|
1
|
Padwal MK, Nazar AK, Parghane RV, Basu S, Basu B. Evaluating the prognostic significance of the pre-treatment neutrophil-to-lymphocyte and monocyte-to-lymphocyte ratios in 177Lu-DOTATATE PRRT treated patients with advanced metastatic neuroendocrine tumors. Endocrine 2025:10.1007/s12020-025-04212-z. [PMID: 40131599 DOI: 10.1007/s12020-025-04212-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2025] [Accepted: 03/13/2025] [Indexed: 03/27/2025]
Abstract
PURPOSE This study aimed to investigate the role of pre-treatment neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR) in the prognosis assessment of 177Lu-DOTATATE Peptide Receptor Radionuclide Therapy (PRRT) treated patients with advanced metastatic neuroendocrine tumors (NETs). METHODS Eligible PRRT-treated patients (n = 247, 2010-2019) were included. Pre-PRRT NLR and MLR were calculated from complete blood count data. Data on tumor characteristics, response to PRRT, progression-free survival (PFS), and overall survival (OS) were evaluated using COXPH analyses. RESULTS In NET patients, median values of NLR and MLR were 2.21 (IQR = 1.66-3.00) and 0.14 (IQR = 0.06-0.24), respectively. NLR showed significant positive association with G3 tumors (median = 3.64, IQR = 2.1-4.26, p = 0.022) and high 18F-FDG avidity (SUVmax>5) (median = 2.5, IQR = 1.82-3.56, p = 0.003). MLR was significantly associated with high disease burden (median = 0.18, IQR = 0.08-0.29, p = 0.0083). MLR distinguished between the PRRT non-responders with progressive disease and responders with complete/partial response (median 0.19 versus 0.12, p = 0.043) or responders with stable disease (median 0.19 versus 0.14, p = 0.045). The ratios independently correlated with disease progression and OS. Patients in NLRhigh (>3.5) group displayed significantly shorter median PFS and OS (48 and 58 months) compared to NLRlow (≤3.5) group (108 and 96 months) (p < 0.01). Patients in MLRhigh (>0.25) group displayed significantly shorter median PFS and OS (40 and 52 months) compared to MLRlow (≤0.25) group (108 and 102 months) (p < 0.01). CONCLUSION Pre-treatment NLR and MLR had an independent prognostic impact on disease progression and OS in PRRT-treated NET patients. This routine, inexpensive CBC-based test in the standard pre-PRRT workup demonstrates the prognostic value and may aid clinicians in the risk stratification of NET patients.
Collapse
Affiliation(s)
- Mahesh K Padwal
- Molecular Biology Division, Bhabha Atomic Research Centre, Mumbai, India
- Homi Bhabha National Institute, Mumbai, India
| | - Amir K Nazar
- Homi Bhabha National Institute, Mumbai, India
- Radiation Medicine Centre, Bhabha Atomic Research Centre, Tata Memorial Centre Annexe, Mumbai, India
| | - Rahul V Parghane
- Homi Bhabha National Institute, Mumbai, India
- Radiation Medicine Centre, Bhabha Atomic Research Centre, Tata Memorial Centre Annexe, Mumbai, India
| | - Sandip Basu
- Homi Bhabha National Institute, Mumbai, India.
- Radiation Medicine Centre, Bhabha Atomic Research Centre, Tata Memorial Centre Annexe, Mumbai, India.
| | - Bhakti Basu
- Molecular Biology Division, Bhabha Atomic Research Centre, Mumbai, India.
- Homi Bhabha National Institute, Mumbai, India.
| |
Collapse
|
|
2
|
Padwal MK, Parghane RV, Chakraborty A, Ujaoney AK, Anaganti N, Basu S, Basu B. Developing a peripheral blood RNA-seq based NETseq ensemble classifier: A potential novel tool for non-invasive detection and treatment response assessment in neuroendocrine tumor patients receiving 177Lu-DOTATATE PRRT. J Neuroendocrinol 2025; 37:e13462. [PMID: 39539072 PMCID: PMC11919474 DOI: 10.1111/jne.13462] [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: 07/03/2024] [Revised: 09/12/2024] [Accepted: 10/24/2024] [Indexed: 11/16/2024]
Abstract
Neuroendocrine tumors (NETs) are presented with metastases due to delayed diagnosis. We aimed to identify NET-related biomarkers from peripheral blood. The development and validation of a multi-gene NETseq ensemble classifier using peripheral blood RNA-Seq is reported. RNA-Seq was performed on peripheral blood samples from 178 NET patients and 73 healthy donors. Distinguishing gene features were identified from a learning cohort (59 PRRT-naïve GEP-NET patients and 38 healthy donors). Ensemble classifier combining the output of five machine learning algorithms viz. Random Forest (RF), Extreme Gradient Boosting (XGBOOST), Gradient Boosting Machine (GBM), Support Vector Machine (SVM), and Logistic Regression (LR) were trained and independently validated in the evaluation cohort (n = 106). The response to PRRT was evaluated in the PRRT cohort (n = 46) and the PRRT response monitoring cohort (n = 16). The response to 177Lu-DOTATATE PRRT was assessed using RECIST 1.1 criteria. The Ensemble classifier trained on 61 gene features, distinguished NET from healthy samples with 100% accuracy in the learning cohort. In an evaluation cohort, the classifier achieved 93% sensitivity (95% CI: 87.8%-98.03%) and 91.4% specificity (95% CI: 82.1%-100%) for PRRT-naïve GEP-NETs (AUROC = 95.4%). The classifier returned >87.5% sensitivity across different tumor characteristics and outperformed serum Chromogranin A sensitivity (χ2 = 21.89, p = 4.161e-6). In the PRRT cohort, RECIST 1.1 responders showed significantly lower NETseq prediction scores after 177Lu-DOTATATE PRRT, in comparison to the non-responders. In an independent response monitoring cohort, paired samples (before PRRT and after 2nd or 3rd cycle of PRRT) were analyzed. The NETseq prediction score significantly decreased in partial responders (p = .002) and marginally reduced in stable disease (p = .068). The NETseq ensemble classifier identified PRRT-naïve GEP-NETs with high accuracy (≥92%) and demonstrated a potential role in early treatment response monitoring in the PRRT setting. This blood-based, non-invasive, multi-analyte molecular method could be developed as a valuable adjunct to conventional methods in the detection and treatment response assessment in NET patients.
Collapse
Affiliation(s)
- Mahesh K. Padwal
- Molecular Biology DivisionBhabha Atomic Research CentreMumbaiIndia
- Homi Bhabha National InstituteMumbaiIndia
| | - Rahul V. Parghane
- Homi Bhabha National InstituteMumbaiIndia
- Radiation Medicine Centre, Bhabha Atomic Research CentreTata Memorial Centre AnnexeMumbaiIndia
| | - Avik Chakraborty
- Homi Bhabha National InstituteMumbaiIndia
- Radiation Medicine Centre, Bhabha Atomic Research CentreTata Memorial Centre AnnexeMumbaiIndia
| | | | - Narasimha Anaganti
- Molecular Biology DivisionBhabha Atomic Research CentreMumbaiIndia
- Homi Bhabha National InstituteMumbaiIndia
| | - Sandip Basu
- Homi Bhabha National InstituteMumbaiIndia
- Radiation Medicine Centre, Bhabha Atomic Research CentreTata Memorial Centre AnnexeMumbaiIndia
| | - Bhakti Basu
- Molecular Biology DivisionBhabha Atomic Research CentreMumbaiIndia
- Homi Bhabha National InstituteMumbaiIndia
| |
Collapse
|
|
3
|
Bao X, Li S, Yao S, Chen Q. Research process of PET tracers for neuroendocrine tumors diagnosis. AMERICAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING 2025; 15:1-14. [PMID: 40124763 PMCID: PMC11929009 DOI: 10.62347/jxly1661] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/22/2025] [Accepted: 02/14/2025] [Indexed: 03/25/2025]
Abstract
Neuroendocrine tumors (NETs) can affect several organ systems and present a variety of clinical symptoms, which are difficult to diagnose by conventional methods. Somatostatin receptor (SSTR) is a group of specific receptors expressed on the well-differentiated NET cell membrane. [68Ga]-labeled somatostatin analogues (SSAs) PET/CT, endogenous ligands targeting SSTR, is widely used in currently clinical NETs diagnosis. The dual-tracer strategy ([68Ga]Ga-SSAs + [18F]FDG) allows for a more detailed evaluation of tumor metabolism and receptor expression. The NETPET score, integrating [68Ga]Ga-SSAs PET/CT and [18F]FDG PET/CT results, enhances the accuracy of predicting treatment response and prognosis. In addition, novel isotopes ([18F]/[64Cu]) labeled SSAs and SSTR antagonists outperformed [68Ga]-SSAs in lesion detection, tumor uptake, and tumor-to-background ratio. Due to undifferentiated or dedifferentiated NETs, SSTR may not be expressed. [68Ga]Ga-Pentixafor and [18F]-FDG PET/CT are applicable for SSTR-negative NET diagnosis. [18F]-MFBG and [18F]-DOPA have a higher sensitivity for identifying non-metastatic pheochromocytoma and paraganglioma (PPGL) than other radiotracers. This review addressed NET diagnosis with conventional imaging techniques, the clinical application of novel radiotracers, and the merits and limitations of the various radiotracers.
Collapse
Affiliation(s)
- Xiangyuan Bao
- Department of PET/CT Diagnostic, Tianjin Key Lab of Functional Imaging and Tianjin Institute of Radiology, Tianjin Medical University General HospitalTianjin 300052, China
- The Clinical Research and Translational Center, The First Affiliated Hospital of Fujian Medical UniversityFuzhou 350005, Fujian, China
| | - Shuai Li
- Department of PET/CT Diagnostic, Tianjin Key Lab of Functional Imaging and Tianjin Institute of Radiology, Tianjin Medical University General HospitalTianjin 300052, China
| | - Shaobo Yao
- Department of PET/CT Diagnostic, Tianjin Key Lab of Functional Imaging and Tianjin Institute of Radiology, Tianjin Medical University General HospitalTianjin 300052, China
- The Clinical Research and Translational Center, The First Affiliated Hospital of Fujian Medical UniversityFuzhou 350005, Fujian, China
| | - Qiusong Chen
- Department of PET/CT Diagnostic, Tianjin Key Lab of Functional Imaging and Tianjin Institute of Radiology, Tianjin Medical University General HospitalTianjin 300052, China
| |
Collapse
|
|
4
|
Courtel T, Orbach D, Lacour B, Roumy M, Hescot S, Desandes E, Philippe-Chomette P, Sarnacki S, Irtan S, Dijoud F, Kubicek P, Brisse H, Fresneau B, Pire A, Réguerre Y, Mallebranche C. Childhood pancreatic neuroendocrine neoplasms: A national experience. Pediatr Blood Cancer 2025; 72:e31258. [PMID: 39135330 DOI: 10.1002/pbc.31258] [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: 06/06/2024] [Revised: 07/23/2024] [Accepted: 07/26/2024] [Indexed: 12/24/2024]
Abstract
Pancreatic neuroendocrine neoplasms (pNENs) diagnosed in childhood are very rare, with few data available. The aim was to describe the clinical presentation and behavior of children with pNENs at a national level. METHODS National multicenter retrospective study of all patients, aged from 0 to 17 years at diagnosis, treated from 2011 to 2020 for a pNEN and registered in the French National Registry of Childhood Cancers or FRACTURE database. RESULTS Fifteen patients, 13 well-differentiated pancreatic neuroendocrine tumors (pNETs) and two neuroendocrine carcinomas (pNECs), were selected. Median age at diagnosis was 14 years (range, 7-17). Eight patients, all with localized disease, had a cancer predisposition syndrome (CPS), including five cases diagnosed during systematic screening. Five (31%) had metastatic disease at diagnosis: three grade 2 pNETs and two pNECs. First line therapy included exclusive pancreatectomy (seven cases, all M0), active surveillance (three cases, all M0), medical therapies (somatostatin analogues, chemotherapy; four cases, all M1), and surgery with medical therapy (one M1 case). Three-year progression-free survival was 57% (confidence interval [CI] 95%: 27-78) and was significantly better for patients with low-grade well differentiated (73 vs. 0%; p < 10-4) and localized (76 vs. 20%; p = .02) tumors. The two patients with pNECs died. Three-year overall survival was 92% (CI95%: 59-99) and was significantly better in patients with low-grade tumor (100 vs. 50%; p = 10-4). CONCLUSION Childhood pNENs occur more frequently in adolescents with CPS. Localized low-grade pNETs in children have a very good prognosis, whereas the treatment of high-grade and metastatic pNETs/pNECs should be better defined.
Collapse
Affiliation(s)
- Tiphaine Courtel
- Unité d'Onco-Hémato-Immunologie pédiatrique, CHU Angers, Angers, France
| | - Daniel Orbach
- SIREDO Oncology Center (Care, Innovation and Research for Children, Adolescents and Young Adults with Cancer), Institut Curie, Paris-Saclay University (PSL), Paris, France
| | - Brigitte Lacour
- French National Registry of Childhood Solid Tumors, CHU Nancy, Nancy, France
- Inserm UMR 1153, Centre of Research in Epidemiology and StatisticS (CRESS), Paris University, Epidemiology of Childhood and Adolescent Cancers Team (EPICEA), Paris, France
| | - Marianne Roumy
- Plateforme de recherche clinique pédiatrique, CHU Angers, Angers, France
| | - Ségolène Hescot
- Department of Drug Development and Innovation (D3i), Institut Curie, Paris, France
| | - Emmanuel Desandes
- French National Registry of Childhood Solid Tumors, CHU Nancy, Nancy, France
- Inserm UMR 1153, Centre of Research in Epidemiology and StatisticS (CRESS), Paris University, Epidemiology of Childhood and Adolescent Cancers Team (EPICEA), Paris, France
| | - Pascale Philippe-Chomette
- Department of Pediatric Surgery, Assistance Publique des Hôpitaux de Paris, Hôpital Robert Debré, Paris, France
| | - Sabine Sarnacki
- Department of Pediatric Surgery, Urology and Transplantation, Necker-Enfants Malades Hospital, APHP, Université de Paris Cité, Paris, France
| | - Sabine Irtan
- APHP-Sorbonne University, Paris, France
- Department of Pediatric Visceral and Neonatal Surgery, Armand-Trousseau Children's Hospital, APHP, Paris, France
| | | | - Pierre Kubicek
- Department of Medical Oncology, Institut de Cancérologie de l'Ouest, Angers, France
| | - Hervé Brisse
- Department of Imaging, Institut Curie, PSL University, Paris, France
| | - Brice Fresneau
- Gustave Roussy, Université Paris-Saclay, Department of Children and Adolescent Oncology, Paris-Saclay University, Paris-Sud University, CESP, INSERM, Villejuif, France
| | - Aurore Pire
- Department of Pediatric Surgery, Urology and Transplantation, Necker-Enfants Malades Hospital, APHP, Université de Paris Cité, Paris, France
| | - Yves Réguerre
- Unité d'oncologie et d'hématologie pédiatrique, CHU Saint Denis de la Réunion, Bellepierre, France
| | - Coralie Mallebranche
- Unité d'Onco-Hémato-Immunologie pédiatrique, CHU Angers, Angers, France
- Université d'Angers, Université de Nantes, CHU Angers, INSERM, CRCI2NA, SFR ICAT, Angers, France
| |
Collapse
|
|
5
|
Metser U, Kulanthaivelu R, Duder J, Hinzpeter R, Singh S, Wong R, Myrehaug S, Gray D, Veit-Haibach P, Singnurkar A, Li X, Ezzat S. 68Ga-DOTATATE PET/CT in the Initial Staging of Well-Differentiated Gastroenteropancreatic and Non-Gastroenteropancreatic Neuroendocrine Tumors: Results of a Prospective Registry. Cancers (Basel) 2025; 17:434. [PMID: 39941805 PMCID: PMC11815848 DOI: 10.3390/cancers17030434] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2024] [Revised: 01/09/2025] [Accepted: 01/22/2025] [Indexed: 02/16/2025] Open
Abstract
Background and Objectives: At diagnosis, the initial staging of well-differentiated neuroendocrine tumors (WD NETs) aids in treatment planning. The somatostatin receptor (SSTR)-PET has been recommended for staging of WD NETs although limited data are available on its impact on non-gastroeneteropancreatic (GEP) NETs. The main purpose of this study was to compare the stage migration after the addition of SSTR-PET to the workup of patients at the initial staging of GEP NETs to those with non-GEP NETs, and its potential impact on patient management. Methods: This prospective study included patients with WD NETs at initial staging. Demographic data, results of conventional and SSTR-PET staging, and SUVmax were recorded. Three panels of experts assessed the potential impact of SSTR-PET to management. Results: There were 482 patients, including 376 with gastroenteropancreatic (GEP) NETs and 106 non-GEP NETs with a median SUVmax of 34.7 [Q1, Q3: 22.8, 59.1]) and 19.0 [Q1, Q3: 7.9, 39.8]), respectively; p < 0.001. The discordant M-stage was recorded in 111/473 patients (23.5%). PET suggested a higher stage in 78/369 GEP NETs (21.1%), including the detection of extrahepatic metastatic disease in 42/114 (36.8%) patients with liver metastases only on CI. For non-GEP NETs, PET suggested a higher stage in 10/104 (9.6%) and CI suggested a higher stage in 15/104 (14.4%), with CI detecting liver metastases more frequently. The potential impact to management for patients with discordant M-stage was scored as moderate to high between 57/101 (56.4%) and 79/101 (78.2%) of patients. Conclusions: One in five patients are upstaged following SSTR-PET, more frequently with GEP NETs than others. SSTR-PET identifies extrahepatic metastatic disease in >1/3 of patients with presumed liver-only metastases on CI. Stage migration following SSTR-PET may result in frequent moderate or significant management change.
Collapse
Affiliation(s)
- Ur Metser
- University Medical Imaging Toronto, University Health Network, Mount Sinai Hospital & Women’s College Hospital, 610 University Ave, Suite 3-920, Toronto, ON M5G 2M9, Canada (J.D.); (P.V.-H.)
- Department of Medical Imaging, University of Toronto, Toronto, ON M5T 1W7, Canada;
| | - Roshini Kulanthaivelu
- University Medical Imaging Toronto, University Health Network, Mount Sinai Hospital & Women’s College Hospital, 610 University Ave, Suite 3-920, Toronto, ON M5G 2M9, Canada (J.D.); (P.V.-H.)
