSION Patients with EOPC who underwent surgical resection had similar oncological outcomes compared to patients with COPC.
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Affiliation(s)
- Andrea Zironda
- Hepatobiliary and Pancreas Surgery Division, Mayo Clinic, Rochester MN, USA
| | - Chi Zhang
- Department of Surgery, Mayo Clinic, Phoenix, AZ, USA; Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA
| | - Courtney Day
- Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA
| | | | - Patrick Starlinger
- Hepatobiliary and Pancreas Surgery Division, Mayo Clinic, Rochester MN, USA
| | - Susanne G Warner
- Hepatobiliary and Pancreas Surgery Division, Mayo Clinic, Rochester MN, USA
| | - Rory L Smoot
- Hepatobiliary and Pancreas Surgery Division, Mayo Clinic, Rochester MN, USA
| | - Sean P Cleary
- Hepatobiliary and Pancreas Surgery Division, Mayo Clinic, Rochester MN, USA
| | - Micheal L Kendrick
- Hepatobiliary and Pancreas Surgery Division, Mayo Clinic, Rochester MN, USA
| | - Mark J Truty
- Hepatobiliary and Pancreas Surgery Division, Mayo Clinic, Rochester MN, USA
| | - Cornelius A Thiels
- Hepatobiliary and Pancreas Surgery Division, Mayo Clinic, Rochester MN, USA.
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21
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Gao F, Xu X, Sun Y. Clinical characteristics and prognosis of early-onset cholangiocarcinoma: a population-based study. Scand J Gastroenterol 2024; 59:183-191. [PMID: 37921657 DOI: 10.1080/00365521.2023.2277663] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2023] [Revised: 10/25/2023] [Accepted: 10/25/2023] [Indexed: 11/04/2023]
Abstract
BACKGROUND Little is known about the disease of early-onset cholangiocarcinoma (EOC). The primary objective of this study was to compare EOC with later-onset cholangiocarcinoma (LOC) concerning clinical features and survival prognosis. METHODS 19325 cholangiocarcinoma patients were extracted from 1975 to 2020 in the SEER database. Cox regression analysis and Kaplan-Meier survival curves were used for the evaluation of cause-specific survival (CSS) and overall survival (OS). To reduce confounding, we compared survival differences between the EOC and LOC groups using propensity score matching (PSM). RESULTS 4037 cholangiocarcinoma patients were included in the study, of which 274 were EOC and 3763 were LOC. Early-onset patients were more likely to be non-white, and intrahepatic cholangiocarcinoma. At diagnosis, patients had advanced AJCC stage, lymph node metastase and distant metastase. The EOC patients were more likely to receive surgery, radiotherapy, and chemotherapy than later-onset patients. Multifactorial COX analysis indicated that EOC patients had lower mortality risk than later-onset patients, and similar results were obtained after PSM; Kaplan-Meier survival curves corroborated that early-onset patients exhibited better OS than later-onset patients, and this survival advantage persisted after PSM. Further subgroup analysis following matching demonstrated that early-onset patients had better OS than later-onset patients in the surgical subgroup, while there were no statistically significant differences in the radiotherapy and chemotherapy subgroups. CONCLUSION The EOC patients typically exhibit an intrahepatic presentation and generally experience a more favorable prognosis. Surgery emerged as a critical treatment modality significantly influencing the overall prognosis of EOC.
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Affiliation(s)
- Fuli Gao
- Department of Gastroenterology, Changshu Hospital Affiliated to Soochow University, First People's Hospital of Changshu City, Changshu, Jiangsu, China
| | - Xiaodan Xu
- Department of Gastroenterology, Changshu Hospital Affiliated to Soochow University, First People's Hospital of Changshu City, Changshu, Jiangsu, China
| | - Ying Sun
- Department of Gastroenterology, Changshu Hospital Affiliated to Soochow University, First People's Hospital of Changshu City, Changshu, Jiangsu, China
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Mima K, Hamada T, Inamura K, Baba H, Ugai T, Ogino S. The microbiome and rise of early-onset cancers: knowledge gaps and research opportunities. Gut Microbes 2023; 15:2269623. [PMID: 37902043 PMCID: PMC10730181 DOI: 10.1080/19490976.2023.2269623] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Accepted: 10/06/2023] [Indexed: 10/31/2023] Open
Abstract
Accumulating evidence indicates an alarming increase in the incidence of early-onset cancers, which are diagnosed among adults under 50 years of age, in the colorectum, esophagus, extrahepatic bile duct, gallbladder, liver, stomach, pancreas, as well as the bone marrow (multiple myeloma), breast, head and neck, kidney, prostate, thyroid, and uterine corpus (endometrium). While the early-onset cancer studies have encompassed research on the wide variety of organs, this article focuses on research on digestive system cancers. While a minority of early-onset cancers in the digestive system are associated with cancer-predisposing high penetrance germline genetic variants, the majority of those cancers are sporadic and multifactorial. Although potential etiological roles of diets, lifestyle, environment, and the microbiome from early life to adulthood (i.e. in one's life course) have been hypothesized, exact contribution of each of these factors remains uncertain. Diets, lifestyle patterns, and environmental exposures have been shown to alter the oral and intestinal microbiome. To address the rising trend of early-onset cancers, transdisciplinary research approaches including lifecourse epidemiology and molecular pathological epidemiology frameworks, nutritional and environmental sciences, multi-omics technologies, etc. are needed. We review current evidence and discuss emerging research opportunities, which can improve our understanding of their etiologies and help us design better strategies for prevention and treatment to reduce the cancer burden in populations.
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Affiliation(s)
- Kosuke Mima
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Tsuyoshi Hamada
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
- Department of Hepato-Biliary-Pancreatic Medicine, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Kentaro Inamura
- Division of Pathology, The Cancer Institute, Japanese Foundation for Cancer Research, Tokyo, Japan
- Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Hideo Baba
- Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
| | - Tomotaka Ugai
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Cancer Epidemiology Program, Dana-Farber Harvard Cancer Center, Boston, MA, USA
| | - Shuji Ogino
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Cancer Epidemiology Program, Dana-Farber Harvard Cancer Center, Boston, MA, USA
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Cancer Immunology Program, Dana-Farber Harvard Cancer Center, Boston, MA, USA
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23
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Whitley A, Kocián P, Nikov A, Krejčí D, Pehalová L, Blaha M, Dušek L, Gürlich R. Early-onset pancreatic cancer: A national cancer registry study from the Czech Republic and review of the literature. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2023; 30:1324-1333. [PMID: 37750364 DOI: 10.1002/jhbp.1359] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/17/2023] [Revised: 05/22/2023] [Accepted: 05/24/2023] [Indexed: 09/27/2023]
Abstract
BACKGROUND The aim of this study was to compare trends in mortality and incidence, clinicopathological features and survival of patients diagnosed with pancreatic ductal adenocarcinoma under 50 years of age (early-onset pancreatic cancer [EOPC]) with patients diagnosed over 50 years of age (late-onset pancreatic cancer [LOPC]). METHODS The national oncological registry of the Czech Republic was reviewed to identify all patients with histologically confirmed pancreatic ductal adenocarcinoma diagnosed between the years 1985 and 2015. Incidence, mortality, clinicopathological and survival data were analyzed and compared between patients with EOPC and LOPC. RESULTS From a total of 18 888 patients included in the study, 1324 patients were under the age of 50 years (7.0%). The average annual percentage changes (AAPC) in incidence of all patients with EOPC was -1.0%. The APPC for male patients with EOPC was -2.0% and for female patients was +0.6%. The AAPC in incidence for LOPC was +1.3%. There were no differences in tumor stage, grade or location between EOPC and LOPC. Young patients were more frequently male (64.4% vs. 52.9%), more frequently underwent treatment and had better overall survival. The median survival interval for EOPC was 5.9 months and for LOPC was 4.5 months (p < .001). CONCLUSIONS The clinicopathological features of pancreatic ductal adenocarcinoma were similar in patients under and over the age of 50 years. Patients with EOPC survived longer than patients with LOPC. Continued efforts should be made to diagnose early and treat young patients aggressively.
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Affiliation(s)
- Adam Whitley
- Department of Surgery, University Hospital Kralovske Vinohrady, Prague, Czech Republic
- Department of Anatomy, Second Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Petr Kocián
- Department of Surgery, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic
| | - Andrej Nikov
- Department of Surgery, University Hospital Kralovske Vinohrady, Prague, Czech Republic
| | - Denisa Krejčí
- Institute of Health Information and Statistics of the Czech Republic, Prague, Czech Republic
- Institute of Biostatistics and Analyses, Faculty of Medicine, Masaryk University, Brno, Czech Republic
| | - Lucie Pehalová
- Institute of Health Information and Statistics of the Czech Republic, Prague, Czech Republic
- Institute of Biostatistics and Analyses, Faculty of Medicine, Masaryk University, Brno, Czech Republic
| | - Milan Blaha
- Institute of Health Information and Statistics of the Czech Republic, Prague, Czech Republic
- Institute of Biostatistics and Analyses, Faculty of Medicine, Masaryk University, Brno, Czech Republic
| | - Ladislav Dušek
- Institute of Health Information and Statistics of the Czech Republic, Prague, Czech Republic
- Institute of Biostatistics and Analyses, Faculty of Medicine, Masaryk University, Brno, Czech Republic
| | - Robert Gürlich
- Department of Surgery, University Hospital Kralovske Vinohrady, Prague, Czech Republic
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Castet F, Fabregat-Franco C, Castillo G, Navarro V, Sierra A, Acosta DA, López-Valbuena D, Dienstmann R, Tabernero J, Vivancos A, Tian TV, Macarulla T. Clinical and genomic characterisation of early-onset pancreatic cancer. Eur J Cancer 2023; 194:113338. [PMID: 37793216 DOI: 10.1016/j.ejca.2023.113338] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2023] [Revised: 08/31/2023] [Accepted: 09/04/2023] [Indexed: 10/06/2023]
Abstract
BACKGROUND The incidence of early-onset pancreatic cancer (EOPC) has risen dramatically in recent years. We aimed to characterise the clinical and genomic features of EOPC and evaluate their therapeutic implications. METHODS We performed a comparative, single-centre, retrospective analysis of clinical, germline, and genomic features in EOPC (≤50 years) patients and compared them with a control group of average-onset pancreatic cancer patients (AOPC, ≥70 years). Key molecular findings were compared with an external, publicly available cohort. RESULTS We reviewed 336 patients who met all inclusion criteria (EOPC N = 139, AOPC N = 197). EOPC was associated with smoking status, lower prevalence of diabetes, better performance status, higher CA19.9 levels, and higher albumin levels at diagnosis. After adjustment for baseline covariates, we observed no differences in overall survival (OS). Age was associated with an increase in the incidence of KRASMUT both in our cohort and the validation cohort. EOPC were enriched in potentially actionable alterations according to ESCAT tiers I-IIIA when compared with AOPC in discovery and validation cohorts (19% versus 14% and 14% versus 8%, respectively). In the first-line metastatic setting, EOPC had a longer progression-free survival (hazard ratio [HR] 0.61, 95% confidence interval (CI) 0.43-0.87) and OS (HR 0.65, 95% CI 0.45-0.95), although there were no differences in response rate. After adjusting for the number of treatment lines, EOPC patients who did receive targeted therapies exhibited longer OS compared with EOPC who did not (HR 0.34, 95% CI 0.12-0.93). CONCLUSIONS EOPC patients have improved outcomes in the metastatic setting when compared to AOPC and are enriched for targetable alterations that open opportunities for precision oncology-based approaches.
