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Yang H, Qi M, Chen Z, Liu F, Xu J, Xu X, Kong Q, Zhang J, Song S. Predicting [177Lu]Lu-DOTA-TATE dosimetry by using pre-therapy [68Ga]Ga-DOTA-TATE PET/CT and biomarkers in patient with neuroendocrine tumors. Med Phys 2025. [PMID: 40268670 DOI: 10.1002/mp.17852] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2024] [Revised: 11/28/2024] [Accepted: 04/10/2025] [Indexed: 04/25/2025] Open
Abstract
BACKGROUND Lutetium-177 DOTA-TATE peptide receptor radionuclide therapy (PRRT) is an established and effective treatment modality for patients with metastatic neuroendocrine tumors (NETs). PURPOSE This study aims to predict patient-absorbed doses from [177Lu]Lu-DOTA-TATE PRRT in the liver, kidney and lesion by utilizing patient-specific absorbed doses from pre-therapeutic [68Ga]Ga-DOTA-TATE PET/CT. METHODS Before the treatment of cycle 1, 11 patients with NETs underwent PET/CT scans at 0.5, 1.0, 2.0 and 4.0 h after the injection of [68Ga]Ga-DOTA-TATE. Patients then received [177Lu]Lu-DOTA-TATE PRRT and underwent SPECT/CT scans at 4, 24, 96, and 168 h post-administration. The segmentations and dosimetry were performed by using a professional software. The linear regression model used the absorbed doses from [68Ga]Ga-DOTA-TATE alone as the predictor variable. The multiple linear regression model used the absorbed doses from [68Ga]Ga-DOTA-TATE and the relevant clinical biomarkers as the predictor variables. RESULTS The mean absorbed doses from [177Lu]Lu-DOTA-TATE PRRT in kidney and liver were 4.1 and 2.1 Gy, respectively. In comparison, the mean absorbed doses from [68Ga]Ga-DOTA-TATE were significantly lower: 18.0 mGy and 11.0 mGy, respectively. For lesions, the maximum absorbed dose from [68Ga]Ga-DOTA-TATE ranged from 24.1 to 170.4 mGy, while the maximum absorbed dose from [177Lu]Lu-DOTA-TATE PRRT was significantly higher, ranging from 9.6 to 77.9 Gy. The linear regression model yielded moderate R-squared values of 0.50, 0.59, and 0.36 for kidney, liver and lesion, respectively. The performance of multiple linear regression model was better, with R-squared values increasing to 0.81, 0.77, and 0.84. CONCLUSION Absorbed doses from [177Lu]Lu-DOTA-TATE PRRT can be accurately predicted. Moreover, our models are formalized into simple equations.
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Affiliation(s)
- Hongxing Yang
- Key Laboratory of Nuclear Physics and Ion-Beam Application (MOE), Fudan University, Shanghai, People's Republic of China
- Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
- Center for Biomedical Imaging, Fudan University, Shanghai, People's Republic of China
- Shanghai Engineering Research Center for Molecular Imaging Probes, Shanghai, People's Republic of China
- Institute of Modern Physics, Fudan University, Shanghai, People's Republic of China
| | - Ming Qi
- Key Laboratory of Nuclear Physics and Ion-Beam Application (MOE), Fudan University, Shanghai, People's Republic of China
- Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
- Center for Biomedical Imaging, Fudan University, Shanghai, People's Republic of China
- Shanghai Engineering Research Center for Molecular Imaging Probes, Shanghai, People's Republic of China
| | - Zhihao Chen
- Key Laboratory of Nuclear Physics and Ion-Beam Application (MOE), Fudan University, Shanghai, People's Republic of China
- Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
- Center for Biomedical Imaging, Fudan University, Shanghai, People's Republic of China
- Shanghai Engineering Research Center for Molecular Imaging Probes, Shanghai, People's Republic of China
| | - Fei Liu
- Key Laboratory of Nuclear Physics and Ion-Beam Application (MOE), Fudan University, Shanghai, People's Republic of China
- Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
- Center for Biomedical Imaging, Fudan University, Shanghai, People's Republic of China
- Shanghai Engineering Research Center for Molecular Imaging Probes, Shanghai, People's Republic of China
| | - Junyan Xu
- Key Laboratory of Nuclear Physics and Ion-Beam Application (MOE), Fudan University, Shanghai, People's Republic of China
- Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
- Center for Biomedical Imaging, Fudan University, Shanghai, People's Republic of China
- Shanghai Engineering Research Center for Molecular Imaging Probes, Shanghai, People's Republic of China
| | - Xiaoping Xu
- Key Laboratory of Nuclear Physics and Ion-Beam Application (MOE), Fudan University, Shanghai, People's Republic of China
- Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
- Center for Biomedical Imaging, Fudan University, Shanghai, People's Republic of China
- Shanghai Engineering Research Center for Molecular Imaging Probes, Shanghai, People's Republic of China
| | - Qing Kong
- Key Laboratory of Nuclear Physics and Ion-Beam Application (MOE), Fudan University, Shanghai, People's Republic of China
- Institute of Modern Physics, Fudan University, Shanghai, People's Republic of China
| | - Jianping Zhang
- Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
- Center for Biomedical Imaging, Fudan University, Shanghai, People's Republic of China
- Shanghai Engineering Research Center for Molecular Imaging Probes, Shanghai, People's Republic of China
- Shanghai Key Laboratory of Bioactive Small Molecules, Fudan University, Shanghai, People's Republic of China
| | - Shaoli Song
- Key Laboratory of Nuclear Physics and Ion-Beam Application (MOE), Fudan University, Shanghai, People's Republic of China
- Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Shanghai, People's Republic of China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
- Center for Biomedical Imaging, Fudan University, Shanghai, People's Republic of China
- Shanghai Engineering Research Center for Molecular Imaging Probes, Shanghai, People's Republic of China
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Aouf A, Speicher T, Blickle A, Bastian MB, Burgard C, Rosar F, Ezziddin S, Sabet A. Prediction of lesion-based response to PRRT using baseline somatostatin receptor PET. Front Med (Lausanne) 2025; 12:1523862. [PMID: 40160333 PMCID: PMC11949938 DOI: 10.3389/fmed.2025.1523862] [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: 11/06/2024] [Accepted: 02/26/2025] [Indexed: 04/02/2025] Open
Abstract
Aim The heterogeneous expression of somatostatin receptors in gastroenteropancreatic neuroendocrine tumors (GEP-NET) leads to significant intra-individual variability in tracer uptake during pre-therapeutic [68Ga]Ga-DOTATOC PET/CT for patients receiving peptide receptor radionuclide therapy (PRRT). This study aims to evaluate the lesion-based relationship between receptor-mediated tracer uptake and the functional response to PRRT. Methods A retrospective analysis was conducted on 32 patients with metastatic GEP-NET (12 pancreatic and 20 non-pancreatic), all treated with [177Lu]Lu-octreotate (4 cycles, with a mean of 7.9 GBq per cycle). [68Ga]Ga-DOTATOC PET/CT was performed at baseline and 3 months after the final PRRT cycle. Tumor uptake was quantified using the standardized uptake value (SUV). For each patient, 2 to 3 well-delineated tumor lesions were selected as target lesions. SUVmax, SUVmean (automated segmentation with a 50% SUVmax threshold), and corresponding tumor-to-liver ratios (SUVmaxT/L and SUVmeanT/L) were calculated. Functional tumor response was assessed based on the relative change in metabolic tumor volume (%ΔTVPET). The correlation between baseline SUV parameters and lesion-based functional response was analyzed using Spearman's rank correlation. Results A total of 71 lesions were included in the analysis. The mean baseline SUVmax and SUVmean were 28.1 ± 15.9 and 13.6 ± 5.1, respectively. Three months after PRRT completion, the mean %ΔTVPET was 39.6 ± 52.1%. Baseline SUVmax and SUVmean demonstrated a poor correlation with lesion-based response (p = 0.706 and p = 0.071, respectively). In contrast, SUVmaxT/L and SUVmeanT/L were significantly correlated with lesion-based response (SUVmeanT/L: p = 0.011, r = 0.412; SUVmaxT/L: p = 0.004, r = 0.434). Among patient characteristics-including primary tumor origin, baseline tumor volume, and metastatic sites-only pancreatic origin was significantly associated with functional tumor volume reduction (ΔTVPET%: 56.8 ± 39.8 in pancreatic vs. 28.4 ± 50.1 in non-pancreatic NET; p = 0.020). Conclusion The lesion-based molecular response to PRRT correlates with pretreatment somatostatin receptor PET uptake, particularly when expressed as tumor-to-liver SUV ratios (SUVmaxT/L and SUVmeanT/L).
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Affiliation(s)
- Anas Aouf
- Department of Nuclear Medicine, University Hospital Bonn, Bonn, Germany
| | - Tilman Speicher
- Department of Nuclear Medicine, Saarland University Hospital, Homburg, Germany
| | - Arne Blickle
- Department of Nuclear Medicine, Saarland University Hospital, Homburg, Germany
| | - Moritz B. Bastian
- Department of Nuclear Medicine, Saarland University Hospital, Homburg, Germany
| | - Caroline Burgard
- Department of Nuclear Medicine, Saarland University Hospital, Homburg, Germany
| | - Florian Rosar
- Department of Nuclear Medicine, Saarland University Hospital, Homburg, Germany
| | - Samer Ezziddin
- Department of Nuclear Medicine, Saarland University Hospital, Homburg, Germany
| | - Amir Sabet
- Department of Nuclear Medicine, University Hospital Bonn, Bonn, Germany
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Kuiper J, Zoetelief E, Brabander T, de Herder WW, Hofland J. Current status of peptide receptor radionuclide therapy in grade 1 and 2 gastroenteropancreatic neuroendocrine tumours. J Neuroendocrinol 2025; 37:e13469. [PMID: 39563515 PMCID: PMC11919478 DOI: 10.1111/jne.13469] [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: 07/31/2024] [Revised: 10/11/2024] [Accepted: 11/01/2024] [Indexed: 11/21/2024]
Abstract
Peptide receptor radionuclide therapy (PRRT) using [177Lu-DOTA0,Tyr3]octreotate (177Lu-DOTATATE) represents an established treatment modality for somatostatin receptor-positive, locally advanced or metastatic gastroenteropancreatic neuroendocrine tumours (GEP NET) of grade 1 or 2. The studies have demonstrated that four cycles of PRRT with 177Lu-DOTATATE prolongs progression-free survival and preserves quality of life, in patients with grade 1 and 2 advanced GEP NET. Notably, first-line PRRT using 177Lu-DOTATATE in grade 2 and 3 GEP NET patients has also shown efficacy and safety. Furthermore, PRRT can ameliorate symptoms in patients with NET-associated functioning syndromes. Although various studies have explored alternative radionuclides for PRRT, none currently meet the criteria for routine clinical implementation. Ongoing research aims to further enhance PRRT, and the results from large clinical trials comparing PRRT with other NET treatments are anticipated, potentially leading to significant modifications in NET treatment strategies and PRRT protocols. The results of these studies are likely to help address existing knowledge gaps in the coming years. This review describes the clinical practice, recent developments and future treatment options of PRRT in patients with grade 1 and 2 GEP NET.
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Affiliation(s)
- Jelka Kuiper
- Department of Internal Medicine, Section of Endocrinology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Eline Zoetelief
- Department of Radiology & Nuclear Medicine, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Tessa Brabander
- Department of Radiology & Nuclear Medicine, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Wouter W de Herder
- Department of Internal Medicine, Section of Endocrinology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
| | - Johannes Hofland
- Department of Internal Medicine, Section of Endocrinology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
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Parghane RV, Basu S. Toxicity manifestations encountered in peptide receptor radionuclide therapy setting. J Neuroendocrinol 2025; 37:e13464. [PMID: 39531370 DOI: 10.1111/jne.13464] [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: 08/07/2024] [Revised: 10/10/2024] [Accepted: 10/24/2024] [Indexed: 11/16/2024]
Abstract
Peptide receptor radionuclide therapy (PRRT) has demonstrated immense promise as a treatment for patients with neuroendocrine tumors (NET) who have somatostatin receptor (SSTR) expression. PRRT significantly reduces tumor growth, stabilizes the disease, and prolongs survival in a significant percentage of patients with metastatic/advanced NET. It produces an important beneficial effect on the quality of life (QOL) and effectively alleviates symptoms in patients with NET. Overall, PRRT is typically well-tolerated and most of the side effects are usually transient and subside on their own. It is, however, crucial to be cognizant of the potential toxicities associated with this treatment. This awareness will enable physicians to promptly detect, effectively manage, and prevent these toxicities by identifying high-risk factors in NET patients. This review provides an in-depth overview for clinicians managing NET about the toxicity of PRRT. The toxicities are stratified into acute, subacute, and long-term based on their onset following PRRT. Potential high-risk factors in order to treat effectively and prevent these toxicities in NET patients are presented including the management strategy. This review also discusses novel insights, perspectives, and recent advancements in predicting, preventing, and managing toxicity associated with PRRT, while offering prospective future research directions to minimize clinical toxicity and maximize the therapeutic benefits of PRRT as a treatment strategy for NET patients.
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Affiliation(s)
- Rahul V Parghane
- Radiation Medicine Centre (BARC), Tata Memorial Hospital, Mumbai, India
- Homi Bhabha National Institute, Mumbai, India
| | - Sandip Basu
- Radiation Medicine Centre (BARC), Tata Memorial Hospital, Mumbai, India
- Homi Bhabha National Institute, Mumbai, India
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Prasad V, Koumarianou A, Denecke T, Sundin A, Deroose CM, Pavel M, Christ E, Lamarca A, Caplin M, Castaño JP, Dromain C, Falconi M, Grozinsky-Glasberg S, Hofland J, Knigge UP, Kos-Kudla B, Krishna BA, Reed NS, Scarpa A, Srirajaskanthan R, Toumpanakis C, Kjaer A, Hicks RJ, Ambrosini V. Challenges in developing response evaluation criteria for peptide receptor radionuclide therapy: A consensus report from the European Neuroendocrine Tumor Society Advisory Board Meeting 2022 and the ENETS Theranostics Task Force. J Neuroendocrinol 2025; 37:e13479. [PMID: 39653582 DOI: 10.1111/jne.13479] [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: 10/05/2024] [Revised: 11/18/2024] [Accepted: 11/25/2024] [Indexed: 01/06/2025]
Abstract
Assessing the response to systemic therapy in neuroendocrine tumors (NET) is challenging since morphological imaging response is often delayed and not necessarily reflective of clinical benefit. Peptide receptor radionuclide therapy (PRRT) has a complex mechanism of action, further complicating response assessment. In response to these challenges, the European Neuroendocrine Tumor Society (ENETS) Theranostics Task Force conducted a statement-based survey among experts to identify the current landscape and unmet needs in PRRT response assessment. The survey, presented at the 2022 ENETS Advisory Board (AB) meeting in Vienna, was completed by 70% of AB members, most of whom (81%) were from ENETS Centers of Excellence (CoE). It comprised a set of 13 questions with two substatements in three questions. Six (46%) of the statements achieved more than 75% agreement, while five (39%) additional statements reached over 60% consensus. Key points from the survey include: AB members agreed that lesions deemed equivocal on computed tomography (CT) or magnetic resonance imaging (MRI) should be characterized by somatostatin receptor (SST) positron emission tomography (PET)/CT before being designated as target lesions. It was agreed that interim response assessments should occur after the second or third PRRT cycle. Over half (54%) preferred using both conventional cross-sectional imaging (CT and/or MRI) and hybrid imaging (SST PET/CT) for this purpose. Almost all AB members supported further response assessment 3 months after the final PRRT cycle. A majority (62%) preferred using a combination of conventional cross-sectional imaging and SST PET/CT. For cases showing equivocal progression (ambiguous lesions or nontarget lesions) on CT and/or MRI, further confirmation using SST PET/CT was recommended. A significant majority (74%) preferred assessing pseudo-progression and delayed response by combining SST PET with diagnostic CT and/ or MRI. Though just below the 75% consensus threshold, there was substantial agreement on selecting target lesions based on SST PET/CT uptake intensity and homogeneity. Sixty-nine percent noted the importance of documenting and closely following heterogeneity in lesions in liver, lymph nodes, primary tumors, or other organs. As to the statement on parameters for new response criteria, AB members recommended exploring maximum standard unit value, tumor-to-background ratio, Hounsfield Unit (Choi Criteria), total tumor burden, and novel serum or molecular markers for future response evaluation criteria. Sixty-five percent supported the use of a single SST PET/CT for response assessment of NET lesions treated with PRRT. These findings highlight the importance of integrating advanced imaging techniques and recognizing the need for more nuanced criteria in assessing the efficacy of PRRT in NET patients. This approach aims to enhance the accuracy of treatment monitoring and improve patient outcomes.
