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1
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Zhang B, Xue L, Wu ZB. Structure and Function of Somatostatin and Its Receptors in Endocrinology. Endocr Rev 2025; 46:26-42. [PMID: 39116368 DOI: 10.1210/endrev/bnae022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/27/2023] [Revised: 07/16/2024] [Accepted: 07/26/2024] [Indexed: 08/10/2024]
Abstract
Somatostatin analogs, such as octreotide, lanreotide, and pasireotide, which function as somatostatin receptor ligands (SRLs), are the main drugs used for the treatment of acromegaly. These ligands are also used as important molecules for radiation therapy and imaging of neuroendocrine tumors. Somatostatin receptors (SSTRs) are canonical G protein-coupled proteins that play a role in metabolism, growth, and pathological conditions such as hormone disorders, neurological diseases, and cancers. Cryogenic electron microscopy combined with the protein structure prediction platform AlphaFold has been used to determine the 3-dimensional structures of many proteins. Recently, several groups published a series of papers illustrating the 3-dimensional structure of SSTR2, including that of the inactive/activated SSTR2-G protein complex bound to different ligands. The results revealed the residues that contribute to the ligand binding pocket and demonstrated that Trp8-Lys9 (the W-K motif) in somatostatin analogs is the key motif in stabilizing the bottom part of the binding pocket. In this review, we discuss the recent findings related to the structural analysis of SSTRs and SRLs, the relationships between the structural data and clinical findings, and the future development of novel structure-based therapies.
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Affiliation(s)
- Bo Zhang
- Department of Neurosurgery, Center of Pituitary Tumor, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Li Xue
- Department of Neurosurgery, Center of Pituitary Tumor, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Zhe Bao Wu
- Department of Neurosurgery, Center of Pituitary Tumor, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
- Department of Neurosurgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325005, China
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2
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Prado Wohlwend S, Bello Arques P. Radio theranostics in paragangliomas and pheochromocytomas. Rev Esp Med Nucl Imagen Mol 2024; 43:500017. [PMID: 38735639 DOI: 10.1016/j.remnie.2024.500017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2024] [Accepted: 05/02/2024] [Indexed: 05/14/2024]
Abstract
This continuing education aims to present in a clear and easy-to-understand manner the biology of paragangliomas and pheochromocytomas (PPGLs), the functional imaging studies available for their diagnosis and therapeutic planning, the requirements necessary to administer radioligand therapy (RLT) and the characteristics of these treatments (inclusion criteria, administration protocols, adverse effects and future perspectives). In this pathology we have two RLT options: [131I]MIBG and [177Lu]Lu-DOTA-TATE. The indication for treatment is determined by the expression of its therapeutic target in functional imaging studies, allowing precision and personalized medicine. Although most of the results we have for both treatments have as origin small retrospective series, RLT is presented as a safe and well-tolerated therapeutic option in PPGLs with slow-moderate progression or with uncontrollable symptoms, obtaining high disease control rates.
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Affiliation(s)
- Stefan Prado Wohlwend
- Servicio de Medicina Nuclear, Hospital Universitario y Politécnico La Fe, Valencia, Spain; Clinical Center of Excellence Pheo Para Alliance.
| | - Pilar Bello Arques
- Servicio de Medicina Nuclear, Hospital Universitario y Politécnico La Fe, Valencia, Spain; Clinical Center of Excellence Pheo Para Alliance
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3
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Banerjee J, Ranjan RP, Alam MT, Deshmukh S, Tripathi PP, Gandhi S, Banerjee S. Virus-associated neuroendocrine cancers: Pathogenesis and current therapeutics. Pathol Res Pract 2023; 248:154720. [PMID: 37542862 DOI: 10.1016/j.prp.2023.154720] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/05/2023] [Revised: 07/22/2023] [Accepted: 07/26/2023] [Indexed: 08/07/2023]
Abstract
Neuroendocrine neoplasms (NENs) comprise malignancies involving neuroendocrine cells that often lead to fatal pathological conditions. Despite escalating global incidences, NENs still have poor prognoses. Interestingly, research indicates an intricate association of tumor viruses with NENs. However, there is a dearth of comprehension of the complete scenario of NEN pathophysiology and its precise connections with the tumor viruses. Interestingly, several cutting-edge experiments became helpful for further screening of NET for the presence of polyomavirus, Human papillomavirus (HPV), Kaposi sarcoma-associated herpesvirus (KSHV), Epstein Barr virus (EBV), etc. Current research on the neuroendocrine tumor (NET) pathogenesis provides new information concerning their molecular mechanisms and therapeutic interventions. Of note, scientists observed that metastatic neuroendocrine tumors still have a poor prognosis with a palliative situation. Different oncolytic vector has already demonstrated excellent efficacies in clinical studies. Therefore, oncolytic virotherapy or virus-based immunotherapy could be an emerging and novel therapeutic intervention. In-depth understanding of all such various aspects will aid in managing, developing early detection assays, and establishing targeted therapeutic interventions for NENs concerning tumor viruses. Hence, this review takes a novel approach to discuss the dual role of tumor viruses in association with NENs' pathophysiology as well as its potential therapeutic interventions.
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Affiliation(s)
- Juni Banerjee
- Institute of Advanced Research, Koba Institutional Area, Gandhinagar, Gujarat 382426, India.
| | - Ramya P Ranjan
- National Institute of Animal Biotechnology (NIAB), Gachibowli, Hyderabad, Telangana 500032, India
| | - Md Tanjim Alam
- CSIR-Indian Institute of Chemical Biology (IICB), 4, Raja S. C. Mullick Road, Kolkata 700032, India; IICB-Translational Research Unit of Excellence(IICB-TRUE), Kolkata 700091, India
| | - Sanika Deshmukh
- Institute of Advanced Research, Koba Institutional Area, Gandhinagar, Gujarat 382426, India
| | - Prem Prakash Tripathi
- CSIR-Indian Institute of Chemical Biology (IICB), 4, Raja S. C. Mullick Road, Kolkata 700032, India; IICB-Translational Research Unit of Excellence(IICB-TRUE), Kolkata 700091, India.
| | - Sonu Gandhi
- National Institute of Animal Biotechnology (NIAB), Gachibowli, Hyderabad, Telangana 500032, India.
| | - Shuvomoy Banerjee
- Institute of Advanced Research, Koba Institutional Area, Gandhinagar, Gujarat 382426, India.
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Al-Ibraheem A, Scott AM. 161Tb-PSMA Unleashed: a Promising New Player in the Theranostics of Prostate Cancer. Nucl Med Mol Imaging 2023; 57:168-171. [PMID: 37483873 PMCID: PMC10359225 DOI: 10.1007/s13139-023-00804-7] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2023] [Revised: 04/12/2023] [Accepted: 04/13/2023] [Indexed: 07/25/2023] Open
Abstract
Radiotheranostics with 177Lu-PSMA have changed the treatment paradigm in patients with prostate cancer, becoming the new standard in certain settings. Terbium-161 (161Tb) has been recently investigated as a potential radionuclide for radiotheranostics in various types of cancer, including metastatic castration-resistant prostate cancer (mCRPC). The nuclear medicine team at King Hussein Cancer Center (KHCC) in Amman, Jordan, recently published the first-in-human SPECT/CT imaging results following a well-tolerated dose of 161Tb-PSMA radioligand therapy with no treatment-related adverse events, adding to the potential of radiotheranostics in prostate cancer. Two clinical trials for 161Tb-PSMA radioligand therapy in prostate cancer are currently underway and will provide valuable insights. This review will shed light on the expanding field of radiotheranostics in prostate cancer, which is not without challenges, and will discuss how the introduction of a new therapeutic option like 161Tb-PSMA may help to combat these challenges and build on the proven success of 177Lu-PSMA-based radiotheranostics for the benefit of prostate cancer patients worldwide.
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Affiliation(s)
- Akram Al-Ibraheem
- Department of Nuclear Medicine and PET/CT, King Hussein Cancer Center (KHCC), P.O. Box 1269, Al-Jubeiha, Amman, 11941 Jordan
- Department of Radiology and Nuclear Medicine, Division of Nuclear Medicine, University of Jordan, Amman, 11942 Jordan
| | - Andrew M. Scott
- Tumour Targeting Laboratory, Olivia Newton-John Cancer Research Institute, Melbourne, Victoria Australia
- Department of Molecular Imaging and Therapy, Austin Health, Melbourne, Victoria Australia
- School of Cancer Medicine, La Trobe University, Melbourne, Victoria Australia
- Department of Medicine, University of Melbourne, Melbourne, Victoria Australia
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Al-Ibraheem A, Al-Adhami DA, Abdlkadir AS, Al-Hajaj N, Ghanem R, Abu-Hijlih R, Salah S. Molecular Imaging in Recurrent Prostate Cancer Presented as a Mixed Small Neuroendocrine Tumor/Acinar Adenocarcinoma. Nucl Med Mol Imaging 2023; 57:209-211. [PMID: 37483874 PMCID: PMC10359224 DOI: 10.1007/s13139-023-00800-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 03/20/2023] [Accepted: 03/21/2023] [Indexed: 04/08/2023] Open
Abstract
Molecular imaging is an important tool for evaluating patients with prostate cancer, including those with hybrid histopathology. Although rare, mixed small neuroendocrine tumor/acinar adenocarcinoma exhibit aggressive behavior that necessitates optimal therapy. Molecular imaging has been implemented previously to assess radioligand therapy eligibility in such cases. Interestingly, the uptake of radiotracers targeting prostate-specific membrane antigen (PSMA) and somatostatin receptor may be reduced and can potentially lead to false negative readings in certain tumor types with hybrid features. Therefore, physicians should be aware of different kinds of disparities when assessing these tumor types with the aforementioned modalities.