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Affiliation(s)
- Florian Castet
- Gastrointestinal and Endocrine Tumor Unit, Vall d'Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, C/ Natzaret, 115-117, 08035 Barcelona, Spain; Upper Gastrointestinal Cancer Translational Research Group, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, C/ Natzaret, 115-117, 08035 Barcelona, Spain
| | - Carles Fabregat-Franco
- Gastrointestinal and Endocrine Tumor Unit, Vall d'Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, C/ Natzaret, 115-117, 08035 Barcelona, Spain; Upper Gastrointestinal Cancer Translational Research Group, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, C/ Natzaret, 115-117, 08035 Barcelona, Spain
| | - Gloria Castillo
- Oncology Data Science (ODysSey) Group, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, C/ Natzaret, 115-117, 08035 Barcelona, Spain
| | - Víctor Navarro
- Oncology Data Science (ODysSey) Group, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, C/ Natzaret, 115-117, 08035 Barcelona, Spain
| | - Alexandre Sierra
- Gastrointestinal and Endocrine Tumor Unit, Vall d'Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, C/ Natzaret, 115-117, 08035 Barcelona, Spain
| | - Daniel Alejandro Acosta
- Gastrointestinal and Endocrine Tumor Unit, Vall d'Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, C/ Natzaret, 115-117, 08035 Barcelona, Spain
| | - Daniel López-Valbuena
- Gastrointestinal and Endocrine Tumor Unit, Vall d'Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, C/ Natzaret, 115-117, 08035 Barcelona, Spain; Upper Gastrointestinal Cancer Translational Research Group, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, C/ Natzaret, 115-117, 08035 Barcelona, Spain
| | - Rodrigo Dienstmann
- Oncology Data Science (ODysSey) Group, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, C/ Natzaret, 115-117, 08035 Barcelona, Spain
| | - Josep Tabernero
- Gastrointestinal and Endocrine Tumor Unit, Vall d'Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, C/ Natzaret, 115-117, 08035 Barcelona, Spain; University of Vic-Central University of Catalonia, Carrer del Dr. Junyent, 1, 08500 Vic, Barcelona, Spain; International Oncology Bureau-Quiron, Plaça d'Alfonso Comín, 5, 08023 Barcelona, Spain
| | - Ana Vivancos
- Cancer Genomics Group, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, C/ Natzaret, 115-117, 08035 Barcelona, Spain
| | - Tian V Tian
- Upper Gastrointestinal Cancer Translational Research Group, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, C/ Natzaret, 115-117, 08035 Barcelona, Spain
| | - Teresa Macarulla
- Gastrointestinal and Endocrine Tumor Unit, Vall d'Hebron Institute of Oncology (VHIO), Hospital Universitari Vall d'Hebron, Vall d'Hebron Barcelona Hospital Campus, C/ Natzaret, 115-117, 08035 Barcelona, Spain; Upper Gastrointestinal Cancer Translational Research Group, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Barcelona Hospital Campus, C/ Natzaret, 115-117, 08035 Barcelona, Spain; International Oncology Bureau-Quiron, Plaça d'Alfonso Comín, 5, 08023 Barcelona, Spain.
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25
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Nodari Y, Gentiluomo M, Mohelnikova-Duchonova B, Kreivenaite E, Milanetto AC, Skieceviciene J, Landi S, Lawlor RT, Petrone MC, Arcidiacono PG, Lovecek M, Gazouli M, Bijlsma MF, Morelli L, Kiudelis V, Tacelli M, Zanette DL, Soucek P, Uzunoglu F, Kaaks R, Izbicki J, Boggi U, Pezzilli R, Mambrini A, Pasquali C, van Laarhoven HW, Katzke V, Cavestro GM, Sperti C, Loos M, Latiano A, Erőss B, Oliverius M, Johnson T, Basso D, Neoptolemos JP, Aoki MN, Greenhalf W, Vodicka P, Archibugi L, Vanella G, Lucchesi M, Talar-Wojnarowska R, Jamroziak K, Saeedi MA, van Eijck CHJ, Kupcinskas J, Hussein T, Puzzono M, Bunduc S, Götz M, Carrara S, Szentesi A, Tavano F, Moz S, Hegyi P, Luchini C, Capurso G, Perri F, Ermini S, Theodoropoulos G, Capretti G, Palmieri O, Ginocchi L, Furbetta N, Canzian F, Campa D. Genetic and non-genetic risk factors for early-onset pancreatic cancer. Dig Liver Dis 2023; 55:1417-1425. [PMID: 36973108 DOI: 10.1016/j.dld.2023.02.023] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Revised: 02/23/2023] [Accepted: 02/27/2023] [Indexed: 03/29/2023]
Abstract
BACKGROUND Early-onset pancreatic cancer (EOPC) represents 5-10% of all pancreatic ductal adenocarcinoma (PDAC) cases, and the etiology of this form is poorly understood. It is not clear if established PDAC risk factors have the same relevance for younger patients. This study aims to identify genetic and non-genetic risk factors specific to EOPC. METHODS A genome-wide association study was performed, analysing 912 EOPC cases and 10 222 controls, divided into discovery and replication phases. Furthermore, the associations between a polygenic risk score (PRS), smoking, alcohol consumption, type 2 diabetes and PDAC risk were also assessed. RESULTS Six novel SNPs were associated with EOPC risk in the discovery phase, but not in the replication phase. The PRS, smoking, and diabetes affected EOPC risk. The OR comparing current smokers to never-smokers was 2.92 (95% CI 1.69-5.04, P = 1.44 × 10-4). For diabetes, the corresponding OR was 14.95 (95% CI 3.41-65.50, P = 3.58 × 10-4). CONCLUSION In conclusion, we did not identify novel genetic variants associated specifically with EOPC, and we found that established PDAC risk variants do not have a strong age-dependent effect. Furthermore, we add to the evidence pointing to the role of smoking and diabetes in EOPC.
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Affiliation(s)
- Ylenia Nodari
- Department of Biology, University of Pisa, Pisa, Italy
| | | | | | - Edita Kreivenaite
- Gastroenterology Department and Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Anna Caterina Milanetto
- Dept. of Surgery, Oncology and Gastroenterology, University of Padova Chirurgia Generale 3, Padova, Italy
| | - Jurgita Skieceviciene
- Gastroenterology Department and Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Stefano Landi
- Department of Biology, University of Pisa, Pisa, Italy
| | - Rita T Lawlor
- Department of Diagnostics and Public Health, and ARC-Net Research Centre, University of Verona, Verona, Italy
| | - Maria Chiara Petrone
- PancreatoBiliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center Vita Salute San Raffaele University San Raffaele Scientific Institute, Milan, Italy
| | - Paolo Giorgio Arcidiacono
- PancreatoBiliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center Vita Salute San Raffaele University San Raffaele Scientific Institute, Milan, Italy
| | - Martin Lovecek
- Department of Surgery I, University Hospital Olomouc, Olomouc, Czech Republic
| | - Maria Gazouli
- Laboratory of Biology, Department of Basic Medical Science, School of Medicine, National Kapodistrian University of Athens, Athens, Greece
| | - Maarten F Bijlsma
- Center for Experimental and Molecular Medicine, Laboratory for Experimental Oncology and Radiobiology, Amsterdam UMC, location University of Amsterdam, Amsterdam, The Netherlands; Imaging and Biomarkers, Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - Luca Morelli
- General Surgery Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Vytautas Kiudelis
- Gastroenterology Department and Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Matteo Tacelli
- PancreatoBiliary Endoscopy and Endosonography Division, Pancreas Translational and Clinical Research Center Vita Salute San Raffaele University San Raffaele Scientific Institute, Milan, Italy
| | - Dalila Lucíola Zanette
- Laboratory for Applied Science and Technology in Health, Carlos Chagas Institute, Oswaldo Cruz Foundation (Fiocruz), Curitiba, Brazil
| | - Pavel Soucek
- Laboratory of Pharmacogenomics, Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic
| | - Faik Uzunoglu
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Rudolf Kaaks
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Jakob Izbicki
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Ugo Boggi
- Divisione di Chirurgia Generale e dei Trapianti, Università di Pisa, Pisa, Italy
| | | | - Andrea Mambrini
- Oncological Department, Massa Carrara Azienda USL Toscana Nord Ovest, Carrara, Italy
| | - Claudio Pasquali
- Dept. of Surgery, Oncology and Gastroenterology, University of Padova Chirurgia Generale 3, Padova, Italy
| | - Hanneke W van Laarhoven
- Department of Medical Oncology, Amsterdam UMC, location University of Amsterdam, Amsterdam, The Netherlands; Imaging and Biomarkers, Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - Verena Katzke
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Giulia Martina Cavestro
- Gastroenterology and Gastrointestinal Endoscopy Unit, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
| | - Cosimo Sperti
- Deptartment of Surgery, Oncology and Gastroenterology, University of Padova Chirurgia Generale 1, Padova, Italy
| | - Martin Loos
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Anna Latiano
- Division of Gastroenterology, Fondazione IRCCS "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo, Italy
| | - Bálint Erőss
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary; Center for Translational Medicine, Semmelweis University, Budapest, Hungary; Division of Pancreatic Diseases, Heart and Vascular Center, Semmelweis University, Budapest, Hungary
| | - Martin Oliverius
- Department of General Surgery, University Hospital Kralovske Vinohrady, Third Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Theron Johnson
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Daniela Basso
- Department of Medicine-DIMED, Laboratory Medicine-University of Padova, Padova, Italy
| | - John P Neoptolemos
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Mateus Nóbrega Aoki
- Laboratory for Applied Science and Technology in Health, Carlos Chagas Institute, Oswaldo Cruz Foundation (Fiocruz), Curitiba, Brazil
| | - William Greenhalf
- Molecular and Clinical Cancer Medicine, The University of Liverpool, Liverpool, United Kingdom
| | - Pavel Vodicka
- Department of Molecular Biology of Cancer, Institute of Experimental Medicine of the Czech Academy of Sciences, Prague, Czech Republic; Biomedical Center, Faculty of Medicine in Pilsen, Charles University, Pilsen, Czech Republic; Institute of Biology and Medical Genetics, First Faculty of Medicine, Charles University, Prague, Czech Republic
| | - Livia Archibugi
- Digestive and Liver Disease Unit, S. Andrea Hospital, "Sapienza" University of Rome, Rome, Italy; Pancreato-Biliary Endoscopy and Endosonography Division, IRCCS San Raffaele Scientific Institute, Pancreas Translational and Clinical Research Center, Vita-Salute San Raffaele University, Milan, Italy
| | - Giuseppe Vanella
- Digestive and Liver Disease Unit, S. Andrea Hospital, "Sapienza" University of Rome, Rome, Italy; Pancreato-Biliary Endoscopy and Endosonography Division, IRCCS San Raffaele Scientific Institute, Pancreas Translational and Clinical Research Center, Vita-Salute San Raffaele University, Milan, Italy
| | - Maurizio Lucchesi
- Oncological Department, Massa Carrara Azienda USL Toscana Nord Ovest, Carrara, Italy
| | | | - Krzysztof Jamroziak
- Department of Hematology, Transplantation and Internal Medicine, University Clinical Center of the Medical University of Warsaw, Warsaw, Poland
| | - Mohammed Al Saeedi
- Department of General, Visceral and Transplantation Surgery, University Hospital Heidelberg, Heidelberg, Germany
| | - Casper H J van Eijck
- Department of Surgery, Erasmus MC University Medical Center, Rotterdam, the Netherlands
| | - Juozas Kupcinskas
- Gastroenterology Department and Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - Tamás Hussein
- Center for Translational Medicine, Semmelweis University, Budapest, Hungary; Division of Pancreatic Diseases, Heart and Vascular Center, Semmelweis University, Budapest, Hungary
| | - Marta Puzzono
- Gastroenterology and Gastrointestinal Endoscopy Unit, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
| | - Stefania Bunduc
- Carol Davila University of Medicine and Pharmacy, Bucharest, Romania; Center for Translational Medicine, Semmelweis University, Budapest, Hungary; Division of Pancreatic Diseases, Heart and Vascular Center, Semmelweis University, Budapest, Hungary
| | - Mara Götz
- Department of General, Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Silvia Carrara
- Endoscopic Unit, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, Italy
| | - Andrea Szentesi
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary; Centre for Translational Medicine, Department of Medicine, University of Szeged, Szeged, Hungary; János Szentágothai Research Center, University of Pécs, Pécs, Hungary
| | - Francesca Tavano
- Division of Gastroenterology, Fondazione IRCCS "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo, Italy
| | - Stefania Moz
- Department of Medicine-DIMED, Laboratory Medicine-University of Padova, Padova, Italy
| | - Péter Hegyi
- Institute for Translational Medicine, Medical School, University of Pécs, Pécs, Hungary; Center for Translational Medicine, Semmelweis University, Budapest, Hungary; Division of Pancreatic Diseases, Heart and Vascular Center, Semmelweis University, Budapest, Hungary; János Szentágothai Research Center, University of Pécs, Pécs, Hungary
| | - Claudio Luchini
- Department of Diagnostics and Public Health, and ARC-Net Research Centre, University of Verona, Verona, Italy
| | - Gabriele Capurso
- Digestive and Liver Disease Unit, S. Andrea Hospital, "Sapienza" University of Rome, Rome, Italy; Pancreato-Biliary Endoscopy and Endosonography Division, IRCCS San Raffaele Scientific Institute, Pancreas Translational and Clinical Research Center, Vita-Salute San Raffaele University, Milan, Italy
| | - Francesco Perri
- Division of Gastroenterology, Fondazione IRCCS "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo, Italy
| | - Stefano Ermini
- Blood Transfusion Service, Children's Hospital, Azienda Ospedaliero-Universitaria Meyer, Florence, Italy
| | - George Theodoropoulos
- First Department of Propaedeutic Surgery, Hippokration General Hospital of Athens, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Giovanni Capretti
- Pancreatic Unit, IRCCS Humanitas Research Hospital, Rozzano, Italy; Department of Biomedical Sciences, Humanitas University, Milan, Italy
| | - Orazio Palmieri
- Division of Gastroenterology, Fondazione IRCCS "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo, Italy
| | - Laura Ginocchi
- Oncological Department, Massa Carrara Azienda USL Toscana Nord Ovest, Carrara, Italy
| | - Niccolò Furbetta
- General Surgery Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Federico Canzian
- Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Daniele Campa
- Department of Biology, University of Pisa, Pisa, Italy.
