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Kersch CN, Grossberg AJ. Perioperative Radiation for Patients with Resectable Pancreatic Cancer: an Updated Review After the Initial RTOG 0848 Results. J Gastrointest Cancer 2025; 56:70. [PMID: 39987276 DOI: 10.1007/s12029-025-01185-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/27/2025] [Indexed: 02/24/2025]
Abstract
PURPOSE Pancreatic cancer remains one of the most lethal malignancies, with limited long-term survival despite advances in treatment strategies. While surgical resection offers the best chance for cure in localized disease, high rates of recurrence underscore the need for effective adjuvant therapies. Over four decades, the role of adjuvant chemoradiation (CRT) has been the subject of significant debate, with numerous trials yielding mixed outcomes regarding its impact on survival. Improvements in chemotherapy regimens and radiotherapy techniques have prompted renewed efforts to define the value of CRT, particularly in comparison to chemotherapy alone. The recent initial results of RTOG 0848 mark a critical milestone in this ongoing discussion, providing contemporary evidence that challenges established assumptions and refines patient selection criteria. By identifying specific subgroups-such as lymph node-negative patients-which may benefit from CRT, the trial offers clarity while highlighting the limitations of CRT in other populations. METHODS Herein, we review prior prospective and retrospective trials that investigated the role of perioperative CRT, in particular radiation therapy, for resectable pancreatic cancer. RESULTS This review examines the trajectory of research on CRT in pancreatic cancer, assesses the implications of RTOG 0848 for current clinical practice, and underscores the importance of further studies to optimize the integration of multimodal therapy in the management of this aggressive disease. CONCLUSION The combination of results from RTOG 0848 in conjunction with the results of prior prospective and retrospective trials lend support for the use of adjuvant RT for patients with both lymph node-negative and lymph node-positive disease. However, several open questions remain about the role of this therapy in select patient cohorts, and whether neoadjuvant versus advent radiation is optimal.
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Affiliation(s)
- Cymon N Kersch
- Department of Radiation Medicine, Oregon Health & Science University, Portland, OR, USA
| | - Aaron J Grossberg
- Department of Radiation Medicine, Oregon Health & Science University, Portland, OR, USA.
- Brenden-Colson Center for Pancreatic Care, Oregon Health & Science University, Portland, OR, USA.
- Cancer Early Detection Advanced Research Center, Oregon Health & Science University, Portland, OR, USA.
- Department of Cell, Developmental, and Cancer Biology, Oregon Health & Science University, Portland, OR, USA.
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Keltner S, Nelson B, Kharofa J. Indications for Radiation in Pancreatic Adenocarcinoma: A Review. Surg Clin North Am 2024; 104:1007-1016. [PMID: 39237160 DOI: 10.1016/j.suc.2024.05.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/07/2024]
Abstract
Pancreatic adenocarcinoma remains a deadly disease with 5 year overall survival of 10% among all stages. Standard of care for resectable disease remains surgical resection and adjuvant systemic therapy, but paradigms for borderline resectable and unresectable cases remain more nuanced. Radiation has been explored in the neoadjuvant, adjuvant, and definitive settings in a variety of randomized and non-randomized trials with mixed results. There is strong evidence to support the use of neoadjuvant radiation for borderline resectable pancreatic cancer. Utilization of radiation in the adjuvant setting remains unclear while the results of radiation therapy oncology group (RTOG) 0848 are pending.
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Affiliation(s)
- Samuel Keltner
- Department of Radiation Oncology, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Bailey Nelson
- Department of Radiation Oncology, University of Cincinnati College of Medicine, Cincinnati, OH, USA
| | - Jordan Kharofa
- Department of Radiation Oncology, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
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Wishart G, Gupta P, Nisbet A, Velliou E, Schettino G. Enhanced effect of X-rays in the presence of a static magnetic field within a 3D pancreatic cancer model. Br J Radiol 2023; 96:20220832. [PMID: 36475863 PMCID: PMC9975369 DOI: 10.1259/bjr.20220832] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Revised: 11/23/2022] [Accepted: 12/02/2022] [Indexed: 12/12/2022] Open
Abstract
OBJECTIVE To evaluate the impact of static magnetic field (SMF) presence on the radiation response of pancreatic cancer cells in polyurethane-based highly macro-porous scaffolds in hypoxic (1% O2) and normoxic (21% O2) conditions, towards understanding MR-guided radiotherapy, shedding light on the potential interaction phenomenon between SMF and radiation in a three-dimensional (3D) microenvironment. METHODS Pancreatic cancer cells (PANC-1, ASPC-1) were seeded into fibronectin-coated highly porous polyethene scaffolds for biomimicry and cultured for 4 weeks in in vitro normoxia (21% O2) followed by a 2-day exposure to either in vitro hypoxia (1% O2) or maintenance in in vitro normoxia (21% O2). The samples were then irradiated with 6 MV photons in the presence or absence of a 1.5 T field. Thereafter, in situ post-radiation monitoring (1 and 7 days post-irradiation treatment) took place via quantification of (i) live dead and (ii) apoptotic profiles. RESULTS We report: (i) pancreatic ductal adenocarcinoma hypoxia-associated radioprotection, in line with our previous findings, (ii) an enhanced effect of radiation in the presence of SMFin in vitro hypoxia (1% O2) for both short- (1 day) and long-term (7 days) post -radiation analysis and (iii) an enhanced effect of radiation in the presence of SMF in in vitro normoxia (21% O2) for long-term (7 days) post-radiation analysis within a 3D pancreatic cancer model. CONCLUSION With limited understanding of the potential interaction phenomenon between SMF and radiation, this 3D system allows combination evaluation for a cancer in which the role of radiotherapy is still evolving. ADVANCES IN KNOWLEDGE This study examined the use of a 3D model to investigate MR-guided radiotherapy in a hypoxic microenvironment, indicating that this could be a useful platform to further understanding of SMF influence on radiation.
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Affiliation(s)
| | | | - Andrew Nisbet
- Department of Medical Physics and Biomedical Engineering, University College London (UCL), London, UK
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Yanagi T, Takama N, Kato E, Baba F, Kitase M, Shimohira M, Sawai H, Kato T, Matsuo Y, Shibamoto Y. Clinical Outcomes of Intraoperative Radiotherapy, Postoperative Radiotherapy, and Definitive Radiotherapy for Non-metastatic Pancreatic Cancer. Kurume Med J 2023; 67:163-170. [PMID: 36450483 DOI: 10.2739/kurumemedj.ms674002] [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] [Indexed: 12/03/2022]
Abstract
OBJECTIVE The aim of this study is to evaluate the utility of adjuvant radiotherapy (intraoperative radiotherapy, IORT; postoperative radiotherapy, PORT), and definitive radiotherapy for non-metastatic pancreatic cancer. METHODS Ninety-nine patients were analyzed. Thirty patients underwent IORT with surgery, 31 underwent PORT after surgery, and 38 underwent definitive radiotherapy. Tumor stage [Union for International Cancer Control (UICC) 2009] was as follows: Stage I, 7; IIA, 16; IIB, 31; III, 45. The doses for IORT, PORT, and definitive radio therapy were 20 to 30, 40 to 64.6, and 50.4 to 61.2 Gy, respectively. Associations between clinical parameters including age, gender, tumor site, stage, performance status, surgical margin, and use of chemotherapy and local control (LC) or overall survival (OS) were analyzed. RESULTS Follow-up periods for all patients were 1.1-145 months (median, 11). OS rate in the IORT, PORT, and definitive radiotherapy groups was 22%, 16%, and 6%, respectively, at 2 years. The 5-year OS rate was 13%, 3.2%, and 0%, respectively. Local control rate at 2 years was 33%, 35%, and 0%, respectively. No Grade ≥ 3 tox icities were observed. Distant metastasis was less common in the IORT group. Stage and surgical margin were sig nificant factors for OS after IORT. Performance status and chemotherapy were significant factors for OS after PORT and definitive radiotherapy. CONCLUSIONS The present study showed the safety of the three treatment modalities, but the outcomes were not satisfactory. More intensive strategies including radiotherapy should be investigated.
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Affiliation(s)
| | | | - Eriko Kato
- Department of Radiation Oncology, Nagoya Medical Center
| | - Fumiya Baba
- Department of Radiation Oncology, Nagoya West Medical Center
| | | | - Masashi Shimohira
- Department of Radiology, Nagoya City University Graduate School of Medical Sciences
| | | | - Tomokatsu Kato
- Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences
| | - Yoichi Matsuo
- Department of Gastroenterological Surgery, Nagoya City University Graduate School of Medical Sciences
| | - Yuta Shibamoto
- Department of Radiology, Nagoya City University Graduate School of Medical Sciences
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Cui J, Jiao F, Li Q, Wang Z, Fu D, Liang J, Liang H, Xia T, Zhang T, Zhang Y, Dai G, Zhang Z, Wang J, Bai Y, Bai Y, Bi F, Chen D, Cao D, Chen J, Fang W, Gao Y, Guo J, Hao J, Hua H, Huang X, Liu W, Liu X, Li D, Li J, Li E, Li Z, Pan H, Shen L, Sun Y, Tao M, Wang C, Wang F, Xiong J, Zhang T, Zhang X, Zhan X, Zheng L, Ren G, Zhang T, Zhou J, Ma Q, Qin S, Hao C, Wang L. Chinese Society of Clinical Oncology (CSCO): Clinical guidelines for the diagnosis and treatment of pancreatic cancer. JOURNAL OF THE NATIONAL CANCER CENTER 2022; 2:205-215. [PMID: 39036552 PMCID: PMC11256594 DOI: 10.1016/j.jncc.2022.08.006] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Revised: 07/30/2022] [Accepted: 08/18/2022] [Indexed: 11/25/2022] Open
Abstract
Pancreatic cancer is one of the leading causes of cancer-related mortality in both developed and developing countries. The incidence of pancreatic cancer in China accounts for about a quater of the global incidence, and the epidemiological characteristics and therapeutic strategies differ due to social, economic, cultural, environmental, and public health factors. Non-domestic guidelines do not reflect the clinicopathologic characteristics and treatment patterns of Chinese patients. Thus, in 2018, the Chinese Society of Clinical Oncology (CSCO) organized a panel of senior experts from all sub-specialties within the field of pancreatic oncology to compile the Chinese guidelines for the diagnosis and treatment of pancreatic cancer. The guidelines were made based on both the Western and Eastern clinical evidence and updated every one or two years. The experts made consensus judgments and classified evidence-based recommendations into various grades according to the regional differences, the accessibility of diagnostic and treatment resources, and health economic indexes in China. Here we present the latest version of the guidelines, which covers the diagnosis, treatment, and follow-up of pancreatic cancer. The guidelines might standardize the diagnosis and treatment of pancreatic cancer in China and will encourage oncologists to design and conduct more clinical trials about pancreatic cancer.
