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Lancellotti F, Patel A, Tsaramanidis S, Edy E, Satyadas T, Filobbos R, Jamdar S, Barker S, Siriwardena AK, de Liguori-Carino N. The role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography-derived parameters as prognostic factors in patients undergoing resection for pancreatic ductal adenocarcinoma. Surgery 2025; 181:109271. [PMID: 40081150 DOI: 10.1016/j.surg.2025.109271] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Revised: 01/16/2025] [Accepted: 02/01/2025] [Indexed: 03/15/2025]
Abstract
BACKGROUND The aim of this study is to investigate the role of maximum standardized uptake and tumor-to-liver ratio derived from preoperative 18F-fluorodeoxyglucose positron emission tomography/computed tomography in patients with pancreatic ductal adenocarcinoma. METHODS Patients who underwent pancreatic resection from January 2015 to December 2022 were reviewed. Patients were grouped based on disease-free survival of 1 year, disease-free survival of 6 months, overall survival of 1 year, and resectability. RESULTS A total of 133 patients were included in the study. The median maximum standardized uptake was significantly greater in patients with shorter survival than in those with longer survival (disease-free survival <1 year vs >1 year: 7.1 [4.3-9.1] vs 4.9 [3.3-6.5], P < .001; disease-free survival <6 months vs >6 months: 8 [4.5-9.7] vs 5.2 [3.4-6.8], P = .001; overall survival <1 year vs >1 year: 6.9 [4.4-8.8] vs 5 [3.4-6.9], P = .01). Median maximum standardized uptake was significantly greater in patients with intraoperative findings of unresectable disease than in those who underwent surgical resection (7.4 [5.5-9.5] vs 5.5 [3.8-7.8], P = .02). These findings were consistent for tumor-to-liver ratio for all groupings. The area under the curve based on receiver operating characteristic analysis was 0.7 for both maximum standardized uptake and tumor-to-liver ratio for predicting disease-free survival, overall survival, and resectability. CONCLUSION Preoperative 18F-fluorodeoxyglucose positron emission tomography/computed tomography maximum standardized uptake and tumor-to-liver ratio are indicators of resectability, early recurrence, and poor prognosis in patients with pancreatic ductal adenocarcinoma. A maximum standardized uptake value between 5 and 7 is a potential red flag, and further investigations should be considered before proceeding to a pancreatic resection.
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Affiliation(s)
- Francesco Lancellotti
- Hepatobiliary and Pancreatic Unit, Manchester University NHS FT, UK; Robotic and Minimally Invasive Digestive Surgery Unit, Sant'Anna Hospital, Ferrara, Italy.
| | - Agastya Patel
- Hepatobiliary and Pancreatic Unit, Manchester University NHS FT, UK
| | | | - Elbert Edy
- Hepatobiliary and Pancreatic Unit, Manchester University NHS FT, UK
| | - Thomas Satyadas
- Hepatobiliary and Pancreatic Unit, Manchester University NHS FT, UK
| | - Rafik Filobbos
- Department of Radiology, Manchester University NHS FT, UK
| | - Saurabh Jamdar
- Hepatobiliary and Pancreatic Unit, Manchester University NHS FT, UK
| | - Sharon Barker
- Hepatobiliary and Pancreatic Unit, Manchester University NHS FT, UK
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Dong S, Li W, Li X, Wang Z, Chen Z, Shi H, He R, Chen C, Zhou W. Glucose metabolism and tumour microenvironment in pancreatic cancer: A key link in cancer progression. Front Immunol 2022; 13:1038650. [PMID: 36578477 PMCID: PMC9792100 DOI: 10.3389/fimmu.2022.1038650] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Accepted: 11/28/2022] [Indexed: 12/14/2022] Open
Abstract
Early and accurate diagnosis and treatment of pancreatic cancer (PC) remain challenging endeavors globally. Late diagnosis lag, high invasiveness, chemical resistance, and poor prognosis are unresolved issues of PC. The concept of metabolic reprogramming is a hallmark of cancer cells. Increasing evidence shows that PC cells alter metabolic processes such as glucose, amino acids, and lipids metabolism and require continuous nutrition for survival, proliferation, and invasion. Glucose metabolism, in particular, regulates the tumour microenvironment (TME). Furthermore, the link between glucose metabolism and TME also plays an important role in the targeted therapy, chemoresistance, radiotherapy ineffectiveness, and immunosuppression of PC. Altered metabolism with the TME has emerged as a key mechanism regulating PC progression. This review shed light on the relationship between TME, glucose metabolism, and various aspects of PC. The findings of this study provide a new direction in the development of PC therapy targeting the metabolism of cancer cells.
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Affiliation(s)
- Shi Dong
- The Second School of Clinical Medicine, Lanzhou University, Lanzhou, China
| | - Wancheng Li
- The Second School of Clinical Medicine, Lanzhou University, Lanzhou, China
| | - Xin Li
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, China
| | - Zhengfeng Wang
- Department of General Surgery, The First Hospital of Lanzhou University, Lanzhou, China
| | - Zhou Chen
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, China
| | - Huaqing Shi
- The Second School of Clinical Medicine, Lanzhou University, Lanzhou, China
| | - Ru He
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, China
| | - Chen Chen
- The First School of Clinical Medicine, Lanzhou University, Lanzhou, China
| | - Wence Zhou
- Department of General Surgery, Lanzhou University Second Hospital, Lanzhou, China
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Mokhtar HM, Youssef A, Naguib TM, Magdy AA, Salama SA, Kabel AM, Sabry NM. The Significance of FDG PET/CT-Derived Parameters in Determining Prognosis of Cases with Pancreatic Adenocarcinoma: A Prospective Study. MEDICINA (KAUNAS, LITHUANIA) 2022; 58:1027. [PMID: 36013494 PMCID: PMC9414036 DOI: 10.3390/medicina58081027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/26/2022] [Revised: 07/26/2022] [Accepted: 07/27/2022] [Indexed: 12/24/2022]
Abstract
Background and objectives: Pancreatic adenocarcinoma represents one of the common malignancies with a relatively poor prognosis. However, early detection of this type of cancer may prove to be curable. Recent advancements in the radiological techniques might represent a hope for the early diagnosis and prediction of prognosis of pancreatic adenocarcinoma. This study aimed to assess the prognostic value of the primary tumor volumetric parameters obtained from FDG PET/CT first stage for the overall survival (OS) and progression-free survival (PFS) of patients with pancreatic adenocarcinoma and to explore the possible correlation between serum matrix metalloproteinase-2 (MMP-2) and the patients’ characteristics. Methods: Fifty patients with pancreatic adenocarcinoma were subjected to FDG PET/CT scan. The SUVpeak, SUVmax, and the metabolic tumor volume (MTV) were determined, as well as the SUVmean of the liver. Moreover, serum levels of MMP-2 were assessed. Follow-up of the patients was carried out for sixty months with determination of PFS and OS. Results: Peak SUV ≥ 3.9 was significantly correlated with the primary pancreatic lesions’ mean total glycolytic activity of >92 g, and MTV and was directly correlated with mortality. There was a positive correlation between peak SUV ≥ 3.9 and 50% SUVmax threshold > 82. Moreover, there was significant correlation between the total glycolytic activity and the studied clinicopathologic factors, except the age and sex of the patients and ECOG performance status. In addition, FDG uptake and the tumor glycolytic activity were substantially linked with a shorter PFS. Similarly, a strong correlation was found between MTV and PFS. Serum MMP-2 levels showed a significant relationship with the performance status, tumor stage, SUVmax threshold, and the glycolytic activity. Conclusions: Peak SUV, main lesion SUVmax, serum MMP-2, and the tumor glycolytic activity are good predictors of PFS of patients with pancreatic adenocarcinoma.
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Affiliation(s)
- Hwaida M. Mokhtar
- Radiodiagnosis Department, Faculty of Medicine, Tanta University, Tanta 31527, Egypt;
| | - Amira Youssef
- Clinical Pathology Department, Faculty of Medicine, Tanta University, Tanta 31527, Egypt;
| | - Tamer M. Naguib
- Anesthesia and ICU Department, Faculty of Medicine, Tanta University, Tanta 31527, Egypt; (T.M.N.); (A.A.M.)
| | - Amr A. Magdy
- Anesthesia and ICU Department, Faculty of Medicine, Tanta University, Tanta 31527, Egypt; (T.M.N.); (A.A.M.)
| | - Samir A. Salama
- Division of Biochemistry, Department of Pharmacology, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia;
| | - Ahmed M. Kabel
- Department of Pharmacology, Faculty of Medicine, Tanta University, Tanta 31527, Egypt
| | - Nesreen M. Sabry
- Clinical Oncology Department, Faculty of Medicine, Tanta University, Tanta 31527, Egypt;
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Einama T, Yamagishi Y, Takihata Y, Konno F, Kobayashi K, Yonamine N, Fujinuma I, Tsunenari T, Kouzu K, Nakazawa A, Iwasaki T, Shinto E, Ishida J, Ueno H, Kishi Y. Clinical Impact of Dual Time Point 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography Fusion Imaging in Pancreatic Cancer. Cancers (Basel) 2022; 14:cancers14153688. [PMID: 35954351 PMCID: PMC9367454 DOI: 10.3390/cancers14153688] [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: 05/15/2022] [Revised: 07/13/2022] [Accepted: 07/13/2022] [Indexed: 01/27/2023] Open
Abstract
We examined the value of preoperative dual time point (DTP) 18F-fluorodeoxyglucose positron emission tomography/computed tomography fusion imaging (FDG PET/CT) as a predictor of early recurrence or the outcomes in patients with pancreatic cancer. Standardized uptake values (SUVs) in DTP FDG PET/CT were performed as preoperative staging. SUVmax1 and SUVmax2 were obtained in 60 min and 120 min, respectively. ΔSUVmax% was defined as (SUVmax2 − SUVmax1)/SUVmax1 × 100. The optimal cut-off values for SUVmax parameters were selected based on tumor relapse within 1 year of surgery. Optimal cut-off values for SUVmax1 and ΔSUVmax% were 7.18 and 24.25, respectively. The combination of SUVmax1 and ΔSUVmax% showed higher specificity and sensitivity, and higher positive and negative predictive values for tumor relapse within 1 year than SUVmax1 alone. Relapse-free survival (RFS) was significantly worse in the subgroups of high SUVmax1 and high ΔSUVmax% (median 7.0 months) than in the other subgroups (p < 0.0001). The multivariate Cox analysis of RFS identified high SUVmax1 and high ΔSUVmax% as independent prognostic factors (p = 0.0060). DTP FDG PET/CT may effectively predict relapse in patients with pancreatic cancer. The combination of SUVmax1 and ΔSUVmax% identified early recurrent patient groups more precisely than SUVmax1 alone.
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Affiliation(s)
- Takahiro Einama
- Department of Surgery, National Defense Medical College, Saitama 359-8513, Japan; (T.E.); (Y.Y.); (Y.T.); (F.K.); (K.K.); (N.Y.); (I.F.); (T.T.); (K.K.); (A.N.); (T.I.); (E.S.); (H.U.)
| | - Yoji Yamagishi
- Department of Surgery, National Defense Medical College, Saitama 359-8513, Japan; (T.E.); (Y.Y.); (Y.T.); (F.K.); (K.K.); (N.Y.); (I.F.); (T.T.); (K.K.); (A.N.); (T.I.); (E.S.); (H.U.)
| | - Yasuhiro Takihata
- Department of Surgery, National Defense Medical College, Saitama 359-8513, Japan; (T.E.); (Y.Y.); (Y.T.); (F.K.); (K.K.); (N.Y.); (I.F.); (T.T.); (K.K.); (A.N.); (T.I.); (E.S.); (H.U.)
| | - Fukumi Konno
- Department of Surgery, National Defense Medical College, Saitama 359-8513, Japan; (T.E.); (Y.Y.); (Y.T.); (F.K.); (K.K.); (N.Y.); (I.F.); (T.T.); (K.K.); (A.N.); (T.I.); (E.S.); (H.U.)
| | - Kazuki Kobayashi
- Department of Surgery, National Defense Medical College, Saitama 359-8513, Japan; (T.E.); (Y.Y.); (Y.T.); (F.K.); (K.K.); (N.Y.); (I.F.); (T.T.); (K.K.); (A.N.); (T.I.); (E.S.); (H.U.)
| | - Naoto Yonamine
- Department of Surgery, National Defense Medical College, Saitama 359-8513, Japan; (T.E.); (Y.Y.); (Y.T.); (F.K.); (K.K.); (N.Y.); (I.F.); (T.T.); (K.K.); (A.N.); (T.I.); (E.S.); (H.U.)
| | - Ibuki Fujinuma
- Department of Surgery, National Defense Medical College, Saitama 359-8513, Japan; (T.E.); (Y.Y.); (Y.T.); (F.K.); (K.K.); (N.Y.); (I.F.); (T.T.); (K.K.); (A.N.); (T.I.); (E.S.); (H.U.)
| | - Takazumi Tsunenari
- Department of Surgery, National Defense Medical College, Saitama 359-8513, Japan; (T.E.); (Y.Y.); (Y.T.); (F.K.); (K.K.); (N.Y.); (I.F.); (T.T.); (K.K.); (A.N.); (T.I.); (E.S.); (H.U.)
| | - Keita Kouzu
- Department of Surgery, National Defense Medical College, Saitama 359-8513, Japan; (T.E.); (Y.Y.); (Y.T.); (F.K.); (K.K.); (N.Y.); (I.F.); (T.T.); (K.K.); (A.N.); (T.I.); (E.S.); (H.U.)
| | - Akiko Nakazawa
- Department of Surgery, National Defense Medical College, Saitama 359-8513, Japan; (T.E.); (Y.Y.); (Y.T.); (F.K.); (K.K.); (N.Y.); (I.F.); (T.T.); (K.K.); (A.N.); (T.I.); (E.S.); (H.U.)
| | - Toshimitsu Iwasaki
- Department of Surgery, National Defense Medical College, Saitama 359-8513, Japan; (T.E.); (Y.Y.); (Y.T.); (F.K.); (K.K.); (N.Y.); (I.F.); (T.T.); (K.K.); (A.N.); (T.I.); (E.S.); (H.U.)
| | - Eiji Shinto
- Department of Surgery, National Defense Medical College, Saitama 359-8513, Japan; (T.E.); (Y.Y.); (Y.T.); (F.K.); (K.K.); (N.Y.); (I.F.); (T.T.); (K.K.); (A.N.); (T.I.); (E.S.); (H.U.)
| | - Jiro Ishida
- Tokorozawa PET Diagnostic Imaging Clinic, Saitama 359-1124, Japan;
| | - Hideki Ueno
- Department of Surgery, National Defense Medical College, Saitama 359-8513, Japan; (T.E.); (Y.Y.); (Y.T.); (F.K.); (K.K.); (N.Y.); (I.F.); (T.T.); (K.K.); (A.N.); (T.I.); (E.S.); (H.U.)
| | - Yoji Kishi
- Department of Surgery, National Defense Medical College, Saitama 359-8513, Japan; (T.E.); (Y.Y.); (Y.T.); (F.K.); (K.K.); (N.Y.); (I.F.); (T.T.); (K.K.); (A.N.); (T.I.); (E.S.); (H.U.)
