Reference Citation Analysis: Find an Article, Find a Category, Find a Journal, Find a Scholar

For: Teunissen JJM, Kwekkeboom DJ, Krenning EP. Quality of life in patients with gastroenteropancreatic tumors treated with [177Lu-DOTA0,Tyr3]octreotate. J Clin Oncol 2004;22:2724-9. [PMID: 15226340 DOI: 10.1200/jco.2004.10.016] [Citation(s) in RCA: 139] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open

For:	Teunissen JJM, Kwekkeboom DJ, Krenning EP. Quality of life in patients with gastroenteropancreatic tumors treated with [177Lu-DOTA0,Tyr3]octreotate. J Clin Oncol 2004;22:2724-9. [PMID: 15226340 DOI: 10.1200/jco.2004.10.016] [Citation(s) in RCA: 139] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [What about the content of this article? (0)] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open

Number

Cited by Other Article(s)

Kong G, Noe G, Chiang C, Herrmann K, Hope TA, Michael M. Assessment of response to PRRT including anatomical and molecular imaging as well as novel biomarkers. J Neuroendocrinol 2025;37:e13461. [PMID: 39520276 PMCID: PMC11919480 DOI: 10.1111/jne.13461] [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: 06/30/2024] [Revised: 09/05/2024] [Accepted: 10/24/2024] [Indexed: 11/16/2024]

Hanu AR, Atanackovic J, Boyd C, Johnston EM, Waker AJ. Characterization and mapping of the neutron fields around Bruce Power's ¹⁷⁷Lu isotope production system. Appl Radiat Isot 2024;208:111284. [PMID: 38492278 DOI: 10.1016/j.apradiso.2024.111284] [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: 12/14/2023] [Revised: 02/14/2024] [Accepted: 03/09/2024] [Indexed: 03/18/2024]

Milanetto AC, Armellin C, Brigiari G, Lorenzoni G, Pasquali C. Younger Age and Parenchyma-Sparing Surgery Positively Affected Long-Term Health-Related Quality of Life after Surgery for Pancreatic Neuroendocrine Neoplasms. J Clin Med 2023;12:6529. [PMID: 37892667 PMCID: PMC10607516 DOI: 10.3390/jcm12206529] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2023] [Revised: 10/11/2023] [Accepted: 10/12/2023] [Indexed: 10/29/2023] Open

The Effects of Radioligand Therapy on Quality of Life and Sexual Function in Patients with Neuroendocrine Neoplasms. Cancers (Basel) 2022;15:cancers15010115. [PMID: 36612112 PMCID: PMC9817532 DOI: 10.3390/cancers15010115] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2022] [Accepted: 12/20/2022] [Indexed: 12/28/2022] Open

Strøm L, Danielsen JT, Amidi A, Cardenas Egusquiza AL, Wu LM, Zachariae R. Sleep During Oncological Treatment - A Systematic Review and Meta-Analysis of Associations With Treatment Response, Time to Progression and Survival. Front Neurosci 2022;16:817837. [PMID: 35516799 PMCID: PMC9063131 DOI: 10.3389/fnins.2022.817837] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Accepted: 02/02/2022] [Indexed: 01/20/2023] Open

Abstract

Introduction

Disrupted sleep and sleep-wake activity are frequently observed in cancer patients undergoing oncological treatment. These disruptions are often associated with aggravated symptom burden and diminished health-related quality of life that in turn may compromise treatment adherence and, thus, effectiveness. In addition, disrupted sleep has been linked to carcinogenic processes, which ultimately could result in worse prognostic outcomes.

Aims

Our aim was to systematically review and conduct a meta-analysis of studies examining the associations between sleep and sleep-wake activity and prognostic outcomes in cancer patients undergoing oncological treatment.

Methods

A comprehensive systematic search of English language papers was undertaken in June 2020 using PubMed, The Cochrane Library, and CINAHL. Two reviewers independently screened 4,879 abstracts. A total of 26 papers were included in the narrative review. Thirteen papers reporting hazard ratios reflecting associations between a dichotomized predictor variable (sleep) and prognostic outcomes were subjected to meta-analysis.

Results

Nineteen of the 26 eligible studies on a total of 7,092 cancer patients reported associations between poorer sleep and poorer response to treatment, shorter time to progression, and/or reduced overall survival, but were highly heterogeneous with respect to the sleep and outcome parameters investigated. Meta-analysis revealed statistically significant associations between poor self-reported sleep and reduced overall survival (HR = 1.33 [95% CI 1.09-1.62], k = 11), and shorter time to progression (HR = 1.40 [95% CI 1.23-1.59], k = 3) and between poor objectively assessed sleep and reduced overall survival (HR = 1.74 [95% CI 1.05-2.88], k = 4).

Conclusion

The current findings indicate that disturbed sleep during treatment may be a relevant behavioral marker of poor cancer prognosis. The limited number of studies, the common use of single item sleep measures, and potential publication bias highlight the need for further high quality and longitudinal studies.

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Gosain R, Gupta M, Roy AM, Strosberg J, Glaser KM, Iyer R. Health-Related Quality of Life (HRQoL) in Neuroendocrine Tumors: A Systematic Review. Cancers (Basel) 2022;14:1428. [PMID: 35326587 PMCID: PMC8946839 DOI: 10.3390/cancers14061428] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Revised: 03/08/2022] [Accepted: 03/08/2022] [Indexed: 12/28/2022] Open

Uccelli L, Boschi A, Cittanti C, Martini P, Panareo S, Tonini E, Nieri A, Urso L, Caracciolo M, Lodi L, Carnevale A, Giganti M, Bartolomei M. ⁹⁰Y/¹⁷⁷Lu-DOTATOC: From Preclinical Studies to Application in Humans. Pharmaceutics 2021;13:1463. [PMID: 34575538 PMCID: PMC8469896 DOI: 10.3390/pharmaceutics13091463] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2021] [Revised: 08/31/2021] [Accepted: 09/10/2021] [Indexed: 12/30/2022] Open

Affiliation(s)