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He TC, Li JA, Xu ZH, Chen QD, Yin HL, Pu N, Wang WQ, Liu L. Biological and clinical implications of early-onset cancers: A unique subtype. Crit Rev Oncol Hematol 2023; 190:104120. [PMID: 37660930 DOI: 10.1016/j.critrevonc.2023.104120] [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: 06/21/2023] [Accepted: 08/30/2023] [Indexed: 09/05/2023] Open
Abstract
In recent years, the incidence of cancers is continuously increasing in young adults. Early-onset cancer (EOC) is usually defined as patients with cancers under the age of 50, and may represent a unique subgroup due to its special disease features. Overall, EOCs often initiate at a young age, present as a better physical performance but high degree of malignancy. EOCs also share common epidemiological and hereditary risk factors. In this review, we discuss several representative EOCs which were well studied previously. By revealing their clinical and molecular similarities and differences, we consider the group of EOCs as a unique subtype compared to ordinary cancers. In consideration of EOC as a rising threat to human health, more researches on molecular mechanisms, and large-scale, prospective clinical trials should be carried out to further translate into improved outcomes.
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Affiliation(s)
- Tao-Chen He
- Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Jian-Ang Li
- Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Zhi-Hang Xu
- Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Qiang-Da Chen
- Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Han-Lin Yin
- Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China
| | - Ning Pu
- Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
| | - Wen-Quan Wang
- Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
| | - Liang Liu
- Department of Pancreatic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Cancer Center, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
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27
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Doleschal B, Niedersüß-Beke D, Kirchweger P, Petzer A, Thaler J, Rumpold H. Survival Outcome in Early-Onset Metastatic Colorectal Cancer: A Multicenter-Matched Pair Analysis. Oncology 2023; 102:107-113. [PMID: 37699362 DOI: 10.1159/000533429] [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: 07/05/2023] [Accepted: 08/03/2023] [Indexed: 09/14/2023]
Abstract
INTRODUCTION Survival of patients suffering from metastatic colorectal cancer (mCRC) has increased over the last decades. These benefits appear to be restricted to patients aged 50 and above. However, among the population aged <50, colorectal cancer incidence and mortality rates are significantly rising. The clinical benefit of treatment in this population still is a matter of debate. We aim to compare the clinical outcome between patients aged 50 and younger. METHODS In this retrospective, observational study, we analyzed data from 1,077 patients treated for mCRC at three cancer centers in Austria from January 2005 to December 2019. Patients were divided into two groups based on age at diagnosis: <50 years (eo-CRC) and >50 years (regular-onset CRC, ro-CRC). Propensity score matching was used to control for potential biases, and survival outcomes were compared between the two groups. RESULTS The differences in tumor characteristics between eo-CRC and ro-CRC in the overall population were primarily related to tumor sidedness and disease-free survival following intended curative resection. Our data show that eo-CRC patients underwent metastases resection more often and received significantly more lines of treatment in the palliative setting. Overall survival was superior in eo-CRC compared to ro-CRC, even after adjusting for sidedness, timing of metastases, sex, number of treatment lines, and resection of metastases by propensity scoring. CONCLUSION Our study suggests that younger patients benefit at least to the same magnitude or even more from mCRC-treatment than patients aged 50 or above.
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Affiliation(s)
- Bernhard Doleschal
- Department of Internal Medicine I for Hematology with Stem Cell Transplantation, Hemostaseology, and Medical Oncology, Ordensklinikum Linz, Linz, Austria
| | | | - Patrick Kirchweger
- Medical Faculty, Johannes Kepler University Linz, Linz, Austria
- Department of General and Visceral Surgery, Ordensklinikum Linz, Linz, Austria
- Gastrointestinal Cancer Center, Ordensklinikum Linz, Linz, Austria
| | - Andreas Petzer
- Department of Internal Medicine I for Hematology with Stem Cell Transplantation, Hemostaseology, and Medical Oncology, Ordensklinikum Linz, Linz, Austria
| | - Josef Thaler
- Department of Internal Medicine IV, Hospital Wels-Grieskirchen, Wels, Austria
| | - Holger Rumpold
- Medical Faculty, Johannes Kepler University Linz, Linz, Austria
- Gastrointestinal Cancer Center, Ordensklinikum Linz, Linz, Austria
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Ogobuiro I, Baca Y, Ribeiro JR, Walker P, Wilson GC, Gulhati P, Marshall JL, Shroff RT, Spetzler D, Oberley MJ, Abbott DE, Kim HJ, Kooby DA, Maithel SK, Ahmad SA, Merchant NB, Xiu J, Hosein PJ, Datta J. Multiomic Characterization Reveals a Distinct Molecular Landscape in Young-Onset Pancreatic Cancer. JCO Precis Oncol 2023; 7:e2300152. [PMID: 37944072 PMCID: PMC10645414 DOI: 10.1200/po.23.00152] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2023] [Revised: 06/28/2023] [Accepted: 08/25/2023] [Indexed: 11/12/2023] Open
Abstract
PURPOSE Using a real-world database with matched genomic-transcriptomic molecular data, we sought to characterize the distinct molecular correlates underlying clinical differences between patients with young-onset pancreatic cancer (YOPC; younger than 50 years) and patients with average-onset pancreatic cancer (AOPC; 70 years and older). METHODS We analyzed matched whole-transcriptome and DNA sequencing data from 2,430 patient samples (YOPC, n = 292; AOPC, n = 2,138) from the Caris Life Sciences database (Phoenix, AZ). Immune deconvolution was performed using the quanTIseq pipeline. Overall survival (OS) data were obtained from insurance claims (n = 4,928); Kaplan-Meier estimates were calculated for age- and molecularly defined cohorts. Significance was determined as FDR-corrected P values (Q) < .05. RESULTS Patients with YOPC had higher proportions of mismatch repair-deficient/microsatellite instability-high, BRCA2-mutant, and PALB2-mutant tumors compared with patients with AOPC, but fewer SMAD4-, RNF43-, CDKN2A-, and SF3B1-mutant tumors. Notably, patients with YOPC demonstrated significantly lower incidence of KRAS mutations compared with patients with AOPC (81.3% v 90.9%; Q = .004). In the KRAS wild-type subset (n = 227), YOPC tumors demonstrated fewer TP53 mutations and were more likely driven by NRG1 and MET fusions, whereas BRAF fusions were exclusively observed in patients with AOPC. Immune deconvolution revealed significant enrichment of natural killer cells, CD8+ T cells, monocytes, and M2 macrophages in patients with YOPC relative to patients with AOPC, which corresponded with lower rates of HLA-DPA1 homozygosity. There was an association with improved OS in patients with YOPC compared with patients with AOPC with KRAS wild-type tumors (median, 16.2 [YOPC-KRASWT] v 10.6 [AOPC-KRASWT] months; P = .008) but not KRAS-mutant tumors (P = .084). CONCLUSION In this large, real-world multiomic characterization of age-stratified molecular differences in pancreatic ductal adenocarcinoma, YOPC is associated with a distinct molecular landscape that has prognostic and therapeutic implications.
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Affiliation(s)
- Ifeanyichukwu Ogobuiro
- Department of Surgery, Sylvester Comprehensive Cancer Center, University of Miami Leonard M. Miller School of Medicine, Miami, FL
| | | | | | | | | | - Prateek Gulhati
- Robert Wood Johnson Medical School, The Cancer Institute of NJ, New Brunswick, NJ
| | | | | | | | | | | | - Hong Jin Kim
- The University of North Carolina at Chapel Hill, Chapel Hill, NC
| | | | | | - Syed A. Ahmad
- University of Cincinnati Medical Center, Cincinnati, OH
| | - Nipun B. Merchant
- Department of Surgery, Sylvester Comprehensive Cancer Center, University of Miami Leonard M. Miller School of Medicine, Miami, FL
| | | | - Peter J. Hosein
- Department of Medicine, University of Miami Leonard M. Miller School of Medicine, Miami, FL
| | - Jashodeep Datta
- Department of Surgery, Sylvester Comprehensive Cancer Center, University of Miami Leonard M. Miller School of Medicine, Miami, FL
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29
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Lintern N, Smith AM, Jayne DG, Khaled YS. Photodynamic Stromal Depletion in Pancreatic Ductal Adenocarcinoma. Cancers (Basel) 2023; 15:4135. [PMID: 37627163 PMCID: PMC10453210 DOI: 10.3390/cancers15164135] [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: 07/05/2023] [Revised: 08/13/2023] [Accepted: 08/14/2023] [Indexed: 08/27/2023] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest solid malignancies, with a five-year survival of less than 10%. The resistance of the disease and the associated lack of therapeutic response is attributed primarily to its dense, fibrotic stroma, which acts as a barrier to drug perfusion and permits tumour survival and invasion. As clinical trials of chemotherapy (CT), radiotherapy (RT), and targeted agents have not been successful, improving the survival rate in unresectable PDAC remains an urgent clinical need. Photodynamic stromal depletion (PSD) is a recent approach that uses visible or near-infrared light to destroy the desmoplastic tissue. Preclinical evidence suggests this can resensitise tumour cells to subsequent therapies whilst averting the tumorigenic effects of tumour-stromal cell interactions. So far, the pre-clinical studies have suggested that PDT can successfully mediate the destruction of various stromal elements without increasing the aggressiveness of the tumour. However, the complexity of this interplay, including the combined tumour promoting and suppressing effects, poses unknowns for the clinical application of photodynamic stromal depletion in PDAC.