- Correspondence: ; Tel.: +81-4-2995-1211
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Gnanasegaran G, Agrawal K, Wan S. 18F-Fluorodeoxyglucose-PET-Computerized Tomography and non-Fluorodeoxyglucose PET-Computerized Tomography in Hepatobiliary and Pancreatic Malignancies. PET Clin 2022; 17:369-388. [PMID: 35717098 DOI: 10.1016/j.cpet.2022.03.007] [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: 02/07/2023]
Abstract
Molecular imaging with PET-computerized tomography (PET-CT) plays an important role in oncology. There is current and evolving evidence supporting the use of fluorodeoxyglucose (FDG) and non-FDG tracers in assessment patients with hepatobiliary and pancreatic cancers in various clinical scenarios. In this chapter, we discuss the advantages and limitations of FDG and non-FDG PET-CT in the management of patients with hepatobiliary and pancreatic cancers.
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Affiliation(s)
| | | | - Simon Wan
- University College London Hospitals NHS Foundation Trust, London, United Kingdom
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Farrukh J, Balasubramaniam R, James A, Wadhwani SS, Albazaz R. Pancreatic adenocarcinoma: imaging techniques for diagnosis and management. Br J Hosp Med (Lond) 2022; 83:1-12. [PMID: 35653327 DOI: 10.12968/hmed.2022.0065] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2023]
Abstract
Pancreatic cancer is a leading cause of death from cancer but only a minority of patients with pancreatic ductal adenocarcinomas are eligible for curative resection. The increasing role of neoadjuvant therapy provides hope of improving outcomes. However, progress is also reliant on advances in imaging that can identify disease earlier and accurately assess treatment response. Computed tomography remains the cornerstone in evaluation of resectability, offering excellent spatial resolution. However, in high-risk patients, additional magnetic resonance imaging and positron emission tomography-computed tomography may further guide treatment decisions. Conventional computed tomography can be limited in its ability to determine disease response after neoadjuvant therapy. Dual-energy computed tomography and computed tomography or magnetic resonance imaging perfusion studies emerging as potentially better alternatives. Combined with pioneering advances in radiomic analysis, these modalities also show promise in analysing tumour heterogeneity and thereby more accurately predicting outcomes. This article reviews these imaging techniques.
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Affiliation(s)
- Jawaad Farrukh
- Department of Radiology, Royal Stoke University Hospital, University Hospitals of North Midlands NHS Trust, Stoke-on-Trent, UK
| | - Ravivarma Balasubramaniam
- Department of Radiology, Royal Stoke University Hospital, University Hospitals of North Midlands NHS Trust, Stoke-on-Trent, UK
| | - Anitha James
- Department of Radiology, Royal Stoke University Hospital, University Hospitals of North Midlands NHS Trust, Stoke-on-Trent, UK
| | - Sharan S Wadhwani
- Department of Radiology, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK
| | - Raneem Albazaz
- Department of Radiology, St James's University Hospital, The Leeds Teaching Hospitals NHS Trust, Leeds, UK
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Tabacchi E, Nanni C, Bossert I, Maffione AM, Fanti S. Diagnostic Applications of Nuclear Medicine: Pancreatic Cancer. NUCLEAR ONCOLOGY 2022:891-917. [DOI: 10.1007/978-3-031-05494-5_17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Andersen HB, Ialchina R, Pedersen SF, Czaplinska D. Metabolic reprogramming by driver mutation-tumor microenvironment interplay in pancreatic cancer: new therapeutic targets. Cancer Metastasis Rev 2021; 40:1093-1114. [PMID: 34855109 DOI: 10.1007/s10555-021-10004-4] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/14/2021] [Accepted: 11/22/2021] [Indexed: 12/12/2022]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers globally with a mortality rate exceeding 95% and very limited therapeutic options. A hallmark of PDAC is its acidic tumor microenvironment, further characterized by excessive fibrosis and depletion of oxygen and nutrients due to poor vascularity. The combination of PDAC driver mutations and adaptation to this hostile environment drives extensive metabolic reprogramming of the cancer cells toward non-canonical metabolic pathways and increases reliance on scavenging mechanisms such as autophagy and macropinocytosis. In addition, the cancer cells benefit from metabolic crosstalk with nonmalignant cells within the tumor microenvironment, including pancreatic stellate cells, fibroblasts, and endothelial and immune cells. Increasing evidence shows that this metabolic rewiring is closely related to chemo- and radioresistance and immunosuppression, causing extensive treatment failure. Indeed, stratification of human PDAC tumors into subtypes based on their metabolic profiles was shown to predict disease outcome. Accordingly, an increasing number of clinical trials target pro-tumorigenic metabolic pathways, either as stand-alone treatment or in conjunction with chemotherapy. In this review, we highlight key findings and potential future directions of pancreatic cancer metabolism research, specifically focusing on novel therapeutic opportunities.
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Affiliation(s)
- Henriette Berg Andersen
- Section for Cell Biology and Physiology, Department of Biology, University of Copenhagen, 2100, Copenhagen, Denmark
| | - Renata Ialchina
- Section for Cell Biology and Physiology, Department of Biology, University of Copenhagen, 2100, Copenhagen, Denmark
| | - Stine Falsig Pedersen
- Section for Cell Biology and Physiology, Department of Biology, University of Copenhagen, 2100, Copenhagen, Denmark.
| | - Dominika Czaplinska
- Section for Cell Biology and Physiology, Department of Biology, University of Copenhagen, 2100, Copenhagen, Denmark
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Lee W, Oh M, Kim JS, Park Y, Kwon JW, Jun E, Song KB, Lee JH, Hwang DW, Yoo C, Kim KP, Jeong JH, Chang HM, Ryoo BY, Park SY, Kim SC. Metabolic activity by FDG-PET/CT after neoadjuvant chemotherapy in borderline resectable and locally advanced pancreatic cancer and association with survival. Br J Surg 2021; 109:61-70. [PMID: 34378010 DOI: 10.1093/bjs/znab229] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2021] [Revised: 04/11/2021] [Accepted: 05/19/2021] [Indexed: 11/14/2022]
Abstract
BACKGROUND The optimal prognostic markers for neoadjuvant chemotherapy in patients with borderline resectable or locally advanced pancreatic cancer are not yet established. METHOD Patients who received neoadjuvant chemotherapy prior to surgery and underwent FDG-PET/CT between July 2012 and December 2017 were included. Metabolic parameters including standardised uptake value (SUV), metabolic tumour volume (MTV), and total lesion glycolysis (TLG) on PET/CT, and response evaluations using PERCIST criteria, were investigated for its impact on survival and recurrence. Cox proportional hazards model was performed. Differences in risk were expressed as hazard ratio [HR] with 95% confidence interval [c.i.]. RESULTS The patients with borderline resectable (N = 106) or locally advanced pancreatic cancer (N = 82) were identified. The median survival was 33.6 months. Decreased metabolic parameters of PET/CT after neoadjuvant chemotherapy were associated with positive impacts on survival and recurrence such as SUVmax (HR 1.16, 95% c.i. 1.01 to 1.32, P = 0.025), SUVpeak (HR 1.26, 95% c.i. 1.05 to 1.51, P = 0.011), and MTV (HR 1.15, 95% c.i. 1.04 to 1.26, P = 0.005). Large delta values were related to a positive impact on recurrence such as SUVmax (HR 1.21, 95% c.i. 1.06 to 1.38, P = 0.005). Post-neoadjuvant chemotherapy SUVmax ≥3 (HR 3.46, 95% c.i. 1.21 to 9.91; P = 0.036) was an independent prognostic factor for negative impact on survival. Patients with post-neoadjuvant chemotherapy SUVmax <3 showed more chemotherapy cycles (8.7 versus 6.2, P = 0.001), more frequent complete metabolic response (25 vs 2.2%, P = 0.002), smaller tumour size (2.1 vs 3.1 cm, P = 0.002), and less frequent lymphovascular invasion (23.7 vs 51.1%, P = 0.020) than patients with SUVmax ≥3. CONCLUSION Reduction in metabolic tumour parameters of FDG- PET/CT after neoadjuvant chemotherapy indicates improved overall survival and recurrence-free survival.
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Affiliation(s)
- Woohyung Lee
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Minyoung Oh
- Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jae Seung Kim
- Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Yejong Park
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Jae Woo Kwon
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Eunsung Jun
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Ki Byung Song
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Jae Hoon Lee
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Dae Wook Hwang
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Changhoon Yoo
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Kyu-Pyo Kim
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Jae Ho Jeong
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Heung-Moon Chang
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Baek-Yeol Ryoo
- Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Seo Young Park
- Department of Clinical Epidemiology and Biostatistics, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea.,Department of Statistics and Data Science, Korea National Open University, Seoul, Republic of Korea
| | - Song Cheol Kim
- Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
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Nappo G, Donisi G, Zerbi A. Borderline resectable pancreatic cancer: Certainties and controversies. World J Gastrointest Surg 2021; 13:516-528. [PMID: 34194610 PMCID: PMC8223708 DOI: 10.4240/wjgs.v13.i6.516] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Revised: 04/09/2021] [Accepted: 05/25/2021] [Indexed: 02/06/2023] Open
Abstract
Borderline resectable (BR) pancreatic ductal adenocarcinoma (PDAC) is currently a well-recognized entity, characterized by some specific anatomic, biological and conditional features: It includes patients with a stage of disease intermediate between the resectable and the locally advanced ones. The term BR identifies a tumour with an aggressive biological behaviour, on which a neoadjuvant approach instead of an upfront surgery one should be preferred, in order to obtain a radical resection (R0) and to avoid an early recurrence after surgery. Even if during the last decades several studies on this topic have been published, some aspects of BR-PDAC still represent a matter of debate. The aim of this review is to critically analyse the available literature on this topic, particularly focusing on: The problem of the heterogeneity of definition of BR-PDAC adopted, leading to a misinterpretation of published data; its current management (neoadjuvant vs upfront surgery); which neoadjuvant regimen should be preferably adopted; the problem of radiological restaging and the determination of resectability after neoadjuvant therapy; the post-operative outcomes after surgery; and the role and efficacy of adjuvant treatment for resected patients that already underwent neoadjuvant therapy.
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Affiliation(s)
- Gennaro Nappo
- Pancreatic Surgery Unit, Humanitas Clinical and Research Center-IRCCS, Rozzano 20089, Italy
| | - Greta Donisi
- Pancreatic Surgery Unit, Humanitas Clinical and Research Center-IRCCS, Rozzano 20089, Italy
| | - Alessandro Zerbi
- Pancreatic Surgery Unit, Humanitas Clinical and Research Center-IRCCS, Rozzano 20089, Italy
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Maloney S, Itchins M, Arena J, Sahni S, Howell VM, Hayes SA, Gill AJ, Clarke SJ, Samra J, Mittal A, Pavlakis N. Optimal Upfront Treatment in Surgically Resectable Pancreatic Cancer Candidates: A High-Volume Center Retrospective Analysis. J Clin Med 2021; 10:2700. [PMID: 34207372 PMCID: PMC8235361 DOI: 10.3390/jcm10122700] [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: 04/18/2021] [Revised: 06/14/2021] [Accepted: 06/15/2021] [Indexed: 12/17/2022] Open
Abstract
Pancreatic adenocarcinoma is a devastating disease with only 15-20% of patients resectable at diagnosis. Neoadjuvant chemotherapy for this cohort is becoming increasingly popular; however, there are no published randomized trials that support the use of neoadjuvant chemotherapy over upfront surgery in resectable disease. This retrospective cohort analysis was conducted to compare both treatment pathways and to identify any potential prognostic markers. Medical records from one large volume pancreatic cancer center from 2013-2019 were reviewed and 126 patients with upfront resectable disease were analyzed. Due to a change in practice in our center patients treated prior to December 2016 received upfront surgery and those treated after this date received neoadjuvant chemotherapy. Of these, 86 (68%) patients were treated with upfront surgery and 40 (32%) of patients were treated with neoadjuvant chemotherapy. Our results demonstrated that patients treated with upfront surgery with early-stage (1a) disease had a longer median OS compared to those treated with neoadjuvant chemotherapy (24 vs. 21 months, p = 0.028). This survival difference was not evident for all patients (regardless of stage). R0 resections were similar between groups (p = 0.605). We identified that both tumor viability (in neoadjuvant chemotherapy-treated patients) and tumor grade were useful prognostic markers. Upfront surgery for certain patients with low volume disease may be suitable despite the global trend towards neoadjuvant chemotherapy for all upfront resectable patients. A prospective clinical trial in this cohort incorporating biomarkers is needed to determine optimal therapy pathway.
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Affiliation(s)
- Sarah Maloney
- Faculty of Medicine and Health Sciences, Northern Clinical School, The University of Sydney, Sydney, NSW 2065, Australia; (M.I.); (J.A.); (S.S.); (V.M.H.); (S.A.H.); (A.J.G.); (S.J.C.); (J.S.); (A.M.); (N.P.)
- Bill Walsh Translational Cancer Research Laboratory, Kolling Institute, The University of Sydney, Sydney, NSW 2065, Australia
- Department of Medical Oncology, Royal North Shore Hospital, St. Leonards, Sydney, NSW 2065, Australia
| | - Malinda Itchins
- Faculty of Medicine and Health Sciences, Northern Clinical School, The University of Sydney, Sydney, NSW 2065, Australia; (M.I.); (J.A.); (S.S.); (V.M.H.); (S.A.H.); (A.J.G.); (S.J.C.); (J.S.); (A.M.); (N.P.)
- Bill Walsh Translational Cancer Research Laboratory, Kolling Institute, The University of Sydney, Sydney, NSW 2065, Australia
- Department of Medical Oncology, Royal North Shore Hospital, St. Leonards, Sydney, NSW 2065, Australia
| | - Jennifer Arena
- Faculty of Medicine and Health Sciences, Northern Clinical School, The University of Sydney, Sydney, NSW 2065, Australia; (M.I.); (J.A.); (S.S.); (V.M.H.); (S.A.H.); (A.J.G.); (S.J.C.); (J.S.); (A.M.); (N.P.)
- Department of Medical Oncology, Royal North Shore Hospital, St. Leonards, Sydney, NSW 2065, Australia
- Upper Gastrointestinal Surgical Unit, Royal North Shore Hospital, St. Leonards, Sydney, NSW 2065, Australia
| | - Sumit Sahni
- Faculty of Medicine and Health Sciences, Northern Clinical School, The University of Sydney, Sydney, NSW 2065, Australia; (M.I.); (J.A.); (S.S.); (V.M.H.); (S.A.H.); (A.J.G.); (S.J.C.); (J.S.); (A.M.); (N.P.)
- Bill Walsh Translational Cancer Research Laboratory, Kolling Institute, The University of Sydney, Sydney, NSW 2065, Australia
| | - Viive M. Howell
- Faculty of Medicine and Health Sciences, Northern Clinical School, The University of Sydney, Sydney, NSW 2065, Australia; (M.I.); (J.A.); (S.S.); (V.M.H.); (S.A.H.); (A.J.G.); (S.J.C.); (J.S.); (A.M.); (N.P.)
- Bill Walsh Translational Cancer Research Laboratory, Kolling Institute, The University of Sydney, Sydney, NSW 2065, Australia
| | - Sarah A. Hayes
- Faculty of Medicine and Health Sciences, Northern Clinical School, The University of Sydney, Sydney, NSW 2065, Australia; (M.I.); (J.A.); (S.S.); (V.M.H.); (S.A.H.); (A.J.G.); (S.J.C.); (J.S.); (A.M.); (N.P.)