- Department of Medical Imaging, University of Toronto, Toronto, ON M5T 1W7, Canada;
| | - Julia Duder
- University Medical Imaging Toronto, University Health Network, Mount Sinai Hospital & Women’s College Hospital, 610 University Ave, Suite 3-920, Toronto, ON M5G 2M9, Canada (J.D.); (P.V.-H.)
- Department of Medical Imaging, University of Toronto, Toronto, ON M5T 1W7, Canada;
| | - Ricarda Hinzpeter
- University Medical Imaging Toronto, University Health Network, Mount Sinai Hospital & Women’s College Hospital, 610 University Ave, Suite 3-920, Toronto, ON M5G 2M9, Canada (J.D.); (P.V.-H.)
- Department of Medical Imaging, University of Toronto, Toronto, ON M5T 1W7, Canada;
| | - Simron Singh
- Odette Cancer Centre, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada
- Division of Medical Oncology, Department of Medicine, University of Toronto, Toronto, ON M5T 1P5, Canada
| | - Rebecca Wong
- Radiation Medicine Program, Princess Margaret Cancer Centre, 610 University Ave, Toronto, ON M5G 2M9, Canada
- Radiation Oncology, University of Toronto, Toronto, ON M5T 1P5, Canada
| | - Sten Myrehaug
- Department of Radiation Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada;
| | - Daryl Gray
- Department of Surgery, London Health Sciences Centre—Victoria Hospital, Western University, 800 Commissioners Road East, London, ON N6A 3K7, Canada;
| | - Patrick Veit-Haibach
- University Medical Imaging Toronto, University Health Network, Mount Sinai Hospital & Women’s College Hospital, 610 University Ave, Suite 3-920, Toronto, ON M5G 2M9, Canada (J.D.); (P.V.-H.)
- Department of Medical Imaging, University of Toronto, Toronto, ON M5T 1W7, Canada;
| | - Amit Singnurkar
- Department of Medical Imaging, University of Toronto, Toronto, ON M5T 1W7, Canada;
- Department of Medical Imaging, Sunnybrook Health Sciences Center, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada
| | - Xuan Li
- Department of Biostatistics, University Health Network, 700 University Ave, Toronto, ON M5G 1X6, Canada;
| | - Shereen Ezzat
- Department of Medicine, University of Toronto, Toronto, ON M5S 3H2, Canada;
- Princess Margaret Cancer Centre, 610 University Ave, Toronto, ON M5G 2M9, Canada
| |
Collapse
|
|
6
|
Prela O, Caveney B, Strawderman M, Linehan D, Galka E, Schoeniger L, Hezel A, Badri N, Carpizo DR. A Reassessment of the Clinical Utility of 68Ga-DOTATATE PET/CT in Patients With Gastroenteropancreatic Neuroendocrine Tumors. J Surg Oncol 2025. [PMID: 39757730 DOI: 10.1002/jso.28061] [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: 11/27/2024] [Accepted: 12/03/2024] [Indexed: 01/07/2025]
Abstract
BACKGROUND Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a rare and biologically diverse group of tumors that are challenging to image. 68Ga-DOTATATE PET/CT is the most sensitive imaging tool for these tumors, and while its use has increased over time, its clinical impact remains unclear, particularly for clinical scenarios involving surveillance after treatment. We sought to reassess its clinical utility across all stages. METHODS Retrospective study of pathologically confirmed GEP-NET patients between 1/1/2020 and 9/1/2022 at a tertiary care center. Demographic, clinical, and radiographic data were analyzed. The primary objective was to determine if PET/CT use was associated with a change in clinical management. The secondary objective was to determine if PET/CT was superior in identifying primary or metastatic lesions compared to traditional imaging. RESULTS One hundred twenty-four patients with GEP-NETs underwent 207 PET/CT scans. The majority of scans were obtained for disease surveillance (70.2%) or staging (37.9%), and the remaining (3.2%) were used to aid in diagnosis or before PRRT initiation (3.2%). Following PET/CT scan, 51 patients (41.1%) had a change in clinical management, with change being higher among those with metastatic disease (44.9% vs. 14.5%). Of the 124, 72 patients had traditional imaging available for comparison. In this subgroup, 34 patients (47.2%) had new lesions identified on PET/CT that were not identified using traditional imaging resulting in a change in management in 79.4% favoring patients with M1 versus M0 disease (26.9% M0 vs. 58.7% M1, p = 0.010). CONCLUSION 68Ga-DOTATATE PET/CT imaging is clinically most useful for initial staging and in surveillance and monitoring response to therapy in the metastatic setting. It is least useful for surveillance in the early-stage setting and does not support its use following curative intent surgery. It remains superior to unlabeled imaging in sensitivity and the additional disease burden detected is highly likely to change management.
Collapse
Affiliation(s)
- Orjola Prela
- Department of Surgery, Division of General Surgery, University of Rochester, Rochester, New York, USA
| | - Brennen Caveney
- University of Rochester School of Medicine and Dentistry, Rochester, New York, USA
| | - Myla Strawderman
- Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York, USA
- Department of Biostatistics and Computational Biology, University of Rochester, Rochester, New York, USA
| | - David Linehan
- University of Rochester School of Medicine and Dentistry, Rochester, New York, USA
| | - Eva Galka
- Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York, USA
- Department of Surgery, Division of Surgical Oncology, University of Rochester, Rochester, New York, USA
| | - Luke Schoeniger
- Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York, USA
- Department of Surgery, Division of Surgical Oncology, University of Rochester, Rochester, New York, USA
| | - Aram Hezel
- Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York, USA
- Department of Medicine, Division of Hematology/Oncology, University of Rochester, Rochester, New York, USA
| | - Nabeel Badri
- Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York, USA
- Department of Medicine, Division of Hematology/Oncology, University of Rochester, Rochester, New York, USA
| | - Darren R Carpizo
- Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, New York, USA
- Department of Surgery, Division of Surgical Oncology, University of Rochester, Rochester, New York, USA
| |
Collapse
|
|
7
|
Pan S, Chen S, Richard SA, Lan Z. Primary intracranial neuroendocrine tumor at the sphenoid ridge with metastasis to the spinal cord: A case report. Medicine (Baltimore) 2024; 103:e40996. [PMID: 39686427 PMCID: PMC11651498 DOI: 10.1097/md.0000000000040996] [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: 08/31/2024] [Accepted: 11/28/2024] [Indexed: 12/18/2024] Open
Abstract
RATIONALE Neuroendocrine tumors (NETs) originate from neuroendocrine cells and they are depicted with both nerve cells as well as hormone-producing cells. These tumors were initially discovered in extracranial locations and central nervous system involvement is often a result of metastasis. Herein, we present a very rare case of primary intracranial neuroendocrine tumor (PINET) that masqueraded as meningioma at the sphenoid ridge with metastasis to the spinal cord in a patient without a known history of extracranial NET at the time of diagnosis. PATIENT CONCERNS A 52-year-old male presented with a 2-month history of headache and decreased vision in the left eye accompanied by inarticulation in speech for 1 month. DIAGNOSES Magnetic resonance imaging of the head showed a space-occupying lesion in the left sphenoid ridge which was mistaken for meningioma. INTERVENTIONS The lesion was surgically resected and immunohistochemical evaluation revealed PINET. Postoperative positron emission tomography scan and magnetic resonance imaging of the thoracolumbar spine detected a tumor nodule in the thoracolumbar region which was a metastatic tumor. The metastatic lesion at the thoracolumbar spine was surgically resected and spinal fixation was carried out to stabilize the spine. Immunohistochemical evaluation of the spinal lesion also confirmed NET. He was further treated with several cycles of adjuvant chemotherapy and radiotherapy. OUTCOMES Two years' follow-up revealed no recurrence of the tumor and he is currently well. However, we are still following the patient because of the nature of the tumor. LESSON PINET may be capable of metastasizing to spinal cord.
Collapse
Affiliation(s)
- Siyuan Pan
- Department of Neurosurgery, Xiamen Branch of West China Hospital, Sichuan University, Xiamen, P.R. China
- Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, P.R. China
| | - Shuide Chen
- Department of Neurosurgery, Xiamen Branch of West China Hospital, Sichuan University, Xiamen, P.R. China
- Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, P.R. China
| | - Seidu A. Richard
- Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, P.R. China
- Institute of Neuroscience, Third Affiliated Hospital, Zhengzhou University, Zhengzhou, P.R. China
- Department of Biochemistry and Forensic Sciences, School of Chemical and Biochemical Sciences, C. K. Tedam University of Technology and Applied Sciences (CKT-UTAS), Navrongo, Ghana
| | - Zhigang Lan
- Department of Neurosurgery, Xiamen Branch of West China Hospital, Sichuan University, Xiamen, P.R. China
- Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu, P.R. China
| |
Collapse
|
|
8
|
Sakurai Y, Karaki H, Nakamura Y, Fukuda H, Okaya T, Oheda Y, Yokoyama Y, Hirai F, Abe M, Sugano I. A case of early-stage type 3 gastric neuroendocrine tumor in the upper body of the stomach: is endoscopic resection feasible? Clin J Gastroenterol 2024; 17:814-819. [PMID: 38865017 DOI: 10.1007/s12328-024-01999-8] [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: 03/25/2024] [Accepted: 06/03/2024] [Indexed: 06/13/2024]
Abstract
Although gastric neuroendocrine tumors (NETs) are uncommon compared with gastric carcinomas, the incidence of NETs has been recently increasing. Gastric NETs are classified into three subgroups, and among these, gastrin-independent sporadic type 3 gastric NETs have a poor prognosis because of frequent lymph node or distant metastasis. We experienced a case of an early-stage type 3 gastric NET associated with lymphovascular and submucosal invasion. In a 54 year-old woman, esophagogastroduodenoscopy performed during a health screening identified an elevated lesion of the upper body of the stomach. The results of immunohistochemical analyses of endoscopic biopsy specimens obtained from the lesion were positive for chromogranin A and synaptophysin, indicating an NET. Because the patient's serum gastrin level was normal and she had no predisposing conditions for NET development, the tumor was diagnosed as a type 3 gastric NET. The patient underwent local resection of the tumor and regional lymph node dissection. The resected specimen indicated a diagnosis of type 3 gastric NET with invasion into the submucosa and lymphatic duct. This is an extremely rare case of an early-stage type 3 gastric NET. Our discussion provides insight into the pathogenesis and development of these tumors and the appropriate therapeutic strategy.
Collapse
Affiliation(s)
- Yoichi Sakurai
- Department of Surgery, Chiba-Ken Saiseikai Narashino Hospital, Social Welfare Organization, Saiseikai Imperial Gift Foundation, 1-1 1-Chome Izumi-Cho, Narashino City, Chiba, 275-8580, Japan.
| | - Hirokazu Karaki
- Department of Surgery, Chiba-Ken Saiseikai Narashino Hospital, Social Welfare Organization, Saiseikai Imperial Gift Foundation, 1-1 1-Chome Izumi-Cho, Narashino City, Chiba, 275-8580, Japan
| | - Yusuke Nakamura
- Department of Surgery, Chiba-Ken Saiseikai Narashino Hospital, Social Welfare Organization, Saiseikai Imperial Gift Foundation, 1-1 1-Chome Izumi-Cho, Narashino City, Chiba, 275-8580, Japan
| | - Hiroyuki Fukuda
- Department of Surgery, Chiba-Ken Saiseikai Narashino Hospital, Social Welfare Organization, Saiseikai Imperial Gift Foundation, 1-1 1-Chome Izumi-Cho, Narashino City, Chiba, 275-8580, Japan
| | - Tomohisa Okaya
- Department of Surgery, Chiba-Ken Saiseikai Narashino Hospital, Social Welfare Organization, Saiseikai Imperial Gift Foundation, 1-1 1-Chome Izumi-Cho, Narashino City, Chiba, 275-8580, Japan
| | - Yoshio Oheda
- Department of Surgery, Chiba-Ken Saiseikai Narashino Hospital, Social Welfare Organization, Saiseikai Imperial Gift Foundation, 1-1 1-Chome Izumi-Cho, Narashino City, Chiba, 275-8580, Japan
| | - Yuya Yokoyama
- Department of Gastroenterology, Chiba-Ken Saiseikai Narashino Hospital, Social Welfare Organization, Saiseikai Imperial Gift Foundation, Narashino City, Chiba, Japan
| | - Futoshi Hirai
- Department of Gastroenterology, Chiba-Ken Saiseikai Narashino Hospital, Social Welfare Organization, Saiseikai Imperial Gift Foundation, Narashino City, Chiba, Japan
| | - Michikazu Abe
- Department of Gastroenterology, Chiba-Ken Saiseikai Narashino Hospital, Social Welfare Organization, Saiseikai Imperial Gift Foundation, Narashino City, Chiba, Japan
| | - Isamu Sugano
- Pathology Division, Chiba-Ken Saiseikai Narashino Hospital, Social Welfare Organization, Saiseikai Imperial Gift Foundation, Narashino City, Chiba, Japan
| |
Collapse
|
|
9
|
Zhu Y. Incidence trend of neuroendocrine tumors and disparities by sex and race/ethnicity in adults from the United States, 2000-2020. Eur J Cancer Prev 2024; 33:475-484. [PMID: 38375858 DOI: 10.1097/cej.0000000000000877] [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: 02/21/2024]
Abstract
OBJECTIVE The incidence of neuroendocrine tumors (NET) has been increasing globally for several decades. The objective of the study was to examine the most recent trend in the incidence of NET as well as disparities by sex and race/ethnicity in adults in the USA. METHODS Patients with NET aged ≥20 years were identified from the SEER 22 Registries from 2000 to 2020. The age-adjusted incidence rate was calculated for overall NET and by primary site. The incidence trend was assessed by annual percent change. Disparities by sex and race/ethnicity were examined using the incidence rate ratio. RESULTS Age-adjusted incidence rate of overall NET in adults was 9.39 per 100 000 in 2000-2020. The incidence rate increased from 2000 but reached a plateau with no significant change since 2015. The lung and bronchus, small intestine, and rectum were the most common primary sites. Sex and racial/ethnic disparities in NET incidence varied by primary sites. For example, there was a female excess in NET of the lung and bronchus, stomach, and appendix; and there was a male excess in the small intestine, pancreas, colon, rectum and other/unknown NET. Compared to non-Hispanic white, non-Hispanic black had higher incidences of stomach, small intestine, liver, pancreas, colon, rectum, and other/unknown NET; they had lower incidences of lung and bronchus, and appendix NET than non-Hispanic white. CONCLUSION Age-adjusted incidence rate of overall NET has reached a plateau since 2015. However, there were sex and racial/ethnic disparities in such incidence, which varied depending on the primary site of NET.
Collapse
Affiliation(s)
- Yong Zhu
- Wayzek Science, St Paul, Minnesota, USA
| |
Collapse
|
|
10
|
Ito S, Hotta K, Sekiguchi M, Takeuchi Y, Oka S, Yamamoto H, Shinmura K, Harada K, Uraoka T, Hisabe T, Sano Y, Kondo H, Horimatsu T, Kikuchi H, Kawamura T, Nagata S, Yamamoto K, Tajika M, Tsuji S, Kusaka T, Okuyama Y, Yoshida N, Moriyama T, Hasebe A, So S, Saito Y, Nakahira H, Ishikawa H, Matsuda T. Short-term outcomes of endoscopic resection for colorectal neuroendocrine tumors: Japanese multicenter prospective C-NET STUDY. Dig Endosc 2024; 36:942-951. [PMID: 37986226 DOI: 10.1111/den.14728] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2023] [Accepted: 11/19/2023] [Indexed: 11/22/2023]
Abstract
OBJECTIVES The incidence of colorectal neuroendocrine tumors (NETs) has increased with colorectal cancer screening programs and increased colonoscopies. The management of colorectal NETs has recently shifted from radical surgery to endoscopic resection. We aimed to evaluate the short-term outcomes of various methods of endoscopic resection for colorectal NETs. METHODS Among those registered in the C-NET STUDY, patients with colorectal NETs who underwent endoscopic treatment as the initial therapy were included. Short-term outcomes, such as the en bloc resection rate and R0 resection (en bloc resection with tumor-free margin) rate, were analyzed based on treatment modalities. RESULTS A total of 472 patients with 477 colorectal NETs received endoscopic treatment. Of these, 418 patients with 421 lesions who met the eligibility criteria were included in the analysis. The median age of the patients was 55 years, and 56.9% of them were men. The lower rectum was the most commonly affected site (88.6%), and lesions <10 mm accounted for 87% of the cases. Endoscopic submucosal resection with a ligation device (ESMR-L, 56.5%) was the most common method, followed by endoscopic submucosal dissection (ESD, 31.4%) and endoscopic mucosal resection using a cap (EMR-C, 8.5%). R0 resection rates <10 mm were 95.5%, 94.8%, and 94.3% for ESMR-L, ESD, and EMR-C, respectively. All 16 (3.8%) patients who developed treatment-related complications could be treated conservatively. Overall, 23 (5.5%) patients had incomplete resection without independent clinicopathological risk factors. CONCLUSION ESMR-L, ESD, and EMR-C were equally effective and safe for colorectal NETs with a diameter <10 mm.