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Affiliation(s)
- Jiujie Cui
- Department of Medical Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Feng Jiao
- Department of Medical Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Qi Li
- Department of Medical Oncology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Zheng Wang
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Deliang Fu
- Department of Pancreatic Surgery, Huashan Hospital, Pancreatic Disease Institute, Fudan University, Shanghai, China
| | - Jun Liang
- Department of Oncology, Peking University International Hospital, Beijing, China
| | - Houjie Liang
- Department of Oncology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing, China
| | - Tingyi Xia
- Beijing Huaxia Jingfang Cancer Radiotherapy Center, Former Air Force General Hospital and PLA General Hospital, Beijing, China
| | - Tao Zhang
- Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yang Zhang
- Department of Oncology, The Second Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Guanghai Dai
- Department of Oncology, Chinese PLA General Hospital, Beijing, China
| | - Zhihong Zhang
- Department of Pathology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jian Wang
- Department of Imaging, Changzheng Hospital, Naval Military Medical University, Shanghai, China
| | - Yongrui Bai
- Department of Radiation Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Yuxian Bai
- Oncology Department of Internal Medicine, Harbin Medical University Cancer Hospital, Harbin, China
| | - Feng Bi
- Department of Medical Oncology, West China Hospital, Sichuan University, Chengdu, China
| | - Donghui Chen
- Department of Medical Oncology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Dan Cao
- Department of Medical Oncology, West China Hospital, Sichuan University, Chengdu, China
| | - Jie Chen
- Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Weijia Fang
- Department of Medical Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China
| | - Yong Gao
- Department of Oncology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Jianwei Guo
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Jihui Hao
- Department of Pancreatic Cancer, National Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
| | - Haiqing Hua
- Department of Medical Oncology, Eastern Theater Command General Hospital, Qinhuai Medical District, Nanjing, China
| | - Xinyu Huang
- Department of General Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Wenchao Liu
- Department of Clinical Oncology, Xijing Hospital, Air Force Medical University, Xian, China
| | - Xiufeng Liu
- Department of Medical Oncology, Eastern Theater Command General Hospital, Qinhuai Medical District, Nanjing, China
| | - Da Li
- Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine, Hangzhou, China
| | - Ji Li
- Department of Pancreatic Surgery, Huashan Hospital, Pancreatic Disease Institute, Fudan University, Shanghai, China
| | - Enxiao Li
- Department of Medical Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Zhiwei Li
- Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China
| | - Hongming Pan
- Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, School of Medicine, Hangzhou, China
| | - Lin Shen
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing, China
| | - Yongwei Sun
- Department of Biliary-Pancreatic Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Renji Hospital, Shanghai, China
| | - Min Tao
- Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - Chengfeng Wang
- State Key Lab of Molecular Oncology & Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Fenghua Wang
- Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Jianping Xiong
- Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Taiping Zhang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xuebin Zhang
- Department of Interventional Oncology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China
| | - Xianbao Zhan
- Department of Medical Oncology, Changhai Hospital of Shanghai, Navy Medical University, Shanghai, China
| | - Leizhen Zheng
- Department of Oncology, Xin Hua Hospital Affiliated To Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Gang Ren
- Peking University Shougang Hospital, Beijing, China
| | - Tingting Zhang
- Oncology Department of Internal Medicine, Harbin Medical University Cancer Hospital, Harbin, China
| | - Jun Zhou
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing, China
| | - Qingyong Ma
- Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Shukui Qin
- Department of Medical Oncology, Eastern Theater Command General Hospital, Qinhuai Medical District, Nanjing, China
| | - Chunyi Hao
- Department of Hepato-Pancreato-Biliary Surgery, Peking University Cancer Hospital, Beijing, China
| | - Liwei Wang
- Department of Medical Oncology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
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Wishart G, Gupta P, Nisbet A, Schettino G, Velliou E. On the Evaluation of a Novel Hypoxic 3D Pancreatic Cancer Model as a Tool for Radiotherapy Treatment Screening. Cancers (Basel) 2021; 13:6080. [PMID: 34885188 PMCID: PMC8657010 DOI: 10.3390/cancers13236080] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Revised: 11/24/2021] [Accepted: 11/30/2021] [Indexed: 12/15/2022] Open
Abstract
Tissue engineering is evolving to mimic intricate ecosystems of tumour microenvironments (TME) to more readily map realistic in vivo niches of cancerous tissues. Such advanced cancer tissue models enable more accurate preclinical assessment of treatment strategies. Pancreatic cancer is a dangerous disease with high treatment resistance that is directly associated with a highly complex TME. More specifically, the pancreatic cancer TME includes (i) complex structure and complex extracellular matrix (ECM) protein composition; (ii) diverse cell populations (e.g., stellate cells), cancer associated fibroblasts, endothelial cells, which interact with the cancer cells and promote resistance to treatment and metastasis; (iii) accumulation of high amounts of (ECM), which leads to the creation of a fibrotic/desmoplastic reaction around the tumour; and (iv) heterogeneous environmental gradients such as hypoxia, which result from vessel collapse and stiffness increase in the fibrotic/desmoplastic area of the TME. These unique hallmarks are not effectively recapitulated in traditional preclinical research despite radiotherapeutic resistance being largely connected to them. Herein, we investigate, for the first time, the impact of in vitro hypoxia (5% O2) on the radiotherapy treatment response of pancreatic cancer cells (PANC-1) in a novel polymer (polyurethane) based highly macroporous scaffold that was surface modified with proteins (fibronectin) for ECM mimicry. More specifically, PANC-1 cells were seeded in fibronectin coated macroporous scaffolds and were cultured for four weeks in in vitro normoxia (21% O2), followed by a two day exposure to either in vitro hypoxia (5% O2) or maintenance in in vitro normoxia. Thereafter, in situ post-radiation monitoring (one day, three days, seven days post-irradiation) of the 3D cell cultures took place via quantification of (i) live/dead and apoptotic profiles and (ii) ECM (collagen-I) and HIF-1a secretion by the cancer cells. Our results showed increased post-radiation viability, reduced apoptosis, and increased collagen-I and HIF-1a secretion in in vitro hypoxia compared to normoxic cultures, revealing hypoxia-induced radioprotection. Overall, this study employed a low cost, animal free model enabling (i) the possibility of long-term in vitro hypoxic 3D cell culture for pancreatic cancer, and (ii) in vitro hypoxia associated PDAC radio-protection development. Our novel platform for radiation treatment screening can be used for long-term in vitro post-treatment observations as well as for fractionated radiotherapy treatment.
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Affiliation(s)
- Gabrielle Wishart
- Bioprocess and Biochemical Engineering Group (BioProChem), Department of Chemical and Process Engineering, University of Surrey, Guildford GU2 7XH, UK; (G.W.); (P.G.)
- Department of Physics, University of Surrey, Guildford GU2 7XH, UK;
| | - Priyanka Gupta
- Bioprocess and Biochemical Engineering Group (BioProChem), Department of Chemical and Process Engineering, University of Surrey, Guildford GU2 7XH, UK; (G.W.); (P.G.)
- Centre for 3D Models of Health and Disease, Department of Targeted Intervention, Division of Surgery and Interventional Science, University College London (UCL), London W1W 7TY, UK
| | - Andrew Nisbet
- Department of Medical Physics and Biomedical Engineering, University College London (UCL), London WC1E 6BT, UK;
| | - Giuseppe Schettino
- Department of Physics, University of Surrey, Guildford GU2 7XH, UK;
- National Physical Laboratory, Teddington TW11 0LW, UK
| | - Eirini Velliou
- Bioprocess and Biochemical Engineering Group (BioProChem), Department of Chemical and Process Engineering, University of Surrey, Guildford GU2 7XH, UK; (G.W.); (P.G.)
- Centre for 3D Models of Health and Disease, Department of Targeted Intervention, Division of Surgery and Interventional Science, University College London (UCL), London W1W 7TY, UK
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Xing J, Yang B, Hou X, Jia N, Gong X, Li X, Zhou N, Cheng Y, Bai C. Prognostic Factors and Effect of Adjuvant Chemoradiation Following Chemotherapy in Resected Pancreatic Cancer Patients With Lymph Node Metastasis or R1 Resection. Front Oncol 2021; 11:660215. [PMID: 34631515 PMCID: PMC8493064 DOI: 10.3389/fonc.2021.660215] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Accepted: 09/06/2021] [Indexed: 12/17/2022] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with a poor prognosis. In resectable PDAC, the recurrence rate is still high even when surgery and adjuvant chemotherapy (CT) are applied. Regional lymph node metastasis and positive margins are associated with higher recurrence risk and worse survival. Adjuvant radiotherapy has been explored, but its efficacy remains controversial. In recent years, some characteristics have been reported to stratify patients who may benefit from adjuvant chemoradiation (CRT), such as lymph node metastasis and margin status. Adjuvant chemotherapy followed by chemoradiation (CT-CRT) was also proposed. A total of 266 patients with resectable PDAC who have lymph node metastasis or R1 resection after surgery were enrolled. In multivariate Cox regression analyses, pancreatic body or tail tumor location (HR 0.433, p<0.0001, compared with pancreatic head) and adjuvant CT predicted a better survival, while there were no significant differences among the different CT regimens. Higher T stage indicated poor survival (stage I: reference; stage II: HR 2.178, p=0.014; stage III: HR 3.581, p=0.001). Propensity score matching was applied in 122 patients to explore the role of CRT. A cohort of 51 patients (31 and 20 patients in the CT and CT-CRT groups, respectively) was generated by matching. Further analyses revealed adjuvant CT-CRT was associated with prolonged survival compared with CT alone (HR 0.284, p=0.014) and less frequent local recurrences (56.5% vs. 21.4% in the CT and CT-CRT group, respectively). However, no significant differences in disease-free survival among these two groups were observed.
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Affiliation(s)
- Jiazhang Xing
- Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Bo Yang
- Department of Radiotherapy, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Xiaorong Hou
- Department of Radiotherapy, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Ning Jia
- Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Xiaolei Gong
- Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Xiaoyuan Li
- Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Na Zhou
- Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Yuejuan Cheng
- Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
| | - Chunmei Bai
- Department of Medical Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
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8
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Arcelli A, Bertini F, Strolin S, Macchia G, Deodato F, Cilla S, Parisi S, Sainato A, Fiore M, Gabriele P, Genovesi D, Cellini F, Guido A, Cammelli S, Buwenge M, Loi E, Bisello S, Renzulli M, Golfieri R, Morganti AG, Strigari L. Definition of Local Recurrence Site in Resected Pancreatic Adenocarcinoma: A Multicenter Study (DOLORES-1). Cancers (Basel) 2021; 13:cancers13123051. [PMID: 34207481 PMCID: PMC8234595 DOI: 10.3390/cancers13123051] [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: 05/05/2021] [Revised: 06/09/2021] [Accepted: 06/15/2021] [Indexed: 11/17/2022] Open
Abstract
Simple Summary Pancreatic cancer remains a disease with a dismal outlook for patients, with high relapse rates after surgery and adjuvant treatments. Thanks to the high conformality achievable with advanced radiotherapy techniques, a more robust definition of clinical target volume (CTV) margins is mandatory. Moreover, a precise CTV definition may affect local control, minimizing radiation-related toxicity and allowing dose escalation. Contrary to two recent studies, RTOG contouring guidelines are not based on a pattern of failure analysis. We provided a local failure risk map in resected pancreatic cancer, validating the results of previous studies. Moreover, according to a new probabilistic approach, we provided new CTV contouring guidelines for the postoperative radiotherapy of pancreatic cancer, modeling targets’ margins on a combination of our validated local failure map (30% of local failures) and RTOG guidelines (70% of local failures). Abstract The study aimed to generate a local failure (LF) risk map in resected pancreatic cancer (PC) and validate the results of previous studies, proposing new guidelines for PC postoperative radiotherapy clinical target volume (CTV) delineation. Follow-up computer tomography (CT) of resected PC was retrospectively reviewed by two radiologists identifying LFs and plotting them on a representative patient CT scan. The percentages of LF points randomly extracted based on CTV following the RTOG guidelines and based on the LF database were 70% and 30%, respectively. According to the Kernel density estimation, an LF 3D distribution map was generated and compared with the results of previous studies using a Dice index. Among the 64 resected patients, 59.4% underwent adjuvant treatment. LFs closer to the root of the celiac axis (CA) or the superior mesenteric artery (SMA) were reported in 32.8% and 67.2% cases, respectively. The mean (± standard deviation) distances of LF points to CA and SMA were 21.5 ± 17.9 mm and 21.6 ± 12.1 mm, respectively. The Dice values comparing our iso-level risk maps corresponding to 80% and 90% of the LF probabilistic density and the CTVs-80 and CTVs-90 of previous publications were 0.45–0.53 and 0.58–0.60, respectively. According to the Kernel density approach, a validated LF map was proposed, modeling a new adjuvant CTV based on a PC pattern of failure.