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Affiliation(s)
- Vikas Prasad
- Division of Nuclear Medicine, Mallinckrodt Institute of Radiology, Washington University School of Medicine in Saint Louis, St. Louis, Missouri, USA
| | - Anna Koumarianou
- Hematology Oncology Unit, Fourth Department of Internal Medicine, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Timm Denecke
- Department of Diagnostic and Interventional Radiology, University Medical Centre Leipzig, Leipzig, Germany
| | - Anders Sundin
- Radiology and Molecular Imaging, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - Christophe M Deroose
- Nuclear Medicine, University Hospitals Leuven and Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, KU Leuven, Leuven, Belgium
| | - Marianne Pavel
- Department of Medicine 1, Friedrich-Alexander-University of Erlangen-Nürnberg, Erlangen, Germany
| | - Emanuel Christ
- Center of Endocrine and Neuroendocrine Tumors, ENETS Center of Excellence (CoE), Division of Endocrinology, Diabetology and Metabolism, University Hospital of Basel, Basel, Switzerland
| | - Angela Lamarca
- Department of Oncology-OncoHealth Institute-Instituto de Investigaciones Sanitarias FJD, Fundación Jiménez Díaz University Hospital, Madrid, Spain
| | - Martyn Caplin
- Neuroendocrine Tumour Unit, ENETS Center of Excellence, Royal Free Hospital, London, UK
| | - Justo P Castaño
- Maimonides Institute for Biomedical Research of Cordoba (IMIBIC), Córdoba, Spain
- Department of Cell Biology, Physiology, and Immunology, University of Córdoba, Córdoba, Spain
- Reina Sofia University Hospital, Córdoba, Spain
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Córdoba, Córdoba, Spain
| | - Clarisse Dromain
- Department of Diagnostic and Interventional Radiology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland
| | - Massimo Falconi
- Pancreatic Surgery, Pancreas Translational and Clinical Research Center, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Italy
| | - Simona Grozinsky-Glasberg
- Neuroendocrine Tumor Unit, ENETS Center of Excellence, Division of Medicine, Hadassah Medical Organization and Faculty of Medicine, The Hebrew University, Jerusalem, Israel
| | - Johannes Hofland
- Department of Internal Medicine, Section of Endocrinology, ENETS Center of Excellence, Erasmus MC Cancer Institute, Rotterdam, the Netherlands
| | - Ulrich Peter Knigge
- Department of Surgery and Transplantation, Department of Nephrology and Endocrinology, Center of Cancer and Transplantation, ENETS Center of Excellence, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
| | - Beata Kos-Kudla
- Department of Endocrinology and Neuroendocrine Tumours, Department of Pathophysiology and Endocrinology, Medical University of Silesia, Katowice, Poland
| | - Balkundi A Krishna
- Department of Nuclear Medicine & PET imaging, Lilavati Hospital & Research Centre, Mumbai, India
| | | | - Aldo Scarpa
- Department of Diagnostics and Public Health, University of Verona, Verona, Italy
| | | | - Christos Toumpanakis
- Neuroendocrine Tumour Unit, ENETS Center of Excellence, Royal Free Hospital, London, UK
| | - Andreas Kjaer
- Department of Clinical Physiology and Nuclear Medicine & Cluster for Molecular Imaging, Copenhagen University Hospital-Rigshospitalet
- Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Rodney J Hicks
- St Vincent's Hospital, Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia
- Department of Medicine, Translational Medicine, the Alfred Hospital, Monash University, Melbourne, Victoria, Australia
| | - Valentina Ambrosini
- Nuclear Medicine, Alma Mater Studiorum University of Bologna, Bologna, Italy
- Nuclear Medicine, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
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Hounschell CA, Higginbotham S, Al-Kasspooles M, Selby LV. Gastroenteropancreatic Neuroendocrine Tumor with Peritoneal Metastasis: A Review of Current Management. Cancers (Basel) 2024; 16:3472. [PMID: 39456565 PMCID: PMC11506451 DOI: 10.3390/cancers16203472] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Revised: 10/07/2024] [Accepted: 10/10/2024] [Indexed: 10/28/2024] Open
Abstract
Peritoneal metastasis in gastroenteropancreatic neuroendocrine tumors poses a significant clinical challenge, with limited data guiding management strategies. We review the existing literature on surgical and systemic treatment modalities for peritoneal metastasis from gastroenteropancreatic neuroendocrine tumors. Surgical interventions, including cytoreductive surgery, have shown promise in improving symptom control and overall survival-particularly in cases in which 70% cytoreduction can be achieved. Hyperthermic intraperitoneal chemotherapy remains controversial due to a paucity of high-level evidence and a lack of consensus for routine use. The use of systemic therapy in the setting of peritoneal metastasis from gastroenteropancreatic neuroendocrine tumors is extrapolated from high-quality evidence for its use in the setting of the solid organ metastasis of this disease. The use of somatostatin analogs for symptom control and some antiproliferative effects is supported by large clinical trials. Additional strong evidence exists for the use of interferon-alpha, everolimus, and sunitinib, particularly in pancreatic neuroendocrine tumors. Cytotoxic chemotherapy and peptide receptor radionuclide therapy may be used in select cases, though as an emerging treatment modality, the optimal sequence of peptide receptor radionuclide therapy within the existing algorithms is unknown. Significant gaps in understanding and standardized management exist, particularly for those patients presenting with peritoneal metastasis, and targeted research to optimize outcomes in this population is needed.
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Affiliation(s)
- Corey A. Hounschell
- Department of Surgery, University of Kansas Medical Center, Kansas City, KS 66103, USA; (C.A.H.); (M.A.-K.)
| | | | - Mazin Al-Kasspooles
- Department of Surgery, University of Kansas Medical Center, Kansas City, KS 66103, USA; (C.A.H.); (M.A.-K.)
| | - Luke V. Selby
- Department of Surgery, University of Kansas Medical Center, Kansas City, KS 66103, USA; (C.A.H.); (M.A.-K.)
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Liang M, Huang J, Liu C, Chen M. Predictive Modeling of Long-Term Prognosis After Resection in Typical Pulmonary Carcinoid: A Machine Learning Perspective. Cancer Invest 2024; 42:544-558. [PMID: 39007912 DOI: 10.1080/07357907.2024.2356002] [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: 04/09/2024] [Revised: 04/26/2024] [Accepted: 05/13/2024] [Indexed: 07/16/2024]
Abstract
Typical Pulmonary Carcinoid (TPC) is defined by its slow growth, frequently necessitating surgical intervention. Despite this, the long-term outcomes following tumor resection are not well understood. This study examined the factors impacting Overall Survival (OS) in patients with TPC, leveraging data from the Surveillance, Epidemiology, and End Results database spanning from 2000 to 2018. We employed Lasso-Cox analysis to identify prognostic features and developed various models using Random Forest, XGBoost, and Cox regression algorithms. Subsequently, we assessed model performance using metrics such as Area Under the Curve (AUC), calibration plot, Brier score, and Decision Curve Analysis (DCA). Among the 2687 patients, we identified five clinical features significantly affecting OS. Notably, the Random Forest model exhibited strong performance, achieving 5- and 7-year AUC values of 0.744/0.757 in the training set and 0.715/0.740 in the validation set, respectively, outperforming other models. Additionally, we developed a web-based platform aimed at facilitating easy access to the model. This study presents a machine learning model and a web-based support system for healthcare professionals, assisting in personalized treatment decisions for patients with TPC post-tumor resection.
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Affiliation(s)
- Min Liang
- Department of Respiratory and Critical Care Medicine, Maoming People's Hospital, Maoming, China
- Center of Respiratory Research, Maoming People's Hospital, Maoming, China
| | - Jian Huang
- Department of Thoracic Surgery, Maoming People's Hospital, Maoming, China
| | - Caiyan Liu
- Department of Respiratory and Critical Care Medicine, Maoming People's Hospital, Maoming, China
| | - Mafeng Chen
- Department of Otolaryngology, Maoming People's Hospital, Maoming, China
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van de Weijer T, Bemer F, de Vos-Geelen J, Hermans B, Mitea C, van der Pol JAJ, Lodewick T, Wildberger JE, Mottaghy FM. Altered biodistribution of [ 68Ga]Ga-DOTA-TOC during somatostatin analogue treatment. Eur J Nucl Med Mol Imaging 2024; 51:2420-2427. [PMID: 38403723 PMCID: PMC11178651 DOI: 10.1007/s00259-024-06659-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2023] [Accepted: 02/15/2024] [Indexed: 02/27/2024]
Abstract
PURPOSE The need for an interval between the administration of long-acting Somatostatin Receptor Analogues (SSA) and the [68Ga]Ga-DOTA-TATE PET has been questioned based on recent literature in the new EANM guidelines. Here an earlier studies showed that SSA injection immediately before SSTR PET had minimal effect on normal organ and tumor uptake (1). However, data are scarce and there are (small) differences between [68Ga]Ga-DOTA-TATE and [68Ga]Ga-DOTA-TOC binding affinity, and it remains unknown whether these findings can be directly translated to scans with [68Ga]Ga-DOTA-TOC as well. The purpose of this study was to assess the effect of SSA use on the biodistribution in a subsequent [68Ga]Ga-DOTA-TOC PET/CT and compare this intra-individually across several cycles of SSA treatments. METHODS Retrospectively, 35 patients with NENs were included. [68Ga]Ga-DOTA-TOC PET at staging and after the 1st and 2nd cycle of SSA were included. SUVmean and SUVmax of blood, visceral organs, primary tumor and two metastases were determined. Also, the interval between SSA therapy and the PET scan was registered. RESULTS Treatment with SSA resulted in a significantly higher bloodpool activity and lower visceral tracer uptake. This effect was maintained after a 2nd cycle of SSA therapy. Furthermore, there was an inverse relationship between bloodpool tracer availability and visceral tracer binding and a positive correlation between bloodpool tracer availability and primary tumor tracer uptake. With an interval of up to 5 days, there was a significantly higher bloodpool activity than at longer intervals. CONCLUSION Absolute comparison of the SUV on [68Ga]Ga-DOTA-TOC PET should be done with caution as the altered biodistribution of the tracer after SSA treatment should be taken into account. We recommend not to perform a scan within the first 5 days after the injection of lanreotide.
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Affiliation(s)
- T van de Weijer
- Department of Radiology and Nuclear Medicine, ENETS Center of Excellence, Maastricht University Medical Center (MUMC+), P. Debeylaan 25, P.O. Box 5800, 6202, 6229 HX, AZ, Maastricht, The Netherlands
- School of Nutrition and Translational Research in Metabolism (NUTRIM), University of Maastricht (UM), P. Debeylaan 25, P.O. Box 5800, 6202, 6229 HX, AZ, Maastricht, The Netherlands
| | - F Bemer
- Department of Radiology and Nuclear Medicine, ENETS Center of Excellence, Maastricht University Medical Center (MUMC+), P. Debeylaan 25, P.O. Box 5800, 6202, 6229 HX, AZ, Maastricht, The Netherlands
| | - J de Vos-Geelen
- Department of Medical Oncology, ENETS Center of Excellence, MUMC+, P. Debeylaan 25, P.O. Box 5800, 6202, 6229 HX, AZ, Maastricht, The Netherlands
- School for Oncology and Reproduction (GROW), UM, P. Debeylaan 25, P.O. Box 5800, 6202, 6229 HX, AZ, Maastricht, The Netherlands
| | - B Hermans
- Department of Medical Oncology, ENETS Center of Excellence, MUMC+, P. Debeylaan 25, P.O. Box 5800, 6202, 6229 HX, AZ, Maastricht, The Netherlands
- School for Oncology and Reproduction (GROW), UM, P. Debeylaan 25, P.O. Box 5800, 6202, 6229 HX, AZ, Maastricht, The Netherlands
| | - C Mitea
- Department of Radiology and Nuclear Medicine, ENETS Center of Excellence, Maastricht University Medical Center (MUMC+), P. Debeylaan 25, P.O. Box 5800, 6202, 6229 HX, AZ, Maastricht, The Netherlands
- School for Oncology and Reproduction (GROW), UM, P. Debeylaan 25, P.O. Box 5800, 6202, 6229 HX, AZ, Maastricht, The Netherlands
| | - J A J van der Pol
- Department of Radiology and Nuclear Medicine, ENETS Center of Excellence, Maastricht University Medical Center (MUMC+), P. Debeylaan 25, P.O. Box 5800, 6202, 6229 HX, AZ, Maastricht, The Netherlands
- School for Cardiovascular Diseases (CARIM), UM, P. Debeylaan 25, P.O. Box 5800, 6202, 6229 HX, AZ, Maastricht, The Netherlands
| | - T Lodewick
- Department of Radiology and Nuclear Medicine, ENETS Center of Excellence, Maastricht University Medical Center (MUMC+), P. Debeylaan 25, P.O. Box 5800, 6202, 6229 HX, AZ, Maastricht, The Netherlands
| | - J E Wildberger
- Department of Radiology and Nuclear Medicine, ENETS Center of Excellence, Maastricht University Medical Center (MUMC+), P. Debeylaan 25, P.O. Box 5800, 6202, 6229 HX, AZ, Maastricht, The Netherlands
- School for Cardiovascular Diseases (CARIM), UM, P. Debeylaan 25, P.O. Box 5800, 6202, 6229 HX, AZ, Maastricht, The Netherlands
| | - F M Mottaghy
- Department of Radiology and Nuclear Medicine, ENETS Center of Excellence, Maastricht University Medical Center (MUMC+), P. Debeylaan 25, P.O. Box 5800, 6202, 6229 HX, AZ, Maastricht, The Netherlands.