Licia Uccelli Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy; (L.U.); (A.C.); (M.G.) Nuclear Medicine Unit, University Hospital, 44124 Ferrara, Italy; (S.P.); (A.N.); (L.U.); (M.C.); (L.L.); (M.B.)
Alessandra Boschi Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, 44121 Ferrara, Italy;
Corrado Cittanti Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy; (L.U.); (A.C.); (M.G.) Nuclear Medicine Unit, University Hospital, 44124 Ferrara, Italy; (S.P.); (A.N.); (L.U.); (M.C.); (L.L.); (M.B.)
Petra Martini Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy; (L.U.); (A.C.); (M.G.)
Stefano Panareo Nuclear Medicine Unit, University Hospital, 44124 Ferrara, Italy; (S.P.); (A.N.); (L.U.); (M.C.); (L.L.); (M.B.)
Eugenia Tonini Medical Physics Unit, University Hospital, 44124 Ferrara, Italy;
Alberto Nieri Nuclear Medicine Unit, University Hospital, 44124 Ferrara, Italy; (S.P.); (A.N.); (L.U.); (M.C.); (L.L.); (M.B.)
Luca Urso Nuclear Medicine Unit, University Hospital, 44124 Ferrara, Italy; (S.P.); (A.N.); (L.U.); (M.C.); (L.L.); (M.B.)
Matteo Caracciolo Nuclear Medicine Unit, University Hospital, 44124 Ferrara, Italy; (S.P.); (A.N.); (L.U.); (M.C.); (L.L.); (M.B.)
Luca Lodi Nuclear Medicine Unit, University Hospital, 44124 Ferrara, Italy; (S.P.); (A.N.); (L.U.); (M.C.); (L.L.); (M.B.)
Aldo Carnevale Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy; (L.U.); (A.C.); (M.G.) Radiology Unit, University Hospital, 44124 Ferrara, Italy
Melchiore Giganti Department of Translational Medicine, University of Ferrara, 44121 Ferrara, Italy; (L.U.); (A.C.); (M.G.) Radiology Unit, University Hospital, 44124 Ferrara, Italy
Mirco Bartolomei Nuclear Medicine Unit, University Hospital, 44124 Ferrara, Italy; (S.P.); (A.N.); (L.U.); (M.C.); (L.L.); (M.B.)

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Froelich MF, Schnitzer ML, Holzgreve A, Gassert FG, Gresser E, Overhoff D, Schwarze V, Fabritius MP, Nörenberg D, von Münchhausen N, Hokamp NG, Auernhammer CJ, Ilhan H, Todica A, Rübenthaler J. Cost-Effectiveness Analysis of ⁶⁸Ga DOTA-TATE PET/CT, ¹¹¹In-Pentetreotide SPECT/CT and CT for Diagnostic Workup of Neuroendocrine Tumors. Diagnostics (Basel) 2021;11:diagnostics11020334. [PMID: 33670457 PMCID: PMC7922846 DOI: 10.3390/diagnostics11020334] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Revised: 02/11/2021] [Accepted: 02/15/2021] [Indexed: 02/06/2023] Open

Abstract

Neuroendocrine tumors (NETs) are relatively rare neoplasms arising from the hormone-producing neuroendocrine system that can occur in various organs such as pancreas, small bowel, stomach and lung. As the majority of these tumors express somatostatin receptors (SSR) on their cell membrane, utilization of SSR analogs in nuclear medicine is a promising, but relatively costly approach for detection and localization. The aim of this study was to analyze the cost-effectiveness of ⁶⁸Ga-DOTA-TATE PET/CT (Gallium-68 DOTA-TATE Positron emission tomography/computed tomography) compared to ¹¹¹In-pentetreotide SPECT/CT (Indium-111 pentetreotide Single Photon emission computed tomography/computed tomography) and to CT (computed tomography) alone in detection of NETs. A decision model on the basis of Markov simulations evaluated lifetime costs and quality-adjusted life years (QALYs) related to either a CT, SPECT/CT or PET/CT. Model input parameters were obtained from publicized research projects. The analysis is grounded on the US healthcare system. Deterministic sensitivity analysis of diagnostic parameters and probabilistic sensitivity analysis predicated on a Monte Carlo simulation with 30,000 reiterations was executed. The willingness-to-pay (WTP) was determined to be $ 100,000/QALY. In the base-case investigation, PET/CT ended up with total costs of $88,003.07 with an efficacy of 4.179, whereas CT ended up with total costs of $88,894.71 with an efficacy of 4.165. SPECT/CT ended up with total costs of $89,973.34 with an efficacy of 4.158. Therefore, the strategies CT and SPECT/CT were dominated by PET/CT in the base-case scenario. In the sensitivity analyses, PET/CT remained a cost-effective strategy. This result was due to reduced therapy costs of timely detection. The additional costs of ⁶⁸Ga-DOTA-TATE PET/CT when compared to CT alone are justified in the light of potential savings in therapy costs and better outcomes.

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Affiliation(s)

Matthias Frank Froelich Department of Radiology and Nuclear Medicine, University Medical Center Mannheim, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany; (M.F.F.); (D.O.); (D.N.); (N.v.M.)
Moritz Ludwig Schnitzer Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany; (M.L.S.); (E.G.); (V.S.); (M.P.F.) ENETS Centre of Excellence, Interdisciplinary Center of Neuroendocrine Tumors of the GastroEnteroPancreatic System (GEPNET-KUM), LMU Munich, 81377 Munich, Germany; (A.H.); (C.J.A.); (H.I.); (A.T.)
Adrien Holzgreve ENETS Centre of Excellence, Interdisciplinary Center of Neuroendocrine Tumors of the GastroEnteroPancreatic System (GEPNET-KUM), LMU Munich, 81377 Munich, Germany; (A.H.); (C.J.A.); (H.I.); (A.T.) Department of Nuclear Medicine, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany
Felix Gerhard Gassert Department of Diagnostic and Interventional Radiology, Klinikum rechts der Isar, Technical University of Munich, Ismaninger Str. 22, 81675 Munich, Germany;
Eva Gresser Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany; (M.L.S.); (E.G.); (V.S.); (M.P.F.) ENETS Centre of Excellence, Interdisciplinary Center of Neuroendocrine Tumors of the GastroEnteroPancreatic System (GEPNET-KUM), LMU Munich, 81377 Munich, Germany; (A.H.); (C.J.A.); (H.I.); (A.T.)
Daniel Overhoff Department of Radiology and Nuclear Medicine, University Medical Center Mannheim, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany; (M.F.F.); (D.O.); (D.N.); (N.v.M.)
Vincent Schwarze Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany; (M.L.S.); (E.G.); (V.S.); (M.P.F.) ENETS Centre of Excellence, Interdisciplinary Center of Neuroendocrine Tumors of the GastroEnteroPancreatic System (GEPNET-KUM), LMU Munich, 81377 Munich, Germany; (A.H.); (C.J.A.); (H.I.); (A.T.)
Matthias Philipp Fabritius Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany; (M.L.S.); (E.G.); (V.S.); (M.P.F.) ENETS Centre of Excellence, Interdisciplinary Center of Neuroendocrine Tumors of the GastroEnteroPancreatic System (GEPNET-KUM), LMU Munich, 81377 Munich, Germany; (A.H.); (C.J.A.); (H.I.); (A.T.)
Dominik Nörenberg Department of Radiology and Nuclear Medicine, University Medical Center Mannheim, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany; (M.F.F.); (D.O.); (D.N.); (N.v.M.)
Niklas von Münchhausen Department of Radiology and Nuclear Medicine, University Medical Center Mannheim, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany; (M.F.F.); (D.O.); (D.N.); (N.v.M.)
Nils Große Hokamp Institute for Diagnostic and Interventional Radiology, University Hospital Cologne, 50937 Cologne, Germany;
Christoph J. Auernhammer ENETS Centre of Excellence, Interdisciplinary Center of Neuroendocrine Tumors of the GastroEnteroPancreatic System (GEPNET-KUM), LMU Munich, 81377 Munich, Germany; (A.H.); (C.J.A.); (H.I.); (A.T.) Department of Internal Medicine 4, University Hospital, LMU Munich, 81377 Munich, Germany
Harun Ilhan ENETS Centre of Excellence, Interdisciplinary Center of Neuroendocrine Tumors of the GastroEnteroPancreatic System (GEPNET-KUM), LMU Munich, 81377 Munich, Germany; (A.H.); (C.J.A.); (H.I.); (A.T.) Department of Nuclear Medicine, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany
Andrei Todica ENETS Centre of Excellence, Interdisciplinary Center of Neuroendocrine Tumors of the GastroEnteroPancreatic System (GEPNET-KUM), LMU Munich, 81377 Munich, Germany; (A.H.); (C.J.A.); (H.I.); (A.T.) Department of Nuclear Medicine, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany
Johannes Rübenthaler Department of Radiology, University Hospital, LMU Munich, Marchioninistr. 15, 81377 Munich, Germany; (M.L.S.); (E.G.); (V.S.); (M.P.F.) ENETS Centre of Excellence, Interdisciplinary Center of Neuroendocrine Tumors of the GastroEnteroPancreatic System (GEPNET-KUM), LMU Munich, 81377 Munich, Germany; (A.H.); (C.J.A.); (H.I.); (A.T.) Correspondence:

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Chiapponi C, Lürssen N, Cremer B, Wahba R, Drebber U, Faust M, Schmidt M, Stippel DL. Peptide receptor radionuclide therapy as a two-step strategy for initially unresectable liver disease from neuroendocrine tumors: a single-center experience. Endocrine 2020;70:187-193. [PMID: 32419082 DOI: 10.1007/s12020-020-02341-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/05/2020] [Accepted: 05/04/2020] [Indexed: 02/06/2023]

Watson C, Tallentire CW, Ramage JK, Srirajaskanthan R, Leeuwenkamp OR, Fountain D. Quality of life in patients with gastroenteropancreatic tumours: A systematic literature review. World J Gastroenterol 2020;26:3686-3711. [PMID: 32742136 PMCID: PMC7366058 DOI: 10.3748/wjg.v26.i25.3686] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2020] [Revised: 06/04/2020] [Accepted: 06/16/2020] [Indexed: 02/06/2023] Open

Abstract

BACKGROUND

Gastroenteropancreatic neuroendocrine tumours (GEP-NETs) are slow-growing cancers that arise from diffuse endocrine cells in the gastrointestinal tract (GI-NETs) or the pancreas (P-NETs). They are relatively uncommon, accounting for 2% of all gastrointestinal malignancies. The usual treatment options in advanced GEP-NET patients with metastatic disease include chemotherapy, biological therapies, and peptide receptor radionuclide therapy. Understanding the impact of treatment on GEP-NET patients is paramount given the nature of the disease. Health-related quality of life (HRQoL) is increasingly important as a concept reflecting the patients’ perspective in conjunction with the disease presentation, severity and treatment.

AIM

To conduct a systematic literature review to identify literature reporting HRQoL data in patients with GEP-NETs between January 1985 and November 2019.

METHODS

The PRISMA guiding principles were applied. MEDLINE, Embase and the Cochrane library were searched. Data extracted from the publications included type of study, patient population data (mid-gut/hind-gut/GI-NET/P-NET), sample size, intervention/comparators, HRQoL instruments, average and data spread of overall and sub-scores, and follow-up time for data collection.

RESULTS

Forty-three publications met the inclusion criteria. The heterogeneous nature of the different study populations was evident; the percentage of female participants ranged between 30%-60%, whilst average age ranged from 53.8 to 67.0 years. Eight studies investigated GI-NET patients only, six studies focused exclusively on P-NET patients and the remaining studies involved both patient populations or did not report the location of the primary tumour. The most commonly used instrument was the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (n = 28) with consistent results across studies; the GI-NET-specific module Quality of Life Questionnaire-GINET21 was used in six of these studies. A number of randomised trials demonstrated no HRQoL changes between active treatment and placebo arms. The Phase III NETTER-1 study provides the best data available for advanced GEP-NET patients; it shows that peptide receptor radionuclide therapy can significantly improve GEP-NET patients’ HRQoL.

CONCLUSION

HRQoL instruments offer a means to monitor patients’ general disease condition, disease progression and their physical and mental well-being. Instruments including the commonly used European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 and GINET21 lack, however, validation and a defined minimal clinical important difference specifically for GI-NET and P-NET patients.

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Adams JR, Ray D, Willmon R, Pulgar S, Dasari A. Living With Neuroendocrine Tumors: Assessment of Quality of Life Through a Mobile Application. JCO Clin Cancer Inform 2020;3:1-10. [PMID: 31283354 PMCID: PMC6873920 DOI: 10.1200/cci.19.00025] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open

Abstract

PURPOSE

To understand the quality of life (QoL) for patients with neuroendocrine tumors (NETs) through comparison of QoL questionnaires and symptom tracking as well as journaling via the Carcinoid NETs Health Storylines mobile application (app).

PATIENTS AND METHODS

This was a 12-week prospective, observational study of US patients with NET who were taking long-acting somatostatin analogs. National Institutes of Health Patient-Reported Outcomes Measurement Information System (PROMIS) and European Organisation for Research and Treatment of Cancer (EORTC) questionnaires were administered three times. Patients also monitored symptoms, mood, bowel movements, food, activity, and sleep, and they journaled in their app, which was coded by theme and sentiment for qualitative analysis.

RESULTS

Of the 120 patients with NET, 78% were women (mean age, 57 years); 76% had gastroenteropancreatic NETs, and 88% had metastases. Lanreotide depot and octreotide long-acting release (LAR) were used by 41% and 59%, respectively. The most common symptoms at baseline were fatigue (76.7%), diarrhea (62.5%), abdominal discomfort (64.1%), and trouble sleeping (57.5%). The majority completed five of six survey assessments (median, 5; mean, 5.1) and tracked four symptoms in the app (median, 4; mean, 5.5); the average frequency was 41.6 days for each symptom (median, 43; mean, 41.6; range, 1 to 84 days [12 weeks]). Without treatment change, most EORTC-assessed physical symptoms decreased from baseline to midpoint (eg, 59.3% at baseline v 33% at midpoint reported “quite a bit” or “very much” diarrhea; P = .002). App-based symptom tracking revealed large day-to-day variation, but weekly averages correlated well with survey scores. Journal entries showed that more patients made predominantly negative unsolicited entries about their injection experience with octreotide LAR compared with lanreotide (13 of 17 v two of 13; P < .001).