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Affiliation(s)
- Alessandra Arcelli
- Radiation Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (F.B.); (A.G.); (S.C.); (M.B.); (S.B.); (A.G.M.)
- Department of Experimental, Diagnostic and Specialty Medicine–DIMES, Alma Mater Studiorum, Bologna University, 40138 Bologna, Italy;
- Correspondence: or ; Tel.: +39-051-214-35-64
| | - Federica Bertini
- Radiation Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (F.B.); (A.G.); (S.C.); (M.B.); (S.B.); (A.G.M.)
- Department of Experimental, Diagnostic and Specialty Medicine–DIMES, Alma Mater Studiorum, Bologna University, 40138 Bologna, Italy;
| | - Silvia Strolin
- Medical Physics, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (S.S.); (E.L.); (L.S.)
| | - Gabriella Macchia
- Radiation Oncology Unit, Gemelli Molise Hospital, Università Cattolica del Sacro Cuore, 86100 Campobasso, Italy; (G.M.); (F.D.)
| | - Francesco Deodato
- Radiation Oncology Unit, Gemelli Molise Hospital, Università Cattolica del Sacro Cuore, 86100 Campobasso, Italy; (G.M.); (F.D.)
- Istituto di Radiologia, Università Cattolica del Sacro Cuore, 00168 Roma, Italy;
| | - Savino Cilla
- Medical Physics Unit, Gemelli Molise Hospital, Università Cattolica del Sacro Cuore, 86100 Campobasso, Italy;
| | - Salvatore Parisi
- Unit of Radiation Therapy, IRCCS Casa Sollievo della Sofferenza, 71013 San Giovanni Rotondo, Italy;
| | - Aldo Sainato
- Radiation Oncology, Pisa University Hospital, 56126 Pisa, Italy;
| | - Michele Fiore
- Radiation Oncology, Campus Bio-Medico University, 00128 Rome, Italy;
| | - Pietro Gabriele
- Radiation Therapy, Candiolo Cancer Institute–FPO, IRCCS Candiolo, 10060 Candiolo, Italy;
| | - Domenico Genovesi
- Department of Radiation Oncology, SS. Annunziata Hospital, G. D’Annunzio University of Chieti, 66100 Chieti, Italy;
| | - Francesco Cellini
- Istituto di Radiologia, Università Cattolica del Sacro Cuore, 00168 Roma, Italy;
- Fondazione Policlinico Universitario A. Gemelli, IRCCS, UOC di Radioterapia, Dipartimento di Scienze Radiologiche, Radioterapiche ed Ematologiche, 00168 Roma, Italy
| | - Alessandra Guido
- Radiation Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (F.B.); (A.G.); (S.C.); (M.B.); (S.B.); (A.G.M.)
| | - Silvia Cammelli
- Radiation Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (F.B.); (A.G.); (S.C.); (M.B.); (S.B.); (A.G.M.)
- Department of Experimental, Diagnostic and Specialty Medicine–DIMES, Alma Mater Studiorum, Bologna University, 40138 Bologna, Italy;
| | - Milly Buwenge
- Radiation Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (F.B.); (A.G.); (S.C.); (M.B.); (S.B.); (A.G.M.)
- Department of Experimental, Diagnostic and Specialty Medicine–DIMES, Alma Mater Studiorum, Bologna University, 40138 Bologna, Italy;
| | - Emiliano Loi
- Medical Physics, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (S.S.); (E.L.); (L.S.)
| | - Silvia Bisello
- Radiation Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (F.B.); (A.G.); (S.C.); (M.B.); (S.B.); (A.G.M.)
- Department of Experimental, Diagnostic and Specialty Medicine–DIMES, Alma Mater Studiorum, Bologna University, 40138 Bologna, Italy;
| | - Matteo Renzulli
- Radiology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy;
| | - Rita Golfieri
- Department of Experimental, Diagnostic and Specialty Medicine–DIMES, Alma Mater Studiorum, Bologna University, 40138 Bologna, Italy;
- Radiology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy;
| | - Alessio G. Morganti
- Radiation Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (F.B.); (A.G.); (S.C.); (M.B.); (S.B.); (A.G.M.)
- Department of Experimental, Diagnostic and Specialty Medicine–DIMES, Alma Mater Studiorum, Bologna University, 40138 Bologna, Italy;
| | - Lidia Strigari
- Medical Physics, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy; (S.S.); (E.L.); (L.S.)
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9
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Nehlsen AD, Goodman KA. Controversies in radiotherapy for pancreas cancer. J Surg Oncol 2021; 123:1460-1466. [PMID: 33831248 DOI: 10.1002/jso.26313] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2020] [Accepted: 11/14/2020] [Indexed: 12/31/2022]
Abstract
The management of pancreatic adenocarcinoma remains an area of controversy and ongoing discovery. Despite advances in surgical and radiation techniques, as well as chemotherapeutic agents, outcomes of patients diagnosed with this devastating malignancy remain poor. This article aims to review the available literature evaluating the efficacy of adjuvant, neoadjuvant, and definitive radiation therapy. We will also highlight areas of ongoing research efforts being carried out to improve outcomes in this patient population.
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Affiliation(s)
- Anthony D Nehlsen
- Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, USA
| | - Karyn A Goodman
- Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, USA
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10
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Wishart G, Gupta P, Schettino G, Nisbet A, Velliou E. 3d tissue models as tools for radiotherapy screening for pancreatic cancer. Br J Radiol 2021; 94:20201397. [PMID: 33684308 PMCID: PMC8010544 DOI: 10.1259/bjr.20201397] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Revised: 02/16/2021] [Accepted: 02/17/2021] [Indexed: 12/14/2022] Open
Abstract
The efficiency of radiotherapy treatment regimes varies from tumour to tumour and from patient to patient but it is generally highly influenced by the tumour microenvironment (TME). The TME can be described as a heterogeneous composition of biological, biophysical, biomechanical and biochemical milieus that influence the tumour survival and its' response to treatment. Preclinical research faces challenges in the replication of these in vivo milieus for predictable treatment response studies. 2D cell culture is a traditional, simplistic and cost-effective approach to culture cells in vitro, however, the nature of the system fails to recapitulate important features of the TME such as structure, cell-cell and cell-matrix interactions. At the same time, the traditional use of animals (Xenografts) in cancer research allows realistic in vivo architecture, however foreign physiology, limited heterogeneity and reduced tumour mutation rates impairs relevance to humans. Furthermore, animal research is very time consuming and costly. Tissue engineering is advancing as a promising biomimetic approach, producing 3D models that capture structural, biophysical, biochemical and biomechanical features, therefore, facilitating more realistic treatment response studies for further clinical application. However, currently, the application of 3D models for radiation response studies is an understudied area of research, especially for pancreatic ductal adenocarcinoma (PDAC), a cancer with a notoriously complex microenvironment. At the same time, specific novel and/or more enhanced radiotherapy tumour-targeting techniques such as MRI-guided radiotherapy and proton therapy are emerging to more effectively target pancreatic cancer cells. However, these emerging technologies may have different biological effectiveness as compared to established photon-based radiotherapy. For example, for MRI-guided radiotherapy, the novel use of static magnetic fields (SMF) during radiation delivery is understudied and not fully understood. Thus, reliable biomimetic platforms to test new radiation delivery strategies are required to more accurately predict in vivo responses. Here, we aim to collate current 3D models for radiation response studies of PDAC, identifying the state of the art and outlines knowledge gaps. Overall, this review paper highlights the need for further research on the use of 3D models for pre-clinical radiotherapy screening including (i) 3D (re)-modeling of the PDAC hypoxic TME to allow for late effects of ionising radiation (ii) the screening of novel radiotherapy approaches and their combinations as well as (iii) a universally accepted 3D-model image quantification method for evaluating TME components in situ that would facilitate accurate post-treatment(s) quantitative comparisons.
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Affiliation(s)
| | - Priyanka Gupta
- Bioprocess and Biochemical Engineering Group (BioProChem), Department of Chemical and Process Engineering, University of Surrey, Guildford, UK
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11
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McIntyre CA, Zambirinis CP, Pulvirenti A, Chou JF, Gonen M, Balachandran VP, Kingham TP, D'Angelica MI, Brennan MF, Drebin JA, Jarnagin WR, Allen PJ. Detailed Analysis of Margin Positivity and the Site of Local Recurrence After Pancreaticoduodenectomy. Ann Surg Oncol 2021; 28:539-549. [PMID: 32451945 PMCID: PMC7918294 DOI: 10.1245/s10434-020-08600-9] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2019] [Indexed: 02/06/2023]
Abstract
BACKGROUND The association between a positive surgical margin and local recurrence after resection of pancreatic adenocarcinoma (PDAC) has been reported. Assessment of the location of the a positive margin and the specific site of local recurrence has not been well described. METHODS A prospectively maintained database was queried for patients who underwent R0/R1 pancreaticoduodenectomy for PDAC between 2000 and 2015. The pancreatic, posterior, gastric/duodenal, anterior peritoneal, and bile duct margins were routinely assessed. Postoperative imaging was reviewed for the site of first recurrence, and local recurrence was defined as recurrence located in the remnant pancreas, surgical bed, or retroperitoneal site outside the surgical bed. RESULTS During the study period, 891 patients underwent pancreaticoduodenectomy, and 390 patients had an initial local recurrence with or without distant metastases. The 5-year cumulative incidence of local recurrence by site included the remnant pancreas (4%; 95% confidence interval [CI], 3-5%), the surgical bed (35%; 95% CI, 32-39%), and other regional retroperitoneal site (4%; 95% CI, 3-6%). In the univariate analysis, positive posterior margin (hazard ratio [HR], 1.50; 95% CI, 1.17-1.91; p = 0.001) and positive lymph nodes (HR, 1.36; 95% CI, 1.06-1.75; p = 0.017) were associated with surgical bed recurrence, and in the multivariate analysis, positive posterior margin remained significant (HR, 1.40; 95% CI, 1.09-1.81; p = 0.009). An isolated local recurrence was found in 197 patients, and a positive posterior margin was associated with surgical bed recurrence in this subgroup (HR, 1.51; 95% CI, 1.08-2.10; p = 0.016). CONCLUSION In this study, the primary association between site of margin positivity and site of local recurrence was between the posterior margin and surgical bed recurrence. Given this association and the limited ability to modify this margin intraoperatively, preoperative assessment should be emphasized.
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Affiliation(s)
- Caitlin A McIntyre
- Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan Kettering, New York, NY, USA
| | | | - Alessandra Pulvirenti
- Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan Kettering, New York, NY, USA
| | - Joanne F Chou
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering, New York, NY, USA
| | - Mithat Gonen
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering, New York, NY, USA
| | - Vinod P Balachandran
- Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan Kettering, New York, NY, USA
| | - T Peter Kingham
- Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan Kettering, New York, NY, USA
| | - Michael I D'Angelica
- Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan Kettering, New York, NY, USA
| | - Murray F Brennan
- Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan Kettering, New York, NY, USA
| | - Jeffrey A Drebin
- Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan Kettering, New York, NY, USA
| | - William R Jarnagin
- Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan Kettering, New York, NY, USA
| | - Peter J Allen
- Department of Surgery, Hepatopancreatobiliary Service, Memorial Sloan Kettering, New York, NY, USA.
- Department of Surgery, Hepatopancreatobiliary Service, Duke University School of Medicine, Durham, NC, USA.