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Affiliation(s)
- Akram Al-Ibraheem
- Department of Nuclear Medicine, King Hussein Cancer Center, Queen Rania Street, Al Jubeiha, Amman, 11941 Jordan
- Division of Nuclear Medicine/Department of Radiology and Nuclear Medicine, University of Jordan, Amman, 11942 Jordan
| | - Dhuha Ali Al-Adhami
- Department of Nuclear Medicine, King Hussein Cancer Center, Queen Rania Street, Al Jubeiha, Amman, 11941 Jordan
| | - Ahmed Saad Abdlkadir
- Department of Nuclear Medicine, King Hussein Cancer Center, Queen Rania Street, Al Jubeiha, Amman, 11941 Jordan
| | - Nabeela Al-Hajaj
- Department of Nuclear Medicine, King Hussein Cancer Center, Queen Rania Street, Al Jubeiha, Amman, 11941 Jordan
| | - Rami Ghanem
- Department of Surgery, King Hussein Cancer Center, Amman, 11941 Jordan
| | - Ramiz Abu-Hijlih
- Department of Radiation Oncology, King Hussein Cancer Center, Amman, 11941 Jordan
| | - Samer Salah
- Department of Internal Medicine, King Hussein Cancer Center, Amman, 11941 Jordan
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Diagnosis and Treatment of Lung Neuroendocrine Neoplasms: Somatostatin Receptor PET Imaging and Peptide Receptor Radionuclide Therapy. PET Clin 2023; 18:223-231. [PMID: 36585338 DOI: 10.1016/j.cpet.2022.11.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
Recently, advancement of somatostatin receptor (SSTR) imaging and theragnostic approach using peptide receptor radionuclide therapy (PRRT) have changed the paradigm of diagnosis and management of neuroendocrine tumor. 68Ga-DOTATATE PET/CT can diagnose the lung carcinoids with high SSTR expression. With combination of 68Ga-DOTATATE PET/CT and 18F-FDG PET/CT, tumor heterogeneity of lung carcinoid can be identified, which may guide optimal patient selection for PRRT. PRRT may be an effective and safe treatment of advanced lung carcinoids during progression with first-line somatostatin analog therapy. This review provides updates on the diagnosis and management of lung carcinoids, focusing on SSTR imaging and PRRT.
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177Lu-DOTATATE Efficacy and Safety in Functioning Neuroendocrine Tumors: A Joint Analysis of Phase II Prospective Clinical Trials. Cancers (Basel) 2022; 14:cancers14246022. [PMID: 36551507 PMCID: PMC9776442 DOI: 10.3390/cancers14246022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2022] [Revised: 10/31/2022] [Accepted: 11/25/2022] [Indexed: 12/12/2022] Open
Abstract
INTRODUCTION Neuroendocrine tumors (NETs) are rare malignancies with different prognoses. At least 25% of metastatic patients have functioning neuroendocrine tumors (F-NETs) that secrete bioactive peptides, causing specific debilitating and occasionally life-threatening symptoms such as diarrhea and flushing. Somatostatin analogs (SSAs) are usually effective but beyond them few treatment options are available. We evaluated the clinical efficacy of 177 Lu-DOTATATE in patients with progressive metastatic F-NETs and SSA-refractory syndrome. PATIENTS AND METHODS A non-pre-planned joint analysis was conducted in patients enrolled in phase II clinical trials on metastatic NETs. We extrapolated data from F-NET patients with ≥1 refractory sign/symptom to octreotide, and ≥1 measurable lesion. Syndrome response (SR), overall survival (OS), progression-free survival (PFS), tolerance and disease response were analyzed. RESULTS Sixty-eight patients were enrolled, the majority (88.1%) with a SR. According to RECIST criteria, 1 (1.5%) patient showed a CR, 21 (32.3%) had a PR and 40 (61.5%) SD. At a median follow-up of 28.9 months (range 2.2-63.2) median PFS was 33.0 months (95%CI: 27.1-48.2). Median OS (mOS) had not been reached at the time of the analysis; the 2-year OS was 87.8% (95%CI: 76.1-94.1). Syndromic responders showed better survival than non-responders, with a 2-year OS of 93.9% (95%CI: 92.2-98.0) vs. 40.0% (95%CI: 6.6-73.4), respectively. A total of 233 adverse events were recorded. Grade 1-2 hematological toxicity was the most frequent. CONCLUSION The 177 Lu-DOTATATE improved symptoms and disease control in patients with F-NETs. Treatment was well tolerated. The syndrome had an impact on both quality of life and OS.
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Shi M, Jakobsson V, Greifenstein L, Khong PL, Chen X, Baum RP, Zhang J. Alpha-peptide receptor radionuclide therapy using actinium-225 labeled somatostatin receptor agonists and antagonists. Front Med (Lausanne) 2022; 9:1034315. [PMID: 36569154 PMCID: PMC9767967 DOI: 10.3389/fmed.2022.1034315] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Accepted: 11/21/2022] [Indexed: 12/12/2022] Open
Abstract
Peptide receptor radionuclide therapy (PRRT) has over the last two decades emerged as a very promising approach to treat neuroendocrine tumors (NETs) with rapidly expanding clinical applications. By chelating a radiometal to a somatostatin receptor (SSTR) ligand, radiation can be delivered to cancer cells with high precision. Unlike conventional external beam radiotherapy, PRRT utilizes primarily β or α radiation derived from nuclear decay, which causes damage to cancer cells in the immediate proximity by irreversible direct or indirect ionization of the cells' DNA, which induces apoptosis. In addition, to avoid damage to surrounding normal cells, PRRT privileges the use of radionuclides that have little penetrating and more energetic (and thus more ionizing) radiations. To date, the most frequently radioisotopes are β- emitters, particularly Yttrium-90 (90Y) and Lutetium-177 (177Lu), labeled SSTR agonists. Current development of SSTR-targeting is triggering the shift from using SSTR agonists to antagonists for PRRT. Furthermore, targeted α-particle therapy (TAT), has attracted special attention for the treatment of tumors and offers an improved therapeutic option for patients resistant to conventional treatments or even beta-irradiation treatment. Due to its short range and high linear energy transfer (LET), α-particles significantly damage the targeted cancer cells while causing minimal cytotoxicity toward surrounding normal tissue. Actinium-225 (225Ac) has been developed into potent targeting drug constructs including somatostatin-receptor-based radiopharmaceuticals and is in early clinical use against multiple neuroendocrine tumor types. In this article, we give a review of preclinical and clinical applications of 225Ac-PRRT in NETs, discuss the strengths and challenges of 225Ac complexes being used in PRRT; and envision the prospect of 225Ac-PRRT as a future alternative in the treatment of NETs.
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Affiliation(s)
- Mengqi Shi
- Department of Diagnostic Radiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Nanomedicine Translational Research Program, NUS Center for Nanomedicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Vivianne Jakobsson
- Department of Diagnostic Radiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Academy for Precision Oncology, International Centers for Precision Oncology (ICPO), Wiesbaden, Germany
| | - Lukas Greifenstein
- CURANOSTICUM Wiesbaden-Frankfurt, Center for Advanced Radiomolecular Precision Oncology, Wiesbaden, Germany
| | - Pek-Lan Khong
- Department of Diagnostic Radiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Xiaoyuan Chen
- Department of Diagnostic Radiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Nanomedicine Translational Research Program, NUS Center for Nanomedicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Department of Surgery, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine and College of Design and Engineering, National University of Singapore, Singapore, Singapore
- Agency for Science, Technology, and Research (A*STAR), Institute of Molecular and Cell Biology, Singapore, Singapore
| | - Richard P. Baum
- CURANOSTICUM Wiesbaden-Frankfurt, Center for Advanced Radiomolecular Precision Oncology, Wiesbaden, Germany
| | - Jingjing Zhang
- Department of Diagnostic Radiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Nanomedicine Translational Research Program, NUS Center for Nanomedicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
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Prospective Cohort Real-World Study on Neuroendocrine Tumor Patient's Quality of Life During Peptide Receptor Radionuclide Therapy With 177Lu-DOTATATE. Pancreas 2022; 51:784-789. [PMID: 36395404 DOI: 10.1097/mpa.0000000000002101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Abstract
OBJECTIVE The aim of this study was to report lutetium-177 (177Lu)-DOTATATE radionuclide therapy from a patient perspective and their health-related quality of life. METHODS This prospective cohort study, including adult patients treated with 177Lu-DOTATATE. At the beginning of the follow-up (T1), socioeconomic and clinical information was collected, and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires C30-v3 and GI.NET21 were applied. Follow-up was performed at the third cycle (T2) and 3 months after the end of treatment (T3). Student t test for paired samples was used to compare quality of life at T1, T2, and T3. RESULTS Thirty-eight patients with stage IV disease and mean age of 52.54 (standard deviation, 12.49) years were included. The most prevalent site was the gastrointestinal tract (39.7%). Global health improved between T2 and T3 (P = 0.022) and T1 and T3 (P = 0.038). Functional scales did not indicate significant changes between the periods. Regarding symptoms, significant improvements in nausea and vomiting and gastrointestinal symptoms were observed between T2 and T3 (P = 0.012 and 0.029) and T1 and T3 (P = 0.012 and 0.011), respectively. CONCLUSIONS 177Lu-DOTATATE therapy improved global health and reduced disease-related symptoms in NET patients, positively impacting health-related quality of life.
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Yin F, Wu ZH, Lai JP. New insights in diagnosis and treatment of gastroenteropancreatic neuroendocrine neoplasms. World J Gastroenterol 2022; 28:1751-1767. [PMID: 35633912 PMCID: PMC9099195 DOI: 10.3748/wjg.v28.i17.1751] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2021] [Revised: 01/06/2022] [Accepted: 04/04/2022] [Indexed: 02/06/2023] Open
Abstract
Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are rare epithelial neoplasms derived from pluripotent endocrine cells along the gastrointestinal tract and pancreas. GEP-NENs are classified into well-differentiated neuroendocrine tumors and poorly differentiated neuroendocrine carcinomas. Despite overlapping morphological features, GEP-NENs vary in molecular biology, epigenetic, clinical behavior, treatment response, and prognosis features and remain an unmet clinical challenge. In this review, we introduce recent updates on the histopathologic classification, including the tumor grading and staging system, molecular genetics, and systemic evaluation of the diagnosis and treatment of GEP-NENs at different anatomic sites, together with some insights into the diagnosis of challenging and unusual cases. We also discuss the application of novel therapeutic approaches for GEP-NENs, including peptide receptor radionuclide therapy, targeted therapy, and immunotherapy with immune checkpoint inhibitors. These findings will help improve patient care with precise diagnosis and individualized treatment of patients with GEP-NENs.
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Affiliation(s)
- Feng Yin
- Department of Pathology and Anatomical Sciences, University of Missouri, Columbia, MO 65212, United States
| | - Zi-Hao Wu
- Department of Surgery, University of Missouri, Columbia, MO 65212, United States
| | - Jin-Ping Lai
- Department of Pathology, Kaiser Permanente Sacramento Medical Center, Sacramento, CA 95825, United States
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Sakulpisuti C, Chamroonrat W, Tepmongkol S. Cutaneous Management after Extravasation of High-Concentrated Amino Acid Solution Administered for Renal Protection in PRRT. Tomography 2022; 8:356-363. [PMID: 35202194 PMCID: PMC8880062 DOI: 10.3390/tomography8010029] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2021] [Revised: 01/24/2022] [Accepted: 01/28/2022] [Indexed: 11/25/2022] Open
Abstract
High-concentrated amino acid solution is used to protect the kidneys during peptide receptor radionuclide therapy (PPRT) in patients with neuroendocrine tumors (NETs). Extravasation of the solution can cause cutaneous complications. In this study, we described a 66-year-old man with metastatic medullary thyroid cancer and a 32-year-old woman with metastatic pancreatic NET who developed cutaneous lesions caused by the extravasation of an amino acid solution (25 g of lysine and 25 g of arginine in 1 L of normal saline) during PRRT with [177Lu]Lu-DOTA-TATE. Both were treated conservatively, and these cutaneous lesions gradually improved. The patient with metastatic pancreatic NET rejected the amino acid infusion in subsequent cycles of PRRT and therefore received [177Lu]Lu-DOTA-TATE alone, and her serum creatinine level and estimated glomerular filtration rate (eGFR) remained normal for 2 months after the last treatment. These two cases revealed cutaneous complications resulting from high-concentrated amino acid solution during PRRT because of hyperosmolarity. Health care providers should be aware of this complication to ensure its prevention and appropriate management. Preserved renal function was demonstrated after [177Lu]Lu-DOTA-TATE treatment in the absence of the infusion of a high-concentrated amino acid solution. However, long-term follow-up of renal function is suggested.