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Affiliation(s)
- Nicole Lintern
- School of Biomedical Sciences, University of Leeds, Leeds LS2 9JT, UK
| | - Andrew M. Smith
- Leeds Institute of Medical Research, St James’s University Hospital, Leeds LS9 7TF, UK
| | - David G. Jayne
- Leeds Institute of Medical Research, St James’s University Hospital, Leeds LS9 7TF, UK
| | - Yazan S. Khaled
- Leeds Institute of Medical Research, St James’s University Hospital, Leeds LS9 7TF, UK
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30
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Li Y, Zhang X. Pancreatic cancer in young adults - an evolving entity? Am J Cancer Res 2023; 13:2763-2772. [PMID: 37559978 PMCID: PMC10408474] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2023] [Accepted: 06/20/2023] [Indexed: 08/11/2023] Open
Abstract
The incidence of early-onset pancreatic cancer (EOPC) among young population (<50 years) is rising in the last decade, with gender, medical overtreatment, and genetic factors as the risk factors in EOPC. Nevertheless, the role of genetic factors in the development of EOPC needs further exploration since the studies were carried out with small sample size and ambiguous evidence. Notable, the high incidence of pathogenic germline variant (PGV) appears to be involved in EOPC. Compared with average-age-onset pancreatic cancer (AOPC), EOPC patients display a distinctive genomic feature on several well-known tumor suppressor and oncogenic genes including, including SMAD4, RAS wild wild-type, CDKN2A BRCA1, BRCA2 and FOXC2, which is different from the findings of studies with AOPC and LOPC, suggesting the dynamic evolving entity of EOPC. In addition, the potential gender-related incidence found in several countries also suggests the involvement of genetic or socioenvironmental factors in the development of AOPC. Therefore, further prospective epidemiological and molecular studies are warranted to elucidate the shifting epidemiology of this disease and, most importantly, to better exploit the opportunities for the early diagnosis of the disease.
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Affiliation(s)
- Yifan Li
- Hepatobiliary, Pancreatic and Gastrointestinal Surgery, Shanxi Province Carcinoma Hospital, Shanxi Hospital Affiliated to Carcinoma Hospital, Chinese Academy of Medical Sciences, Carcinoma Hospital Affiliated to Shanxi Medical UniversityTaiyuan 030013, Shanxi, PR China
| | - Xiaojuan Zhang
- Radiology Department, Shanxi Province Cancer Hospital, Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences, Cancer Hospital Affiliated to Shanxi Medical UniversityTaiyuan 030013, Shanxi, PR China
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31
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Gudmundsdottir H, Yonkus JA, Alva-Ruiz R, Kendrick ML, Smoot RL, Warner SG, Starlinger P, Thiels CA, Nagorney DM, Cleary SP, Grotz TE, Truty MJ. Yield of Staging Laparoscopy for Pancreatic Cancer in the Modern Era: Analysis of More than 1,000 Consecutive Patients. J Am Coll Surg 2023; 237:49-57. [PMID: 37026837 PMCID: PMC10262988 DOI: 10.1097/xcs.0000000000000704] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Revised: 02/24/2023] [Accepted: 02/27/2023] [Indexed: 04/08/2023]
Abstract
BACKGROUND Accurate staging prior to resection of pancreatic ductal adenocarcinoma (PDAC) is imperative to avoid unnecessary operative morbidity and oncologic futility in patients with occult intra-abdominal distant metastases. We aimed to determine the diagnostic yield of staging laparoscopy (SL) and to identify factors associated with increased risk of positive laparoscopy (PL) in the modern era. STUDY DESIGN Patients with radiographically localized PDAC who underwent SL from 2017 to 2021 were retrospectively reviewed. The yield of SL was defined as the proportion of patients with PL, including gross metastases and/or positive peritoneal cytology. Factors associated with PL were assessed using univariate analysis and multivariable logistic regression. RESULTS Of 1,004 patients who underwent SL, 180 (18%) had PL due to gross metastases (n = 140) and/or positive cytology (n = 96). Patients who had neoadjuvant chemotherapy prior to laparoscopy had lower rates of PL (14% vs 22%, p = 0.002). When the analysis was restricted to chemo-naive patients who had concurrent peritoneal lavage performed, 95 of 419 patients (23%) had PL. In multivariable analysis, PL was associated with younger (<60) age, indeterminate extrapancreatic lesions on preoperative imaging, body/tail tumor location, larger tumor size, and elevated serum CA 19-9 (all p < 0.05). Among patients with no indeterminate extrapancreatic lesions on preoperative imaging, the rate of PL ranged from 1.6% in patients with no risk factors to 42% in young patients with large body/tail tumors and elevated serum CA 19-9. CONCLUSIONS The rate of PL in patients with PDAC remains high in the modern era. SL with peritoneal lavage should be considered for the majority of patients prior to resection, specifically those with high-risk features, and ideally prior to neoadjuvant chemotherapy.
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Affiliation(s)
| | | | | | | | - Rory L Smoot
- From the Department of Surgery, Mayo Clinic, Rochester, MN
| | | | | | | | | | - Sean P Cleary
- From the Department of Surgery, Mayo Clinic, Rochester, MN
| | - Travis E Grotz
- From the Department of Surgery, Mayo Clinic, Rochester, MN
| | - Mark J Truty
- From the Department of Surgery, Mayo Clinic, Rochester, MN
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32
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Słodkowski M, Wroński M, Karkocha D, Kraj L, Śmigielska K, Jachnis A. Current Approaches for the Curative-Intent Surgical Treatment of Pancreatic Ductal Adenocarcinoma. Cancers (Basel) 2023; 15:cancers15092584. [PMID: 37174050 PMCID: PMC10177138 DOI: 10.3390/cancers15092584] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Revised: 04/24/2023] [Accepted: 04/28/2023] [Indexed: 05/15/2023] Open
Abstract
Radical resection is the only curative treatment for pancreatic cancer. However, only up to 20% of patients are considered eligible for surgical resection at the time of diagnosis. Although upfront surgery followed by adjuvant chemotherapy has become the gold standard of treatment for resectable pancreatic cancer there are numerous ongoing trials aiming to compare the clinical outcomes of various surgical strategies (e.g., upfront surgery or neoadjuvant treatment with subsequent resection). Neoadjuvant treatment followed by surgery is considered the best approach in borderline resectable pancreatic tumors. Individuals with locally advanced disease are now candidates for palliative chemo- or chemoradiotherapy; however, some patients may become eligible for resection during the course of such treatment. When metastases are found, the cancer is qualified as unresectable. It is possible to perform radical pancreatic resection with metastasectomy in selected cases of oligometastatic disease. The role of multi-visceral resection, which involves reconstruction of major mesenteric veins, is well known. Nonetheless, there are some controversies in terms of arterial resection and reconstruction. Researchers are also trying to introduce personalized treatments. The careful, preliminary selection of patients eligible for surgery and other therapies should be based on tumor biology, among other factors. Such selection may play a key role in improving survival rates in patients with pancreatic cancer.
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Affiliation(s)
- Maciej Słodkowski
- Department of General, Gastroenterologic and Oncologic Surgery, Medical University of Warsaw, 02-097 Warsaw, Poland
- Department of Molecular Biology, Institute of Genetics and Animal Biotechnology, Polish Academy of Sciences, 05-552 Jastrzębiec, Poland
| | - Marek Wroński
- Department of General, Gastroenterologic and Oncologic Surgery, Medical University of Warsaw, 02-097 Warsaw, Poland
| | - Dominika Karkocha
- Department of General, Gastroenterologic and Oncologic Surgery, Medical University of Warsaw, 02-097 Warsaw, Poland
| | - Leszek Kraj
- Department of Molecular Biology, Institute of Genetics and Animal Biotechnology, Polish Academy of Sciences, 05-552 Jastrzębiec, Poland
- Department of Oncology, Medical University of Warsaw, 02-097 Warsaw, Poland
| | - Kaja Śmigielska
- Department of General, Gastroenterologic and Oncologic Surgery, Medical University of Warsaw, 02-097 Warsaw, Poland
| | - Aneta Jachnis
- Department of General, Gastroenterologic and Oncologic Surgery, Medical University of Warsaw, 02-097 Warsaw, Poland
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Leonhardt CS, Kinny-Köster B, Hank T, Habib JR, Shoucair S, Klaiber U, Cameron JL, Hackert T, Wolfgang CL, Büchler MW, He J, Strobel O. Resected Early-Onset Pancreatic Cancer: Practices and Outcomes in an International Dual-Center Study. Ann Surg Oncol 2023; 30:2433-2443. [PMID: 36479659 PMCID: PMC10027827 DOI: 10.1245/s10434-022-12901-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Accepted: 11/15/2022] [Indexed: 12/13/2022]
Abstract
BACKGROUND Early-onset pancreatic cancer (EOPC), defined as age ≤ 45 years at diagnosis, accounts for 3% of all pancreatic cancer cases. Although differences in tumor biology have been suggested, available data are sparse and specific treatment recommendations are lacking. This study explores the clinicopathological features and oncologic outcomes of resected EOPC. PATIENTS AND METHODS Patients with EOPC undergoing resection between 2002 and 2018 were identified from the Heidelberg University Hospital and Johns Hopkins University registries. Median overall survival (OS) and recurrence-free survival (RFS) were analyzed, and prognostic factors were identified. RESULTS The final cohort included 164 patients, most of whom had pancreatic ductal adenocarcinoma (PDAC, n = 136; 82.9%) or IPMN-associated pancreatic cancer (n = 17; 10.4%). Twenty (12.1%) patients presented with stage 1 disease, 42 (25.6%) with stage 2, 75 (45.7%) with stage 3, and 22 (13.4%) with oligometastatic stage 4 disease. Most patients underwent upfront resection (n = 113, 68.9%), whereas 51 (31.1%) individuals received preoperative treatment. Median OS and RFS were 26.0 and 12.4 months, respectively. Stage-specific median survival was 70.6, 41.8, 23.8, and 16.9 months for stage 1, 2, 3, and 4 tumors, respectively. Factors independently associated with shorter OS and RFS were R1 resections and AJCC stages 3 and 4. Notably, AJCC 3-N2 and AJCC 3-T4 tumors had a median OS of 20 months versus 29.5 months, respectively. CONCLUSION Despite frequently presenting with advanced disease, oncologic outcomes in EOPC patients are satisfactory even in locally advanced cancers, justifying aggressive surgical approaches. Further research is needed to tailor current guidelines to this rare population.