- School for Oncology and Reproduction (GROW), UM, P. Debeylaan 25, P.O. Box 5800, 6202, 6229 HX, AZ, Maastricht, The Netherlands.
- Department of Nuclear Medicine, University Hospital RWTH Aachen University, Pauwelsstr. 30, 52074, Aachen, Germany.
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9
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Petranović Ovčariček P, Calderoni L, Campenni A, Fanti S, Giovanella L. Molecular imaging of thyroid and parathyroid diseases. Expert Rev Endocrinol Metab 2024; 19:317-333. [PMID: 38899737 DOI: 10.1080/17446651.2024.2365776] [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: 03/24/2024] [Accepted: 06/05/2024] [Indexed: 06/21/2024]
Abstract
INTRODUCTION Molecular imaging of thyroid and parathyroid diseases has changed in recent years due to the introduction of new radiopharmaceuticals and new imaging techniques. Accordingly, we provided an clinicians-oriented overview of such techniques and their indications. AREAS COVERED A review of the literature was performed in the PubMed, Web of Science, and Scopus without time or language restrictions through the use of one or more fitting search criteria and terms as well as through screening of references in relevant selected papers. Literature up to and including December 2023 was included. Screening of titles/abstracts and removal of duplicates was performed and the full texts of the remaining potentially relevant articles were retrieved and reviewed. EXPERT OPINION Thyroid and parathyroid scintigraphy remains integral in patients with thyrotoxicosis, thyroid nodules, differentiated thyroid cancer and, respectively, hyperparathyroidism. In the last years positron-emission tomography with different tracers emerged as a more accurate alternative in evaluating indeterminate thyroid nodules [18F-fluorodeoxyglucose (FDG)], differentiated thyroid cancer [124I-iodide, 18F-tetrafluoroborate, 18F-FDG] and hyperparathyroidism [18F-fluorocholine]. Other PET tracers are useful in evaluating relapsing/advanced forms of medullary thyroid cancer (18F-FDOPA) and selecting patients with advanced follicular and medullary thyroid cancers for theranostic treatments (68Ga/177Ga-somatostatin analogues).
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Affiliation(s)
- Petra Petranović Ovčariček
- Department of Oncology and Nuclear Medicine, University Hospital Center Sestre Milosrdnice, Zagreb, Croatia
- School of Medicine, University of Zagreb, Zagreb, Croatia
| | - Letizia Calderoni
- Nuclear Medicine Division, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico S. Orsola, Bologna, Italy
- Nuclear Medicine, Alma Mater Studiorum, University of Bologna, Bologna, Italy
| | - Alfredo Campenni
- Department of Biomedical and Dental Sciences and Morpho-Functional Imaging, Unit of Nuclear Medicine, University of Messina, Messina, Italy
| | - Stefano Fanti
- Nuclear Medicine Division, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Policlinico S. Orsola, Bologna, Italy
- Nuclear Medicine, Alma Mater Studiorum, University of Bologna, Bologna, Italy
| | - Luca Giovanella
- Department of Nuclear Medicine, Gruppo Ospedaliero Moncucco, Lugano, Switzerland
- Clinic for Nuclear Medicine, University Hospital of Zürich, Zürich, Switzerland
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10
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Ebner R, Rübenthaler J, Ricke J, Sheikh GT, Unterrainer LM, Auernhammer CJ, Spitzweg C, Brendel M, Schmid-Tannwald C, Cyran CC. [Imaging of neuroendocrine tumors of the gastrointestinal tract : Value of (hybrid) imaging diagnostics in radiology]. RADIOLOGIE (HEIDELBERG, GERMANY) 2024; 64:553-558. [PMID: 38713221 DOI: 10.1007/s00117-024-01296-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 03/12/2024] [Indexed: 05/08/2024]
Abstract
CLINICAL/METHODICAL ISSUE Neuroendocrine tumors (NET) represent a heterogeneous group of rare tumors that predominantly arise in the gastrointestinal tract. At the time of initial diagnosis, the NET has already spread locoregionally in about half of the patients, and 27% of patients have already developed distant metastases. Since this plays a crucial role in therapy planning, accurate diagnostic imaging is important. STANDARD RADIOLOGICAL METHODS Due to its high temporal and spatial resolution (multiphasic including arterial phase), computed tomography (CT) plays a decisive role in primary staging and follow-up care, while magnetic resonance imaging (MRI) with its excellent soft tissue contrast offers advantages in the assessment of parenchymal organs in the upper abdomen. METHODICAL INNOVATIONS Somatostatin receptor (SSR) positron emission tomography (PET) provides additional functional information that not only helps to detect the primary tumor and distant metastases, but also has a significant influence on therapeutic management in a theranostic approach. PERFORMANCE Hybrid imaging using SSR-PET/CT has proven to be particularly effective in the detection of NET. Compared to conventional imaging, it provides additional information in 68% of patients, which has a significant impact on clinical management. ACHIEVEMENTS Imaging of NET requires the combined use of various methods such as ultrasound, CT, MRI, and PET/CT to enable accurate diagnosis and effective treatment planning. PRACTICAL RECOMMENDATIONS SSR-PET/CT is a valuable tool for the accurate staging of neuroendocrine tumors of the gastrointestinal tract, especially with small metastases, while MRI with hepatocyte-specific contrast agent and diffusion-weighted imaging is useful for the specific assessment of liver metastases.
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Affiliation(s)
- R Ebner
- Klinik und Poliklinik für Radiologie, LMU Klinikum, LMU München, Marchioninistr. 15, 81377, München, Deutschland.
| | - J Rübenthaler
- Klinik und Poliklinik für Radiologie, LMU Klinikum, LMU München, Marchioninistr. 15, 81377, München, Deutschland
- Interdisziplinäres Zentrum für Neuroendokrine Tumoren des Gastroenteropankreatischen Systems (GEPNET-KUM), LMU Klinikum, LMU München, München, Deutschland
| | - J Ricke
- Klinik und Poliklinik für Radiologie, LMU Klinikum, LMU München, Marchioninistr. 15, 81377, München, Deutschland
- Interdisziplinäres Zentrum für Neuroendokrine Tumoren des Gastroenteropankreatischen Systems (GEPNET-KUM), LMU Klinikum, LMU München, München, Deutschland
| | - G T Sheikh
- Klinik und Poliklinik für Nuklearmedizin, LMU Klinikum, LMU München, München, Deutschland
| | - L M Unterrainer
- Klinik und Poliklinik für Nuklearmedizin, LMU Klinikum, LMU München, München, Deutschland
| | - C J Auernhammer
- Medizinische Klinik und Poliklinik IV, LMU Klinikum, LMU München, München, Deutschland
- Interdisziplinäres Zentrum für Neuroendokrine Tumoren des Gastroenteropankreatischen Systems (GEPNET-KUM), LMU Klinikum, LMU München, München, Deutschland
| | - C Spitzweg
- Medizinische Klinik und Poliklinik IV, LMU Klinikum, LMU München, München, Deutschland
- Interdisziplinäres Zentrum für Neuroendokrine Tumoren des Gastroenteropankreatischen Systems (GEPNET-KUM), LMU Klinikum, LMU München, München, Deutschland
| | - M Brendel
- Klinik und Poliklinik für Nuklearmedizin, LMU Klinikum, LMU München, München, Deutschland
| | - C Schmid-Tannwald
- Klinik und Poliklinik für Radiologie, LMU Klinikum, LMU München, Marchioninistr. 15, 81377, München, Deutschland
| | - C C Cyran
- Klinik und Poliklinik für Radiologie, LMU Klinikum, LMU München, Marchioninistr. 15, 81377, München, Deutschland
- Interdisziplinäres Zentrum für Neuroendokrine Tumoren des Gastroenteropankreatischen Systems (GEPNET-KUM), LMU Klinikum, LMU München, München, Deutschland
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11
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Konuparamban A, Nautiyal A, Jha AK, Mithun S, Srichandan T, Puranik A, Rangarajan V. Optimization of the number of post-therapeutic planar imaging time points for the most reliable organ and tumour dosimetry in peptide receptor radionuclide therapy. HEALTH AND TECHNOLOGY 2024; 14:799-815. [DOI: 10.1007/s12553-024-00867-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/27/2022] [Accepted: 04/09/2024] [Indexed: 01/06/2025]
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12
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Delpassand ES, Yazdi SM, Ghantoji S, Nakasato A, Strickland C, Nunez R, Shafie A, Cork S, Byrne C, Tang J, Patel J. Effectiveness and Safety of Retreatment with 177Lu-DOTATATE in Patients with Progressive Neuroendocrine Tumors: A Retrospective Real-World Study in the United States. J Nucl Med 2024; 65:746-752. [PMID: 38514088 DOI: 10.2967/jnumed.123.265703] [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: 04/27/2023] [Revised: 02/13/2024] [Indexed: 03/23/2024] Open
Abstract
Advanced neuroendocrine tumors (NETs) are associated with a poor prognosis. A regimen of 4 cycles of 177Lu-DOTATATE has been shown to improve both progression-free survival (PFS) and overall survival (OS) in patients with advanced NETs. To the best of our knowledge, this is the first study in the United States to evaluate the effectiveness and safety of additional cycles of 177Lu-DOTATATE therapy in patients with progressive NETs. Methods: This was a retrospective chart review of adults with advanced NETs. The patients had undergone initial treatment with up to 4 cycles of 177Lu-DOTATATE and, after disease progression and a period of at least 6 mo since the end of the initial treatment, were retreated with at least 1 additional cycle at a single center (2010-2020). Patient characteristics, treatment patterns, and clinical outcomes were evaluated descriptively. Response was evaluated according to RECIST 1.1; toxicity was defined using criteria from Common Terminology Criteria for Adverse Events, version 5.0. Kaplan-Meier plots were used to evaluate PFS and OS. Results: Of the 31 patients who received 177Lu-DOTATATE retreatment, 61% were male and 94% were White. Overall, patients received a median of 6 cycles (4 initial cycles and 2 retreatment cycles), and the mean administered activity was 41.9 GBq. Two patients also went on to receive additional retreatment (1 and 2 cycles, individually) after a second period of at least 6 mo and progression after retreatment. Best responses of partial response and stable disease were observed in 35% and 65% of patients after the initial treatment and 23% and 45% of patients after retreatment, respectively. The median PFS after the initial treatment was 20.2 mo and after retreatment was 9.6 mo. The median OS after the initial treatment was 42.6 mo and after retreatment was 12.6 mo. Hematologic parameters decreased significantly during both the initial treatment and retreatment but recovered such that there was little difference between the values before the initial treatment and before the retreatment. Clinically significant hematotoxicity occurred in 1 and 3 patients after the initial treatment and retreatment, respectively. No grade 3 or 4 nephrotoxicity was observed. Conclusion: Retreatment with 177Lu-DOTATATE after progression appeared to be well tolerated and offered disease control in patients with progressive NETs after initial 177Lu-DOTATATE treatment.
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Affiliation(s)
| | - Soheil M Yazdi
- Excel Diagnostics and Nuclear Oncology Center, Houston, Texas
| | | | | | | | - Rodolfo Nunez
- Excel Diagnostics and Nuclear Oncology Center, Houston, Texas
| | - Afshin Shafie
- Excel Diagnostics and Nuclear Oncology Center, Houston, Texas
| | - Susan Cork
- Excel Diagnostics and Nuclear Oncology Center, Houston, Texas
| | | | | | - Jeetvan Patel
- Novartis Pharmaceuticals Corp., East Hanover, New Jersey; and
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13
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Low HC, Tay YS, Ong SYK, Tham WY, Yan SX. Peptide Receptor Radionuclide Therapy Performed Shortly After Administration of Long-Acting Octreotide. Clin Nucl Med 2023; 48:1086-1088. [PMID: 37844418 DOI: 10.1097/rlu.0000000000004906] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2023]
Abstract
ABSTRACT We present a case of a 68-year-old man with metastatic small bowel neuroendocrine tumor who underwent 4 cycles of peptide receptor radionuclide therapy with 177 Lu-DOTATATE. For his first 3 cycles, therapy was performed approximately 4 weeks after his last dose of octreotide LAR. Because of miscommunication in scheduling, his fourth cycle was performed only 48 hours after his last full dose of octreotide LAR. Despite this, we found that the tumoral uptake was not reduced at all, which may add to the increasing evidence on the nonnecessity of stopping somatostatin analogs before peptide receptor radionuclide therapy.
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Affiliation(s)
- Han Chung Low
- From the Department of Nuclear Medicine and Molecular Imaging, Singapore General Hospital
| | - Young Soon Tay
- From the Department of Nuclear Medicine and Molecular Imaging, Singapore General Hospital
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14
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Zhang JM, Zheng CW, Li XW, Fang ZY, Yu MX, Shen HY, Ji X. Typical Zollinger-Ellison syndrome-atypical location of gastrinoma and absence of hypergastrinemia: A case report and review of literature. World J Clin Cases 2023; 11:6223-6230. [PMID: 37731553 PMCID: PMC10507545 DOI: 10.12998/wjcc.v11.i26.6223] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/18/2023] [Revised: 06/25/2023] [Accepted: 08/11/2023] [Indexed: 09/08/2023] Open
Abstract
BACKGROUND Zollinger-Ellison syndrome (ZES) results from hypersecretion of gastrin from pancreatic or duodenal neuroendocrine tumors, commonly referred to as gastrinomas. The high levels of gastrin lead to a typical presentation involving watery diarrhea and multiple ulcers in the duodenum. Here, we have presented the rare case of a patient with ZES and absence of hypergastrinemia as well as an atypical location of gastrinoma. CASE SUMMARY A 72-year-old woman presented with the typical clinical manifestations of ZES, including upper abdominal pain, significant watery diarrhea, and acidic liquid vomitus. Surprisingly, however, she did not have an increased level of serum gastrin. In addition, there was no evidence of gastrinoma or any other ulcerogenic tumor. Esophagogastroduodenoscopy was conducted to examine the upper digestive tract. Revised diagnoses were considered, and an individualized treatment plan was developed. The patient responded to antacid medication while experiencing intermittent, recurring bouts of ZES. 18F-AlF-NOTA-octreotide positron emission tomography (18F-OC PET)/computed tomography (CT) helped locate the tumor. Postoperative pathology and immunohistochemistry results suggested that the tumor was a gastrinoma located at an unconventional site. CONCLUSION This present case study demonstrates the possibility of ZES-like manifestation in patients with absence of hypergastrinemia. 18F-OC PET/CT is a relatively new imaging technique that can be applied for diagnosing even tiny gastrinomas that are atypical in terms of location.