CONCLUSION

Patients with NET experience a large symptom burden that varies daily. A decrease in physical symptoms on QoL surveys suggests an effect from daily app-based monitoring or journaling, which may reduce recall bias and benefit the patient’s experience of symptoms.

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Hofland J, Kaltsas G, de Herder WW. Advances in the Diagnosis and Management of Well-Differentiated Neuroendocrine Neoplasms. Endocr Rev 2020;41:bnz004. [PMID: 31555796 PMCID: PMC7080342 DOI: 10.1210/endrev/bnz004] [Citation(s) in RCA: 122] [Impact Index Per Article: 24.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2020] [Accepted: 02/28/2020] [Indexed: 02/07/2023]

Patient Selection and Toxicities of PRRT for Metastatic Neuroendocrine Tumors and Research Opportunities. Curr Treat Options Oncol 2020;21:25. [PMID: 32172368 DOI: 10.1007/s11864-020-0711-9] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]

Update on Pathophysiology, Treatment, and Complications of Carcinoid Syndrome. JOURNAL OF ONCOLOGY 2020;2020:8341426. [PMID: 32322270 PMCID: PMC7160731 DOI: 10.1155/2020/8341426] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/16/2019] [Revised: 12/07/2019] [Accepted: 12/26/2019] [Indexed: 12/23/2022]

Abstract

Carcinoid syndrome (CS) develops in patients with hormone-producing neuroendocrine neoplasms (NENs) when hormones reach a significant level in the systemic circulation. The classical symptoms of carcinoid syndrome are flushing, diarrhoea, abdominal pain, and wheezing. Neuroendocrine neoplasms can produce multiple hormones: 5-hydroxytryptamine (serotonin) is the most well-known one, but histamine, catecholamines, and brady/tachykinins are also released. Serotonin overproduction can lead to symptoms and also stimulates fibrosis formation which can result in development of carcinoid syndrome-associated complications such as carcinoid heart disease (CaHD) and mesenteric fibrosis. Transforming growth factor beta (TGF-β) is one of the main factors in developing fibrosis, but platelet-derived growth factor (PDGF), basic fibroblast growth factor (FGF2), and connective tissue growth factor (CTGF or CCN2) are also related to fibrosis development. Treatment of CS focuses on reducing serotonin levels with somatostatin analogues (SSA's). Telotristat ethyl and peptide receptor radionuclide therapy (PRRT) have recently become available for patients with symptoms despite being established on SSA's. Screening for CaHD is advised, and early intervention prolongs survival. Mesenteric fibrosis is often present and associated with poorer survival, but the role for prophylactic surgery of this is unclear. Depression, anxiety, and cognitive impairment are frequently present symptoms in patients with CS but not always part of their care plan. The role of antidepressants, mainly SSRIs, is debatable, but recent retrospective studies show evidence for safe use in patients with CS. Carcinoid crisis is a life-threatening complication of CS which can appear spontaneously but mostly described during surgery, anaesthesia, chemotherapy, PRRT, and radiological procedures and may be prevented by octreotide administration.

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Peptide Receptor Radionuclide Therapy. Clin Nucl Med 2020. [DOI: 10.1007/978-3-030-39457-8_32] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]

Lenain R, Hamroun A, Lion G, Chamley P, Bui L, Lionet A, Hazzan M, Provôt F. Description of a transient proximal tubulopathy induced by amino acids perfusion in peptide receptor radionuclide therapy: A case report. Medicine (Baltimore) 2019;98:e18478. [PMID: 31876733 PMCID: PMC6946443 DOI: 10.1097/md.0000000000018478] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open

Abstract

RATIONALE

Peptide receptor radionuclide therapy (PRRT) with radiolabeled somatostatin analogs is a targeted internal radiotherapy method used to treat tumors expressing somatostatin receptors. Concomitant amino acids perfusion is systematically performed in order to inhibit the proximal tubular uptake of the radionuclide and thus prevent nephrotoxicity. PATIENT CONCERNS:: a 67-year-old woman with an intestinal neuroendocrine tumor with multiple lymphadenopathies and liver metastases. The patient displayed a carcinoid syndrome with flushes including facial erythrosis and paresthesia. During the treatment, the patient exhibited emesis and severe cramps.

DIAGNOSIS

We describe incomplete proximal tubulopathy induced by an amino acid therapy with [177Lu]-DOTA0-Tyr3-octreotate, which was reversible after treatment discontinuation. This diagnosis relies on metabolic acidosis, hypophosphatemia due to renal loss, tubular proteinuria and generalized aminoaciduria. Serum creatinine remained stable during and after the procedure.

INTERVENTIONS

PRRT with radiolabeled somatostatin analog ([177Lu]-DOTA0-Tyr3-octreotate). In order to prevent PRRT induced nephrotoxicity, we used a solution of 20 amino acids including 22 g/L Lysine and 16.8 g/L Arginine. Metoclopramide was successfully used to control vomiting. During the treatment and at the time of cramps, the blood sample showed hypophosphatemia at 0.3 mmol/L justifying intravenous phosphate supplementation. The cramps disappeared after this infusion.

OUTCOMES

Hypophosphatemia with low TmPO4/GFR was observed as well as an increase in β2-microglobulinuria, urinary polyclonal light chains, and amino aciduria involving all amino acids. All these disturbances disappeared the day after the treatment and there was no acute kidney injury after 5 PRRT sessions. Six months after PRRT discontinuation, the patient had neither renal failure nor proximal tubulopathy. Aminoacid induced tubulopathy involves the main ligands of the megalin receptor. It has recently been demonstrated that cilastatin is a megalin inhibitor in the proximal tubule and therefore could represent an attractive alternative to amino acids for this purpose.

LESSONS

This case report is a description of a nephroprotective strategy in which partial, and transient tubulopathy is induced, in order to decrease proximal absorption of a tubulotoxic molecule. This little known strategy could be used to prevent proximal tubular injury caused by others megalin-mediated nephrotoxicity medication.