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12
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Huguet F, Rivin Del Campo E, Labidi M, Ménard J, Sergent G, Durand B, Quéro L. Cancers gastriques et pancréatiques : la (chimio)radiothérapie néoadjuvante remplacera-t-elle la chimioradiothérapie adjuvante ? Cancer Radiother 2020; 24:493-500. [DOI: 10.1016/j.canrad.2020.05.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2020] [Revised: 05/24/2020] [Accepted: 05/28/2020] [Indexed: 12/24/2022]
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13
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Patel AK, Rodríguez-López JL, Bahary N, Zureikat AH, Burton SA, Heron DE, Olson AC. Patterns of Failure After Adjuvant Stereotactic Body Radiation Therapy for Pancreatic Cancer With Close or Positive Margins. Adv Radiat Oncol 2020; 5:1197-1205. [PMID: 33305081 PMCID: PMC7718532 DOI: 10.1016/j.adro.2020.08.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2020] [Revised: 07/31/2020] [Accepted: 08/19/2020] [Indexed: 12/15/2022] Open
Abstract
Purpose There is no consensus on treatment volumes for adjuvant stereotactic body radiation therapy (SBRT) for pancreatic cancer. Herein, we report patterns of failure after pancreatic SBRT for close/positive margins, which may inform target volume design. Methods and Materials An institutional review board-approved retrospective review of patients with pancreatic adenocarcinoma treated with adjuvant SBRT for close/positive margins from 2009 to 2018 was conducted. Patterns of failure were defined as local (LF) within the tumor bed, regional (RF) within lymph nodes or anastomoses, or distant (DF). The cumulative incidence of locoregional failure was calculated using the cumulative incidence function accounting for the competing risk of death. LFs were mapped to the planning target volume (PTV) and classified as in-field (completely within the PTV), marginal (partially within the PTV), or out-of-field (completely outside the PTV). The location of LFs was compared with the Radiation Therapy Oncology Group 0848 contouring atlas to determine whether standard postoperative radiation therapy volumes would have included the LF. Results Seventy-six patients were treated with adjuvant SBRT for close (51.3%) or positive (48.7%) margins. Most (81.6%) received 36 Gy in 3 fractions, with a median PTV volume of 17.8 cc (interquartile range, 12.1-25.6). With a median follow-up of 17.0 months (interquartile range, 7.3-28.4), crude rates of first isolated LF, isolated RF, and DF +/- LF or RF were 9.2%, 6.6%, and 56.6%, respectively. Two-year cumulative incidences of LF, RF, locoregional failure, and DF were 34.9%, 30.8%, 49.2%, and 60.4%, respectively. Of 28 reviewable LFs, 21.4% were in-field while the remainder were completely outside (60.7%) or partially outside (17.9%) the PTV. Most LFs (92.9%) would have been encompassed by the Radiation Therapy Oncology Group consensus target volumes. Conclusions After adjuvant pancreatic SBRT for close/positive margins, the majority of LFs were outside the PTV but within contemporary target volumes for conventional radiation therapy.
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Affiliation(s)
- Ankur K Patel
- Department of Radiation Oncology, UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Joshua L Rodríguez-López
- Department of Radiation Oncology, UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Nathan Bahary
- Department of Medicine, Division of Oncology, UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Amer H Zureikat
- Department of Surgery, Division of GI Surgical Oncology, UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Steven A Burton
- Department of Radiation Oncology, UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Dwight E Heron
- Department of Radiation Oncology, UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Adam C Olson
- Department of Radiation Oncology, UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
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14
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Tempero MA, Malafa MP, Chiorean EG, Czito B, Scaife C, Narang AK, Fountzilas C, Wolpin BM, Al-Hawary M, Asbun H, Behrman SW, Benson AB, Binder E, Cardin DB, Cha C, Chung V, Dillhoff M, Dotan E, Ferrone CR, Fisher G, Hardacre J, Hawkins WG, Ko AH, LoConte N, Lowy AM, Moravek C, Nakakura EK, O'Reilly EM, Obando J, Reddy S, Thayer S, Wolff RA, Burns JL, Zuccarino-Catania G. Pancreatic Adenocarcinoma, Version 1.2019. J Natl Compr Canc Netw 2020; 17:202-210. [PMID: 30865919 DOI: 10.6004/jnccn.2019.0014] [Citation(s) in RCA: 269] [Impact Index Per Article: 53.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
The NCCN Guidelines for Pancreatic Adenocarcinoma discuss the diagnosis and management of adenocarcinomas of the exocrine pancreas and are intended to assist with clinical decision-making. These NCCN Guidelines Insights discuss important updates to the 2019 version of the guidelines, focusing on postoperative adjuvant treatment of patients with pancreatic cancers.
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Affiliation(s)
| | | | | | | | | | - Amol K Narang
- The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
| | | | | | | | | | - Stephen W Behrman
- St. Jude Children's Research Hospital/The University of Tennessee Health Science Center
| | - Al B Benson
- Robert H. Lurie Comprehensive Cancer Center of Northwestern University
| | - Ellen Binder
- Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
| | | | | | | | - Mary Dillhoff
- The Ohio State University Comprehensive Cancer Center - James Cancer Hospital and Solove Research Institute
| | | | | | | | - Jeffrey Hardacre
- Case Comprehensive Cancer Center/University Hospitals Seidman Cancer Center and Cleveland Clinic Taussig Cancer Institute
| | - William G Hawkins
- Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
| | - Andrew H Ko
- UCSF Helen Diller Family Comprehensive Cancer Center
| | | | | | | | | | | | | | - Sushanth Reddy
- University of Alabama at Birmingham Comprehensive Cancer Center
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15
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Mas L, Schwarz L, Bachet JB. Adjuvant chemotherapy in pancreatic cancer: state of the art and future perspectives. Curr Opin Oncol 2020; 32:356-363. [PMID: 32541325 DOI: 10.1097/cco.0000000000000639] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
PURPOSE OF REVIEW The modalities of management of resectable pancreatic ductal adenocarcinoma (PDAC) have evolved in recent years with new practice guidelines on adjuvant chemotherapy and results of randomized phase III trials. The aim of this review is to describe the state of the art in this setting and to highlight future possible perspectives. RECENT FINDINGS Resectable PDAC is the tumor without vascular contact or a limited venous contact without vein irregularity. Several pathologic and biologic robust prognostic factors such as an R0 resection defined by a margin at least 1 mm have been validated. In phase III trials, the doublet gemcitabine-capecitabine provided a statistically significant, albeit modest overall survival benefit, but failed to show an improvement in relapse-free survival. Similarly, gemcitabine plus nab-paclitaxel did not increase disease-free survival. Modified FOLFIRINOX led to improved disease-free survival, overall survival, and metastasis-free survival, with acceptable toxicity. In the future, prognostic and/or predictive biomarkers could lead the optimization of therapeutic strategies and neoadjuvant treatment could become a standard of care in PDAC. SUMMARY After curative intent resection, modified FOLFIRINOX is the standard of care in adjuvant in fit patients with PDAC. Others regimens (monotherapy or gemcitabine-based) are an option in unfit patients.
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Affiliation(s)
- Léo Mas
- Department of Hepato-gastroenterology, Groupe Hospitalier Pitié Salpêtrière, Paris
| | - Lilian Schwarz
- Department of Digestive Surgery, Rouen University Hospital
- Department of Genomic and Personalized Medicine in Cancer and Neurological Disorders, Normandie University, UNIROUEN, UMR 1245 INSERM, Rouen University Hospital, Rouen
| | - Jean-Baptiste Bachet
- Department of Hepato-gastroenterology, Groupe Hospitalier Pitié Salpêtrière, Paris
- Sorbonne University, UPMC University, Paris, France
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16
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Basics and Frontiers on Pancreatic Cancer for Radiation Oncology: Target Delineation, SBRT, SIB technique, MRgRT, Particle Therapy, Immunotherapy and Clinical Guidelines. Cancers (Basel) 2020; 12:cancers12071729. [PMID: 32610592 PMCID: PMC7407382 DOI: 10.3390/cancers12071729] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2020] [Revised: 06/11/2020] [Accepted: 06/17/2020] [Indexed: 12/17/2022] Open
Abstract
Pancreatic cancer represents a modern oncological urgency. Its management is aimed to both distal and local disease control. Resectability is the cornerstone of treatment aim. It influences the clinical presentation’s definitions as up-front resectable, borderline resectable and locally advanced (unresectable). The main treatment categories are neoadjuvant (preoperative), definitive and adjuvant (postoperative). This review will focus on (i) the current indications by the available national and international guidelines; (ii) the current standard indications for target volume delineation in radiotherapy (RT); (iii) the emerging modern technologies (including particle therapy and Magnetic Resonance [MR]-guided-RT); (iv) stereotactic body radiotherapy (SBRT), as the most promising technical delivery application of RT in this framework; (v) a particularly promising dose delivery technique called simultaneous integrated boost (SIB); and (vi) a multimodal integration opportunity: the combination of RT with immunotherapy.
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17
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Ren H, Wu CR, Aimaiti S, Wang CF. Development and validation of a novel nomogram for predicting the prognosis of patients with resected pancreatic adenocarcinoma. Oncol Lett 2020; 19:4093-4105. [PMID: 32382348 PMCID: PMC7202273 DOI: 10.3892/ol.2020.11495] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2019] [Accepted: 03/06/2020] [Indexed: 12/15/2022] Open
Abstract
The survival prediction for patients with resected pancreatic adenocarcinoma by using the Tumor-Node-Metastasis (TNM) staging system remains limited. A nomogram is a efficient tool that can be used to predict the outcome of patients with various types of malignancy. The present study aimed to develop and validate a nomogram for patients with resected pancreatic adenocarcinoma. A total of 368 patients (258 in the training set and 110 in the validation set) who underwent pancreatic adenocarcinoma resection at the China National Cancer Center between January 2008 and October 2018 were included in the present study. The nomogram was established according to the results from Cox multivariate analysis, which was validated by discrimination and calibration. The area under the receiver operating characteristic curve (AUC) was determined to assess the accuracy of survival predictions. The results from multivariate analysis in the training set demonstrated that blood transfusion, T-stage, N-stage, tumor grade, capsule invasion, carbohydrate antigen 199, neutrophil percentage and adjuvant therapy were independent prognostic factors for overall survival (OS; all P<0.05). Subsequently, a nomogram predicting the 1-year, 3-year and 5-year OS rates, with favorable calibration, was established based on the independent prognostic factors. The concordance indices of the nomogram were higher compared with the TNM staging system in both training and validation sets. Furthermore, a clear risk stratification system based on the nomogram was used to classify patients into the three following groups: Low-risk group (≤168), moderate-risk group (168–255) and high-risk group (>255). The risk stratification system demonstrated an improved ability in predicting the 1-year, 3-year and 5-year OS rates compared with the TNM system (AUC, 0.758, 0.709 and 0.672 vs. AUC, 0.614, 0.604 and 0.568; all P<0.05). The present study developed and validated a nomogram for patients with resected pancreatic adenocarcinoma by including additional independent prognostic factors, including tumor marker, immune index, surgical information, pathological data and adjuvant therapy. Taken together, the results from the present study indicated an improved performance of the nomogram in predicting the prognosis of patients with resected pancreatic adenocarcinoma compared with the TNM staging system.