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Affiliation(s)
- Chaninart Sakulpisuti
- Division of Nuclear Medicine, Department of Diagnostic and Therapeutic Radiology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand;
| | - Wichana Chamroonrat
- Division of Nuclear Medicine, Department of Diagnostic and Therapeutic Radiology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand;
- Correspondence:
| | - Supatporn Tepmongkol
- Division of Nuclear Medicine, Department of Radiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand;
- Chulalongkorn University Biomedical Imaging Group (CUBIG), Department of Radiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand
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Satapathy S, Bhattacharya A, Sood A, Kapoor R, Gupta R, Sood A, Sharma P, Khosla D, Mittal BR. Hematological Markers as Predictors of Treatment Outcomes with Lutetium 177 ( 177Lu)-DOTATATE in Patients with Advanced Neuroendocrine Tumors. Cancer Biother Radiopharm 2022; 37:23-29. [PMID: 34185573 DOI: 10.1089/cbr.2021.0053] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Background: Chronic inflammation has been linked to the development and prognosis of neuroendocrine tumors (NETs). The current study intended to evaluate the role of peripheral hematological inflammatory markers, viz. the platelet-lymphocyte ratio (PLR), neutrophil-lymphocyte ratio, and monocyte-lymphocyte ratio, as predictors of treatment outcomes in patients with advanced NETs after Lutetium-177(177Lu)-DOTATATE therapy. Materials and Methods: Data of consecutive patients with advanced metastatic and/or inoperable NETs treated with 177Lu-DOTATATE from the year 2012 to 2019 at the authors' center were retrospectively analyzed. Results: Forty-two NET patients (median age: 49.5 years) received a median cumulative activity of 29.6 GBq of 177Lu-DOTATATE over 2-5 cycles at 8-12-week intervals. The median progression-free survival (PFS) of the study cohort was 30 months (95% confidence interval, CI: 18.2-41.9 months). A baseline PLR ≥173.1 was found to be a significant predictor of poor PFS with a univariate hazard ratio of 3.82 (95% CI: 1.21-12.03); however, the association was not significant on multivariate analysis. The median overall survival was not reached and none of the parameters were significantly associated with it. Conclusions: A higher baseline PLR was shown to be associated with a negative outcome on PFS after 177Lu-DOTATATE therapy and is a promising marker for future larger studies.
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Affiliation(s)
- Swayamjeet Satapathy
- Department of Nuclear Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Anish Bhattacharya
- Department of Nuclear Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Ashwani Sood
- Department of Nuclear Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Rakesh Kapoor
- Department of Radiotherapy, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Rajesh Gupta
- Department of Surgical Gastroenterology, and Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Apurva Sood
- Department of Nuclear Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Prashant Sharma
- Department of Hematology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Divya Khosla
- Department of Radiotherapy, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Bhagwant Rai Mittal
- Department of Nuclear Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India
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13
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Prado-Wohlwend S, del Olmo-García MI, Bello-Arques P, Merino-Torres JF. Response to targeted radionuclide therapy with [ 131I]MIBG AND [ 177Lu]Lu-DOTA-TATE according to adrenal vs. extra-adrenal primary location in metastatic paragangliomas and pheochromocytomas: A systematic review. Front Endocrinol (Lausanne) 2022; 13:957172. [PMID: 36339441 PMCID: PMC9630737 DOI: 10.3389/fendo.2022.957172] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Accepted: 09/30/2022] [Indexed: 11/13/2022] Open
Abstract
PURPOSE Targeted radionuclide therapy (TRT) with [131I]MIBG and [177Lu]Lu-DOTA-TATE is an alternative treatment to the classic schemes in slow progressive metastatic/inoperable paraganglioma (PGL) and pheochromocytoma (PHEO). There is no consensus on which treatment to administer and/or the best sequence in patients who are candidates for both therapies. To clarify these questions, this systematic review assesses the prognostic value of [131I]MIBG and [177Lu]Lu-DOTA-TATE (PRRT-Lu) treatments in terms of progression-free survival (PFS) both globally and considering the primary location. METHODS This review was developed according to the PRISMA Statement with 27 final studies (608 patients). Patient characteristics, treatment procedure, and follow-up criteria were evaluated. In addition, a Bayesian linear regression model weighted according to its sample size and an alternative model, which also included an interaction between the treatment and the proportion of PHEOs, were carried out, adjusted by a Student's t distribution. RESULTS In linear regression models, [131I]MIBG overall PFS was, on average, 10 months lower when compared with PRRT-Lu. When considering the interaction between treatment responses and the proportion of PHEOs, PRRT-Lu showed remarkably better results in adrenal location. The PFS of PRRT-Lu was longer when the ratio of PHEOs increased, with a decrease in [131I]MIBG PFS by 1.9 months for each 10% increase in the proportion of PHEOs in the sample. CONCLUSION Methodology, procedure, and PFS from the different studies are quite heterogeneous. PRRT-Lu showed better results globally and specifically in PHEOs. This fact opens the window to prospective trials comparing or sequencing [131I]MIBG and PRRT-Lu.
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Affiliation(s)
- Stefan Prado-Wohlwend
- Nuclear Medicine Department, University and Polytechnic Hospital La Fe, Valencia, Spain
- *Correspondence: Stefan Prado-Wohlwend,
| | | | - Pilar Bello-Arques
- Nuclear Medicine Department, University and Polytechnic Hospital La Fe, Valencia, Spain
| | - Juan Francisco Merino-Torres
- Endocrinology and Nutrition Department, University and Polytechnic Hospital La Fe, Valencia, Spain
- Medicine Department, Universitat de València, Valencia, Spain
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14
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Opalińska M, Sowa-Staszczak A, Grochowska A, Olearska H, Hubalewska-Dydejczyk A. Value of Peptide Receptor Radionuclide Therapy as Neoadjuvant Treatment in the Management of Primary Inoperable Neuroendocrine Tumors. Front Oncol 2021; 11:687925. [PMID: 34868906 PMCID: PMC8633407 DOI: 10.3389/fonc.2021.687925] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Accepted: 10/21/2021] [Indexed: 02/01/2023] Open
Abstract
INTRODUCTION Neuroendocrine neoplasms including neuroendocrine tumors (NETs) are often diagnosed as primary disseminated or inoperable. In those cases, systemic extensive therapy is necessary, but radical treatment is unlikely. As described in the literature, in some selected cases, peptide receptor radionuclide therapy (PRRT) may be used as a first-line/neoadjuvant therapy that allows further successful surgery. Such treatment may enable a reduction of total tumor burden or allow a radical treatment which improves the final outcomes. AIM This study aims to assess whether neoadjuvant PRRT could be a treatment option for patients with initially unresectable NETs. METHODS Among the group of 114 patients treated with PRRT between the years 2005 and 2020, in 32 cases, it was the first-line therapy, mainly due to massive disease burden at the time of diagnosis. Among them, nine patients received PRRT as the first-line treatment due to the primary inoperable tumors with the intention of preoperative reduction of the tumor size in order to allow for a surgical treatment. RESULTS Neoadjuvant PRRT enabled surgery in four out of nine (45%) patients. Finally, in two out of four cases, the goal (radical surgery) has been achieved. CONCLUSION PRRT may be considered not only as a palliative but also as a neoadjuvant therapy in advanced, somatostatin-positive NETs that were initially inoperable.
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Affiliation(s)
- Marta Opalińska
- Nuclear Medicine Unit, Department of Endocrinology, Oncological Endocrinology and Nuclear Medicine, University Hospital, Kraków, Poland
| | - Anna Sowa-Staszczak
- Chair and Department of Endocrinology, Jagiellonian University Medical College, Kraków, Poland
| | - Anna Grochowska
- Department of Radiology, University Hospital, Kraków, Poland
| | - Helena Olearska
- Chair and Department of Endocrinology, Jagiellonian University Medical College, Kraków, Poland
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15
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Ronde EM, Heidsma CM, Eskes AM, Schopman JE, Nieveen van Dijkum EJM. Health-related quality of life and treatment effects in patients with well-differentiated gastroenteropancreatic neuroendocrine neoplasms: A systematic review and meta-analysis. Eur J Cancer Care (Engl) 2021; 30:e13504. [PMID: 34462979 PMCID: PMC9286581 DOI: 10.1111/ecc.13504] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Revised: 07/29/2021] [Accepted: 07/30/2021] [Indexed: 11/30/2022]
Abstract
Introduction Gastroenteropancreatic neuroendocrine neoplasms (GEPNENs) are often diagnosed in an advanced stage. As the optimal sequence of therapy remains largely unclear, all treatment‐related outcomes, including health‐related quality of life (HRQoL) prospects, should be assessed according to patients' preferences. Methods A targeted search was performed in PubMed and EMBASE to identify studies on treatment effect and HRQoL, measured using the EORTC QLQ‐C30 tool, in patients with advanced, well‐differentiated GEPNENs. Study quality was assessed, and meta‐analyses were performed for global health status/QOL and tumour response. Results The search yielded 1,322 records, and 20 studies were included, examining somatostatin analogues (SSA), peptide receptor radionuclide therapies (PRRT), chemotherapy, SSA‐based combination therapies, and targeted therapies. Global HRQoL was stable, and rates for disease stabilisation were moderate to high across all treatments. Meta‐analyses for global health status/QOL after SSA treatment were not significant (mean difference: –0.3 [95% CI: −1.3 to 0.7]). The highest pooled overall tumour response rate was 33% (95% CI: 24–45%) for PRRT. The highest pooled clinical benefit rate was 94% (95% CI: 65–99%) for chemotherapy. Conclusion All treatments appeared beneficial for disease stabilisation while maintaining stable global health status/QOL. High‐quality HRQoL reporting was lacking. HRQoL should be a central outcome next to well‐established outcomes.