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Wang S, Liu Y, Feng Y, Zhang J, Swinnen J, Li Y, Ni Y. A Review on Curability of Cancers: More Efforts for Novel Therapeutic Options Are Needed. Cancers (Basel) 2019;11:E1782. [PMID: 31766180 PMCID: PMC6896199 DOI: 10.3390/cancers11111782] [Citation(s) in RCA: 63] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2019] [Revised: 11/01/2019] [Accepted: 11/04/2019] [Indexed: 02/07/2023] Open

Targeted Systemic Treatment of Neuroendocrine Tumors: Current Options and Future Perspectives. Drugs 2019;79:21-42. [PMID: 30560479 PMCID: PMC6338796 DOI: 10.1007/s40265-018-1033-0] [Citation(s) in RCA: 47] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]

Saravana-Bawan B, Koumna S, Wieler M, McEwan A, McMullen T. Comparison and clinical implementation of quality of life tools in patients with small bowel neuroendocrine tumors treated with Lu-DOTA-TATE PRRT. INTERNATIONAL JOURNAL OF ENDOCRINE ONCOLOGY 2019. [DOI: 10.2217/ije-2019-0003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open

Peptide Receptor Radiotherapy: Current Approaches and Future Directions. Curr Treat Options Oncol 2019;20:77. [DOI: 10.1007/s11864-019-0677-7] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]

Hou X, Zhao W, Beauregard JM, Celler A. Personalized kidney dosimetry in ¹⁷⁷Lu-octreotate treatment of neuroendocrine tumours: a comparison of kidney dosimetry estimates based on a whole organ and small volume segmentations. Phys Med Biol 2019;64:175004. [PMID: 31456584 DOI: 10.1088/1361-6560/ab32a1] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022]

Abstract

Peptide receptor radionuclide therapy (PRRT) with ¹⁷⁷Lu- radiolabeled octreotate is an effective treatment method for inoperable neuroendocrine tumours (NETs). There is growing evidence that estimates of the organ-at-risks (OARs) doses are necessary for the optimization of personalized PRRT (P-PRRT). Dosimetry, however, requires a complicated and time-consuming procedure, which hinders its implementation in the clinic. The aim of this study is to develop a practical and automatic technique to simplify personalized dosimetry of kidney, the major OAR in ¹⁷⁷Lu P-PRRT. The data from 30 NETs patients undergoing 44 personalized ¹⁷⁷Lu-DOTA-TATE therapy cycles were analyzed. To determine the biokinetics of the radiopharmaceutical in the kidneys, for each patient three SPECT/CT scans were acquired, at about 4 h, 24 h and 70 h after injection. The kidneys doses were evaluated using three different approaches: (1) a traditional approach based on whole kidney (WK) segmentation; (2) a small volume (SV) manual approach (M-SV) with observer-defined SV location; and (3) a software based SV-approach that automatically defines SV location (A-SV). Four different methods of automatic SV location selections were investigated. The SV kidney doses estimated using M-SV and A-SV approaches was evaluated and the accuracy of these two approaches were compared to the WK dosimetry. The kidney bio-kinetics, in terms of effective half-lives, obtained from both of the A-SV and M-SV approaches agreed to within 10% with those obtained from the WK segmentation. The average ratios of SV doses to WK doses were mostly about 1.8 ± 0.2 for both A-SV and M-SV approaches. The linear correlation coefficients between SV doses (both A-SV and M-SV) and WK doses were up to 0.9 with p < 0.001. The differences between A-SV and M-SV were minor. By comparing different methods of SV location selections, independently selecting SV in images from each of the acquisitions was proved the most appropriate and accurate approach. An automatic, observer-independent method for selecting the location of the small volume in kidneys was developed. The accuracy of this dose estimation approach has been demonstrated by comparing it with the manual SV dosimetry, as well as the WK dosimetry. The proposed automatic approach can potentially be considered as a practical and simple method for dose estimation in the future clinical studies.

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Mujica-Mota R, Varley-Campbell J, Tikhonova I, Cooper C, Griffin E, Haasova M, Peters J, Lucherini S, Talens-Bou J, Long L, Sherriff D, Napier M, Ramage J, Hoyle M. Everolimus, lutetium-177 DOTATATE and sunitinib for advanced, unresectable or metastatic neuroendocrine tumours with disease progression: a systematic review and cost-effectiveness analysis. Health Technol Assess 2019;22:1-326. [PMID: 30209002 DOI: 10.3310/hta22490] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open

Abstract

BACKGROUND

Neuroendocrine tumours (NETs) are a group of heterogeneous cancers that develop in cells in the diffuse neuroendocrine system.

OBJECTIVES

To estimate the clinical effectiveness of three interventions [everolimus (Afinitor^®; Novartis International AG, Basel, Switzerland), lutetium-177 DOTATATE (177Lu-DOTATATE) (Lutathera^®; Imaging Equipment Ltd, Radstock, UK) and sunitinib (Sutent^®; Pfizer Inc., New York, NY, USA)] for treating unresectable or metastatic NETs with disease progression and establish the cost-effectiveness of these interventions.

DATA SOURCES

The following databases were searched from inception to May 2016: MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE Daily, Epub Ahead of Print, EMBASE, Cochrane Central Register of Controlled Trials and Web of Science.

REVIEW METHODS

We systematically reviewed the clinical effectiveness and cost-effectiveness literature on everolimus, 177Lu-DOTATATE and sunitinib for treating advanced, unresectable or metastatic progressive NETs. The following NET locations were considered separately: pancreas, gastrointestinal (GI) tract and lung, and GI tract (midgut only). We wrote a survival partition cohort-based economic evaluation in Microsoft Excel^® 2013 (Microsoft Corporation, Redmond, WA, USA) from the UK NHS and Personal Social Services perspective. This comprised three health states: (1) progression-free survival (PFS), (2) progressed disease and (3) death.

RESULTS

Three randomised controlled trials (RCTs), RADIANT-3 [RAD001 in Advanced Neuroendocrine Tumors, Third Trial; pancreatic NETs (pNETs): everolimus vs. best supportive care (BSC)], A6181111 (pNETs: sunitinib vs. BSC) and RADIANT-4 (RAD001 in Advanced Neuroendocrine Tumors, Fourth Trial; GI and lung NETs: everolimus vs. BSC), met the inclusion criteria for the clinical effectiveness systematic review. The risk of bias was low. Although the NETTER-1 (Neuroendocrine Tumors Therapy) RCT, of 177Lu-DOTATATE plus 30 mg of octreotide (Sandostatin^®, Novartis) compared with 60 mg of octreotide, was excluded from the review, we nonetheless present the results of this trial, as it informs our estimate of the cost-effectiveness of 177Lu-DOTATATE. The pNETs trials consistently found that the interventions improved PFS and overall survival (OS) compared with BSC. Our indirect comparison found no significant difference in PFS between everolimus and sunitinib. Estimates of OS gain were confounded because of high rates of treatment switching. After adjustment, our indirect comparison suggested a lower, but non-significant, hazard of death for sunitinib compared with everolimus. In GI and lung NETs, everolimus significantly improved PFS compared with BSC and showed a non-significant trend towards improved OS compared with BSC. Adverse events were more commonly reported following treatment with targeted interventions than after treatment with BSC. In the base case for pNETs, assuming list prices, we estimated incremental cost-effectiveness ratios (ICERs) for everolimus compared with BSC of £45,493 per quality-adjusted life-year (QALY) and for sunitinib compared with BSC of £20,717 per QALY. These ICERs increased substantially without the adjustment for treatment switching. For GI and lung NETs, we estimated an ICER for everolimus compared with BSC of £44,557 per QALY. For GI (midgut) NETs, the ICERs were £199,233 per QALY for everolimus compared with BSC and £62,158 per QALY for a scenario analysis comparing 177Lu-DOTATATE with BSC. We judge that no treatment meets the National Institute for Health and Care Excellence's (NICE) end-of-life criteria, although we cannot rule out that sunitinib in the A6181111 trial does.