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Affiliation(s)
- Carl-Stephan Leonhardt
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
- Department of General Surgery, Division of Visceral Surgery, Medical University of Vienna, Vienna, Austria
| | - Benedict Kinny-Köster
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, USA
- Department of Surgery, New York University Grossman School of Medicine and NYU Langone Health, New York, USA
| | - Thomas Hank
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
- Department of General Surgery, Division of Visceral Surgery, Medical University of Vienna, Vienna, Austria
| | - Joseph R Habib
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, USA
| | - Sami Shoucair
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, USA
| | - Ulla Klaiber
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
- Department of General Surgery, Division of Visceral Surgery, Medical University of Vienna, Vienna, Austria
| | - John L Cameron
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, USA
| | - Thilo Hackert
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Christopher L Wolfgang
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, USA
- Department of Surgery, New York University Grossman School of Medicine and NYU Langone Health, New York, USA
| | - Markus W Büchler
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany
| | - Jin He
- Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, USA
| | - Oliver Strobel
- Department of General, Visceral and Transplantation Surgery, Heidelberg University Hospital, Heidelberg, Germany.
- Department of General Surgery, Division of Visceral Surgery, Medical University of Vienna, Vienna, Austria.
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Ogobuiro I, Baca Y, Ribeiro JR, Walker P, Wilson GC, Gulhati P, Marshall JL, Shroff RT, Spetzler D, Oberley MJ, Abbott DE, Kim HJ, Kooby DA, Maithel SK, Ahmad SA, Merchant NB, Xiu J, Hosein PJ, Datta J. Multi-omic characterization reveals a distinct molecular landscape in young-onset pancreatic cancer. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2023:2023.03.28.23287894. [PMID: 37034762 PMCID: PMC10081424 DOI: 10.1101/2023.03.28.23287894] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/19/2023]
Abstract
Purpose Using a real-world database with matched genomic-transcriptomic molecular data, we sought to characterize the distinct molecular correlates underlying clinical differences between young-onset pancreatic cancer (YOPC; <50-yrs.) and average-onset pancreatic cancer (AOPC; ≥70-yrs.) patients. Methods We analyzed matched whole-transcriptome and DNA sequencing data from 2430 patient samples (YOPC, n=292; AOPC, n=2138) from the Caris Life Sciences database (Phoenix, AZ). Immune deconvolution was performed using the quanTIseq pipeline. Overall survival (OS) data was obtained from insurance claims (n=4928); Kaplan-Meier estimates were calculated for age-and molecularly-defined cohorts. Significance was determined as FDR-corrected P -values ( Q )<0.05. Results YOPC patients had higher proportions of mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H), BRCA2 -mutant, and PALB2 -mutant tumors compared with AOPC patients, but fewer SMAD4-, RNF43-, CDKN2A- , and SF3B1- mutant tumors. Notably, YOPC patients demonstrated significantly lower incidence of KRAS mutations compared with AOPC patients (81.3% vs. 90.9%; Q =0.004). In the KRAS- wildtype subset (n=227), YOPC tumors demonstrated fewer TP53 mutations and were more likely driven by NRG1 and MET fusions, while BRAF fusions were exclusively observed in AOPC patients. Immune deconvolution revealed significant enrichment of natural killer (NK) cells, CD8 + T cells, monocytes, and M2 macrophages in YOPC patients relative to AOPC patients, which corresponded with lower rates of HLA-DPA1 homozygosity. There was an association with improved OS in YOPC patients compared with AOPC patients with KRAS -wildtype tumors (median 16.2 [YOPC- KRAS WT ] vs. 10.6 [AOPC- KRAS WT ] months; P =0.008) but not KRAS -mutant tumors ( P =0.084). Conclusion In this large, real-world multi-omic characterization of age-stratified molecular differences in PDAC, YOPC is associated with a distinct molecular landscape that has prognostic and therapeutic implications.
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Ren S, Sadula A, Ye C, Chen Q, Yuan M, Meng M, Lei J, Li G, Yuan C. Clinical characteristics, treatment patterns and survival outcomes of early-onset pancreatic adenocarcinoma: a population-based study. Am J Transl Res 2023; 15:407-421. [PMID: 36777821 PMCID: PMC9908473] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Accepted: 12/08/2022] [Indexed: 02/14/2023]
Abstract
BACKGROUND Pancreatic ductal adenocarcinoma (PDAC) is a rare and refractory malignancy. Early-onset pancreatic cancer (EOPC), defined as pancreatic cancer diagnosed before the age of 50 years, is very rare. Clinical presentation and oncological outcomes of EOPC are confusing according to previous studies. METHODS We performed a retrospective, population-based study by querying the SEER database to analyze patients with PDAC from 2004 to 2018. Data on demographics, pathological characteristics, treatment patterns, and survival outcomes were compared between EOPC and pancreatic cancer in older patients. Propensity score matching (PSM) was used to minimize the potential bias of baseline characteristics between the two groups. The effect of age on changes in treatment modalities was evaluated using the Cochran-Armitage trend test. RESULTS The entire study enrolled 42,414 patients, including 2,916 (6.9%) patients with EOPC. Patients with EOPC were more likely to be male (56.6% vs. 51.0%, P < 0.001) and more frequently to present with a larger tumor size (40 mm vs. 37 mm, P < 0.001), vascular invasion (28.6% vs. 25.9%, P = 0.022) and distant metastasis (56.2% vs. 50.8%, P < 0.001) compared with older group. However, surgical resection rates (29.3% vs. 28.3%, P = 0.284) were fairly comparable, and most clinicopathologic characteristics were similar in the patients underwent resection. Younger patients had longer 5-year overall survival (6.9% vs. 5.5%, P < 0.001) and 5-year cancer-specific survival (8.4% vs. 7.3%, P < 0.001) among the overall cohort but had comparable prognosis among patients received surgery (both P > 0.05). Similar survival outcomes were obtained after PSM. In addition, operated patients tended to receive fewer systemic treatments at an increasing age (Ptrend < 0.001). The survival analysis, which was stratified by age groups, suggested that younger patients only had a better prognosis than those over 70. CONCLUSIONS Patients with EOPC exhibited an advanced stage and a male predilection at diagnosis in the overall cohort but broadly similar clinicopathologic characteristics in the operated patients. In the surgical cohort, although younger patients were more likely to receive systemic treatment, patients with EOPC presented comparable outcomes compared with elderly patients. We suggest that more research should be conducted to uncover the unique characteristics of EOPC for better clinical management.
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Affiliation(s)
- Siqian Ren
- Department of General Surgery, Peking University Third Hospital49 North Garden Road, Haidian District, Beijing 100191, China
| | - Abuduhaibaier Sadula
- Department of General Surgery, Peking University Third Hospital49 North Garden Road, Haidian District, Beijing 100191, China
| | - Chen Ye
- Department of General Surgery, Peking University Third Hospital49 North Garden Road, Haidian District, Beijing 100191, China,Department of Hepatobiliary Surgery, Beijing Chao-Yang Hospital8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing 100020, China
| | - Qing Chen
- Department of Hepatobiliary Surgery, Beijing Chao-Yang Hospital8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing 100020, China
| | - Meng Yuan
- Department of General Surgery, Peking University Third Hospital49 North Garden Road, Haidian District, Beijing 100191, China
| | - Meng Meng
- Department of General Surgery, Peking University Third Hospital49 North Garden Road, Haidian District, Beijing 100191, China
| | - Ji’an Lei
- Department of General Surgery, Peking University Third Hospital49 North Garden Road, Haidian District, Beijing 100191, China
| | - Gang Li
- Department of General Surgery, Peking University Third Hospital49 North Garden Road, Haidian District, Beijing 100191, China
| | - Chunhui Yuan
- Department of General Surgery, Peking University Third Hospital49 North Garden Road, Haidian District, Beijing 100191, China
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Jayakrishnan T, Nair KG, Kamath SD, Wei W, Estfan BN, Krishnamurthi SS, Khorana AA. Comparison of characteristics and outcomes of young-onset versus average onset pancreatico-biliary adenocarcinoma. Cancer Med 2023; 12:7327-7338. [PMID: 36621839 PMCID: PMC10067060 DOI: 10.1002/cam4.5418] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Revised: 09/30/2022] [Accepted: 10/24/2022] [Indexed: 01/10/2023] Open
Abstract
BACKGROUND Young-onset gastrointestinal malignancies appear to be increasing in incidence. There are limited data on young-onset pancreaticobiliary adenocarcinoma (YO-PBA). METHODS The study comprised patients with PBA (pancreatic adenocarcinoma, intra-, and extra-hepatic cholangiocarcinoma) and included in the National Cancer Database (NCDB) between 2004 and 2017. YO-PBA was defined as a diagnosis at age less than 50 years. Logistic regression to assess factors associated with YO-PBA status, and cox proportional hazards modeling to associate relevant factors with overall survival was performed. RESULTS The study cohort comprised 360,764 patients, with 20,822 (5.8%) YO-PBA. YO-PBA was associated with (p-values<0.0001 for all): male sex (6.3% YO-male out of all male patients vs. 5.2% YO-female, OR 1.29, 95% CI 1.25-1.33), Black race (7.9% YO-Black vs. 5.0% YO-White, OR 1.72, 95% CI 1.64-1.80), lower income (6.4% YO-lowest household income based group vs. 5.5% highest, OR 1.08, 95% CI 1.03-1.13). YO-PBA were more likely to present with stage-IV disease (6.4% YO-Stage IV of all stage IV vs. 5.4% YO-Stage I-III, OR 1.25, 95% CI 1.21-1.29 p-value < 0.0001). Factors associated with overall survival (OS) in non-operable patients included-sex - male vs. female, HR 1.12 (95% CI 1.08-1.15); race - Black vs. White, HR 1.23 (95% CI 1.06-1.42); income group - lowest vs. highest, HR 1.33 (95% CI 1.27-1.39), and treatment center type - academic vs. nonacademic center, HR 0.87 (95% CI 0.85-0.90). CONCLUSIONS Socioeconomic factors significantly impact incidence and outcomes for young-onset pancreaticobiliary adenocarcinoma (YO-PBA). More work is needed to help understand the mechanisms involved while addressing the disparities.
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Affiliation(s)
| | - Kanika G Nair
- Taussig Cancer Institute, Cleveland Clinic, Ohio, Cleveland, USA
| | - Suneel D Kamath
- Taussig Cancer Institute, Cleveland Clinic, Ohio, Cleveland, USA
| | - Wei Wei
- Department of Quantitative Health Sciences, Cleveland Clinic, Ohio, Cleveland, USA
| | - Bassam N Estfan
- Taussig Cancer Institute, Cleveland Clinic, Ohio, Cleveland, USA
| | | | - Alok A Khorana
- Taussig Cancer Institute, Cleveland Clinic, Ohio, Cleveland, USA
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Andersson R, Haglund C, Seppänen H, Ansari D. Pancreatic cancer - the past, the present, and the future. Scand J Gastroenterol 2022; 57:1169-1177. [PMID: 35477331 DOI: 10.1080/00365521.2022.2067786] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2022] [Revised: 04/12/2022] [Accepted: 04/13/2022] [Indexed: 02/04/2023]
Abstract
BACKGROUND Pancreatic cancer has been and still is associated with a very poor prognosis. This is due to a lack of major breakthroughs with respect to early diagnosis, prognostication, prediction, as well as novel, targeted therapies. The benefits of surgery and chemotherapy are evident, but the fact that only some 10% of all patients have early, localized disease highlights the unmet need for new early detection methods. An improved understanding of tumor biology and the development of molecular markers detectable both in the circulation and in cancer tissues may underlie the development of new tools for optimizing both diagnosis and treatment. MATERIAL AND METHODS Review of the literature. RESULTS AND CONCLUSION If we do not improve precision oncology for pancreatic ductal adenocarcinoma, the prognosis will still remain dismal and the" burden" on society will increase substantially.