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Affiliation(s)
- Hu Ren
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China
| | - Chao-Rui Wu
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China
| | - Saderbieke Aimaiti
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China
| | - Cheng-Feng Wang
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, P.R. China
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Fenocchio E, Filippi R, Lombardi P, Quarà V, Milanesio M, Aimar G, Leone F, Aglietta M. Is There a Standard Adjuvant Therapy for Resected Pancreatic Cancer? Cancers (Basel) 2019; 11:E1547. [PMID: 31614884 PMCID: PMC6826876 DOI: 10.3390/cancers11101547] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2019] [Revised: 10/07/2019] [Accepted: 10/11/2019] [Indexed: 12/19/2022] Open
Abstract
Surgical resection remains the only treatment that offers a potential chance of long-term survival. Unfortunately, about 80% of patients treated with curative intent will develop recurrence. Since 2001, adjuvant therapy with gemcitabine or 5-fluorouracyle was recommended. This approach allows a median overall survival (OS) of around 23 months, and 5-year survival of 22%. In recent years, two phase-3 trials investigating new chemotherapy regimens resulted in considerably improved survival times. The doublet gemcitabine-capecitabine has shown improvement in OS from 25.5 to 28 months (p = 0.032) compared to gemcitabine, in the ESPAC-4 trial. Later, preliminary results of PRODIGE 24 trial presented at the 2018 ASCO meeting showed a superiority of a combination chemotherapy regimen with fluorouracil, leucovorin, irinotecan, and oxaliplatin (mFOLFIRINOX) when compared to gemcitabine alone, both in terms of median disease-free survival (21.6 vs. 12.8 months, p < 0.0001) and OS (54.4 vs. 35 months, p = 0.003). Contrary to chemotherapy, the role of adjuvant radiotherapy is still controversial, even in the case of R1 surgery. A randomized trial exploring the role of chemoradiotherapy in this setting is now ongoing in the US (RTOG-0848). Overall, the management of localized pancreatic adenocarcinoma is evolving. In this review, we summarize the current status and the most up-to-date developments in adjuvant treatment.
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Affiliation(s)
- Elisabetta Fenocchio
- Multidisciplinary Outpatient Oncology Clinic, Candiolo Cancer Institute, FPO-IRCCS, Strada Provinciale 142, km 3.95, 10060 Candiolo (TO), Italy.
| | - Roberto Filippi
- Department of Oncology, University of Turin Medical School, Strada Provinciale 142, km 3.95, 10060 Candiolo (TO), Italy.
| | - Pasquale Lombardi
- Department of Oncology, University of Turin Medical School, Strada Provinciale 142, km 3.95, 10060 Candiolo (TO), Italy.
| | - Virginia Quarà
- Department of Oncology, University of Turin Medical School, Strada Provinciale 142, km 3.95, 10060 Candiolo (TO), Italy.
| | - Michela Milanesio
- Department of Oncology, University of Turin Medical School, Strada Provinciale 142, km 3.95, 10060 Candiolo (TO), Italy.
| | - Giacomo Aimar
- Department of Oncology, University of Turin Medical School, Strada Provinciale 142, km 3.95, 10060 Candiolo (TO), Italy.
| | - Francesco Leone
- Division of Medical Oncology, Candiolo Cancer Institute, FPO-IRCCS, Strada Provinciale 142, km 3.95, 10060 Candiolo (TO), Italy.
- Department of Oncology, Azienda Sanitaria Locale di Biella, 13875 Ponderano (BI), Italy.
| | - Massimo Aglietta
- Department of Oncology, University of Turin Medical School, Strada Provinciale 142, km 3.95, 10060 Candiolo (TO), Italy.
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Brunner M, Wu Z, Krautz C, Pilarsky C, Grützmann R, Weber GF. Current Clinical Strategies of Pancreatic Cancer Treatment and Open Molecular Questions. Int J Mol Sci 2019; 20:E4543. [PMID: 31540286 PMCID: PMC6770743 DOI: 10.3390/ijms20184543] [Citation(s) in RCA: 76] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2019] [Revised: 09/11/2019] [Accepted: 09/12/2019] [Indexed: 12/24/2022] Open
Abstract
Pancreatic cancer is one of the most lethal malignancies and is associated with a poor prognosis. Surgery is considered the only potential curative treatment for pancreatic cancer, followed by adjuvant chemotherapy, but surgery is reserved for the minority of patients with non-metastatic resectable tumors. In the future, neoadjuvant treatment strategies based on molecular testing of tumor biopsies may increase the amount of patients becoming eligible for surgery. In the context of non-metastatic disease, patients with resectable or borderline resectable pancreatic carcinoma might benefit from neoadjuvant chemo- or chemoradiotherapy followed by surgeryPatients with locally advanced or (oligo-/poly-)metastatic tumors presenting significant response to (neoadjuvant) chemotherapy should undergo surgery if R0 resection seems to be achievable. New immunotherapeutic strategies to induce potent immune response to the tumors and investigation in molecular mechanisms driving tumorigenesis of pancreatic cancer may provide novel therapeutic opportunities in patients with pancreatic carcinoma and help patient selection for optimal treatment.
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Affiliation(s)
- Maximilian Brunner
- Department of General and Visceral Surgery, Friedrich Alexander University, Krankenhausstraße 12, 91054 Erlangen, Germany.
| | - Zhiyuan Wu
- Department of General and Visceral Surgery, Friedrich Alexander University, Krankenhausstraße 12, 91054 Erlangen, Germany.
| | - Christian Krautz
- Department of General and Visceral Surgery, Friedrich Alexander University, Krankenhausstraße 12, 91054 Erlangen, Germany.
| | - Christian Pilarsky
- Department of General and Visceral Surgery, Friedrich Alexander University, Krankenhausstraße 12, 91054 Erlangen, Germany.
| | - Robert Grützmann
- Department of General and Visceral Surgery, Friedrich Alexander University, Krankenhausstraße 12, 91054 Erlangen, Germany.
| | - Georg F Weber
- Department of General and Visceral Surgery, Friedrich Alexander University, Krankenhausstraße 12, 91054 Erlangen, Germany.
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20
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An international comparison of treatment and short-term overall survival for older patients with pancreatic cancer. J Geriatr Oncol 2019; 10:584-590. [PMID: 30799177 DOI: 10.1016/j.jgo.2019.02.006] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2018] [Revised: 10/29/2018] [Accepted: 02/11/2019] [Indexed: 12/25/2022]
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21
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Morganti AG, Cellini F, Buwenge M, Arcelli A, Alfieri S, Calvo FA, Casadei R, Cilla S, Deodato F, Di Gioia G, Di Marco M, Fuccio L, Bertini F, Guido A, Herman JM, Macchia G, Maidment BW, Miller RC, Minni F, Passoni P, Valentini C, Re A, Regine WF, Reni M, Falconi M, Valentini V, Mattiucci GC. Adjuvant chemoradiation in pancreatic cancer: impact of radiotherapy dose on survival. BMC Cancer 2019; 19:569. [PMID: 31185957 PMCID: PMC6560746 DOI: 10.1186/s12885-019-5790-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2019] [Accepted: 05/31/2019] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND To evaluate the impact of radiation dose on overall survival (OS) in patients treated with adjuvant chemoradiation (CRT) for pancreatic ductal adenocarcinoma (PDAC). METHODS A multicenter retrospective analysis on 514 patients with PDAC (T1-4; N0-1; M0) treated with surgical resection with macroscopically negative margins (R0-1) followed by adjuvant CRT was performed. Patients were stratified into 4 groups based on radiotherapy doses (group 1: < 45 Gy, group 2: ≥ 45 and < 50 Gy, group 3: ≥ 50 and < 55 Gy, group 4: ≥ 55 Gy). Adjuvant chemotherapy was prescribed to 141 patients. Survival functions were plotted using the Kaplan-Meier method and compared through the log-rank test. RESULTS Median follow-up was 35 months (range: 3-120 months). At univariate analysis, a worse OS was recorded in patients with higher preoperative Ca 19.9 levels (≥ 90 U/ml; p < 0.001), higher tumor grade (G3-4, p = 0.004), R1 resection (p = 0.004), higher pT stage (pT3-4, p = 0.002) and positive nodes (p < 0.001). Furthermore, patients receiving increasing doses of CRT showed a significantly improved OS. In groups 1, 2, 3, and 4, median OS was 13.0 months, 21.0 months, 22.0 months, and 28.0 months, respectively (p = 0.004). The significant impact of higher dose was confirmed by multivariate analysis. CONCLUSIONS Increasing doses of CRT seems to favorably impact on OS in adjuvant setting. The conflicting results of randomized trials on adjuvant CRT in PDAC could be due to < 45 Gy dose generally used.
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Affiliation(s)
- Alessio G. Morganti
- Radiation Oncology Center, Department of Experimental, Diagnostic and Specialty Medicine-DIMES, University of Bologna, S. Orsola-Malpighi Hospital, via Giuseppe Massarenti 9, 40138 Bologna, Italy
| | - Francesco Cellini
- UOC Radioterapia Oncologica, Dipartimento di Diagnostica per immagini, Radioterapia Oncologica ed Ematologia, Istituto di Radiologia, Fondazione Policlinico A. Gemelli IRCCS, Università Cattolica Sacro Cuore, Roma, Italy
| | - Milly Buwenge
- Radiation Oncology Center, Department of Experimental, Diagnostic and Specialty Medicine-DIMES, University of Bologna, S. Orsola-Malpighi Hospital, via Giuseppe Massarenti 9, 40138 Bologna, Italy
| | - Alessandra Arcelli
- Radiation Oncology Center, Department of Experimental, Diagnostic and Specialty Medicine-DIMES, University of Bologna, S. Orsola-Malpighi Hospital, via Giuseppe Massarenti 9, 40138 Bologna, Italy
| | - Sergio Alfieri
- Istituto di Clinica Chirurgica, Fondazione Policlinico A. Gemelli IRCCS - Università Cattolica Sacro Cuore, Roma, Italy
| | - Felipe A. Calvo
- Department of Oncology, Hospital General Universitario Gregorio Marañón, Complutense University, Madrid, Spain
| | - Riccardo Casadei
- Department of Medical and Surgical Sciences – DIMEC, University of Bologna, Bologna, Italy
| | - Savino Cilla
- Unit of Medical Physics, Fondazione Giovanni Paolo II, Campobasso, Italy
| | | | - Giancarmine Di Gioia
- Radiation Oncology Center, Department of Experimental, Diagnostic and Specialty Medicine-DIMES, University of Bologna, S. Orsola-Malpighi Hospital, via Giuseppe Massarenti 9, 40138 Bologna, Italy
| | - Mariacristina Di Marco
- Department of Experimental, Diagnostic, and Specialty Medicine - DIMES, Sant’Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy
| | - Lorenzo Fuccio
- Department of Medical and Surgical Sciences – DIMEC, University of Bologna, Bologna, Italy
| | - Federica Bertini
- Radiation Oncology Center, Department of Experimental, Diagnostic and Specialty Medicine-DIMES, University of Bologna, S. Orsola-Malpighi Hospital, via Giuseppe Massarenti 9, 40138 Bologna, Italy
| | - Alessandra Guido
- Radiation Oncology Center, Department of Experimental, Diagnostic and Specialty Medicine-DIMES, University of Bologna, S. Orsola-Malpighi Hospital, via Giuseppe Massarenti 9, 40138 Bologna, Italy
| | - Joseph M. Herman
- Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland USA
| | | | - Bert W. Maidment
- Department of Radiation Oncology, University of Virginia, Charlottesville, Virginia USA
| | - Robert C. Miller
- Department of Radiation Oncology, Mayo Clinic, Rochester, MN USA
| | - Francesco Minni
- Department of Medical and Surgical Sciences – DIMEC, University of Bologna, Bologna, Italy
| | | | - Chiara Valentini
- Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
| | - Alessia Re
- UOC Radioterapia Oncologica, Dipartimento di Diagnostica per immagini, Radioterapia Oncologica ed Ematologia, Istituto di Radiologia, Fondazione Policlinico A. Gemelli IRCCS, Università Cattolica Sacro Cuore, Roma, Italy
| | - William F. Regine
- Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, MD USA
| | | | - Massimo Falconi
- Pancreatic Surgery, Pancreas Translational & Clinical Research Center, San Raffaele Hospital, University “Vita e Salute”, Milan, Italy
| | - Vincenzo Valentini
- UOC Radioterapia Oncologica, Dipartimento di Diagnostica per immagini, Radioterapia Oncologica ed Ematologia, Istituto di Radiologia, Fondazione Policlinico A. Gemelli IRCCS, Università Cattolica Sacro Cuore, Roma, Italy
| | - Gian Carlo Mattiucci
- UOC Radioterapia Oncologica, Dipartimento di Diagnostica per immagini, Radioterapia Oncologica ed Ematologia, Istituto di Radiologia, Fondazione Policlinico A. Gemelli IRCCS, Università Cattolica Sacro Cuore, Roma, Italy
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22
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Overexpression of PODXL/ITGB1 and BCL7B/ITGB1 accurately predicts unfavorable prognosis compared to the TNM staging system in postoperative pancreatic cancer patients. PLoS One 2019; 14:e0217920. [PMID: 31166991 PMCID: PMC6550449 DOI: 10.1371/journal.pone.0217920] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2019] [Accepted: 05/21/2019] [Indexed: 12/26/2022] Open
Abstract
We previously reported that overexpression of PODXL, BCL7B, and ARHGEF4 in pancreatic cancer tissue is correlated with pancreatic cancer-related survival. The aim of this study was to investigate the use of PODXL, BCL7B, ARHGEF4, and the integrin family member ITGB1 as useful markers for the prognosis of postoperative pancreatic cancer patients in comparison with tumor size and the tumor node metastasis (TNM) staging system. Immunohistochemistry was performed using an anti-ITGB1 antibody on 102 samples of pancreatic cancer tissue surgically resected at the University of Kochi Medical School Hospital and the Matsuyama Shimin Hospital. Univariate Cox proportional hazards regression analysis showed that TNM stage and overexpression of PODXL, BCL7B, and ITGB1 were correlated with postoperative survival. However, tumor size was not significantly associated with postoperative prognosis of pancreatic cancer compared to these features. Multivariate Cox proportional hazards regression analysis showed that the overexpression of both PODXL and ITGB1 and overexpression of both BCL7B and ITGB1 increased the hazard ratio (6.27, 95% confidence interval [CI] 2.58-15.21; and 3.93, 95% CI 1.74-8.91, respectively) compared to that of TNM stage (IIA and IIB vs. III and IV; 3.05, 95% CI 1.25-7.42). These results imply that the combination of PODXL with ITGB1 and the combination of BCL7B with ITGB1 accurately predicted the postoperative outcomes of pancreatic cancer patients, and they were superior compared to the TNM staging system. The combination of PODXL with ITGB1 would be particularly useful, as it was the most highly correlated with postoperative outcomes. Importantly, the present results are useful to determine which adjuvant therapy should be selected.
