A clinical score for neuroendocrine tumor patients under consideration for Lu-177-DOTATATE therapy

in Endocrine-Related Cancer
Authors:
Satya Das Vanderbilt University Medical Center, Division of Hematology and Oncology, Department of Medicine, Nashville, Tennessee, USA

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https://orcid.org/0000-0002-7625-1039
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Liping Du Vanderbilt University of Medical Center, Department of Biostatistics, Nashville, Tennessee, USA

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Aimee Schad Rush Medical Center, Department of Medicine, Chicago, Illinois, USA

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Shikha Jain Department of Medicine, University of Illinois Chicago, Chicago, Illinois, USA

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Aaron Jessop Department of Radiology, Vanderbilt University Medical Center, Nashville, Tennessee, USA

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Chirayu Shah Department of Radiology, Vanderbilt University Medical Center, Nashville, Tennessee, USA

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David Eisner Vanderbilt University Medical Center, Division of Hematology and Oncology, Department of Medicine, Nashville, Tennessee, USA

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Dana Cardin Vanderbilt University Medical Center, Division of Hematology and Oncology, Department of Medicine, Nashville, Tennessee, USA

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Kristen Ciombor Vanderbilt University Medical Center, Division of Hematology and Oncology, Department of Medicine, Nashville, Tennessee, USA

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Laura Goff Vanderbilt University Medical Center, Division of Hematology and Oncology, Department of Medicine, Nashville, Tennessee, USA

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Marques Bradshaw Department of Radiology, Vanderbilt University Medical Center, Nashville, Tennessee, USA

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Dominique Delbeke Department of Radiology, Vanderbilt University Medical Center, Nashville, Tennessee, USA

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Martin Sandler Department of Radiology, Vanderbilt University Medical Center, Nashville, Tennessee, USA

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Jordan Berlin Vanderbilt University Medical Center, Division of Hematology and Oncology, Department of Medicine, Nashville, Tennessee, USA

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Correspondence should be addressed to S Das: satya.das@vumc.org
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We developed a clinical score (CS) at Vanderbilt Ingram Cancer Center (VICC) that we hoped would predict outcomes for patients with progressive well-differentiated neuroendocrine tumors (NETs) receiving therapy with Lutetium-177 (177Lu)-DOTATATE. Patients under consideration for 177Lu-DOTATATE between March 1, 2016 and March 17, 2020 at VICC were assigned a CS prospectively. The CS included 5 categories: available treatments for tumor type outside of 177Lu-DOTATATE, prior systemic treatments, patient symptoms, tumor burden in critical organs and presence of peritoneal carcinomatosis. The primary outcome of the analysis was progression-free survival (PFS). To evaluate the effect of the CS on PFS, a multivariable Cox regression analysis was performed adjusting for tumor grade, primary tumor location, and the interaction between 177Lu-DOTATATE doses received (zero, 1–2, 3–4) and CS. A total of 91 patients and 31 patients received 3–4 doses and zero doses of 177Lu-DOTATATE, respectively. On multivariable analysis, in patients treated with 3–4 doses of 177Lu-DOTATATE, for each 1-point increase in CS, the estimated hazard ratio (HR) for PFS was 2.0 (95% CI 1.61–2.48). On multivariable analysis, in patients who received zero doses of 177Lu-DOTATATE, for each 1-point increase in CS, the estimated HR for PFS was 1.22 (95% CI 0.91–1.65). Among patients treated with 3–4 doses of 177Lu-DOTATATE, those with lower CS experienced improved PFS with the treatment compared to patients with higher CS. This PFS difference, based upon CS, was not observed in patients who did not receive 177Lu-DOTATATE, suggesting the predictive utility of the score.