- Bill Walsh Translational Cancer Research Laboratory, Kolling Institute, The University of Sydney, Sydney, NSW 2065, Australia
| | - Anthony J. Gill
- Faculty of Medicine and Health Sciences, Northern Clinical School, The University of Sydney, Sydney, NSW 2065, Australia; (M.I.); (J.A.); (S.S.); (V.M.H.); (S.A.H.); (A.J.G.); (S.J.C.); (J.S.); (A.M.); (N.P.)
- Cancer Diagnosis and Pathology Group, Kolling Institute, The University of Sydney, Sydney, NSW 2065, Australia
- NSW Health Pathology, Department of Anatomical Pathology, Royal North Shore Hospital, St. Leonards, Sydney, NSW 2065, Australia
| | - Stephen J. Clarke
- Faculty of Medicine and Health Sciences, Northern Clinical School, The University of Sydney, Sydney, NSW 2065, Australia; (M.I.); (J.A.); (S.S.); (V.M.H.); (S.A.H.); (A.J.G.); (S.J.C.); (J.S.); (A.M.); (N.P.)
- Bill Walsh Translational Cancer Research Laboratory, Kolling Institute, The University of Sydney, Sydney, NSW 2065, Australia
- Department of Medical Oncology, Royal North Shore Hospital, St. Leonards, Sydney, NSW 2065, Australia
| | - Jaswinder Samra
- Faculty of Medicine and Health Sciences, Northern Clinical School, The University of Sydney, Sydney, NSW 2065, Australia; (M.I.); (J.A.); (S.S.); (V.M.H.); (S.A.H.); (A.J.G.); (S.J.C.); (J.S.); (A.M.); (N.P.)
- Bill Walsh Translational Cancer Research Laboratory, Kolling Institute, The University of Sydney, Sydney, NSW 2065, Australia
- Upper Gastrointestinal Surgical Unit, Royal North Shore Hospital, St. Leonards, Sydney, NSW 2065, Australia
| | - Anubhav Mittal
- Faculty of Medicine and Health Sciences, Northern Clinical School, The University of Sydney, Sydney, NSW 2065, Australia; (M.I.); (J.A.); (S.S.); (V.M.H.); (S.A.H.); (A.J.G.); (S.J.C.); (J.S.); (A.M.); (N.P.)
- Bill Walsh Translational Cancer Research Laboratory, Kolling Institute, The University of Sydney, Sydney, NSW 2065, Australia
- Upper Gastrointestinal Surgical Unit, Royal North Shore Hospital, St. Leonards, Sydney, NSW 2065, Australia
| | - Nick Pavlakis
- Faculty of Medicine and Health Sciences, Northern Clinical School, The University of Sydney, Sydney, NSW 2065, Australia; (M.I.); (J.A.); (S.S.); (V.M.H.); (S.A.H.); (A.J.G.); (S.J.C.); (J.S.); (A.M.); (N.P.)
- Bill Walsh Translational Cancer Research Laboratory, Kolling Institute, The University of Sydney, Sydney, NSW 2065, Australia
- Department of Medical Oncology, Royal North Shore Hospital, St. Leonards, Sydney, NSW 2065, Australia
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Han X, Ma L, Gu J, Wang D, Li J, Lou W, Saiyin H, Fu D. Basal microvilli define the metabolic capacity and lethal phenotype of pancreatic cancer. J Pathol 2021; 253:304-314. [PMID: 33159698 PMCID: PMC7898529 DOI: 10.1002/path.5588] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2020] [Revised: 10/22/2020] [Accepted: 11/02/2020] [Indexed: 12/28/2022]
Abstract
Apical microvilli of polarized epithelial cells govern the absorption of metabolites and the transport of fluid in tissues. Previously, we reported that tall and dense basal microvilli present on the endothelial cells of pancreatic cancers, a lethal malignancy with a high metabolism and unusual hypomicrovascularity, contain nutrient trafficking vesicles and glucose; their length and density were related to the glucose uptake of pancreatic cancers in a small-scale analysis. However, the implications of basal microvilli on pancreatic cancers are unknown. Here, we evaluated the clinical implications of basal microvilli in 106 pancreatic cancers. We found that basal microvilli are a dominant change in pancreatic cancers. The presence of longer and denser basal microvilli on the microvessels in pancreatic cancer tissues positively correlated with increased glucose uptake and higher metastatic (or invasive) and proliferative potentials of neoplastic cells and vice versa. Clinically, postoperative patients with longer and denser basal microvilli were more prone to unfavorable pathological characteristics and dismal prognoses. They were even more refractory to adjuvant therapy than those with shorter and thinner basal microvilli were. Our findings show that basal microvilli define the metabolic capacity and lethal phenotype of pancreatic cancers. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
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Affiliation(s)
- Xu Han
- Department of General SurgeryZhongshan Hospital, Fudan UniversityShanghaiPR China
| | - Lixiang Ma
- Department of Anatomy, Histology & Embryology, School of Medical SciencesFudan UniversityShanghaiPR China
| | - Jichun Gu
- Department of Pancreatic Surgery, Pancreatic Disease InstituteHuashan Hospital, Fudan UniversityShanghaiPR China
| | - Dansong Wang
- Department of General SurgeryZhongshan Hospital, Fudan UniversityShanghaiPR China
| | - Ji Li
- Department of Pancreatic Surgery, Pancreatic Disease InstituteHuashan Hospital, Fudan UniversityShanghaiPR China
| | - Wenhui Lou
- Department of General SurgeryZhongshan Hospital, Fudan UniversityShanghaiPR China
| | - Hexige Saiyin
- State Key Laboratory of Genetic Engineering, School of Life SciencesFudan UniversityShanghaiPR China
| | - Deliang Fu
- Department of Pancreatic Surgery, Pancreatic Disease InstituteHuashan Hospital, Fudan UniversityShanghaiPR China
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14
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Mohamed E, Needham A, Psarelli E, Carroll M, Vinjamuri S, Sanghera B, Wong WL, Halloran C, Ghaneh P. Prognostic value of 18FDG PET/CT volumetric parameters in the survival prediction of patients with pancreatic cancer. EUROPEAN JOURNAL OF SURGICAL ONCOLOGY 2020; 46:1532-1538. [PMID: 32070641 DOI: 10.1016/j.ejso.2020.02.002] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2019] [Revised: 01/02/2020] [Accepted: 02/04/2020] [Indexed: 12/12/2022]
Abstract
PURPOSE To investigate the value of 18 FDG PET/CT volumetric parameters in the prediction of overall survival (OS) in patients with pancreatic cancer and also, assess their independence relative to well-established clinico-pathological variables. METHODS We conducted a retrospective analysis of patients with a confirmed diagnosis of pancreatic cancer who underwent 18 FDG PET/CT. The tumour maximum standardised uptake value (SUVmax) in addition to SUVmean, metabolic tumour volume (MTV) and total lesion glycolysis (TLG) were calculated. The prognostic value of 18 FDG PET/CT and clinico-pathological parameters for OS were assessed using univariate and multivariable analyses. RESULTS A sum of 89 patients were analysed in this study. Median survival for patients categorised as having high TLG (≥55) and low TLG (<55) was 18 vs 5 months (p < 0.001). Similarly, the respective high vs low SUVmean, MTV and SUVmax were 18 vs 6 months (p = 0.001), 16 vs 6 months (p = 0.002) and 18 vs 6 months (p = 0.001). Univariate analysis showed SUVmax, SUVmean, MTV, TLG, tumour size, tumour differentiation and presence of distant metastasis as prognostic factors for OS. On multivariable analysis, TLG (HR 2.0, 95% CI 1.26-3.18, p = 0.004) and the presence of distant metastasis (HR 3.37, 95% CI 1.97-5.77, p < 0.001) emerged as independent prognostic factors. Subgroup analysis identified TLG as the only significant PET metric after adjusting for the presence of distant metastasis. CONCLUSIONS 18 FDG PET/CT is a useful tool in the preoperative evaluation of patients with pancreatic cancer. Tumour TLG offer an independent prognostic value in both potentially operable and metastatic disease settings.
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Affiliation(s)
- Eyas Mohamed
- Department of Pancreaticobiliary Surgery, Royal Liverpool University Hospital, Liverpool, UK
| | - Alexander Needham
- Liverpool Cancer Research UK Cancer Trials Unit, Liverpool Cancer Research UK Centre, University of Liverpool, Liverpool, UK
| | - Eftychia Psarelli
- Liverpool Cancer Research UK Cancer Trials Unit, Liverpool Cancer Research UK Centre, University of Liverpool, Liverpool, UK
| | - Melvyn Carroll
- Department of Nuclear Medicine, Royal Liverpool University Hospital, Liverpool, UK
| | - Sobhan Vinjamuri
- Department of Nuclear Medicine, Royal Liverpool University Hospital, Liverpool, UK
| | - Bal Sanghera
- Paul Strickland Scanner Centre, Mount Vernon Hospital, Middlesex, UK
| | - Wai Lup Wong
- Paul Strickland Scanner Centre, Mount Vernon Hospital, Middlesex, UK
| | - Christopher Halloran
- Department of Pancreaticobiliary Surgery, Royal Liverpool University Hospital, Liverpool, UK; Liverpool Cancer Research UK Cancer Trials Unit, Liverpool Cancer Research UK Centre, University of Liverpool, Liverpool, UK
| | - Paula Ghaneh
- Department of Pancreaticobiliary Surgery, Royal Liverpool University Hospital, Liverpool, UK; Liverpool Cancer Research UK Cancer Trials Unit, Liverpool Cancer Research UK Centre, University of Liverpool, Liverpool, UK.
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15
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Ma L, Han X, Gu J, Li J, Lou W, Jin C, Saiyin H. The physiological characteristics of the basal microvilli microvessels in pancreatic cancers. Cancer Med 2020; 9:5535-5545. [PMID: 32488986 PMCID: PMC7402840 DOI: 10.1002/cam4.3177] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2020] [Revised: 04/17/2020] [Accepted: 05/08/2020] [Indexed: 02/06/2023] Open
Abstract
Pancreatic cancer (PC) is a highly lethal tumor with controversial high glucose uptake and hypomicrovascularity, and the hypomicrovasculature, which is considered to have poor perfusion, blocks the delivery of drugs to tumors. The preferential existence of a novel endothelial projection with trafficking vesicles in PCs, referring to basal microvilli, was described previously. However, the perfusion and nutrients delivering status of the basal microvilli microvessels are unknown. Here, we used the perfusion of fluorescently labeled CD31 antibody, lectin, and 2‐NBDG to autochthonous PC‐bearing mice, immunostaining, probe‐based confocal laser endoscopy and three‐dimensional (3D) reconstruction to study the nutrient trafficking, and perfusion status of the basal microvilli microvasculature in PC. Our data showed that the coperfusion of lectin and CD31 is an efficient way to show the microcirculation in most healthy organs. However, coperfusion with lectin and CD31 is inefficient for showing the microcirculation in PCs compared with that in healthy organs and immunostaining. This method does not reflect the nutrient trafficking status in the microvessels, especially in basal microvilli microvessels of PCs. In basal microvilli microvessels that were poorly labeled by lectin, we observed large vesicle‐like structures with 2‐NBDG preferentially located at the base of the basal microvilli or in basal microvilli, and there were long filopodia on the luminal surface of the human PC microvasculature. Our observations suggest that the PC microvasculature, especially basal microvilli microvessels, is well perfused and might be highly efficient in the trafficking of glucose or other nutrients, indicating that macropinocytosis might participate in the nutrient trafficking.
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Affiliation(s)
- Lixiang Ma
- Department of Anatomy, Histology & Embryology, School of Medical Sciences, Fudan University, Shanghai, China
| | - Xu Han
- General Surgery Department, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Jichun Gu
- Department of Pancreatic Surgery, Huashan Hospital, Fudan University, Shanghai, China
| | - Ji Li
- Department of Pancreatic Surgery, Huashan Hospital, Fudan University, Shanghai, China
| | - Wenhui Lou
- General Surgery Department, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Chen Jin
- Department of Pancreatic Surgery, Huashan Hospital, Fudan University, Shanghai, China
| | - Hexige Saiyin
- The State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Sciences, Fudan University, Shanghai, China
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16
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Su W, Ren S, Zhu X, Zhang H, Zuo C. Standardized thresholds of volume-based PET/CT parameters predicting survival of patients with pancreatic head cancer treated with stereotactic body radiation therapy. Ann Nucl Med 2020; 34:379-387. [PMID: 32277421 DOI: 10.1007/s12149-020-01454-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2019] [Accepted: 02/04/2020] [Indexed: 01/08/2023]
Abstract
OBJECTIVE To explore standardized relative thresholds of volume-based parameters on FDG PET/CT, and define the optimal prognosticator among the relative thresholds for patients with locally advanced pancreatic head cancer (LAPHC) treated by stereotactic body radiation therapy (SBRT). METHODS Thirty-five patients with LAPHC were enrolled, and all underwent SBRT and baseline FDG PET/CT scan. Maximum standardized uptake value (SUVmax) was measured, and metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were calculated under the relative (30%, 40%, and 50%) thresholds of SUVmax. Survival analysis was performed via univariate and multivariate analyses, and independent prognostic factors were determined by Cox proportional hazard models and corresponding survival curves and scatter diagram were drawn. RESULTS The median overall survival (OS) and progression-free survival (PFS) were 13.8 and 9.8 months, respectively. On univariate analysis, MTV(40%) < 5.6 cm3, accumulated dose (AD) ≥ 36 Gy and the absence of pancreatic duct (PD) stents were significantly correlated with both superior OS and PFS, TLG (40%) < 29.9 was related to better OS and biological effective dose (BED10) ≥ 57.6 Gy was related to better PFS (all with p < 0.05). Further, multivariate analysis demonstrated both MTV (40%) and AD were independent prognosticators for OS and PFS, and BED10 was an independent predictor for PFS (all with p < 0.05). Scatter diagram showed BED10 to be a stronger clinical prognosis predictor for PFS than AD. CONCLUSIONS MTV (40%) was the optimal prognosticator among the relative thresholds of SUVmax for tumor delineation on PET/CT for LAPHC patients receiving SBRT. AD was also favorable indicators for OS and PFS of patients, and BED10 was more sensitive than AD in predicting the PFS of patients.
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Affiliation(s)
- Weiwei Su
- Departments of Nuclear Medicine, Changhai Hospital Affiliated to the Second Military Medical University, Changhai Road 168, Yangpu District, Shanghai, 200433, People's Republic of China
| | - Shengnan Ren
- Departments of Nuclear Medicine, Changhai Hospital Affiliated to the Second Military Medical University, Changhai Road 168, Yangpu District, Shanghai, 200433, People's Republic of China
| | - Xiaofei Zhu
- Departments of Radiotherapy, Changhai Hospital Affiliated to the Second Military Medical University, Changhai Road 168, Yangpu District, Shanghai, 200433, People's Republic of China
| | - Huojun Zhang
- Departments of Radiotherapy, Changhai Hospital Affiliated to the Second Military Medical University, Changhai Road 168, Yangpu District, Shanghai, 200433, People's Republic of China.
| | - Changjing Zuo
- Departments of Nuclear Medicine, Changhai Hospital Affiliated to the Second Military Medical University, Changhai Road 168, Yangpu District, Shanghai, 200433, People's Republic of China.
