Improved survival in patients with thyroid function test abnormalities secondary to immune-checkpoint inhibitors

Ferreira, Joana Lima; Costa, Cláudia; Marques, Bernardo; Castro, Sofia; Victor, Margarida; Oliveira, J.; Santos, Ana Paula; Sampaio, Inês Lucena; Duarte, Hugo; Marques, Ana Paula; Torres, Isabel

doi:10.1007/s00262-020-02664-y

Cited by 40 publications

(41 citation statements)

References 42 publications

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“…Even after adjusting for sex, age, and cancer type, this same result was consistently obtained. [27]. However, none of them showed a difference in the thyroid dysfunction type.…”

Section: Discussionmentioning

confidence: 92%

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Association between the type of thyroid dysfunction induced by immune checkpoint inhibitors and prognosis in cancer patients

Baek¹,

Jeong²,

Shin³

et al. 2021

Preprint

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Background Immune checkpoint inhibitors (ICIs) cause thyroid immune-related adverse effects (irAEs). However, associations between each type of thyroid immune-related adverse effect (irAE) and the anti-tumor effect of ICI remains unknown. This study aimed to determine the effects of each type of thyroid dysfunction on patient survival. Methods Patients who initiated ICI treatment from January 2015 to December 2019 in Seoul St. Mary’s Hospital were retrospectively analyzed. Thyroid dysfunction was classified into four types: newly developed overt or subclinical hypothyroidism, thyrotoxicosis, worsened hypothyroidism, and subclinical hyperthyroidism. Patients were divided into two groups according to the presence or absence of thyroid dysfunction. Results Among the 196 patients, 66 (33.7%) developed thyroid irAEs. There was no significant difference in age, sex, or cancer type between the two groups. The overall survival in patients with thyroid irAEs was significantly higher than that in patients without thyroid irAEs (38 months vs. 13 months, respectively, p = 0.005). After adjusting for confounding factors, the hazard ratio for mortality in the thyroid irAE group compared to the no thyroid irAE group was 0.520 (p = 0.007). Newly developed overt or subclinical hypothyroidism patients showed a significantly lower hazard ratio for morbidity of 0.309 (p = 0.001). Patients with thyrotoxicosis showed a worse hazard ratio for morbidity than those without thyroid irAE, although the difference was not statistically significant. Conclusions It was verified that ICI treatment-induced thyroid dysfunction was associated with better survival, even in the real-world practice. Thus, endocrinologists should cooperate with oncologists to monitor patients treated with ICIs.

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“…Even after adjusting for sex, age, and cancer type, this same result was consistently obtained. [27]. However, none of them showed a difference in the thyroid dysfunction type.…”

Section: Discussionmentioning

confidence: 92%

“…From previous studies, it could be assumed that thyroid irAEs were associated with prognosis, and some factors were associated with thyroid irAEs [26,27]. However, those previous studies were mostly based on clinical trials or speci c populations with a focus on a particular ICI in each study.…”

Section: Introductionmentioning

confidence: 99%

Association between the type of thyroid dysfunction induced by immune checkpoint inhibitors and prognosis in cancer patients

Baek¹,

Jeong²,

Shin³

et al. 2021

Preprint

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“…If confirmed in larger studies, it could provide a therapeutic strategy for poor prognosis endometrial cancer patients. In metastatic renal cell carcinoma, sunitinib-induced hypothyroidism is associated with improved progression-free survival [8][9][10], and thyroid dysfunction caused by immune checkpoint inhibition portends suitable outcomes in several cancer types [56,57]. Inhibition of the cell adhesion molecule integrin αvβ3 could provide a novel targeted treatment strategy for endometrial and other cancers.…”

Section: Discussionmentioning

confidence: 99%

Does Clinical and Biochemical Thyroid Dysfunction Impact on Endometrial Cancer Survival Outcomes? A Prospective Database Study