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Affiliation(s)
- Jin-Ming Zhang
- Department of Gastroenterology, The Second Affiliated Hospital of Jiaxing University, Jiaxing 314001, Zhejiang Province, China
| | - Chu-Wei Zheng
- Department of Gastroenterology, The Second Affiliated Hospital of Jiaxing University, Jiaxing 314001, Zhejiang Province, China
| | - Xiao-Wen Li
- Department of Pathology, The Second Affiliated Hospital of Jiaxing University, Jiaxing 314001, Zhejiang Province, China
| | - Zhi-Yun Fang
- Department of Gastroenterology, The Second Affiliated Hospital of Jiaxing University, Jiaxing 314001, Zhejiang Province, China
| | - Mu-Xin Yu
- College of Medicine, Jiaxing University, Jiaxing 314001, Zhejiang Province, China
| | - Hai-Yan Shen
- Department of Gastroenterology, The Second Affiliated Hospital of Jiaxing University, Jiaxing 314001, Zhejiang Province, China
| | - Xia Ji
- Department of Gastroenterology, The Second Affiliated Hospital of Jiaxing University, Jiaxing 314001, Zhejiang Province, China
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15
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Weber M, Telli T, Kersting D, Seifert R. Prognostic Implications of PET-Derived Tumor Volume and Uptake in Patients with Neuroendocrine Tumors. Cancers (Basel) 2023; 15:3581. [PMID: 37509242 PMCID: PMC10377105 DOI: 10.3390/cancers15143581] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2023] [Revised: 06/20/2023] [Accepted: 06/22/2023] [Indexed: 07/30/2023] Open
Abstract
Historically, molecular imaging of somatostatin receptor (SSTR) expression in patients with neuroendocrine tumors (NET) was performed using SSTR scintigraphy (SRS). Sustained advances in medical imaging have led to its gradual replacement with SSTR positron-emission tomography (SSTR-PET). The higher sensitivity in comparison to SRS on the one hand and conventional cross-sectional imaging, on the other hand, enables more accurate staging and allows for image quantification. In addition, in recent years, a growing body of evidence has assessed the prognostic implications of SSTR-PET-derived prognostic biomarkers for NET patients, with the aim of risk stratification, outcome prognostication, and prediction of response to peptide receptor radionuclide therapy. In this narrative review, we give an overview of studies examining the prognostic value of advanced SSTR-PET-derived (semi-)quantitative metrics like tumor volume, uptake, and composite metrics. Complementing this analysis, a discussion of the current trends, clinical implications, and future directions is provided.
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Affiliation(s)
- Manuel Weber
- Department of Nuclear Medicine, University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, 45147 Essen, Germany
| | - Tugce Telli
- Department of Nuclear Medicine, University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, 45147 Essen, Germany
| | - David Kersting
- Department of Nuclear Medicine, University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, 45147 Essen, Germany
| | - Robert Seifert
- Department of Nuclear Medicine, University of Duisburg-Essen and German Cancer Consortium (DKTK)-University Hospital Essen, 45147 Essen, Germany
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Abstract
Neuroendocrine neoplasms (NENs) are tumors originating from neuroendocrine cells distributed throughout the human body. With an increasing incidence over the past few decades, they represent a highly heterogeneous group of neoplasms, mostly expressing somatostatin receptors (SSTRs) on their cell surface. Peptide receptor radionuclide therapy (PRRT) has emerged as a crucial strategy for treating advanced, unresectable neuroendocrine tumors by administering radiolabeled somatostatin analogs intravenously to target SSTRs. This article will focus on the multidisciplinary theranostic approach, treatment effectiveness (such as response rates and symptom relief), patient outcomes, and toxicity profile of PRRT for NEN patients. We will review the most significant studies, such as the phase III NETTER-1 trial, and discuss promising new radiopharmaceuticals, including alpha-emitting radionuclide-labeled somatostatin analogs and SSTR antagonists.
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Affiliation(s)
- Elettra Merola
- Gastroenterology Unit, G.B. Grassi Hospital (ASL Roma 3), Lido di Ostia, 00122 Rome, Italy
| | - Chiara Maria Grana
- Radiometabolic Therapy Unit, Division of Nuclear Medicine, IRCCS European Institute of Oncology, 20141 Milan, Italy
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17
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Merola E, Grana CM. Peptide Receptor Radionuclide Therapy (PRRT): Innovations and Improvements. Cancers (Basel) 2023; 15:cancers15112975. [PMID: 37296936 DOI: 10.3390/cancers15112975] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Revised: 05/27/2023] [Accepted: 05/28/2023] [Indexed: 06/12/2023] Open
Abstract
Neuroendocrine neoplasms (NENs) are tumors originating from neuroendocrine cells distributed throughout the human body. With an increasing incidence over the past few decades, they represent a highly heterogeneous group of neoplasms, mostly expressing somatostatin receptors (SSTRs) on their cell surface. Peptide receptor radionuclide therapy (PRRT) has emerged as a crucial strategy for treating advanced, unresectable neuroendocrine tumors by administering radiolabeled somatostatin analogs intravenously to target SSTRs. This article will focus on the multidisciplinary theranostic approach, treatment effectiveness (such as response rates and symptom relief), patient outcomes, and toxicity profile of PRRT for NEN patients. We will review the most significant studies, such as the phase III NETTER-1 trial, and discuss promising new radiopharmaceuticals, including alpha-emitting radionuclide-labeled somatostatin analogs and SSTR antagonists.
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Affiliation(s)
- Elettra Merola
- Gastroenterology Unit, G.B. Grassi Hospital (ASL Roma 3), Lido di Ostia, 00122 Rome, Italy
| | - Chiara Maria Grana
- Radiometabolic Therapy Unit, Division of Nuclear Medicine, IRCCS European Institute of Oncology, 20141 Milan, Italy
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18
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Ladrière T, Faudemer J, Levigoureux E, Peyronnet D, Desmonts C, Vigne J. Safety and Therapeutic Optimization of Lutetium-177 Based Radiopharmaceuticals. Pharmaceutics 2023; 15:pharmaceutics15041240. [PMID: 37111725 PMCID: PMC10145759 DOI: 10.3390/pharmaceutics15041240] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Revised: 03/24/2023] [Accepted: 04/07/2023] [Indexed: 04/29/2023] Open
Abstract
Peptide receptor radionuclide therapy (PRRT) using Lutetium-177 (177Lu) based radiopharmaceuticals has emerged as a therapeutic area in the field of nuclear medicine and oncology, allowing for personalized medicine. Since the first market authorization in 2018 of [¹⁷⁷Lu]Lu-DOTATATE (Lutathera®) targeting somatostatin receptor type 2 in the treatment of gastroenteropancreatic neuroendocrine tumors, intensive research has led to transfer innovative 177Lu containing pharmaceuticals to the clinic. Recently, a second market authorization in the field was obtained for [¹⁷⁷Lu]Lu-PSMA-617 (Pluvicto®) in the treatment of prostate cancer. The efficacy of 177Lu radiopharmaceuticals are now quite well-reported and data on the safety and management of patients are needed. This review will focus on several clinically tested and reported tailored approaches to enhance the risk-benefit trade-off of radioligand therapy. The aim is to help clinicians and nuclear medicine staff set up safe and optimized procedures using the approved 177Lu based radiopharmaceuticals.
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Affiliation(s)
- Typhanie Ladrière
- Department of Nuclear Medicine, CHU de Caen Normandie, Normandie Université, UNICAEN, 14000 Caen, France
- Department of Pharmacy, CHU de Caen Normandie, Normandie Université, UNICAEN, 14000 Caen, France
| | - Julie Faudemer
- Department of Nuclear Medicine, CHU de Caen Normandie, Normandie Université, UNICAEN, 14000 Caen, France
| | - Elise Levigoureux
- Hospices Civils de Lyon, Groupement Hospitalier Est, 69677 Bron, France
- Lyon Neuroscience Research Center, CNRS UMR5292, INSERM U1028, Université Claude Bernard Lyon 1, 69677 Bron, France
| | - Damien Peyronnet
- Department of Nuclear Medicine, CHU de Caen Normandie, Normandie Université, UNICAEN, 14000 Caen, France
- Department of Pharmacy, CHU de Caen Normandie, Normandie Université, UNICAEN, 14000 Caen, France
| | - Cédric Desmonts
- Department of Nuclear Medicine, CHU de Caen Normandie, Normandie Université, UNICAEN, 14000 Caen, France
- INSERM U1086, ANTICIPE, Normandy University, UNICAEN, 14000 Caen, France
| | - Jonathan Vigne
- Department of Nuclear Medicine, CHU de Caen Normandie, Normandie Université, UNICAEN, 14000 Caen, France
- Department of Pharmacy, CHU de Caen Normandie, Normandie Université, UNICAEN, 14000 Caen, France
- PhIND, Centre Cyceron, Institut Blood and Brain @ Caen-Normandie, INSERM U1237, Normandie Université, UNICAEN, 14000 Caen, France
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de Lima BAM, da Silva RG, Carroll C, Vilhena B, Perez C, Felix R, Carneiro M, Neto LM, Vaisman F, Corbo R, Pujatti PB, Bulzico D. Neutrophil to lymphocyte ratio as a prognosis biomarker of PRRT in NET patients. Endocrine 2022; 78:177-185. [PMID: 35829985 DOI: 10.1007/s12020-022-03133-5] [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: 04/25/2022] [Accepted: 06/30/2022] [Indexed: 11/24/2022]
Abstract
PURPOSE Peptide Receptor Radionuclide Therapy (PRRT) with 177Lu-DOTATATE is a palliative therapeutic option for advanced Neuroendocrine Tumors (NETs). Prognostic factors can predict long-term outcomes and determine response to therapy. Among those already explored, biomarkers from full blood count, including neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) has shown value for other solid tumors and for NETs patients submitted to other forms of therapy. However, its relation to PRRT response and patients' prognosis is still to be determined. METHODS Medical records from 96 patients submitted to PRRT between 2010 and 2017 were reviewed, median NLR and PLR were calculated from baseline flood blood count and dichotomized as high or low. Progression-free survival (PFS) and Overall Survival (OS) were calculated. RESULTS NLR and PLR median values were 1.8 and 123, respectively. Patients with low NLR had a significantly longer OS (estimated median of 77.5 months, 95% CI: 27.3-127.7) when compared to patients with high NLR (estimated median of 47.7 months, 95% CI: 34.7-60.8); p = 0.04. Patients with low NLR had a trend toward a longer median PFS when compared to patients with high NLR [estimated medians of 77 months (95% CI: 27.3-127.7), and 47.7 months, (95% CI: 34.7-60.7)], respectively, p = 0.08. CONCLUSION Patients with advanced-stage NET with NLR higher than 1.8 have worse long term clinical outcomes after PPRT. Larger studies are needed to validate the optimal cutoff for this biomarker.
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Affiliation(s)
| | | | - Cibele Carroll
- Abdominopelvic Surgery Section, Brazilian National Cancer Institute-INCA, Rio de Janeiro, Brazil
- Carbone Cancer Center, University of Wisconsin, Madison, WI, USA
| | - Bruno Vilhena
- Clinical Oncology Section, Brazilian National Cancer Institute-INCA, Rio de Janeiro, Brazil
| | - Carolina Perez
- Nuclear Medicine Section, Brazilian National Cancer Institute-INCA, Rio de Janeiro, Brazil
| | - Renata Felix
- Nuclear Medicine Section, Brazilian National Cancer Institute-INCA, Rio de Janeiro, Brazil
| | - Michel Carneiro
- Nuclear Medicine Section, Brazilian National Cancer Institute-INCA, Rio de Janeiro, Brazil
| | - Luiz Machado Neto
- Nuclear Medicine Section, Brazilian National Cancer Institute-INCA, Rio de Janeiro, Brazil
| | - Fernanda Vaisman
- Endocrine Oncology Unit, Brazilian National Cancer Institute-INCA, Rio de Janeiro, Brazil
| | - Rossana Corbo
- Nuclear Medicine Section, Brazilian National Cancer Institute-INCA, Rio de Janeiro, Brazil
- Endocrine Oncology Unit, Brazilian National Cancer Institute-INCA, Rio de Janeiro, Brazil
| | | | - Daniel Bulzico
- Nuclear Medicine Section, Brazilian National Cancer Institute-INCA, Rio de Janeiro, Brazil.
- Endocrine Oncology Unit, Brazilian National Cancer Institute-INCA, Rio de Janeiro, Brazil.
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20
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Zamponi V, La Salvia A, Tarsitano MG, Mikovic N, Rinzivillo M, Panzuto F, Giannetta E, Faggiano A, Mazzilli R. Effect of Neuroendocrine Neoplasm Treatment on Human Reproductive Health and Sexual Function. J Clin Med 2022; 11:jcm11143983. [PMID: 35887747 PMCID: PMC9324753 DOI: 10.3390/jcm11143983] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2022] [Revised: 07/06/2022] [Accepted: 07/07/2022] [Indexed: 02/02/2023] Open
Abstract
Neuroendocrine neoplasms (NEN) are characterized by a wide clinical heterogeneity and biological variability, with slow progression and long survival in most cases. Although these tumors can affect young adults, there are few studies that focus on the sexual and reproductive system. The aim of this review was to evaluate the effect of NEN treatment, including somatostatin analogues (SSA), targeted therapy (Everolimus and Sunitinib), radiolabeled-SSA and chemotherapy, on male and female reproductive systems and sexual function. This narrative review was performed for all available prospective and retrospective studies, case reports and review articles published up to March 2022 in PubMed. To date, few data are available on the impact of SSA on human fertility and most of studies come from acromegalic patients. However, SSAs seem to cross the blood–placental barrier; therefore, pregnancy planning is strongly recommended. Furthermore, the effect of targeted therapy on reproductive function is still undefined. Conversely, chemotherapy has a well-known negative impact on male and female fertility. The effect of temozolomide on reproductive function is still undefined, even if changes in semen parameters after the treatment have been described. Finally, very few data are available on the sexual function of NEN treatment.
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Affiliation(s)
- Virginia Zamponi
- Department of Clinical and Molecular Medicine, ENETS Center of Excellence, Sapienza University of Rome, 00185 Rome, Italy; (V.Z.); (N.M.); (A.F.); (R.M.)
| | - Anna La Salvia
- Medical Oncology 2, IRCCS Regina Elena National Cancer Institute, 00144 Rome, Italy
- Correspondence: ; Tel.: +39-0652665698
| | - Maria Grazia Tarsitano
- Department of Medical and Surgical Science, University Magna Graecia, 88100 Catanzaro, Italy;
| | - Nevena Mikovic
- Department of Clinical and Molecular Medicine, ENETS Center of Excellence, Sapienza University of Rome, 00185 Rome, Italy; (V.Z.); (N.M.); (A.F.); (R.M.)
| | - Maria Rinzivillo
- Digestive Disease Unit, ENETS Center of Excellence, Sant’Andrea University Hospital, 00189 Rome, Italy; (M.R.); (F.P.)
| | - Francesco Panzuto
- Digestive Disease Unit, ENETS Center of Excellence, Sant’Andrea University Hospital, 00189 Rome, Italy; (M.R.); (F.P.)
- Department of Medical-Surgical Sciences and Translational Medicine, Sapienza University of Rome, 00185 Rome, Italy
| | - Elisa Giannetta
- Department of Experimental Medicine, Sapienza University of Rome, 00185 Rome, Italy;
| | - Antongiulio Faggiano
- Department of Clinical and Molecular Medicine, ENETS Center of Excellence, Sapienza University of Rome, 00185 Rome, Italy; (V.Z.); (N.M.); (A.F.); (R.M.)
| | - Rossella Mazzilli
- Department of Clinical and Molecular Medicine, ENETS Center of Excellence, Sapienza University of Rome, 00185 Rome, Italy; (V.Z.); (N.M.); (A.F.); (R.M.)