Collapse
Affiliation(s)
- Sayo Ito
- Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan
| | - Kinichi Hotta
- Division of Endoscopy, Shizuoka Cancer Center, Shizuoka, Japan
| | - Masau Sekiguchi
- Endoscopy Division, Cancer Screening Center, National Cancer Center Hospital, Tokyo, Japan
| | - Yoji Takeuchi
- Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Shiro Oka
- Department of Gastroenterology, Hiroshima University Hospital, Hiroshima, Japan
| | - Hironori Yamamoto
- Division of Gastroenterology, Department of Medicine, Jichi Medical University, Tochigi, Japan
| | - Kensuke Shinmura
- Department of Gastroenterology and Endoscopy, National Cancer Center Hospital East, Chiba, Japan
| | - Keita Harada
- Department of Gastroenterology and Hepatology, Okayama University Hospital, Okayama, Japan
| | - Toshio Uraoka
- Department of Gastroenterology and Hepatology, Gunma University Graduate School of Medicine, Gunma, Japan
| | - Takashi Hisabe
- Department of Gastroenterology, Fukuoka University Chikushi Hospital, Fukuoka, Japan
| | - Yasushi Sano
- Gastrointestinal Center, Sano Hospital, Hyogo, Japan
| | - Hitoshi Kondo
- Department of Gastroenterology, Tonan Hospital, Hokkaido, Japan
| | - Takahiro Horimatsu
- Institute for Advancement of Clinical and Translational Science, Kyoto University Hospital, Kyoto, Japan
| | - Hidezumi Kikuchi
- Department of Gastroenterology and Hepatology, Hirosaki University Graduate School of Medicine, Aomori, Japan
| | - Takuji Kawamura
- Department of Gastroenterology, Kyoto Second Red Cross Hospital, Kyoto, Japan
| | - Shinji Nagata
- Department of Gastroenterology, Hiroshima City North Medical Center Asa Citizens Hospital, Hiroshima, Japan
| | - Katsumi Yamamoto
- Department of Gastroenterology, JCHO Osaka Hospital, Osaka, Japan
| | - Masahiro Tajika
- Department of Endoscopy, Aichi Cancer Center Hospital, Aichi, Japan
| | - Shigetsugu Tsuji
- Department of Gastroenterology, Ishikawa Prefectural Central Hospital, Ishikawa, Japan
| | - Toshihiro Kusaka
- Department of Gastroenterology and Hepatology, Kyoto Katsura Hospital, Kyoto, Japan
| | - Yusuke Okuyama
- Department of Gastroenterology, Kyoto First Red Cross Hospital, Kyoto, Japan
| | - Naohisa Yoshida
- Department of Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Tomohiko Moriyama
- International Medical Department, Kyushu University Hospital, Fukuoka, Japan
| | - Aki Hasebe
- Department of Gastroenterology, Shikoku Cancer Center, Ehime, Japan
| | - Suketo So
- Department of Gastroenterology, Tobata Kyoritsu Hospital, Fukuoka, Japan
| | - Yutaka Saito
- Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan
| | - Hiroko Nakahira
- Department of Gastrointestinal Oncology, Osaka International Cancer Institute, Osaka, Japan
| | - Hideki Ishikawa
- Department of Molecular-Targeting Prevention, Graduate School of Medicine Science, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Takahisa Matsuda
- Division of Gastroenterology and Hepatology, Toho University Omori Medical Center, Tokyo, Japan
| |
Collapse
|
|
11
|
Chi Y, Liu S, Zhang J, Li H, Yang L, Zhang X, Li H, Li Q, Wang N, Lu M, Zhuo M. Epidemiological characteristics of neuroendocrine neoplasms in Beijing: a population-based retrospective study. BMC Public Health 2024; 24:1396. [PMID: 38789981 PMCID: PMC11127419 DOI: 10.1186/s12889-024-18845-8] [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: 08/31/2023] [Accepted: 05/13/2024] [Indexed: 05/26/2024] Open
Abstract
BACKGROUND The incidence of neuroendocrine neoplasms (NENs) is rising rapidly worldwide. However, there are few reports on these heterogeneous diseases in China. Our study aimed to explore the epidemiological characteristics of NENs in Beijing. METHODS We conducted a retrospective cohort study using population-based cancer surveillance data in Beijing, China. All data were extracted from the Beijing Cancer Registry with incidence dates from 1 January 1998 to 31 December 2018; the follow-up period was through 31 December 2021. Segi's world standard population was used to estimate the age-standardized rate. Survival was estimated using the Kaplan-Meier method. RESULTS From 1998 to 2018, the incidence of NENs in Beijing initially showed a significant increasing trend, from 1.07/100,000 to 3.53/100,000; this began to plateau after 2013. The age-specific incidence rate increased with age and peaked in the age group 70-74 years. The incidence in men was significantly higher than that in women (4.41/100,000 vs. 1.69/100,000). The most common sites of NENs were the lung (2.38/100,000) and rectum (0.14/100,000). Most NENs were diagnosed at a late stage. We found that NENs originating from the lung had worse overall survival than extrapulmonary NENs, and male patients had worse survival than female patients. CONCLUSIONS This study retrospectively analyzed the epidemiological characteristics of NENs in Beijing from 1998 to 2018. Our findings provide a reference regarding the epidemiological statistics of NENs in Beijing to contribute to the prevention, diagnosis, and treatment of these specific tumors.
Collapse
Affiliation(s)
- Yujia Chi
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department I of Thoracic Oncology, Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing, 100142, China
| | - Shuo Liu
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing Office for Cancer Prevention and Control, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Jianwei Zhang
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing, 100142, China
| | - Huichao Li
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing Office for Cancer Prevention and Control, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Lei Yang
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing Office for Cancer Prevention and Control, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Xi Zhang
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing Office for Cancer Prevention and Control, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Haoxin Li
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing Office for Cancer Prevention and Control, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Qingyu Li
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing Office for Cancer Prevention and Control, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Ning Wang
- Key laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Beijing Office for Cancer Prevention and Control, Peking University Cancer Hospital & Institute, Beijing, 100142, China
| | - Ming Lu
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing, 100142, China.
| | - Minglei Zhuo
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department I of Thoracic Oncology, Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing, 100142, China.
| |
Collapse
|
|
12
|
Komiyama S, Okusaka T, Maruki Y, Ohba A, Nagashio Y, Kondo S, Hijioka S, Morizane C, Ueno H, Sukeda A, Mizui T, Takamoto T, Nara S, Ban D, Esaki M, Hiraoka N, Shimada K. Clinicopathological Findings and Treatment Outcomes of Patients with Primary Hepatobiliary Neuroendocrine Neoplasms: A Retrospective Single-institution Analysis. Intern Med 2024; 63:891-901. [PMID: 37612088 PMCID: PMC11045373 DOI: 10.2169/internalmedicine.2016-23] [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: 03/31/2023] [Accepted: 07/11/2023] [Indexed: 08/25/2023] Open
Abstract
Objective Primary hepatobiliary neuroendocrine neoplasms (NENs) are rare tumors exhibiting several morphological and behavioral characteristics. Considering the lack of relevant data on this topic, we evaluated the clinicopathological features and treatment outcomes of patients with primary hepatobiliary NENs. Methods/Patients We examined 43 consecutive patients treated at the National Cancer Center Hospital with pathological diagnoses of primary hepatobiliary NEN between 1980 and 2016. Results Nine patients were diagnosed with neuroendocrine tumor (NET) G1, 9 with NET G2, and 25 with neuroendocrine carcinoma (NEC) based on the World Health Organization 2019 classification. Patients with NEC had primary sites across the hepatobiliary organs, although sites in patients with NET G1 and NET G2 only included the liver and ampulla of Vater. Patients with primary extrahepatic bile duct or ampulla of Vater NENs tended to be diagnosed earlier than patients with primary gallbladder NENs. The median survival times in the NET G1, NET G2, and NEC groups were 167.9, 97.4, and 11.1 months, respectively. A good performance status, absence of distant metastases, and low tumor grade were identified as independent predictors of a favorable prognosis. Conclusion The NET-to-NEC ratio and tumor stage distribution at the diagnosis differed depending on the primary site. Patients with G1 and G2 NETs who underwent surgical resection had good prognoses, whereas those with NEC exhibited more advanced disease and poorer prognoses. The performance status, staging classification, and tumor grade are important factors to consider when devising an appropriate treatment strategy and predicting the prognoses of patients with primary hepatobiliary NEN.
Collapse
Affiliation(s)
- Satoshi Komiyama
- Chemotherapy Department, Yokohama City University Medical Center, Japan
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Japan
| | - Takuji Okusaka
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Japan
| | - Yuta Maruki
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Japan
| | - Akihiro Ohba
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Japan
| | - Yoshikuni Nagashio
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Japan
| | - Shunsuke Kondo
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Japan
| | - Susumu Hijioka
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Japan
| | - Chigusa Morizane
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Japan
| | - Hideki Ueno
- Department of Hepatobiliary and Pancreatic Oncology, National Cancer Center Hospital, Japan
| | - Aoi Sukeda
- Pathology and Clinical Laboratories, National Cancer Center Hospital, Japan
- Department of Anatomic Pathology, Tokyo Medical University, Japan
| | - Takahiro Mizui
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Japan
| | - Takeshi Takamoto
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Japan
| | - Satoshi Nara
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Japan
| | - Daisuke Ban
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Japan
| | - Minoru Esaki
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Japan
| | - Nobuyoshi Hiraoka
- Pathology and Clinical Laboratories, National Cancer Center Hospital, Japan
| | - Kazuaki Shimada
- Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital, Japan
| |
Collapse
|
|
13
|
Durma AD, Saracyn M, Kołodziej M, Jóźwik-Plebanek K, Dmochowska B, Kapusta W, Żmudzki W, Mróz A, Kos-Kudła B, Kamiński G. Epidemiology of Neuroendocrine Neoplasms and Results of Their Treatment with [ 177Lu]Lu-DOTA-TATE or [ 177Lu]Lu-DOTA-TATE and [ 90Y]Y-DOTA-TATE-A Six-Year Experience in High-Reference Polish Neuroendocrine Neoplasm Center. Cancers (Basel) 2023; 15:5466. [PMID: 38001726 PMCID: PMC10670106 DOI: 10.3390/cancers15225466] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/09/2023] [Revised: 11/10/2023] [Accepted: 11/16/2023] [Indexed: 11/26/2023] Open
Abstract
Neuroendocrine neoplasms (NENs) are a group of neoplasms arising from neuroendocrine cells. The worldwide incidence and prevalence of the NENs are estimated to be 6/100,000 and 35/100,000, respectively. Those numbers are increasing every decade, requiring higher and higher diagnosis and treatment costs. Radioligand therapy (RLT) using beta-emitting radioisotopes is an efficient and relatively safe method of treatment, typically used as a second-line treatment. RLT tolerability is higher than other available pharmacotherapies (chemotherapy or tyrosine kinase inhibitors). Recent studies show an increase in overall survival among patients treated with RLT. The present study aimed to learn the epidemiology of NENs in Poland and assess the effectiveness of RLT in a high-reference center. A prospective analysis of 167 patients treated with RLT in one of Poland's highest-reference NEN centers was performed. The analysis covered 66 months of observation (1 December 2017-30 May 2023), during which 479 RLT single administrations of radioisotope were given. The standard procedure was to give four courses of [177Lu]Lu-DOTA-TATE alone, or tandem therapy-[177Lu]Lu-DOTA-TATE and [90Y]Y-DOTA-TATE. Grading analysis showed that most patients had non-functioning G2 NEN with a mean Ki-67 of 6.05% (SD ± 6.41). The most common primary tumor location was the pancreas. Over two-thirds of patients did undergo surgery due to primary tumors or distant metastases. The majority of patients were using lanreotide as a chronically injected somatostatin analog. Median progression-free survival (PFS) on somatostatin analogs was 21.0 (IQR = 29.0) months. Directly after the last course of RLT, disease stabilization was noted in 69.46% of patients, partial regression was noted in 20.36% of patients, complete regression was noted in 0.60% of patients, and progression was noted in 9.58% of patients. In long-term follow-up, the median observation time among patients who underwent four treatment cycles (n = 108) was 29.8 (IQR = 23.9) months. Stabilization of the disease was observed in 55.56% of the patients and progression was observed in 26.85% of the patients, while 17.59% of patients died. Median PFS was 29.3 (IQR 23.9), and the median OS was 34.0 months (IQR 16.0). The mean age of NEN diagnosis is the sixth decade of life. It takes almost three years from NEN diagnosis to the start of RLT. In long-term observation, RLT leads to disease stabilization in over half of the patients with progressive disease. No differences in PFS or OS depend on the radioisotope used for RLT. In Poland, organized coordination of NEN treatment in high-reference centers ensures the continuity of patient care.
Collapse
Affiliation(s)
- Adam Daniel Durma
- Department of Endocrinology and Radioisotope Therapy, Military Institute of Medicine—National Research Institute, 04-141 Warsaw, Poland
| | - Marek Saracyn
- Department of Endocrinology and Radioisotope Therapy, Military Institute of Medicine—National Research Institute, 04-141 Warsaw, Poland
| | - Maciej Kołodziej
- Department of Endocrinology and Radioisotope Therapy, Military Institute of Medicine—National Research Institute, 04-141 Warsaw, Poland
| | - Katarzyna Jóźwik-Plebanek
- Department of Endocrinology and Radioisotope Therapy, Military Institute of Medicine—National Research Institute, 04-141 Warsaw, Poland
| | - Beata Dmochowska
- Department of Endocrinology and Radioisotope Therapy, Military Institute of Medicine—National Research Institute, 04-141 Warsaw, Poland
| | - Waldemar Kapusta
- Department of Endocrinology and Radioisotope Therapy, Military Institute of Medicine—National Research Institute, 04-141 Warsaw, Poland
| | - Wawrzyniec Żmudzki
- Department of Endocrinology and Radioisotope Therapy, Military Institute of Medicine—National Research Institute, 04-141 Warsaw, Poland
| | - Adrianna Mróz
- Department of Endocrinology and Radioisotope Therapy, Military Institute of Medicine—National Research Institute, 04-141 Warsaw, Poland
| | - Beata Kos-Kudła
- Department of Endocrinology and Neuroendocrine Tumors, Department of Pathophysiology and Endocrinology in Zabrze, Medical University of Silesia, 40-055 Katowice, Poland
| | - Grzegorz Kamiński
- Department of Endocrinology and Radioisotope Therapy, Military Institute of Medicine—National Research Institute, 04-141 Warsaw, Poland
| |
Collapse
|
|
14
|
Aziz Khan A, Ahuja S, Zaheer S. A rare case of primary neuroendocrine carcinoma of the central nervous system. Neuropathology 2023; 43:421-424. [PMID: 37013337 DOI: 10.1111/neup.12904] [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: 02/14/2023] [Revised: 03/13/2023] [Accepted: 03/15/2023] [Indexed: 04/05/2023]
Abstract
Primary neuroendocrine carcinoma (NEC) of the brain is an extremely rare presentation, with only a few previous case reports. We describe a primary NEC arising from the left parieto-occipital lobe. The 55-year-old patient presented with complaints of headache and dizziness for the preceding 7 months. Magnetic resonance imaging revealed a large ill-defined mass in the left parieto-occipital lobe, with possible differential diagnosis of meningioma. A craniotomy was performed, and a firm vascular tumor was removed. Histopathological examination revealed a large cell NEC. Immunohistochemistry was performed to exclude the possibility of an extracranial primary. Based on the immunohistochemical expression and absence of any extracranial tumor on positron emission tomography, the diagnosis of primary NEC of the brain was made. It is important to differentiate between primary and metastatic neuroendocrine tumors because they show a significant difference in prognosis and treatment.
Collapse
Affiliation(s)
- Adil Aziz Khan
- Department of Pathology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India
| | - Sana Ahuja
- Department of Pathology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India
| | - Sufian Zaheer
- Department of Pathology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India
| |
Collapse
|
|
15
|
Guccione L, Gough K, Drosdowsky A, Price T, Pavlakis N, Wyld D, Ransom D, Michael M, Schofield P. The unmet information needs, quality of life, and care experiences of patients with neuroendocrine tumours (NETs) at follow-up: 6 months from diagnosis. Support Care Cancer 2023; 31:577. [PMID: 37712997 PMCID: PMC10504214 DOI: 10.1007/s00520-023-08034-5] [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: 05/02/2023] [Accepted: 08/31/2023] [Indexed: 09/16/2023]
Abstract
OBJECTIVES To identify changes in the healthcare preferences, patient experiences, and quality of life of patients with NETs at 6-month follow-up, informing the design of supportive care services. METHODS This study presents 6-month follow-up data of a mixed-methods multi-site study. Demographic, clinical, and patient-reported outcome questionnaire data was collected. RESULTS High percentages of suboptimal experiences of care were reported. Patients reported less positive experiences with being involved in decisions about their care and treatment; their family or someone close to them having the opportunity to talk to their cancer doctor, or having their family or someone close to them receive all the information they need to help care for them at home. Patients also reported negative experiences for on the information about their cancer accessible online and the usefulness of the information they accessed. Differences between baseline and follow-up scores were mostly not significant apart from anxiety and sleep disturbance scales, CONCLUSIONS: Patients with NETs report difficulties in accessing and understanding written information that is persistent over time. PRACTICE IMPLICATIONS Outcomes will inform the design and development of an informational resource aimed at facilitating improved understanding for patients with NETs.
Collapse
Affiliation(s)
- Lisa Guccione
- Department of Health Services Research, Peter MacCallum Cancer Centre, Melbourne, VIC Australia
- Sir Peter MacCallum Department of Oncology, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Australia
| | - Karla Gough
- Department of Health Services Research, Peter MacCallum Cancer Centre, Melbourne, VIC Australia
- Sir Peter MacCallum Department of Oncology, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Australia
| | - Allison Drosdowsky
- Department of Health Services Research, Peter MacCallum Cancer Centre, Melbourne, VIC Australia
- Sir Peter MacCallum Department of Oncology, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Australia
| | - Timothy Price
- Haematology and Oncology, The Queen Elizabeth Hospital, Woodville South, South Australia Australia
| | - Nick Pavlakis
- Department of Medical Oncology, Royal North Shore Hospital, St Leonards, New South Wales Australia
| | - David Wyld
- Department of Medical Oncology, Royal Brisbane and Women’s Hospital, Brisbane, QLD Australia
- Faculty of Medicine, University of Queensland, Brisbane, Australia
| | - David Ransom
- Medical Oncology, Fiona Stanley Hospital, Murdoch, WA Australia
| | - Michael Michael
- Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia
- Upper Gastrointestinal Cancer Service, Peter MacCallum Cancer Centre, Melbourne, Australia
| | - Penelope Schofield
- Department of Health Services Research, Peter MacCallum Cancer Centre, Melbourne, VIC Australia
- Sir Peter MacCallum Department of Oncology, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Australia
- Department of Psychology and Iverson Health Innovation Research Institute, Swinburne University, Melbourne, Australia
| |
Collapse
|
|
16
|
Pathak S, Starr JS, Halfdanarson T, Sonbol MB. Understanding the increasing incidence of neuroendocrine tumors. Expert Rev Endocrinol Metab 2023; 18:377-385. [PMID: 37466336 DOI: 10.1080/17446651.2023.2237593] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Accepted: 07/13/2023] [Indexed: 07/20/2023]
Abstract
INTRODUCTION Neuroendocrine tumors (NETs) are a diverse group of tumors with origins from different primary sites such as gastro-entero-pancreatic, lung and endocrine tissue. Worldwide, their incidence has increased in recent decades. Advances in imaging and better clinical awareness are traditionally attributed to this trend; however, other factors such as genetic and environmental contributors are appreciated as well. AREAS COVERED The purpose of this article is to review the worldwide epidemiologic trends in incidence of NET through the decades and discuss the various factors potentially contributing to the observed changes in incidence trends. EXPERT OPINION Overall, the incidence of NET has increased across the globe over the last few decades. Although multiple genetics and environmental factors have been proposed, the majority of this increase in incidence is secondary to earlier detection. Future studies will help in more accurate assessments and an improved understanding of disease incidence among patients with different grades and differentiation.