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Affiliation(s)
- Elsa M Ronde
- Department of Surgery, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - Charlotte M Heidsma
- Department of Surgery, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - Anne M Eskes
- Department of Surgery, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands
| | - Josefine E Schopman
- Department of Medical Oncology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands
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16
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Tsang ES, Funk G, Leung J, Kalish G, Kennecke HF. Supportive Management of Patients with Advanced Pheochromocytomas and Paragangliomas Receiving PRRT. Curr Oncol 2021; 28:2823-2829. [PMID: 34436013 PMCID: PMC8395467 DOI: 10.3390/curroncol28040247] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2021] [Revised: 05/24/2021] [Accepted: 06/02/2021] [Indexed: 11/16/2022] Open
Abstract
Peptide receptor radionuclide therapy (PRRT) is used to treat patients with advanced malignant pheochromocytomas (PCCs) and paragangliomas (PGLs). Patients are at risk of a PRRT-induced catecholamine crisis, and standard guidelines regarding the prevention and management of infusion reactions are lacking. In this case series, the institutional experience of five sequential patients with metastatic PCCs and PGLs receiving PRRT on an outpatient basis is described, of which four had symptomatic tumors and three had a high burden of disease. All patients with symptomatic tumors were treated with preventive management prior to the initiation of PRRT, and no infusion reactions or catecholamine crises were documented. PRRT may be delivered safely on an outpatient basis for patients with metastatic PCCs and PGLs with the involvement of an interdisciplinary team.
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Affiliation(s)
- Erica S. Tsang
- Division of Medical Oncology, BC Cancer, Vancouver, BC V5Z 4E6, Canada;
| | - Gayle Funk
- Virginia Mason Cancer Institute, Seattle, WA 98101, USA; (G.F.); (J.L.); (G.K.)
| | - Janet Leung
- Virginia Mason Cancer Institute, Seattle, WA 98101, USA; (G.F.); (J.L.); (G.K.)
| | - Grace Kalish
- Virginia Mason Cancer Institute, Seattle, WA 98101, USA; (G.F.); (J.L.); (G.K.)
| | - Hagen F. Kennecke
- Providence Cancer Institute & Chiles Research Institute, Portland, OR 97213, USA
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17
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Satapathy S, Mittal BR, Sood A, Sood A, Kapoor R, Gupta R, Khosla D. 177Lu-DOTATATE Plus Radiosensitizing Capecitabine Versus Octreotide Long-Acting Release as First-Line Systemic Therapy in Advanced Grade 1 or 2 Gastroenteropancreatic Neuroendocrine Tumors: A Single-Institution Experience. JCO Glob Oncol 2021; 7:1167-1175. [PMID: 34288699 PMCID: PMC8457785 DOI: 10.1200/go.21.00103] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2021] [Revised: 05/10/2021] [Accepted: 06/23/2021] [Indexed: 01/03/2023] Open
Abstract
PURPOSE To compare the efficacy and safety of 177Lu-DOTATATE plus radiosensitizing capecitabine and octreotide long-acting release (LAR) as first-line systemic therapy in advanced well-differentiated gastroenteropancreatic neuroendocrine tumors (GEP-NETs). MATERIALS AND METHODS Data of consecutive patients of advanced inoperable or metastatic grade 1 or 2 GEP-NETs treated with first-line 177Lu-DOTATATE plus radiosensitizing capecitabine or octreotide LAR from September 2012 to December 2019 were collected and analyzed for response, toxicity, and survival outcomes. RESULTS Seventy-six patients (median age: 53 years; range 14-81 years) with treatment-naïve advanced grade 1 or 2 GEP-NETs were included. Thirty-six patients received a median cumulative dose of 27.3 GBq of 177Lu-DOTATATE intravenously at 8-12 weeks' intervals along with 1,250 mg/m2 oral capecitabine on days 0-14 of each cycle of 177Lu-DOTATATE, whereas 40 patients were administered 30 mg octreotide LAR intramuscularly every 4 weeks. Using response evaluation criteria in solid tumor 1.1, the objective response rate was 38% in the 177Lu-DOTATATE arm compared with 15% in the octreotide LAR arm (P = .025), whereas the disease control rates were 88% and 67% in 177Lu-DOTATATE and octreotide LAR arms, respectively (P = .035). The median durations of progression-free survival in the 177Lu-DOTATATE and octreotide LAR arms were 54 months and 16 months, respectively (P = .017), whereas the median overall survival was not reached and not significantly different across both the arms. Of the treatment-related adverse events, no major difference was observed in the occurrence of grade 3 or 4 toxicities between the two treatment arms. CONCLUSION First-line systemic 177Lu-DOTATATE plus radiosensitizing capecitabine achieved better radiologic response and longer progression-free survival compared with octreotide LAR in patients with advanced grade 1 or 2 GEP-NETs. Future randomized controlled trials are, however, required to determine the best treatment sequence for the treatment-naïve patients with advanced GEP-NETs.
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Affiliation(s)
- Swayamjeet Satapathy
- Department of Nuclear Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Bhagwant R. Mittal
- Department of Nuclear Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Ashwani Sood
- Department of Nuclear Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Apurva Sood
- Department of Nuclear Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Rakesh Kapoor
- Department of Radiotherapy, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Rajesh Gupta
- Department of Surgical Gastroenterology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Divya Khosla
- Department of Radiotherapy, Post Graduate Institute of Medical Education and Research, Chandigarh, India
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18
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Neuroendocrine Tumor Theranostics: An Update and Emerging Applications in Clinical Practice. AJR Am J Roentgenol 2021; 217:495-506. [PMID: 34076455 DOI: 10.2214/ajr.20.23349] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
OBJECTIVE. Theranostics have shown great promise for delivering precision medicine, particularly in neuroendocrine tumors (NETs). The clinical applications of radiolabeled somatostatin analogues in imaging and radionuclide therapy have been rapidly increasing over the past 2 decades and are currently integrated into the management guidelines of NETs. This article summarizes the available literature on different somatostatin receptor-targeting radiopharmaceuticals with theranostic potential in NETs, pheochromocytomas, and paragangliomas. We discuss the clinical application, administration, and toxicity of recent FDA-approved radionuclide therapies, including 177Lu-DOTATATE in advanced gastroenteropancreatic NETs and 131I-MIBG in advanced paragangliomas and pheochromocytomas. CONCLUSION. Several studies support the safety and clinical efficacy of peptide receptor radionuclide therapies in disease control and quality-of-life improvement in patients with NETs and report potential benefits of combined radionuclide treatment approaches. The utility and pitfalls of functional imaging in therapy response assessment and surveillance of NETs remain to be established.
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19
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Kim YI. Salvage peptide receptor radionuclide therapy in patients with progressive neuroendocrine tumors: a systematic review and meta-analysis. Nucl Med Commun 2021; 42:451-458. [PMID: 33346603 DOI: 10.1097/mnm.0000000000001350] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
OBJECTIVE Peptide receptor radionuclide therapy (PRRT) is an effective treatment option in patients with metastatic neuroendocrine tumors (NETs). Recently, salvage PRRT has been introduced for progressing NET patients. This systematic review and meta-analysis evaluated the therapeutic efficacy, survival, and toxicity of salvage PRRT in patients with progressive NETs. METHODS A systematic (PubMed, Embase, Cochrane, and Scopus) were performed. To determine therapeutic efficacy, objective response rate (ORR), and disease control rate (DCR) were identified using radiologic response criteria. To determine survival, progression-free survival (PFS), and overall survival (OS) were verified. To determine toxicity, information was collected on serious (grades 3 or 4) hematologic and renal adverse events. RESULTS Nine articles featuring 426 patients were included in this study. Salvage PRRT achieved pooled proportions of ORR in 17.1% [95% confidence interval (CI) 11.6-23.5] and DCR in 76.9% (95% CI 72.3-81.0) of patients. Salvage PRRT demonstrated pooled estimates of PFS of 14.1 months (95% CI 12.2-15.9) and OS of 26.8 months (95% CI 18.8-34.9). Pooled proportions of hematologic and renal toxicities were 10.8% (95% CI 5.9-16.8) and 0.7% (95% CI 0.2-1.8), respectively. A subgroup direct comparison study with initial PRRT revealed that salvage PRRT showed significantly lower therapeutic efficacy (ORR and DCR, all P < 0.001) and shorter PFS (P = 0.03) despite similar hematologic toxicity (P = 0.25) and renal toxicity (P = 0.45). CONCLUSION Salvage PRRT is effective in patients with progressive NETs, and toxicity appeared to be similar to initial PRRT which could be a feasible treatment option.
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Affiliation(s)
- Yong-Il Kim
- Department of Nuclear Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
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20
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Drug Development in Neuroendocrine Tumors: What Is on the Horizon? Curr Treat Options Oncol 2021; 22:43. [PMID: 33786683 DOI: 10.1007/s11864-021-00834-3] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/18/2021] [Indexed: 02/08/2023]
Abstract
OPINION STATEMENT Neuroendocrine neoplasms (NENs) constitute a heterogenous group of malignancies. Translational research into NEN cell biology is the cornerstone for drug development strategies in this field. Somatostatin receptor type 2 (SSTR2) expression is the hallmark of well-differentiated neuroendocrine tumors (NETs). Somatostatin analogs and peptide receptor radionuclide therapy (PRRT) form the basis of anti-SSTR2 treatment onto new combination strategies, antibody-drug conjugates and bispecific antibodies. Classical pathways involved in NET development (PI3K-Akt-mTOR and antiangiogenics) are reviewed but new potential targets for NET treatment will be explored. Epigenetic drugs have shown clinical activity in monotherapy and preclinical combination strategies are more than attractive. Immunotherapy has shown opposite results in different NEN settings. Although the NOTCH pathway has been targeted with disappointing results, new strategies are being developed. Finally, after years of solid preclinical evidence on different genetically engineered oncolytic viruses, clinical trials for refractory NET patients are now ongoing.