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21
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Jiang Y, Liu Q, Wang G, Sui H, Wang R, Wang J, Zhu Z. A prospective head-to-head comparison of 68 Ga-NOTA-3P-TATE-RGD and 68 Ga-DOTATATE in patients with gastroenteropancreatic neuroendocrine tumours. Eur J Nucl Med Mol Imaging 2022; 49:4218-4227. [PMID: 35657429 DOI: 10.1007/s00259-022-05852-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Accepted: 05/24/2022] [Indexed: 11/30/2022]
Abstract
PURPOSE The aim of this study was to compare 68 Ga-NOTA-3P-TATE-RGD, a dual somatostatin receptor 2- and integrin αVβ3-targeting tracer, to 68 Ga-DOTATATE in a single group of patients with gastroenteropancreatic (GEP)-neuroendocrine tumours (NETs). METHODS Thirty-five patients with histologically confirmed GEP-NETs (5 grade 1, 28 grade 2, and 2 grade 3 tumours) were prospectively enrolled with informed consent. The primary tumour mainly originated from the pancreas and rectum. All patients were scanned with both 68 Ga-NOTA-3P-TATE-RGD PET/CT and 68 Ga-DOTATATE PET/CT within a week and compared on a head-to-head basis. Sixteen patients also had conventional 18F-FDG PET/CT. Images were evaluated semi-quantitatively using maximum standardized uptake values (SUVmax) of tumour and tumour-to-background ratio. RESULTS All patients had at least one positive lesion on each of the two scans. A total of 1190 and 1106 lesions were detected on 68 Ga-NOTA-3P-TATE-RGD images and 68 Ga-DOTATATE images, respectively (P = 0.152). 68 Ga-NOTA-3P-TATE-RGD PET/CT revealed significantly more lesions in the liver than 68 Ga-DOTATATE PET/CT (634 vs. 532, P = 0.021). Both tracers produced comparable results for detecting primary tumours (20 vs. 20, P = 1.000), lymph node metastases (101 vs. 102, P = 0.655), and bone metastases (381 vs. 398, P = 0.244). The tumour SUVmax in 12 patients was significantly higher for 68 Ga-NOTA-3P-TATE-RGD than for 68 Ga-DOTATATE (27.2 ± 13.6 vs. 19.5 ± 10.0, P < 0.001); among them, 9 had 18F-FDG PET/CT and all were found to be FDG-positive. The remaining 23 patients had significantly higher 68 Ga-DOTATATE uptake than 68 Ga-NOTA-3P-TATE-RGD uptake (22.3 ± 16.4 vs. 11.9 ± 7.5, P < 0.001); among them, 7 had 18F-FDG PET/CT and 6 were FDG-negative. Generally, 68 Ga-DOTATATE demonstrated higher tumour SUVmax than 68 Ga-NOTA-3P-TATE-RGD (20.8 ± 16.0 vs. 14.2 ± 8.9, P < 0.001), including primary tumours, liver lesions, lymph node lesions, and bone lesions. However, the tumour-to-background ratio of liver lesions was significantly higher when using 68 Ga-NOTA-3P-TATE-RGD compared with that when using 68 Ga-DOTATATE (8.4 ± 5.5 vs. 4.7 ± 3.7, P < 0.001). CONCLUSION 68 Ga-NOTA-3P-TATE-RGD performed better than 68 Ga-DOTATATE in detection of liver metastases with a higher tumour-to-background ratio. Moreover, 68 Ga-NOTA-3P-TATE-RGD tended to demonstrate higher uptake over 68 Ga-DOTATATE in FDG-avid NETs. TRIAL REGISTRATION Dual SSTR2 and Integrin αvβ3 Targeting PET/CT Imaging (NCT02817945, registered 5 November 2018). URL OF REGISTRY: https://clinicaltrials.gov/ct2/show/NCT02817945.
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Affiliation(s)
- Yuanyuan Jiang
- Department of Nuclear Medicine, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.,State Key Laboratory of Complex Severe and Rare Diseases, Beijing, 100730, China
| | - Qingxing Liu
- Department of Nuclear Medicine, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.,State Key Laboratory of Complex Severe and Rare Diseases, Beijing, 100730, China
| | - Guochang Wang
- Department of Nuclear Medicine, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.,State Key Laboratory of Complex Severe and Rare Diseases, Beijing, 100730, China
| | - Huimin Sui
- Department of Nuclear Medicine, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.,State Key Laboratory of Complex Severe and Rare Diseases, Beijing, 100730, China
| | - Rongxi Wang
- Department of Nuclear Medicine, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.,State Key Laboratory of Complex Severe and Rare Diseases, Beijing, 100730, China
| | - Jiarou Wang
- Department of Nuclear Medicine, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China.,State Key Laboratory of Complex Severe and Rare Diseases, Beijing, 100730, China
| | - Zhaohui Zhu
- Department of Nuclear Medicine, Beijing Key Laboratory of Molecular Targeted Diagnosis and Therapy in Nuclear Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100730, China. .,State Key Laboratory of Complex Severe and Rare Diseases, Beijing, 100730, China.
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22
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Una Cidon E. Vasoactive intestinal peptide secreting tumour: An overview. World J Gastrointest Oncol 2022; 14:808-819. [PMID: 35582098 PMCID: PMC9048535 DOI: 10.4251/wjgo.v14.i4.808] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2021] [Revised: 05/15/2021] [Accepted: 03/25/2022] [Indexed: 02/06/2023] Open
Abstract
Vasoactive intestinal peptide (VIP) secreting tumour (VIPoma) is a rare functional neuroendocrine tumour that typically arises from pancreatic islet cells. These present as sporadic, solitary pancreatic neoplasias with an estimated incidence of one in ten million individuals per year. Only around 5% of VIPomas are associated with multiple endocrine neoplasia type I syndrome. Excessive VIP secretion produces a clinical syndrome characterized by refractory watery diarrhoea, hypokalemia and metabolic acidosis. These coupled with elevated plasma levels of VIP are diagnostic. The majority of VIPomas are malignant and have already metastasized at the time of diagnosis (60%). Metastases occur most frequently in the liver, or regional lymph nodes, lungs, kidneys and bones. Some reports of skin metastases have been documented. Complete surgical resection continues to be the only potentially curative treatment. However, when the neoplasia cannot be excised completely, surgical debulking may provide palliative benefit. Other palliative options have included recently the peptide receptor radionuclide therapy which has shown to be effective and well-tolerated. This article will review all aspects of pancreatic VIPomas highlighting aspects such as clinical presentation, diagnosis and management.
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Affiliation(s)
- Esther Una Cidon
- Department of Medical Oncology, University Hospitals Dorset, Bournemouth BH7 7DW, Dorset, United Kingdom
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23
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Puliani G, Chiefari A, Mormando M, Bianchini M, Lauretta R, Appetecchia M. New Insights in PRRT: Lessons From 2021. Front Endocrinol (Lausanne) 2022; 13:861434. [PMID: 35450421 PMCID: PMC9016202 DOI: 10.3389/fendo.2022.861434] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Accepted: 03/07/2022] [Indexed: 11/16/2022] Open
Abstract
Peptide receptor radionuclide therapy (PRRT) using radiolabeled somatostatin analogs has been used for over two decades for the treatment of well-differentiated neuroendocrine tumors (NETs), and the publication of the NETTER-1 trials has further strengthened its clinical use. However, many aspects of this treatment are still under discussion. The purpose of this review is to collect and discuss the new available evidence, published in 2021, on the use of 177Lu-Oxodotreotide (DOTATATE) or 90Y-Edotreotide (DOTATOC) in adult patients with NETs focusing on the following hot topics: 1) PRRT use in new clinical settings, broaden its indications; 2) the short- and long-term safety; and 3) the identification of prognostic and predictive factors. The review suggests a possible future increase of PRRT applications, using it in other NETs, as a neoadjuvant treatment, or for rechallenge. Regarding safety, available studies, even those with long follow-up, supported the low rates of adverse events, even though 1.8% of treated patients developed a second malignancy. Finally, there is a lack of prognostic and predictive factors for PRRT, with the exception of the crucial role of nuclear imaging for both patient selection and treatment response estimation.
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Affiliation(s)
- Giulia Puliani
- Oncological Endocrinology Unit, Scientific Institute for Research, Hospitalization and Healthcare (IRCCS) Regina Elena National Cancer Institute, Rome, Italy
- Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy
| | - Alfonsina Chiefari
- Oncological Endocrinology Unit, Scientific Institute for Research, Hospitalization and Healthcare (IRCCS) Regina Elena National Cancer Institute, Rome, Italy
| | - Marilda Mormando
- Oncological Endocrinology Unit, Scientific Institute for Research, Hospitalization and Healthcare (IRCCS) Regina Elena National Cancer Institute, Rome, Italy
| | - Marta Bianchini
- Oncological Endocrinology Unit, Scientific Institute for Research, Hospitalization and Healthcare (IRCCS) Regina Elena National Cancer Institute, Rome, Italy
| | - Rosa Lauretta
- Oncological Endocrinology Unit, Scientific Institute for Research, Hospitalization and Healthcare (IRCCS) Regina Elena National Cancer Institute, Rome, Italy
| | - Marialuisa Appetecchia
- Oncological Endocrinology Unit, Scientific Institute for Research, Hospitalization and Healthcare (IRCCS) Regina Elena National Cancer Institute, Rome, Italy
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24
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Merola E, Michielan A, Rozzanigo U, Erini M, Sferrazza S, Marcucci S, Sartori C, Trentin C, de Pretis G, Chierichetti F. Therapeutic strategies for gastroenteropancreatic neuroendocrine neoplasms: State-of-the-art and future perspectives. World J Gastrointest Surg 2022; 14:78-106. [DOI: - merola e, michielan a, rozzanigo u, et al.therapeutic strategies for gastroenteropancreatic neuroendocrine neoplasms: state-of-the-art and future perspectives.world j gastrointestinal surgery, volume 14 number 2 february 27, 2022, doi: 10.4240/wjgs.v14.i2.78] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 04/16/2025] Open
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25
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Merola E, Michielan A, Rozzanigo U, Erini M, Sferrazza S, Marcucci S, Sartori C, Trentin C, de Pretis G, Chierichetti F. Therapeutic strategies for gastroenteropancreatic neuroendocrine neoplasms: State-of-the-art and future perspectives. World J Gastrointest Surg 2022; 14:78-106. [PMID: 35317548 PMCID: PMC8908345 DOI: 10.4240/wjgs.v14.i2.78] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2021] [Revised: 10/18/2021] [Accepted: 01/25/2022] [Indexed: 02/06/2023] Open
Abstract
Although gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) have always been considered rare tumors, their incidence has risen over the past few decades. They represent a highly heterogeneous group of neoplasms with several prognostic factors, including disease stage, proliferative index (Ki67), and tumor differentiation. Most of these neoplasms express somatostatin receptors on the cell surface, a feature that has important implications in terms of prognosis, diagnosis, and therapy. Although International Guidelines propose algorithms aimed at guiding therapeutic strategies, GEP-NEN patients are still very different from one another, and the need for personalized treatment continues to increase. Radical surgery is always the best option when feasible; however, up to 80% of cases are metastatic upon diagnosis. Regarding medical treatments, as GEP-NENs are characterized by relatively long overall survival, multiple therapy lines are adopted during the lifetime of these patients, but the optimum sequence to be followed has never been clearly defined. Furthermore, although new molecular markers aimed at predicting the response to therapy, as well as prognostic scores, are currently being studied, their application is still far from being part of daily clinical practice. As they represent a complex disease, with therapeutic protocols that are not completely standardized, GEP-NENs require a multidisciplinary approach. This review will provide an overview of the available therapeutic options for GEP-NENs and attempts to clarify the possible approaches for the management of these patients and to discuss future perspectives in this field.
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Affiliation(s)
- Elettra Merola
- Department of Gastroenterology, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Trento 38122, Italy
| | - Andrea Michielan
- Department of Gastroenterology, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Trento 38122, Italy
| | - Umberto Rozzanigo
- Department of Radiology, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Trento 38122, Italy
| | - Marco Erini
- Department of Nuclear Medicine, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Trento 38122, Italy
| | - Sandro Sferrazza
- Department of Gastroenterology, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Trento 38122, Italy
| | - Stefano Marcucci
- Department of Surgery, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Trento 38122, Italy
| | - Chiara Sartori
- Department of Pathology, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Trento 38122, Italy
| | - Chiara Trentin
- Department of Medical Oncology, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Trento 38122, Italy
| | - Giovanni de Pretis
- Department of Gastroenterology, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Trento 38122, Italy
| | - Franca Chierichetti
- Department of Nuclear Medicine, Santa Chiara Hospital, Azienda Provinciale per i Servizi Sanitari (APSS), Trento 38122, Italy
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26
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Ambrosini V, Zanoni L, Filice A, Lamberti G, Argalia G, Fortunati E, Campana D, Versari A, Fanti S. Radiolabeled Somatostatin Analogues for Diagnosis and Treatment of Neuroendocrine Tumors. Cancers (Basel) 2022; 14:1055. [PMID: 35205805 PMCID: PMC8870358 DOI: 10.3390/cancers14041055] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2021] [Revised: 02/10/2022] [Accepted: 02/17/2022] [Indexed: 02/04/2023] Open
Abstract
Neuroendocrine neoplasms (NENs) are rare and heterogeneous tumors that require multidisciplinary discussion for optimal care. The theranostic approach (DOTA peptides labelled with 68Ga for diagnosis and with 90Y or 177Lu for therapy) plays a crucial role in the management of NENs to assess disease extension and as a criteria for peptide receptor radionuclide therapy (PRRT) eligibility based on somatostatin receptor (SSTR) expression. On the diagnostic side, [68Ga]Ga-DOTA peptides PET/CT (SSTR PET/CT) is the gold standard for imaging well-differentiated SSTR-expressing neuroendocrine tumors (NETs). [18F]FDG PET/CT is useful in higher grade NENs (NET G2 with Ki-67 > 10% and NET G3; NEC) for more accurate disease characterization and prognostication. Promising emerging radiopharmaceuticals include somatostatin analogues labelled with 18F (to overcome the limits imposed by 68Ga), and SSTR antagonists (for both diagnosis and therapy). On the therapeutic side, the evidence gathered over the past two decades indicates that PRRT is to be considered as an effective and safe treatment option for SSTR-expressing NETs, and is currently included in the therapeutic algorithms of the main scientific societies. The positioning of PRRT in the treatment sequence, as well as treatment personalization (e.g., tailored dosimetry, re-treatment, selection criteria, and combination with other alternative treatment options), is warranted in order to improve its efficacy while reducing toxicity. Although very preliminary (being mostly hampered by lack of methodological standardization, especially regarding feature selection/extraction) and often including small patient cohorts, radiomic studies in NETs are also presented. To date, the implementation of radiomics in clinical practice is still unclear. The purpose of this review is to offer an overview of radiolabeled SSTR analogues for theranostic use in NENs.
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Affiliation(s)
- Valentina Ambrosini
- Department of Experimental Diagnostic and Specialized Medicine, University of Bologna, 40138 Bologna, Italy; (V.A.); (G.L.); (G.A.); (E.F.); (D.C.); (S.F.)