Collapse
Affiliation(s)
- Surabhi Pathak
- Attending Hematology-Oncology, King's Daughters Medical Center, Ashland, KY, USA
| | - Jason S Starr
- Division of Hematology- Oncology, Mayo Clinic Jacksonville Campus, Jacksonville, FL, USA
| | - Thorvardur Halfdanarson
- Division of Hematology- Oncology, Mayo Clinic, Mayo Clinic Cancer Center, Rochester, MN, USA
| | | |
Collapse
|
|
17
|
Durma AD, Saracyn M, Kołodziej M, Jóźwik-Plebanek K, Dmochowska B, Mróz A, Żmudzki W, Kamiński G. Radioligand Therapy with [ 177Lu]Lu-DOTA-TATE or [ 177Lu]Lu-DOTA-TATE and [ 90Y]Y-DOTA-TATE in Patients with Neuroendocrine Neoplasms of Unknown Locations, or Locations Other Than the Midgut and Pancreas as Primaries in a G1, G2 and G3 Grade. Pharmaceuticals (Basel) 2023; 16:1205. [PMID: 37765013 PMCID: PMC10537132 DOI: 10.3390/ph16091205] [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: 07/03/2023] [Revised: 08/14/2023] [Accepted: 08/23/2023] [Indexed: 09/29/2023] Open
Abstract
BACKGROUND Neuroendocrine neoplasms (NENs) are a rare group of tumors with a different clinical course, prognosis and location. Radioligand therapy (RLT) can be used as a first or second line of treatment. It is registered in gastroenteropancreatic NENs (GEP-NENs) as grades G1 and G2. Tumors with an unknown point of origin, diagnosed outside the gastrointestinal tract and pancreas (non-GEP) or at the G3 grade, remain in the "grey area" of treatment. MATERIALS AND METHODS Analysis of 51 patients with NENs who underwent RLT in a single highest reference center from 2018 to 2023 was performed. Treatment was administrated to the patients with neoplasms of unknown origin, non-GEP-NENs, and ones with G3 grade. In total, 35 patients received 177-Lutetium (7.4 GBq), while 16 received 177-Lutetium and 90-Yttrium with equal activities (1.85 + 1.85 GBq). RESULTS The progression-free survival (PFS) before RLT qualification was 34.39 ± 35.88 months for the whole study group. In subgroups of patients with an unknown tumor location (n = 25), the median PFS was 19 months (IQR = 23), with "other" locations (n = 21) at 31 months (IQR = 28), and with NEN G3 (n = 7) at 18 months (IQR = 40). After RLT, disease stabilization or regression was observed in 42 (87.5% of) patients. RLT did not cause statistical changes in creatinine or GFR values. Hematological parameters (RBC, WBC, PLT, HGB) as well as chromogranin A concentration decreased significantly. There were no statistical differences between both subgroups regarding the type of radioisotope (177-Lutetium vs. 177-Lutetium and 90-Yttrium). After RLT in long-term observation, the median observation time (OT) was 14 months (IQR = 18 months). In patients with progression (n = 8), the median PFS was 20 months (IQR = 16 months), while in patients with confirmed death (n = 9), the median overall survival (OS) was 8 months (IQR = 14 months). CONCLUSIONS Our study showed that 87.5% of NEN patients with unknown origin, non-GEP-NENs, and those with GEP-NEN G3 grade had benefited from the radioligand therapy. There were no significantly negative impacts on renal parameters. The decrease of bone marrow parameters was acceptable in relation to beneficial disease course. The decrease of chromogranin concentration was confirmed as a predictive factor for disease stabilization or regression.
Collapse
Affiliation(s)
- Adam Daniel Durma
- Department of Endocrinology and Radioisotope Therapy, Military Institute of Medicine—National Research Institute, Szaserów 128, 04-141 Warsaw, Poland
| | | | | | | | | | | | | | | |
Collapse
|
|
18
|
Kiesewetter B, Melhorn P, Macheiner S, Wolff L, Kretschmer-Chott E, Haug A, Mazal P, Raderer M. Does the dose matter? Antiproliferative efficacy and toxicity of everolimus in patients with neuroendocrine tumors - Experiences from a tertiary referral center. J Neuroendocrinol 2023; 35:e13319. [PMID: 37485760 DOI: 10.1111/jne.13319] [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: 01/08/2023] [Revised: 05/12/2023] [Accepted: 06/26/2023] [Indexed: 07/25/2023]
Abstract
The mTOR-inhibitor everolimus has been approved for the treatment of advanced neuroendocrine tumors (NETs) but is associated with relevant toxicities in clinical practice. Hence, optimal treatment sequencing and the impact of dose reductions have yet to be clarified. This retrospective analysis assessed patients with advanced, well-differentiated NET treated with everolimus at the Medical University of Vienna. The primary objective was to evaluate the efficacy of everolimus in a real-world cohort. A total of 52 patients treated with everolimus for advanced NET grade 1 (G1) or G2 (or typical or atypical carcinoid) 2010-2021 were included in this analysis. The most common sites of origin were pancreas (44%) and lung (29%). The initial dose was decided by the treating physician based on clinical assessment and 25 patients (48%) each were started at 10 mg/day and 5 mg/day. Median progression-free survival (PFS) following everolimus in the overall cohort was 9.8 months (95% CI: 4.3-15.3), with a statistically significant PFS difference (p = .03) between NET G1/typical carcinoids (42.9 months) and NET G2/atypical carcinoids (8.9 months). PFS was numerically but not significantly shorter in patients treated with a reduced dose (7.5 months vs. 12.4 months, p = .359). Even in this mixed full/half dose cohort, 93% developed treatment-related side effects (mostly grade I, no grade IV), 63% had dose reductions or interruptions, and five stopped due to toxicity. Median survival following treatment was 40.9 months (95% CI: 21.5-60.3) and no difference with regard to dosing was observed (p = .517). These data from an unselected patient cohort show long-term outcomes similar to those reported in the pivotal studies. Comparing everolimus starting dose, median PFS did not significantly differ for patients treated at a lower dose. While this finding is limited by the sample size and warrants prospective verification, initiating therapy at a reduced dose might be practicable and safe in a distinct subset of patients.
Collapse
Affiliation(s)
- Barbara Kiesewetter
- Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria
| | - Philipp Melhorn
- Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria
| | - Simon Macheiner
- Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria
| | - Ladislaia Wolff
- Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria
| | - Elisabeth Kretschmer-Chott
- Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria
| | - Alexander Haug
- Department of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria
| | - Peter Mazal
- Department of Pathology, Medical University of Vienna, Vienna, Austria
| | - Markus Raderer
- Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, Austria
| |
Collapse
|
|
19
|
Andrini E, Lamberti G, Alberici L, Ricci C, Campana D. An Update on Appendiceal Neuroendocrine Tumors. Curr Treat Options Oncol 2023; 24:742-756. [PMID: 37140773 PMCID: PMC10271885 DOI: 10.1007/s11864-023-01093-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/05/2023] [Indexed: 05/05/2023]
Abstract
The mainstay of appendiceal neuroendocrine neoplasm (aNEN) treatment is surgery, based on simple appendectomy or right-sided hemicolectomy with lymphadenectomy (RHC). The majority of aNENs are adequately treated with appendectomy, but current guidelines have poor accuracy in terms of selecting patients requiring RHC, especially in aNENs 1-2 cm in size. Simple appendectomy is curative for appendiceal NETs (G1-G2) < 1 cm (if the resection status is R0), whereas RHC with lymph node dissection is recommended in tumors ≥ 2 cm in diameter, based on the high risk of nodal metastases in these cases. The clinical management of aNENs 1-2 cm in size is more controversial because lymph node or distant metastases are uncommon but possible. In our opinion, patients with tumor size > 15 mm or with grading G2 (according to WHO 2010) and/or lympho-vascular invasion should be referred for radicalization with RHC. However, decision-making in these cases should include discussion within a multidisciplinary tumor board at referral centers with the aim of offering each patient a tailored treatment, also considering that relatively young patients with long-life expectancy represent the majority of cases.
Collapse
Affiliation(s)
- Elisa Andrini
- Department of Experimental, Diagnostic & Specialty Medicine (DIMES), University of Bologna, 40138, Bologna, Italy
- Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Via P. Albertoni, 15, 40138, Bologna, Italy
| | - Giuseppe Lamberti
- Department of Experimental, Diagnostic & Specialty Medicine (DIMES), University of Bologna, 40138, Bologna, Italy
- Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Via P. Albertoni, 15, 40138, Bologna, Italy
| | - Laura Alberici
- Department of Internal Medicine and Surgery (DIMEC), Alma Mater Studiorum, S. Orsola-Malpighi Hospital, University of Bologna, Policlinico S. Orsola-Malpighi Via Massarenti N. 9, 40138, Bologna, Italy
- Division of Pancreatic Surgery, IRCCS, Azienda Ospedaliero Universitaria Di Bologna, 40138, Bologna, Italy
| | - Claudio Ricci
- Department of Internal Medicine and Surgery (DIMEC), Alma Mater Studiorum, S. Orsola-Malpighi Hospital, University of Bologna, Policlinico S. Orsola-Malpighi Via Massarenti N. 9, 40138, Bologna, Italy
- Division of Pancreatic Surgery, IRCCS, Azienda Ospedaliero Universitaria Di Bologna, 40138, Bologna, Italy
| | - Davide Campana
- Department of Experimental, Diagnostic & Specialty Medicine (DIMES), University of Bologna, 40138, Bologna, Italy.
- Medical Oncology, IRCCS Azienda Ospedaliero-Universitaria Di Bologna, Via P. Albertoni, 15, 40138, Bologna, Italy.
| |
Collapse
|
|
20
|
Hiyoshi Y, Daitoku N, Mukai T, Nagasaki T, Yamaguchi T, Akiyoshi T, Yasue C, Chino A, Saito S, Takamatsu M, Fukunaga Y. Risk Factors for Lymph Node Metastasis of Rectal Neuroendocrine Tumor and Its Prognostic Impact: A Single-Center Retrospective Analysis of 195 Cases with Radical Resection. Ann Surg Oncol 2023; 30:3944-3953. [PMID: 36935432 DOI: 10.1245/s10434-023-13348-z] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Accepted: 01/16/2023] [Indexed: 03/21/2023]
Abstract
PURPOSE The incidence of rectal neuroendocrine tumors (NETs) has been steadily increasing. The risk factors for and prognostic impact of lymph node (LN) metastasis were analyzed in 195 patients with stage I-III rectal NET who underwent radical surgery. METHODS This retrospective, single-center study analyzed risk factors for LN metastasis focusing on previously identified factors and a novel risk factor: multiple rectal NETs. The association between LN metastasis and the prognosis was also analyzed. RESULTS Pathologically, the LN metastasis rate (also the rate of stage III disease) was 39%, which was higher than the clinical LN metastasis rate of 14%. Tumor size > 10 mm, presence of central depression, tumor grade G2, depth of invasion, LN swelling on preoperative imaging (cN1), venous invasion and multiple NETs were identified as risk factors for LN metastasis. As the tumor size and risk factors increased, the rate of LN metastasis increased. Among these 7 factors, venous invasion, cN1, and multiple NETs were identified as independent predictors of LN metastasis. LN metastasis of rectal NETs was associated with significantly poor disease-free and disease-specific survival. CONCLUSIONS As risk factors increase, the potential for rectal NETs to metastasize to the LNs increases and LN metastasis is associated with a poor prognosis. This is the first study to report multiple NETs as a risk factor for LN metastasis. A future study examining the survival benefit of radical surgery accompanying LN dissection compared with local resection is warranted.
Collapse
Affiliation(s)
- Yukiharu Hiyoshi
- Gastroenterological Center, Department of Gastroenterological Surgery, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan.
| | - Nobuya Daitoku
- Gastroenterological Center, Department of Gastroenterological Surgery, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Toshiki Mukai
- Gastroenterological Center, Department of Gastroenterological Surgery, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Toshiya Nagasaki
- Gastroenterological Center, Department of Gastroenterological Surgery, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Tomohiro Yamaguchi
- Gastroenterological Center, Department of Gastroenterological Surgery, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Takashi Akiyoshi
- Gastroenterological Center, Department of Gastroenterological Surgery, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Chihiro Yasue
- Gastroenterological Center, Department of Lower Gastrointestinal Medicine, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Akiko Chino
- Gastroenterological Center, Department of Lower Gastrointestinal Medicine, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Shoichi Saito
- Gastroenterological Center, Department of Lower Gastrointestinal Medicine, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Manabu Takamatsu
- Department of Pathology, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| | - Yosuke Fukunaga
- Gastroenterological Center, Department of Gastroenterological Surgery, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research, Tokyo, Japan
| |
Collapse
|
|
21
|
Folkestad O, Hauso Ø, Mjønes P, Fougner R, Wasmuth HH, Fossmark R. Survival Trends in Patients with Small Intestinal Neuroendocrine Tumours-A Cohort Study in Central Norway. Cancers (Basel) 2023; 15:3272. [PMID: 37444383 DOI: 10.3390/cancers15133272] [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: 05/19/2023] [Revised: 06/16/2023] [Accepted: 06/20/2023] [Indexed: 07/15/2023] Open
Abstract
Improved surgical resection and oncological treatment, or an earlier diagnosis may increase survival in small intestinal neuroendocrine tumours (SI-NETs), but only few studies have examined survival trends. We aimed to examine the trend in overall survival and associated factors in SI-NET patients. All patients with SI-NETs at a regional hospital from June 2005 to December 2021 (n = 242) were identified, and the cohort was divided in half, constituting a first period (until November 2012) and a second period (from November 2012). Disease and treatment characteristics, including European Neuroendocrine Tumour Society (ENETS) stage, surgery, oncological treatment and survival, were recorded. The majority (n = 205 (84.7%)) were treated surgically and surgery was considered curative in 137 (66.8%) patients. Median survival was longer in the second period (9.0 years 95% CI 6.4-11.7 in the first period vs. median not reached in the second period, p = 0.014), with 5-year survival rates of 63.5% and 83.5%, respectively. ENETS stage and oncological treatment did not differ between the periods, but factors associated with surgical quality, such as lymph node harvest and resection of multiple SI-NETs, were significantly higher in the second period. Age, ENETS stage, time period and tumour resection were independently associated with survival in a multivariate analysis.
Collapse
Affiliation(s)
- Oddry Folkestad
- Department of Gastrointestinal Surgery, St. Olav's Hospital, Trondheim University Hospital, 7030 Trondheim, Norway
- Department of Gastrointestinal Surgery, Vestfold Hospital Thrust, 3103 Tønsberg, Norway
| | - Øyvind Hauso
- Department of Gastroenterology and Hepatology, St. Olav's Hospital, Trondheim University Hospital, 7030 Trondheim, Norway
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway
| | - Patricia Mjønes
- Department of Gastroenterology and Hepatology, St. Olav's Hospital, Trondheim University Hospital, 7030 Trondheim, Norway
- Department of Pathology, St. Olav's Hospital, Trondheim University Hospital, 7030 Trondheim, Norway
| | - Reidun Fougner
- Department of Radiology, St. Olav's Hospital, Trondheim University Hospital, 7030 Trondheim, Norway
| | - Hans H Wasmuth
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway
| | - Reidar Fossmark
- Department of Gastroenterology and Hepatology, St. Olav's Hospital, Trondheim University Hospital, 7030 Trondheim, Norway
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway
| |
Collapse
|
|
22
|
Zheng R, Zhao H, An L, Zhang S, Chen R, Wang S, Sun K, Zeng H, Wei W, He J. Incidence and survival of neuroendocrine neoplasms in China with comparison to the United States. Chin Med J (Engl) 2023; 136:1216-1224. [PMID: 37022941 PMCID: PMC10278748 DOI: 10.1097/cm9.0000000000002643] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2022] [Indexed: 04/07/2023] Open
Abstract
BACKGROUND Neuroendocrine neoplasms (NENs) are rare tumors characterized by variable biology and delayed diagnosis. However, the nationwide epidemiology of NENs has never been reported in China. We aimed to estimate the incidence and survival statistics of NENs in China, in comparison to those in the United States during the same period. METHODS Based on the data from 246 population-based cancer registries covering 272.5 million people of China, we calculated age-specific incidence on NENs in 2017 and multiplied by corresponding national population to estimate the nationwide incidence in China. The data of 22 population-based cancer registries were used to estimate the trends of NENs incidence from 2000 to 2017 through the Joinpoint regression model. We used the cohort approach to analyze the 5-year age-standardized relative survival by sex, age group, and urban-rural area between 2008 and 2013, based on data from 176 high-quality cancer registries. We used data from the Surveillance, Epidemiology, and End Results (SEER) 18 program to estimate the comparable incidence and survival of NENs in the United States. RESULTS The overall age-standardized rate (ASR) of NENs incidence was lower in China (1.14 per 100,000) than in the United States (6.26 per 100,000). The most common primary sites were lungs, pancreas, stomach, and rectum in China. The ASRs of NENs incidence increased by 9.8% and 3.6% per year in China and the United States, respectively. The overall 5-year relative survival in China (36.2%) was lower than in the United States (63.9%). The 5-year relative survival was higher for female patients than male patients, and was higher in urban areas than in rural areas. CONCLUSIONS The disparities in burden of NENs persist across sex, area, age group, and site in China and the United States. These findings may provide a scientific basis on prevention and control of NENs in the two countries.
