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Poyia F, Neophytou CM, Christodoulou MI, Papageorgis P. The Role of Tumor Microenvironment in Pancreatic Cancer Immunotherapy: Current Status and Future Perspectives. Int J Mol Sci 2024; 25:9555. [PMID: 39273502 PMCID: PMC11395109 DOI: 10.3390/ijms25179555] [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] [Received: 07/26/2024] [Revised: 08/29/2024] [Accepted: 08/30/2024] [Indexed: 09/15/2024] Open
Abstract
Pancreatic cancer comprises different subtypes, where most cases include ductal adenocarcinoma (PDAC). It is one of the deadliest tumor types, with a poor prognosis. In the majority of patients, the disease has already spread by the time of diagnosis, making full recovery unlikely and increasing mortality risk. Despite developments in its detection and management, including chemotherapy, radiotherapy, and targeted therapies as well as advances in immunotherapy, only in about 13% of PDAC patients does the overall survival exceed 5 years. This may be attributed, at least in part, to the highly desmoplastic tumor microenvironment (TME) that acts as a barrier limiting perfusion, drug delivery, and immune cell infiltration and contributes to the establishment of immunologically 'cold' conditions. Therefore, there is an urgent need to unravel the complexity of the TME that promotes PDAC progression and decipher the mechanisms of pancreatic tumors' resistance to immunotherapy. In this review, we provide an overview of the major cellular and non-cellular components of PDAC TME, as well as their biological interplays. We also discuss the current state of PDAC therapeutic treatments and focus on ongoing and future immunotherapy efforts and multimodal treatments aiming at remodeling the TME to improve therapeutic efficacy.
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Affiliation(s)
- Fotini Poyia
- Tumor Microenvironment, Metastasis and Experimental Therapeutics Laboratory, Basic and Translational Cancer Research Center, Department of Life Sciences, European University Cyprus, Nicosia 2404, Cyprus
| | - Christiana M Neophytou
- Apoptosis and Cancer Chemoresistance Laboratory, Basic and Translational Cancer Research Center, Department of Life Sciences, European University Cyprus, Nicosia 2404, Cyprus
| | - Maria-Ioanna Christodoulou
- Tumor Immunology and Biomarkers Laboratory, Basic and Translational Cancer Research Center, Department of Life Sciences, European University Cyprus, Nicosia 2404, Cyprus
| | - Panagiotis Papageorgis
- Tumor Microenvironment, Metastasis and Experimental Therapeutics Laboratory, Basic and Translational Cancer Research Center, Department of Life Sciences, European University Cyprus, Nicosia 2404, Cyprus
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Pekarek L, Fraile-Martinez O, Garcia-Montero C, Alvarez-Mon MA, Acero J, Ruiz-Llorente L, García-Honduvilla N, Albillos A, Buján J, Alvarez-Mon M, Guijarro LG, Ortega MA. Towards an updated view on the clinical management of pancreatic adenocarcinoma: Current and future perspectives. Oncol Lett 2021; 22:809. [PMID: 34630716 PMCID: PMC8490971 DOI: 10.3892/ol.2021.13070] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Accepted: 09/03/2021] [Indexed: 12/13/2022] Open
Abstract
Pancreatic cancer has a dire prognosis and will represent the second leading cause of cancer death in the next 10 years. The multifactorial approach represents one of the main issues in controlling the extension of this neoplasm. In recent years, the characteristics of the tumor microenvironment, metastasis mechanisms and the relationship between immune system and neoplastic cells have been described, which has made it possible to understand the pathophysiology of pancreatic adenocarcinoma. Currently, there is a failure to provide an effective preventive method or early detection, so patients present with an advanced stage at the time of diagnosis. Despite numerous efforts, little progress has been made in clinical outcome and in improving survival in long term. Therefore, in the recent years, diverse diagnostic tests, treatments and possible approaches have been developed in the fields of radiotherapy, chemotherapy and surgery to find a combination of them that improves life expectancy in patients diagnosed with pancreatic cancer. At the moment, numerous clinical trials are being conducted to evaluate preventive diagnostic procedures such as serological markers or perfecting available imaging tests. On the other hand, implementation of immunotherapy is being studied in a neoplasm that has lagged in the application of this procedure since present possible treatments do not substantially improve quality of life. Therefore, the purpose of our study is to summarize the main progresses that have been made in the diagnosis, treatment and screening of this disease, explaining the limitations that have been observed and analyzing future prospects in the management of this illness.