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21
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Satapathy S, Mittal BR, Sood A, Verma R, Panda N. Efficacy and safety of concomitant 177Lu-DOTATATE and low-dose capecitabine in advanced medullary thyroid carcinoma: a single-centre experience. Nucl Med Commun 2021; 41:629-635. [PMID: 32371670 DOI: 10.1097/mnm.0000000000001205] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
AIMS Peptide receptor radionuclide therapy (PRRT) has been shown to be useful in inoperable/metastatic medullary thyroid carcinoma (MTC). However, the role of concomitant PRRT and low-dose capecitabine therapy has not yet been studied in these patients. This study was conducted to evaluate the efficacy and safety of this combination approach in advanced MTC. MATERIALS AND METHODS This was a retrospective, single-centre study. Data of consecutive patients of advanced inoperable/metastatic MTC treated with concomitant Lu-DOTATATE+capecitabine, from January 2014 to August 2018, were collected and analysed for radiological, molecular and biochemical responses and treatment-related toxicity. RESULTS Eight patients with advanced MTC received a median cumulative dose of 20.9 GBq (interquartile range 8.9-27.7 GBq) Lu-DOTATATE over 1-4 cycles and 1250 mg/m capecitabine from days 0 to 14 of each PRRT cycle. Radiological response according to Response Evaluation Criteria in Solid Tumours 1.1 criteria could be assessed in seven patients. Six out of seven patients (86%) had stable disease, while disease progression was observed in 1/7 (14%) patients. However, molecular response, as per the European Organization for Research and Treatment of Cancer criteria, was observed in all the seven patients. Biochemical response with reduction in serum calcitonin levels was observed in 3/5 (60%) patients. With the exception of grade 2 anaemia in one patient, no other significant toxicity was observed in this cohort. CONCLUSION Our results indicate the efficacy and safety of concomitant Lu-DOTATATE and capecitabine in advanced MTC. Larger randomized controlled trials are, however, required to establish the role of capecitabine as a radiosensitizer along with PRRT in these patients.
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Affiliation(s)
| | | | | | - Roshan Verma
- Otolaryngology (Head and Neck Surgery), Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
| | - Naresh Panda
- Otolaryngology (Head and Neck Surgery), Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India
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22
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Koustoulidou S, Hoorens MWH, Dalm SU, Mahajan S, Debets R, Seimbille Y, de Jong M. Cancer-Associated Fibroblasts as Players in Cancer Development and Progression and Their Role in Targeted Radionuclide Imaging and Therapy. Cancers (Basel) 2021; 13:1100. [PMID: 33806468 PMCID: PMC7961537 DOI: 10.3390/cancers13051100] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2021] [Revised: 02/19/2021] [Accepted: 02/20/2021] [Indexed: 12/12/2022] Open
Abstract
Cancer Associated Fibroblasts (CAFs) form a major component of the tumour microenvironment, they have a complex origin and execute diverse functions in tumour development and progression. As such, CAFs constitute an attractive target for novel therapeutic interventions that will aid both diagnosis and treatment of various cancers. There are, however, a few limitations in reaching successful translation of CAF targeted interventions from bench to bedside. Several approaches targeting CAFs have been investigated so far and a few CAF-targeting tracers have successfully been developed and applied. This includes tracers targeting Fibroblast Activation Protein (FAP) on CAFs. A number of FAP-targeting tracers have shown great promise in the clinic. In this review, we summarize our current knowledge of the functional heterogeneity and biology of CAFs in cancer. Moreover, we highlight the latest developments towards theranostic applications that will help tumour characterization, radioligand therapy and staging in cancers with a distinct CAF population.
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Affiliation(s)
- Sofia Koustoulidou
- Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands; (M.W.H.H.); (S.U.D.); (Y.S.); (M.d.J.)
| | - Mark W. H. Hoorens
- Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands; (M.W.H.H.); (S.U.D.); (Y.S.); (M.d.J.)
| | - Simone U. Dalm
- Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands; (M.W.H.H.); (S.U.D.); (Y.S.); (M.d.J.)
| | - Shweta Mahajan
- Department of Medical Oncology, Erasmus University Medical Center, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands; (R.D.); (S.M.)
| | - Reno Debets
- Department of Medical Oncology, Erasmus University Medical Center, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands; (R.D.); (S.M.)
| | - Yann Seimbille
- Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands; (M.W.H.H.); (S.U.D.); (Y.S.); (M.d.J.)
| | - Marion de Jong
- Department of Radiology and Nuclear Medicine, Erasmus University Medical Center, Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands; (M.W.H.H.); (S.U.D.); (Y.S.); (M.d.J.)
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23
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Zacho MD, Iversen P, Villadsen GE, Baunwall SMD, Arveschoug AK, Grønbaek H, Dam G. Clinical efficacy of first and second series of peptide receptor radionuclide therapy in patients with neuroendocrine neoplasm: a cohort study. Scand J Gastroenterol 2021; 56:289-297. [PMID: 33470864 DOI: 10.1080/00365521.2021.1872095] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVES Peptide receptor radionuclide therapy (PRRT) is an established treatment for metastatic neuroendocrine neoplasms (NEN). However, only limited data exists for the effect of multiple series of PRRT. The aim of this study was to investigate PFS and OS inNEN patients treated with multiple series of PRRT conforming to the ENETS treatment protocol. METHODS We included all patients with gastrointestinal (GI), pancreatic and bronchopulmonary (BP) NEN treated with PRRT from 2008 to 2018. We used Kaplan-Meier estimation to evaluate PFS and OS with subgroup analysis of primary tumor, Ki67-index, type of radioisotope and number of PRRT series. RESULTS 133 patients (female/male 61/72) were included, median age 70 (interquartile range 64-76) years. GI-NEN comprised 62%, pancreatic 23% and BP 11%. Median Ki67-index was 5%. After first PRRTG1- and G2-tumors had PFS of 25 and 22 months, compared to 11 months in G3-NENs (p < .05) and PFS was longer in G1/G2 GI-NENs than BP-NEN (30vs. 12 months, p < .05). After retreatment with a second series of PRRT, the overall PFS (G1-G3) was 19 months, with G1- and G2-tumors having the highest PFS of 19 and 22 months, respectively. Overall, the GI and BP tumors had an OS of 54 and 51 months. CONCLUSIONS PRRT is an effective therapy with long-term PFS and OS, especially in G1 and G2 NENs, and with better prognosis in GI-NEN compared with BP-NENs. OS and PFS was shorter after the second series of PRRT compared with the first, however results were still encouraging.
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Affiliation(s)
- M D Zacho
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - P Iversen
- Department of Nuclear Medicine and PET-Centre, Aarhus University Hospital, Aarhus, Denmark
| | - G E Villadsen
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - S M D Baunwall
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - A K Arveschoug
- Department of Nuclear Medicine and PET-Centre, Aarhus University Hospital, Aarhus, Denmark
| | - H Grønbaek
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
| | - G Dam
- Department of Hepatology and Gastroenterology, Aarhus University Hospital, Aarhus, Denmark
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24
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Das S, Du L, Schad A, Jain S, Jessop A, Shah C, Eisner D, Cardin D, Ciombor K, Goff L, Bradshaw M, Delbeke D, Sandler M, Berlin J. A clinical score for neuroendocrine tumor patients under consideration for Lu-177-DOTATATE therapy. Endocr Relat Cancer 2021; 28:203-212. [PMID: 33608484 PMCID: PMC8026653 DOI: 10.1530/erc-20-0482] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Accepted: 02/11/2021] [Indexed: 01/01/2023]
Abstract
We developed a clinical score (CS) at Vanderbilt Ingram Cancer Center (VICC) that we hoped would predict outcomes for patients with progressive well-differentiated neuroendocrine tumors (NETs) receiving therapy with Lutetium-177 (177Lu)-DOTATATE. Patients under consideration for 177Lu-DOTATATE between March 1, 2016 and March 17, 2020 at VICC were assigned a CS prospectively. The CS included 5 categories: available treatments for tumor type outside of 177Lu-DOTATATE, prior systemic treatments, patient symptoms, tumor burden in critical organs and presence of peritoneal carcinomatosis. The primary outcome of the analysis was progression-free survival (PFS). To evaluate the effect of the CS on PFS, a multivariable Cox regression analysis was performed adjusting for tumor grade, primary tumor location, and the interaction between 177Lu-DOTATATE doses received (zero, 1-2, 3-4) and CS. A total of 91 patients and 31 patients received 3-4 doses and zero doses of 177Lu-DOTATATE, respectively. On multivariable analysis, in patients treated with 3-4 doses of 177Lu-DOTATATE, for each 1-point increase in CS, the estimated hazard ratio (HR) for PFS was 2.0 (95% CI 1.61-2.48). On multivariable analysis, in patients who received zero doses of 177Lu-DOTATATE, for each 1-point increase in CS, the estimated HR for PFS was 1.22 (95% CI 0.91-1.65). Among patients treated with 3-4 doses of 177Lu-DOTATATE, those with lower CS experienced improved PFS with the treatment compared to patients with higher CS. This PFS difference, based upon CS, was not observed in patients who did not receive 177Lu-DOTATATE, suggesting the predictive utility of the score.
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Affiliation(s)
- Satya Das
- Vanderbilt University Medical Center, Department of Medicine, Division of Hematology Oncology, Nashville, TN, USA
| | - Liping Du
- Vanderbilt University of Medical Center, Department of Biostatistics, Nashville, TN, USA
| | - Aimee Schad
- Rush Medical Center, Department of Medicine, Chicago, IL, USA
| | - Shikha Jain
- University of Illinois Chicago, Department of Medicine, Chicago, IL, USA
| | - Aaron Jessop
- Vanderbilt University Medical Center, Department of Radiology, Nashville, TN, USA
| | - Chirayu Shah
- Vanderbilt University Medical Center, Department of Radiology, Nashville, TN, USA
| | - David Eisner
- Vanderbilt University Medical Center, Department of Medicine, Division of Hematology Oncology, Nashville, TN, USA
| | - Dana Cardin
- Vanderbilt University Medical Center, Department of Medicine, Division of Hematology Oncology, Nashville, TN, USA
| | - Kristen Ciombor
- Vanderbilt University Medical Center, Department of Medicine, Division of Hematology Oncology, Nashville, TN, USA
| | - Laura Goff
- Vanderbilt University Medical Center, Department of Medicine, Division of Hematology Oncology, Nashville, TN, USA
| | - Marques Bradshaw
- Vanderbilt University Medical Center, Department of Radiology, Nashville, TN, USA
| | - Dominique Delbeke
- Vanderbilt University Medical Center, Department of Radiology, Nashville, TN, USA
| | - Martin Sandler
- Vanderbilt University Medical Center, Department of Radiology, Nashville, TN, USA
| | - Jordan Berlin
- Vanderbilt University Medical Center, Department of Medicine, Division of Hematology Oncology, Nashville, TN, USA
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Radzik M, Pijarowska-Kruszyna J, Jaroń A, Maurin M, Decristoforo C, Mikołajczak R, Garnuszek P. Development and validation of the HPLC method for quality control of radiolabelled DOTA-TATE and DOTA-TOC preparations. Nucl Med Biol 2021; 93:63-73. [PMID: 33360498 DOI: 10.1016/j.nucmedbio.2020.11.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2020] [Revised: 10/30/2020] [Accepted: 11/15/2020] [Indexed: 11/29/2022]
Abstract
INTRODUCTION The information on the presence of cold metal complexes in radiolabeled DOTA-TATE or DOTA-TOC is important in assessing the cause of the radiolabeling failure, poor radiolabeling yield and/or low effective molar activity. DOTA-peptide complexes are detectable using UV-Vis detector. The main limitation in the quantitative analysis is the limited availability of standard substances and the lack of data on their molar absorption coefficients. The aim of our study was development and validation of HPLC method enabling RCP analysis and identification and quantification of metal complexes impurities in the radiopharmaceutical preparations of DOTA-chelated peptides. METHODS Complexes of DOTA-TATE and DOTA-TOC with several metals, were prepared. Their molar absorption coefficients at 220 nm were determined. The developed HPLC method has been validated in terms of quantitative determination of non-complexed DOTA-TATE and DOTA-TOC and their respective complexes with metallic individuals. RESULTS Good chromatographic separation of the individual metal-DOTA-peptide complexes was achieved. The resolution between peaks of interest in radioactive preparations (complexes with: yttrium-90, lutetium-177, gallium-68) and metallic impurities was well above 1.5 (except gallium-68 DOTA-TOC preparations). Limits of detection and quantification were determined based on the parameters of the calibration curves. Based on the spectrophotometric and HPLC-DAD studies and statistical analysis of the results obtained, the average molar absorption coefficient was determined for studied DOTA-TATE and DOTA-TOC complexes, εHPLC-DAD = 48 × 103M-1 cm-1. With the use of the determined molar absorption coefficient the method enabled quantitative determination of non-labelled peptide in the radioactive preparation in the linearity range of 0.5-100 μg/mL for DOTA-TATE(net) and 0.5-100 μg/mL for DOTA-TOC(net). CONCLUSION The developed HPLC method is suitable for RCP determination of radiolabelled DOTA-TATE and DOTA-TOC preparations. Determination of the average molar absorption coefficient for DOTA-TATE and DOTA-TOC complexes allows assessment of the total content of the peptide in radiopharmaceutical preparation regardless of its chemical form (free ligand, associated with radionuclide, in the form of a complex with metal ions being the impurity) using the HPLC method with UV detection.