Collapse
Affiliation(s)
- Rongshou Zheng
- National Central Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Hong Zhao
- Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Lan An
- National Central Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Siwei Zhang
- National Central Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Ru Chen
- National Central Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Shaoming Wang
- National Central Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Kexin Sun
- National Central Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Hongmei Zeng
- National Central Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Wenqiang Wei
- National Central Cancer Registry, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Jie He
- Department of Thoracic Surgery, National Cancer Registry Office, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| |
Collapse
|
|
23
|
Yagi K, Ono H, Kudo A, Kinowaki Y, Asano D, Watanabe S, Ishikawa Y, Ueda H, Akahoshi K, Tanaka S, Tanabe M. MGMT is frequently inactivated in pancreatic NET-G2 and is associated with the therapeutic activity of STZ-based regimens. Sci Rep 2023; 13:7535. [PMID: 37161026 PMCID: PMC10170117 DOI: 10.1038/s41598-023-34666-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2022] [Accepted: 05/05/2023] [Indexed: 05/11/2023] Open
Abstract
O6-methylguanine-DNA methyltransferase (MGMT) has been linked with alkylating agent resistance and tumor growth suppression. However, its role remains undetermined in pancreatic neuroendocrine tumors (Pan-NET). The MGMT expression was examined by immunohistochemistry in 142 patients to evaluate MGMT immunoreactivity and clinicopathological factors. We analyzed the relationship between MGMT expression and treatment efficacy in 19 patients who received STZ-based regimens. In 142 Pan-NET, 97 cases (68.3%) were judged as MGMT-positive and 45 cases (31.6%) as negative. MGMT negativity was significantly more common in NET-G2 (62.5%) than in NET-G1 (11.2%, p < 0.001). MGMT-negative cases were associated significantly with larger tumor size (p < 0.01), higher Ki-67 index (p < 0.01), higher mitotic index (p < 0.05), and more frequent liver metastasis (p < 0.05). Of the 19 cases treated with STZ, 6 cases were determined as SD and 4 cases as PD in MGMT-positive patients (N = 10), while 5 cases were determined as PR and 4 cases as SD in MGMT-negative patients (N = 9). Progression-free survival in MGMT-negative cases was significantly better than in MGMT-positive cases (p < 0.05). MGMT expression was lower in NET-G2 than in NET-G1, and STZ-based regimens improved the therapeutic outcomes of MGMT-negative Pan-NET. These findings indicate that NET-G2 may represent a better therapeutic target for STZ treatment.
Collapse
Affiliation(s)
- Kohei Yagi
- Department of Hepatobiliary and Pancreatic Surgery, Tokyo Medical and Dental University, Tokyo, Japan
| | - Hiroaki Ono
- Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-Ku, Tokyo, 113-8519, Japan.
| | - Atsushi Kudo
- Department of Hepatobiliary and Pancreatic Surgery, Tokyo Medical and Dental University, Tokyo, Japan
| | - Yuko Kinowaki
- Department of Comprehensive Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
| | - Daisuke Asano
- Department of Hepatobiliary and Pancreatic Surgery, Tokyo Medical and Dental University, Tokyo, Japan
| | - Shuichi Watanabe
- Department of Hepatobiliary and Pancreatic Surgery, Tokyo Medical and Dental University, Tokyo, Japan
| | - Yoshiya Ishikawa
- Department of Hepatobiliary and Pancreatic Surgery, Tokyo Medical and Dental University, Tokyo, Japan
| | - Hiroki Ueda
- Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-Ku, Tokyo, 113-8519, Japan
| | - Keiichi Akahoshi
- Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-Ku, Tokyo, 113-8519, Japan
| | - Shinji Tanaka
- Department of Molecular Oncology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan
| | - Minoru Tanabe
- Department of Hepatobiliary and Pancreatic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-Ku, Tokyo, 113-8519, Japan
| |
Collapse
|
|
24
|
Hertelendi M, Belguenani O, Cherfi A, Folitar I, Kollar G, Polack BD. Efficacy and Safety of [177Lu]Lu-DOTA-TATE in Adults with Inoperable or Metastatic Somatostatin Receptor-Positive Pheochromocytomas/Paragangliomas, Bronchial and Unknown Origin Neuroendocrine Tumors, and Medullary Thyroid Carcinoma: A Systematic Literature Review. Biomedicines 2023; 11:biomedicines11041024. [PMID: 37189646 DOI: 10.3390/biomedicines11041024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Revised: 03/20/2023] [Accepted: 03/22/2023] [Indexed: 03/29/2023] Open
Abstract
Background: We have performed a systematic review to evaluate the efficacy and safety of [177Lu]Lu-DOTA-TATE, a radioligand therapy, in advanced somatostatin receptor-positive pheochromocytoma/paraganglioma (PPGL), thymic neuroendocrine tumor (NET), bronchial NET, unknown primary NET, or medullary thyroid carcinoma (MTC). Methods: Studies identified in PubMed from inception to 13 May 2021 must have assessed [177Lu]Lu-DOTA-TATE as a single agent and reported outcome data for the specific NET types of interest. Results: Two independent reviewers performed the screening and data extraction, resulting in 16 publications: PPGL (n = 7), bronchial NETs (n = 6; one also included NETs of unknown origin), and MTC (n = 3). Overall, [177Lu]Lu-DOTA-TATE offers encouraging antitumor activity (overall tumor response rates and disease control rates) across NET types. Safety was favorable with most adverse events mild to moderate in severity, transient, and consistent with those seen in patients with gastroenteropancreatic (GEP)-NETs. Conclusions: [177Lu]Lu-DOTA-TATE has been used effectively in clinical practice to treat NETs of non-GEP origin.
Collapse
|
|
25
|
Horie M, Tanaka H, Suzuki M, Sato Y, Takata S, Takai E, Miyashita N, Saito A, Nakatani Y, Yachida S. An integrative epigenomic approach identifies ELF3 as an oncogenic regulator in ASCL1-positive neuroendocrine carcinoma. Cancer Sci 2023. [PMID: 36840413 DOI: 10.1111/cas.15764] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2022] [Revised: 01/16/2023] [Accepted: 02/17/2023] [Indexed: 02/26/2023] Open
Abstract
Neuroendocrine carcinoma (NEC) is a highly aggressive subtype of the neuroendocrine tumor with an extremely poor prognosis. We have previously conducted a comprehensive genomic analysis of over 100 cases of NEC of the gastrointestinal system (GIS-NEC) and unraveled its unique and organ-specific genomic drivers. However, the epigenomic features of GIS-NEC remain unexplored. In this study, we have described the epigenomic landscape of GIS-NEC and small cell lung carcinoma (SCLC) by integrating motif enrichment analysis from the assay of transposase-accessible chromatin sequencing (ATAC-seq) and enhancer profiling from a novel cleavage under targets and tagmentation (CUT&Tag) assay for H3K27ac and identified ELF3 as one of the super-enhancer-related transcriptional factors in NEC. By combining CUT&Tag and knockdown RNA sequencing for ELF3, we uncovered the transcriptional network regulated by ELF3 and defined its distinctive gene signature, including AURKA, CDC25B, CLDN4, ITGB6, and YWAHB. Furthermore, a loss-of-function assay revealed that ELF3 depletion led to poor cell viability. Finally, using gene expression of clinical samples, we successfully divided GIS-NEC patients into two subgroups according to the ELF3 signature and demonstrated that tumor-promoting pathways were activated in the ELF3 signature-high group. Our findings highlight the transcriptional regulation of ELF3 as an oncogenic transcription factor and its tumor-promoting properties in NEC.
Collapse
Affiliation(s)
- Masafumi Horie
- Department of Molecular and Cellular Pathology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.,Department of Cancer Genome Informatics, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Hidenori Tanaka
- Department of Cancer Genome Informatics, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Masami Suzuki
- Department of Cancer Genome Informatics, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Yoshihiko Sato
- Department of Cancer Genome Informatics, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - So Takata
- Department of Cancer Genome Informatics, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Erina Takai
- Department of Cancer Genome Informatics, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Naoya Miyashita
- Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.,Department of Cell Biology, Duke University School of Medicine, Durham, North Carolina, USA
| | - Akira Saito
- Department of Respiratory Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yoichiro Nakatani
- Department of Cancer Genome Informatics, Graduate School of Medicine, Osaka University, Osaka, Japan
| | - Shinichi Yachida
- Department of Cancer Genome Informatics, Graduate School of Medicine, Osaka University, Osaka, Japan.,Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Osaka, Japan.,Division of Genomic Medicine, National Cancer Center Research Institute, Tokyo, Japan
| |
Collapse
|
|
26
|
Wang JD, Sebastian C, Walther Z, Suresh T, Lacy J, Zhang X, Jain D. An Appraisal of Immunohistochemical Stain Use in Hepatic Metastasis Highlights the Effectiveness of the Individualized, Case-Based Approach: Analysis of Data From a Tertiary Care Medical Center. Arch Pathol Lab Med 2023; 147:185-192. [PMID: 35512224 DOI: 10.5858/arpa.2021-0457-oa] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/02/2021] [Indexed: 02/05/2023]
Abstract
CONTEXT.— Liver biopsy plays an important role in the clinical management of metastases and often requires workup using immunohistochemical (IHC) markers, but the approach varies among institutions. OBJECTIVE.— To evaluate the utility of a morphologic pattern-based, individualized approach in the workup of hepatic metastases. DESIGN.— All liver biopsies with metastasis between 2015 and 2018 were identified from our institutional database and were reviewed. The morphologic pattern of the metastasis and IHC markers used in each case were recorded. The final identification of primary site of the tumor was assessed based on all the available clinicopathologic data. The academic ranking and practice pattern of the pathologist signing out the case were also recorded. RESULTS.— A total of 406 liver biopsies with metastasis were identified, and the cases were classified as adenocarcinoma (253 of 406; 62%), carcinoma not otherwise specified (12 of 406; 3%), neuroendocrine neoplasm (54 of 406; 13%), poorly differentiated carcinoma (43 of 406; 11%), nonepithelial tumor (24 of 406; 6%), and squamous cell carcinoma (20 of 406; 5%). The primary site was unknown in 39% (158 of 406) at the time of liver biopsy. A primary site was determined in 97% (395 of 406) of all cases, and only 3% (11 of 406) remained true carcinoma of unknown primary. The average number of IHC markers/case in patients with known primary was 2.6, compared with 5.9 with an initial unknown primary and 9.5 in cases of true carcinoma of unknown primary. CONCLUSIONS.— An individualized, case-based approach seems to be highly cost-effective and uses fewer IHC markers compared with preset panels that often comprise 10 or more IHC markers.
Collapse
Affiliation(s)
- Jeff D Wang
- From the Department of Pathology (Wang, Sebastian, Walther, Zhang, Jain), Yale University School of Medicine, New Haven, Connecticut
| | - Christopher Sebastian
- From the Department of Pathology (Wang, Sebastian, Walther, Zhang, Jain), Yale University School of Medicine, New Haven, Connecticut
| | - Zenta Walther
- From the Department of Pathology (Wang, Sebastian, Walther, Zhang, Jain), Yale University School of Medicine, New Haven, Connecticut
| | - Tejas Suresh
- From the Section of Medical Oncology (Suresh, Lacy), Yale University School of Medicine, New Haven, Connecticut
| | - Jill Lacy
- From the Section of Medical Oncology (Suresh, Lacy), Yale University School of Medicine, New Haven, Connecticut
| | - Xuchen Zhang
- From the Department of Pathology (Wang, Sebastian, Walther, Zhang, Jain), Yale University School of Medicine, New Haven, Connecticut
| | - Dhanpat Jain
- From the Department of Pathology (Wang, Sebastian, Walther, Zhang, Jain), Yale University School of Medicine, New Haven, Connecticut
- Authors Zhang and Jain contributed equally
| |
Collapse
|
|
27
|
Živojinov M, Panić Ž, Ilić A, Ilić Sabo J, Vasilijević M, Lakić T. Morphological and immunohistochemical features of neuroendocrine neoplasms in gastroenteropancreatic tract. Arab J Gastroenterol 2023; 24:24-28. [PMID: 35927198 DOI: 10.1016/j.ajg.2022.05.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2021] [Revised: 03/16/2022] [Accepted: 05/12/2022] [Indexed: 11/29/2022]
Abstract
BACKGROUND AND AIMS Neuroendocrine neoplasms (NENs) result from neuroendocrine cell neoplastic proliferation, with both characteristics of endocrine and nerve cells. NENs arise in different localizations but the most common site is the gastrointestinal tract, including the pancreas. The morphology and frequency of NENs in our hospital were evaluated, as well as the correlation between lymph node status and Ki67 proliferative index. MATERIALS AND METHODS Retrospectively, we analyzed NEN pathohistological reports of patients who underwent surgical excision of gastroenteropancreatic tumors in the Clinical Center of Vojvodina in Novi Sad, from 2011 to 2018. The descriptive and correlation statistics were done. Chromogranin A, synaptophysin, CD56, and Ki67 were usually used as immunohistochemical markers. RESULTS The study registered 78 surgical specimens. The average age of patients was 58.88 (±17) years, whereby 53.8% were males. The most frequent site was the pancreas (29.5%), followed by the large intestine (26.9%). The mean tumor size was 3.71 (±3.13) cm. No significance was found in tumor differentiation degree (G1 = 32.1%, G2 = 26.9%, and G3 = 29.5%). Lymph node metastases were found in 47.44%. Positive correlation was found between the Ki67 index and the percentage of positive lymph nodes (r = 0.343, p = 0.046, p < 0.05, respectively). The correlation between tumor size and lymph node metastases revealed no significance in our study (r = 0.015, p = 0.480, p > 0.05, respectively). CONCLUSION Most NENs lymph node metastases originated from tumors with a high Ki67 index. The results confirm the use of proliferative index Ki67 as a prognostic marker for the presence of metastases, disease progression, and neuroendocrine tumor prognosis.
Collapse
Affiliation(s)
- Mirjana Živojinov
- Faculty of Medicine Novi Sad, University of Novi Sad, 21000, Serbia; Center for Pathology and Histology, Clinical Center of Vojvodina Novi Sad, 21000, Serbia
| | - Željka Panić
- Center for Pathology and Histology, Clinical Center of Vojvodina Novi Sad, 21000, Serbia; Faculty of Pharmacy Novi Sad, Business Academy University in Novi Sad, Serbia.
| | - Aleksandra Ilić
- Faculty of Medicine Novi Sad, University of Novi Sad, 21000, Serbia; Center for Pathology and Histology, Clinical Center of Vojvodina Novi Sad, 21000, Serbia
| | - Jelena Ilić Sabo
- Faculty of Medicine Novi Sad, University of Novi Sad, 21000, Serbia; Center for Pathology and Histology, Clinical Center of Vojvodina Novi Sad, 21000, Serbia
| | - Milena Vasilijević
- Center for Pathology and Histology, Clinical Center of Vojvodina Novi Sad, 21000, Serbia
| | - Tanja Lakić
- Faculty of Medicine Novi Sad, University of Novi Sad, 21000, Serbia; Center for Pathology and Histology, Clinical Center of Vojvodina Novi Sad, 21000, Serbia
| |
Collapse
|
|
28
|
Sammartano A, Migliari S, Serreli G, Scarlattei M, Baldari G, Ruffini L. Validation of the HPLC Analytical Method for the Determination of Chemical and Radiochemical Purity of Ga-68-DOTATATE. Indian J Nucl Med 2023; 38:1-7. [PMID: 37180199 PMCID: PMC10171759 DOI: 10.4103/ijnm.ijnm_11_22] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Revised: 03/18/2022] [Accepted: 04/04/2022] [Indexed: 02/25/2023] Open
Abstract
Purpose of the Study Ga-68-DOTA-peptides targeting somatostatin receptors have been assessed as a valuable tool in neuroendocrine tumors imaging using positron emission tomography (PET). A new selective and sensitive high-pressure liquid chromatography (HPLC) method was developed for determining chemical and radiochemical purity of Ga-68-DOTATATE (PET) tracer. The identification of peaks was achieved on a symmetry C18 column 3 μm 120Å (3.0 mm × 150 mm spherical particles) using (A) water + 0.1% trifluoroacetic acid (TFA) and (B) acetonitrile + 0.1% TFA, as the mobile phases at a flow rate of 0.600 mL/min and monitored at 220 nm. The run time was 16 min. Materials and Methods The method was validated to fulfill International Conference on Harmonization requirements and EDQM guidelines, and it included specificity, linearity, limit of detection (LOD), limit of quantification (LOQ), accuracy, and precision. Results The calibration curve was linear over the concentration range from 0.5 to 3 μg/ml, with a correlation coefficient (r2) equal to 0.999, average coefficient of variation (CV%) 2%, and average bias% did not deviate more than 5% for all concentrations. The LOD and LOQ for DOTATATE were 0.5 and 0.1 μg/mL, respectively. The method was considered precise, obtaining coefficients of variation between 0.22% and 0.52% for intraday and 0.20% and 0.61% for interday precision. Accuracy of method was confirmed with average bias% that did not deviate more than 5% for all concentrations. Conclusion All results were acceptable and this confirmed that the method is suitable for its intended use in routine quality control of Ga-68-DOTATATE to guarantee the high quality of the finished product before release.
Collapse
Affiliation(s)
- Antonino Sammartano
- Department of Nuclear Medicine and Molecular Imaging, University Hospital of Parma, Via Gramsci, Italy
| | - Silvia Migliari
- Department of Nuclear Medicine and Molecular Imaging, University Hospital of Parma, Via Gramsci, Italy
| | - Giulio Serreli
- Department of Diagnostic, Medical Physics Unit, University Hospital of Parma, Via Gramsci, Parma, Italy
| | - Maura Scarlattei
- Department of Nuclear Medicine and Molecular Imaging, University Hospital of Parma, Via Gramsci, Italy
| | - Giorgio Baldari
- Department of Nuclear Medicine and Molecular Imaging, University Hospital of Parma, Via Gramsci, Italy
| | - Livia Ruffini
- Department of Nuclear Medicine and Molecular Imaging, University Hospital of Parma, Via Gramsci, Italy
| |
Collapse
|
|
29
|
Rectal neuroendocrine neoplasms: what the radiologists should know. ABDOMINAL RADIOLOGY (NEW YORK) 2022; 47:4016-4031. [PMID: 35288791 DOI: 10.1007/s00261-022-03474-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Revised: 02/18/2022] [Accepted: 02/21/2022] [Indexed: 02/06/2023]
Abstract
Neuroendocrine neoplasms of the rectum (R-NENs) are rare; however, their incidence has increased almost threefold in the last few decades. Imaging of R-NENs includes two primary categories: anatomic/morphologic imaging comprised of endoscopic ultrasound (EUS), computed tomography (CT), magnetic resonance imaging (MRI), and functional/molecular imaging comprising of planar scintigraphy, single-photon emission computed tomography (SPECT), and positron emission tomography (PET). The management depends on stage, dimension, atypical features, histological grade, and lymphovascular invasion (LVI). Low-risk local R-NENs can be resected endoscopically, and high-risk or locally advanced neoplasms can be treated with radical surgery and lymphadenectomy and/or chemoradiation. The review article focuses on imaging illustrations and discusses applications of different imaging modalities in diagnosing and managing R-NENs.