- Nuclear Medicine Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Lucia Zanoni
- Nuclear Medicine Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Angelina Filice
- Nuclear Medicine Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy; (A.F.); (A.V.)
| | - Giuseppe Lamberti
- Department of Experimental Diagnostic and Specialized Medicine, University of Bologna, 40138 Bologna, Italy; (V.A.); (G.L.); (G.A.); (E.F.); (D.C.); (S.F.)
- Division of Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Giulia Argalia
- Department of Experimental Diagnostic and Specialized Medicine, University of Bologna, 40138 Bologna, Italy; (V.A.); (G.L.); (G.A.); (E.F.); (D.C.); (S.F.)
| | - Emilia Fortunati
- Department of Experimental Diagnostic and Specialized Medicine, University of Bologna, 40138 Bologna, Italy; (V.A.); (G.L.); (G.A.); (E.F.); (D.C.); (S.F.)
| | - Davide Campana
- Department of Experimental Diagnostic and Specialized Medicine, University of Bologna, 40138 Bologna, Italy; (V.A.); (G.L.); (G.A.); (E.F.); (D.C.); (S.F.)
- Division of Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Annibale Versari
- Nuclear Medicine Unit, Azienda USL-IRCCS di Reggio Emilia, 42123 Reggio Emilia, Italy; (A.F.); (A.V.)
| | - Stefano Fanti
- Department of Experimental Diagnostic and Specialized Medicine, University of Bologna, 40138 Bologna, Italy; (V.A.); (G.L.); (G.A.); (E.F.); (D.C.); (S.F.)
- Nuclear Medicine Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
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Cavicchioli M, Bitencourt AGV, Lima ENP. 68Ga-DOTATATE PET/CT versus 111In-octreotide scintigraphy in patients with neuroendocrine tumors: a prospective study. Radiol Bras 2022; 55:13-18. [PMID: 35210659 PMCID: PMC8864693 DOI: 10.1590/0100-3984.2021.0038] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Accepted: 03/11/2021] [Indexed: 01/15/2023] Open
Abstract
Objective To compare 68Ga-DOTA-DPhe1,Tyr3-octreotate
(68Ga-DOTATATE) positron-emission tomography/computed tomography
(PET/CT) findings with those of conventional 111In-octreotide
scintigraphy in patients with neuroendocrine tumors (NETs). Materials and Methods This was a single-center prospective study including 41 patients (25 males;
mean age, 55.4 years) with biopsy-proven NETs who underwent whole-body
111In-octreotide scintigraphy and whole-body
68Ga-DOTATATE PET/CT. The patients had been referred for tumor
staging (34.1%), tumor restaging (61.0%), or response evaluation (4.9%).
Images were compared in a patient-by-patient analysis to identify additional
lesions, and we attempted to determine the impact that discordant findings
had on treatment planning. Results Compared with 111In-octreotide scintigraphy,
68Ga-DOTATATE PET/CT revealed more lesions, the additional
lesions typically being in the liver or bowel. Changes in management owing
to the additional information provided by 68Ga-DOTATATE PET/CT
occurred in five patients (12.2%), including intermodal changes in three
(7.3%) and intramodal changes in two (4.9%). In addition,
68Ga-DOTATATE PET/CT yielded incidental findings unrelated to the
primary NET in three patients (7.3%): Hürthle cell carcinoma of the
thyroid, bowel non-Hodgkin lymphoma, and a suspicious breast lesion. Conclusion We conclude that 68Ga-DOTATATE PET/CT is superior to conventional
111In-octreotide scintigraphy for the management of NETs
because of its ability to determine the extent of the disease more
accurately, which, in some cases, translates to changes in the treatment
plan.
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28
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Kabasakal L, Demirci E, Selçuk NA. Radionuclide Therapy in Neuroendocrine Tumors. RADIONUCLIDE THERAPY 2022:173-186. [DOI: 10.1007/978-3-030-97220-2_9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Tabacchi E, Nanni C, Bossert I, Maffione AM, Fanti S. Diagnostic Applications of Nuclear Medicine: Pancreatic Cancer. NUCLEAR ONCOLOGY 2022:891-917. [DOI: 10.1007/978-3-031-05494-5_17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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Elgazzar AH, Sarikaya I. Basis of Therapeutic Nuclear Medicine. THE PATHOPHYSIOLOGIC BASIS OF NUCLEAR MEDICINE 2022:569-594. [DOI: 10.1007/978-3-030-96252-4_13] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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31
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Ebbers SC, Heimgartner M, Barentsz MW, van Leeuwaarde RS, van Treijen MJC, Lam MMEG, Braat AJAT. Gallium-68-somatostatin receptor PET/CT parameters as potential prognosticators for clinical time to progression after peptide receptor radionuclide therapy: a cohort study. Eur J Hybrid Imaging 2021; 5:22. [PMID: 34881405 PMCID: PMC8655066 DOI: 10.1186/s41824-021-00116-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Accepted: 10/08/2021] [Indexed: 12/02/2022] Open
Abstract
Background Early [68Ga]Ga-DOTA-TOC PET/CT imaging after peptide receptor radionuclide therapy (PRRT) in neuroendocrine neoplasm patients is often used as a prognosticator for survival, but lacks validity. This study investigates the prognostic value of changes in PET parameters after PRRT. Methods Baseline and follow-up [68Ga]Ga-DOTA-TOC PET/CT scans of all patients treated with PRRT were delineated automatically. Total lesion somatostatin receptor expression (TL-SSTR) and somatostatin receptor expressing tumor volume (SSTR-TV) were used as covariates in Cox proportional hazard models to predict time-to-new treatment. Results In twenty patients, median time-to-new treatment was 19.3 months (range [3.8; 36.2]). Absolute and percentual changes in both PET parameters were not associated with time-to-new treatment. A significant relation between independent baseline and follow-up SSTR-TV and follow-up TL-SSTR, and time-to-new treatment was identified. Conclusions Automatically derived [68Ga]Ga-DOTA-TOC PET/CT parameters are easy to acquire and may be of prognostic value after completing PRRT. Acquiring SSTR-TV or TL-SSTR parameters at baseline and during follow-up can be of value in identifying a patient’s prognosis.
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Affiliation(s)
- Sander C Ebbers
- Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.
| | - Muriël Heimgartner
- Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands
| | - Maarten W Barentsz
- Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands
| | - Rachel S van Leeuwaarde
- Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands
| | - Mark J C van Treijen
- Department of Endocrine Oncology, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands
| | - Marnix M E G Lam
- Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands
| | - Arthur J A T Braat
- Department of Radiology and Nuclear Medicine, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands
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de Vries–Huizing DMV, Versleijen MWJ, Sinaasappel M, Walraven I, Geluk–Jonker MM, Tesselaar MET, Hendrikx JJMA, de Wit–van der Veen BJ, Stokkel MPM. Haematotoxicity during peptide receptor radionuclide therapy: Baseline parameters differences and effect on patient's therapy course. PLoS One 2021; 16:e0260073. [PMID: 34793530 PMCID: PMC8601524 DOI: 10.1371/journal.pone.0260073] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Accepted: 11/02/2021] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND Mainly severe (CTCAE grade 3-4) haematotoxicity during peptide receptor radionuclide therapy (PRRT) is reported in literature due to major clinical impact, however moderate (CTCAE grade 2) haematotoxicity is common and could affect therapy management. The aim of this study was to evaluate the haematotoxicity course during PRRT and to compare baseline parameters between haematotoxicity grades. METHODS In this retrospective study, 100 patients with a neuroendocrine tumour treated with PRRT were included. Patients were treated with an aimed number of four cycles with 7.4 GBq [177Lu]Lu-DOTA-TATE administered every 10 weeks. Haematological assessment was performed at baseline and frequently up to 10 weeks after the fourth cycle. The lowest haematological value was graded according to CTCAE v5.0, and patients were classified using the highest observed grade. Differences in baseline parameters, including [68Ga]Ga-DOTA-TATE positive tumour volume, were evaluated between CTCAE grades. RESULTS Four cycles were completed by 86/100 of patients, 4/100 patients discontinued due to haematotoxicity, and 10/100 patients due to progressive disease. The treatment course was adjusted due to haematotoxicity in 24/100 patients, including postponed next cycle (n = 17), reduced administered activity (n = 13), and both adjustments (n = 10). The most observed haematotoxicity grade was grade 0-1 in 54/100 patients, grade 2 in 38/100 and grade 3-4 in 8/100. Significant differences in baseline leucocyte, neutrophil and platelet counts were observed between grade 0-1 and grade 2. However, the correlation between baseline and lowest observed values was poor to moderate. No differences between haematotoxicity grades and baseline parameters or somatostatin receptor positive tumour volume was observed. CONCLUSIONS The incidence of severe haematotoxicity was low with extensive screening and monitoring. The vast majority of patients (96/100) was not restricted in treatment continuation by haematotoxicity; therefore, our selection criteria appeared appropriate for safe PRRT treatment. Baseline parameters showed limited correlation with the degree of decline in haematological values.
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Affiliation(s)
| | | | - Michiel Sinaasappel
- Department of Clinical Physics and Instrumentation, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Iris Walraven
- Department for Health Evidence, Radboudumc, Nijmegen, The Netherlands
| | | | - Margot E. T. Tesselaar
- Department of Medical Oncology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Jeroen J. M. A. Hendrikx
- Department of Nuclear Medicine, Netherlands Cancer Institute, Amsterdam, The Netherlands
- Department of Pharmacy & Pharmacology, Netherlands Cancer Institute, Amsterdam, The Netherlands
| | | | - Marcel P. M. Stokkel
- Department of Nuclear Medicine, Netherlands Cancer Institute, Amsterdam, The Netherlands
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Zanata I, Ambrosio MR, Zatelli MC. Neoadjuvant PRRT for advanced pNEN: an unusual highlander. Endocrine 2021; 73:493-495. [PMID: 33661459 PMCID: PMC8263537 DOI: 10.1007/s12020-021-02662-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/14/2021] [Accepted: 02/10/2021] [Indexed: 11/06/2022]
Affiliation(s)
- Isabella Zanata
- Section of Endocrinology and Internal Medicine, Department of Medical Sciences, University of Ferrara, Ferrara, Italy
| | - Maria Rosaria Ambrosio
- Section of Endocrinology and Internal Medicine, Department of Medical Sciences, University of Ferrara, Ferrara, Italy
| | - Maria Chiara Zatelli
- Section of Endocrinology and Internal Medicine, Department of Medical Sciences, University of Ferrara, Ferrara, Italy.
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Does 68Ga-DOTA-NOC-PET/CT impact staging and therapeutic decision making in pulmonary carcinoid tumors? Nucl Med Commun 2021; 41:1040-1046. [PMID: 32732596 DOI: 10.1097/mnm.0000000000001248] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE Purpose of this study was to assess the utility of Ga-DOTA-NOC-PET/computed tomography (CT) (Ga-NOC-PET) in tumor detection, pathological differentiation and baseline staging of pulmonary carcinoids as well as to study its impact on therapeutic decision making. PATIENTS AND METHODS Patients who underwent a Ga-NOC-PET for initial evaluation of bronchopulmonary carcinoid tumors from August 2014 to December 2019 were included. Detection rate of Ga-NOC-PET for the primary lesion was calculated by visual estimation of tracer uptake as per Krenning score. SUVmax of typical and atypical carcinoid tumors was measured and difference compared using nonparametric statistical tests. Proportion of patients with distant metastases was also calculated and its impact on intended treatment was assessed. RESULTS Imaging, histopathology and treatment details of 119 patients were available for analysis. Majority of tumors had an endobronchial location (74.7%) and showed histopathologic features of typical carcinoid (82.3%). Ga-NOC-PET showed a detection rate/sensitivity of 92.4%. Oncocytic variant on histopathology and smaller tumor size accounted for majority of negative results. Typical carcinoids showed significantly higher SUVmax than atypical tumors (median SUVmax 38.4 vs. 15.7, P = 0.002). Metastases to distant sites outside the thorax were seen in 14 patients (11.7%), primarily in liver and bones changing the intent of treatment from surgery to systemic therapy. CONCLUSION Ga-NOC-PET detects asymptomatic distant metastatic disease in a sizeable number of patients (11.7%) with pulmonary carcinoid and thus contribute to clinical management by precluding futile surgeries. It shows a high sensitivity for tumor detection and can help differentiate between typical and atypical carcinoid variants by virtue of their variable tracer uptake. PET/CT using Ga-labeled DOTA peptides should be an integral part of diagnostic workup of patients with lung carcinoid.
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Ebbers SC, Barentsz MW, de Keizer B, Krijger GC, Lam MGEH, Braat AJAT. A Rapid and Safe Infusion Protocol for 177Lu Peptide Receptor Radionuclide Therapy. J Nucl Med 2021; 62:816-822. [PMID: 33246981 DOI: 10.2967/jnumed.120.252494] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2020] [Accepted: 09/29/2020] [Indexed: 11/16/2022] Open
Abstract
Peptide receptor radionuclide therapy (PRRT) with 177Lu-labeled somatostatin analogs in patients with somatostatin receptor-expressing tumors is often performed using administration protocols prescribing a 30-min infusion time. The most often used method of infusion is the gravity method, by which the complete dose is effectively administered exponentially. However, there is no evidence to explicitly support an infusion time of 30 min. This study aims to investigate the safety of an infusion time of less than 5 min. Methods: A cohort study was performed, examining the biochemical and clinical toxicity after PRRT when using a fast-infusion protocol with a maximum infusion time of 5 min. Data on patient characteristics, laboratory tests, follow-up visits, and pre- and posttreatment imaging using 68Ga-DOTATOC PET/CT from patients treated with PRRT at the University Medical Center Utrecht (UMC Utrecht) were collected. All patients receiving PRRT using the fast-infusion protocol were included. If no laboratory or clinical follow-up was available, patients were excluded. In addition, a laboratory experiment was performed, simulating the standard-infusion protocol using the gravity method. Results: Thirty-one patients, treated using the fast-infusion protocol, were included. Clinical toxicity mainly consisted of grade 1/2 fatigue (87.1%) and grade 1 nausea or vomiting (67.7%) during follow-up. No acute or long-term clinical toxicity possibly related to the fast-infusion protocol was reported. Grade 3/4 hematologic toxicity occurred after PRRT in 1 patient (3.2%). No grade 3/4 renal toxicity occurred. The laboratory experiment showed that when using the gravity method for infusion, half of the activity is infused after 3.5 min, and 95% is infused within 15 min. Conclusion: A faster infusion of PRRT using an infusion time of less than 5 min is safe and feasible in clinical practice.