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23
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Tomasello G, Ghidini M, Costanzo A, Ghidini A, Russo A, Barni S, Passalacqua R, Petrelli F. Outcome of head compared to body and tail pancreatic cancer: a systematic review and meta-analysis of 93 studies. J Gastrointest Oncol 2019; 10:259-269. [PMID: 31032093 DOI: 10.21037/jgo.2018.12.08] [Citation(s) in RCA: 58] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Background Even when resectable pancreatic cancer (PC) is associated with a dismal prognosis. Initial presentation varies according with primary tumor location. Aim of this systematic review and meta-analysis was to evaluate the prognosis associated with site (head versus body/tail) in patients with PC. Methods We searched PubMed, Cochrane Library, SCOPUS, Web of Science, EMBASE, Google Scholar, LILACS, and CINAHL databases from inception to March 2018. Studies reporting information on the independent prognostic role of site in PC and comparing overall survival (OS) in head versus body/tail tumors were selected. Data were aggregated using hazard ratios (HRs) for OS of head versus body/tail PC according to fixed- or random-effect model. Results A total of 93 studies including 254,429 patients were identified. Long-term prognosis of head was better than body/tail cancers (HR =0.96, 95% CI: 0.92-0.99; P=0.02). A pooled HR of 0.95 (95% CI: 0.92-0.99, P=0.02) from multivariate analysis only (n=77 publications) showed that head site was an independent prognostic factor for survival. Conclusions Primary tumor location in the head of the pancreas at the time of diagnosis is a predictor of better survival. Such indicator should be acknowledged when designing future studies, in particular in the operable and neoadjuvant setting.
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Affiliation(s)
| | - Michele Ghidini
- Oncology Department, ASST Ospedale di Cremona, Cremona, Italy
| | - Antonio Costanzo
- Surgical Oncology Unit, Surgery Department, ASST Bergamo Ovest, Treviglio (BG), Italy
| | | | - Alessandro Russo
- Surgical Oncology Unit, Surgery Department, ASST Bergamo Ovest, Treviglio (BG), Italy
| | - Sandro Barni
- Oncology Unit, Oncology Department, ASST Bergamo Ovest, Treviglio (BG), Italy
| | | | - Fausto Petrelli
- Oncology Unit, Oncology Department, ASST Bergamo Ovest, Treviglio (BG), Italy
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25
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Bernard ME, Sutera PA, Iarrobino NA, Quan K, Burton SA, Bahary N, Hogg M, Zureikat A, Heron DE. Initial Results of a Prospective Study of Adjuvant Pancreatic Stereotactic Body Radiation Therapy for Close or Positive Margins. Adv Radiat Oncol 2018; 4:294-301. [PMID: 31011674 PMCID: PMC6460098 DOI: 10.1016/j.adro.2018.11.007] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2018] [Accepted: 11/16/2018] [Indexed: 12/31/2022] Open
Abstract
Purpose Patients with close or positive margins after surgery for pancreatic carcinoma are at a high risk for recurrence. Stereotactic body radiation therapy (SBRT) allows for safe dose escalation with great conformity and short duration of treatment. Herein, we report the initial results of a prospective observational study that evaluated the efficacy and safety of this treatment option. Methods and Materials Patients eligible for the study had pathologically proven T1-4N0-1M0 pancreatic adenocarcinoma with a positive margin (≤1 mm) or a close margin defined as <2.5 mm. Patients were treated with either neoadjuvant or adjuvant chemotherapy, if eligible for systemic therapy. All patients received 36 Gy in 3 fractions to the close or positive margin site. Results From February 2013 to January 2018, 50 patients were enrolled with 49 patients treated on protocol and included in the analysis. The median age was 71 years. The median clinical target volume was 11.3 cc and median planning target volume 22.0 cc. The median overall survival was 23.7 months (95% confidence interval, 13.6-33.8). Local progression-free survival at 1 and 2 years was 85% and 77%, respectively. Regional progression-free survival at 1 and 2 years was 73% and 73%, respectively. Distant metastases-free survival was 57% and 49% at 1 and 2 years, respectively. Grade 3+ radiation toxicity was only 4.1% and occurred in 2 patients. Conclusions Adjuvant pancreatic SBRT was shown to be a safe and feasible treatment option for patients with high-risk pancreatic adenocarcinoma and close or positive margins. This is the first prospective study of SBRT in high-risk postoperative pancreatic cancer. Our results yielded significant local and regional control with low rates of acute toxicity. This technique does not interrupt the administration of systemically dosed multiagent chemotherapy and can be safely interdigitated between cycles because SBRT is only 1 week of treatment.
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Affiliation(s)
- Mark E. Bernard
- Department of Radiation Oncology, UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
- Department of Radiation Medicine, University of Kentucky, Lexington, Kentucky
| | - Philip A. Sutera
- Department of Radiation Oncology, UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Nicholas A. Iarrobino
- Department of Radiation Oncology, UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Kimmen Quan
- Department of Radiation Oncology, UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Steven A. Burton
- Department of Radiation Oncology, UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Nathan Bahary
- Department of Medical Oncology, UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Melissa Hogg
- Department of Surgical Oncology, UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Amer Zureikat
- Department of Surgical Oncology, UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
| | - Dwight E. Heron
- Department of Radiation Oncology, UPMC Hillman Cancer Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
- Corresponding author. Department of Radiation Oncology, UPMC Hillman Cancer Center, 5230 Centre Ave, Suite 544, Pittsburgh, PA 15232.
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26
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Nevler A, Muller AJ, Sutanto-Ward E, DuHadaway JB, Nagatomo K, Londin E, O'Hayer K, Cozzitorto JA, Lavu H, Yeo TP, Curtis M, Villatoro T, Leiby BE, Mandik-Nayak L, Winter JM, Yeo CJ, Prendergast GC, Brody JR. Host IDO2 Gene Status Influences Tumor Progression and Radiotherapy Response in KRAS-Driven Sporadic Pancreatic Cancers. Clin Cancer Res 2018; 25:724-734. [PMID: 30266763 DOI: 10.1158/1078-0432.ccr-18-0814] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2018] [Revised: 07/16/2018] [Accepted: 09/25/2018] [Indexed: 12/31/2022]
Abstract
PURPOSE Heritable genetic variations can affect the inflammatory tumor microenvironment, which can ultimately affect cancer susceptibility and clinical outcomes. Recent evidence indicates that IDO2, a positive modifier in inflammatory disease models, is frequently upregulated in pancreatic ductal adenocarcinoma (PDAC). A unique feature of IDO2 in humans is the high prevalence of two inactivating single-nucleotide polymorphisms (SNP), which affords the opportunity to carry out loss-of-function studies directly in humans. In this study, we sought to address whether genetic loss of IDO2 may influence PDAC development and responsiveness to treatment.Experimental Design: Transgenic Ido2 +/+ and Ido2 -/- mice in which oncogenic KRAS is activated in pancreatic epithelial cells were evaluated for PDAC. Two patient data sets (N = 200) were evaluated for the two IDO2-inactivating SNPs together with histologic, RNA expression, and clinical survival data. RESULTS PDAC development was notably decreased in the Ido2 -/- mice (30% vs. 10%, P < 0.05), with a female predominance similar to the association observed for one of the human SNPs. In patients, the biallelic occurrence of either of the two IDO2-inactivating SNPs was significantly associated with markedly improved disease-free survival in response to adjuvant radiotherapy (P < 0.01), a treatment modality that has been highly debated due to its variable efficacy. CONCLUSIONS The results of this study provide genetic support for IDO2 as a contributing factor in PDAC development and argue that IDO2 genotype analysis has the immediate potential to influence the PDAC care decision-making process through stratification of those patients who stand to benefit from adjuvant radiotherapy.