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Affiliation(s)
- Marcin Radzik
- National Centre for Nuclear Research Radioisotope Centre POLATOM, 7 A. Soltana Street, 05-400 Otwock, Poland
| | - Justyna Pijarowska-Kruszyna
- National Centre for Nuclear Research Radioisotope Centre POLATOM, 7 A. Soltana Street, 05-400 Otwock, Poland
| | - Antoni Jaroń
- National Centre for Nuclear Research Radioisotope Centre POLATOM, 7 A. Soltana Street, 05-400 Otwock, Poland
| | - Michał Maurin
- National Centre for Nuclear Research Radioisotope Centre POLATOM, 7 A. Soltana Street, 05-400 Otwock, Poland
| | - Clemens Decristoforo
- Department of Nuclear Medicine, Innsbruck Medical University, Anichstrasse 35, A-6020 Innsbruck, Austria
| | - Renata Mikołajczak
- National Centre for Nuclear Research Radioisotope Centre POLATOM, 7 A. Soltana Street, 05-400 Otwock, Poland
| | - Piotr Garnuszek
- National Centre for Nuclear Research Radioisotope Centre POLATOM, 7 A. Soltana Street, 05-400 Otwock, Poland.
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Chemotherapy-Induced Upregulation of Somatostatin Receptor-2 Increases the Uptake and Efficacy of 177Lu-DOTA-Octreotate in Neuroendocrine Tumor Cells. Cancers (Basel) 2021; 13:cancers13020232. [PMID: 33435224 PMCID: PMC7828052 DOI: 10.3390/cancers13020232] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2020] [Revised: 01/05/2021] [Accepted: 01/06/2021] [Indexed: 12/14/2022] Open
Abstract
Simple Summary The peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTA-octreotate (LuTate) is recommended for neuroendocrine tumors (NETs) which overexpress somatostatin receptors (SSTR). A combination of LuTate with chemotherapy improves its objective response in NET patients, and here we characterized chemotherapy-induced upregulation of SSTR2 receptors as a cause for this improved response to LuTate. Using multiple NET and non-NET cell lines, we examined the SSTR2 expression for up to 7 days after exposure to drugs and its effect on LuTate uptake and cell proliferation. We report that the exposure to varying doses of chemotherapeutic drugs such as temozolomide for 24 h or 5 days results in upregulation of SSTR2 receptors between 3–7 days. This effect is more pronounced in low SSTR2 expressing BON-1 cells than in high SSTR2 expressing NCI-H727 or non-NET cancer or non-cancer cells. Thus, a properly-timed pre-treatment with low doses of chemotherapy could improve therapeutic efficacy of LuTate in NET patients. Abstract The peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTA-octreotate (LuTate) is recommended for different types of neuroendocrine tumors (NETs) which overexpress somatostatin receptors (SSTR). A combination with chemotherapy improves objective response to LuTate in NET patients and here we characterized chemotherapy-induced upregulation of SSTR2 receptors as a cause for this improved response to LuTate. The NET cell lines with low (BON-1) or relatively high (NCI-H727) SSTR2-expression levels, and non-NET cancer and normal cells were treated with chemotherapeutic drugs and assessed for upregulation of SSTR2. We report that an exposure to low or high doses of drugs, such as temozolomide for 24 h or 5 day results in upregulation of SSTR2 between 3–7 days, increased LuTate uptake and decreased rate of cell proliferation. This effect is at the level of SSTR2-mRNA and is more pronounced in low SSTR2 expressing BON-1 than in high SSTR2 expressing NCI-H727 or non-NET cancer or normal cells. Thus, a properly timed pre-treatment with low-dose chemotherapy could not only improve therapeutic efficacy of LuTate in NET patients who are presently eligible for PRRT, but also allow PRRT to be administered to patients with low SSTR-expressing NETs, who would otherwise not respond to this modality because of insufficient radiation delivery.
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Thomas KE, Boudreaux JP, Thiagarajan R, Marsala A, Voros BA, Ramirez RA. A Peptide Meets a Radionuclide to Combat a Rare Tumor. Ochsner J 2021; 21:306-311. [PMID: 34566515 PMCID: PMC8442225 DOI: 10.31486/toj.20.0098] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022] Open
Abstract
Background: Neuroendocrine carcinomas (NECs) are rare malignancies with limited treatment options beyond surgery. Peptide receptor radionuclide therapy (PRRT) is a process by which a somatostatin analog (octreotate) is combined with a chelator (DOTA) and a radionuclide (lutetium-177 [177Lu-dotatate]). This therapy targets receptors on neuroendocrine cells, causing internalization of the radionuclide by the tumor cell, which results in cellular damage and apoptosis. Case Report: We describe the clinical and therapeutic course of a 69-year-old male with a metastatic rectal NEC in whom progressive disease was noted after multiple therapies were attempted. After PRRT with 177Lu-dotatate, the patient was asymptomatic and demonstrated a near-complete radiologic response. Conclusion: This case illustrates that treatment with PRRT may improve the outcome of patients with metastatic rectal NEC. Our case highlights the importance of further research into the use of PRRT in patients with a Ki-67 <55% and uptake on somatostatin receptor imaging.
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Affiliation(s)
- Katharine E. Thomas
- Neuroendocrine Tumor Clinic, Ochsner Clinic Foundation, Kenner, LA
- Department of Hematology/Oncology, Louisiana State University Health Sciences Center, New Orleans, LA
| | - J. Philip Boudreaux
- Neuroendocrine Tumor Clinic, Ochsner Clinic Foundation, Kenner, LA
- Department of Surgery, Louisiana State University Health Sciences Center, New Orleans, LA
| | - Ramcharan Thiagarajan
- Neuroendocrine Tumor Clinic, Ochsner Clinic Foundation, Kenner, LA
- Department of Surgery, Louisiana State University Health Sciences Center, New Orleans, LA
| | - Andrew Marsala
- Department of Radiology, Division of Interventional Radiology, Ochsner Clinic Foundation, New Orleans, LA
| | - Brianne A. Voros
- Neuroendocrine Tumor Clinic, Ochsner Clinic Foundation, Kenner, LA
- Department of Surgery, Louisiana State University Health Sciences Center, New Orleans, LA
| | - Robert A. Ramirez
- Neuroendocrine Tumor Clinic, Ochsner Clinic Foundation, Kenner, LA
- Department of Internal Medicine, Division of Hematology/Oncology, Ochsner Clinic Foundation, New Orleans, LA
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Lania A, Ferraù F, Rubino M, Modica R, Colao A, Faggiano A. Neoadjuvant Therapy for Neuroendocrine Neoplasms: Recent Progresses and Future Approaches. Front Endocrinol (Lausanne) 2021; 12:651438. [PMID: 34381421 PMCID: PMC8350565 DOI: 10.3389/fendo.2021.651438] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2021] [Accepted: 04/27/2021] [Indexed: 12/12/2022] Open
Abstract
Neuroendocrine neoplasms (NENs) are a heterogeneous group of tumors, their treatment being challenging and requiring a multidisciplinary approach. Though the only curative treatment is surgery, up to 50% of patients are diagnosed with metastatic disease. In the last years, neoadjuvant chemo(radio)therapy has become part of the standard of care in the treatment of different cancer types. However, evidence of its efficacy and safety in NEN patients has not yet been confirmed in the literature. The aim of the present review is to perform an extensive review of the scientific evidence for neoadjuvant therapy in patients with gastroenteropancreatic and thoracic NENs.