Collapse
|
|
30
|
Gonulal B, Bilgic Y, Akbulut S, Karabulut E, Samdanci ET. Management and Survival Analysis of Gastrointestinal Neuroendocrine Tumors by Different Tumor Characteristics: Tertiary Center Experience. J Gastrointest Cancer 2022; 53:915-920. [PMID: 34524616 DOI: 10.1007/s12029-021-00709-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/05/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND Gastrointestinal neuroendocrine tumor (GI-NET) is a group of neoplasia consisting of amine and acid producing cells with different hormonal profiles. Although the entire GIS accounts for about 2% of tumors, recent research reveals that the incidence rate has increased. Given the increasing incidence in GI-NETs, more and more extensive research is needed on this subject. In this regard, the demographic and clinicopathological features of the patients diagnosed with GI-NET and their relationship with survival were investigated in the present study. METHODS Thirty-four patients diagnosed with GI-NETs between January 2009 and December 2019 at the Department of Gastroenterology, Inonu University Faculty of Medicine were analyzed retrospectively. Gender, age, tumor localization, metastasis status, tumor number, tumor diameter, tumor grade, Ki-67 index, and the relationships of these factors with overall survival were examined. RESULTS Of the patients, 61.8% included in the study were male and 38.2% were female. The average age of the patients was 60.74 years. The most common tumor location was in the stomach (26.5%) and liver (26.5%). Apart from this, 17.6% of NETs were seen in the pancreas, 11.8% in the colon, 8.8% in the rectum, 5.9% in the small intestine, and 2.9% in the appendix. No significant relationship was observed between tumor location and gender (p = .326) and age (p = .641). The tumor diameter ranged from 0.2 cm to 13.91 cm, but the average tumor diameter was 3.84 cm. Solitary tumor was found in 51.5% of cases and multiple tumors in 48.5% of cases. The most common grade was Grade 1 with 41.2% of occurrence. The average of Ki-67 index was 18.36%. There was metastasis in 52.9% of cases. The rate of medical treatment was 48.5%. The median overall survival time of the patients was 23.1 months. In addition, 1-year overall survival was 74.9%, 2-year overall survival was 44.6%, and 5-year overall survival was 35.7%. A statistically significant difference was found between tumor grade and the presence of metastasis, and the overall survival (p = .003 and p = .005). CONCLUSIONS The tumor grade and the presence of metastasis in gastrointestinal neuroendocrine tumors were found to be the most important prognostic factors affecting overall survival.
Collapse
Affiliation(s)
- Bedia Gonulal
- Department of Internal Medicine, Faculty of Medicine, Inonu University, Malatya, 44280, Turkey
| | - Yilmaz Bilgic
- Department of Gastroenterology, Faculty of Medicine, Inonu University, Malatya, 44280, Turkey.
| | - Sami Akbulut
- Department of Surgery, Faculty of Medicine, Inonu University, Malatya, 44280, Turkey
| | - Ertugrul Karabulut
- Department of Surgery, Faculty of Medicine, Inonu University, Malatya, 44280, Turkey
| | | |
Collapse
|
|
31
|
White BE, Rous B, Chandrakumaran K, Wong K, Bouvier C, Van Hemelrijck M, George G, Russell B, Srirajaskanthan R, Ramage JK. Incidence and survival of neuroendocrine neoplasia in England 1995–2018: A retrospective, population-based study. Lancet Reg Health Eur 2022; 23:100510. [PMID: 36176500 PMCID: PMC9513765 DOI: 10.1016/j.lanepe.2022.100510] [Citation(s) in RCA: 60] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Background Neuroendocrine neoplasia (NEN) incidence is rising internationally. We aimed to evaluate the epidemiology of NEN in England and examine changes in survival over time. Methods A retrospective, population-based study using nationally representative data between 1995 and 2018 from the National Cancer Registry and Analysis Service (NCRAS) in England was conducted on 63,949 tumours. Age-standardized incidence was calculated using Office for National Statistics (ONS) data. Overall survival (OS) was calculated using the Kaplan-Meier estimator. Multivariable analysis was performed using an accelerated failure time model. Findings Of 63,949 cases, 50.5% (32,309) were female. Age-adjusted incidence increased 3.7-fold between 1995 and 2018 from 2.35 to 8.61 per 100,000. In 2018, highest incidence occurred in lung (1.47 per 100,000), small intestine (1.46 per 100,000), pancreas (1.00 per 100,000) and appendix (0.95 per 100,000). In multivariable analysis, age, sex, morphology, stage, site and deprivation were independent predictors of survival (p < 0.001). Survival of the entire cohort, and by primary site, is improving over time. Interpretation NEN incidence continues to rise in England with survival improving over time. Relatively high survival compared to other cancers is an issue for long-term outcomes and funding of care. Funding Data were extracted and transferred using a grant from Neuroendocrine cancer UK.
Collapse
|
|
32
|
Hernandez-Rienda L, del Olmo-García MI, Merino-Torres JF. Impact of Diabetes Mellitus in Patients with Pancreatic Neuro-Endocrine Tumors: Causes, Consequences, and Future Perspectives. Metabolites 2022; 12:1103. [PMID: 36422243 PMCID: PMC9698930 DOI: 10.3390/metabo12111103] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Revised: 11/03/2022] [Accepted: 11/07/2022] [Indexed: 09/05/2023] Open
Abstract
Diabetes mellitus (DM) and pancreatic neuroendocrine tumors (pNETs) are two entities closely linked together. DM has been described as a risk factor for the development of pNETs and for the aggressiveness of the disease. On the other hand, DM due to pNETs is frequently undiagnosed or misclassified as type 2 DM when it is due to type 3 DM. In addition, metformin, a commonly prescribed drug for type 2 DM, has an antiproliferative property and is gaining increasing attention as an antitumor agent. This review article presents the findings published in the last few years on pNETs and DMs. Emphasis will be placed on DM as a risk factor, pNET as a risk factor for the development of type 3 DM, the management of type 3 DM on pNET, and DM as a prognostic factor in patients with pNET, as well as the future clinical implications of DM in these patients. The coexistence of DM and pNET is extensively presented. It is important to perform future clinical trials, which are necessary to establish the role of metformin on pNET disease. Increasing awareness among professionals managing pNET on the importance of a correct DM diagnosis and management of the disease must be a priority due to the implications on mortality and comorbidities it may have in these patients.
Collapse
Affiliation(s)
- Lorena Hernandez-Rienda
- Endocrinology and Nutrition Department, University and Politecnic Hospital La Fe, 46026 Valencia, Spain
- Joint Research Unit on Endocrinology, Nutrition and Clinical Dietetics, Health Research Institute Hospital La Fe-University of Valencia, 46026 Valencia, Spain
| | - Maria Isabel del Olmo-García
- Endocrinology and Nutrition Department, University and Politecnic Hospital La Fe, 46026 Valencia, Spain
- Joint Research Unit on Endocrinology, Nutrition and Clinical Dietetics, Health Research Institute Hospital La Fe-University of Valencia, 46026 Valencia, Spain
| | - Juan Francisco Merino-Torres
- Endocrinology and Nutrition Department, University and Politecnic Hospital La Fe, 46026 Valencia, Spain
- Joint Research Unit on Endocrinology, Nutrition and Clinical Dietetics, Health Research Institute Hospital La Fe-University of Valencia, 46026 Valencia, Spain
- Department of Medicine, Faculty of Medicine, University of Valencia, 46010 Valencia, Spain
| |
Collapse
|
|
33
|
Yao J, Bergsland E, Aggarwal R, Aparicio A, Beltran H, Crabtree JS, Hann CL, Ibrahim T, Byers LA, Sasano H, Umejiego J, Pavel M. DLL3 as an Emerging Target for the Treatment of Neuroendocrine Neoplasms. Oncologist 2022; 27:940-951. [PMID: 35983951 PMCID: PMC9632312 DOI: 10.1093/oncolo/oyac161] [Citation(s) in RCA: 32] [Impact Index Per Article: 10.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2022] [Accepted: 07/01/2022] [Indexed: 01/05/2023] Open
Abstract
INTRODUCTION Neuroendocrine neoplasms (NEN) are heterogeneous malignancies that can arise at almost any anatomical site and are classified as biologically distinct well-differentiated neuroendocrine tumors (NET) and poorly differentiated neuroendocrine carcinomas (NEC). Current systemic therapies for advanced disease, including targeted therapies, chemotherapy, and immunotherapy, are associated with limited duration of response. New therapeutic targets are needed. One promising target is delta-like ligand 3 (DLL3), an inhibitory ligand of the Notch receptor whose overexpression on the surface of NEN is associated with tumorigenesis. METHODS This article is a narrative review that highlights the role of DLL3 in NEN progression and prognosis, the potential for therapeutic targeting of DLL3, and ongoing studies of DLL3-targeting therapies. Classification, incidence, pathogenesis, and current management of NEN are reviewed to provide biological context and illustrate the unmet clinical needs. DISCUSSION DLL3 is overexpressed in many NENs, implicated in tumor progression, and is typically associated with poor clinical outcomes, particularly in patients with NEC. Targeted therapies using DLL3 as a homing beacon for cytotoxic activity mediated via several different mechanisms (eg, antibody-drug conjugates, T-cell engager molecules, CAR-Ts) have shown promising clinical activity in small-cell lung cancer (SCLC). DLL3 may be a clinically actionable target across NEN. CONCLUSIONS Current treatment options for NEN do not provide sustained responses. DLL3 is expressed on the cell surface of many NEN types and is associated with poor clinical outcomes. Initial clinical studies targeting DLL3 therapeutically in SCLC have been promising, and additional studies are expanding this approach to the broader group of NEN.
Collapse
Affiliation(s)
- James Yao
- Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Emily Bergsland
- Department of Medicine, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA
| | - Rahul Aggarwal
- Department of Medicine, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA
| | - Ana Aparicio
- The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Himisha Beltran
- Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA
| | - Judy S Crabtree
- Department of Genetics, Louisiana State University Health Sciences Center, New Orleans, LA, USA
| | - Christine L Hann
- Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Toni Ibrahim
- Osteoncology, Bone and Soft Tissue Sarcomas and Innovative Therapies Unit, IRCSS Istituto Ortopedico Rizzoli, Bologna, Italy
| | - Lauren A Byers
- Thoracic Head and Neck Medical Oncology, MD Anderson Cancer Center, Houston, TX, USA
| | - Hironobu Sasano
- Department of Pathology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
| | | | - Marianne Pavel
- Department of Medicine 1, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nürnberg, Erlangen, Germany
| |
Collapse
|
|
34
|
Wang S, Wei J, Guo Y, Xu Q, Lv X, Yu Y, Liu M. Construction and validation of nomograms based on the log odds of positive lymph nodes to predict the prognosis of lung neuroendocrine tumors. Front Immunol 2022; 13:987881. [PMID: 36211370 PMCID: PMC9539638 DOI: 10.3389/fimmu.2022.987881] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2022] [Accepted: 08/11/2022] [Indexed: 11/18/2022] Open
Abstract
Background This research aimed to investigate the predictive performance of log odds of positive lymph nodes (LODDS) for the long-term prognosis of patients with node-positive lung neuroendocrine tumors (LNETs). Methods We collected 506 eligible patients with resected N1/N2 classification LNETs from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015. The study cohort was split into derivation cohort (n=300) and external validation cohort (n=206) based on different geographic regions. Nomograms were constructed based on the derivation cohort and validated using the external validation cohort to predict the 1-, 3-, and 5-year cancer-specific survival (CSS) and overall survival (OS) of patients with LNETs. The accuracy and clinical practicability of nomograms were tested by Harrell’s concordance index (C-index), integrated discrimination improvement (IDI), net reclassification improvement (NRI), calibration plots, and decision curve analyses. Results The Cox proportional-hazards model showed the high LODDS group (-0.79≤LODDS) had significantly higher mortality compared to those in the low LODDS group (LODDS<-0.79) for both CSS and OS. In addition, age at diagnosis, sex, histotype, type of surgery, radiotherapy, and chemotherapy were also chosen as predictors in Cox regression analyses using stepwise Akaike information criterion method and included in the nomograms. The values of C-index, NRI, and IDI proved that the established nomograms were better than the conventional eighth edition of the TNM staging system. The calibration plots for predictions of the 1-, 3-, and 5-year CSS/OS were in excellent agreement. Decision curve analyses showed that the nomograms had value in terms of clinical application. Conclusions We created visualized nomograms for CSS and OS of LNET patients, facilitating clinicians to bring individually tailored risk assessment and therapy.
Collapse
Affiliation(s)
- Suyu Wang
- Department of Anesthesiology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
- Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
- Department of Cardiothoracic Surgery, Changzheng Hospital, Naval Medical University, Shanghai, China
| | - Juan Wei
- Department of Anesthesiology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Yibin Guo
- Department of Health Statistics, Naval Medical University, Shanghai, China
| | - Qiumeng Xu
- Department of Orthopaedics, Changzheng Hospital, Naval Medical University, Shanghai, China
| | - Xin Lv
- Department of Anesthesiology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Yue Yu
- Department of Cardiothoracic Surgery, Changzheng Hospital, Naval Medical University, Shanghai, China
- *Correspondence: Meiyun Liu, ; Yue Yu,
| | - Meiyun Liu
- Department of Anesthesiology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
- *Correspondence: Meiyun Liu, ; Yue Yu,
| |
Collapse
|
|
35
|
Fernandes CJ, Leung G, Eads JR, Katona BW. Gastroenteropancreatic Neuroendocrine Tumors. Gastroenterol Clin North Am 2022; 51:625-647. [PMID: 36153114 DOI: 10.1016/j.gtc.2022.06.002] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/21/2023]
Abstract
Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are the most common type of neuroendocrine tumors and are being increasingly identified in clinical practice. The diagnosis, staging, management, and surveillance of GEP-NETs rely heavily on endoscopy, and consequently, it is important for gastroenterologists to have a solid understanding of these tumors. This article reviews the presentation, diagnosis, and management of both localized and advanced GEP-NETs, with increased emphasis on the role of endoscopy, to enable gastroenterologists and other practitioners to have the necessary tools for the care of patients with these tumors.
Collapse
Affiliation(s)
- Conrad J Fernandes
- Department of Medicine, Hospital of the University of Pennsylvania, 3400 Civic Center Boulevard, 751 South Pavilion, Philadelphia, PA 19104, USA
| | - Galen Leung
- Division of Gastroenterology and Hepatology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, 3400 Civic Center Boulevard, 751 South Pavilion, Philadelphia, PA 19104, USA
| | - Jennifer R Eads
- Division of Hematology/Oncology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, 3400 Civic Center Boulevard, 751 South Pavilion, Philadelphia, PA 19104, USA
| | - Bryson W Katona
- Division of Gastroenterology and Hepatology, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, 3400 Civic Center Boulevard, 751 South Pavilion, Philadelphia, PA 19104, USA.
| |
Collapse
|
|
36
|
Analysis of Prognostic Risk Factors of Endoscopic Submucosal Dissection (ESD) and Curative Resection of Gastrointestinal Neuroendocrine Neoplasms. CONTRAST MEDIA & MOLECULAR IMAGING 2022; 2022:5248256. [PMID: 35854772 PMCID: PMC9286938 DOI: 10.1155/2022/5248256] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Revised: 04/08/2022] [Accepted: 06/02/2022] [Indexed: 11/22/2022]
Abstract
Objective To explore the prognostic risk factors of ESD curative resection of gastrointestinal-neuroendocrine neoplasms (GI-NENs). Methods A total of 97 patients treated with ESD successfully in our hospital were selected, their surgical site, size, number of resection lesions, operation time, intraoperative complications (such as bleeding and perforation), and treatment status were recorded, and the number of hemostatic clamps used after the postoperative follow-up results and the independent risk factors for ESD complications were obtained through the comparison between the noncomplication group and the ESD complication group using regression analysis. Results A total of 97 patients with gastrointestinal neuroendocrine tumors were treated with ESD. 61 were males, 36 were females, the ratio of male to female was 1.7 : 1, onset age was 20–78 years old, and median onset age was 50 years old. In 81 cases, tumors were located in the stomach, 10 in the duodenum, and 6 in the rectum. A total of 103 lesions were detected by endoscopy, including 1 case with 2 sites in the stomach, 5 cases with 2 sites in the rectum, and the rest were single. The tumor diameter was 0.3 ∼ 2.5 cm, and the median diameter was 0.6 cm; there were 25 sites with a diameter less than 5 cm. There were 57 places with 10 mm, 16 places with 10–15 mm, and 5 places with >15 mm. All ESD operations were performed in one piece, with a total resection rate of 100%; 89.6% (60/67) of postoperative pathology showed negative basal, and 90.3% (56/62) showed negative resection margin, with a complete resection rate of 88.9% (48/54). ESD's operation time is 6 ∼ 66 min, and the median time is 18 min. During the operation, 5 cases had small amount of bleeding, 3 cases were perforated, 2 cases of delayed postoperative bleeding, 1 case of bleeding was caused by the patient's failure to follow the advice of the doctor to eat a large amount of solid food too early, and 1 case of delayed perforation (all recovered and discharged). ESD operation that bled, age, gender, and perforation location, pathological grade, pathological classification, tumor diameter, tumor surface, operation time, number of titanium clips, origin, echo uniformity, and echo level were statistically insignificant (P > 0.05). Postoperative bleeding was related to the operation time (P=0.017), but it was not an independent risk factor for postoperative bleeding (P=0.118; OR, 0.226; 95% CI, 0.035–1.461). 59 cases were followed up by endoscopy after the operation, and recurrence or no new tumors were found. Conclusion ESD is an effective and safe treatment method for gastrointestinal neuroendocrine tumors with a diameter of 1-2 cm without invading the muscularis propria. The intraoperative complications seem to have little relationship with the patient; postoperative delayed bleeding is closely related to the ESD operation time but it is not an independent risk factor.
Collapse
|
|
37
|
Takeda Y, Kobayashi N, Kessoku T, Okubo N, Suzuki A, Tokuhisa M, Miwa H, Udaka N, Ichikawa Y. Case reports: chemoradiotherapy for locally advanced neuroendocrine carcinoma of the gallbladder. Clin J Gastroenterol 2022; 15:803-808. [PMID: 35653037 PMCID: PMC9334423 DOI: 10.1007/s12328-022-01645-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Accepted: 05/09/2022] [Indexed: 11/11/2022]
Abstract
Neuroendocrine carcinoma (NEC) is a rare subtype of malignant gallbladder tumor. Although surgical resection is the only potentially curative therapy for gallbladder NEC, most cases are surgically unresectable because of advanced stage disease and/or biologically aggressive behavior. The standard palliative treatment for malignant gallbladder tumors is chemotherapy; however, the efficacy of chemoradiotherapy in the treatment of gallbladder tumors is controversial. Here, we report a case of gallbladder NEC that showed a durable response to chemoradiotherapy. A 68-year-old Japanese man presented with a huge gallbladder tumor with liver and duodenal invasion. Pathological findings revealed poorly differentiated NEC of the gallbladder. After seven cycles of chemotherapy comprising cisplatin and irinotecan, computed tomography (CT) revealed remarkable tumor shrinkage, but an enlarged portal lymph node. The patient was treated with 50.4 Gy in 28 fractions with two cycles of cisplatin and etoposide. After chemoradiotherapy, the enlarged lymph node also decreased in size. Maximum standardized uptake value of fluorodeoxyglucose-positron emission tomography/CT(FDG-PET/CT) changed from 8.2 to physiological accumulation. We defined this condition as a complete response on both enhanced CT and FDG-PET/CT; therefore, we did not perform systemic treatment and only observed his condition. This patient remained healthy with no recurrence at 3 years after chemoradiotherapy.