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Affiliation(s)
- Avinoam Nevler
- Departments of Surgery and the Jefferson Pancreas, Biliary and Related Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.,Sidney Kimmel Medical College and Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.,The Dr. P. Borenstein Talpiot Medical Leadership Program (2012), ChaimSheba Medical Center, Israel
| | - Alexander J Muller
- Sidney Kimmel Medical College and Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.,Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, Pennsylvania.,Lankenau Institute for Medical Research, Wynnewood, Pennsylvania
| | | | | | - Kei Nagatomo
- Lankenau Institute for Medical Research, Wynnewood, Pennsylvania
| | - Eric Londin
- Departments of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania
| | - Kevin O'Hayer
- Departments of Surgery and the Jefferson Pancreas, Biliary and Related Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania
| | - Joseph A Cozzitorto
- Departments of Surgery and the Jefferson Pancreas, Biliary and Related Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania
| | - Harish Lavu
- Departments of Surgery and the Jefferson Pancreas, Biliary and Related Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.,Sidney Kimmel Medical College and Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania
| | - Theresa P Yeo
- Departments of Surgery and the Jefferson Pancreas, Biliary and Related Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.,Sidney Kimmel Medical College and Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania
| | - Mark Curtis
- Departments of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania
| | - Tatiana Villatoro
- Departments of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania
| | - Benjamin E Leiby
- Sidney Kimmel Medical College and Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.,Division of Biostatistics, Thomas Jefferson University, Philadelphia, Pennsylvania
| | | | - Jordan M Winter
- Departments of Surgery and the Jefferson Pancreas, Biliary and Related Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.,Sidney Kimmel Medical College and Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania
| | - Charles J Yeo
- Departments of Surgery and the Jefferson Pancreas, Biliary and Related Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.,Sidney Kimmel Medical College and Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania
| | - George C Prendergast
- Sidney Kimmel Medical College and Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania. .,Lankenau Institute for Medical Research, Wynnewood, Pennsylvania.,Departments of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania
| | - Jonathan R Brody
- Departments of Surgery and the Jefferson Pancreas, Biliary and Related Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.,Sidney Kimmel Medical College and Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania
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27
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Mattiucci GC, Morganti AG, Cellini F, Buwenge M, Casadei R, Farioli A, Alfieri S, Arcelli A, Bertini F, Calvo FA, Cammelli S, Fuccio L, Giaccherini L, Guido A, Herman JM, Macchia G, Maidment BW, Miller RC, Minni F, Regine WF, Reni M, Partelli S, Falconi M, Valentini V. Prognostic Impact of Presurgical CA19-9 Level in Pancreatic Adenocarcinoma: A Pooled Analysis. Transl Oncol 2018; 12:1-7. [PMID: 30237099 PMCID: PMC6143718 DOI: 10.1016/j.tranon.2018.08.017] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2018] [Revised: 08/26/2018] [Accepted: 08/29/2018] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND: Presurgical carbohydrate antigen 19-9 (CA19-9) level predicts overall survival (OS) in resected pancreatic adenocarcinoma (PaC). The aim of this pooled analysis was to evaluate if presurgical CA19-9 level can also predict local control (LC) and distant metastasis-free survival (DMFS). METHODS: Seven hundred patients with PaC from eight institutions who underwent surgical resection ± adjuvant treatment between 2000 and 2014 were analyzed. Patients were divided based on four presurgical CA19-9 level cutoffs (5, 37, 100, 353 U/ml). Weibull regression model to identify independent predictors of OS on 404 patients with complete information was fitted. RESULTS: Median follow-up was 17 months (range: 2-225 months). Univariate analysis showed a better prognosis in pT1-2, pN0, diameter <30 mm, or grade 1 tumors and in patients undergoing R0 resection, distal pancreatectomy, or adjuvant chemotherapy and with lower CA19-9 levels. Five-year OS, LC, and DMFS were as follows: CA19-9 <5.0: 5.7%, 47.2%, 17.0%; CA19-9 5.1-37.0: 37.9%, 63.3%, 46.0%; CA19-9 37.1-100.0: 27.1%, 59.4%, 39.0%; CA19-9 100.1-353.0: 17.4%, 43.4%, 26.7%; CA19-9 >353.1: 10.9%, 50.2%, and 23.4%, respectively. At multivariate analysis, CA19-9 >100 and <353 level (P=.002), CA19-9 ≥353.1 (P<.001) level, G3 tumor (P=.002), and tumor diameter >30 mm (P<.001) correlated with worse OS. Patients treated with postoperative chemoradiation doses >50.0 Gy showed improved OS (P<.001). CONCLUSION: Presurgical CA19-9 predicts both OS and pattern of failure. Therefore, CA19-9 should be included in predictive models in order to customize treatments based on prognostic factors. Moreover, future studies should stratify patients according to presurgical CA19-9 level.
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Affiliation(s)
- Gian Carlo Mattiucci
- UOC Radioterapia Oncologica, Dipartimento di Diagnostica per immagini, Radioterapia Oncologica ed Ematologia, Istituto di Radiologia, Fondazione Policlinico A. Gemelli IRCCS - Università Cattolica Sacro Cuore, Roma, Italia
| | - Alessio G Morganti
- Radiation Oncology Center, Dept of Experimental, Diagnostic and Specialty Medicine - DIMES, University of Bologna, Bologna, Italy
| | - Francesco Cellini
- UOC Radioterapia Oncologica, Dipartimento di Diagnostica per immagini, Radioterapia Oncologica ed Ematologia, Istituto di Radiologia, Fondazione Policlinico A. Gemelli IRCCS - Università Cattolica Sacro Cuore, Roma, Italia.
| | - Milly Buwenge
- Radiation Oncology Center, Dept of Experimental, Diagnostic and Specialty Medicine - DIMES, University of Bologna, Bologna, Italy
| | - Riccardo Casadei
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Andrea Farioli
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Sergio Alfieri
- Istituto di Clinica Chirurgica, Fondazione Policlinico A. Gemelli IRCCS - Università Cattolica Sacro Cuore, Roma, Italia
| | - Alessandra Arcelli
- Radiation Oncology Center, Dept of Experimental, Diagnostic and Specialty Medicine - DIMES, University of Bologna, Bologna, Italy
| | - Federica Bertini
- Radiation Oncology Center, Dept of Experimental, Diagnostic and Specialty Medicine - DIMES, University of Bologna, Bologna, Italy
| | - Felipe A Calvo
- Department of Oncology, Hospital General Universitario Gregorio Marañón, Complutense University, Madrid, Spain
| | - Silvia Cammelli
- Radiation Oncology Center, Dept of Experimental, Diagnostic and Specialty Medicine - DIMES, University of Bologna, Bologna, Italy
| | - Lorenzo Fuccio
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - Lucia Giaccherini
- Radiation Oncology Center, Dept of Experimental, Diagnostic and Specialty Medicine - DIMES, University of Bologna, Bologna, Italy
| | - Alessandra Guido
- Radiation Oncology Center, Dept of Experimental, Diagnostic and Specialty Medicine - DIMES, University of Bologna, Bologna, Italy
| | - Joseph M Herman
- Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Mariland, USA
| | - Gabriella Macchia
- Radiotherapy Unit, General Oncology Unit, Fondazione Giovanni Paolo II, Campobasso, Italy
| | - Bert W Maidment
- Department of Radiation Oncology, University of Virginia, Charlottesville, Virginia, USA
| | - Robert C Miller
- Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota, USA
| | - Francesco Minni
- Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy
| | - William F Regine
- Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, Maryland, USA
| | - Michele Reni
- Department of Medical Oncology, IRCCS Ospedale S. Raffaele, Milan, Italy
| | - Stefano Partelli
- Department of Medical Oncology, IRCCS Ospedale S. Raffaele, Milan, Italy
| | - Massimo Falconi
- Pancreatic Surgery, Pancreas Translational & Clinical Research Center, San Raffaele Hospital, University "Vita e Salute", Milan, Italy
| | - Vincenzo Valentini
- UOC Radioterapia Oncologica, Dipartimento di Diagnostica per immagini, Radioterapia Oncologica ed Ematologia, Istituto di Radiologia, Fondazione Policlinico A. Gemelli IRCCS - Università Cattolica Sacro Cuore, Roma, Italia
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Nonmetastatic pancreatic cancer : Improved survival with chemoradiotherapy > 40 Gy after systemic treatment. Strahlenther Onkol 2018; 194:627-637. [PMID: 29497791 PMCID: PMC6008353 DOI: 10.1007/s00066-018-1281-7] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2017] [Accepted: 02/12/2018] [Indexed: 12/25/2022]
Abstract
Purpose The role of radiotherapy (RT) for nonmetastatic pancreatic cancer is still a matter of debate since randomized control trials have shown inconsistent results. The current retrospective single-institution study includes both resected and unresected patients with nonmetastasized pancreatic cancer. The aim is to analyze overall survival (OS) after irradiation combined with induction chemotherapy. Patients and methods Of the 73 patients with nonmetastatic pancreatic cancer eligible for the present analysis, 42 (58%) patients had adjuvant chemoradiotherapy (CRT), while 31 (42%) received CRT as primary treatment. In all, 65 (89%) had chemotherapy at any time before, during, or after RT, and 39 (53%) received concomitant CRT. The median total dose was 50 Gy (range 12–77 Gy), while 61 (84%) patients received >40 Gy. Results With a median follow-up of 22 months (range 1.2–179.8 months), 14 (19%) are still alive and 59 (81%) of the patients have died, whereby 51 (70%) were cancer-related deaths. Median OS and the 2‑year survival rate were 22.9 months (1.2–179.8 months) and 44%, respectively. In addition, 61 (84%) patients treated with >40 Gy had a survival advantage (median OS 23.7 vs. 17.3 months, p = 0.026), as had patients with 4 months minimum of systemic treatment (median OS 27.5 vs. 14.3 months, p = 0.0004). Conclusion CRT with total doses >40 Gy after induction chemotherapy leads to improved OS in patients with nonmetastatic pancreatic cancer. Electronic supplementary material The online version of this article (10.1007/s00066-018-1281-7) contains supplementary material, which is available to authorized users.
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Radiation Therapy in Pancreatic Cancer. Radiat Oncol 2018. [DOI: 10.1007/978-3-319-52619-5_43-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2022] Open
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30
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Apisarnthanarax S, Jabbour SK, Liauw SL, Murphy JD, Olsen JR, Chang DT. Gastrointestinal Cancers: Timing Is Everything. Int J Radiat Oncol Biol Phys 2017; 99:1051-1058. [PMID: 29165271 PMCID: PMC10910571 DOI: 10.1016/j.ijrobp.2017.05.040] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2017] [Accepted: 05/24/2017] [Indexed: 11/18/2022]
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Adjuvant chemoradiotherapy (gemcitabine-based) in pancreatic adenocarcinoma: the Pisa University experience. TUMORI JOURNAL 2017; 103:577-582. [PMID: 28708229 DOI: 10.5301/tj.5000664] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/12/2017] [Indexed: 12/16/2022]
Abstract
INTRODUCTION The role of adjuvant chemoradiotherapy in patients with pancreatic adenocarcinoma (PA) is controversial. In this study we aimed to assess the feasibility, disease-free survival (DFS) and overall survival (OS) of adjuvant chemoradiotherapy (gemcitabine based) in patients with resected PA and their correlation with prognostic factors. METHODS 122 resected patients (stage ≥IIa) treated between February 1999 and December 2013 were analyzed. Two cycles of gemcitabine (1,000 mg/m2 on days 1, 8 and 15 every 28 days) were administered before concomitant radiotherapy (45 Gy/25 fractions) and chemotherapy (gemcitabine 300 mg/m2 weekly). RESULTS Median follow-up was 22.7 months (range 4-109). Gastrointestinal toxicity (G3), neutropenia (G3-G4) and cardiac toxicity (G2-G3) were observed in 2.4%, 10.6% and 1.6% of patients, respectively. OS at 12, 24 and 60 months was 79%, 55% and 31%, respectively (median 25 months). Two-year OS in patients with postoperative Karnofsky performance status (KPS) ≤70 and ≥80 was 37.1% and 62.3%, respectively (p<0.0001). OS was better in the group of patients with a postoperative CA 19-9 level ≤100 U/mL (p = 0.014). Median DFS was 17 months. CONCLUSIONS The combination of concomitant gemcitabine and radiotherapy in patients with radically resected PA was well tolerated and associated with a low incidence of local recurrences. Five-year OS was significantly influenced by postoperative KPS and CA 19-9 values.
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Silvestris N, Brunetti O, Vasile E, Cellini F, Cataldo I, Pusceddu V, Cattaneo M, Partelli S, Scartozzi M, Aprile G, Casadei Gardini A, Morganti AG, Valentini V, Scarpa A, Falconi M, Calabrese A, Lorusso V, Reni M, Cascinu S. Multimodal treatment of resectable pancreatic ductal adenocarcinoma. Crit Rev Oncol Hematol 2017; 111:152-165. [PMID: 28259290 DOI: 10.1016/j.critrevonc.2017.01.015] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2016] [Revised: 01/11/2017] [Accepted: 01/24/2017] [Indexed: 01/17/2023] Open
Abstract
After a timing preoperative staging, treatment of resectable pancreatic adenocarcinoma (PDAC) includes surgery and adjuvant therapies, the former representing the initial therapeutic option and the latter aiming to reduce the incidence of both distant metastases (chemotherapy) and locoregional failures (chemoradiotherapy). Herein, we provide a critical overview on the role of multimodal treatment in PDAC and on new opportunities related to current more active poli-chemotherapy regimens, targeted therapies, and the more recent immunotherapy approaches. Moreover, an analysis of pathological markers and clinical features able to help clinicians in the selection of the best therapeutic strategy will be discussed. Lastly, the role of neoadjuvant treatment of initially resectable disease will be considered mostly in patients whose malignancy shows morphological but not clinical or biological criteria of resectability. Depending on the results of these investigational studies, today a multidisciplinary approach can offer the best address therapy for these patients.