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Affiliation(s)
- Leonel Pekarek
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, Alcala de Henares, 28871 Madrid, Spain
- Ramón y Cajal Institute of Sanitary Research, 28034 Madrid, Spain
- Oncology Service, Guadalajara University Hospital, 19002 Guadalajara, Spain
| | - Oscar Fraile-Martinez
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, Alcala de Henares, 28871 Madrid, Spain
- Ramón y Cajal Institute of Sanitary Research, 28034 Madrid, Spain
| | - Cielo Garcia-Montero
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, Alcala de Henares, 28871 Madrid, Spain
- Ramón y Cajal Institute of Sanitary Research, 28034 Madrid, Spain
| | - Miguel A. Alvarez-Mon
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, Alcala de Henares, 28871 Madrid, Spain
- Ramón y Cajal Institute of Sanitary Research, 28034 Madrid, Spain
| | - Julio Acero
- Ramón y Cajal Institute of Sanitary Research, 28034 Madrid, Spain
- Department of Surgery, Medical and Social Sciences, Faculty of Medicine and Health Sciences, University of Alcalá, Alcala de Henares, 28871 Madrid, Spain
| | - Lidia Ruiz-Llorente
- Ramón y Cajal Institute of Sanitary Research, 28034 Madrid, Spain
- Unit of Biochemistry and Molecular Biology, Department of System Biology, University of Alcalá, Alcala de Henares, 28871 Madrid, Spain
| | - Natalio García-Honduvilla
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, Alcala de Henares, 28871 Madrid, Spain
- Ramón y Cajal Institute of Sanitary Research, 28034 Madrid, Spain
| | - Agustin Albillos
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, Alcala de Henares, 28871 Madrid, Spain
- Ramón y Cajal Institute of Sanitary Research, 28034 Madrid, Spain
- Department of Gastroenterology and Hepatology, Ramón y Cajal University Hospital, University of Alcalá, Ramón y Cajal Institute for Health Research, 28034 Madrid, Spain
- Biomedical Research Networking Center of Hepatic and Digestive Diseases, Institute of Health Carlos III, 28034 Madrid, Spain
| | - Julia Buján
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, Alcala de Henares, 28871 Madrid, Spain
- Ramón y Cajal Institute of Sanitary Research, 28034 Madrid, Spain
| | - Melchor Alvarez-Mon
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, Alcala de Henares, 28871 Madrid, Spain
- Ramón y Cajal Institute of Sanitary Research, 28034 Madrid, Spain
- Biomedical Research Networking Center of Hepatic and Digestive Diseases, Institute of Health Carlos III, 28034 Madrid, Spain
- Immune System Diseases-Rheumatology, Oncology Service and Internal Medicine, Prince of Asturias University Hospital, Alcala de Henares, 28806 Madrid, Spain
| | - Luis G. Guijarro
- Ramón y Cajal Institute of Sanitary Research, 28034 Madrid, Spain
- Unit of Biochemistry and Molecular Biology, Department of System Biology, University of Alcalá, Alcala de Henares, 28871 Madrid, Spain
- Immune System Diseases-Rheumatology, Oncology Service and Internal Medicine, Prince of Asturias University Hospital, Alcala de Henares, 28806 Madrid, Spain
| | - Miguel A. Ortega
- Department of Medicine and Medical Specialities, Faculty of Medicine and Health Sciences, University of Alcalá, Alcala de Henares, 28871 Madrid, Spain
- Ramón y Cajal Institute of Sanitary Research, 28034 Madrid, Spain
- Cancer Registry and Pathology Department, Prince of Asturias University Hospital, Alcala de Henares, 28806 Madrid, Spain
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Yu W, Hu W, Shui Y, Zhu X, Li C, Ren X, Bai X, Yu R, Shen L, Liang T, Zheng L, Wei Q. Pancreatic cancer adjuvant radiotherapy target volume design: based on the postoperative local recurrence spatial location. Radiat Oncol 2016; 11:138. [PMID: 27756417 PMCID: PMC5070214 DOI: 10.1186/s13014-016-0714-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2016] [Accepted: 10/13/2016] [Indexed: 12/13/2022] Open
Abstract
Objectives To explore the areas at highest risk for postoperative pancreatic cancer local recurrence according to the spatial location of local failures, with the aim to provide a precise target volume for pancreatic cancer adjuvant radiotherapy. Methods Patients with pancreatic cancer who had undergone surgery for the primary tumor in pancreas at our institution from January 2010 to August 2015 were retrospectively analyzed. All local recurrences were plotted on the computed tomography (CT) image of a representative patient according to their relative coordinates to superior mesenteric artery (SMA) or celiac axis (CA). Adjuvant radiation clinical target volume (CTV)-90 and CTV-80 were created to cover 90 % and 80 % plotted recurrences. This planning approach was applied in four simulated cases with comparison to the plan according to RTOG 0848 contouring consensus guidelines. Raystation v4.5.1.14 was used for analyzing high throughput physics data. Results Eighty-three patients with local recurrence were included from 305 postoperative pancreatic cancer patients who did not receive adjuvant radiotherapy. Thirty-one (37 %) patients did not have adjuvant therapy at all, 52 (63 %) patients undergone adjuvant chemotherapy alone. Spatial location of local failure was created. Most recurrences occurred near CA or SMA. CTV-90 was generated through expanding the combined SMA and CA contours by 30 mm right-lateral, 21 mm left-lateral, 20 mm anterior, 13 mm posterior, 10 mm superior, and 20 mm inferior. CTV-80, smaller in volume, was also created for simultaneous integrated boost. Through comparison and analysis of the simulated cases, the radiation volumes proposed were much smaller than those with RTOG 0848 contouring consensus guidelines (average volume: PTV-80 = 120 ml, PTV-90 = 220 ml, RTOG PTV = 490 ml). Accordingly, the organs at risk received less irradiation dose with the proposed CTV-90 and CTV-80. Conclusions Smaller adjuvant radiotherapy CTVs targeting the high-risk local failure areas of postoperative pancreatic cancer were proposed, according to the three-dimensional spatial location of local recurrences. This may help to minimize radiation-related toxicities, achieve dose escalation, and finally reduce local recurrence.
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Affiliation(s)
- Wei Yu
- Department of Radiation Oncology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310009, People's Republic of China
| | - Wei Hu
- Department of Radiation Oncology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310009, People's Republic of China
| | - Yongjie Shui
- Department of Radiation Oncology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310009, People's Republic of China
| | - Xiaoyang Zhu
- Department of Radiation Oncology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310009, People's Republic of China
| | - Chao Li
- Department of Radiation Oncology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310009, People's Republic of China
| | - Xiaoqiu Ren
- Department of Radiation Oncology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310009, People's Republic of China
| | - Xueli Bai
- Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310009, People's Republic of China
| | - Risheng Yu
- Department of Radiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310009, People's Republic of China
| | - Li Shen
- Department of Radiation Oncology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310009, People's Republic of China
| | - Tingbo Liang
- Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310009, People's Republic of China
| | - Lei Zheng
- The Sidney Kimmel Comprehensive Cancer Center, the Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Qichun Wei
- Department of Radiation Oncology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310009, People's Republic of China. .,Department of Radiation Oncology, the Second Affiliated Hospital, Ministry of Education Key Laboratory of Cancer Prevention and Intervention, Zhejiang University School of Medicine, Jiefang Road 88, Hangzhou, 310009, People's Republic of China.
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Roeder F. Neoadjuvant radiotherapeutic strategies in pancreatic cancer. World J Gastrointest Oncol 2016; 8:186-197. [PMID: 26909133 PMCID: PMC4753169 DOI: 10.4251/wjgo.v8.i2.186] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2015] [Revised: 10/12/2015] [Accepted: 12/11/2015] [Indexed: 02/05/2023] Open
Abstract
This review summarizes the current status of neoadjuvant radiation approaches in the treatment of pancreatic cancer, including a description of modern radiation techniques, and an overview on the literature regarding neoadjuvant radio- or radiochemotherapeutic strategies both for resectable and irresectable pancreatic cancer. Neoadjuvant chemoradiation for locally-advanced, primarily non- or borderline resectable pancreas cancer results in secondary resectability in a substantial proportion of patients with consecutively markedly improved overall prognosis and should be considered as possible alternative in pretreatment multidisciplinary evaluations. In resectable pancreatic cancer, outstanding results in terms of response, local control and overall survival have been observed with neoadjuvant radio- or radiochemotherapy in several phase I/II trials, which justify further evaluation of this strategy. Further investigation of neoadjuvant chemoradiation strategies should be performed preferentially in randomized trials in order to improve comparability of the current results with other treatment modalities. This should include the evaluation of optimal sequencing with newer and more potent systemic induction therapy approaches. Advances in patient selection based on new molecular markers might be of crucial interest in this context. Finally modern external beam radiation techniques (intensity-modulated radiation therapy, image-guided radiation therapy and stereotactic body radiation therapy), new radiation qualities (protons, heavy ions) or combinations with alternative boosting techniques widen the therapeutic window and contribute to the reduction of toxicity.