Collapse
Affiliation(s)
- Yuma Takeda
- Department of Oncology, Yokohama City University School of Medicine Graduate School of Medicine, Yokohama, Japan
| | - Noritoshi Kobayashi
- Department of Oncology, Yokohama City University School of Medicine Graduate School of Medicine, Yokohama, Japan.
| | - Takaomi Kessoku
- Department of Palliative Medicine, Yokohama City University Hospital, Yokohama, Japan.,Department of Gastroenterology and Hepatology, Yokohama City University School of Medicine Graduate School of Medicine, Yokohama, Japan
| | - Naoki Okubo
- Department of Oncology, Yokohama City University School of Medicine Graduate School of Medicine, Yokohama, Japan
| | - Akihiro Suzuki
- Department of Oncology, Yokohama City University School of Medicine Graduate School of Medicine, Yokohama, Japan
| | - Motohiko Tokuhisa
- Department of Oncology, Yokohama City University School of Medicine Graduate School of Medicine, Yokohama, Japan
| | - Haruo Miwa
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Naoko Udaka
- Department of Pathology, Yokohama City University Hospital, 3-9, Fuku-ura, Kanazawa-ku, Yokohama, 2360004, Japan
| | - Yasushi Ichikawa
- Department of Oncology, Yokohama City University School of Medicine Graduate School of Medicine, Yokohama, Japan
| |
Collapse
|
|
38
|
Zhang X, Lu L, Liu J, Liu W, Li L, Wei Y, Fan J, Ma L, Gong P. A Nomogram to Accurately Identify Pancreatic Neuroendocrine Tumors Metastasizing to Distant Organs: A Study Based on Two National Population-Based Cohorts From the United States and China. Clin Med Insights Oncol 2022; 16:11795549221099853. [PMID: 35620244 PMCID: PMC9127860 DOI: 10.1177/11795549221099853] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Accepted: 04/17/2022] [Indexed: 11/17/2022] Open
Abstract
Background: Distant organ metastasis is the leading cause of death in pancreatic neuroendocrine tumor (pNET) patients. In the present study, we aimed to develop and validate a nomogram that could accurately identify pNET metastasizing to distant organs. Methods: The cases extracted from the Surveillance, Epidemiology, and End Results (SEER) program were assigned to the training cohort and validation cohort. The cases from the Chinese Gastrointestinal Neuroendocrine Tumors program were assigned to the external validation cohort. The strategy was developed with the support of a nomogram, and the predictive value of this strategy was evaluated by the receiver operating characteristic (ROC) curve analysis. Results: In total, 2024 American cases were involved in the present study. Besides, 1450 and 574 patients were allocated into training and internal validation cohorts, respectively. In addition, 122 Chinese patients were assigned to the external validation cohort. The results of the univariate logistic regression analysis suggested that tumor grade, tumor size, and the number of metastatic lymph nodes were the risk of metastasis to distant organs, and these 3 clinicopathological characteristics were used to develop the nomogram. We observed that the accuracy of the nomogram for predicting metastasis to distant organs was 0.797, 0.819, and 0.837 in the training cohort, internal validation cohort, and external validation cohort, respectively. Conclusions: A predictive nomogram was developed and validated, and it showed an acceptable performance in predicting metastasis to distant organs. The results will enable clinicians to identify pNETs, metastasizing to distant organs, and develop an effective individualized therapeutic strategy for these patients.
Collapse
Affiliation(s)
- Xianbin Zhang
- Department of General Surgery and Institute of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, Shenzhen, China.,Guangdong Provincial Key Laboratory for Biomedical Measurements and Ultrasound Imaging, School of Biomedical Engineering, Shenzhen University Health Science Center, Shenzhen, China.,Carson International Cancer Center and Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Shenzhen University Health Science Center, Shenzhen, China
| | - Lili Lu
- Department of General Surgery and Institute of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, Shenzhen, China.,Carson International Cancer Center and Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Shenzhen University Health Science Center, Shenzhen, China
| | - Jun Liu
- Department of General Surgery and Institute of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, Shenzhen, China.,Department of Epidemiology, Dalian Medical University, Dalian, China
| | - Weihan Liu
- Department of General Surgery and Institute of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, Shenzhen, China.,Department of Epidemiology, Dalian Medical University, Dalian, China
| | - Li Li
- Department of General Surgery and Institute of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, Shenzhen, China.,Carson International Cancer Center and Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Shenzhen University Health Science Center, Shenzhen, China
| | - Yushan Wei
- Department of Scientific Research, First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Jinhu Fan
- Department of Cancer Epidemiology, Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Li Ma
- Department of Epidemiology, Dalian Medical University, Dalian, China
| | - Peng Gong
- Department of General Surgery and Institute of Precision Diagnosis and Treatment of Gastrointestinal Tumors, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, Shenzhen, China.,Carson International Cancer Center and Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Shenzhen University Health Science Center, Shenzhen, China
| |
Collapse
|
|
39
|
Deleu AL, Laenen A, Decaluwé H, Weynand B, Dooms C, De Wever W, Jentjens S, Goffin K, Vansteenkiste J, Van Laere K, De Leyn P, Nackaerts K, Deroose CM. Value of [ 68Ga]Ga-somatostatin receptor PET/CT in the grading of pulmonary neuroendocrine (carcinoid) tumours and the detection of disseminated disease: single-centre pathology-based analysis and review of the literature. EJNMMI Res 2022; 12:28. [PMID: 35524900 PMCID: PMC9079198 DOI: 10.1186/s13550-022-00900-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2022] [Accepted: 04/25/2022] [Indexed: 12/12/2022] Open
Abstract
BACKGROUND Although most guidelines suggest performing a positron emission tomography/computed tomography (PET/CT) with somatostatin receptor (SSTR) ligands for staging of pulmonary carcinoid tumours (PC), only a limited number of studies have evaluated the role of this imaging tool in this specific patient population. The preoperative differentiation between typical carcinoid (TC) and atypical carcinoid (AC) and the extent of dissemination (N/M status) are crucial factors for treatment allocation and prognosis of these patients. Therefore, we performed a pathology-based retrospective analysis of the value of SSTR PET/CT in tumour grading and detection of nodal and metastatic involvement of PC and compared this with the previous literature and with [18F]FDG PET/CT in a subgroup of patients. METHODS SSTR PET/CT scans performed between January 2007 and May 2020 in the context of PC were included. If available, [18F]FDG PET/CT images were also evaluated. The maximum standardized uptake (SUVmax) values of the primary tumour, of the pathologically examined hilar and mediastinal lymph node stations, as well as of the distant metastases, were recorded. Tumoural SUVmax values were related to the tumour type (TC versus AC) for both SSTR and [18F]FDG PET/CT in diagnosing and differentiating both tumour types. Nodal SUVmax values were compared to the pathological status (N+ versus N-) to evaluate the diagnostic accuracy of SSTR PET/CT in detecting lymph node involvement. Finally, a mixed model analysis of all pathologically proven distant metastatic lesions was performed. RESULTS A total of 86 SSTR PET/CT scans performed in 86 patients with PC were retrospectively analysed. [18F]FDG PET/CT was available in 46 patients. Analysis of the SUVmax values in the primary tumour showed significantly higher SSTR uptake in TC compared with AC (median SUVmax 18.4 vs 3.8; p = 0.003) and significantly higher [18F]FDG uptake in AC compared to TC (median SUVmax 5.4 vs 3.5; p = 0.038). Receiver operating characteristic (ROC) curve analysis resulted in an area under the curve (AUC) of 0.78 for the detection of TC on SSTR PET/CT and of 0.73 for the detection of AC on [18F]FDG PET/CT. A total of 267 pathologically evaluated hilar and mediastinal lymph node stations were analysed. ROC analysis of paired SSTR/[18F]FDG SUVmax values for the detection of metastasis of TC in 83 lymph node stations revealed an AUC of 0.91 for SSTR PET/CT and of 0.74 for [18F]FDG PET/CT (difference 0.17; 95% confidence interval - 0.03 to 0.38; p = 0.10). In a sub-cohort of 10 patients with 12 distant lesions that were pathologically examined due to a suspicious aspect on SSTR PET/CT, a positive predictive value (PPV) of 100% was observed. CONCLUSION Our findings confirm the higher SSTR ligand uptake in TC compared to AC and vice versa for [18F]FDG uptake. More importantly, we found a good diagnostic performance of SSTR PET/CT for the detection of hilar and mediastinal lymph node metastases of TC. Finally, a PPV of 100% for SSTR PET/CT was found in a small sub-cohort of patients with pathologically investigated distant metastatic lesions. Taken together, SSTR PET/CT has a very high diagnostic value in the TNM assessment of pulmonary carcinoids, particularly in TC, which underscores its position in European guidelines.
Collapse
Affiliation(s)
- Anne-Leen Deleu
- Nuclear Medicine, University Hospitals Leuven, Herestraat 49, 3000, Louvain, Belgium
| | - Annouschka Laenen
- Interuniversity Institute for Biostatistics and Statistical Bioinformatics, Louvain, Belgium
| | | | - Birgit Weynand
- Pathology, University Hospitals Leuven, Louvain, Belgium
| | - Christophe Dooms
- Department of Respiratory Diseases and Respiratory Oncology Unit, University Hospitals Leuven, Louvain, Belgium
| | | | - Sander Jentjens
- Nuclear Medicine, University Hospitals Leuven, Herestraat 49, 3000, Louvain, Belgium
| | - Karolien Goffin
- Nuclear Medicine, University Hospitals Leuven, Herestraat 49, 3000, Louvain, Belgium
- Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology KU Leuven, Louvain, Belgium
| | - Johan Vansteenkiste
- Department of Respiratory Diseases and Respiratory Oncology Unit, University Hospitals Leuven, Louvain, Belgium
| | - Koen Van Laere
- Nuclear Medicine, University Hospitals Leuven, Herestraat 49, 3000, Louvain, Belgium
- Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology KU Leuven, Louvain, Belgium
| | - Paul De Leyn
- Thoracic Surgery, University Hospitals Leuven, Louvain, Belgium
| | - Kristiaan Nackaerts
- Department of Respiratory Diseases and Respiratory Oncology Unit, University Hospitals Leuven, Louvain, Belgium
| | - Christophe M Deroose
- Nuclear Medicine, University Hospitals Leuven, Herestraat 49, 3000, Louvain, Belgium.
- Nuclear Medicine and Molecular Imaging, Department of Imaging and Pathology KU Leuven, Louvain, Belgium.
| |
Collapse
|
|
40
|
Kiesewetter B, Mazal P, Kretschmer-Chott E, Mayerhoefer ME, Raderer M. Pulmonary neuroendocrine tumours and somatostatin receptor status: an assessment of unlicensed use of somatostatin analogues in the clinical practice. ESMO Open 2022; 7:100478. [PMID: 35525183 PMCID: PMC9271480 DOI: 10.1016/j.esmoop.2022.100478] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Revised: 03/14/2022] [Accepted: 03/18/2022] [Indexed: 11/30/2022] Open
Abstract
Background The use of somatostatin analogues (SSAs) has not been formally approved in pulmonary neuroendocrine tumours (NETs) in the absence of positive controlled trials, even though it is recommended as a potential therapeutic option in recent guidelines. Patients and methods We have assessed the use of SSA in the general practice in Austria by retrospectively analysing patients with pulmonary NETs referred to our European Neuroendocrine Tumor Society centre in Vienna for second opinion or further therapy. In addition, we have analysed the somatostatin receptor (SSTR) expression of those patients by immunohistochemistry (IHC) and SSTR imaging, e.g. 68Ga-DOTANOC-positron emission tomography/computed tomography, and whether such analyses had been carried out before referral at our centre. Results Out of 34 patients (19 atypical and 15 typical carcinoids) with metastatic or advanced disease, 10/34 (29%) had been prescribed SSA before referral. No IHC for SSTR had been carried out, and only 9/34 (27%) had undergone SSTR imaging by nuclear medicine. Sufficient material for IHC was available in 29/34 (85%) patients and SSTR-IHC was rated negative in 13/29 (45%), weakly positive in 4/29 (14%), moderately positive in 5/29 (17%) and strongly positive in 7/29 (24%) patients. On SSTR imaging, 8/34 patients (24%) were positive, 13/34 (38%) negative and 13/34 patients (38%) showed a mix of positive and negative NET lesions. In 11/29 (38%) patients with both IHC and imaging available, discordance of SSTR expression on imaging and histological assessment was detected. Conclusions These data show that uncritical use of SSA should be discouraged, and assessment of SSTR, preferably by imaging, is mandatory before prescription of SSA in pulmonary NETs.
SSAs are not formally approved in pulmonary NETs. SSAs are recommended as a potential therapeutic option for advanced lung NETs in guidelines. We assessed the use of SSAs for lung NET in the general practice in Austria. Only 27% had undergone SSTR imaging before referral and receptor status was highly heterogeneous. Our data emphasize that uncritical use of SSAs should be discouraged; assessment of SSTRs is recommended.
Collapse
Affiliation(s)
| | | | - E Kretschmer-Chott
- Departments of Biomedical Imaging and Image-guided Therapy, Division of Nuclear Medicine, Medical University of Vienna, Vienna, Austria
| | - M E Mayerhoefer
- Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, USA; Department of Biomedical Imaging and Image-guided Therapy, Division of General and Paediatric Radiology, Medical University of Vienna, Vienna, Austria
| | - M Raderer
- Departments of Medicine I, Division of Oncology.
| |
Collapse
|
|
41
|
Koizumi T, Otsuki K, Tanaka Y, Kanda S. Epidemiology of neuroendocrine neoplasmas in Japan: based on analysis of hospital-based cancer registry data, 2009 - 2015. BMC Endocr Disord 2022; 22:105. [PMID: 35443668 PMCID: PMC9022253 DOI: 10.1186/s12902-022-01016-4] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2021] [Accepted: 04/04/2022] [Indexed: 11/24/2022] Open
Abstract
PURPOSE Neuroendocrine neoplasms are rare disease and could originate from throughout the body, however, there have been little epidemiological studies in Japan, especially the organ distribution. This study was to examine the epidemiological information of neuroendocrine neoplasms in the Japanese population using data from a hospital-based cancer registry. METHODS Using data from the national database of hospital-based cancer registries, we examined the organ distribution, the stage and initial treatment of neuroendocrine neoplasms newly diagnosed and treated in designated and non-designated cancer care hospitals between 2009 and 2015. In the present study, neuroendocrine neoplasms consisted of neuroendocrine tumors and carcinoma. RESULTS A total of 33,215 (17,485 neuroendocrine carcinomas and 15,730 neuroendocrine tumors) cases were diagnosed. The majority in neuroendocrine carcinoma occur in lung (31.1%) followed in decreasing frequency by stomach (12.9%), pancreas (7.5%), rectum (6.7%) and esophagus (5.8%). On the other hand, the half of neuroendocrine tumor originated rectum (50.9%) and followed by pancreas (13.9%), duodenum (9.0%), lung/bronchus (8.9%), and stomach (8.7%). Neuroendocrine carcinoma presented at more advanced stage and higher age than neuroendocrine tumors. Most cases of neuroendocrine tumors were treated surgically, while half of neuroendocrine carcinomas were treated with non-surgical therapy consisting of chemotherapy with or without radiotherapy. CONCLUSIONS Our results demonstrated that neuroendocrine neoplasms could originate from various organs and the site distribution was different between neuroendocrine carcinoma and tumor. The national database of hospital-based cancer registries in Japan is a valuable source for evaluating the organ distribution of the rare systemic disease.
Collapse
Affiliation(s)
- Tomonobu Koizumi
- Department of Hematology and Medical Oncology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan.
| | - Kengo Otsuki
- Department of Hematology and Medical Oncology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan
| | - Yuriko Tanaka
- Department of Hematology and Medical Oncology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan
| | - Shintaro Kanda
- Department of Hematology and Medical Oncology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano, 390-8621, Japan
| |
Collapse
|
|
42
|
Gerbaudo VH, Latif MA. A Step Forward in PET-Based Quantitation of G3 Neuroendocrine Tumor Aggressiveness - The FDZ Score…. Acad Radiol 2022; 29:1317-1319. [PMID: 35365399 DOI: 10.1016/j.acra.2022.03.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Accepted: 03/01/2022] [Indexed: 12/01/2022]
Affiliation(s)
- Victor H Gerbaudo
- Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, MA 02115.
| | - Muhammad A Latif
- Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Brigham and Women's Hospital and Harvard Medical School, 75 Francis Street, Boston, MA 02115
| |
Collapse
|
|
43
|
Sun TY, Hendifar A, Padda SK. Lung Neuroendocrine Tumors: How Does Molecular Profiling Help? Curr Oncol Rep 2022; 24:819-824. [PMID: 35305210 DOI: 10.1007/s11912-022-01253-9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/15/2021] [Indexed: 01/01/2023]
Abstract
PURPOSE OF REVIEW Lung neuroendocrine tumors (NETs)-typical carcinoids and atypical carcinoids-have unique molecular alterations that are distinct from neuroendocrine carcinomas of the lung and non-small cell lung cancers. Here, we review the role of molecular profiling in the prognosis and treatment of lung NETs. RECENT FINDINGS There have been no recently identified molecular prognostic factors for lung NETs and none that have been routinely used to guide management of patients with lung NETs. Previous findings suggest that patients with loss of chromosome 11q may have a worse prognosis along with upregulation of anti-apoptotic pathways (e.g., loss of CD44 and OTP protein expression). Lung NETs rarely harbor driver mutations commonly found in non-small cell lung cancer (NSCLC) or TP53/RB1 mutations found universally in small cell lung cancer. Lung NETs also have low tumor mutation burden and low PD-L1 expression. Everolimus, an mTOR inhibitor and the only FDA approved therapy for unresectable lung NETs, is an effective treatment but the presence of a molecular alteration in the PI3K/AKT/mTOR pathway is not known to predict treatment response. The predominant mutations in lung NETs occur in genes regulating chromatin remodeling and histone modification, with potential targeted therapies emerging in clinical trials. Lung NETs have recurring alterations in genes that regulate the epigenome. Future targeted therapy interfering with epigenetic pathways may hold promise.