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Affiliation(s)
- Roland Andersson
- Surgery, Department of Clinical Sciences Lund Lund University, Skåne University Hospital, Lund, Sweden
| | - Caj Haglund
- Department of Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Hanna Seppänen
- Department of Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Daniel Ansari
- Surgery, Department of Clinical Sciences Lund Lund University, Skåne University Hospital, Lund, Sweden
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Ugai T, Sasamoto N, Lee HY, Ando M, Song M, Tamimi RM, Kawachi I, Campbell PT, Giovannucci EL, Weiderpass E, Rebbeck TR, Ogino S. Is early-onset cancer an emerging global epidemic? Current evidence and future implications. Nat Rev Clin Oncol 2022; 19:656-673. [PMID: 36068272 PMCID: PMC9509459 DOI: 10.1038/s41571-022-00672-8] [Citation(s) in RCA: 246] [Impact Index Per Article: 82.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/22/2022] [Indexed: 02/07/2023]
Abstract
Over the past several decades, the incidence of early-onset cancers, often defined as cancers diagnosed in adults <50 years of age, in the breast, colorectum, endometrium, oesophagus, extrahepatic bile duct, gallbladder, head and neck, kidney, liver, bone marrow, pancreas, prostate, stomach and thyroid has increased in multiple countries. Increased use of screening programmes has contributed to this phenomenon to a certain extent, although a genuine increase in the incidence of early-onset forms of several cancer types also seems to have emerged. Evidence suggests an aetiological role of risk factor exposures in early life and young adulthood. Since the mid-20th century, substantial multigenerational changes in the exposome have occurred (including changes in diet, lifestyle, obesity, environment and the microbiome, all of which might interact with genomic and/or genetic susceptibilities). However, the effects of individual exposures remain largely unknown. To study early-life exposures and their implications for multiple cancer types will require prospective cohort studies with dedicated biobanking and data collection technologies. Raising awareness among both the public and health-care professionals will also be critical. In this Review, we describe changes in the incidence of early-onset cancers globally and suggest measures that are likely to reduce the burden of cancers and other chronic non-communicable diseases.
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Affiliation(s)
- Tomotaka Ugai
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA.
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
| | - Naoko Sasamoto
- Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Boston, MA, USA
- Department of Obstetrics, Gynecology, and Reproductive Biology, Harvard Medical School, Boston, MA, USA
| | - Hwa-Young Lee
- Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Institute of Convergence Science, Convergence Science Academy, Yonsei University, Seoul, Republic of Korea
| | - Mariko Ando
- Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Mingyang Song
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA
| | - Rulla M Tamimi
- Department of Population Health Sciences, Weill Cornell Medicine, New York, NY, USA
| | - Ichiro Kawachi
- Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Peter T Campbell
- Department of Epidemiology and Population Health, Albert Einstein College of Medicine, New York, NY, USA
| | - Edward L Giovannucci
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | | | - Timothy R Rebbeck
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Division of Population Sciences, Dana-Farber Cancer Institute, Boston, MA, USA
- Zhu Family Center for Global Cancer Prevention, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Shuji Ogino
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital, and Harvard Medical School, Boston, MA, USA.
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
- Broad Institute of MIT and Harvard, Cambridge, MA, USA.
- Cancer Immunology and Cancer Epidemiology Programs, Dana-Farber Harvard Cancer Center, Boston, MA, USA.
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Lumish MA, Cercek A. Practical Considerations in Diagnosing and Managing Early-Onset GI Cancers. J Clin Oncol 2022; 40:2662-2680. [PMID: 35839438 PMCID: PMC9390825 DOI: 10.1200/jco.21.02708] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2021] [Revised: 03/12/2022] [Accepted: 04/18/2022] [Indexed: 12/24/2022] Open
Abstract
The incidence of early-onset (EO) GI cancers occurring in individuals younger than age 50 years has been rising at an alarming rate over the past two decades. Although this rise in incidence among young patients correlates with increased rates of obesity, changes in diet, and alterations in the environment, the effects of these environmental factors on carcinogenesis, metastasis, and treatment response are unknown. Although several unique clinical trends exist among EO-GI cancers and their average-onset GI cancer counterparts, GI cancers are molecularly indistinct between younger and older patients, and no data support distinct treatment paradigms for patients with EO disease. The majority of EO-GI cancers are not explained by germline changes. There remains a critical need for further research to understand the pathogenesis and optimal management of EO-GI cancers. In addition, current screening strategies are not adequate to identify EO-GI cancers, and early biomarkers are needed. Specialized centers, with a focus on psychosocial aspects of cancer management, can address the unique care needs of patients with EO-GI cancers.
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Affiliation(s)
- Melissa A. Lumish
- Memorial Sloan Kettering Cancer Center, Department of Medicine, New York, NY
| | - Andrea Cercek
- Memorial Sloan Kettering Cancer Center, Department of Medicine, New York, NY
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Barreto SG. Young-Onset Pancreatobiliary Cancers—Whereto from Here? Indian J Surg 2022; 84:349-351. [DOI: 10.1007/s12262-022-03533-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2022] [Accepted: 07/20/2022] [Indexed: 11/28/2022] Open
Abstract
AbstractThis Invited Editorial towards the Special Issue on Hepatobiliary and Pancreatic Surgery highlights the global problem of young-onset cancers. The paucity of data on young-onset pancreatobiliary cancers is presented in the context of its relevance to India (and its large component of adults in the at-risk age group for these cancers). In the face of limited information on the underlying cause of young-onset cancers, the author draws attention to evidence from colorectal cancer. The readers are encouraged to develop collaborative efforts in India to address answers to much needed questions on the management of young-onset pancreatobiliary cancers, some of which are listed in this Editorial.
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Huang BZ, Liu L, Zhang J, Pandol SJ, Grossman SR, Setiawan VW. Rising Incidence and Racial Disparities of Early-Onset Pancreatic Cancer in the United States, 1995-2018. Gastroenterology 2022; 163:310-312.e1. [PMID: 35288111 PMCID: PMC9232973 DOI: 10.1053/j.gastro.2022.03.011] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2021] [Revised: 02/12/2022] [Accepted: 03/07/2022] [Indexed: 01/28/2023]
Affiliation(s)
- Brian Z Huang
- Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, California; Department of Research & Evaluation, Kaiser Permanente Southern California, Pasadena, California
| | - Lihua Liu
- Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, California; Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California
| | - Juanjuan Zhang
- Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, California
| | - Stephen J Pandol
- Division of Gastroenterology, Departments of Medicine, Cedars-Sinai Medical Center; Department of Veterans Affairs, Los Angeles, California
| | - Steven R Grossman
- Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California; Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California
| | - Veronica Wendy Setiawan
- Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, California; Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California; Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California
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Zambrano CN, Lu W, Johnson C, Beeber M, Panitz A, Ibrahim S, Fraser M, Ma GX, Navder K, Yeh MC, Ogunwobi OO. Dietary behavior and urinary gallic acid concentration differences among underserved elder racial and ethnic minorities in New York City. Cancer Causes Control 2022; 33:929-937. [PMID: 35438359 PMCID: PMC9188520 DOI: 10.1007/s10552-022-01581-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2020] [Accepted: 03/29/2022] [Indexed: 11/30/2022]
Abstract
Purpose Diet and nutrition are important for cancer prevention. To investigate associations between dietary behavior, demographics, and risk of cancer, we assessed dietary behavior and urinary concentration of gallic acid, a polyphenol with anticancer properties found in various fruits and vegetables, in racial and ethnic minorities. Methods Ninety-one (91) participants were recruited from senior centers in East Harlem, New York City, a racially diverse and underserved community. A National Institute of Health (NIH)—validated dietary survey questionnaire—was used to collect dietary fruits and vegetables consumption data. Demographic and cancer information were also collected. All 91 participants completed the survey and forty-five (45) participants provided urine samples for gallic acid analysis. Results Gender differences were significantly associated with dietary behavior and urinary gallic acid concentration (UGAC). Female participants had a higher total daily intake of fruits and a significantly higher UGAC compared to male participants (p < 0.05). Age was negatively associated with the serving quantity of French fries/fried potatoes and white potatoes (p < 0.05), while positively associated with the daily intake frequency and daily intake of fruits (p < 0.05). Furthermore, Asian race was associated with higher daily intake frequencies of fruits and vegetable soup (p < 0.05), compared to other races. In a multivariate analysis, a significant association was observed between the serving quantities of fruits and other vegetables and UGAC (p < 0.05) after controlling for demographic characteristics. Conclusion The observed differences in dietary behavior and UGAC in this study provide limited information on the association between demographic differences and cancer prevalence in elder racial and ethnic minorities. Future research should investigate this association further for potential implications in cancer prevention. Supplementary Information The online version contains supplementary material available at 10.1007/s10552-022-01581-y.
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Affiliation(s)
- Cristina N Zambrano
- Department of Biological Sciences, Hunter College of the City University of New York, New York, USA
- Hunter College Center for Cancer Health Disparities Research (CCHDR), Hunter College of the City University of New York, 695 Park Avenue, HN310A, New York, 10065, USA
| | - Wenyue Lu
- Center for Asian Health, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA
- Sociology Department, College of Liberal Arts, Temple University, Philadelphia, PA, USA
| | - Cicely Johnson
- Hunter College Center for Cancer Health Disparities Research (CCHDR), Hunter College of the City University of New York, 695 Park Avenue, HN310A, New York, 10065, USA
| | - Maayan Beeber
- Nutrition Program, School of Urban Public Health, Hunter College of the City University of New York, New York, USA
| | - April Panitz
- Nutrition Program, School of Urban Public Health, Hunter College of the City University of New York, New York, USA
| | - Safa Ibrahim
- Department of Biological Sciences, Hunter College of the City University of New York, New York, USA
- Hunter College Center for Cancer Health Disparities Research (CCHDR), Hunter College of the City University of New York, 695 Park Avenue, HN310A, New York, 10065, USA
| | - Marilyn Fraser
- Arthur Ashe Institute for Urban Health, Brooklyn, New York, USA
| | - Grace X Ma
- Center for Asian Health, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA
- Department of Clinical Sciences, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USA
| | - Khursheed Navder
- Hunter College Center for Cancer Health Disparities Research (CCHDR), Hunter College of the City University of New York, 695 Park Avenue, HN310A, New York, 10065, USA
- Nutrition Program, School of Urban Public Health, Hunter College of the City University of New York, New York, USA
| | - Ming-Chin Yeh
- Hunter College Center for Cancer Health Disparities Research (CCHDR), Hunter College of the City University of New York, 695 Park Avenue, HN310A, New York, 10065, USA
- Nutrition Program, School of Urban Public Health, Hunter College of the City University of New York, New York, USA
| | - Olorunseun O Ogunwobi
- Department of Biological Sciences, Hunter College of the City University of New York, New York, USA.
- Hunter College Center for Cancer Health Disparities Research (CCHDR), Hunter College of the City University of New York, 695 Park Avenue, HN310A, New York, 10065, USA.