Supplementary Materials

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  • Akirov A, Larouche V, Alshehri S, Asa SL & Ezzat S 2019 Treatment options for pancreatic neuroendocrine tumors. Cancers 11 E828. (https://doi.org/10.3390/cancers11060828)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Ballal S, Yadav M, Bal C, Sahoo R & Tripathi M 2019 Broadening horizons with 225Ac-DOTATATE targeted alpha therapy for gastroenteropancreatic neuroendocrine tumour patients stable or refractory to 177Lu-DOTATATE PRRT: first clinical experience on the efficacy and safety. European Journal of Nuclear Medicine and Molecular Imaging 47 943946. (https://doi.org/10.1007/s00259-019-04567-2)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Baum RP, Kulkarni HR, Singh A, Kaemmerer D, Mueller D, Prasad V, Homman M, Robiller FC, Niepsch K & Franz H et al.2018 Results and adverse events of personalized peptide receptor radionuclide therapy with 90Yttrium and 177Lutetium in 1048 patients with neuroendocrine neoplasms. Oncotarget 9 1693216950. (https://doi.org/10.18632/oncotarget.24524)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Bodei L, Kidd MS, Singh A, van der Zwan WA, Severi S, Drozdov IA, Cwikla J, Baum RP, Kwekkeboom DJ & Paganelli G et al.2018 PRRT genomic signature in blood for prediction of 177Lu-octreotate efficacy. European Journal of Nuclear Medicine and Molecular Imaging 45 11551169. (https://doi.org/10.1007/s00259-018-3967-6)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Bodei L, Kidd MS, Singh A, Drozdov IA, Malczewska A, Baum RP, Krenning E & Modlin IM 2020 The utility of blood-based molecular tools-the NETest-to monitor and evaluate the efficacy of PRRT in neuroendocrine tumors. Journal of Clinical Oncology 38 35683568. (https://doi.org/10.1200/JCO.2020.38.15_suppl.3568)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Brabander T, van der Zwan WA, Teunissen JJM, Kam BLR, Feelders RA, de Herder WW, van Eijck CHJ, Franssen GJH, Krenning EP & Kwekkeboom DJ 2017 Long-term efficacy, survival, and safety of [(177)Lu-DOTA(0),Tyr(3)]octreotate in patients with gastroenteropancreatic and bronchial neuroendocrine tumors. Clinical Cancer Research 23 46174624. (https://doi.org/10.1158/1078-0432.CCR-16-2743)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Cerfolio RJ, Maniscalco L & Bryant AS 2008 The treatment of patients with stage IIIA non-small cell lung cancer from N2 disease: who returns to the surgical arena and who survives. Annals of Thoracic Surgery 86 91292 0; discussion 912. (https://doi.org/10.1016/j.athoracsur.2008.04.073)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Dalm SU, Nonnekens J, Doeswijk GN, de Blois E, van Gent DC, Konijenberg MW & de Jong M 2016 Comparison of the therapeutic response to treatment with a 177Lu-labeled somatostatin receptor agonist and antagonist in preclinical models. Journal of Nuclear Medicine 57 260265. (https://doi.org/10.2967/jnumed.115.167007)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Deppen SA, Blume J, Bobbey AJ, Shah C, Graham MM, Lee P, Delbeke D & Walker RC 2016a 68Ga-DOTATATE compared to 111In-DTPA-octreotide and conventional imaging for pulmonary and gastroenteropancreatic neuroendocrine tumors: a systematic review and meta-analysis. Journal of Nuclear Medicine 57 872878. (https://doi.org/10.2967/jnumed.115.165803)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Deppen SA, Liu E, Blume JD, Clanton J, Shi C, Jones-Jackson LB, Lakhani V, Baum RP, Berlin J & Smith GT et al.2016b Safety and efficacy of 68Ga-DOTATATE PET/CT for diagnosis, staging and treatment management of neuroendocrine tumors. Journal of Nuclear Medicine 57 708714. (https://doi.org/10.2967/jnumed.115.163865)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Hirmas N, Jadaan R & Al-Ibraheem A 2018 Peptide receptor radionuclide therapy and the treatment of gastroentero-pancreatic neuroendocrine tumors: current findings and future perspectives. Nuclear Medicine and Molecular Imaging 52 190199. (https://doi.org/10.1007/s13139-018-0517-x)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Hope TA, Bodei L, Chan JA, El-Haddad G, Fieldman N, Kunz PL, Mailman J, Menda Y, Metz DC & Mittra ES et al.2020 NANETS/SNMMI consensus statement on patient selection and appropriate use of 177 Lu-DOTATATE peptide receptor radionuclide therapy. Journal of Nuclear Medicine 61 222227. (https://doi.org/10.2967/jnumed.119.240911)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Huizing DMV, Aalbersberg EA, Versleijen MWJ, Tesselaar MET, Walraven I, Lahaye MJ, de Wit-van der Veen BJ & Stokkel MPM 2020 Early response assessment and prediction of overall survival after peptide receptor radionuclide therapy. Cancer Imaging 20 57. (https://doi.org/10.1186/s40644-020-00335-w)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Ianniello A, Sansovini M, Severi S, Nicolini S, Grana CM, Massri K, Bongiovanni A, Antonuzzo L, Di lorio V & Sarnelli A et al.2016 Peptide receptor radionuclide therapy with (177)Lu-DOTATATE in advanced bronchial carcinoids: prognostic role of thyroid transcription factor 1 and (18)F-FDG PET. European Journal of Nuclear Medicine and Molecular Imaging 43 10401046. (https://doi.org/10.1007/s00259-015-3262-8)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Kwekkeboom DJ, Krenning EP, Lebtahi R, Komminoth P, Kos-Kudla B, de Werder WW, Plockinger UMallorca Consensus Conference participants & European Neuroendocrine Tumor Society 2009 Enets Consensus Guidelines for the standards of care in neuroendocrine tumors: peptide receptor radionuclide therapy with radiolabeled somatostatin analogs. Neuroendocrinology 90 220226. (https://doi.org/10.1159/000225951)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Mariniello A, Bodei L, Tinelli C, Baio SM, Gilardi L, Colandrea M, Papi S, Valmadre G, Fazio N & Galetta D et al.2016 Long-term results of PRRT in advanced bronchopulmonary carcinoid. European Journal of Nuclear Medicine and Molecular Imaging 43 441452. (https://doi.org/10.1007/s00259-015-3190-7)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Merola E, Prasad V, Pascher A, Pape UF, Arsenic R, Denecke T, Fehrenbach U, Wiedenmann B & Pavel ME 2020 Peritoneal carcinomatosis in gastro-entero-pancreatic neuroendocrine neoplasms: clinical impact and effectiveness of the available therapeutic options. Neuroendocrinology 110 517524. (https://doi.org/10.1159/000503144)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Otte A, Herrmann R, Heppeler A, Behe M, Jermann E, Powell P, Maecke HR & Muller J 1999 Yttrium-90 DOTATOC: first clinical results. European Journal of Nuclear Medicine 26 14391447. (https://doi.org/10.1007/s002590050476)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Reidy-Lagunes D, Pandit-Taskar N, O’Donoghue JA, Krebs S, Staton KD, Lyashchenko SK, Lewis JS, Raj N, Gonen M & Lohrmann C et al.2019 Phase I trial of well-differentiated neuroendocrine tumors (NETs) with radiolabeled somatostatin antagonist 177Lu-Satoreotide tetraxetan. Clinical Cancer Research 25 69396947. (https://doi.org/10.1158/1078-0432.CCR-19-1026)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Sansovini M, Severi S, Ambrosetti A, Monti M, Nanni O, Sarnelli A, Bodei L, Garaboldi L, Bartolomei M & Paganelli G 2013 Treatment with the radiolabelled somatostatin analog 177Lu-DOTATATE for advanced pancreatic neuroendocrine tumors. Neuroendocrinology 97 347354. (https://doi.org/10.1159/000348394)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Stallons TAR, Saidi A, Tworowska I, Delpassand ES & Torgue JJ 2019 Preclinical investigation of 212 Pb-DOTAMTATE for peptide receptor radionuclide therapy in a neuroendocrine tumor model. Molecular Cancer Therapeutics 18 10121021. (https://doi.org/10.1158/1535-7163.MCT-18-1103)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Strosberg J, El-Haddad G, Wolin E, Hendifar A, Yao J, Chasen B, Mittra E, Kunz PL, Kulke MH & Jacene H et al.2017 Phase 3 trial of 177Lu-dotatate for midgut neuroendocrine tumors. New England Journal of Medicine 376 125135. (https://doi.org/10.1056/NEJMoa1607427)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Strosberg J, Al-Toubah T, Pelle E, Smith J, Haider M, Hutchinson T, Fleming J & El-Haddad G 2020a Risk of bowel obstruction in patients with mesenteric/peritoneal disease receiving peptide receptor radionuclide therapy (PRRT ). Journal of Nuclear Medicine 62 6972. (https://doi.org/10.2967/jnumed.120.242875)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Strosberg J, Kunz PL, Hendifar A, Yao J, Bushnell D, Kulke MH, Baum RP, Caplin M, Ruszniewski P & Delpassand E et al.2020b Impact of liver tumour burden, alkaline phosphatase elevation, and target lesion size on treatment outcomes with 177 Lu-Dotatate: an analysis of the NETTER-1 study. European Journal of Nuclear Medicine and Molecular Imaging 47 23722382. (https://doi.org/10.1007/s00259-020-04709-x)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Valkema R, De Jong M, Bakker WH, Breeman WA, Kooij PP, Lugtenberg PJ, De Jong FH, Christiansen A, Kam BL & De Herder WW et al.2002 Phase I study of peptide receptor radionuclide therapy with [In-DTPA]octreotide: the Rotterdam experience. Seminars in Nuclear Medicine 32 110122. (https://doi.org/10.1053/snuc/2002.31025)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • van der Zwan WA, Bodei L, Mueller-Brand J, de Herder WW, Kvols LK & Kwekkeboom DJ 2015 GEPNETs update: radionuclide therapy in neuroendocrine tumors. European Journal of Endocrinology 172 R1R8. (https://doi.org/10.1530/EJE-14-0488)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • Zandee WT, Brabander T, Blazevic A, Kam BLR, Teunissen JJM, Feelders RA, Hofland J & de Herder WW 2019 Symptomatic and radiological response to 177Lu-DOTATATE for the treatment of functioning pancreatic neuroendocrine tumors. Journal of Clinical Endocrinology and Metabolism 104 13361344. (https://doi.org/10.1210/jc.2018-01991)

    • PubMed
    • Search Google Scholar
    • Export Citation