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Affiliation(s)
- Sander C Ebbers
- Department of Nuclear Medicine, University Medical Center Utrecht, Utrecht, The Netherlands; and
| | - Maarten W Barentsz
- Department of Radiology, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Bart de Keizer
- Department of Nuclear Medicine, University Medical Center Utrecht, Utrecht, The Netherlands; and
| | - Gerard C Krijger
- Department of Nuclear Medicine, University Medical Center Utrecht, Utrecht, The Netherlands; and
| | - Marnix G E H Lam
- Department of Nuclear Medicine, University Medical Center Utrecht, Utrecht, The Netherlands; and
| | - Arthur J A T Braat
- Department of Nuclear Medicine, University Medical Center Utrecht, Utrecht, The Netherlands; and
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Lu X, Lu C, Yang Y, Shi X, Wang H, Yang N, Yang K, Zhang X. Current Status and Trends in Peptide Receptor Radionuclide Therapy in the Past 20 Years (2000-2019): A Bibliometric Study. Front Pharmacol 2021; 12:624534. [PMID: 33986664 PMCID: PMC8111084 DOI: 10.3389/fphar.2021.624534] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2020] [Accepted: 02/15/2021] [Indexed: 12/26/2022] Open
Abstract
Background: Peptide receptor radionuclide therapy (PRRT) is an emerging therapeutic option for the treatment of neuroendocrine tumors (NETs), and the number of publications in this field has been increasing in recent years. The aim of the present study was to present the research status and summarize the key topics through bibliometric analysis of published PRRT literature. Methods: A literature search for PRRT research from 2000 to 2019 was conducted using the Science Citation Index Expanded of Web of Science Core Collection (limited to SCIE) on August 4, 2020. The VOSviewer, R-bibliometrix, and CiteSpace software were used to conduct the bibliometric analysis. Results: From 2000 to 2019, a total of 681 publications (523 articles and 158 reviews) were retrieved. Annual publication outputs grew from three to 111 records. Germany had the largest number of publications, making the largest contribution to the field (n = 151, 22.17%). Active cooperation between countries/regions was observed. Kwekkeboom from the Erasmus Medical Center is perhaps a key researcher in the field of PRRT. The European Journal of Nuclear Medicine and Molecular Imaging and Journal of Nuclear Medicine ranked first for productive (n = 84, 12.33%) and co-cited (n = 3,438) journals, respectively. Important topics mainly included matters related to the efficacy of PRRT (e.g., 90Y-dotatoc and 177Lu-dotatate), the long-term adverse effects of PRRT (e.g., hematologic and renal toxicities), standardization of NETs and PRRT in practice, the development of medical imaging techniques, and the individual dose optimization of PRRT. Conclusion: Using bibliometric analysis, we gained deep insight into the global status and trends of studies investigating PRRT for the first time. The PRRT field is undergoing a period of rapid development, and our study provides a valuable reference for clinical researchers and practitioners.
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Affiliation(s)
- Xiaojing Lu
- Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Cuncun Lu
- Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.,Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, China
| | - Yongjie Yang
- Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Xiangfen Shi
- Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Haibo Wang
- School of Integrated Traditional Chinese and Western Medicine, Gansu University of Chinese Medicine, Lanzhou, China
| | - Nan Yang
- Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China
| | - Kehu Yang
- Evidence-Based Medicine Center, School of Basic Medical Sciences, Lanzhou University, Lanzhou, China
| | - Xiaojian Zhang
- Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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Peptide Receptor Radionuclide Therapy of Pulmonary Neuroendocrine Neoplasms: a Single-Centre Experience. Nucl Med Mol Imaging 2021; 55:38-45. [PMID: 33643488 DOI: 10.1007/s13139-020-00679-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2020] [Revised: 11/25/2020] [Accepted: 12/07/2020] [Indexed: 10/22/2022] Open
Abstract
Purpose Peptide receptor radionuclide therapy represents a therapeutic option for neuroendocrine neoplasms; to date, experiences with peptide receptor radionuclide therapy of pulmonary neuroendocrine neoplasms are still limited. We report our experience with peptide receptor radionuclide therapy of pulmonary neuroendocrine neoplasm patients. Materials and Methods Clinical records of 14 pulmonary neuroendocrine neoplasm patients (7 female and 7 male) who received at least 2 cycles of peptide receptor radionuclide therapy were retrospectively reviewed. Tumoural uptake of somatostatin analogues at pre-treatment imaging was graded as 2 to 3 in all patients. RECIST criteria were used to evaluate response. Results No treated patient had significant toxicity. Partial response was found in 3 (21.4%) patients, stable disease in 7 (50%), and progressive disease in 4 (28.6%). A statistically significant difference between disease state at enrolment and after peptide receptor radionuclide therapy was found. Conclusions Our data furtherly support peptide receptor radionuclide therapy as a safe and effective treatment of patients affected by pulmonary neuroendocrine neoplasms allowing disease control in about 71% of patients without showing significant toxicity. Other studies are needed to confirm our results.
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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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Jackson P, McIntosh L, Hofman MS, Kong G, Hicks RJ. Technical Note: Rapid multiexponential curve fitting algorithm for voxel-based targeted radionuclide dosimetry. Med Phys 2020; 47:4332-4339. [PMID: 32426853 DOI: 10.1002/mp.14243] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2019] [Revised: 04/24/2020] [Accepted: 05/11/2020] [Indexed: 11/06/2022] Open
Abstract
BACKGROUND Dosimetry in nuclear medicine often relies on estimating pharmacokinetics based on sparse temporal data. As analysis methods move toward image-based three-dimensional computation, it becomes important to interpolate and extrapolate these data without requiring manual intervention; that is, in a manner that is highly efficient and reproducible. Iterative least-squares solvers are poorly suited to this task because of the computational overhead and potential to optimize to local minima without applying tight constraints at the outset. METHODOLOGY This work describes a fully analytical method for solving three-phase exponential time-activity curves based on three measured time points in a manner that may be readily employed by image-based dosimetry tools. The methodology uses a series of conditional statements and a piecewise approach for solving exponential slope directly through measured values in most instances. The proposed algorithm is tested against a purpose-designed iterative fitting technique and linear piecewise method followed by single exponential in a cohort of ten patients receiving 177 Lu-DOTA-Octreotate therapy. RESULTS Tri-exponential time-integrated values are shown to be comparable to previously published methods with an average difference between organs when computed at the voxel level of 9.8 ± 14.2% and -3.6 ± 10.4% compared to iterative and interpolated methods, respectively. Of the three methods, the proposed tri-exponential algorithm was most consistent when regional time-integrated activity was evaluated at both voxel- and whole-organ levels. For whole-body SPECT imaging, it is possible to compute 3D time-integrated activity maps in <5 min processing time. Furthermore, the technique is able to predictably and reproducibly handle artefactual measurements due to noise or spatial misalignment over multiple image times. CONCLUSIONS An efficient, analytical algorithm for solving multiphase exponential pharmacokinetics is reported. The method may be readily incorporated into voxel-dose routines by combining with widely available image registration and radiation transport tools.
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Affiliation(s)
- Price Jackson
- Department of Molecular Imaging & Therapeutic Nuclear Medicine, Peter MacCallum Cancer Centre, Melbourne, 3000, Australia.,Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, 3010, Australia
| | - Lachlan McIntosh
- Department of Molecular Imaging & Therapeutic Nuclear Medicine, Peter MacCallum Cancer Centre, Melbourne, 3000, Australia
| | - Michael S Hofman
- Department of Molecular Imaging & Therapeutic Nuclear Medicine, Peter MacCallum Cancer Centre, Melbourne, 3000, Australia.,Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, 3010, Australia
| | - Grace Kong
- Department of Molecular Imaging & Therapeutic Nuclear Medicine, Peter MacCallum Cancer Centre, Melbourne, 3000, Australia.,Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, 3010, Australia
| | - Rodney J Hicks
- Department of Molecular Imaging & Therapeutic Nuclear Medicine, Peter MacCallum Cancer Centre, Melbourne, 3000, Australia.,Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, 3010, Australia
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Signore A, Lauri C, Auletta S, Varani M, Onofrio L, Glaudemans AWJM, Panzuto F, Marchetti P. Radiopharmaceuticals for Breast Cancer and Neuroendocrine Tumors: Two Examples of How Tissue Characterization May Influence the Choice of Therapy. Cancers (Basel) 2020; 12:cancers12040781. [PMID: 32218303 PMCID: PMC7226069 DOI: 10.3390/cancers12040781] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2020] [Revised: 03/23/2020] [Accepted: 03/24/2020] [Indexed: 12/12/2022] Open
Abstract
Molecular medicine has gained clinical relevance for the detection and staging of oncological diseases, to guide therapy decision making and for therapy follow-up due to the availability of new highly sensitive hybrid imaging camera systems and the development of new tailored radiopharmaceuticals that target specific molecules. The knowledge of the expression of different receptors on the primary tumor and on metastases is important for both therapeutic and prognostic purposes and several approaches are available aiming to achieve personalized medicine in different oncological diseases. In this review, we describe the use of specific radiopharmaceuticals to image and predict therapy response in breast cancer and neuroendocrine tumors since they represent a paradigmatic example of the importance of tumoral characterization of hormonal receptors in order to plan a tailored treatment. The most attractive radiopharmaceuticals for breast cancer are 16α-[18F]-fluoro-17β-estradiol for PET assessment of the estrogen expression, radiolabeled monoclonal antibody trastuzumab to image the human epidermal growth factor receptor 2, but also the imaging of androgen receptors with [18F]-fluorodihydrotestosterone.
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Affiliation(s)
- Alberto Signore
- Nuclear Medicine Unit, Department of Medical-Surgical Sciences and of Translational Medicine, “Sapienza” University of Rome, 00189 Rome, Italy; (C.L.); (S.A.); (M.V.); (L.O.)
- Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, 9700 Groningen, The Netherlands;
- Correspondence:
| | - Chiara Lauri
- Nuclear Medicine Unit, Department of Medical-Surgical Sciences and of Translational Medicine, “Sapienza” University of Rome, 00189 Rome, Italy; (C.L.); (S.A.); (M.V.); (L.O.)
- Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, 9700 Groningen, The Netherlands;
| | - Sveva Auletta
- Nuclear Medicine Unit, Department of Medical-Surgical Sciences and of Translational Medicine, “Sapienza” University of Rome, 00189 Rome, Italy; (C.L.); (S.A.); (M.V.); (L.O.)
- Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, 9700 Groningen, The Netherlands;
| | - Michela Varani
- Nuclear Medicine Unit, Department of Medical-Surgical Sciences and of Translational Medicine, “Sapienza” University of Rome, 00189 Rome, Italy; (C.L.); (S.A.); (M.V.); (L.O.)
| | - Livia Onofrio
- Nuclear Medicine Unit, Department of Medical-Surgical Sciences and of Translational Medicine, “Sapienza” University of Rome, 00189 Rome, Italy; (C.L.); (S.A.); (M.V.); (L.O.)
| | - Andor W. J. M. Glaudemans
- Department of Nuclear Medicine and Molecular Imaging, University of Groningen, University Medical Center Groningen, 9700 Groningen, The Netherlands;
| | - Francesco Panzuto
- Digestive Disease Unit, AOU Sant’Andrea and ENETS Center of Excellence, 00189 Rome, Italy;
| | - Paolo Marchetti
- Oncology Unit, Department of Clinical and Molecular Medicine, “Sapienza” University of Rome, and IDI-IRCCS, 00189 Rome, Italy;
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Schneider JR, Shatzkes DR, Scharf SC, Tham TM, Kulason KO, Buteau FA, Del Prete M, Chakraborty S, Anderson TA, Asiry S, Beauregard JM, Langer DJ, Costantino PD, Boockvar JA. Neuroradiological and Neuropathological Changes After 177Lu-Octreotate Peptide Receptor Radionuclide Therapy of Refractory Esthesioneuroblastoma. Oper Neurosurg (Hagerstown) 2019; 15:100-109. [PMID: 29554305 DOI: 10.1093/ons/opy028] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2018] [Accepted: 01/29/2018] [Indexed: 01/01/2023] Open
Abstract
BACKGROUND AND IMPORTANCE Olfactory neuroblastoma, also known as esthesioneuroblastoma (ENB), is a malignant neoplasm with an unpredictable behavior. Currently, the widely accepted treatment is inductive chemotherapy, with or without surgery, followed by radiotherapy. Since data on genetics and molecular alterations of ENB are lacking, there is no standard molecularly targeted therapy. However, ENB commonly expresses the somatostatin receptor (SSTR) that is also expressed by neuroendocrine tumors. Peptide receptor radionuclide therapy (PRRT) using radiolabeled somatostatin analogues, such as 177Lu-octreotate, is an effective treatment for the latter. We present the complex neuroradiological and neuropathological changes associated with 177Lu-octreotate treatment of a patient with a highly treatment-resistant ENB. CLINICAL PRESENTATION A 60-yr-old male presented with an ENB that recurred after chemotherapy, surgery, stereotactic radiosurgery, and immunotherapy. Pathology revealed a Hyams grade 3 ENB and the tumor had metastasized to lymph nodes. Tumor SSTR expression was seen on 68Ga-octreotate positron emission tomography (PET)/computed tomography (CT), suggesting that PRRT may be an option. He received 4 cycles of 177Lu-octreotate over 6 mo, with a partial response of all lesions and symptomatic improvement. Four months after the last PRRT cycle, 2 of the lesions rapidly relapsed and were successfully resected. Three months later, 68Ga-octreotate PET/CT and magnetic resonance imaging indicate no progression of the disease. CONCLUSION We describe imaging changes associated with 177Lu-octreotate PRRT of relapsing ENB. To our knowledge, this is the first report describing neuropathological changes associated with this treatment. PRRT is a promising therapeutic option to improve the disease control, and potentially, the survival of patients with refractory ENB.
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Affiliation(s)
- Julia R Schneider
- Department of Neurosurgery, Lenox Hill Hospital, Zucker School of Medicine at Hofstra/Northwell, New York, New York
| | - Deborah R Shatzkes
- Department of Radiology, Lenox Hill Hospital, Zucker School of Medicine at Hofstra/Northwell, New York, New York.,Department of Otolaryngology, Lenox Hill Hospital, Zucker School of Medicine at Hofstra/Northwell, New York, New York.,New York Head and Neck Institute, Zucker School of Medicine at Hofstra/Northwell, New York, New York
| | - Stephen C Scharf
- Department of Nuclear Medicine, Lenox Hill Hospital, Zucker School of Medicine at Hofstra/Northwell, New York, New York
| | - Tristan M Tham
- Department of Otolaryngology, Lenox Hill Hospital, Zucker School of Medicine at Hofstra/Northwell, New York, New York.,New York Head and Neck Institute, Zucker School of Medicine at Hofstra/Northwell, New York, New York
| | - Kay O Kulason
- Department of Neurosurgery, Lenox Hill Hospital, Zucker School of Medicine at Hofstra/Northwell, New York, New York
| | | | - Michela Del Prete
- Department of Medical Imaging, CHU de Québec-Université Laval, Quebec City, Canada
| | - Shamik Chakraborty
- Department of Neurosurgery, Lenox Hill Hospital, Zucker School of Medicine at Hofstra/Northwell, New York, New York
| | - Todd A Anderson
- Department of Pathology, Lenox Hill Hospital, Zucker School of Medicine at Hofstra/Northwell, New York, New York
| | - Saeed Asiry
- Department of Pathology, Lenox Hill Hospital, Zucker School of Medicine at Hofstra/Northwell, New York, New York
| | | | - David J Langer
- Department of Neurosurgery, Lenox Hill Hospital, Zucker School of Medicine at Hofstra/Northwell, New York, New York.,Department of Radiology, Lenox Hill Hospital, Zucker School of Medicine at Hofstra/Northwell, New York, New York.,Department of Otolaryngology, Lenox Hill Hospital, Zucker School of Medicine at Hofstra/Northwell, New York, New York
| | - Peter D Costantino
- Department of Neurosurgery, Lenox Hill Hospital, Zucker School of Medicine at Hofstra/Northwell, New York, New York.,Department of Otolaryngology, Lenox Hill Hospital, Zucker School of Medicine at Hofstra/Northwell, New York, New York.,New York Head and Neck Institute, Zucker School of Medicine at Hofstra/Northwell, New York, New York
| | - John A Boockvar
- Department of Neurosurgery, Lenox Hill Hospital, Zucker School of Medicine at Hofstra/Northwell, New York, New York.,Department of Otolaryngology, Lenox Hill Hospital, Zucker School of Medicine at Hofstra/Northwell, New York, New York.,New York Head and Neck Institute, Zucker School of Medicine at Hofstra/Northwell, New York, New York
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Saravana-Bawan B, Koumna S, Wieler M, McEwan A, McMullen T. Comparison and clinical implementation of quality of life tools in patients with small bowel neuroendocrine tumors treated with Lu-DOTA-TATE PRRT. INTERNATIONAL JOURNAL OF ENDOCRINE ONCOLOGY 2019. [DOI: 10.2217/ije-2019-0003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Aim: This study assesses if clinically developed quality of life (QoL) tools are as effective in small bowel neuroendocrine tumors (NETs) as NET-specific research questionnaires. Methods: QoL in patients with small bowel NETs treated with Lu-DOTA-TATE was assessed with The European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, QLQ-GI.NET21 and Edmonton Symptom Assessment System Revised (ESAS-r) at baseline and after four treatments. Repeated measures ANOVA was performed. Results: Both EORTC and ESAS-r demonstrated maintained overall QoL. EORTC demonstrated statistically and clinically significant improvement in insomnia, diarrhea, gastrointestinal, endocrine symptoms and social function. ESAS-r demonstrated statistically and clinically significant improvement in overall total symptom distress score. Conclusion: ESAS-r is quick and easy to interpret. It is not as sensitive to individual symptoms but does track overall function. EORTC assessment is more complex, but better reflects QoL for NET specific symptoms.