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Ulanja MB, Moody AE, Beutler BD, Antwi-Amoabeng D, Rahman GA, Alese OB. Early-onset pancreatic cancer: a review of molecular mechanisms, management, and survival. Oncotarget 2022; 13:828-841. [PMID: 35720978 PMCID: PMC9200435 DOI: 10.18632/oncotarget.28242] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Accepted: 05/30/2022] [Indexed: 11/25/2022] Open
Abstract
OBJECTIVES Early-onset pancreatic cancer (EOPC) - defined as pancreatic cancer diagnosed before the age of 50 years - is associated with a poor prognosis as compared to later-onset pancreatic cancer (LOPC). Emerging evidence suggests that EOPC may exhibit a genetic signature and tumor biology that is distinct from that of LOPC. We review genetic mutations that are more prevalent in EOPC relative to LOPC and discuss the potential impact of these mutations on treatment and survival. MATERIALS AND METHODS Using PubMed and Medline, the following terms were searched and relevant citations assessed: "early onset pancreatic cancer," "late onset pancreatic cancer," "pancreatic cancer," "pancreatic cancer genes," and "pancreatic cancer targeted therapy." RESULTS Mutations in CDKN2, FOXC2, and SMAD4 are significantly more common in EOPC as compared to LOPC. In addition, limited data suggest that PI3KCA mutations are more frequently observed in EOPC as compared to LOPC. KRAS mutations are relatively rare in EOPC. CONCLUSIONS Genetic mutations associated with EOPC are distinct from those of LOPC. The preponderance of the evidence suggest that poor outcomes in EOPC are related both to advanced stage of presentation and unique tumor biology. The molecular and genetic features of EOPC warrant further investigation in order to optimize management.
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Affiliation(s)
- Mark B. Ulanja
- Christus Ochsner Saint Patrick Hospital, Lake Charles, LA 70601, USA
| | - Alastair E. Moody
- Department of Anesthesiology, University of Utah, Salt Lake City, UT 84112, USA
| | - Bryce D. Beutler
- Department of Radiology, University of Southern California, Keck School of Medicine, Los Angeles, CA 90033, USA
| | | | - Ganiyu A. Rahman
- Department of Surgery, University of Cape Coast, School of Medical Sciences, Cape Coast, Ghana
| | - Olatunji B. Alese
- Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA
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Zhong J, Liao X, Peng S, Cao J, Liu Y, Liu C, Qiu J, Guan X, Zhang Y, Liu X, Peng S. A Visualized Dynamic Prediction Model for Overall Survival in Elderly Patients With Pancreatic Cancer for Smart Medical Services. Front Public Health 2022; 10:885624. [PMID: 35685764 PMCID: PMC9171143 DOI: 10.3389/fpubh.2022.885624] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Accepted: 04/06/2022] [Indexed: 11/13/2022] Open
Abstract
Background Pancreatic cancer (PC) is a highly malignant tumor of the digestive system. The number of elderly patients with PC is increasing, and older age is related to a worse prognosis. Accurate prognostication is crucial in treatment decisions made for people diagnosed with PC. However, an accurate predictive model for the prognosis of these patients is still lacking. We aimed to construct nomograms for predicting the overall survival (OS) of elderly patients with PC. Methods Patients with PC, older than 65 years old from 2010 to 2015 in the Surveillance, Epidemiology, and End Results database, were selected and randomly divided into training cohort (n = 4,586) and validation cohort (n = 1,966). Data of patients in 2016-2018 (n = 1,761) were used for external validation. Univariable and forward stepwise multivariable Cox analysis was used to determine the independent prognostic factors. We used significant variables in the training set to construct nomograms predicting prognosis. The performance of the models was evaluated for their discrimination and calibration power based on the concordance index (C-index), calibration curve, and the decision curve analysis (DCA). Results Age, insurance, grade, surgery, radiation, chemotherapy, T, N, and American Joint Commission on Cancer were independent predictors for OS and thus were included in our nomogram. In the training cohort and validation cohort, the C-indices of our nomogram were 0.725 (95%CI: 0.715-0.735) and 0.711 (95%CI: 0.695-0.727), respectively. The 1-, 3-, and 5-year areas under receiver operating characteristic curves showed similar results. The calibration curves showed a high consensus between observations and predictions. In the external validation cohort, C-index (0.797, 95%CI: 0.778-0.816) and calibration curves also revealed high consistency between observations and predictions. The nomogram-related DCA curves showed better clinical utility compared to tumor-node-metastasis staging. In addition, we have developed an online prediction tool for OS. Conclusions A web-based prediction model for OS in elderly patients with PC was constructed and validated, which may be useful for prognostic assessment, treatment strategy selection, and follow-up management of these patients.
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Affiliation(s)
- Jiang Zhong
- College of Computer Science, Chongqing University, Chongqing, China
| | - XingShu Liao
- College of Computer Science, Chongqing University, Chongqing, China
| | - Shuang Peng
- General Affairs Section, The People's Hospital of Tongnan District, Chongqing, China
| | - Junyi Cao
- Department of Medical Quality Control, First People's Hospital of Zigong City, Zigong, China
| | - Yue Liu
- Department of Pediatrics, First People's Hospital of Zigong City, Zigong, China
| | - Chunyang Liu
- Scientific Research Department, First People's Hospital of Zigong City, Zigong, China
| | - Ju Qiu
- Scientific Research Department, First People's Hospital of Zigong City, Zigong, China
| | - Xiaoyan Guan
- Department of Pediatrics, First People's Hospital of Zigong City, Zigong, China
| | - Yang Zhang
- College of Medical Information, Chongqing Medical University, Chongqing, China
| | - Xiaozhu Liu
- Department of Cardiology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Shengxian Peng
- Scientific Research Department, First People's Hospital of Zigong City, Zigong, China
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Lin RT, Chen PL, Yang CY, Yeh CC, Lin CC, Huang WH, Chung AK, Lin JT. Risk factors related to age at diagnosis of pancreatic cancer: a retrospective cohort pilot study. BMC Gastroenterol 2022; 22:243. [PMID: 35568803 PMCID: PMC9107247 DOI: 10.1186/s12876-022-02325-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2021] [Accepted: 05/09/2022] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND Increased pancreatic cancer incidence has been observed among younger than in older adults. This pilot study aimed to determine the feasibility of a large study that would compare the age at diagnosis of pancreatic cancer among patients with different risk factors. METHODS We compared the age at diagnosis of pancreatic cancer between groups of pancreatic cancer patients exposed and not exposed to the identified risk factors. We estimated the age at which exposure started, average exposure quantity, and total years of exposure and investigated their relationships with age at diagnosis of pancreatic cancer. RESULTS Sixteen out of 24 (67%) subjects carried known genetic factors and/or had smoking and/or drinking habits; however, an earlier age of pancreatic cancer diagnosis was not observed. Conversely, we found a significant correlation between the age at which alcohol consumption was started and the age at diagnosis of pancreatic cancer (r = 0.8124, P = 0.0043). CONCLUSIONS Our pilot study suggested that a large study following this study design is feasible and that the following should be conducted in a large study: mediation analysis for disease-related factors, advanced genomic analysis for new candidate genes, and the correlation between age of first exposure to risk factors and pancreatic cancer onset.
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Affiliation(s)
- Ro-Ting Lin
- Department of Occupational Safety and Health, College of Public Health, China Medical University, Taichung, 406040 Taiwan
| | - Pei-Lung Chen
- Department of Medical Genetics, National Taiwan University Hospital, Taipei, 100226 Taiwan
- Graduate Institute of Medical Genomics and Proteomics, National Taiwan University, Taipei, 100025 Taiwan
| | - Chi-Ying Yang
- Department of Internal Medicine, Digestive Medicine Center, China Medical University Hospital, Taichung, 404332 Taiwan
| | - Chun-Chieh Yeh
- Department of Surgery, China Medical University Hospital, Taichung, 404332 Taiwan
- Department of Surgery, Asia University Hospital, Taichung, 413505 Taiwan
| | - Chun-Che Lin
- Department of Internal Medicine, Digestive Medicine Center, China Medical University Hospital, Taichung, 404332 Taiwan
| | - Wen-Hsin Huang
- Department of Internal Medicine, Digestive Medicine Center, China Medical University Hospital, Taichung, 404332 Taiwan
| | - An-Ko Chung
- Graduate Institute of Medical Genomics and Proteomics, National Taiwan University, Taipei, 100025 Taiwan
| | - Jaw-Town Lin
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Hospital, No. 1, Yida Rd., Yanchao Dist., Kaohsiung, 824005 Taiwan
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Takeda T, Sasaki T, Inoue Y, Okamoto T, Mori C, Mie T, Furukawa T, Yamada Y, Kasuga A, Matsuyama M, Ozaka M, Takahashi Y, Saiura A, Sasahira N. Early-onset pancreatic cancer: Clinical characteristics and survival outcomes. Pancreatology 2022; 22:507-515. [PMID: 35422382 DOI: 10.1016/j.pan.2022.04.003] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Revised: 03/24/2022] [Accepted: 04/04/2022] [Indexed: 02/08/2023]
Abstract
BACKGROUND Early-onset pancreatic cancer (≤50 years, EOPC) is uncommon. This study aims to characterize the clinical and survival characteristics of EOPC in comparison to late-onset pancreatic cancer (>50 years, LOPC). METHODS We retrospectively investigated consecutive PC patients treated at our institution between 2010 and 2019. We analyzed and compared clinicopathological characteristics, treatments, and outcomes of EOPC and LOPC. RESULTS Of 1646 PC patients identified (768 resectable/borderline resectable; 248 locally advanced; 630 metastatic), 127 (8%) had EOPC. Current smoking and heavy drinking were associated with EOPC. EOPC presented at a more advanced stage and had higher neutrophil-to-lymphocyte ratios than LOPC. Survival outcomes were similar between the two groups, both in the entire cohort and in each resectability group. In patients undergoing resection, EOPC tended to have a higher N stage (p = 0.099) and had a higher pathological stage (stage IV, 20% vs. 7%, p = 0.005) and a lower rate of macroscopically curative resection (80% vs. 93%, p = 0.006). Liver recurrence was more commonly observed in EOPC (42% vs. 23%, p = 0.015). In the metastatic cohort, combination chemotherapy regimens were more frequently administered in EOPC as first-line treatment (79% vs. 64%, p = 0.028). Both median PFS (4.4 vs. 5.3 months, p = 0.647) and OS (11.5 vs. 9.5 months, p = 0.183) were not significantly different between the two groups. CONCLUSIONS EOPC presented with a more aggressive tumor biology. Survival outcomes were similar to LOPC due to more intensive treatment.
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Affiliation(s)
- Tsuyoshi Takeda
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
| | - Takashi Sasaki
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
| | - Yosuke Inoue
- Department of Hepato-Biliary-Pancreatic Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
| | - Takeshi Okamoto
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
| | - Chinatsu Mori
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
| | - Takafumi Mie
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
| | - Takaaki Furukawa
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
| | - Yuto Yamada
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
| | - Akiyoshi Kasuga
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
| | - Masato Matsuyama
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
| | - Masato Ozaka
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
| | - Yu Takahashi
- Department of Hepato-Biliary-Pancreatic Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
| | - Akio Saiura
- Department of Hepato-Biliary-Pancreatic Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan; Department of Hepato-Biliary-Pancreatic Surgery, Juntendo University School of Medicine, Tokyo, Japan.
| | - Naoki Sasahira
- Department of Hepato-Biliary-Pancreatic Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.