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Unterrainer M, Eze C, Ilhan H, Marschner S, Roengvoraphoj O, Schmidt-Hegemann NS, Walter F, Kunz WG, Rosenschöld PMA, Jeraj R, Albert NL, Grosu AL, Niyazi M, Bartenstein P, Belka C. Recent advances of PET imaging in clinical radiation oncology. Radiat Oncol 2020; 15:88. [PMID: 32317029 PMCID: PMC7171749 DOI: 10.1186/s13014-020-01519-1] [Citation(s) in RCA: 77] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2020] [Accepted: 03/19/2020] [Indexed: 12/25/2022] Open
Abstract
Radiotherapy and radiation oncology play a key role in the clinical management of patients suffering from oncological diseases. In clinical routine, anatomic imaging such as contrast-enhanced CT and MRI are widely available and are usually used to improve the target volume delineation for subsequent radiotherapy. Moreover, these modalities are also used for treatment monitoring after radiotherapy. However, some diagnostic questions cannot be sufficiently addressed by the mere use standard morphological imaging. Therefore, positron emission tomography (PET) imaging gains increasing clinical significance in the management of oncological patients undergoing radiotherapy, as PET allows the visualization and quantification of tumoral features on a molecular level beyond the mere morphological extent shown by conventional imaging, such as tumor metabolism or receptor expression. The tumor metabolism or receptor expression information derived from PET can be used as tool for visualization of tumor extent, for assessing response during and after therapy, for prediction of patterns of failure and for definition of the volume in need of dose-escalation. This review focuses on recent and current advances of PET imaging within the field of clinical radiotherapy / radiation oncology in several oncological entities (neuro-oncology, head & neck cancer, lung cancer, gastrointestinal tumors and prostate cancer) with particular emphasis on radiotherapy planning, response assessment after radiotherapy and prognostication.
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Affiliation(s)
- M Unterrainer
- Department of Nuclear Medicine, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany. .,Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany. .,German Cancer Consortium (DKTK), partner site Munich; and German Cancer Research Center (DKFZ), Heidelberg, Germany.
| | - C Eze
- Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany
| | - H Ilhan
- Department of Nuclear Medicine, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany
| | - S Marschner
- Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany
| | - O Roengvoraphoj
- Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany
| | - N S Schmidt-Hegemann
- Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany
| | - F Walter
- Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany
| | - W G Kunz
- Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany
| | - P Munck Af Rosenschöld
- Radiation Physics, Department of Hematology, Oncology and Radiation Physics, Skåne University Hospital, and Lund University, Lund, Sweden
| | - R Jeraj
- Department of Medical Physics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, USA
| | - N L Albert
- Department of Nuclear Medicine, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany.,German Cancer Consortium (DKTK), partner site Munich; and German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - A L Grosu
- Department of Radiation Oncology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.,German Cancer Consortium (DKTK), partner Site Freiburg, Freiburg, Germany
| | - M Niyazi
- German Cancer Consortium (DKTK), partner site Munich; and German Cancer Research Center (DKFZ), Heidelberg, Germany.,Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany
| | - P Bartenstein
- Department of Nuclear Medicine, University Hospital, LMU Munich, Marchioninistr. 15, 81377, Munich, Germany.,German Cancer Consortium (DKTK), partner site Munich; and German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - C Belka
- German Cancer Consortium (DKTK), partner site Munich; and German Cancer Research Center (DKFZ), Heidelberg, Germany.,Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany
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18
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Ren S, Zhu X, Zhang A, Li D, Zuo C, Zhang H. Prognostic value of 18F-FDG PET /CT metabolic parameters in patients with locally advanced pancreatic Cancer treated with stereotactic body radiation therapy. Cancer Imaging 2020; 20:22. [PMID: 32156306 PMCID: PMC7063714 DOI: 10.1186/s40644-020-00301-6] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2019] [Accepted: 03/02/2020] [Indexed: 02/07/2023] Open
Abstract
Background 18F-FDG PET/CT metabolic parameters have been applied as prognostic factors in multi-malignancies. However, the role in locally advanced pancreatic cancer (LAPC) was not confirmed. In this study, we investigated the prognostic value of 18F-FDG PET/CT metabolic parameters in LAPC patients treated with stereotactic body radiation therapy (SBRT). Methods Seventy three LAPC patients who received SBRT therapy and pre-treatment 18F-FDG PET/CT imaging from January 2012 to January 2016 were included in this retrospective study. The study aim was to evaluate the relationship between metabolic parameters with clinical factors, and the value of metabolic parameters in the prognosis of LAPC. The median of parameters was set as the cut-off value for statistical analysis. Univariate survival analysis was performed by the Kaplan Meier method and log-rank test, and multivariate analysis was carried out by a Cox proportional hazards model. Results Patients with lymph node metastasis or longer tumor diameters were associated with higher TLG (P < 0.05). Univariate analysis showed MTV, TLG, radiotherapy dose and chemotherapy were significantly associated with disease progression-free survival (PFS) and overall survival (OS) (P < 0.05). Lymph node metastasis and tumor longest diameter were associated with OS. Multivariate analysis demonstrated TLG, radiotherapy dose, and chemotherapy were independent factors of PFS and OS (HR: 2.307, 0.591, 0.572 and 2.145, 0.480, 0.471, P < 0.05). Conclusions TLG was found to be the independent prognostic factor of OS and PFS. Among clinical factors, radiotherapy dose and chemotherapy were independent prognostic factors of OS and PFS.
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Affiliation(s)
- Shengnan Ren
- Department of Nuclear Medicine, Shanghai Changhai Hospital, No. 168 Changhai Road, Shanghai, 200433, China
| | - Xiaofei Zhu
- Department of Radiation Oncology, Shanghai Changhai Hospital, No. 168 Changhai Road, Shanghai, 200433, China
| | - Anyu Zhang
- Department of Nuclear Medicine, Shanghai Changhai Hospital, No. 168 Changhai Road, Shanghai, 200433, China
| | - Danni Li
- Department of Nuclear Medicine, Shanghai Changhai Hospital, No. 168 Changhai Road, Shanghai, 200433, China
| | - Changjing Zuo
- Department of Nuclear Medicine, Shanghai Changhai Hospital, No. 168 Changhai Road, Shanghai, 200433, China.
| | - Huojun Zhang
- Department of Radiation Oncology, Shanghai Changhai Hospital, No. 168 Changhai Road, Shanghai, 200433, China.
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Evaluation of Fluorodeoxyglucose Positron Emission Tomography Scanning in the Neoadjuvant Therapy Paradigm in Pancreatic Ductal Adenocarcinoma. Pancreas 2020; 49:224-229. [PMID: 32011525 DOI: 10.1097/mpa.0000000000001472] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
OBJECTIVES Little data exist on the utility of fluorodeoxyglucose positron emission tomography (FDG-PET) in operable pancreatic ductal adenocarcinoma (PDAC) treated with neoadjuvant (NA) therapy. METHODS Consecutively treated patients with potentially operable PDAC were recruited from a quaternary referral center between 2015 and 2018. Data were collated on demographic, clinical, radiological, treatment, and disease-free and overall survival (OS) outcome measures, correlated with FDG-PET findings. RESULTS Of 115 patients recruited, 61% were deemed upfront operable (n = 70), 33% borderline (n = 38), and 6% (n = 7) locally advanced. Ninety-five (83%) received NA chemotherapy with 23 (24%) sequential radiotherapy. Sixty-nine (73%) treated with NA were resected, 37 (54%) attained an R0 resection, 43 (62%) had N1 disease with median tumor viability of 50%. The median OS in the entire cohort was 30.48 months and in those who received NA chemotherapy followed by resection 37.98 months. Twelve percent (n = 13) were upstaged during NA therapy by PET. Preoperative standardized uptake value maximum of less than 5 versus 5 or greater after NA predicted for improved OS, 42.95 months versus 26.05 months, P = 0.02. CONCLUSIONS In this real-world cohort study of PDAC, the utility of FDG-PET in informing the patient treatment pathway was meaningfully demonstrated.
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PET in Gastrointestinal, Pancreatic, and Liver Cancers. Clin Nucl Med 2020. [DOI: 10.1007/978-3-030-39457-8_19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Duan H, Baratto L, Iagaru A. The Role of PET/CT in the Imaging of Pancreatic Neoplasms. Semin Ultrasound CT MR 2019; 40:500-508. [PMID: 31806148 DOI: 10.1053/j.sult.2019.04.006] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Pancreas cancer is a complex disease and its prognosis is related to the origin of the tumor cell as well as the stage of disease at the time of diagnosis. Pancreatic adenocarcinomas derive from the exocrine pancreas and are the fourth leading cause of cancer-related deaths in the United States, while well-differentiated pancreatic neuroendocrine tumors (pNETs) derived from the endocrine part of the pancreas are rare and characterized by a slow growth and good life expectancy. Surgery is the only curative treatment approach, and an accurate assessment of resectability is of paramount importance in order to avoid futile procedures. The role of molecular imaging with positron emission tomography and computed tomography ranges from indispensable for pNETs to controversial for certain scenarios in pancreatic adenocarcinomas. This review article aims to overview molecular pancreatic imaging.
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Affiliation(s)
- Heying Duan
- Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Stanford University, Stanford, CA
| | - Lucia Baratto
- Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Stanford University, Stanford, CA
| | - Andrei Iagaru
- Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Stanford University, Stanford, CA.
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22
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Oar A, Lee M, Le H, Hruby G, Dalfsen R, Pryor D, Lee D, Chu J, Holloway L, Briggs A, Barbour A, Chander S, Ng SP, Samra J, Shakeshaft J, Goldstein D, Nguyen N, Goodman KA, Chang DT, Kneebone A. Australasian Gastrointestinal Trials Group (AGITG) and Trans-Tasman Radiation Oncology Group (TROG) Guidelines for Pancreatic Stereotactic Body Radiation Therapy (SBRT). Pract Radiat Oncol 2019; 10:e136-e146. [PMID: 31761541 DOI: 10.1016/j.prro.2019.07.018] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2019] [Revised: 07/28/2019] [Accepted: 07/31/2019] [Indexed: 02/07/2023]
Abstract
PURPOSE Nonrandomized data exploring pancreas stereotactic body radiation therapy (SBRT) has demonstrated excellent local control rates and low toxicity. Before commencing a randomized trial investigating pancreas SBRT, standardization of prescription dose, dose constraints, simulation technique, and clinical target volume delineation are required. METHODS AND MATERIALS Specialists in radiation oncology, medical oncology, hepatobiliary surgery, and gastroenterology attended 2 consecutive Australasian Gastrointestinal Trials Group workshops in 2017 and 2018. Sample cases were discussed during workshop contact with specifically invited international speakers highly experienced in pancreas SBRT. Furthermore, sample cases were contoured and planned between workshop contact to finalize dose constraints and clinical target volume delineation. RESULTS Over 2 separate workshops, consensus was reached on dose and simulation technique. The working group recommended a dose prescription of 40 Gy in 5 fractions. Treatment delivery during end-expiratory breath hold with triple-phase contrast enhanced computed tomography was recommended. In addition, dose constraints, stepwise contouring guidelines, and an anatomic atlas for pancreatic SBRT were developed. CONCLUSIONS Pancreas SBRT is emerging as a promising treatment modality requiring prospective evaluation in randomized studies. This work attempts to standardize dose, simulation technique, and volume delineation to support the delivery of high quality SBRT in a multicenter study.
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Affiliation(s)
- Andrew Oar
- Icon Cancer Centre, Gold Coast University Hospital, Gold Coast; Liverpool and Macarthur Cancer Therapy Centres, Sydney, Australia.
| | - Mark Lee
- Icon Cancer Centre, Gold Coast University Hospital, Gold Coast
| | - Hien Le
- Department of Radiation Oncology, Royal Adelaide Hospital, Adelaide, Australia
| | - George Hruby
- Royal North Shore Hospital, Sydney, Australia; University of Sydney, Sydney, Australia
| | - Raymond Dalfsen
- Department of Radiation Oncology, Royal Adelaide Hospital, Adelaide, Australia
| | - David Pryor
- Princess Alexandra Hospital, Brisbane, Australia
| | | | - Julie Chu
- Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia
| | - Lois Holloway
- Liverpool and Macarthur Cancer Therapy Centres, Sydney, Australia; South Western Clinical School, University of New South Wales, Sydney, Australia; Institute of Medical Physics, University of Sydney, Sydney, Australia; Centre for Medical Radiation Physics, University of Wollongong, Wollongong, Australia
| | - Adam Briggs
- Royal North Shore Hospital, Sydney, Australia
| | - Andrew Barbour
- Princess Alexandra Hospital, Brisbane, Australia; University of Queensland, Diamantina Institute, Translational Research Institute, Woolloongabba, Australia
| | - Sarat Chander
- Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia
| | - Sweet Ping Ng
- Department of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia
| | - Jas Samra
- Royal North Shore Hospital, Sydney, Australia; University of Sydney, Sydney, Australia
| | - John Shakeshaft
- Icon Cancer Centre, Gold Coast University Hospital, Gold Coast
| | - David Goldstein
- Department of Medical Oncology, Nelune Cancer Centre, Prince of Wales Hospital, Sydney, Australia; Prince of Wales Clinical School, University of New South Wales, Sydney, Australia
| | - Nam Nguyen
- Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Discipline of Medicine, University of Adelaide, Adelaide, Australia
| | - Karyn A Goodman
- Department of Radiation Oncology, University of Colorado School of Medicine, Aurora, Colorado
| | | | - Andrew Kneebone
- Royal North Shore Hospital, Sydney, Australia; University of Sydney, Sydney, Australia
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23
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Fiorentino A, Laudicella R, Ciurlia E, Annunziata S, Lancellotta V, Mapelli P, Tuscano C, Caobelli F, Evangelista L, Marino L, Quartuccio N, Fiore M, Borghetti P, Chiaravalloti A, Ricci M, Desideri I, Alongi P. Positron emission tomography with computed tomography imaging (PET/CT) for the radiotherapy planning definition of the biological target volume: PART 2. Crit Rev Oncol Hematol 2019; 139:117-124. [PMID: 30940428 DOI: 10.1016/j.critrevonc.2019.03.008] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2019] [Revised: 03/14/2019] [Accepted: 03/14/2019] [Indexed: 02/07/2023] Open
Abstract
AIM Positron Emission Tomography with Computed Tomography (PET/CT) has been proven to be useful in the definition of Radiotherapy (RT) target volume. In this regard, the present expert review summarizes existing data for pancreas, prostate, gynecological and rectum/anal cancer. METHODS A comprehensive search of published original article was made, based on SCOPUS and PubMed database, selecting the paper that evaluated the role of PET/CT in the definition of RT volume. RESULTS FDG-PET has an important and promising role for pancreatic cancer. Choline PET/CT could be useful for identifying high-risk volumes for prostate cancer; while PSMA PET/CT is still under evaluation. FDG PET/CT in gynecological cancers has been shown to impact external-beam RT planning. The role of FDG-PET for Gross Tumor volume identification is crucial, representing a useful and powerful tool for anal and rectal cancer. CONCLUSION Taken together, molecular and functional imaging approaches offer a major step to individualize radiotherapeutic approach.