Collapse
Affiliation(s)
- Thomas Yang Sun
- Department of Medicine, Division of Oncology, Stanford University School of Medicine, 875 Blake Wilbur Drive, Stanford, CA, USA
| | - Andrew Hendifar
- Department of Medicine, Division of Oncology, Cedars-Sinai Medical Center, 127 S San Vicente Blvd, 7th Floor, Los Angeles, CA, USA
| | - Sukhmani K Padda
- Department of Medicine, Division of Oncology, Cedars-Sinai Medical Center, 127 S San Vicente Blvd, 7th Floor, Los Angeles, CA, USA.
| |
Collapse
|
|
44
|
Abstract
PURPOSE OF REVIEW The field of neuroendocrine oncology has changed much since the time of Oberndorfer first described and coined the term carcinoid. The purpose of this review is to summarize recent findings and highlight clinically relevant updates in the management of NENs, particularly those that are practice changing. RECENT FINDINGS Neuroendocrine tumors (NETs) have replaced carcinoid tumor, for the most part. The classification of neuroendocrine neoplasms (NENs) improved, and the epidemiological understanding of this disease group also expanded with global collaborations and maturation of large tumor registries. Clarity in the utility of some NET biomarkers continues to be evolving. Knowledge of molecular drivers of tumorigenesis increases, and scientific/technological advancements lead the way to multiple drug approvals for the treatment of advanced NETs. The incidence and prevalence of NENs continue to increase, and patients are living longer. Better understanding of molecular drivers and further understanding of the role of immunotherapy in NENs will further elevate the level of care and transform care for all patients with NENs.
Collapse
|
|
45
|
Massironi S, Facciotti F, Cavalcoli F, Amoroso C, Rausa E, Centonze G, Cribiù FM, Invernizzi P, Milione M. Intratumor Microbiome in Neuroendocrine Neoplasms: A New Partner of Tumor Microenvironment? A Pilot Study. Cells 2022; 11:692. [PMID: 35203339 PMCID: PMC8870382 DOI: 10.3390/cells11040692] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2022] [Revised: 02/09/2022] [Accepted: 02/11/2022] [Indexed: 02/05/2023] Open
Abstract
Neuroendocrine neoplasms (NENs) are rare neoplasms with heterogeneous clinical behavior. Alteration in human microbiota was reported in association with carcinogenesis in different solid tumors. However, few studies addressed the role of microbiota in NEN. We here aimed at evaluating the presence of bacterial infiltration in neuroendocrine tumoral tissue. To assess the presence of bacteria, 20 specimens from pancreatic NEN (pan-NEN) and 20 from intestinal NEN (I-NEN) were evaluated through Fluorescent In situ Hybridization and confocal microscopy. Demographic data, pre-operative investigations, operative findings, pathological diagnosis, follow-up, and survival data were evaluated. Among I-NEN, bacteria were detected in 15/20 (75%) specimens, with high variability in microbial distribution. In eight patients, a high infiltration of microorganisms was observed. Among pan-NEN, 18/20 (90%) showed microorganisms' infiltration, with a homogeneous microbial distribution. Bacterial localization in pan-NEN was observed in the proximity of blood vessels. A higher bacterial infiltration in the tumoral specimen as compared with non-tumoral tissue was reported in 10/20 pan-NEN (50%). No significant differences were observed in mean bacterial count according to age, sex, ki67%, site, tumor stage. Mean bacterial count did not result to be a predictor of disease-specific survival. This preliminary study demonstrates the presence of a significant microbiota in the NEN microenvironment. Further research is needed to investigate the potential etiological or clinical role of microbiota in NEN.
Collapse
Affiliation(s)
- Sara Massironi
- Division of Gastroenterology, Center for Autoimmune Liver Diseases, Ospedale San Gerardo, Department of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy;
| | - Federica Facciotti
- Department of Biotechnology and Bioscience, University of Milano-Bicocca, 20126 Milan, Italy;
| | - Federica Cavalcoli
- Diagnostic and Therapeutic Endoscopy Unit, Fondazione IRCCS Istituto Nazionale Tumori, 20133 Milan, Italy;
| | - Chiara Amoroso
- Department of Experimental Oncology, European Institute of Oncology IRCCS, 20141 Milan, Italy;
| | - Emanuele Rausa
- General, Emergency and Trauma Surgery Department, Papa Giovanni XXIII Hospital, 24121 Bergamo, Italy;
| | - Giovanni Centonze
- First Pathology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy; (G.C.); (M.M.)
| | - Fulvia Milena Cribiù
- Division of Pathology, Fondazione IRCCS Cá Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy;
| | - Pietro Invernizzi
- Division of Gastroenterology, Center for Autoimmune Liver Diseases, Ospedale San Gerardo, Department of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy;
| | - Massimo Milione
- First Pathology Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy; (G.C.); (M.M.)
| |
Collapse
|
|
46
|
Matsuoka S, Koizumi T, Otsuki K, Tanaka Y, Kanda S, Ide S, Mishima S, Takeda T, Miura K, Eguchi T, Hamanaka K, Shimizu K. Epidemiological analysis of lung and mediastinal neuroendocrine neoplasms in Japan based on the national database. Cancer Epidemiol 2022; 77:102116. [PMID: 35144127 DOI: 10.1016/j.canep.2022.102116] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2021] [Revised: 01/20/2022] [Accepted: 01/22/2022] [Indexed: 01/09/2023]
Abstract
BACKGROUND Neuroendocrine neoplasms (NENs) are rare and can originate from any body part. However, there are only few epidemiological studies, especially on lung and mediastinal NENs. This study investigated the epidemiological trends and differences between lung and mediastinal NENs in Japan. METHODS Patients with lung and mediastinal NENs were identified in a national hospital-based cancer registry between 2009 and 2015 in Japan. NENs were subclassified into neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs). NECs were further subdivided into large neuroendocrine carcinomas (LCNECs) and small cell carcinomas (SCCs). We examined the patient characteristics: sex, age, histology, year of diagnosis, diagnostic opportunity, and initial treatment. RESULTS We identified 48,433 patients with 47,888 lung (98.9%) and 545 mediastinal (1.1%) NENs. The commonest subtype of lung NENs was SCCs (87%), followed by LCNECs (10%) and NETs (3%). In the mediastinum, SCCs were also the commonest (48%), followed by NETs (38%) and LCNECs (14%). The number of lung NEN annually increased; however, that of mediastinal NENs did not change over time. The mean age of patients with lung NETs was lower than that of patients with lung LCNECs and SCCs (NETs, 62 ± 14 years; LCNECs, 70 ± 9 years; SCCs, 71 ± 9 years; p < .001). The lung and mediastinal NENs were mainly detected based on symptoms, except for lung NETs. Surgical intervention, including multimodal therapy, was performed for 89.3% of lung NETs (surgery alone: 83.6%), while only 15.6% of lung NECs were treated with surgery. For the mediastinum, 75.9% of NETs were treated with surgery, with 27.1% of cases treated with surgery plus multimodal therapy. Surgery was performed more frequently for mediastinal NECs (37%) than for lung NECs (15.6%). CONCLUSIONS This study highlights differences in trends of lung and mediastinal NENs. This study's findings support the importance of epidemiological evaluations based on the primary sites and histological subtypes.
Collapse
Affiliation(s)
- Shunichiro Matsuoka
- Division of General Thoracic Surgery, Department of Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan
| | - Tomonobu Koizumi
- Department of Hematology and Medical Oncology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan.
| | - Kengo Otsuki
- Department of Hematology and Medical Oncology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan
| | - Yuriko Tanaka
- Department of Hematology and Medical Oncology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan
| | - Shintaro Kanda
- Department of Hematology and Medical Oncology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan
| | - Shogo Ide
- Division of General Thoracic Surgery, Department of Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan
| | - Shuji Mishima
- Division of General Thoracic Surgery, Department of Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan
| | - Tetsu Takeda
- Division of General Thoracic Surgery, Department of Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan
| | - Kentaro Miura
- Division of General Thoracic Surgery, Department of Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan
| | - Takashi Eguchi
- Division of General Thoracic Surgery, Department of Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan
| | - Kazutoshi Hamanaka
- Division of General Thoracic Surgery, Department of Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan
| | - Kimihiro Shimizu
- Division of General Thoracic Surgery, Department of Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan
| |
Collapse
|
|
47
|
Şentürk M, Acar B, Yildirim MA, Çakir M, Küçükkartallar T, Vatansev C. Clinicopathological Characteristics of Gastroenteropancreatic Neuroendocrine Tumors: 10 Years of Experience From a Single Center. Pancreas 2022; 51:159-163. [PMID: 35404891 DOI: 10.1097/mpa.0000000000001981] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
OBJECTIVES Gastorenteropancreatic neuroendocrine (GEP-NET) tumors are the second most common tumors of the gastrointestinal tract. We aimed to investigate the clinicopathological features and factors affecting the prognosis of patients with GEP-NET. METHODS Clinicopathological features of 158 patients were evaluated, including tumor location, TNM stage and grade, pathological features, presence of lymph nodes and distant metastases at the time of diagnosis, maximum tumor diameter and treatment details. Also, follow-up information was analyzed to discover possible prognostic factors. RESULTS The most common primary site is pancreas (45.6%, n = 72). Most of the GEP-NETs were nonfunctional (93.6%, n = 148). Of the 158 patients, 94 (59.5%) were grade 1, 46 (29.1%) grade 2, and 18 (11.4%) grade 3. The 1-year, 3-year, and 5-year survival rates were 82.3% (130/158), 61.4% (70/114), and 47.2% (35/74), respectively. In multivariate analysis, histological grade (P = 0.04) and TNM stage (P < 0.001) were independent prognostic factors for survival in patients with GEP-NET. CONCLUSIONS They are increasing in frequency and are the most common tumors in the pancreas. Nonfunctional tumors made up the majority of cases. The main treatment was surgical resection. Histological grade and TNM stage are independent prognostic factors.
Collapse
Affiliation(s)
- Mustafa Şentürk
- From the Department of General Surgery, Necmettin Erbakan University Meram Faculty of Medicine, Konya, Turkey
| | | | | | | | | | | |
Collapse
|
|
48
|
Zhao J, Wang H. Differential diagnostic value of 18F-FDG PET/CT in pulmonary carcinoids versus hamartomas. Acad Radiol 2022; 29 Suppl 2:S41-S46. [PMID: 33183953 DOI: 10.1016/j.acra.2020.10.022] [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: 09/19/2020] [Revised: 10/21/2020] [Accepted: 10/21/2020] [Indexed: 11/25/2022]
Abstract
RATIONALE AND OBJECTIVE To assess the possibility of differentiating pulmonary carcinoids from hamartomas and typical from atypical carcinoids by means of 18F-FDG PET/CT. MATERIALS AND METHODS We retrospectively reviewed 139 patients with pathologically proven pulmonary carcinoids and hamartomas who underwent 18F-FDG PET/CT before surgical resection. Receiver operating characteristics curves were calculated to determine the potential of SUVmax to discriminate between pulmonary carcinoids and hamartomas, typical and atypical carcinoids. The correlation between SUVmax and tumor size was analyzed by Spearman correlation analysis. RESULTS SUVmax was significantly higher in pulmonary carcinoids than in hamartomas (p<0.001), and also higher in atypical carcinoids than in typical carcinoids (p = 0.034). With a SUVmax of 2.0 as a cutoff, the sensitivity, specificity, positive predictive value, and negative predictive value for 18F-FDG PET/CT to differentiate pulmonary carcinoids from hamartomas were 85.3%, 82.9%, 61.7%, and 94.6%, respectively. The cutoff value of SUVmax for differentiating atypical carcinoids from typical carcinoids was 4.1. The area under the receiver operating characteristics curve of SUVmax was 0.900 for carcinoids and hamartomas, and 0.722 for typical and atypical carcinoids. SUVmax was correlated with maximum tumor size in pulmonary carcinoids (r = 0.658, p <0.001) and in pulmonary hamartomas (r = 0.672, p <0.001). CONCLUSION 18F-FDG PET/CT might be a useful tool in the differential diagnosis of carcinoids and hamartomas, and can also distinguish atypical from typical carcinoids. This may facilitate improved selection of patients for surgical resection and radiological follow-up.
Collapse
|
|
49
|
Coelho S, Costa C, Santos AP, Souteiro P, Oliveira J, Oliveira J, Azevedo I, Torres I, Bento MJ. Pancreatic neuroendocrine neoplasms: survival trend analysis of a comprehensive center. ENDOCRINE ONCOLOGY (BRISTOL, ENGLAND) 2022; 2:32-41. [PMID: 37435456 PMCID: PMC10259287 DOI: 10.1530/eo-22-0043] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Accepted: 04/20/2022] [Indexed: 07/13/2023]
Abstract
Objectives Therapeutic options for pancreatic neuroendocrine neoplasia (Pan-NEN) have increased over the last decade. We aim to understand the evolution of the prognosis of patients with diagnosis of Pan-NEN within a 12-year period, considering the implementation of new treatments. Methods This study is a retrospective cohort study of patients diagnosed with Pan-NENs between 2006 and 2017. Survival outcome estimates were calculated by Kaplan-Meier method. The impact of baseline clinicopathological characteristics on survival was explored with the use of Cox proportional hazard model. Results Of the 97 patients, 77 (79.9%) had well-differentiated neuroendocrine tumor (NET) according to WHO 2010 classification, and 52 (53.6%) had localized or locoregional disease. There were no differences between clinicopathological characteristics and survival outcomes when comparing patients diagnosed between 2006-2011 and 2012-2017. Neuroendocrine carcinoma - HR 2.76, 95% CI 1.17-6.55 - and stages III and IV at diagnosis were independent poor prognostic factors - HR 6.02, 95% CI 2.22-16.33 and HR 6.93, 95% CI 2.94-16.32, respectively. Conclusions The new therapeutic approaches did not induce better survival outcomes on Pan-NEN in recent years. This is possibly due to the indolent nature of NET grades 1 and 2, even metastatic, allowing patients to be submitted to new target therapies along their disease course.
Collapse
Affiliation(s)
- Sara Coelho
- Department of Medical Oncology, Portuguese Oncology Institute of Porto, EPE, Porto, Portugal
| | - Cláudia Costa
- Department of Endocrinology, Portuguese Oncology Institute of Porto, EPE, Porto, Portugal
| | - Ana Paula Santos
- Department of Endocrinology, Portuguese Oncology Institute of Porto, EPE, Porto, Portugal
- Research Center, Portuguese Oncology Institute of Porto, EPE, Porto, Portugal
| | - Pedro Souteiro
- Department of Endocrinology, Portuguese Oncology Institute of Porto, EPE, Porto, Portugal
| | - Joana Oliveira
- Department of Endocrinology, Portuguese Oncology Institute of Porto, EPE, Porto, Portugal
| | - Júlio Oliveira
- Department of Medical Oncology, Portuguese Oncology Institute of Porto, EPE, Porto, Portugal
| | - Isabel Azevedo
- Department of Medical Oncology, Portuguese Oncology Institute of Porto, EPE, Porto, Portugal
| | - Isabel Torres
- Department of Endocrinology, Portuguese Oncology Institute of Porto, EPE, Porto, Portugal
| | - Maria José Bento
- Department of Epidemiology, Portuguese Oncology Institute of Porto, EPE, Porto, Portugal
- School of Medicine and Biomedical Sciences, University of Porto, Porto, Portugal
| |
Collapse
|
|
50
|
Guccione L, Gough K, Drosdowsky A, Price T, Pavlakis N, Wyld D, Ransom D, Michael M, Schofield P. The unmet supportive care needs, quality of life, and care experiences of patients with functioning and non-functioning Neuroendocrine tumours (NETs) at early diagnosis. PATIENT EDUCATION AND COUNSELING 2022; 105:212-220. [PMID: 34030927 DOI: 10.1016/j.pec.2021.05.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/10/2020] [Revised: 04/22/2021] [Accepted: 05/05/2021] [Indexed: 06/12/2023]
Abstract
OBJECTIVE Healthcare experiences, quality of life and psychosocial needs of patients with Neuroendocrine tumours (NETs) will be assessed to identify differences between NET sub-groups and inform the design of supportive care services. METHODS This study constitutes phase one of a three-phase mixed-methods multi-site study with NET patients (n = 123). Demographic, clinical and patient reported outcome questionnaire data was collected. RESULTS No differences in patient reported outcomes were found beyond symptoms of diarrhoea and flushing between NET sub-groups. For combined NET patients, the majority reported negative experiences in their understanding of the explanation of what was wrong with them (67%); receiving written information about their cancer (69%), their family/carer receiving all the information required to care for them (61%); and the usefulness of information about NETs online (66%). NET patients reported at least one moderate-to-high need for disease specific information (63%). Medium- to large-sized differences in quality of life subscales were also observed with the functioning group reporting more anxiety compared to population norms. CONCLUSIONS There is a need to improve the current provision of information for people with NETs. PRACTICE IMPLICATIONS These findings will inform the design and development of an informational resource to facilitate improved understanding for patients with NETs.
Collapse
Affiliation(s)
- Lisa Guccione
- Department of Health Services Research, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Sir Peter MacCallum Department on Oncology, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Australia.
| | - Karla Gough
- Department of Health Services Research, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Department of Nursing, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Victoria, Australia.
| | - Allison Drosdowsky
- Department of Health Services Research, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
| | - Timothy Price
- Haematology and Oncology, The Queen Elizabeth Hospital, South Australia, Australia.
| | - Nick Pavlakis
- Department of Medical Oncology, Royal North Shore Hospital, New South Wales, Australia.
| | - David Wyld
- Department of Medical Oncology, Royal Brisbane and Women's Hospital, Queensland, Australia; Faculty of Medicine, University of Queensland, Brisbane, Australia.
| | - David Ransom
- Medical Oncology, Fiona Stanley Hospital, Western Australia, Australia.
| | - Michael Michael
- Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia; Neuroendocrine Unit, an ENETs Centre of Excellence, Peter MacCallum Cancer Centre, Melbourne, Australia.
| | - Penelope Schofield
- Department of Health Services Research, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia; Sir Peter MacCallum Department on Oncology, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Australia; Department of Psychology and Iverson Health Innovation Research Institute, Swinburne University, Melbourne, Australia.
| |
Collapse
|