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Affiliation(s)
- Nicola Silvestris
- Medical Oncology Unit, Cancer Institute "Giovanni Paolo II", Bari, Italy.
| | - Oronzo Brunetti
- Medical Oncology Unit, Cancer Institute "Giovanni Paolo II", Bari, Italy.
| | - Enrico Vasile
- Department of Oncology, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
| | - Francesco Cellini
- Radiation Oncology Department, Gemelli ART, Università Cattolica del Sacro Cuore, Roma, Italy.
| | - Ivana Cataldo
- ARC-NET Research Centre, University of Verona, Verona, Italy.
| | | | - Monica Cattaneo
- Department of Medical Oncology, University and General Hospital, Udine, Italy.
| | - Stefano Partelli
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Centre, San Raffaele Scientific Institute, 'Vita-Salute' University, Milan, Italy.
| | - Mario Scartozzi
- Medical Oncology Unit, University of Cagliari, Cagliari, Italy.
| | - Giuseppe Aprile
- Department of Medical Oncology, University and General Hospital, Udine, Italy; Department of Medical Oncology, General Hospital of Vicenza, Vicenza, Italy.
| | | | - Alessio Giuseppe Morganti
- Radiation Oncology Center, Dept. of Experimental, Diagnostic and Specialty Medicine - DIMES, University of Bologna, Italy.
| | - Vincenzo Valentini
- Radiation Oncology Department, Gemelli ART, Università Cattolica del Sacro Cuore, Roma, Italy.
| | - Aldo Scarpa
- ARC-NET Research Centre, University of Verona, Verona, Italy.
| | - Massimo Falconi
- Pancreatic Surgery Unit, Pancreas Translational and Clinical Research Centre, San Raffaele Scientific Institute, 'Vita-Salute' University, Milan, Italy.
| | - Angela Calabrese
- Radiology Unit, Cancer Institute "Giovanni Paolo II", Bari, Italy.
| | - Vito Lorusso
- Medical Oncology Unit, Cancer Institute "Giovanni Paolo II", Bari, Italy.
| | - Michele Reni
- Medical Oncology Department, IRCCS San Raffaele Scientific Institute, Milan, Italy.
| | - Stefano Cascinu
- Modena Cancer Center, Policlinico di Modena Università di Modena e Reggio Emilia, Italy.
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Kantor O, Talamonti MS, Lutfi W, Wang CH, Winchester DJ, Marsh R, Prinz RA, Baker MS. External radiation is associated with limited improvement in overall survival in resected margin-negative stage IIB pancreatic adenocarcinoma. Surgery 2016; 160:1466-1476. [DOI: 10.1016/j.surg.2016.07.033] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2016] [Revised: 05/26/2016] [Accepted: 07/19/2016] [Indexed: 11/26/2022]
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Nayır E, Ermis E. Chemoradiation of pancreatic carcinoma. JOURNAL OF ONCOLOGICAL SCIENCES 2016. [DOI: 10.1016/j.jons.2016.10.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
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GONG JUN, TULI RICHARD, SHINDE ARVIND, HENDIFAR ANDREWE. Meta-analyses of treatment standards for pancreatic cancer. Mol Clin Oncol 2016; 4:315-325. [PMID: 26998283 PMCID: PMC4774516 DOI: 10.3892/mco.2015.716] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2015] [Accepted: 11/23/2015] [Indexed: 01/05/2023] Open
Abstract
Pancreatic cancer is the most lethal common cancer with an estimated 5-year survival rate of 6-7% (across all stages). The only potential curative therapy is surgical resection in those with localized disease. Adjuvant (postoperative) therapy confers a survival advantage over postoperative observation alone. Neoadjuvant (preoperative) therapy offers the potential to downstage initially unresectable tumors for resection, sterilize resection margins and decrease locoregional recurrence, and identify a subset of patients with aggressive disease for whom surgery will not be beneficial. Induction chemotherapy followed by consolidation chemoradiation is another recommended approach in those with locally advanced disease. For those who cannot be downstaged, cannot tolerate surgery, or were diagnosed with metastatic disease, treatment remains palliative with chemotherapy being a critical component of this approach. Recently, intensive combination chemotherapy has been shown to improve survival rates in comparison to gemcitabine alone in advanced disease. The past few decades have afforded an accumulation of high-level evidence regarding neoadjuvant, adjuvant and palliative therapies in pancreatic cancer. There are numerous reviews discussing recent retrospective studies, prospective studies and randomized controlled trials in each of these areas. However, reviews of optimal and recommended treatment strategies across all stages of pancreatic cancer that focus on the highest levels of hierarchical evidence, such as meta-analyses, are limited. The discussion of novel therapeutics is beyond the scope of this review. However, an extensive and the most current collection of meta-analyses of first-line systemic and locoregional treatment options for all stages of pancreatic cancer to date has been accumulated.
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Affiliation(s)
- JUN GONG
- Department of Internal Medicine, Samuel Oschin Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - RICHARD TULI
- Department of Radiation Oncology, Samuel Oschin Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - ARVIND SHINDE
- Department of Hematology and Oncology, Samuel Oschin Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - ANDREW E. HENDIFAR
- Gastrointestinal and Neuroendocrine Malignancies, Samuel Oschin Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
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Lim YJ, Kim K, Chie EK, Kim B, Ha SW. Role of Adjuvant Radiotherapy in Left-Sided Pancreatic Cancer-Population-Based Analysis with Propensity Score Matching. J Gastrointest Surg 2015; 19:2183-91. [PMID: 26376994 DOI: 10.1007/s11605-015-2941-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/25/2015] [Accepted: 09/08/2015] [Indexed: 01/31/2023]
Abstract
This population-based study evaluated the survival impact of postoperative radiotherapy (PORT) in left-sided pancreatic cancer. The Surveillance, Epidemiology, and End Results (SEER) database was used to identify patients with surgically resected left-sided pancreatic adenocarcinoma from 2004 to 2010. Propensity score matching was conducted to compare PORT and non-PORT groups. A total of 445 patients were identified, and PORT was performed in 180 (40 %) patients. In the unmatched population, there were no significant differences in overall survival (OS) (P = 0.197) and cause-specific survival (CSS) (P = 0.379) between the PORT and non-PORT groups. After propensity score matching, the patients treated with PORT had longer median OS (P = 0.012) and CSS (P = 0.039) than the non-PORT group. In propensity-adjusted multivariate analysis, non-receipt of PORT was a poor prognostic factor in OS (hazard ratio [HR] 1.39, 95 % confidence interval [CI] 1.08-1.79), and CSS (HR 1.31, 95 % CI 1.01-1.71). The log odds of positive lymph nodes (LOODS) (≥-0.73) was also associated with worse OS (P = 0.003) and CSS (P = 0.001). In left-sided pancreatic cancer, considering the addition of PORT is a reasonable option as in pancreatic head cancer. The LOODS was suggested as a strong predictive indicator of the patients' prognoses.
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Affiliation(s)
- Yu Jin Lim
- Department of Radiation Oncology, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Republic of Korea
| | - Kyubo Kim
- Department of Radiation Oncology, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Republic of Korea.
| | - Eui Kyu Chie
- Department of Radiation Oncology, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Republic of Korea.,Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul, Republic of Korea
| | - BoKyong Kim
- Department of Radiation Oncology, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Republic of Korea
| | - Sung W Ha
- Department of Radiation Oncology, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 110-744, Republic of Korea.,Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul, Republic of Korea
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Lu F, Poruk KE, Weiss MJ. Surgery for oligometastasis of pancreatic cancer. Chin J Cancer Res 2015; 27:358-67. [PMID: 26361405 DOI: 10.3978/j.issn.1000-9604.2015.05.02] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2015] [Accepted: 04/08/2015] [Indexed: 12/17/2022] Open
Abstract
The incidence of pancreatic adenocarcinoma (PDAC) has steadily increased over the past several decades. The majority of PDAC patients will present with distant metastases, limiting surgical management in this population. Hepatectomy and pulmonary metastasectomy (PM) has been well established for colorectal cancer patients with isolated, resectable hepatic or pulmonary metastatic disease. Recent advancements in effective systemic therapy for PDAC have led to the selection of certain patients where metastectomy may be potentially indicated. However, the indication for resection of oligometastases in PDAC is not well defined. This review will discuss the current literature on the surgical management of metastatic disease for PDAC with a specific focus on surgical resection for isolated hepatic and pulmonary metastases.
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Affiliation(s)
- Fengchun Lu
- 1 Department of General Surgery, Union Hospital, Fujian Medical University, Fuzhou 350001, China ; 2 Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Katherine E Poruk
- 1 Department of General Surgery, Union Hospital, Fujian Medical University, Fuzhou 350001, China ; 2 Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
| | - Matthew J Weiss
- 1 Department of General Surgery, Union Hospital, Fujian Medical University, Fuzhou 350001, China ; 2 Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
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Cid-Arregui A, Juarez V. Perspectives in the treatment of pancreatic adenocarcinoma. World J Gastroenterol 2015; 21:9297-9316. [PMID: 26309356 PMCID: PMC4541382 DOI: 10.3748/wjg.v21.i31.9297] [Citation(s) in RCA: 102] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2015] [Revised: 05/12/2015] [Accepted: 07/18/2015] [Indexed: 02/06/2023] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an incurable lethal disease whose incidence rate is growing. There is no effective screening for detection of early stage tumors and, in most cases, PDAC is diagnosed at advanced disease stages, when radical pancreatic resection is not possible. The aggressive nature of pancreatic tumor cells lies in the complex genetic mechanisms behind their uncontrolled capability to grow and metastasize, which involve essential adaptive changes in cellular metabolism, signaling, adhesion and immunoediting. In addition, PDAC cells promote a dense functional stroma that facilitates tumor resistance to chemotherapy and radiation. During the last two decades, gemcitabine has been the reference for the systemic treatment of PDAC. However, recently, a regimen combining fluorouracil, irinotecan, oxaliplatin, and leucovorin (FOLFIRINOX) and another combining albumin-bound paclitaxel with gemcitabine have shown clear therapeutic advantage in advanced PDAC, with survival outcomes of 11.3 and 8.5 mo on phase III trials, respectively, over single-agent gemcitabine. With the pending issue of their higher toxicities, these regimens set the reference for ongoing and future clinical studies in advanced PDAC. In addition, the efficacy of oral fluoropyrimidine (S-1) has been well documented in Asiatic PDAC patients. The development of therapeutic approaches other than cytotoxic drugs has proven difficult in the past, with only one drug (erlotinib) approved to date. Besides, a number of agents targeting signaling pathways in tumor or stroma cells are being investigated. Likewise, immunotherapies that target PDAC in various ways are the subject of a number of clinical trials. The search for reliable biomarkers with diagnostic and prognostic value using genomics and mass spectrometry methods may facilitate monitoring and refinement of therapies. This review focuses on current understanding of the pathogenesis of PDAC and the latest developments in the treatment of advanced PDAC.
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Morganti AG, Mattiucci GC, Valentini V, van Stiphout RG. In Reply to Yamazaki et al. Int J Radiat Oncol Biol Phys 2015; 91:877-8. [DOI: 10.1016/j.ijrobp.2014.12.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2014] [Indexed: 11/24/2022]
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40
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In Regard to Morganti et al. Int J Radiat Oncol Biol Phys 2015; 91:876. [DOI: 10.1016/j.ijrobp.2014.12.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2014] [Revised: 12/02/2014] [Accepted: 12/02/2014] [Indexed: 12/20/2022]
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