Psycho-Oncological Screening Identifies High-Risk Subgroups Among Neuroendocrine Tumor Patients Undergoing PRRT with [¹⁷⁷Lu]Lu-DOTATATE: Implications for Survival

Abstract

Purpose

Neuroendocrine tumors (NETs) are a heterogeneous group of malignancies characterized by variable clinical presentations and significant psychological burdens. Peptide receptor radionuclide therapy (PRRT) with [¹⁷⁷Lu]Lu-DOTATATE is a cornerstone in managing somatostatin receptor-positive NETs. This study investigates the role of psycho-oncological screening using the Hornheider Screening Instrument (HSI) in identifying psychosocial distress and its impact on overall survival (OS) and progression-free survival (PFS) in NET patients undergoing PRRT.

Methods

A cohort of 100 NET patients with progressive disease scheduled for PRRT was retrospectively analyzed. All patients underwent psycho-oncological screening before PRRT using HSI. Patients were stratified into four groups, based on their screening results and acceptance or refusal of psycho-oncological support. Clinical outcomes, including PFS and OS, were assessed, and subgroup analyses were performed to identify potential predictors of survival.

Results

Among 38 patients identified as needing psycho-oncological support, 9 accepted and 29 declined treatment. Patients who accepted psycho-oncological care demonstrated a 100% survival rate, comparable to patients with no significant distress. In contrast, patients who declined care exhibited a significantly shorter OS (median 83.7 months) and a higher death rate (38%). No differences were observed in PFS across groups. Subgroup analysis revealed similar tumor grading, pretreatment, and therapeutic regimens, suggesting that psychosocial factors influence OS independent of disease progression. Notably, women were more likely to accept psycho-oncological support than men.

Conclusion

Psycho-oncological distress significantly impacts OS in NET patients undergoing PRRT. Acceptance of psycho-oncological care was associated with improved survival, highlighting the importance of integrating psychological support into routine NET management. These findings underscore the need for tailored psycho-oncological interventions, especially for patients at high risk who decline care. Further studies are warranted to elucidate the mechanisms linking psychosocial factors with clinical outcomes.

Zusammenfassung

Zielsetzung

Neuroendokrine Tumoren (NET) sind eine heterogene Gruppe von malignen Erkrankungen mit variabler klinischer Präsentation und einer erheblichen psychischen Belastung für die Betroffenen. Die Peptidrezeptor-Radionuklidtherapie (PRRT) mit [¹⁷⁷Lu]Lu-DOTATATE ist ein zentraler Bestandteil der Behandlung somatostatinrezeptor-positiver NET. Diese Studie untersucht den Nutzen psychoonkologischer Screenings mittels des Hornheider Screening-Instruments (HSI) zur Erkennung psychosozialer Belastungen sowie deren Einfluss auf das Gesamtüberleben (OS) und das progressionsfreie Überleben (PFS) bei NET-Patienten unter PRRT.

Methoden

Eine Kohorte von 100 NET-Patienten mit progredienter Erkrankung, die für eine PRRT vorgesehen waren, wurde retrospektiv analysiert. Vor Beginn der PRRT unterzogen sich alle Patienten einem psychoonkologischen Screening mittels HSI. Die Patienten wurden in vier Gruppen eingeteilt – basierend auf dem Screening-Ergebnis und der Annahme oder Ablehnung psychoonkologischer Unterstützung. Klinische Endpunkte wie PFS und OS wurden analysiert und Subgruppenanalysen zur Identifikation möglicher Überlebensprädiktoren durchgeführt.

Ergebnisse

Von 38 Patienten mit ermitteltem Unterstützungsbedarf nahmen 9 eine psychoonkologische Betreuung in Anspruch, während 29 diese ablehnten. Patienten, die die Unterstützung annahmen, wiesen eine 100%ige Überlebensrate auf – vergleichbar mit jenen ohne signifikanten Unterstützungsbedarf. Im Gegensatz dazu zeigten Patienten, die eine Betreuung ablehnten, ein signifikant kürzeres OS (Median 83,7 Monate) sowie eine erhöhte Sterberate (38%). Zwischen den Gruppen bestanden keine Unterschiede im PFS. Subgruppenanalysen zeigten vergleichbare Tumorgrade, Vorbehandlungen und therapeutische Schemata, was darauf hindeutet, dass psychosoziale Faktoren das OS unabhängig vom Krankheitsverlauf beeinflussen. Auffällig war, dass Frauen häufiger psychoonkologische Unterstützung annahmen als Männer.