LIMITATIONS

A RCT with included comparators was not identified for 177Lu-DOTATATE. The indirect treatment comparison that our economic analysis was based on was of a simple Bucher type, unadjusted for any differences in the baseline characteristics across the two trials.

CONCLUSIONS

Given NICE's current stated range of £20,000-30,000 per QALY for the cost-effectiveness threshold, based on list prices, only sunitinib might be considered good value for money in England and Wales.

FUTURE WORK

Further analysis of individual patient data from RADIANT-3 would allow assessment of the robustness of our findings. The data were not made available to us by the company sponsoring the trial.

STUDY REGISTRATION

This study is registered as PROSPERO CRD42016041303.

FUNDING

The National Institute for Health Research Health Technology Assessment programme.

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Magalhães D, Sampaio IL, Ferreira G, Bogalho P, Martins-Branco D, Santos R, Duarte H. Peptide receptor radionuclide therapy with ¹⁷⁷Lu-DOTA-TATE as a promising treatment of malignant insulinoma: a series of case reports and literature review. J Endocrinol Invest 2019;42:249-260. [PMID: 29949120 DOI: 10.1007/s40618-018-0911-3] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2018] [Accepted: 06/04/2018] [Indexed: 12/11/2022]

Maqsood MH, Tameez Ud Din A, Khan AH. Neuroendocrine Tumor Therapy with Lutetium-177: A Literature Review. Cureus 2019;11:e3986. [PMID: 30972265 PMCID: PMC6443107 DOI: 10.7759/cureus.3986] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2019] [Accepted: 01/30/2019] [Indexed: 12/14/2022] Open

Surgery Provides Long-Term Survival in Patients with Metastatic Neuroendocrine Tumors Undergoing Resection for Non-Hormonal Symptoms. J Gastrointest Surg 2019;23:122-134. [PMID: 30334178 PMCID: PMC10183101 DOI: 10.1007/s11605-018-3986-4] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2018] [Accepted: 09/20/2018] [Indexed: 01/31/2023]

Abstract

INTRODUCTION

Patients with metastatic neuroendocrine tumor (NET) often have an indolent disease course yet the outcomes for patients with metastatic NET undergoing surgery for non-hormonal (NH) symptoms of GI obstruction, bleeding, or pain is not known.

METHODS

We identified patients with metastatic gastroenteropancreatic NET who underwent resection from 2000 to 2016 at 8 academic institutions who participated in the US Neuroendocrine Tumor Study Group.

RESULTS

Of 581 patients with metastatic NET to liver (61.3%), lymph nodes (24.1%), lung (2.1%), and bone (2.5%), 332 (57.1%) presented with NH symptoms of pain (n = 223, 67.4%), GI bleeding (n = 54, 16.3%), GI obstruction (n = 49, 14.8%), and biliary obstruction (n = 22, 6.7%). Most patients were undergoing their first operation (85.4%) within 4 weeks of diagnosis. The median overall survival was 110.4 months, and operative intent predicted survival (p < 0.001) with 66.3% undergoing curative resection. Removal of all metastatic disease was associated with the longest median survival (112.5 months) compared to debulking (89.2 months), or palliative resection (50.0 months; p < 0.001). The 1-, 3-, and 12-month mortality was 3.0%, 4.5%, and 9.0%, respectively. Factors associated with 1-year mortality included palliative operations (OR 6.54, p = 0.006), foregut NET (5.62, p = 0.042), major complication (4.91, p = 0.001), and high tumor grade (11.2, p < 0.001). The conditional survival for patients who lived past 1 year was 119 months.

CONCLUSIONS

Patients with metastatic NET and NH symptoms that necessitate surgery have long-term survival, and goals of care should focus on both oncologic and quality of life impact. Surgical intervention remains a critical component of multidisciplinary care of symptomatic patients.

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Martini C, Buxbaum S, Rodrigues M, Nilica B, Scarpa L, Holzner B, Virgolini I, Gamper EM. Quality of Life in Patients with Metastatic Gastroenteropancreatic Neuroendocrine Tumors Receiving Peptide Receptor Radionuclide Therapy: Information from a Monitoring Program in Clinical Routine. J Nucl Med 2018;59:1566-1573. [PMID: 30042164 DOI: 10.2967/jnumed.117.204834] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2017] [Accepted: 01/31/2018] [Indexed: 12/16/2022] Open

Abstract

In patients with metastatic gastroenteropancreatic neuroendocrine tumors (NETs), we evaluated health-related quality of life (HRQoL) from the first peptide receptor radionuclide therapy (PRRT) to the first restaging and compared the scores with general-population (GP) norms. Methods: The data were from routine HRQoL monitoring using the core quality-of-life questionnaire of the European Organization for Research and Treatment of Cancer (EORTC QLQ-C30). Patients received 4-6 cycles of ¹⁷⁷Lu-DOTATATE or ⁹⁰Y-DOTATOC. To be eligible for analysis, patients had to have at least one HRQoL assessment before PRRT and at least one HRQoL assessment at the end of or after treatment completion. Linear mixed models were used to consider HRQoL changes over time. Results: In total, 61 gastroenteropancreatic NET patients (small-intestine NETs, n = 37; pancreatic NETs, n = 24) were eligible for analysis. Clear improvements from baseline to the first restaging were found for diarrhea in small-intestine NET patients, showing a decrease of 16 points, which represents a moderately large change. We observed a clinically relevant decrease in appetite loss (17 points), but for female small-intestine NET patients only. Other HRQoL changes were also restricted to sociodemographic or clinical subgroups and mainly reflected improvements, except for physical and social functioning, which showed decreasing scores in older small-intestine NET patients. Compared with HRQoL GP norms, patients had impairments consisting of diarrhea; fatigue; appetite loss; reduced physical, social, and role functioning; and reduced global HRQoL. Except for diarrhea and appetite loss, patient scores at the first restaging did not reach GP levels. Conclusion: Our analyses support previous findings of overall stable HRQoL under PRRT. Yet, significant HRQoL impairments compared with the GP and potentially specific subgroup patterns need to be considered.