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Affiliation(s)
| | - Stella Koumna
- Department of Oncology, University of Alberta, Edmonton, AB, T6G 2R3, Canada
| | - Marguerite Wieler
- Department of Physical Therapy, University of Alberta, Edmonton, AB, T6G 2R3, Canada
| | - Alexander McEwan
- Department of Oncology, University of Alberta, Edmonton, AB, T6G 2R3, Canada
| | - Todd McMullen
- Department of Surgery, University of Alberta, Edmonton, AB, T6G 2R3, Canada
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43
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Prognostic Significance of Somatostatin Receptor Heterogeneity in Progressive Neuroendocrine Tumor Treated with Lu-177 DOTATOC or Lu-177 DOTATATE. Eur J Nucl Med Mol Imaging 2019; 47:881-894. [PMID: 31414209 DOI: 10.1007/s00259-019-04439-9] [Citation(s) in RCA: 55] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2018] [Accepted: 07/11/2019] [Indexed: 12/21/2022]
Abstract
AIM One of the primary prerequisites for peptide receptor radionuclide therapy (PRRT) in patients with neuroendocrine tumors (NET) is the presence of somatostatin receptors (SSTR) on NET cells. NET are highly heterogeneous and an individual patient as well as separate metastases can harbor cells with different clones, which influence the SSTR expression on NET cells. With this background we looked into our institutional database to assess the prognostic significance of quality of SSTR expression on SSTR PET/CT imaging in patients treated with at least two cycles of Lu-177 DOTATOC or Lu-177 DOTATATE. METHOD Clinical reports and images from 65 (25 females, 40 males; 65 ± 11 years old) patients with progressive grade 1 or grade 2 NET with 2-5 therapy cycles of PRRT with an average administered dose of 6.6 ± 0.97 GBq Lu-177 DOTATOC or Lu-177 DOTATATE were analyzed. All patients were examined with baseline Ga-68 DOTATATE or Ga-68 DOTATOC PET/CT (PET). Quality of SSTR expression as a measure of heterogeneity on indexed lesions was assessed visually. Patients were followed for a median duration of 25 months after the first PRRT (range 5-77 months). RESULTS A total of 70% of the patients received three or more therapy cycles. Twenty-six patients (40%) were treated with PRRT as first or second line while 39 (60%) as third line or more. SSTR expression was heterogeneous in 28 (44.4%) and homogeneous in 35 (55.6%) patients. Disease stabilization could be achieved in 23 patients (35.4%), whereas 17 (26.1%) showed partial remission and 25 patients (38.5%) had disease progression. Median OS was not reached. The 24-month survival rate of the whole study cohort was 83%. In univariate analyses, factors influencing OS were carcinoid heart disease, carcinoid syndrome and quality of SSTR expression (p < 0.05). Patients with heterogeneous SSTR expression on target lesions had a significantly lower OS (p = 0.01). Median time to progression in total patient population was found to be 40 months. Patients with heterogeneous SSTR expression on target lesions had significantly lower TTP (26 months vs 54 months log Rank p = 0.013). By multivariate analyses, quality of SSTR was found to be the only prognostic factor for OS (p = 0.04; HR = 3.68) and also for TTP (p = 0.03; HR = 3.09). CONCLUSION Visual assessment of SSTR heterogeneity has both predictive and prognostic value in progressive grade 1 or grade 2 NET patients undergoing PRRT.
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44
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Huang HL, Tong AKT, Thang SP, Yan SX, Lam WWC, Loke KSH, Tang CYL, Cheng LTJ, Ooi GSK, Low HC, Magsombol BM, Tham WY, Goh CXY, Tan CJ, Khor YM, Zaheer S, Bharadwaj P, Xie W, Ng DCE. Current Status and Growth of Nuclear Theranostics in Singapore. Nucl Med Mol Imaging 2019; 53:96-101. [DOI: 10.1007/s13139-019-00580-3] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2019] [Revised: 01/13/2019] [Accepted: 01/14/2019] [Indexed: 11/30/2022] Open
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45
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Aalbersberg EA, Huizing DM, Walraven I, de Wit-van der Veen BJ, Kulkarni HR, Singh A, Stokkel MP, Baum RP. Parameters to Predict Progression-Free and Overall Survival After Peptide Receptor Radionuclide Therapy: A Multivariate Analysis in 782 Patients. J Nucl Med 2019; 60:1259-1265. [PMID: 30850483 DOI: 10.2967/jnumed.118.224386] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2018] [Accepted: 02/06/2019] [Indexed: 12/15/2022] Open
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46
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Giovannini E, Giovacchini G, Borsò E, Lazzeri P, Riondato M, Leoncini R, Duce V, Ciarmiello A. [68Ga]-Dota Peptide PET/CT in Neuroendocrine Tumors: Main Clinical Applications. Curr Radiopharm 2019; 12:11-22. [PMID: 30539709 DOI: 10.2174/1874471012666181212101244] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2018] [Revised: 11/28/2018] [Accepted: 11/29/2018] [Indexed: 12/14/2022]
Abstract
Objective:
Neuroendocrine Neoplasms (NENs) are generally defined as rare and heterogeneous
tumors. The gastrointestinal system is the most frequent site of NENs localization, however they
can be found in other anatomical regions, such as pancreas, lungs, ovaries, thyroid, pituitary, and adrenal
glands. Neuroendocrine neoplasms have significant clinical manifestations depending on the
production of active peptide.
Methods:
Imaging modalities play a fundamental role in initial diagnosis as well as in staging and
treatment monitoring of NENs, in particular they vastly enhance the understanding of the physiopathology
and diagnosis of NENs through the use of somatostatin analogue tracers labeled with appropriate
radioisotopes. Additionally, the use of somatostatin analogues provides the ability to in-vivo measure
the expression of somatostatin receptors on NEN cells, a process that might have important therapeutic
implications.
Results:
A large body of evidences showed improved accuracy of molecular imaging based on PET/CT
radiotracer with SST analogues (e.g. [68Ga]-DOTA peptide) for the detection of NEN lesions in comparison
to morphological imaging modalities. So far, the role of imaging technologies in assessing
treatment response is still under debate.
Conclusion:
This review offers the systems of classification and grading of NENs and summarizes the
more useful recommendations based on data recently published for the management of patients with
NENs, with special focus on the role of imaging modalities based on SST targeting with PET / CT
radiotracers.
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Affiliation(s)
| | | | - Elisa Borsò
- Department of Nuclear Medicine, S. Andrea Hospital, La Spezia, Italy
| | - Patrizia Lazzeri
- Department of Nuclear Medicine, S. Andrea Hospital, La Spezia, Italy
| | - Mattia Riondato
- Department of Nuclear Medicine, S. Andrea Hospital, La Spezia, Italy
| | - Rossella Leoncini
- Department of Nuclear Medicine, S. Andrea Hospital, La Spezia, Italy
| | - Valerio Duce
- Department of Nuclear Medicine, S. Andrea Hospital, La Spezia, Italy
| | - Andrea Ciarmiello
- Department of Nuclear Medicine, S. Andrea Hospital, La Spezia, Italy
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47
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Al Bulushi N, Al Suqri B, Al Aamri M, Al Hadidi A, Al Jahdami H, Al Zadjali M, Al Risi M. Diagnostic accuracy of technetium-99m-octreotide in imaging neuroendocrine tumors, Oman hospital experience with literature review. World J Nucl Med 2019; 18:137-142. [PMID: 31040744 PMCID: PMC6476243 DOI: 10.4103/wjnm.wjnm_36_18] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
The aim of this observational cross-sectional study with retrospective review of the data is to evaluate the efficacy of using technetium-99m-octreotide (Tc-99m-OCT) in imaging neuroendocrine tumors (NETs) in our tertiary care hospital. A total of 58 patients had Tc-99m-OCT were identified in our database, from January 2013 to December 2016. Forty-one patients (age range of 15–75 years) meet our inclusion criteria, namely histopathology proven NETs, Tc-99m-OCT scan, computed tomography (CT), or magnetic resonance imaging (MRI) done in our institute for correlation. Twenty-three patients had true positive Tc-99m-OCT scan. In addition to the primary tumors, the octreotide scan revealed metastasis in the lung, liver, and retroperitoneal lymph nodes. The smallest lesion detected on octreotide scan was a 4-mm pulmonary nodule that was missed on lung window CT scan. The Tc-99m-OCT had 17 true negative, one false negative, and no false positive. The CT and MRI scans had 18 true positive, 17 true negative, 5 false negative, and one false positive. The overall sensitivity, specificity, accuracy, positive, and negative predictive values of Tc-99m-OCT scan were 96%, 100%, 97%, 100%, and 94%, respectively. Whereas those of CT and MRI were 78%, 94%, 85%, 94%, and 77%, respectively. Our diagnostic accuracy of Tc-99m-OCT is high. We recommend that, in addition to the conventional radiological investigations, Tc-99m-OCT scan, or other somatostatin receptor imaging (SSR) is a mandate for better and accurate staging of patients with NETs.
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Affiliation(s)
- Naima Al Bulushi
- Department of Nuclear Medicine and Molecular Imaging Center, Royal Hospital, Muscat, Oman
| | - Badriya Al Suqri
- Department of Nuclear Medicine and Molecular Imaging Center, Royal Hospital, Muscat, Oman
| | - Marwa Al Aamri
- Department of Nuclear Medicine and Molecular Imaging Center, Royal Hospital, Muscat, Oman
| | | | - Hafidh Al Jahdami
- Department of Nuclear Medicine and Molecular Imaging Center, Royal Hospital, Muscat, Oman
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Hanaoka K, Maeda T, Miyaji N, Sakaguchi K, Yoneyama H, Ogawa M, Tsushima H. [Global Trends Survey for Targeted Radionuclide Therapy]. Nihon Hoshasen Gijutsu Gakkai Zasshi 2018; 74:1443-1448. [PMID: 30568095 DOI: 10.6009/jjrt.2018_jsrt_74.12.1443] [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: 11/11/2022]
Abstract
Radionuclide therapy has been used to help manage a range of diseases and has a role of growing importance, with an increasing impact on clinical practice globally. A survey in the field of Radionuclide therapy was conducted by reviewing 4199 science abstracts of main conference (Japanese Society of Radiological Technology, Japanese Society of Nuclear Medicine, Japanese Society of Nuclear Medicine Technology, Society of Nuclear Medicine and Molecular Imaging, European Association of Nuclear Medicine) held in 2016. This survey consisted of research content, modality for evaluation, dosimetry, radionuclide, and researcher's country. There tend to be a lot of studies related to targeted radionuclide therapy more than Japan (4%) in the United States (11%) or Europe (13%). Radiopharmaceuticals still un-approving in Japan were used in some of these studies. And many studies on dosimetry using PET or SPECT imaging were confirmed in the United States (37%) or in Europe (25%) compared with in Japan (14%). This survey has clarified the current status of Japan and global trend in the field of radionuclide therapy.
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Affiliation(s)
- Kohei Hanaoka
- Institute of Advanced Clinical Medicine, Kindai University
| | - Takamasa Maeda
- Radiological Technology Section, Hospital of the National Institute of Radiological Sciences, QST
| | - Noriaki Miyaji
- Department of Nuclear Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research
| | | | - Hiroto Yoneyama
- Department of Radiological Technology, Kanazawa University Hospital
| | | | - Hiroyuki Tsushima
- Department of Radiological Sciences, Ibaraki Prefectural University of Health Sciences
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Well differentiated neuroendocrine tumors, a single center experience. JOURNAL OF ONCOLOGICAL SCIENCES 2018. [DOI: 10.1016/j.jons.2018.10.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
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Huang K, Brenner W, Prasad V. Tumor Lysis Syndrome: A Rare but Serious Complication of Radioligand Therapies. J Nucl Med 2018; 60:752-755. [PMID: 30464038 DOI: 10.2967/jnumed.118.217380] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2018] [Accepted: 11/07/2018] [Indexed: 11/16/2022] Open
Abstract
Radioligand therapy (RLT) is considered a safe treatment for patients with metastasized neuroendocrine tumors and prostate cancer, and the occurrence of tumor lysis syndrome (TLS) with 177Lu-labeled peptides has not yet been reported. We retrospectively screened our patient database for TLS after RLT in neuroendocrine tumors and prostate cancer. Methods: The database was searched for patients receiving RLT with 177Lu-DOTATATE, -DOTATOC, or -prostate-specific membrane antigen and showing laboratory or clinical abnormalities typical of TLS within 7 d after the start of treatment. Results: In total, 205 patients (539 cycles) were screened; 4 patients developed TLS with clinical symptoms and characteristic changes in laboratory parameters, which normalized after appropriate treatment. Follow-up revealed partial remission in 2 patients, a mixed response in one, and progressive disease in one. Conclusion: Clinical TLS is a rare but definite complication of RLT, suggesting that patient monitoring for TLS should be mandatory.
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Affiliation(s)
- Kai Huang
- Department of Nuclear Medicine, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
| | - Winfried Brenner
- Department of Nuclear Medicine, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.,German Cancer Consortium, DKTK Partner Site Berlin, Berlin, Germany; and
| | - Vikas Prasad
- Department of Nuclear Medicine, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany .,Department of Nuclear Medicine, Universitätsklinikum Ulm, Ulm, Germany
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