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Wolfgang CL, Herman JM, Laheru DA, Klein AP, Erdek MA, Fishman EK, Hruban RH. Recent progress in pancreatic cancer. CA Cancer J Clin 2013; 63:318-48. [PMID: 23856911 PMCID: PMC3769458 DOI: 10.3322/caac.21190] [Citation(s) in RCA: 676] [Impact Index Per Article: 56.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2013] [Revised: 03/22/2013] [Accepted: 03/22/2013] [Indexed: 02/06/2023] Open
Abstract
Pancreatic cancer is currently one of the deadliest of the solid malignancies. However, surgery to resect neoplasms of the pancreas is safer and less invasive than ever, novel drug combinations have been shown to improve survival, advances in radiation therapy have resulted in less toxicity, and enormous strides have been made in the understanding of the fundamental genetics of pancreatic cancer. These advances provide hope but they also increase the complexity of caring for patients. It is clear that multidisciplinary care that provides comprehensive and coordinated evaluation and treatment is the most effective way to manage patients with pancreatic cancer.
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Affiliation(s)
- Christopher L. Wolfgang
- Department of Surgery, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine
- Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine
| | - Joseph M. Herman
- Department of Radiation Oncology & Molecular Radiation Sciences, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine
| | - Daniel A. Laheru
- Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine
| | - Alison P. Klein
- Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine
- Department of Epidemiology, the Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA
| | - Michael A. Erdek
- Department of Anesthesiology and Critical Care Medicine, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine
| | - Elliot K. Fishman
- Department of Radiology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine
| | - Ralph H. Hruban
- Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine
- Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine
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Wolfgang CL, Herman JM, Laheru DA, Klein AP, Erdek MA, Fishman EK, Hruban RH. Recent progress in pancreatic cancer. CA Cancer J Clin 2013. [PMID: 23856911 DOI: 10.1002/caac.21190] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022] Open
Abstract
Pancreatic cancer is currently one of the deadliest of the solid malignancies. However, surgery to resect neoplasms of the pancreas is safer and less invasive than ever, novel drug combinations have been shown to improve survival, advances in radiation therapy have resulted in less toxicity, and enormous strides have been made in the understanding of the fundamental genetics of pancreatic cancer. These advances provide hope but they also increase the complexity of caring for patients. It is clear that multidisciplinary care that provides comprehensive and coordinated evaluation and treatment is the most effective way to manage patients with pancreatic cancer.
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Affiliation(s)
- Christopher L Wolfgang
- Associate Professor, Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD; Associate Professor, Department of Oncology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD; Associate Professor, Department of Pathology, The Sol Goldman Pancreatic Cancer Research Center, The Johns Hopkins University School of Medicine, Baltimore, MD
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Wang F, Kumar P. The role of radiotherapy in management of pancreatic cancer. J Gastrointest Oncol 2012; 2:157-67. [PMID: 22811846 DOI: 10.3978/j.issn.2078-6891.2011.032] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2011] [Accepted: 07/26/2011] [Indexed: 12/14/2022] Open
Abstract
Pancreatic cancer is one of the leading causes of cancer death. The treatment options in pancreatic cancer remain limited. This review provides an overview of the role of radiotherapy (RT) alone or in combination with systemic treatment at different settings of treatment strategy. Neoadjuvant chemoradiotherapy (CRT) may downstage the borderline resectable disease and make resection possible, which could translate to a survival benefit. Although the benefit of adjuvant CRT remains controversial due to inconsistent outcome of randomized trials, in North America it is still a common recommendation of the treatment. For locally advanced pancreatic cancer, the treatment option could either be chemotherapy or chemoradiotherapy. By using advanced radiotherapy modalities, the toxicity of RT could be reduced and RT dose escalation becomes possible to improve locoregional control.