Schlussfolgerung

Psychosoziale Belastung beeinflusst das Gesamtüberleben von NET-Patienten unter PRRT signifikant. Die Annahme psychoonkologischer Betreuung war mit einem verbesserten Überleben assoziiert und unterstreicht die Bedeutung der Integration psychologischer Unterstützung in die reguläre NET-Versorgung. Die Ergebnisse verdeutlichen den Bedarf an gezielten psychoonkologischen Interventionen, insbesondere für Hochrisikopatienten, die bislang keine Unterstützung annehmen. Weitere Studien sind notwendig, um die zugrunde liegenden Mechanismen des Zusammenhangs zwischen psychosozialen Faktoren und klinischem Verlauf besser zu verstehen.

Keywords

Neuroendocrine Tumors - Radionuclide Therapy - Psycho-oncology

Publication History

Received: 07 May 2025

Accepted: 23 June 2025

Article published online:
30 June 2025

• References

• 1 Strosberg J, El-Haddad G, Wolin E. et al. Phase 3 trial of 177Lu-Dotatate for midgut neuroendocrine tumors. N Engl J Med 2017; 376 (02) 125-135
• 2 Strosberg JR, Caplin ME, Kunz PL. et al. 177Lu-Dotatate plus long-acting octreotide versus high-dose long-acting octreotide in patients with progressive midgut neuroendocrine tumours (NETTER-1): final overall survival and long-term safety results from an open-label, randomised, controlled, phase 3 trial. Lancet Oncol 2021; 22 (12) 1752-1763
• 3 Singh S, Halperin D, Myrenhaug S. et al. [177Lu]Lu-DOTA-TATE plus long-acting octreotide versus high‑dose long-acting octreotide for the treatment of newly diagnosed, advanced grade 2–3, well-differentiated, gastroenteropancreatic neuroendocrine tumours (NETTER-2): an open-label, randomised, phase 3 study. The Lancet 2024; 403: 2807-2817
• 4 Kwekkeboom DJ, de Herder WW, Kam BL. et al. Treatment with the radiolabeled somatostatin analog [177Lu-DOTA0,Tyr3]octreotate: toxicity, efficacy, and survival. J Clin Oncol 2008; 26 (13) 2124-2130
• 5 Baudin E. et al. First multicentric randomized phase II trial investigating the antitumor efficacy of peptide receptor radionucleide therapy with 177Lutetium-Octreotate (OCLU) in unresectable progressive neuroendocrine pancreatic tumor: Results of the OCLURANDOM trial. Annals of Oncology 2022; 33 (Suppl. 7) S410-S416
• 6 Bodei L, Mueller-Brand J, Baum RP. et al. The joint IAEA, EANM, and SNMMI practical guidance on peptide receptor radionuclide therapy (PRRNT) in neuroendocrine tumours. Eur J Nucl Med Mol Imaging 2013; 40 (05) 800-816
• 7 Haug AR, Auernhammer CJ, Wängler B. et al. Intraindividual comparison of 68Ga-DOTATATE and 68Ga-DOTATOC PET/CT in patients with well-differentiated metastatic neuroendocrine tumors. J Nucl Med 2010; 51 (05) 692-696
• 8 Pavel M, Öberg K, Falconi M. et al. Gastroenteropancreatic neuroendocrine neoplasms: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 2020; 31 (07) 844-860
• 9 Strosberg J, Wolin E, Chasen B. et al. Health-related quality of life in patients with progressive midgut neuroendocrine tumors treated with 177Lu-Dotatate in the phase III NETTER-1 trial. J Clin Oncol 2018; 36 (25) 2578-2584
• 10 Hicks RJ, Kwekkeboom DJ, Krenning E. et al. ENETS consensus guidelines for the standards of care in neuroendocrine neoplasia: peptide receptor radionuclide therapy with radiolabelled somatostatin analogues. Neuroendocrinology 2017; 105 (03) 295-309
• 11 Kunz PL, Reidy-Lagunes D, Anthony LB. et al. Consensus guidelines for the management and treatment of neuroendocrine tumors. Pancreas 2013; 42 (04) 557-577
• 12 Stickel A, Pallauf A, Goerling U. Neuroendokrine Tumoren aus psychoonkologischer Sicht – ein Überblick. Der Onkologe 2018; 24 (02) 163-168
• 13 Singh S, Granberg D, Wolin E. et al. Patient-reported burden of a neuroendocrine tumor (NET) diagnosis: results from the first global survey of patients with NETs. J Glob Oncol 2016; 2 (05) 407-417