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Neuroendocrine Tumor Therapy: ¹⁷⁷Lu-DOTATATE. AJR Am J Roentgenol 2018;211:278-285. [PMID: 29949416 DOI: 10.2214/ajr.18.19953] [Citation(s) in RCA: 69] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]

Health-Related Quality of Life After Surgery for Small Intestinal Neuroendocrine Tumours. World J Surg 2018;42:3231-3239. [DOI: 10.1007/s00268-018-4638-2] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]

Concomitant 177Lu-DOTATATE and Capecitabine Therapy in Patients With Advanced Neuroendocrine Tumors: A Long-term-Outcome, Toxicity, Survival, and Quality-of-Life Study. Clin Nucl Med 2018;42:e457-e466. [PMID: 28872545 DOI: 10.1097/rlu.0000000000001816] [Citation(s) in RCA: 51] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]

Abstract

PURPOSE

The purpose of this study was to evaluate the outcome, toxicity, survival, and quality of life in patients with advanced neuroendocrine tumors.

METHODS

One hundred sixty-seven patients were enrolled in the study. All patients underwent baseline Ga-DOTANOC PET/CT scans. Lu-DOTATATE therapy was administered quarterly along with oral capecitabine therapy in group 1 patients (n = 88), whereas group 2 patients (n = 79) were treated only with Lu-DOTATATE. Hematologic, kidney function, liver function tests and chromogranin A levels were recorded before and after therapy at 2-week, 4-week, and 3-month intervals. Biochemical and morphological responses were assessed with the trend in chromogranin A levels and Response Evaluation Criteria in Solid Tumors 1.1 criteria, respectively.

RESULTS

There was no significant difference in the hemoglobin levels after Lu-DOTATATE therapy (P = 0.4892). In most patients, there was a decrease in the platelet levels; however, all the patients had platelet counts greater than 100,000/μL with no platelet toxicity. There was no toxicity related to leukocytes. Two patients showed renal insufficiencies. No hepatotoxicity was observed in any of the patients. According to Response Evaluation Criteria in Solid Tumors 1.1 criteria, in group 1 patients, the response was partial response in 34% of the patients, stable disease in 50.2%, and progressive disease in 6.8% versus partial response in 6.3%, stable disease in 60.9%, and progressive disease in 26.5% among group 2 patients. The median overall survival (OS) and progression-free survival (PFS) was not reached in group 1 patients. The median OS and PFS in group 2 patients were 48 months. Ki-67 tumor proliferation index was significantly associated with increased risk of disease progression.

CONCLUSIONS

Addition of capecitabine therapy with Lu-DOTATATE therapy lengthens the OS and PFS. Patients with aggressive disease may benefit from this synergetic therapeutic approach.

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Paradigm shift in theranostics of neuroendocrine tumors: conceptual horizons of nanotechnology in nuclear medicine. Ann Nucl Med 2018;32:151-164. [PMID: 29374820 DOI: 10.1007/s12149-018-1235-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2017] [Accepted: 01/22/2018] [Indexed: 01/18/2023]

Tumor Cystic Necrosis Following Peptide Receptor Radionuclide Therapy in Neuroendocrine Tumors. Clin Nucl Med 2018;43:186-187. [PMID: 29356741 DOI: 10.1097/rlu.0000000000001970] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]

Karppinen N, Lindén R, Sintonen H, Tarkkanen M, Roine R, Heiskanen I, Matikainen N, Schalin-Jäntti C. Health-Related Quality of Life in Patients with Small Intestine Neuroendocrine Tumors. Neuroendocrinology 2018;107:366-374. [PMID: 30293074 DOI: 10.1159/000494293] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2018] [Accepted: 10/02/2018] [Indexed: 01/09/2023]

Abstract

BACKGROUND

The prevalence of small intestine neuroendocrine tumors (SI-NETs) is increasing. Disease progression is often slow and treatment options and long-term survival rates have improved, but little is known about health-related quality of life (HRQoL) in these patients.

OBJECTIVE

To assess HRQoL and its predictors in SI-NET patients receiving contemporary treatments.

METHODS

We measured HRQoL with 15D and SF-36 questionnaires in 134 SI-NET patients and compared the 15D results to those of an age- and gender-standardized sample of the general population (n = 1,153). In the patients, we studied the impact of treatments, Ki-67, liver metastases, circulating tumor markers, comorbidities, and/or socioeconomic factors on HRQoL with linear regression analysis.

RESULTS

The mean disease duration of the patients was 81 (4-468) months, 91% had metastatic disease, and 79% received somatostatin analog treatment. Hepatic tumor load was 0% in 44.8%, < 10-25% in 44.0%, and > 25% in 11.2%, respectively. Mean fP-CgA and S-5HIAA concentrations were 15 (1.3-250) and 344 (24-7,470) nmol/L, respectively. Overall, HRQoL was significantly impaired in patients compared to controls (15D score 0.864 ± 0.105 vs. 0.905 ± 0.028, p < 0.001). SI-NET patients scored worse on 9 of 15 dimensions: sleep, excretion (i.e., bladder and bowel function), depression, distress, vitality, sexual activity (p < 0.001), breathing, usual activities, and discomfort and symptoms (p < 0.01-0.05). SF-36 scores were impaired and highly correlated with 15D scores (p < 0.001). HRQoL was impaired in patients with (n = 85) compared to patients without (n = 49) impaired excretion (0.828 vs. 0.933, p < 0.001). In the patient group, number of medications predicted impaired HRQoL.

CONCLUSIONS

Despite contemporary treatments, SI-NET patients have severely impaired HRQoL, including diarrhea, sleep, depression, vitality, and sexual activity.

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Peptide Receptor Radionuclide Therapy With 177Lu-Octreotate in Patients With Somatostatin Receptor Expressing Neuroendocrine Tumors: Six Years' Assessment. Clin Nucl Med 2017;42:436-443. [PMID: 28263217 DOI: 10.1097/rlu.0000000000001629] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]

Abstract

OBJECTIVES

Peptide receptor radionuclide therapy (PRRT) with radiolabeled somatostatin analogues is a promising treatment for patients with inoperable, well to moderately differentiated metastatic neuroendocrine tumors (NETs). In continuation of our novel study with the radionuclide lutetium Lu, we now present further results of Lu DOTATATE therapy in managing NETs and other somatostatin receptor-expressing tumors in a larger and more diverse patient group.