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Affiliation(s)
- Alba Fiorentino
- Radiotherapy Oncology Department, General Regional Hospital "F. Miulli", Acquaviva delle Fonti-Bari, Italy.
| | - Riccardo Laudicella
- Department of Biomedical and Dental Sciences and of Morphofunctional Imaging, University of Messina, Italy
| | - Elisa Ciurlia
- Radiotherapy Oncology Department, Vito Fazzi Hospital, Lecce, Italy
| | - Salvatore Annunziata
- Fondazione Policlinico A. Gemelli IRCCS-Università Cattolica Sacro Cuore, Roma, Italy
| | - Valentina Lancellotta
- Fondazione Policlinico Universitario A. Gemelli IRCCS, UOC di Radioterapia, Dipartimento di Scienze Radiologiche, Radioterapiche ed Ematologiche, Roma, Italy
| | - Paola Mapelli
- Department of Nuclear Medicine, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - Carmelo Tuscano
- Radiotherapy Oncology Department, Azienda Ospedaliera Bianchi-Melacrino-Morelli, Reggio Calabria, Italy
| | - Federico Caobelli
- Clinic of Radiology and Nuclear Medicine, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Laura Evangelista
- Nuclear Medicine Unit, Veneto Institute of Oncology IOV - IRCCS, Padua, Italy
| | - Lorenza Marino
- Radiotherapy Oncology Department, REM, Viagrande, Catania, Italy
| | | | - Michele Fiore
- Radiation Oncology, Campus Bio-Medico University, Rome, Italy
| | - Paolo Borghetti
- Radiation Oncology Department University and Spedali Civili, Brescia, Italy
| | - Agostino Chiaravalloti
- IRCCS Istituto Neurologico Mediterraneo (INM) Neuromed, Pozzilli, Italy; Department of Biomedicine and Prevention, University of Rome Tor Vergata, Italy
| | - Maria Ricci
- Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Rome, Italy
| | - Isacco Desideri
- Department of Biomedical, Experimental and Clinical Sciences "Mario Serio", Section of Radiation Oncology, University of Florence, Italy
| | - Pierpaolo Alongi
- Department of Radiological Sciences, Nuclear Medicine Service, Fondazione Istituto G. Giglio, Cefalu, Italy
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Panda A, Garg I, Johnson GB, Truty MJ, Halfdanarson TR, Goenka AH. Molecular radionuclide imaging of pancreatic neoplasms. Lancet Gastroenterol Hepatol 2019; 4:559-570. [DOI: 10.1016/s2468-1253(19)30081-0] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2019] [Revised: 02/26/2019] [Accepted: 03/02/2019] [Indexed: 02/07/2023]
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Barreto SG, Loveday B, Windsor JA, Pandanaboyana S. Detecting tumour response and predicting resectability after neoadjuvant therapy for borderline resectable and locally advanced pancreatic cancer. ANZ J Surg 2019; 89:481-487. [PMID: 30117669 DOI: 10.1111/ans.14764] [Citation(s) in RCA: 27] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2018] [Revised: 05/27/2018] [Accepted: 06/04/2018] [Indexed: 12/14/2022]
Abstract
BACKGROUND This systematic review aimed to determine the accuracy of imaging modalities to predict resectability and R0 resection for borderline resectable (BRPC) or locally advanced pancreatic cancer (LAPC) after neoadjuvant therapy (NAT). METHODS A systematic search of major databases was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS Fifteen studies identified 995 patients of which 683 had BRPC and 312 LAPC. Computed tomography (CT) scan was the most common modality for re-staging (n = 14), followed by positron emission tomography (PET)-CT (n = 3) and endosonography (EUS) (n = 2). Stable disease on RECIST criteria was found in 67% of patients (range 53-80%) with 20% demonstrating reduction in tumour size. A total of 60% of patients underwent surgery post-NAT (range 31-85%) with a R0 rate of 88% (range 57-100%). Accuracy for predicting R0 resectability and T-stage on CT scan was 71 and 49%. A reduction in SUVmax on PET-CT and reduction of tumour stiffness on EUS elastography positively correlated with resectability. CONCLUSIONS More than half the patients undergo resection post-NAT for LAPC and BRPC. Stable, or reduction of, tumour disease may predict resectability. Reduction in tumour SUVmax on PET-CT and decreased tumour stiffness on EUS elastography may be potential markers of NAT response and resectability.
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Affiliation(s)
- Savio G Barreto
- Hepatobiliary and Oesophagogastric Unit, Division of Surgery and Perioperative Medicine, Flinders Medical Centre, Adelaide, South Australia, Australia
- College of Medicine and Public Health, Flinders University, Adelaide, South Australia, Australia
| | - Benjamin Loveday
- Department of Surgery, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand
- Hepatobiliary and Pancreatic Unit, Department of General Surgery, Auckland City Hospital, Auckland, New Zealand
| | - John A Windsor
- Department of Surgery, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand
- Hepatobiliary and Pancreatic Unit, Department of General Surgery, Auckland City Hospital, Auckland, New Zealand
| | - Sanjay Pandanaboyana
- Department of Surgery, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand
- Hepatobiliary and Pancreatic Unit, Department of General Surgery, Auckland City Hospital, Auckland, New Zealand
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26
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Omiya Y, Ichikawa S, Satoh Y, Motosugi U, Nakajima N, Onishi H. Prognostic value of preoperative fluorodeoxyglucose positron emission tomography/computed tomography in patients with potentially resectable pancreatic cancer. Abdom Radiol (NY) 2018; 43:3381-3389. [PMID: 30043215 DOI: 10.1007/s00261-018-1647-4] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
PURPOSE To evaluate the prognostic value of preoperative 18-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) in patients with potentially resectable pancreatic cancer. METHODS The study included 103 consecutive patients with potentially resectable pancreatic cancer who underwent preoperative FDG-PET/CT. Age, sex, blood glucose level, tumor marker levels (carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9)), PET-related parameters (maximum standardized uptake value (SUVmax)), and contrast-enhanced CT-related factors (tumor size, location, enhancement pattern, and CT-based T and N factors by tumor nodes metastasis (TNM) classification) were assessed for their ability to independently predict postoperative tumor recurrence using Cox proportional hazards model. RESULTS Median follow-up was 23.1 months. Univariate analyses revealed that SUVmax (P = 0.0004), tumor size (P = 0.0002), T factor (P = 0.0102), N factor (P = 0.0049), and CA19-9 levels (P = 0.0059) were significantly associated with disease-free survival (DFS). In multivariate analysis, SUVmax (P = 0.0163) and CA19-9 levels (P = 0.0364) independently predicted DFS. Kaplan-Meier analysis revealed that patients with low (< 2.5) SUVmax had a significantly better prognosis than those with higher SUVmax (P = 0.0006). The DFS in patients with SUVmax < 2.5 (n = 23) and SUVmax ≥ 2.5 (n = 80) was 61.9% and 9.7%, respectively, 3 years postoperatively. CONCLUSIONS SUVmax can predict DFS in patients with resectable pancreatic cancer. A SUVmax < 2.5 heralds a better prognosis.
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Affiliation(s)
- Yoshie Omiya
- Department of Radiology, University of Yamanashi, 1110 Shimokato, Chuo-Shi, Yamanashi, 409-3898, Japan
- Department of Radiology, Shizuoka Prefectural Hospital, 4-27-1 Kita Ando Aoi-ku, Shizuoka City, Shizuoka, 420-8527, Japan
| | - Shintaro Ichikawa
- Department of Radiology, University of Yamanashi, 1110 Shimokato, Chuo-Shi, Yamanashi, 409-3898, Japan
| | - Yoko Satoh
- Yamanashi PET Imaging Clinic, 3046-2 Shimokato, Chuo-Shi, Yamanashi, 409-3821, Japan
| | - Utaroh Motosugi
- Department of Radiology, University of Yamanashi, 1110 Shimokato, Chuo-Shi, Yamanashi, 409-3898, Japan.
| | - Nobuaki Nakajima
- Department of Radiology, Shizuoka Prefectural Hospital, 4-27-1 Kita Ando Aoi-ku, Shizuoka City, Shizuoka, 420-8527, Japan
| | - Hiroshi Onishi
- Department of Radiology, University of Yamanashi, 1110 Shimokato, Chuo-Shi, Yamanashi, 409-3898, Japan
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27
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Abstract
PET/MR imaging has the potential to markedly alter pancreatic care in both the malignant, and premalignant states with the ability to perform robust, high-resolution, quantitative molecular imaging. The ability of PET/MR imaging to monitor disease processes, potentially correct for motion in the upper abdomen, and provide novel biomarkers that may be a combination of MR imaging and PET biomarkers, offers a unique, precise interrogation of the pancreatic milieu going forward.
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Affiliation(s)
- Nadine Mallak
- Department of Diagnostic Radiology, Oregon Health & Sciences University, 3181 Southwest Sam Jackson Park Road, Portland, OR 97239, USA
| | - Thomas A Hope
- Department of Radiology and Biomedical Imaging, University of California, San Francisco, 505 Parnassus Avenue, M391, San Francisco, CA 94158, USA
| | - Alexander R Guimaraes
- Department of Diagnostic Radiology, Oregon Health & Sciences University, 3181 Southwest Sam Jackson Park Road, Portland, OR 97239, USA.
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28
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Choi SH, Park SW, Seong J. A nomogram for predicting survival of patients with locally advanced pancreatic cancer treated with chemoradiotherapy. Radiother Oncol 2018; 129:340-346. [PMID: 30177371 DOI: 10.1016/j.radonc.2018.08.006] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/26/2018] [Revised: 07/13/2018] [Accepted: 08/06/2018] [Indexed: 12/30/2022]
Abstract
BACKGROUND We developed a nomogram for predicting survival of patients with locally advanced pancreatic cancer (LAPC) after concurrent chemoradiotherapy (CRT) using 18F-flurodeoxyglucose-positron emission tomography (FDG-PET) parameters and CA 19-9 levels. METHODS Based on 426 patients with LAPC who received concurrent CRT between 2004 and 2015, we investigated significant prognostic factors for survival to build a nomogram, including the maximum standardized uptake value (SUVmax) and CA 19-9 levels. Predictive accuracy and discriminative ability were then measured. RESULTS Median progression-free survival and overall survival (OS) were 9.4 and 15.4 months, respectively, at a median 15-month follow-up. High-dose radiation (EQD2, ≥61 Gy), initial SUVmax <3.5 and CA 19-9 ≤400 U/mL, and surgical resection after CRT were significantly related to prolonged OS by multivariate analysis (p < 0.05). A nomogram model for OS was established and showed good calibration and acceptable discrimination (c-index 0.656). Using the nomogram, 3 different prognosis groups could be identified with a median OS of 25, 15, and 11 months (p < 0.001). CONCLUSION A nomogram was developed with high-dose radiation (EQD2, ≥61 Gy), initial SUVmax <3.5, CA 19-9 ≤400 U/mL, and surgical resection after CRT for patients with LAPC. This will help in clinical decision-making and in selecting patients for CRT.
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Affiliation(s)
- Seo Hee Choi
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea
| | - Seung Woo Park
- Division of Gastroenterology, Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, South Korea
| | - Jinsil Seong
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, South Korea.
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29
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Toesca DAS, Koong AJ, Poultsides GA, Visser BC, Haraldsdottir S, Koong AC, Chang DT. Management of Borderline Resectable Pancreatic Cancer. Int J Radiat Oncol Biol Phys 2018; 100:1155-1174. [PMID: 29722658 DOI: 10.1016/j.ijrobp.2017.12.287] [Citation(s) in RCA: 37] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2017] [Revised: 11/07/2017] [Accepted: 12/27/2017] [Indexed: 12/13/2022]
Abstract
With the rapid development of imaging modalities and surgical techniques, the clinical entity representing tumors that are intermediate between resectable and unresectable pancreatic adenocarcinoma has been identified has been termed "borderline resectable" (BR). These tumors are generally amenable for resection but portend an increased risk for positive margins after surgery and commonly necessitate vascular resection and reconstruction. Although there is a lack of consensus regarding the appropriate definition of what constitutes a BR pancreatic tumor, it has been demonstrated that this intermediate category carries a particular prognosis that is in between resectable and unresectable disease. In order to downstage the tumor and increase the probability of clear surgical margins, neoadjuvant therapy is being increasingly utilized and studied. There is a lack of high-level evidence to establish the optimal treatment regimen for BR tumors. When resection with negative margins is achieved after neoadjuvant therapy, the prognosis for BR tumors approaches and even exceeds that for resectable disease. This review presents the current definitions, different treatment approaches, and the clinical outcomes of BR pancreatic cancer.
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Affiliation(s)
- Diego A S Toesca
- Department of Radiation Oncology, Stanford Cancer Institute, Stanford, California
| | - Amanda J Koong
- Department of Radiation Oncology, Stanford Cancer Institute, Stanford, California
| | | | - Brendan C Visser
- Department of Surgery, Stanford Cancer Institute, Stanford, California
| | | | - Albert C Koong
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Daniel T Chang
- Department of Radiation Oncology, Stanford Cancer Institute, Stanford, California.
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30
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Gkika E, Oehlke O, Bunea H, Wiedenmann N, Adebahr S, Nestle U, Zamboglou C, Kirste S, Fennell J, Brunner T, Gainey M, Baltas D, Langer M, Urbach H, Bock M, Meyer PT, Grosu AL. Biological imaging for individualized therapy in radiation oncology: part II medical and clinical aspects. Future Oncol 2018. [DOI: 10.2217/fon-2017-0465] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Positron emission tomography and multiparametric MRI provide crucial information concerning tumor extent and normal tissue anatomy. Moreover, they are able to visualize biological characteristics of the tumor, which can be considered in the radiation treatment planning and monitoring. In this review we discuss the impact of biological imaging positron emission tomography and multiparametric MRI for radiation oncology, based on the data of the literature and on the experience of our own institution in this field.
