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Incidence of psychiatric illness in patients with neuroendocrine tumors: a comparative population-based analysis

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Abstract

Purpose

Diversion of tryptophan to tumoral hormonal production has been suggested to result in psychiatric illnesses in neuroendocrine tumors (NET). We measured the occurrence of psychiatric illness after NET diagnosis and compare it to colon cancer (CC).

Methods

We conducted a population-based retrospective cohort study. Adults with NET were matched 1:1 to CC (2000–2019). Psychiatric illness was defined by mental health diagnoses and mental health care use after a cancer diagnosis, categorized as severe, other, and none. Cumulative incidence functions accounted for death as a competing risk.

Results

A total of 11,223 NETs were matched to CC controls. Five-year cumulative incidences of severe psychiatric illness for NETs vs. CC was 7.7% (95%CI 7.2–8.2%) vs 7.6% (95%CI 7.2–8.2%) (p = 0.50), and that of other psychiatric illness was 32.9% (95%CI 32.0–33.9%) vs 31.6% (95%CI 30.8–32.6%) (p = 0.005). In small bowel and lung NETs, 5-year cumulative incidences of severe (8.1% [95%CI 7.3–8.9%] vs. 7.0% [95%CI 6.3–7.8%]; p = 0.01) and other psychiatric illness (34.7% [95%CI 33.3–36.1%] vs. 31.1% [95%CI 29.7–32.5%]; p < 0.01) were higher than for matched CC. The same was observed for serotonin-producing NETs for both severe (7.9% [95%CI 6.5–9.4%] vs. 6.8% [95%CI 5.5–8.2%]; p = 0.02) and other psychiatric illness (35.4% [95%CI 32.8–38.1%] vs. 31.9% [95%CI 29.3–34.4%]; p = 0.02).

Conclusions

In all NETs, there was no difference observed in the incidence of psychiatric illness compared to CC. For sub-groups of small bowel and lung NETs and of serotonin-producing NETs, the incidence of psychiatric illness was higher than for CC. These data suggest a signal towards a relationship between those sub-groups of NETs and psychiatric illness.

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Acknowledgements

This study was supported by ICES, which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care (MOHLTC). This study also received funding from the Canadian Institutes of Health Research (CIHR) and the North American Neuroendocrine Society (NANETS) New Clinical Investigator Scholarship. Parts of this material are based on data and information compiled and/or information provided by: Cancer Care Ontario (CCO) and CIHI. The analyses, conclusions, opinions, and statements expressed herein are solely those of the authors and do not reflect those of the funding or data sources; no endorsement is intended or should be inferred.

The datasets from this study are held securely in coded form at ICES. While data sharing agreements prohibit ICES from making the datasets publicly available, access may be granted to those who meet pre-specified criteria for confidential access, available at www.ices.on.ca/DAS. The dataset creation plan and underlying analytic code are available from the authors upon reasonable request, understanding that the computer programs may rely upon coding templates or macros that are unique to ICES and are therefore either inaccessible or may require modification.

Funding

This work was supported by the NANETS New Clinical Investigator Scholarship and an operating grant from the Canadian Institute of Health Research (FRN #407301).

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Authors and Affiliations

  1. Department of Surgery, University of Toronto, Toronto, ON, Canada

    Julie Hallet, Calvin H. L. Law, Jesse Zuckerman & Natalie G. Coburn

  2. Susan Leslie Clinic for Neuroendocrine Tumors, Odette Cancer Centre – Sunnybrook Health Sciences Centre, Toronto, ON, Canada

    Julie Hallet, Elie Isenberg-Grzeda, Calvin H. L. Law, Simron Singh, Sten D. Myrehaug & Angela Assal

  3. Clinical Evaluative Sciences, Sunnybrook Research Institute, Toronto, ON, Canada

    Julie Hallet, Calvin H. L. Law, Victoria Barabash, Simron Singh, Sten D. Myrehaug, Angela Assal & Natalie G. Coburn

  4. ICES, Toronto, ON, Canada

    Julie Hallet, Calvin H. L. Law, Simron Singh, Wing C. Chan & Natalie G. Coburn

  5. Department of Medicine, University of Toronto, Toronto, ON, Canada

    Simron Singh & Angela Assal

  6. Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada

    Sten D. Myrehaug

  7. Department of Community Health Sciences, University of Manitoba, Winnipeg, MB, Canada

    Alyson L. Mahar

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Contributions

Concept and study design: JH, EIG, CL, SS, SDM, and ALM. Data acquisition, analysis, and interpretation: JH, EIG, CL, VB, JZ, SS, SDM, AA, WCC, NGC, and ALM. Funding and administration: JH, EIG, CL, VB, NGC, and ALM. Manuscript draft: JH and ALM. Manuscript critical revision and final approval: JH, EIG, CL, VB, JZ, SS, SDM, AA, WCC, NGC, and ALM.

Corresponding author

Correspondence to Julie Hallet.

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Competing interests

JH has received speaking honoraria from Ipsen Biopharmaceuticals and Advanced Accelerator Applications. EIG has a consulting agreement with Celgene USA CL has received speaking honoraria from Ipsen Biopharmaceuticals and Novartis Oncology. SS has received speaking honoraria from Ipsen Biopharmaceuticals Canada and Novartis Oncology, and research grants from Novartis Oncology and EMD Serono. NC receives salary support from Cancer Care Ontario as Lead for Patient-Reported Outcomes, and an honorarium from Astra-Zeneca. All remaining authors have declared no conflict of interest.

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Implications for practice

Sub-groups of small bowel and lung neuroendocrine tumors (NETs) and of serotonin-producing NETs have a higher incidence of psychiatric illness than other cancers. It is critical to provide patients with appropriate and tailored psycho-social supportive care. Particular attention should be paid to patients with lung and small bowel NETs, and those with functional NETs, regarding symptoms indicating psychiatric illness or distress. Routine screening of patient-reported outcomes, as implemented in various cancer centres, can be used to do so.

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Hallet, J., Isenberg-Grzeda, E., Law, C.H.L. et al. Incidence of psychiatric illness in patients with neuroendocrine tumors: a comparative population-based analysis. Support Care Cancer 30, 9635–9646 (2022). https://doi.org/10.1007/s00520-022-07365-z

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