PATIENTS AND METHODS

One hundred forty-four consecutive patients (85 men and 59 women; age range, 11-87 years; mean age, 58.5 years) with histologically confirmed NET were enrolled. One hundred forty-three patients received at least 1 cycle of treatment. Among them, 132 were deemed evaluable by having at least 1 cycle of treatment and a posttreatment MRI or CT scan for assessment based on modified Response Evaluation Criteria in Solid Tumors. Response to therapy was evaluated in terms of progression-free survival, overall survival, as well as radiologic, biochemical, and clinical responses. Further, analysis of symptoms was reviewed during therapy and also in subsequent follow-ups for safety evaluation. Renal, gastrointestinal (GI), hepatic, and hematological adverse events were evaluated using National Cancer Institute common toxicities criteria V4.03, through full blood panels, as well as consultation with patients for any symptoms and/or adverse events.

RESULTS

As of July 2016, median progression-free survival was about to be reached. Of 28 patients who have completed Lu DOTATATE therapy (completion of 4 or more cycles of treatment and all designated follow-ups), no patient showed complete response (CR), 8 patients (28.57%) showed partial response (PR), 16 patients (57.14%) showed stable disease (SD), and progressive disease (PD) was observed in 4 patients (14.28%). The objective response rate (CR + PR) of this group was 28.57% (n = 8) with a cumulative disease control (CR + PR + SD) of 85.71% (n = 24).Among 132 evaluable patients, assessment of treatment response using modified Response Evaluation Criteria in Solid Tumors criteria revealed CR in none of the patients, PR in 12 patients (9.09%), SD in 66 patients (50%), whereas PD, which included patients who passed away, was observed in 54 patients (40.90%), yielding an objective response rate of 9.09% (n = 12) and a cumulative disease control rate of 59.09% (n = 78).Symptoms including abdominal pain, diarrhea, flushing, and fatigue improved in over 50% of the patients, whereas weight loss improved in 28.26% of the patients. No grade 3 or grade 4 renal toxicities were found, though eleven grade 3 and five grade 4 hematological as well as three grade 3 hepatotoxicities were reported. Grade 3 hematotoxicity lasted an average of 2.7 months, and grade 4 lasted for only 0.9 months, whereas grade 3 hepatotoxicity lasted an average of 3.1 months.

CONCLUSIONS

Lu-octreotate peptide receptor radionuclide therapy has shown promising potential as a safe and effective targeted therapy in inoperable, well to moderately differentiated metastatic neuroendocrine cancers. The results of the multicenter randomized clinical trial conducted in United States and Europe are concordant with current study.

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Levine R, Krenning EP. Clinical History of the Theranostic Radionuclide Approach to Neuroendocrine Tumors and Other Types of Cancer: Historical Review Based on an Interview of Eric P. Krenning by Rachel Levine. J Nucl Med 2017;58:3S-9S. [PMID: 28864612 DOI: 10.2967/jnumed.116.186502] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2017] [Accepted: 04/13/2017] [Indexed: 12/15/2022] Open

Improving quality of life in patients with pancreatic neuroendocrine tumor following peptide receptor radionuclide therapy assessed by EORTC QLQ-C30. Eur J Nucl Med Mol Imaging 2017;45:38-46. [DOI: 10.1007/s00259-017-3816-z] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2017] [Accepted: 08/22/2017] [Indexed: 01/01/2023]

177 Lu-DOTATATE treatment in neuroendocrine tumors. A preliminary study. Rev Esp Med Nucl Imagen Mol 2017. [DOI: 10.1016/j.remnie.2017.01.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]

Estorch M. Tratamiento con 177Lu-DOTATATE: pasado, presente y futuro. Rev Esp Med Nucl Imagen Mol 2017;36:69-71. [DOI: 10.1016/j.remn.2017.01.009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2017] [Accepted: 01/23/2017] [Indexed: 11/30/2022]

A Patient With Metastatic Sarcoma was Successfully Treated With Radiolabeled Somatostatin Analogs. Clin Nucl Med 2017;41:705-7. [PMID: 27355848 PMCID: PMC4979627 DOI: 10.1097/rlu.0000000000001288] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]

Bodei L, Kwekkeboom DJ, Kidd M, Modlin IM, Krenning EP. Radiolabeled Somatostatin Analogue Therapy Of Gastroenteropancreatic Cancer. Semin Nucl Med 2016;46:225-38. [PMID: 27067503 DOI: 10.1053/j.semnuclmed.2015.12.003] [Citation(s) in RCA: 73] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]

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Abstract

BACKGROUND AND OBJECTIVE

Illness stories have attracted growing attention in health care research in the context of learning from looking at the world through the patients' eyes. No narrative studies were found about the patients with neuroendocrine tumors (NETs); a rare illness including tumors usually starting in hormone-producing cells. The aim of this article was to develop an extended understanding of these patients' experiences and struggles, as well as their solutions to a common problem.

METHODS

The data source was 21 letters written by the patients with NETs treated at an ambulatory treatment center at a large urban hospital in Italy. The letters were analyzed using the Arthur Frank's narrative method. We paid particular attention to statements of self-experience, which is crucial to get the character of the story.

RESULTS

We identified four different typologies: "Not illness stories", "Living in imbalance", "Living a new life in balance", and "Living a normal life". The main characteristics of these four groups could be linked to Frank's typologies. However, the patients with this periodically changing disease were continuously in the process of attaining balance in life, and they might move between these various typologies.

CONCLUSION

The NETs are incurable illnesses that challenged the peoples to attaining a new balance in life. We will highlight stories focusing on the patients' imbalance and chaos because they illuminated the patients' concrete suffering, which might provide clinicians with specific information about the patients' emotional, physical, and spiritual state. Through learning from the stories of the patients attaining new balance, it seems possible to move forward to acceptance and to develop a model for a new way of living. However, we are skeptical about labeling these stories as a model for clinical practice because they might contribute to individualistic and heroic prescriptions for life that are impossible for others to achieve.

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Is there a role for peptide receptor radionuclide therapy in medullary thyroid cancer? Clin Nucl Med 2015;40:123-7. [PMID: 25546220 DOI: 10.1097/rlu.0000000000000628] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]

Health-related quality of life in well-differentiated metastatic gastroenteropancreatic neuroendocrine tumors. Cancer Metastasis Rev 2015;34:381-400. [DOI: 10.1007/s10555-015-9573-1] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]

Basuroy R, Sarker D, Quaglia A, Srirajaskanthan R, Ramage J. Personalized medicine for gastroenteropancreatic neuroendocrine tumors: a distant dream? INTERNATIONAL JOURNAL OF ENDOCRINE ONCOLOGY 2015. [DOI: 10.2217/ije.15.9] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open