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Affiliation(s)
- Eleni Gkika
- Department of Radiation Oncology, Medical Center, Faculty of Medicine, University of Freiburg, D-79106, Germany
- German Cancer Consortium (DKTK), Partner Site Freiburg, German Cancer Research Center (DKFZ), Heidelberg, D-69120, Germany
| | - Oliver Oehlke
- Department of Radiation Oncology, Medical Center, Faculty of Medicine, University of Freiburg, D-79106, Germany
- German Cancer Consortium (DKTK), Partner Site Freiburg, German Cancer Research Center (DKFZ), Heidelberg, D-69120, Germany
| | - Hatice Bunea
- Department of Radiation Oncology, Medical Center, Faculty of Medicine, University of Freiburg, D-79106, Germany
- German Cancer Consortium (DKTK), Partner Site Freiburg, German Cancer Research Center (DKFZ), Heidelberg, D-69120, Germany
| | - Nicole Wiedenmann
- Department of Radiation Oncology, Medical Center, Faculty of Medicine, University of Freiburg, D-79106, Germany
- German Cancer Consortium (DKTK), Partner Site Freiburg, German Cancer Research Center (DKFZ), Heidelberg, D-69120, Germany
| | - Sonja Adebahr
- Department of Radiation Oncology, Medical Center, Faculty of Medicine, University of Freiburg, D-79106, Germany
- German Cancer Consortium (DKTK), Partner Site Freiburg, German Cancer Research Center (DKFZ), Heidelberg, D-69120, Germany
| | - Ursula Nestle
- Department of Radiation Oncology, Medical Center, Faculty of Medicine, University of Freiburg, D-79106, Germany
- German Cancer Consortium (DKTK), Partner Site Freiburg, German Cancer Research Center (DKFZ), Heidelberg, D-69120, Germany
| | - Constantinos Zamboglou
- Department of Radiation Oncology, Medical Center, Faculty of Medicine, University of Freiburg, D-79106, Germany
- German Cancer Consortium (DKTK), Partner Site Freiburg, German Cancer Research Center (DKFZ), Heidelberg, D-69120, Germany
| | - Simon Kirste
- Department of Radiation Oncology, Medical Center, Faculty of Medicine, University of Freiburg, D-79106, Germany
- German Cancer Consortium (DKTK), Partner Site Freiburg, German Cancer Research Center (DKFZ), Heidelberg, D-69120, Germany
| | - Jamina Fennell
- Department of Radiation Oncology, Medical Center, Faculty of Medicine, University of Freiburg, D-79106, Germany
- German Cancer Consortium (DKTK), Partner Site Freiburg, German Cancer Research Center (DKFZ), Heidelberg, D-69120, Germany
| | - Thomas Brunner
- Department of Radiation Oncology, Medical Center, Faculty of Medicine, University of Freiburg, D-79106, Germany
- German Cancer Consortium (DKTK), Partner Site Freiburg, German Cancer Research Center (DKFZ), Heidelberg, D-69120, Germany
| | - Mark Gainey
- Department of Radiation Oncology, Medical Center, Faculty of Medicine, University of Freiburg, D-79106, Germany
- German Cancer Consortium (DKTK), Partner Site Freiburg, German Cancer Research Center (DKFZ), Heidelberg, D-69120, Germany
| | - Dimos Baltas
- Department of Radiation Oncology, Medical Center, Faculty of Medicine, University of Freiburg, D-79106, Germany
- German Cancer Consortium (DKTK), Partner Site Freiburg, German Cancer Research Center (DKFZ), Heidelberg, D-69120, Germany
| | - Mathias Langer
- Department of Radiology, Medical Center, Faculty of Medicine, University of Freiburg, D-79106, Germany
| | - Horst Urbach
- Department of Neuroradiology, Medical Center, Faculty of Medicine, University of Freiburg, D-79106, Germany
| | - Michael Bock
- Department of Radiology – Medical Physics, Department of Radiology, Faculty of Medicine, Medical Center, University of Freiburg, D-79106, Germany
| | - Philipp T Meyer
- German Cancer Consortium (DKTK), Partner Site Freiburg, German Cancer Research Center (DKFZ), Heidelberg, D-69120, Germany
- Department of Nuclear Medicine, Medical Center, Faculty of Medicine, University of Freiburg, D-79106, Germany
| | - Anca-Ligia Grosu
- Department of Radiation Oncology, Medical Center, Faculty of Medicine, University of Freiburg, D-79106, Germany
- German Cancer Consortium (DKTK), Partner Site Freiburg, German Cancer Research Center (DKFZ), Heidelberg, D-69120, Germany
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31
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Ariake K, Motoi F, Shimomura H, Mizuma M, Maeda S, Terao C, Tatewaki Y, Ohtsuka H, Fukase K, Masuda K, Hayashi H, Takadate T, Naitoh T, Taki Y, Unno M. 18-Fluorodeoxyglucose Positron Emission Tomography Predicts Recurrence in Resected Pancreatic Ductal Adenocarcinoma. J Gastrointest Surg 2018; 22:279-287. [PMID: 29119533 DOI: 10.1007/s11605-017-3627-3] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2017] [Accepted: 10/31/2017] [Indexed: 01/31/2023]
Abstract
BACKGROUND We aimed to determine whether treatment should be stratified according to 18-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) maximum standardized uptake values (SUVmax) in pancreatic ductal adenocarcinoma. METHODS Patients who underwent preoperative 18F-FDG PET/CT between 2006 and 2014 (n = 138) were stratified into high (≥ 4.85) and low (< 4.85) PET groups. The clinicopathological characteristics and prognostic outcomes were analyzed retrospectively. RESULTS The primary tumor SUVmax was positively correlated with preoperative CA19-9 levels (P < 0.001). The high PET group failed to achieve postoperative CA19-9 normalization (P = 0.014). Disease-specific (P < 0.001), recurrence-free (P < 0.001), liver recurrence-free (P < 0.001), and peritoneal recurrence-free (P = 0.020) survivals were significantly shorter in the high PET group. The primary tumor SUVmax was an independent predictive risk factor for liver metastasis (hazard ratio 3.46, 95% confidence interval 1.61-7.87; P = 0.001) and peritoneal recurrence (hazard ratio 3.36, 95% confidence interval 1.18-10.89; P = 0.023). CONCLUSIONS Surgical resection failed to achieve CA19-9 normalization in the high PET group and distant recurrence was frequent. This suggests the potential for residual cancer at distant sites, even after curative resection. Stronger preoperative systemic chemotherapy is preferred for the high PET group patients.
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Affiliation(s)
- Kyohei Ariake
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.
| | - Fuyuhiko Motoi
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan
| | - Hideo Shimomura
- Division of Nuclear Medicine and Radiology, Institute of Development, Aging, and Cancer, Tohoku University, Sendai, Japan
| | - Masamichi Mizuma
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan
| | - Shimpei Maeda
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan
| | - Chiaki Terao
- Division of Nuclear Medicine and Radiology, Institute of Development, Aging, and Cancer, Tohoku University, Sendai, Japan
| | - Yasuko Tatewaki
- Division of Nuclear Medicine and Radiology, Institute of Development, Aging, and Cancer, Tohoku University, Sendai, Japan
| | - Hideo Ohtsuka
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan
| | - Koji Fukase
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan
| | - Kunihiro Masuda
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan
| | - Hiroki Hayashi
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan
| | - Tatsuyuki Takadate
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan
| | - Takeshi Naitoh
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan
| | - Yasuyuki Taki
- Division of Nuclear Medicine and Radiology, Institute of Development, Aging, and Cancer, Tohoku University, Sendai, Japan
| | - Michiaki Unno
- Department of Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan
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Yeh R, Dercle L, Garg I, Wang ZJ, Hough DM, Goenka AH. The Role of 18F-FDG PET/CT and PET/MRI in Pancreatic Ductal Adenocarcinoma. Abdom Radiol (NY) 2018; 43:415-434. [PMID: 29143875 DOI: 10.1007/s00261-017-1374-2] [Citation(s) in RCA: 53] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) remains a difficult disease to treat and continues to portend a poor prognosis, as most patients are unresectable at diagnosis. 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) combined with CT (PET/CT) has been a cornerstone in oncological imaging of different cancers; however, the role of PET/CT in PDAC is continually evolving and currently not well established. Studies have shown the potential of PET/CT in guiding the management of patients with PDAC, with possible added benefit over anatomic imaging with CT or MRI in certain scenarios. PET/CT may be useful in diagnosis, initial staging, treatment response assessment, differentiation of recurrent tumor from post-treatment fibrosis, and radiotherapy planning. Additionally, PET/CT may be a cost-effective modality due to upstaging of patients originally deemed as surgical candidates. Recently, the advent of simultaneous PET/MRI represents an exciting advancement in hybrid functional imaging with potential applications in the imaging of PDAC. The advantages of PET/MRI include simultaneous acquisition to improve registration of fusion images, lower radiation dose, superior soft tissue contrast, and availability of multiparametric imaging. Studies are underway to evaluate the utility of PET/MRI in PDAC, including in initial staging and treatment response assessment and to determine the subgroup of patients that will benefit from PET/MRI. Further studies are warranted in both PET/CR and PET/MRI to better understand the role of these modalities in PDAC.
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Affiliation(s)
- Randy Yeh
- Department of Radiology, New York Presbyterian Hospital, Columbia University Medical Center, 622 W. 168th Street, PB 1-301, New York, NY, 10032, USA.
| | - Laurent Dercle
- Department of Radiology, New York Presbyterian Hospital, Columbia University Medical Center, 622 W. 168th Street, PB 1-301, New York, NY, 10032, USA
- Gustave Roussy, UMR1015, Villejuif, France
| | - Ishan Garg
- Department of Radiology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN, 55905, USA
| | - Zhen Jane Wang
- Department of Radiology and Biomedical Imaging, University of California, San Francisco, 505 Parnassus Ave, M-372, Box 0628, San Francisco, CA, 94143, USA
| | - David M Hough
- Department of Radiology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN, 55905, USA
| | - Ajit H Goenka
- Department of Radiology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN, 55905, USA
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Picchio M, Giovannini E, Passoni P, Busnardo E, Landoni C, Giovacchini G, Bettinardi V, Crivellaro C, Gianolli L, Di Muzio N, Messa C. Role of PET/CT in the Clinical Management of Locally Advanced Pancreatic Cancer. TUMORI JOURNAL 2018; 98:643-51. [DOI: 10.1177/030089161209800516] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/01/2023]
Abstract
Aim To evaluate the role of 18F-fluorodeoxyglucose (FDG) PET/CT in: a) the selection of patients with locally advanced pancreatic cancer for helical tomotherapy with concurrent chemotherapy (HTT-ChT); b) monitoring HTT-ChT treatment efficacy in comparison with contrast-enhanced CT (c.e.CT). Methods Forty-two consecutive patients with unresectable locally advanced pancreatic cancer referred for HTT-ChT were enrolled in the study. All patients were pretreated with induction ChT. Before the beginning of HTT-ChT treatment patients underwent diagnostic c.e.CT (CT0) and FDG PET/CT (PET/CT0) for staging. After staging, patients received HTT-ChT. Three months after the end of HTT-ChT a control c.e.CT (CT1) was done. FDG PET/CT (PET/CT1) was repeated only in patients with positive PET/CT0. PET/CT1 and CT1 were compared with baseline imaging results to assess treatment efficacy. Results In 31/42 cases (74%) PET/CT0 documented pathological uptake in pancreatic lesions, while in the remaining 11/42 cases it showed no uptake. In 7/42 (17%) patients, PET/CT0 also detected distant metastases, prompting a change in the therapeutic approach. Compared to PET/CT0, PET/CT1 (n = 18) documented 3 complete metabolic responses, 9 partial metabolic responses, 2 instances of stable metabolic disease, and 4 instances of progressive metabolic disease. In the same group of 18 patients, CT1 showed 0 complete responses, 3 partial responses, 8 instances of stable disease, and 7 instances of progressive disease compared to CT0. Concordance between PET/CT and CT response was seen in 33% of cases. In 50% of cases, PET/CT1 documented a response to therapy that was not evident on CT. Conclusions PET/CT influenced the treatment strategy by detecting distant metastases not documented by CT, thus accurately selecting patients for HTT-ChT after induction ChT. In monitoring treatment efficacy, PET/CT can detect a metabolic response to treatment not identified by CT.
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Affiliation(s)
- Maria Picchio
- Nuclear Medicine, San Raffaele Scientific Institute, Milan, Italy
- Institute for Bioimaging and Molecular Physiology, National Research Council (IBFM-CNR), Milan, Italy
| | | | - Paolo Passoni
- Radiation Oncology, San Raffaele Scientific Institute, Milan, Italy
| | - Elena Busnardo
- Nuclear Medicine, San Raffaele Scientific Institute, Milan, Italy
| | - Claudio Landoni
- Nuclear Medicine, San Raffaele Scientific Institute, Milan, Italy
- Tecnomed Foundation, University of Milano-Bicocca, Milan, Italy
| | - Giampiero Giovacchini
- Tecnomed Foundation, University of Milano-Bicocca, Milan, Italy
- Nuclear Medicine Department, Stadtspital Triemli, Zurich, Switzerland
| | - Valentino Bettinardi
- Nuclear Medicine, San Raffaele Scientific Institute, Milan, Italy
- Institute for Bioimaging and Molecular Physiology, National Research Council (IBFM-CNR), Milan, Italy
| | | | - Luigi Gianolli
- Nuclear Medicine, San Raffaele Scientific Institute, Milan, Italy
| | - Nadia Di Muzio
- Radiation Oncology, San Raffaele Scientific Institute, Milan, Italy
| | - Cristina Messa
- Institute for Bioimaging and Molecular Physiology, National Research Council (IBFM-CNR), Milan, Italy
- Tecnomed Foundation, University of Milano-Bicocca, Milan, Italy
- Nuclear Medicine, San Gerardo Hospital, Monza, Italy
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Zhang Y, Qin L, Zhang C. Investigation of Association Between Borderline Pancreatic Head Cancer and Glucose Uptake by Using Positron-Emission Tomographic Studies. Med Sci Monit 2017; 23:4947-4953. [PMID: 29036034 PMCID: PMC5655162 DOI: 10.12659/msm.904746] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
BACKGROUND In the background of the well-known importance of positron-emission tomographic studies (PET) in the prediction of pancreatic oncologic problems, we designed and performed this investigation to study the link between borderline pancreatic head cancer and glucose uptake by using PET. MATERIAL AND METHODS We retrospectively investigated patients during the period of almost 4 years (May 2013 to December 2016). Patients underwent potentially curative resection for borderline exocrine pancreatic head adenocarcinoma without undergoing neoadjuvant therapy. We divided our PET protocol into 2 sets of methods as per renal calyces: 1) U-RC type in which renal calyx (RC) has relatively higher value than that of 18F-fluoro-2-deoxyglucose (18F-FDG) uptake and 2) S-RC type in which renal calyx has similar value than that of 18F-FDG uptake. RESULTS A total of 67 patients were enrolled after reclassification on the basis of majority-agreement. Among these patients, U-RC type was found in 22 patients (32.8%) while S-RC type was found in 45 patients (67.2%). Significant statistical differences were observed for each of the 2 types of pancreatic head cancer (U-RC type and S-RC type) in terms of adjusted cancer antigen 19-9 (CA 19-9), size of the tumor, tumor volume (TV2.8), maximum standard uptake value (SUV↑), and lesion glycolysis (LG). A significantly longer disease-free survival time was shown by U-RC type (n=18) pancreatic cancer in comparison to S-RC type (n=42) (25.3 vs. 11.2 months). Additionally, U-RC type (n=4) had higher disease-free survival than did aS-RC type (n=3) (29.4 vs. 12.5 months). CONCLUSIONS Our PET protocol appears to be an indicator for estimation of recurrence of pancreatic head cancer and is as an indispensable asset to oncologists.