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Affiliation(s)
- Andrea Lania
- Endocrinology, Diabetology and Andrology Unit, Humanitas Clinical and Research Center—IRCCS, Rozzano, Italy
- Department of Biomedical Sciences, Humanitas University, Rozzano, Italy
- *Correspondence: Andrea Lania,
| | - Francesco Ferraù
- Department of Human Pathology of Adulthood and Childhood ‘G. Barresi’, University of Messina, Messina, Italy
- Endocrine Unit, University Hospital G. Martino, Messina, Italy
| | - Manila Rubino
- Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, IEO, IRCCS, Milan, Italy
| | - Roberta Modica
- Endocrinology, Department of Clinical Medicine and Surgery, “Federico II” University of Napoli, Napoli, Italy
| | - Annamaria Colao
- Endocrinology, Department of Clinical Medicine and Surgery, “Federico II” University of Napoli, Napoli, Italy
| | - Antongiulio Faggiano
- Endocrinology, Department of Experimental Medicine, “Sapienza”, University of Rome, Rome, Italy
- Department of Experimental Medicine, Division of Medical Physiopathology, Sapienza University of Rome, Rome, Italy
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Collimator and energy window optimization for practical imaging protocol and quantification of Yttrium-90 bremsstrahlung spect/ct: A phantom study. Radiat Phys Chem Oxf Engl 1993 2021. [DOI: 10.1016/j.radphyschem.2020.109080] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/19/2022]
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Peptide Receptor Radionuclide Therapy as First-Line Systemic Treatment in Advanced Inoperable/Metastatic Neuroendocrine Tumors. Clin Nucl Med 2020; 45:e393-e399. [PMID: 32604121 DOI: 10.1097/rlu.0000000000003170] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
PURPOSE Advanced inoperable/metastatic neuroendocrine tumors (NETs) pose a therapeutic challenge with limited treatment options. Peptide receptor radionuclide therapy (PRRT), being specific in targeting the somatostatin receptors, is a promising and viable option in this setting. In this study, we intended to evaluate the role of PRRT as the first-line systemic therapy in advanced inoperable/metastatic NETs. METHODS Data of consecutive patients of advanced inoperable/metastatic NETs treated with first-line Lu-DOTATATE at our center, from September 2012 to August 2019, were collected and analyzed. RESULTS Forty-five patients (median age, 50 years; range, 14-72 years) with treatment-naive advanced NETs received a median cumulative dose of 27 GBq (range, 13.3-41.3 GBq; over 2-7 cycles) Lu-DOTATATE and 1250 mg/m capecitabine from days 0 to 14 of each PRRT cycle. Three patients were lost to follow-up, 2 had nonmeasurable lesions on CT, and hence, radiological response using Response Evaluation Criteria in Solid Tumors version 1.1 could be assessed in 40 patients. Twelve of 40 patients (30%) showed a partial response, whereas stable disease was observed in 22 of 40 patients (55%). Disease progression was limited to 6 of 40 patients (15%). Treatment-related adverse effects were minimal with grade 3/4 anemia, leukopenia, neutropenia, and hepatotoxicity observed in 2%, 2%, 4%, and 4% of the patients, respectively. Median progression-free survival was 48 months (95% confidence interval, 34.7-61.3 months). CONCLUSIONS Our results indicate the efficacy and safety of first-line PRRT in advanced NETs. Future randomized trials, comparing PRRT and somatostatin analogs in treatment-naive patients, are required to identify the definite sequence of treatment options for these patients.
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Chiapponi C, Lürssen N, Cremer B, Wahba R, Drebber U, Faust M, Schmidt M, Stippel DL. Peptide receptor radionuclide therapy as a two-step strategy for initially unresectable liver disease from neuroendocrine tumors: a single-center experience. Endocrine 2020; 70:187-193. [PMID: 32419082 DOI: 10.1007/s12020-020-02341-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Accepted: 05/04/2020] [Indexed: 02/06/2023]
Abstract
PURPOSE In this study, we describe our experience with peptide receptor radionuclide therapy (PRRT) for initially unresectable liver disease as a two-steps therapeutic strategy, first in neoadjuvant intention before surgery and then later on in case of disease relapse. METHODS We performed a retrospective evaluation of four cases of unresectable liver metastases of NET of different origins treated with neoadjuvant Lu-177-DotaTATE for conversion into resectability first and as rechallenging treatment after disease relapse. RESULTS After treatment with Lu-177-DotaTAE, resectability was reached in three of four cases. In one case, SIRT was additionally performed preoperatively. Relapse occurred in three of four cases after 32, 34, and 37 months, respectively, and was managed with Re-PRRT-treatment. CONCLUSION Although more data are needed, our retrospective study suggests that treatment with Lu-177-DotaTATE is an important adjunct to surgery not only in neoadjuvant intention but also for treating disease relapse. A register study might deliver more evidence for supporting this strategy.
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Affiliation(s)
- Costanza Chiapponi
- Department for General, Visceral, Cancer and Transplantation Surgery, University Hospital of Cologne, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.
| | - Nadine Lürssen
- Department for General, Visceral, Cancer and Transplantation Surgery, University Hospital of Cologne, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany
| | - Birgit Cremer
- Department for Hemato-Oncology, University Hospital of Cologne, Univeristy of Cologne, Cologne, Germany
| | - Roger Wahba
- Department for General, Visceral, Cancer and Transplantation Surgery, University Hospital of Cologne, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany
| | - Uta Drebber
- Department for Pathology, University Hospital of Cologne, University of Cologne, Cologne, Germany
| | - Michael Faust
- Polyclinic for Endocrinology, Diabetes and Preventive Medicine, University Hospital of Cologne, Univeristy of Cologne, Cologne, Germany
| | - Matthias Schmidt
- Department of Nuclear Medicine, University Hospital of Cologne, University of Cologne, Cologne, Germany
| | - Dirk L Stippel
- Department for General, Visceral, Cancer and Transplantation Surgery, University Hospital of Cologne, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany
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68Ga DOTA-TOC Uptake in Non-ossifying Fibroma: a Case Report. Nucl Med Mol Imaging 2020; 54:199-203. [PMID: 32831966 DOI: 10.1007/s13139-020-00650-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2019] [Revised: 05/29/2020] [Accepted: 06/26/2020] [Indexed: 10/23/2022] Open
Abstract
Non-ossifying fibroma (NOF) is a common benign bone tumor with a high probability of occurrence in children and adolescents. It is commonly seen in the metaphysis of long bones, eccentrically located, and can coexist with other malignant tumors such as neuroendocrine tumors (NET). To date, plain radiographs play a major role in the diagnosis of these benign bone tumors. Herein, we report the case of a 13-year-old male patient who was diagnosed with pulmonary NET and underwent right lung lobectomy for a hilar mass which later revealed a well-differentiated NET. The follow-up 68Ga DOTA-TOC PET/CT showed a focal somatostatin receptor expression in the left distal femur, with corresponding CT component findings of a well-defined osteolytic bone lesion located within the medial aspect of the left distal femoral metaphysis, strongly indicative of NOF. To the best of our knowledge, this is the first reported case of such an occurrence.
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Megdanova-Chipeva VG, Lamarca A, Backen A, McNamara MG, Barriuso J, Sergieva S, Gocheva L, Mansoor W, Manoharan P, Valle JW. Systemic Treatment Selection for Patients with Advanced Pancreatic Neuroendocrine Tumours (PanNETs). Cancers (Basel) 2020; 12:E1988. [PMID: 32708210 PMCID: PMC7409353 DOI: 10.3390/cancers12071988] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2020] [Revised: 06/19/2020] [Accepted: 07/09/2020] [Indexed: 02/07/2023] Open
Abstract
Pancreatic neuroendocrine tumours (PanNETs) are rare diseases and a good example of how research is not only feasible, but also of crucial importance in the scenario of rare tumours. Many clinical trials have been performed over the past two decades expanding therapeutic options for patients with advanced PanNETs. Adequate management relies on optimal selection of treatment, which may be challenging for clinicians due to the fact that multiple options of therapy are currently available. A number of therapies already exist, which are supported by data from phase III studies, including somatostatin analogues and targeted therapies (sunitinib and everolimus). In addition, chemotherapy remains an option, with temozolomide and capecitabine being one of the most popular doublets to use. Peptide receptor radionuclide therapy was successfully implemented in patients with well-differentiated gastro-entero-pancreatic neuroendocrine tumours, but with certain questions waiting to be solved for the management of PanNETs. Finally, the role of immunotherapy is still poorly understood. In this review, the data supporting current systemic treatment options for locally advanced or metastatic PanNETs are summarized. Strategies for treatment selection in patients with PanNETs based on patient, disease, or drug characteristics is provided, as well as a summary of current evidence on prognostic and predictive biomarkers. Future perspectives are discussed, focusing on current and forthcoming challenges and unmet needs of patients with these rare tumours.
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Affiliation(s)
- Vera G. Megdanova-Chipeva
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M204BX, UK; (V.G.M.-C.); (A.B.); (M.G.M.); (J.B.); (W.M.)
- Department of Radiotherapy and Medical Oncology, University Hospital “Queen Yoanna” ISUL, 1000 Sofia, Bulgaria;
- Department of Nuclear Medicine, Radiotherapy and Medical Oncology, Medical University—Sofia, 1000 Sofia, Bulgaria
| | - Angela Lamarca
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M204BX, UK; (V.G.M.-C.); (A.B.); (M.G.M.); (J.B.); (W.M.)
- Division of Cancer Sciences, University of Manchester, Manchester M204BX, UK
| | - Alison Backen
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M204BX, UK; (V.G.M.-C.); (A.B.); (M.G.M.); (J.B.); (W.M.)
- Division of Cancer Sciences, University of Manchester, Manchester M204BX, UK
| | - Mairéad G. McNamara
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M204BX, UK; (V.G.M.-C.); (A.B.); (M.G.M.); (J.B.); (W.M.)
- Division of Cancer Sciences, University of Manchester, Manchester M204BX, UK
| | - Jorge Barriuso
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M204BX, UK; (V.G.M.-C.); (A.B.); (M.G.M.); (J.B.); (W.M.)
- Division of Cancer Sciences, University of Manchester, Manchester M204BX, UK
| | - Sonia Sergieva
- Nuclear Medicine Department, SBALOZ, Sofia grad, 1000 Sofia, Bulgaria;
| | - Lilia Gocheva
- Department of Radiotherapy and Medical Oncology, University Hospital “Queen Yoanna” ISUL, 1000 Sofia, Bulgaria;
- Department of Nuclear Medicine, Radiotherapy and Medical Oncology, Medical University—Sofia, 1000 Sofia, Bulgaria
| | - Was Mansoor
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M204BX, UK; (V.G.M.-C.); (A.B.); (M.G.M.); (J.B.); (W.M.)
- Division of Cancer Sciences, University of Manchester, Manchester M204BX, UK
| | - Prakash Manoharan
- Department of Radiology and Nuclear Medicine, The Christie NHS Foundation Trust, Manchester M204BX, UK;
| | - Juan W. Valle
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M204BX, UK; (V.G.M.-C.); (A.B.); (M.G.M.); (J.B.); (W.M.)
- Division of Cancer Sciences, University of Manchester, Manchester M204BX, UK
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Hoppenz P, Els-Heindl S, Beck-Sickinger AG. Peptide-Drug Conjugates and Their Targets in Advanced Cancer Therapies. Front Chem 2020; 8:571. [PMID: 32733853 PMCID: PMC7359416 DOI: 10.3389/fchem.2020.00571] [Citation(s) in RCA: 154] [Impact Index Per Article: 30.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2020] [Accepted: 06/03/2020] [Indexed: 12/15/2022] Open
Abstract
Cancer became recently the leading cause of death in industrialized countries. Even though standard treatments achieve significant effects in growth inhibition and tumor elimination, they cause severe side effects as most of the applied drugs exhibit only minor selectivity for the malignant tissue. Hence, specific addressing of tumor cells without affecting healthy tissue is currently a major desire in cancer therapy. Cell surface receptors, which bind peptides are frequently overexpressed on cancer cells and can therefore be considered as promising targets for selective tumor therapy. In this review, the benefits of peptides as tumor homing agents are presented and an overview of the most commonly addressed peptide receptors is given. A special focus was set on the bombesin receptor family and the neuropeptide Y receptor family. In the second part, the specific requirements of peptide-drug conjugates (PDC) and intelligent linker structures as an essential component of PDC are outlined. Furthermore, different drug cargos are presented including classical and recent toxic agents as well as radionuclides for diagnostic and therapeutic approaches. In the last part, boron neutron capture therapy as advanced targeted cancer therapy is introduced and past and recent developments are reviewed.