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Ma M, Li W, Xu L, Ping F, Zhang H, Li Y. Diabetes duration and weight loss are associated with onset age and remote metastasis of pancreatic cancer in patients with diabetes mellitus. J Diabetes 2022; 14:261-270. [PMID: 35167190 PMCID: PMC9060030 DOI: 10.1111/1753-0407.13259] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2021] [Revised: 01/24/2022] [Accepted: 01/27/2022] [Indexed: 11/28/2022] Open
Abstract
OBJECTIVE To analyze the clinical characteristics of patients with pancreatic cancer (PC) and diabetes and to explore the impact of diabetes duration, weight loss, and hypoglycemic drugs on the tumor biological behavior of PC. METHODS This is a retrospective study on patients with PC and diabetes. Subjects were grouped according to the onset age of PC, distant metastasis, duration of diabetes, degree of weight loss (∆Wt), and type of hypoglycemic drugs. Logistic regression analysis was used to evaluate the association between diabetes duration, weight loss, hypoglycemic drugs, and early-onset PC, distant metastasis. RESULTS Compared with late-onset PC, patients with early-onset PC had a higher proportion of new-onset DM (35 [79.5%] vs. 217 [46.9%], p < 0.001), smoker, drinker, and more obvious weight loss (8.5 [3.8, 15] kg vs. 5 [0, 10] kg, p < 0.001). Patients with remote metastasis had an earlier diagnosis age, heavier weight loss, lower body mass index, and were more likely to be smokers but had cancer less likely to be localized in the head of pancreas. Regression analysis showed that new-onset diabetes and weight loss were independently correlated to early-onset PC: odds ratio (OR) = 3.38 (95% CI 1.36-8.4, p = 0.09; OR = 1.56 (95% CI 1.16-2.1), p = 0.003, respectively. In contrast, long-term diabetes, and heavy weight loss were independently associated with remote metastasis: OR = 3.38 (95% CI 1.36-8.4, p = 0.09; OR = 1.56 (95% CI 1.16-2.1), p = 0.003, respectively. CONCLUSION New-onset diabetes and weight loss were common presentation and risk factors of early-onset PC, which required more attention. Long-term diabetes and heavy weight loss were risk factors contributing to distant metastases, indicating potential risk factors contributing to the adverse prognosis of patients with PC.
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Affiliation(s)
- Minglei Ma
- Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of HealthPeking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical SciencesBeijingChina
- Department of Endocrinology, Beijing Shijitan HospitalCapital Medical UniversityBeijingChina
| | - Wei Li
- Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of HealthPeking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical SciencesBeijingChina
| | - Lingling Xu
- Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of HealthPeking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical SciencesBeijingChina
| | - Fan Ping
- Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of HealthPeking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical SciencesBeijingChina
| | - Huabing Zhang
- Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of HealthPeking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical SciencesBeijingChina
| | - Yuxiu Li
- Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of HealthPeking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical SciencesBeijingChina
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Pijnappel EN, Schuurman M, Wagner AD, de Vos-Geelen J, van der Geest LGM, de Groot JWB, Koerkamp BG, de Hingh IHJT, Homs MYV, Creemers GJ, Cirkel GA, van Santvoort HC, Busch OR, Besselink MG, van Eijck CH, Wilmink JW, van Laarhoven HWM. Sex, Gender and Age Differences in Treatment Allocation and Survival of Patients With Metastatic Pancreatic Cancer: A Nationwide Study. Front Oncol 2022; 12:839779. [PMID: 35402271 PMCID: PMC8987273 DOI: 10.3389/fonc.2022.839779] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Accepted: 02/24/2022] [Indexed: 12/17/2022] Open
Abstract
Background Biological sex, gender and age have an impact on the incidence and outcome in patients with metastatic pancreatic cancer. The aim of this study is to investigate whether biological sex, gender and age are associated with treatment allocation and overall survival (OS) of patients with metastatic pancreatic cancer in a nationwide cohort. Methods Patients with synchronous metastatic pancreatic cancer diagnosed between 2015 and 2019 were selected from the Netherlands Cancer Registry (NCR). The association between biological sex and the probability of receiving systemic treatment were examined with multivariable logistic regression analyses. Kaplan Meier analyses with log-rank test were used to describe OS. Results A total of 7470 patients with metastatic pancreatic cancer were included in this study. Fourty-eight percent of patients were women. Women received less often systemic treatment (26% vs. 28%, P=0.03), as compared to men. Multivariable logistic regression analyses with adjustment for confounders showed that women ≤55 years of age, received more often systemic treatment (OR 1.82, 95% CI 1.24-2.68) compared to men of the same age group. In contrast, women at >55 years of age had a comparable probability to receive systemic treatment compared to men of the same age groups. After adjustment for confounders, women had longer OS compared to men (HR 0.89, 95% CI 0.84-0.93). Conclusion This study found that women in general had a lower probability of receiving systemic treatment compared to men, but this can mainly be explained by age differences. Women had better OS compared to men after adjustment for confounders.
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Affiliation(s)
- Esther N. Pijnappel
- Department of Medical Oncology, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, Netherlands
| | - Melinda Schuurman
- Netherlands Cancer Registry, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, Netherlands
| | - Anna D. Wagner
- Department of Oncology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Judith de Vos-Geelen
- Department of Internal Medicine, Division of Medical Oncology, GROW–School for Oncology and Developmental Biology, Maastricht UMC+, Maastricht, Netherlands
| | - Lydia G. M. van der Geest
- Netherlands Cancer Registry, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, Netherlands
| | | | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, Netherlands
| | | | | | - Geert-Jan Creemers
- Department of Medical Oncology, Catharina Hospital, Eindhoven, Netherlands
| | - Geert A. Cirkel
- Department of Medical Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands
- Department of Medical Oncology, Meander Medical Center, Amersfoort, Netherlands
| | - Hjalmar C. van Santvoort
- Department of Surgery, St Antonius Hospital, Nieuwegein, Netherlands
- Department of Surgery, University Medical Centre Utrecht, Utrecht, Netherlands
| | - Olivier R. Busch
- Department of surgery, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, Netherlands
| | - Marc G. Besselink
- Department of surgery, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, Netherlands
| | | | - Johanna W. Wilmink
- Department of Medical Oncology, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, Netherlands
| | - Hanneke W. M. van Laarhoven
- Department of Medical Oncology, Amsterdam UMC, University of Amsterdam, Cancer Center Amsterdam, Amsterdam, Netherlands
- *Correspondence: Hanneke W. M. van Laarhoven,
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van Dongen JC, van der Geest LGM, de Meijer VE, van Santvoort HC, de Vos-Geelen J, Besselink MG, Groot Koerkamp B, Wilmink JW, van Eijck CHJ. Age and prognosis in patients with pancreatic cancer: a population-based study. Acta Oncol 2022; 61:286-293. [PMID: 34935577 DOI: 10.1080/0284186x.2021.2016949] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
BACKGROUND The diagnosis of pancreatic ductal adenocarcinoma (PDAC) has an enormous impact on patients, and even more so if they are of younger age. It is unclear how their treatment and outcome compare to older patients. This study compares clinicopathological characteristics and overall survival (OS) of PDAC patients aged <60 years to older PDAC patients. METHOD This is a retrospective, population-based cohort study using Netherlands Cancer Registry data of patients diagnosed with PDAC (1 January 2015-31 December 2018). Kaplan-Meier curves and Cox proportional hazards models were used to assess OS. RESULTS Overall, 10,298 patients were included, of whom 1551 (15%) were <60 years. Patients <60 years were more often male, had better performance status, less comorbidities and less stage I disease, and more often received anticancer treatment (67 vs. 33%, p < 0.001) than older patients. Patients <60 years underwent resection of the tumour more often (22 vs. 14%p < 0.001), more often received chemotherapy, and had a better median OS (6.9 vs. 3.3 months, p < 0.001) compared to older patients. No differences in median OS were demonstrated between both age groups of patients who underwent resection (19.7 vs. 19.4 months, p = 0.123), received chemotherapy alone (7.8 vs. 8.5 months, p = 0.191), or received no anticancer treatment (1.8 vs. 1.9 months, p = 0.600). Patients <60 years with stage-IV disease receiving chemotherapy had a somewhat better OS (7.5 vs. 6.3 months, p = 0.026). CONCLUSION Patients with PDAC <60 years more often underwent resection despite less stage I disease and had superior OS. Stratified for treatment, however, survival was largely similar.
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Affiliation(s)
| | | | - Vincent E. de Meijer
- Department of Surgery, University of Groningen, University Medical Centre Groningen, Groningen, Netherlands
| | | | - Judith de Vos-Geelen
- Division of Medical Oncology, Department of Internal Medicine, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, Netherlands
| | - Marc G. Besselink
- Department of Surgery, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
| | - Bas Groot Koerkamp
- Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, Netherlands
| | - Johanna W. Wilmink
- Department of Medical Oncology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands
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Wang D, Ge H, Tian M, Li C, Zhao L, Pei Q, Tan F, Li Y, Ling C, Güngör C. The Survival Effect of Radiotherapy on Stage IIB/III Pancreatic Cancer Undergone Surgery in Different Age and Tumor Site Groups: A Propensity Scores Matching Analysis Based on SEER Database. Front Oncol 2022; 12:799930. [PMID: 35174085 PMCID: PMC8841859 DOI: 10.3389/fonc.2022.799930] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2021] [Accepted: 01/07/2022] [Indexed: 11/23/2022] Open
Abstract
Background It remains controversial whether radiotherapy (RT) improves survival in patients with stage IIB/III PDAC. A growing number of studies have found that patients’ age at diagnosis and tumor site not only affect prognosis, but also may lead to different treatment responses. Therefore, the purpose of this study was to verify whether the survival effect of radiotherapy in patients with stage IIB/III PDAC varies across age and tumor site groups. Methods The target population was selected from PDAC patients undergone surgery in the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2016. This study performed the Pearson’s chi-square test, Cox regression analysis, Kaplan-Meier (K-M) method, and focused on propensity frequency matching analysis. Results Neither neoadjuvant radiotherapy (nRT) nor adjuvant radiotherapy (aRT) patient group had probably improved survival among early-onset patients. For middle-aged patients, nRT seemed to fail to extend overall survival (OS), while aRT might improve the OS. Plus, both nRT and aRT were associated with improved survival in elderly patients. The aRT might be related with survival benefits in patients with pancreatic head cancer, while nRT was not. And RT in patients with PDAC at other sites did not appear to provide a survival benefit. Conclusion Carefully selected data from the SEER database suggested that age and tumor location may be the reference factors to guide the selection of RT for patients with stage IIB/III PDAC. These findings are likely to contribute to the development of personalized treatment for patients with stage IIB/III PDAC.
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Affiliation(s)
- Dan Wang
- Department of General Surgery, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- Department of General Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
| | - Heming Ge
- Department of General Surgery, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Mengxiang Tian
- Department of General Surgery, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Chenglong Li
- Department of General Surgery, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Lilan Zhao
- Department of Thoracic Surgery, Fujian Provincial Hospital, Fuzhou, China
| | - Qian Pei
- Department of General Surgery, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Fengbo Tan
- Department of General Surgery, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
| | - Yuqiang Li
- Department of General Surgery, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- Department of General Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
- *Correspondence: Yuqiang Li, ; Chen Ling,
| | - Chen Ling
- Department of General Surgery, Xiangya Hospital, Central South University, Changsha, China
- National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
- *Correspondence: Yuqiang Li, ; Chen Ling,
| | - Cenap Güngör
- Department of General Visceral and Thoracic Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
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