Barr

Njoku

Hotchkies

et al. 2021

Cancers

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Endometrial cancer is the commonest gynaecological malignancy in developed countries, and women presenting with high risk or advanced disease have poor outcomes. Thyroid hormones play a key role in cellular metabolism and can influence cancer growth and invasion. Our aim was to evaluate the association between clinical and biochemical thyroid dysfunction and endometrial cancer survival outcomes. This was a prospective cohort study of women treated for endometrial cancer at a specialist centre. Clinical diagnosis of hypothyroidism was based on clinical and biochemical assessment, verified by general practitioner (GP) records. Pre-treatment serum samples were tested for thyrotropin (TSH), thyroid hormones (free T4 and total T3), and thyroid peroxidase antibodies. Kaplan–Meier survival estimates and log-rank tests were used to compare survival between groups, while Cox regression was used for multivariable analysis, adjusting for known confounders and effect modifications. In total, 333 women with median age and body mass index (BMI) of 66 years (interquartile range (IQR) 56, 73) and 33 kg/m2 (IQR 27, 41) respectively were included. A total of 51 (15.3%) women had a diagnosis of hypothyroidism, 39 (11.9%) had biochemical evidence of overt or subclinical hypothyroidism. Median follow-up was 35 months (IQR 21, 45) with 38 (11.7%) relapses and 50 (15.0%) deaths. Women with a diagnosis of hypothyroidism had improved overall survival (adjusted HR = 0.22, 95%CI 0.06–0.74, p = 0.02), cancer-specific survival (adjusted HR = 0.21, 95%CI 0.05–0.98, p = 0.04) and fewer recurrences (adjusted HR = 0.17, 95%CI 0.04–0.77, p = 0.02) than those who did not. Confirmatory studies should explore underlying mechanisms and the potential for therapeutic exploitation.

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“…• Development of endocrinopathy is associated with longer overall survival versus those patients without and therefore, lifelong hormonal treatment with specialist care from both endocrinologists and oncologists is required. D L Morganstein Endocrine toxicity of immunotheraphy R121 10:3 better cancer outcomes and longer overall survival than controls without endocrinopathy (78,79,80). Therefore the cohort of long term survivors is likely to include many with endocrinopathy, with the associated need for hormone replacement, impact on quality of life and need for specialist follow up.…”

Section: Long Term Implicationsmentioning

confidence: 99%

“…This is particularly important as it is now emerging that the development of endocrinopathy, specifically hypophysitis or thyroid dysfunction, is associated with better cancer outcomes and longer overall survival than controls without endocrinopathy ( 78 , 79 , 80 ). Therefore the cohort of long term survivors is likely to include many with endocrinopathy, with the associated need for hormone replacement, impact on quality of life and need for specialist follow up.…”

Section: Long Term Implicationsmentioning

confidence: 99%

Endocrine toxicity of cancer immunotherapy: clinical challenges

Anderson

Morganstein

2021

Endocrine Connections

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Immune checkpoint inhibitors are now widely used in the treatment of multiple cancers. The major toxicities of these treatments are termed immune related adverse events and endocrine dysfunction is common. Thyroid disease, hypopituitarism and a form of diabetes resembling type 1 diabetes are now all well described, with different patterns emerging with different checkpoint inhibitors. We review the presentation and management of the common endocrine immune related adverse events, and discuss a number of recent advances in the understanding of these important, potentially life threatening toxicities. We also discuss some remaining dilemmas in management.

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Improved survival in patients with thyroid function test abnormalities secondary to immune-checkpoint inhibitors

Cited by 40 publications

References 42 publications

Association between the type of thyroid dysfunction induced by immune checkpoint inhibitors and prognosis in cancer patients

Association between the type of thyroid dysfunction induced by immune checkpoint inhibitors and prognosis in cancer patients

Does Clinical and Biochemical Thyroid Dysfunction Impact on Endometrial Cancer Survival Outcomes? A Prospective Database Study

Endocrine toxicity of cancer immunotherapy: clinical challenges

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