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Affiliation(s)
- Ying Zhang
- Department of Nuclear Medicine, Liaocheng People's Hospital, Liaocheng, Shandong, China (mainland)
| | - Lei Qin
- Department of Nuclear Medicine, Liaocheng People's Hospital, Liaocheng, Shandong, China (mainland)
| | - Changming Zhang
- Department of Nuclear Medicine, Liaocheng People's Hospital, Liaocheng, Shandong, China (mainland)
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Dohopolski MJ, Glaser SM, Vargo JA, Balasubramani GK, Beriwal S. Stereotactic body radiotherapy for locally-advanced unresectable pancreatic cancer-patterns of care and overall survival. J Gastrointest Oncol 2017; 8:766-777. [PMID: 29184680 PMCID: PMC5674248 DOI: 10.21037/jgo.2017.08.04] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2017] [Accepted: 06/19/2017] [Indexed: 12/29/2022] Open
Abstract
BACKGROUND Unresectable pancreatic cancer remains a challenging disease to treat. Stereotactic body radiotherapy (SBRT) allows for a higher biologically equivalent dose in an abbreviated course more convenient for patients and the integration of systemic therapy. We sought to investigate utilization trends and survival outcomes for patients treated with pancreatic SBRT versus conventionally fractionated radiotherapy (CFRT). METHODS We engaged the National Cancer Database (NCDB) from 1998-2012 and identified locally-advanced unresectable patients with histologically confirmed, non-metastatic, pancreatic adenocarcinoma who received radiotherapy. Patients who received CFRT (1.5-4.0 Gy per fraction to a dose of ≥45 Gy, n=11,879) were compared to those who received SBRT (6-15 Gy per fraction to a dose of ≥20 Gy, n=474). RESULTS Median follow-up was 11.0 months (18.4 months for survivors). SBRT utilization increased from 0.2% to 7.4% from 1998 to 2012 (P<0.05). On multivariable analysis, factors predictive for preferential utilization of SBRT over CFRT were later year of diagnosis, age ≥75 years, increased facility volume, and no chemotherapy in the initial treatment plan. Unadjusted median survival was 11.2 months for CFRT vs. 12.6 months for SBRT (P=0.002). Results were consistent in the propensity matched model. Variables predictive for improved survival on multivariable analysis were diagnosis after 2010, younger age, lower comorbidity score, tumor size <3 cm, nodal stage zero, and receipt of chemotherapy (P<0.05). CONCLUSIONS SBRT utilization has increased significantly and is associated with a small absolute improvement in overall survival (OS) compared to CFRT. The decreased treatment time, without apparent compromise in survival, makes SBRT an attractive option for patients with unresectable pancreatic cancer warranting further research.
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Affiliation(s)
- Michael J. Dohopolski
- Department of Radiation Oncology, University Pittsburgh School of Medicine, Pittsburgh, PA, USA
| | - Scott M. Glaser
- Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA
| | - John A. Vargo
- Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA
| | | | - Sushil Beriwal
- Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, PA, USA
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PET–Computed Tomography and Precision Medicine in Pancreatic Adenocarcinoma and Pancreatic Neuroendocrine Tumors. PET Clin 2017; 12:407-421. [DOI: 10.1016/j.cpet.2017.05.003] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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Zhu D, Wang L, Zhang H, Chen J, Wang Y, Byanju S, Liao M. Prognostic value of 18F-FDG-PET/CT parameters in patients with pancreatic carcinoma: A systematic review and meta-analysis. Medicine (Baltimore) 2017; 96:e7813. [PMID: 28816978 PMCID: PMC5571715 DOI: 10.1097/md.0000000000007813] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2017] [Revised: 07/13/2017] [Accepted: 07/31/2017] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND The identification of pancreatic carcinoma (PC) patients with poor prognosis is a priority in clinical oncology because of their high 5-year mortality. However, the prognostic value of pretreatment F-fluorodeoxyglucose (F-FDG)- positron emission tomography (PET)/computed tomography (CT) parameters in PC patients is controversial and no consensus exists as to its predictive capability. This meta-analysis was performed to comprehensively explore the prognostic significance of F-FDG-PET/CT parameters in patients with pancreatic carcinoma. METHODS Extensive literature searches of the PubMed, Embase, Web of Science, and Cochrane Library databases were conducted to identify literature published until March 5, 2017. Comparative analyses of the pooled hazard ratios (HRs) for event-free survival (EFS) and overall survival (OS) were performed to assess their correlations with pretreatment maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG). Either the fixed- or the random-effects model was adopted, depending on the heterogeneity observed across studies. Subgroup and sensitivity analyses were performed to assess the robustness of the results. RESULTS Sixteen studies including 1146 patients were identified. The pooled HRs for the probability of EFS were 1.90 (95% confidential interval (CI): 1.48-2.45) for SUVmax, 1.76 (95% CI: 1.20-2.58) for MTV, and 1.81 (95% CI: 1.27-2.58) for TLG. The pooled HRs for the probability of OS were 1.21 (95% CI: 1.12-1.31) for SUVmax, 1.56 (95% CI: 1.13-2.16) for MTV, and 1.70 (95% CI: 1.25-2.30) for TLG. A slight publication bias was detected using Begg test. After adjustment using the trim and fill procedure, the corrected HRs were not significantly different. The results of the subgroup analyses by SUVmax, MTV, and TLG showed that these factors may have similar prognostic significance. CONCLUSION F-FDG-PET/CT parameters, such as SUVmax, MTV, and TLG, may be significant prognostic factors in patients with pancreatic carcinoma. F-FDG-PET/CT imaging could be a promising tool to provide prognostic information for these patients.
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Affiliation(s)
| | - Lisha Wang
- Department of Neurology, ZhongNan Hospital of WuHan University, Wuhan City, People's Republic of China
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Gunda V, Souchek J, Abrego J, Shukla SK, Goode GD, Vernucci E, Dasgupta A, Chaika NV, King RJ, Li S, Wang S, Yu F, Bessho T, Lin C, Singh PK. MUC1-Mediated Metabolic Alterations Regulate Response to Radiotherapy in Pancreatic Cancer. Clin Cancer Res 2017; 23:5881-5891. [PMID: 28720669 DOI: 10.1158/1078-0432.ccr-17-1151] [Citation(s) in RCA: 74] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2017] [Revised: 06/03/2017] [Accepted: 07/14/2017] [Indexed: 11/16/2022]
Abstract
Purpose:MUC1, an oncogene overexpressed in multiple solid tumors, including pancreatic cancer, reduces overall survival and imparts resistance to radiation and chemotherapies. We previously identified that MUC1 facilitates growth-promoting metabolic alterations in pancreatic cancer cells. The present study investigates the role of MUC1-mediated metabolism in radiation resistance of pancreatic cancer by utilizing cell lines and in vivo models.Experimental Design: We used MUC1-knockdown and -overexpressed cell line models for evaluating the role of MUC1-mediated metabolism in radiation resistance through in vitro cytotoxicity, clonogenicity, DNA damage response, and metabolomic evaluations. We also investigated whether inhibition of glycolysis could revert MUC1-mediated metabolic alterations and radiation resistance by using in vitro and in vivo models.Results: MUC1 expression diminished radiation-induced cytotoxicity and DNA damage in pancreatic cancer cells by enhancing glycolysis, pentose phosphate pathway, and nucleotide biosynthesis. Such metabolic reprogramming resulted in high nucleotide pools and radiation resistance in in vitro models. Pretreatment with the glycolysis inhibitor 3-bromopyruvate abrogated MUC1-mediated radiation resistance both in vitro and in vivo, by reducing glucose flux into nucleotide biosynthetic pathways and enhancing DNA damage, which could again be reversed by pretreatment with nucleoside pools.Conclusions: MUC1-mediated nucleotide metabolism plays a key role in facilitating radiation resistance in pancreatic cancer and targeted effectively through glycolytic inhibition. Clin Cancer Res; 23(19); 5881-91. ©2017 AACR.
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Affiliation(s)
- Venugopal Gunda
- The Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska
| | - Joshua Souchek
- The Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska
| | - Jaime Abrego
- The Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska
| | - Surendra K Shukla
- The Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska
| | - Gennifer D Goode
- The Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska
| | - Enza Vernucci
- The Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska
| | - Aneesha Dasgupta
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska
| | - Nina V Chaika
- The Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska
| | - Ryan J King
- The Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska
| | - Sicong Li
- Department of Radiation Oncology, University of Nebraska Medical Center, Omaha, Nebraska
| | - Shuo Wang
- Department of Radiation Oncology, University of Nebraska Medical Center, Omaha, Nebraska
| | - Fang Yu
- Department of Biostatistics, University of Nebraska Medical Center, Omaha, Nebraska
| | - Tadayoshi Bessho
- The Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska
| | - Chi Lin
- Department of Radiation Oncology, University of Nebraska Medical Center, Omaha, Nebraska
| | - Pankaj K Singh
- The Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, Nebraska. .,Department of Biostatistics, University of Nebraska Medical Center, Omaha, Nebraska.,Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska.,Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, Nebraska
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Nakajo M, Kajiya Y, Tani A, Jinguji M, Nakajo M, Nihara T, Fukukura Y, Yoshiura T. A pilot study of the diagnostic and prognostic values of FLT-PET/CT for pancreatic cancer: comparison with FDG-PET/CT. Abdom Radiol (NY) 2017; 42:1210-1221. [PMID: 27891549 DOI: 10.1007/s00261-016-0987-1] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/02/2023]
Abstract
PURPOSE The purpose of the study was to examine the diagnostic and prognostic values of 18F-fluorothymidine (FLT)-PET/CT for pancreatic cancer by comparing with 18F-fluorodeoxyglucose (FDG)-PET/CT. METHODS Fifteen patients with newly diagnosed pancreatic cancer underwent both FLT and FDG-PET/CT scans before treatment. The sensitivity, specificity, and accuracy in detecting nodal and distant metastases were compared between both scans using McNemar exact or χ 2 test. Progression-free survival (PFS) and overall survival (OS) were calculated by Kaplan-Meier method. Prognostic significance was assessed by Cox proportional hazards analysis. RESULTS Both scans visualized all primary cancers. The sensitivity, specificity, and accuracy per patient basis for detecting nodal metastasis were equal and 63.6% (7/11), 100% (4/4), and 73.3% (11/15) for both scans, and for detecting distant metastasis were 100% (6/6), 88.9% (8/9), and 93.3% (14/15) for FDG-PET/CT, and 50.0% (3/6), 100% (9/9), and 80.0% (12/15) for FLT-PET/CT, respectively, without significant difference in each of them between both scans (p > 0.05). However, of 4 patients with multiple liver metastases, FDG-PET/CT was positive in all, but FLT-PET/CT was negative in three patients. At univariate analysis, only FLT-SUVmax correlated with PFS (hazard ratio, 1.306, p = 0.048), and FDG total lesion glycolysis (TLG), FLT-SUVmax, and FLT-total lesion proliferation (TLP) correlated with OS (p = 0.021, p = 0.005, and p = 0.022, respectively). At bivariate analysis, FLT-SUVmax was superior to FDG-TLG or FLT-TLP for prediction of OS [HR (adjusted for FDG-TLG), 1.491, p = 0.034, HR (adjusted for FLT-TLP), 1.542, p = 0.023]. CONCLUSION FLT-PET/CT may have a potential equivalent to FDG-PET/CT for detecting primary and metastatic cancers except liver metastasis. FLT-SUVmax can provide the most significant prognostic information.
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Affiliation(s)
- Masatoyo Nakajo
- Department of Radiology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan.
- Department of Radiology, Nanpuh Hospital, 14-3 Nagata, Kagoshima, 892-8512, Japan.
| | - Yoriko Kajiya
- Department of Radiology, Nanpuh Hospital, 14-3 Nagata, Kagoshima, 892-8512, Japan
| | - Atsushi Tani
- Department of Radiology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan
| | - Megumi Jinguji
- Department of Radiology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan
| | - Masayuki Nakajo
- Department of Radiology, Nanpuh Hospital, 14-3 Nagata, Kagoshima, 892-8512, Japan
| | - Tohru Nihara
- Department of Gastroenterology, Nanpuh Hospital, 14-3 Nagata, Kagoshima, 892-8512, Japan
| | - Yoshihiko Fukukura
- Department of Radiology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan
| | - Takashi Yoshiura
- Department of Radiology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan
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Hong JC, Czito BG, Willett CG, Palta M. A current perspective on stereotactic body radiation therapy for pancreatic cancer. Onco Targets Ther 2016; 9:6733-6739. [PMID: 27826200 PMCID: PMC5096771 DOI: 10.2147/ott.s99826] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Pancreatic cancer is a formidable malignancy with poor outcomes. The majority of patients are unable to undergo resection, which remains the only potentially curative treatment option. The management of locally advanced (unresectable) pancreatic cancer is controversial; however, treatment with either chemotherapy or chemoradiation is associated with high rates of local tumor progression and metastases development, resulting in low survival rates. An emerging local modality is stereotactic body radiation therapy (SBRT), which uses image-guided, conformal, high-dose radiation. SBRT has demonstrated promising local control rates and resultant quality of life with acceptable rates of toxicity. Over the past decade, increasing clinical experience and data have supported SBRT as a local treatment modality. Nevertheless, additional research is required to further evaluate the role of SBRT and improve upon the persistently poor outcomes associated with pancreatic cancer. This review discusses the existing clinical experience and technical implementation of SBRT for pancreatic cancer and highlights the directions for ongoing and future studies.
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Affiliation(s)
- Julian C Hong
- Department of Radiation Oncology, Duke University, Durham, NC, USA
| | - Brian G Czito
- Department of Radiation Oncology, Duke University, Durham, NC, USA
| | | | - Manisha Palta
- Department of Radiation Oncology, Duke University, Durham, NC, USA
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Wartski M. La tomographie par émission de positons (TEP) en oncologie digestive. Presse Med 2016; 45:734-41. [DOI: 10.1016/j.lpm.2016.06.028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2016] [Accepted: 06/16/2016] [Indexed: 10/21/2022] Open
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Prognostic impact of tumour burden assessed by metabolic tumour volume on FDG PET/CT in anal canal cancer. Eur J Nucl Med Mol Imaging 2016; 44:63-70. [PMID: 27503193 DOI: 10.1007/s00259-016-3475-5] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2016] [Accepted: 07/25/2016] [Indexed: 12/22/2022]
Abstract
PURPOSE The aim of this study was to confirm the prognostic value of metabolic tumour volume (MTV) at the primary site on initial work-up FDG PET/CT in patients with squamous cell carcinoma (SCC) of the anal canal. METHODS Patients with a recent diagnosis of SCC of the anal canal without metastases undergoing PET/CT for initial work-up and treated with (chemo)radiotherapy were retrospectively reviewed. Computer-aided MTV and SUVmax were determined. Survival rates were estimated using the Kaplan-Meier method. Cox regression analysis was used to evaluate prognostic variables of progression-free survival and overall survival (OS). RESULTS The study group comprised 75 patients who had an initial work-up PET/CT. Five patients (6.7 %) had stage I disease, 22 (29.3 %) stage II disease, 20 (26.7 %) stage IIIA disease, and 28 (37.3 %) stage IIIB disease. Median follow-up was 51 months (range 10 - 117 months). Global 4-year OS was 82.7 %, ranging from 100 % in patients with stage I disease to 75 % in patients with stage IIIB disease. MTV at the primary site was significantly and independently correlated with OS (p < 0.05), as patients with MTV less than 7 cm3 had a better prognosis. SUVmax was not correlated with survival parameters. Metabolic involvement of the inguinal lymph nodes was also correlated with a poor outcome in the univariate analysis (p < 0.05). CONCLUSION MTV at the primary site is a prognostic biomarker in anal canal cancer. Hypermetabolic inguinal lymph nodes also appear to be correlated with survival.