• 14 Haugland T, Wahl AK, Hofoss D. et al. Association between general self-efficacy, social support, cancer-related stress and physical health in patients with neuroendocrine tumors. Psychooncology 2016; 25 (06) 700-707
• 15 Wolin EM, Leyden J, Goldstein G. et al. Patient-reported experience of diagnosis, management, and burden of neuroendocrine tumors: results from a large patient survey in the USA. Pancreas 2017; 46: 639-647
• 16 Haugland T, Wahl AK, Hofoss D. et al. Association between general self-efficacy, social support, cancer-related stress and physical health-related quality of life: a path model study in patients with neuroendocrine tumors. Health Qual Life Outcomes 2016; 19: 14-11
• 17 Yadegarfar G, Friend L, Jones L. et al. Validation of the EORTC QLQ-GINET21 questionnaire for assessing quality of life of patients with gastrointestinal neuroendocrine tumors. Br J Cancer 2013; 108 (02) 301-310
• 18 Marinova M, Mücke M, Fischer F. et al. Quality of life in patients with midgut NET following peptide receptor radionuclide therapy. Eur J Nucl Med Mol Imaging 2019; 46 (11) 2252-2259
• 19 Haugland T, Vatn MH, Veenstra M. et al. Health related quality of life in patients with neuroendocrine tumors compared with the general Norwegian population. Qual Life Res 2009; 18: 719-726
• 20 Fröjd C, Larsson G, Lampic C. et al. Health-related quality of life and psychosocial function among patients with carcinoid tumours: patients with midgut carcinoid tumours compared with the general population. Health Qual Life Outcomes 2007; 11: 5-18
• 21 Haugland T, Wahl AK, Hofoss D. et al. Association between demographic and clinical variables and health-related quality of life in patients with neuroendocrine tumors. Health Qual Life Outcomes 2016; 14: 11
• 22 Larsson G, Sjödén PO, Oberg K. et al. Health-related quality of life, anxiety and depression in patients with midgut carcinoid tumours. Acta Oncol 2001; 40 (07) 825-831
• 23 Gerhards F, Augustin M, Zschocke I. et al. The validity of the Hornheide questionnaire for psychosocial support in skin tumor patients: a survey in an Austrian and German outpatient population with melanoma. Psychother Psychosom Med Psychol 2001; 51 (01) 25-33
• 24 Söllner W, DeVries A, Steixner E. et al. How successful are oncologists in identifying patient distress, perceived social support, and need for psychosocial counselling?. Br J Cancer 2001; 84 (02) 179-185
• 25 Sumnitsch P, Hartmann BL, Zanolin D. et al. Screening in psycho-oncology: Systematic assessment of the need for care in cancer patients using the Hornheide Screening Instrument. ProCare 2017; 22 (1/2) 7-14
• 26 Rumpold G, Augustin M, Zschocke I. et al. The validity of the Hornheide questionnaire for psychosocial support in skin tumor patients: a survey in an Austrian and German outpatient population with melanoma. Psychother Psychosom Med Psychol 2001; 51: 25-33
• 27 Yordanova A, Mayer K, Brossart P. et al. Safety of multiple repeated cycles of 177Lu-octreotate in patients with recurrent neuroendocrine tumour. Eur J Nucl Med Mol Imaging 2017; 44 (07) 1207-1214
• 28 Kröz M, Reif M, Büssing A. et al. Does self-regulation and autonomic regulation have an influence on survival in breast and colon carcinoma patients? Results of a prospective outcome study. Health Qual Life Outcomes 2011; 9: 85
• 29 Osborn RL, Demoncada AC, Feuerstein M. Psychosocial interventions for depression, anxiety, and quality of life in cancer survivors: meta-analyses. Int J Psychiatry Med 2006; 36: 13-34
• 30 Hinnen C, Hagedoorn M, Sanderman R. et al. The role of distress, neuroticism and time since diagnosis in explaining support behaviors in partners of women with breast cancer: results of a longitudinal analysis. Psychooncology 2007; 16: 913-919
• 31 Calderon C, Carmona-Bayonas A, Hernández R. et al. Coping strategies and depressive symptoms in cancer patients. Clin Transl Oncol 2020; 22: 330-336