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Affiliation(s)
- Paul Hoppenz
- Faculty of Life Sciences, Institute of Biochemistry, Leipzig University, Leipzig, Germany
| | - Sylvia Els-Heindl
- Faculty of Life Sciences, Institute of Biochemistry, Leipzig University, Leipzig, Germany
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Worm DJ, Els‐Heindl S, Beck‐Sickinger AG. Targeting of peptide‐binding receptors on cancer cells with peptide‐drug conjugates. Pept Sci (Hoboken) 2020. [DOI: 10.1002/pep2.24171] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Affiliation(s)
- Dennis J. Worm
- Faculty of Life Sciences, Institute of BiochemistryLeipzig University Leipzig Germany
| | - Sylvia Els‐Heindl
- Faculty of Life Sciences, Institute of BiochemistryLeipzig University Leipzig Germany
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Satapathy S, Mittal BR, Bhansali A. 'Peptide receptor radionuclide therapy in the management of advanced pheochromocytoma and paraganglioma: A systematic review and meta-analysis'. Clin Endocrinol (Oxf) 2019; 91:718-727. [PMID: 31569282 DOI: 10.1111/cen.14106] [Citation(s) in RCA: 73] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/11/2019] [Revised: 09/16/2019] [Accepted: 09/27/2019] [Indexed: 12/18/2022]
Abstract
OBJECTIVE Inoperable and metastatic pheochromocytomas and paragangliomas (PPGLs) present a therapeutic challenge with current treatment options being limited to radiolabelled meta-iodo-benzyl-guanidine (MIBG) and systemic chemotherapy. Peptide receptor radionuclide therapy (PRRT) seems to be a promising option for these patients with few studies reporting favourable response. This systematic review was conducted to evaluate the efficacy and safety of PRRT in patients with advanced PPGLs. METHODS This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Searches in PubMed, Scopus and Embase were made using relevant keywords and articles up to May 2019 were included. Data on efficacy and toxicity were extracted from the individual articles, and pooled estimates were generated using meta-analysis. RESULTS Twelve articles consisting of 201 patients with advanced PPGLs were included. Overall, treatment with PRRT achieved an objective response rate of 25% (95% CI: 19%-32%) and a disease control rate of 84% (95% CI: 77%-89%). Clinical and biochemical responses were seen in 61% and 64% of the patients, respectively. Among the PRRTs, similar tumour response rates were noted for 90 Y-yttrium- and 177 Lu-lutetium-based agents. Treatment-related adverse effects were minimal with grade 3/4 neutropenia, thrombocytopenia, lymphopenia and nephrotoxicity observed in 3%, 9%, 11% and 4% of the patients, respectively. Treatment discontinuation was noted in five out of 102 patients. CONCLUSIONS Peptide receptor radionuclide therapy is a safe and efficacious treatment option for advanced PPGLs and may be considered a viable alternative to chemotherapy and I-131 MIBG.
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Affiliation(s)
- Swayamjeet Satapathy
- Department of Nuclear Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Bhagwant Rai Mittal
- Department of Nuclear Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India
| | - Anil Bhansali
- Department of Endocrinology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
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Dermine S, Palmieri LJ, Lavolé J, Barré A, Dohan A, Abou Ali E, Cottereau AS, Gaujoux S, Brezault C, Chaussade S, Coriat R. Non-Pharmacological Therapeutic Options for Liver Metastases in Advanced Neuroendocrine Tumors. J Clin Med 2019; 8:jcm8111907. [PMID: 31703375 PMCID: PMC6912565 DOI: 10.3390/jcm8111907] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2019] [Revised: 10/29/2019] [Accepted: 11/05/2019] [Indexed: 12/18/2022] Open
Abstract
The incidence of liver metastasis in digestive neuroendocrine tumors is high. Their presence appears as an important prognostic factor in terms of quality of life and survival. These tumors may be symptomatic because of the tumor burden itself and/or the hormonal hyper-secretion induced by the tumor. Surgery is the treatment of choice for resectable tumors and metastasis. Nevertheless, surgery is only possible in a small number of cases. The management of non-resectable liver metastasis is a challenge. The literature is rich but consists predominantly in small retrospective series with a low level of proof. Thus, the choice of one technique over another could be difficult. Local ablative techniques (radiofrequency) or trans-catheter intra-arterial liver-directed treatments (hepatic artery embolization, chemo-embolization, and radio-embolization) are frequently considered for liver metastasis. In the present review, we focus on these different therapeutic approaches in advanced neuroendocrine tumors, results (clinical and radiological), and overall efficacy, and summarize recommendations to help physicians in their clinical practice.
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Affiliation(s)
- Solène Dermine
- Gastroenterology and Digestive Oncology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France; (L.-J.P.); (J.L.); (A.B.); (E.A.A.); (C.B.); (S.C.)
- Department of Gastroenterology, Cochin Teaching Hospital, Université de Paris, 75014 Paris, France; (A.D.); (A.-S.C.); (S.G.)
- Correspondence: (S.D.); (R.C.); Tel.: +33-(1)58411952 (R.C.); Fax: +33-(1)58411965 (R.C.)
| | - Lola-Jade Palmieri
- Gastroenterology and Digestive Oncology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France; (L.-J.P.); (J.L.); (A.B.); (E.A.A.); (C.B.); (S.C.)
| | - Julie Lavolé
- Gastroenterology and Digestive Oncology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France; (L.-J.P.); (J.L.); (A.B.); (E.A.A.); (C.B.); (S.C.)
| | - Amélie Barré
- Gastroenterology and Digestive Oncology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France; (L.-J.P.); (J.L.); (A.B.); (E.A.A.); (C.B.); (S.C.)
- Department of Gastroenterology, Cochin Teaching Hospital, Université de Paris, 75014 Paris, France; (A.D.); (A.-S.C.); (S.G.)
| | - Antony Dohan
- Department of Gastroenterology, Cochin Teaching Hospital, Université de Paris, 75014 Paris, France; (A.D.); (A.-S.C.); (S.G.)
- Department of Radiology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France
| | - Einas Abou Ali
- Gastroenterology and Digestive Oncology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France; (L.-J.P.); (J.L.); (A.B.); (E.A.A.); (C.B.); (S.C.)
- Department of Gastroenterology, Cochin Teaching Hospital, Université de Paris, 75014 Paris, France; (A.D.); (A.-S.C.); (S.G.)
| | - Anne-Ségolène Cottereau
- Department of Gastroenterology, Cochin Teaching Hospital, Université de Paris, 75014 Paris, France; (A.D.); (A.-S.C.); (S.G.)
- Department of Nuclear Medicine, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France
| | - Sébastien Gaujoux
- Department of Gastroenterology, Cochin Teaching Hospital, Université de Paris, 75014 Paris, France; (A.D.); (A.-S.C.); (S.G.)
- Digestive Surgery Unit, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France
| | - Catherine Brezault
- Gastroenterology and Digestive Oncology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France; (L.-J.P.); (J.L.); (A.B.); (E.A.A.); (C.B.); (S.C.)
| | - Stanislas Chaussade
- Gastroenterology and Digestive Oncology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France; (L.-J.P.); (J.L.); (A.B.); (E.A.A.); (C.B.); (S.C.)
- Department of Gastroenterology, Cochin Teaching Hospital, Université de Paris, 75014 Paris, France; (A.D.); (A.-S.C.); (S.G.)
| | - Romain Coriat
- Gastroenterology and Digestive Oncology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France; (L.-J.P.); (J.L.); (A.B.); (E.A.A.); (C.B.); (S.C.)
- Department of Gastroenterology, Cochin Teaching Hospital, Université de Paris, 75014 Paris, France; (A.D.); (A.-S.C.); (S.G.)
- Correspondence: (S.D.); (R.C.); Tel.: +33-(1)58411952 (R.C.); Fax: +33-(1)58411965 (R.C.)
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Fung AK, Chong CC. Surgical strategy for neuroendocrine liver metastases. SURGICAL PRACTICE 2019. [DOI: 10.1111/1744-1633.12364] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Affiliation(s)
- Andrew Kai‐Yip Fung
- Department of SurgeryThe Chinese University of Hong Kong, Prince of Wales Hospital Hong Kong
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Al-Ibraheem A, Mohamedkhair A. Current Status of Theranostics in Jordan. Nucl Med Mol Imaging 2019; 53:7-10. [PMID: 30828393 DOI: 10.1007/s13139-018-0562-5] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2018] [Accepted: 12/06/2018] [Indexed: 12/24/2022] Open
Abstract
Exploring the unknown is one of the key factors that lead to great discoveries in mankind history. With the advances in medicine and the development of new approaches towards patient care, like next-generation sequencing and patient-centered care, the need for treatments tailored to patient through personalized medicine has become more compelling. Theranostics has been introduced as a combination of a diagnostic tool and a therapeutic tool on the same vector for a specific disease, to facilitate personalized medicine. Nuclear medicine has shown the capability of providing a strong platform for this new approach through its arms, molecular imaging, and targeted molecular therapies. Though the prototype of theranostics has been practiced in Jordan since decades in the field of diagnosis and treatment of well-differentiated thyroid cancer, recently, the King Hussein Cancer Center (KHCC), a leading and comprehensive cancer center in Jordan and in the Middle East, has leaped forward to introduce the new approaches of theranostics through the nuclear medicine applications. This paper sheds the light on the most important aspects of this new theranostics practice in Jordan such as peptide receptor radionuclide therapy (PRRT) and prostate-specific membrane antigen (PSMA)-based theranostics.
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Affiliation(s)
- Akram Al-Ibraheem
- Department of Nuclear Medicine, King Hussein Cancer Center, 202 Queen Rania St., P.O. Box 1269, Amman, 11941 Jordan
| | - Ali Mohamedkhair
- Department of Nuclear Medicine, King Hussein Cancer Center, 202 Queen Rania St., P.O. Box 1269, Amman, 11941 Jordan
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Ahn BC. Contribution of Radionuclide Theranostics for Managing Intractable Malignancies. Nucl Med Mol Imaging 2018; 52:168-169. [PMID: 29942395 PMCID: PMC5995783 DOI: 10.1007/s13139-018-0526-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2018] [Revised: 05/03/2018] [Accepted: 05/04/2018] [Indexed: 11/25/2022] Open
Affiliation(s)
- Byeong-Cheol Ahn
- Department of Nuclear Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, 50, Samduk 2-ga, Jung Gu, Daegu, Republic of Korea 700-721
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