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Cui Y, Song J, Pollom E, Alagappan M, Shirato H, Chang DT, Koong AC, Li R. Quantitative Analysis of (18)F-Fluorodeoxyglucose Positron Emission Tomography Identifies Novel Prognostic Imaging Biomarkers in Locally Advanced Pancreatic Cancer Patients Treated With Stereotactic Body Radiation Therapy. Int J Radiat Oncol Biol Phys 2016; 96:102-9. [PMID: 27511850 DOI: 10.1016/j.ijrobp.2016.04.034] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2015] [Revised: 04/16/2016] [Accepted: 04/27/2016] [Indexed: 12/11/2022]
Abstract
PURPOSE To identify prognostic biomarkers in pancreatic cancer using high-throughput quantitative image analysis. METHODS AND MATERIALS In this institutional review board-approved study, we retrospectively analyzed images and outcomes for 139 locally advanced pancreatic cancer patients treated with stereotactic body radiation therapy (SBRT). The overall population was split into a training cohort (n=90) and a validation cohort (n=49) according to the time of treatment. We extracted quantitative imaging characteristics from pre-SBRT (18)F-fluorodeoxyglucose positron emission tomography, including statistical, morphologic, and texture features. A Cox proportional hazard regression model was built to predict overall survival (OS) in the training cohort using 162 robust image features. To avoid over-fitting, we applied the elastic net to obtain a sparse set of image features, whose linear combination constitutes a prognostic imaging signature. Univariate and multivariate Cox regression analyses were used to evaluate the association with OS, and concordance index (CI) was used to evaluate the survival prediction accuracy. RESULTS The prognostic imaging signature included 7 features characterizing different tumor phenotypes, including shape, intensity, and texture. On the validation cohort, univariate analysis showed that this prognostic signature was significantly associated with OS (P=.002, hazard ratio 2.74), which improved upon conventional imaging predictors including tumor volume, maximum standardized uptake value, and total legion glycolysis (P=.018-.028, hazard ratio 1.51-1.57). On multivariate analysis, the proposed signature was the only significant prognostic index (P=.037, hazard ratio 3.72) when adjusted for conventional imaging and clinical factors (P=.123-.870, hazard ratio 0.53-1.30). In terms of CI, the proposed signature scored 0.66 and was significantly better than competing prognostic indices (CI 0.48-0.64, Wilcoxon rank sum test P<1e-6). CONCLUSION Quantitative analysis identified novel (18)F-fluorodeoxyglucose positron emission tomography image features that showed improved prognostic value over conventional imaging metrics. If validated in large, prospective cohorts, the new prognostic signature might be used to identify patients for individualized risk-adaptive therapy.
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Affiliation(s)
- Yi Cui
- Department of Radiation Oncology, Stanford University, Palo Alto, California; Global Institution for Collaborative Research and Education, Hokkaido University, Sapporo, Japan
| | - Jie Song
- Department of Radiation Oncology, Stanford University, Palo Alto, California
| | - Erqi Pollom
- Department of Radiation Oncology, Stanford University, Palo Alto, California
| | | | - Hiroki Shirato
- Global Institution for Collaborative Research and Education, Hokkaido University, Sapporo, Japan
| | - Daniel T Chang
- Department of Radiation Oncology, Stanford University, Palo Alto, California; Stanford Cancer Institute, Stanford, California
| | - Albert C Koong
- Department of Radiation Oncology, Stanford University, Palo Alto, California; Stanford Cancer Institute, Stanford, California
| | - Ruijiang Li
- Department of Radiation Oncology, Stanford University, Palo Alto, California; Global Institution for Collaborative Research and Education, Hokkaido University, Sapporo, Japan; Stanford Cancer Institute, Stanford, California.
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The Role of Positron Emission Tomography/Computed Tomography in Management and Prediction of Survival in Pancreatic Cancer. J Comput Assist Tomogr 2016; 40:142-51. [DOI: 10.1097/rct.0000000000000323] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
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Wang SL, Cao S, Sun YN, Wu R, Chi F, Tang MY, Jin XY, Chen XD. Standardized uptake value on positron emission tomography/computed tomography predicts prognosis in patients with locally advanced pancreatic cancer. ABDOMINAL IMAGING 2015; 40:3117-21. [PMID: 26350284 DOI: 10.1007/s00261-015-0544-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
BACKGROUND The aim of the present study was to investigate the use and value of maximum standardized uptake value (SUV max) on positron emission tomography/computed tomography (PET/CT) images as a prognostic marker for patients with locally advanced pancreatic cancer (LAPC). MATERIALS AND METHODS The medical records of all consecutive patients who underwent PET/CT examination in our institution were retrospectively reviewed. Inclusion criteria were histologically or cytologically proven LAPC. Patients with distant metastasis were excluded. For statistical analysis, the SUV max of primary pancreatic cancer was measured. Survival rates were calculated using the Kaplan-Meier method, and multivariable analysis was performed to determine the association of SUV max with overall survival (OS) and progression-free survival (PFS) using a Cox proportional hazards model. RESULTS Between July 2006 and June 2013, 69 patients were enrolled in the present study. OS and PFS were 14.9 months [95% confidence interval (CI) 13.1-16.7] and 8.3 months (95% CI 7.1-9.5), respectively. A high SUV max (>5.5) was observed in 35 patients, who had significantly worse OS and PFS than the remaining patients with a low SUV max (P = 0.025 and P = 0.003). Univariate analysis showed that SUV max and tumor size were prognostic factors for OS, with a hazard ratio of 1.90 and 1.81, respectively. A high SUV max was an independent prognostic factor, with a hazard ratio of 1.89 (95% CI 1.015-3.519, P = 0.045). CONCLUSION The present study suggests that increased SUV max is a predictor of poor prognosis in patients with LAPC.
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Affiliation(s)
- Si-Liang Wang
- Department of Medical Oncology, Shengjing Hospital of China Medical University, 36 Sanhao Road, Shenyang, 110004, China
| | - Shuo Cao
- Department of Medical Oncology, Shengjing Hospital of China Medical University, 36 Sanhao Road, Shenyang, 110004, China
| | - Yu-Nan Sun
- Department of Medical Oncology, Shengjing Hospital of China Medical University, 36 Sanhao Road, Shenyang, 110004, China
| | - Rong Wu
- Department of Medical Oncology, Shengjing Hospital of China Medical University, 36 Sanhao Road, Shenyang, 110004, China.
| | - Feng Chi
- Department of Medical Oncology, Shengjing Hospital of China Medical University, 36 Sanhao Road, Shenyang, 110004, China
| | - Mei-Yue Tang
- Department of Medical Oncology, Shengjing Hospital of China Medical University, 36 Sanhao Road, Shenyang, 110004, China
| | - Xue-Ying Jin
- Department of Medical Oncology, Shengjing Hospital of China Medical University, 36 Sanhao Road, Shenyang, 110004, China
| | - Xiao-Dong Chen
- Department of Medical Oncology, Shengjing Hospital of China Medical University, 36 Sanhao Road, Shenyang, 110004, China
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Sakane M, Tatsumi M, Kim T, Hori M, Onishi H, Nakamoto A, Eguchi H, Nagano H, Wakasa K, Hatazawa J, Tomiyama N. Correlation between apparent diffusion coefficients on diffusion-weighted MRI and standardized uptake value on FDG-PET/CT in pancreatic adenocarcinoma. Acta Radiol 2015; 56:1034-41. [PMID: 25267921 DOI: 10.1177/0284185114549825] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2013] [Accepted: 08/10/2014] [Indexed: 12/13/2022]
Abstract
BACKGROUND Diffusion-weighted magnetic resonance imaging (DW-MRI) and 2-deoxy-2-[18F]fluoro-D-glucose-positron emission tomography/computed tomography (PET/CT) is increasingly recognized as important for assessing tumor malignancy in oncology. Apparent diffusion coefficient (ADC) and standardized uptake value (SUV) are negatively correlated in some types of cancer based on tumor aggressiveness. PURPOSE To evaluate relationships between ADC of magnetic resonance imaging and SUV of PET/CT in pancreatic adenocarcinomas. MATERIAL AND METHODS Twenty-nine patients histopathologically diagnosed with pancreatic adenocarcinomas were evaluated. ADC maps were generated from 3 T-MRI using b values (b = 0, 800 s/mm(2)). PET/CT was performed 60 min after intravenous injection of FDG (3.7 MBq/kg). The margins of tumors on DW-MRI and PET/CT were assessed to measure ADC and SUV of tumor appropriately. For tumors considered well-marginated, minimal and mean ADC as well as maximal and mean SUV were measured. The correlation of ADC and SUV were statistically evaluated and survival period stratified on ADC and SUV also evaluated. RESULTS Twenty-two tumors on DW-MRI and 25 on PET/CT were deemed well-marginated. Minimal ADC was significantly and negatively correlated with maximal and mean SUV (r = -0.61, P = 0.0040; r = -0.66, P = 0.0015), and mean ADC also showed significantly and negatively correlation with maximal and mean SUV (r = -0.50, P = 0.024; r = -0.54, P = 0.012). There was no significant difference on overall survival stratified on ADC and SUV. CONCLUSION ADC and SUV were significantly correlated in pancreatic adenocarcinomas, although no significant findings were observed in overall survival.
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Affiliation(s)
- Makoto Sakane
- Department of Radiology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Mitsuaki Tatsumi
- Department of Nuclear Medicine and Tracer Kinetics, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Tonsok Kim
- Department of Radiology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Masatoshi Hori
- Department of Radiology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Hiromitsu Onishi
- Department of Radiology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Atsushi Nakamoto
- Department of Radiology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Hidetoshi Eguchi
- Department of Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Hiroaki Nagano
- Department of Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Kenichi Wakasa
- Department of Diagnostic Pathology, Osaka City University Graduate School of Medicine, Osaka, Japan
| | - Jun Hatazawa
- Department of Nuclear Medicine and Tracer Kinetics, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Noriyuki Tomiyama
- Department of Radiology, Osaka University Graduate School of Medicine, Osaka, Japan
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Hybrid imaging for pancreatic malignancy: clinical applications, merits, limitations, and pitfalls. Clin Nucl Med 2015; 40:206-13. [PMID: 25608151 DOI: 10.1097/rlu.0000000000000677] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
The role of PET/CT in pancreatic malignancy is evolving with new scientific evidence emerging continuously. PET/CT applications in imaging the pancreas and its organ-specific merits, limitations, and potential pitfalls are still evolving. This article provides an overview of the state-of-the-art applications of PET/CT imaging in evaluating pancreatic malignancy, comparing with conventional imaging modalities, such as contrast-enhanced CT and MRI. Current PET/MRI is also reviewed, along with brief discussion on cost-benefit analysis.
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Prognostic Value of FDG PET/CT-Derived Parameters in Pancreatic Adenocarcinoma at Initial PET/CT Staging. AJR Am J Roentgenol 2015; 204:1093-9. [PMID: 25905947 DOI: 10.2214/ajr.14.13156] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
OBJECTIVE The purpose of this study is to evaluate the performance of PET-derived parameters as prognostic markers for overall survival (OS) and progression-free survival (PFS) outcome in patients with pancreatic adenocarcinoma. MATERIALS AND METHODS We conducted a retrospective study of 106 patients (62 men and 44 women) with histologically proven pancreatic adenocarcinoma who underwent initial staging FDG PET/CT before treatment. Peak standardized uptake value (SUV), maximum SUV (SUVmax), metabolic tumor volume, and tumor glycolytic activity of the primary pancreatic tumor were measured. Two segmentation methods were performed to obtain the metabolic tumor volume and tumor glycolytic activity for all tumors: a gradient-based segmentation model (metabolic tumor volume and tumor glycolytic activity by gradient edge detection) and a fixed-threshold model with a threshold of 50% of the lesion's SUVmax and peak SUV. Univariate and multivariate Cox regression models were developed including clinical and imaging parameters for OS and PFS. RESULTS Multivariate Cox regression analysis showed a statistically significant association between PFS and age, SUVmax, peak SUV, and tumor glycolytic activity by gradient edge detection. There was a statistically significant difference in PFS for patients with values above and below the median cutoff points for SUVmax (hazard ratio [HR], 1.12; p < 0.01), peak SUV (HR, 1.25; p < 0.02), and tumor glycolytic activity measured by gradient edge detection (HR, 1.00; p < 0.02) of the primary tumor. However, multivariate Cox regression analysis showed a statistically significant association only between tumor glycolytic activity by gradient edge detection and OS (p = 0.04), and there was a statistically significant difference in OS between patients with values above and below the median cutoff point for the tumor glycolytic activity by gradient edge detection of the primary tumor (HR, 1.42; p = 0.05). CONCLUSION Age, SUVmax, peak SUV, and total lesion glycolysis (i.e., tumor glycolytic activity) of the primary tumor are associated with PFS, and tumor glycolytic activity is associated with OS in patients with pancreatic adenocarcinoma.
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Hexige S, Ardito-Abraham CM, Wu Y, Wei Y, Fang Y, Han X, Li J, Zhou P, Yi Q, Maitra A, Liu JO, Tuveson DA, Lou W, Yu L. Identification of novel vascular projections with cellular trafficking abilities on the microvasculature of pancreatic ductal adenocarcinoma. J Pathol 2015; 236:142-154. [PMID: 25561062 PMCID: PMC5089710 DOI: 10.1002/path.4506] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2014] [Revised: 12/08/2014] [Accepted: 12/30/2014] [Indexed: 12/12/2022]
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a nearly lethal neoplasm. It is a remarkably stroma-rich, vascular-poor and hypo-perfused tumour, which prevents efficient drug delivery. Paradoxically, the neoplastic cells have robust glucose uptake, suggesting that the microvasculature has adopted an alternative method for nutrient uptake and cellular trafficking. Using adapted thick tumour section immunostaining and three-dimensional (3D) construction imaging in human tissue samples, we identified an undiscovered feature of the mature microvasculature in advanced PDAC tumours; long, hair-like projections on the basal surface of microvessels that we refer to as 'basal microvilli'. Functionally, these basal microvilli have an actin-rich cytoskeleton and endocytic and exocytic properties, and contain glucose transporter-1 (GLUT-1)-positive vesicles. Clinically, as demonstrated by PET-CT, the tumour microvasculature with the longest and most abundant basal microvilli correlated with high glucose uptake of the PDAC tumour itself. In addition, these basal microvilli were found in regions of the tumour with low GLUT-1 expression, suggesting that their presence could be dependent upon the glucose concentration in the tumour milieu. Similar microvasculature features were also observed in a K-Ras-driven model of murine PDAC. Altogether, these basal microvilli mark a novel pathological feature of PDAC microvasculature. Because basal microvilli are pathological features with endo- and exocytic properties, they may provide a non-conventional method for cellular trafficking in PDAC tumours.
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Affiliation(s)
- Saiyin Hexige
- State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, 200433, People's Republic of China
| | | | - Yanhua Wu
- State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, 200433, People's Republic of China
| | - Youheng Wei
- State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, 200433, People's Republic of China
| | - Yuan Fang
- Cold Spring Harbor Laboratory, New York, NY11724, United States of America
| | - Xu Han
- Cold Spring Harbor Laboratory, New York, NY11724, United States of America
| | - Jianang Li
- Cold Spring Harbor Laboratory, New York, NY11724, United States of America
| | - Ping Zhou
- State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, 200433, People's Republic of China
| | - Qing Yi
- General Surgery Department, Zhongshan Hospital, Fudan University, Shanghai, 20032, People's Republic of China
| | - Anirban Maitra
- Cleveland Clinic, Lerner Research Institute, Cleveland, Ohio, 44195
- Department of Pathology, The University of Texas MD Anderson Cancer Center
| | - Jun O Liu
- Departments of Pharmacology and Oncology, Johns Hopkins School of Medicine, MD 21205, United States of America
| | - David A Tuveson
- Cold Spring Harbor Laboratory, New York, NY11724, United States of America
| | - Wenhui Lou
- Cold Spring Harbor Laboratory, New York, NY11724, United States of America
| | - Long Yu
- State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, 200433, People's Republic of China
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