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Affiliation(s)
- Fen Wang
- Department of Radiation Oncology, University of Kansas Medical Center, Kansas City, Kansas, USA
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Auriemma WS, Berger AC, Bar-Ad V, Boland PM, Cohen SJ, Roche-Lima CMS, Morris GJ. Locally Advanced Pancreatic Cancer. Semin Oncol 2012; 39:e9-22. [DOI: 10.1053/j.seminoncol.2012.05.015] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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Adjuvant stereotactic body radiotherapy for resected pancreatic adenocarcinoma with close or positive margins. J Gastrointest Cancer 2012; 43:70-6. [PMID: 20809393 DOI: 10.1007/s12029-010-9203-7] [Citation(s) in RCA: 36] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
PURPOSE The aim of this study was to evaluate the role of stereotactic body radiotherapy (SBRT) as adjuvant therapy for resected pancreatic adenocarcinoma with close or positive margins. METHODS Between September 2006 and January 2010, 24 patients were treated with adjuvant SBRT following surgical resection. Eight (33.3%) patients had close margins of 1-2.5 mm to the retroperitoneal, vascular structures, and periduodenal adipose tissue. Sixteen (66.7%) patients had positive margins at retroperitoneal margin and vascular structures. Twenty-three patients received 24 Gy (20-24 Gy) in one fraction, and one had 30 Gy in three fractions. The median target volume was 11 cc (4.5-30 cc). Eighteen patients were treated with the Cyberknife® Robotic Radiosurgery System and six patients were treated with Trilogy™ intensity-modulated radiosurgery. Kaplan-Meier survival analyses were used to estimate freedom-from-local-progression (FFLP), and overall survival (OS) rates. PET/CT or CT was used to monitor disease recurrence following SBRT. RESULTS The median follow-up for all patients was 12.5 months (1.4-39.5 months), and among surviving patients it was 16.3 months (2-39.5 months). The FFLP rates at 6 months, 1 and 2 years were 94.7%, 66%, and 44%, respectively. Overall, FFLP was achieved in seven (87.5%) patients with close margins, and 10 (62.5%) with positive margins. After SBRT, 19 patients resumed or started a 6-month course of gemcitabine-based chemotherapy at a median interval of 18 days (range, 9-31 days) post-SBRT. The median OS was 26.7 months and the 1- and 2-year OS rates were 80.4% and 57.2%, respectively. Of the 24 patients, 12 (50%) developed distant metastases of whom two (25%) had close margins and 10 (62.5%) had positive margins. Ten patients (41.7%) were free of progression at last follow-up (range, 3-39.5 months). Three patients (12.5%) had grade 1-2 acute GI toxicities, and two patients (8.3%) had grade 1 and 2 late toxicities. No patients experienced grade 3 or 4 toxicity, including bowel perforation, secondary to SBRT. CONCLUSIONS Our data suggest that adjuvant SBRT for resected pancreatic cancer can be achieved with minimal toxicity. This shorter treatment course allowed initiation of systemic chemotherapy shortly after the completion of SBRT.
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Abstract
INTRODUCTION The revolution of epigenetics has revitalized cancer research, shifting focus away from somatic mutation toward a more holistic perspective involving the dynamic states of chromatin. Disruption of chromatin organization can directly and indirectly precipitate genomic instability and transformation. DISCUSSION One group of epigenetic mediators, the Polycomb group (PcG) proteins, establishes heritable gene repression through methylation of histone tails. Although classically considered regulators of development and cellular differentiation, PcG proteins engage in a variety of neoplastic processes, including cellular proliferation and invasion. Due to their multifaceted potential, PcG proteins rest at the intersection of transcriptional memory and malignancy. Expression levels of PcG proteins hold enormous diagnostic and prognostic value in breast, prostate, and more recently, gastrointestinal cancers. CONCLUSION In this review, we briefly summarize the function of PcG proteins and report the latest developments in understanding their role in pancreatic cancer.
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Sharma C, Eltawil KM, Renfrew PD, Walsh MJ, Molinari M. Advances in diagnosis, treatment and palliation of pancreatic carcinoma: 1990-2010. World J Gastroenterol 2011; 17:867-97. [PMID: 21412497 PMCID: PMC3051138 DOI: 10.3748/wjg.v17.i7.867] [Citation(s) in RCA: 149] [Impact Index Per Article: 10.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2010] [Revised: 12/08/2010] [Accepted: 12/15/2010] [Indexed: 02/06/2023] Open
Abstract
Several advances in genetics, diagnosis and palliation of pancreatic cancer (PC) have occurred in the last decades. A multidisciplinary approach to this disease is therefore recommended. PC is relatively common as it is the fourth leading cause of cancer related mortality. Most patients present with obstructive jaundice, epigastric or back pain, weight loss and anorexia. Despite improvements in diagnostic modalities, the majority of cases are still detected in advanced stages. The only curative treatment for PC remains surgical resection. No more than 20% of patients are candidates for surgery at the time of diagnosis and survival remains quite poor as adjuvant therapies are not very effective. A small percentage of patients with borderline non-resectable PC might benefit from neo-adjuvant chemoradiation therapy enabling them to undergo resection; however, randomized controlled studies are needed to prove the benefits of this strategy. Patients with unresectable PC benefit from palliative interventions such as biliary decompression and celiac plexus block. Further clinical trials to evaluate new chemo and radiation protocols as well as identification of genetic markers for PC are needed to improve the overall survival of patients affected by PC, as the current overall 5-year survival rate of patients affected by PC is still less than 5%. The aim of this article is to review the most recent high quality literature on this topic.
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Affiliation(s)
- Virginia Sun
- Department of Population Sciences, City of Hope, Duarte, Calif, USA
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