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Associations between immune-related thyroid dysfunction and efficacy of immune checkpoint inhibitors: a systematic review and meta-analysis

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Abstract

Background

There is growing evidence suggesting that the occurrence of immune-related adverse events (irAEs) may be a predictor of immune checkpoint inhibitor efficacy. Whether this association extends to all irAEs or just those within particular organs/systems is yet to be resolved. As immune-related thyroid dysfunction (thyroid irAE) is one of the most commonly reported irAEs, this study aims to summarize the available data and determine if thyroid irAE is a surrogate marker for improved cancer outcomes during ICI therapy.

Methods

PubMed, EMBASE and Cochrane Library were searched up to July 1st 2021 for studies assessing the relationship between thyroid irAE development during ICI therapy and cancer outcomes. Outcome measures of interest include overall survival (OS) and progression free survival (PFS). Sub-group analyses based on cancer type and adjustment for immortal time bias (ITB) were also performed.

Results

Forty-seven studies were included in the systematic review. Twenty-one studies were included in the OS meta-analysis whilst 15 were included in the PFS meta-analysis. Development of thyroid irAE during ICI therapy was associated with improved OS and PFS (OS: HR 0.52, CI 0.43–0.62, p < 0.001; PFS: HR 0.58, CI 0.50–0.67, p < 0.001). Sub-group analyses involving non-small cell lung cancer populations and studies where ITB was accounted for, observed similar results (HR 0.37, CI 0.24–0.57, p < 0.001) and (HR 0.51, CI 0.39–0.69, p < 0.001), respectively.

Conclusion

Despite the heterogeneity and biases identified, the evidence does suggest that the development of thyroid irAE is associated with anti-tumor effects of ICIs and therefore, can be used as a surrogate marker for clinical response.

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References

  1. Wolchok JD, Chiarion-Sileni V, Gonzalez R et al (2018) Overall survival with combined nivolumab and ipilimumab in advanced melanoma. N Engl J Med 377:1345–1356

    Article  Google Scholar 

  2. Antonia SJ, Villegas A, Daniel D et al (2017) Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer. N Engl J Med 377:1919–1929

    Article  CAS  PubMed  Google Scholar 

  3. Borghaei H, Paz-Ares L, Horn L et al (2015) Nivolumab versus docetaxel in advanced nonsquamous non-small-cell lung cancer. N Engl J Med 373:1627–1639

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Overman MJ, McDermott R, Leach JL et al (2017) Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study. Lancet Oncol 18:1182–1191

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Yamauchi I, Yasoda A, Matsumoto S et al (2019) Incidence, features, and prognosis of immune-related adverse events involving the thyroid gland induced by nivolumab. PLoS One 14:e0216954

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Shankar B, Zhang J, Naqash AR et al (2020) Multisystem immune-related adverse events associated with immune checkpoint inhibitors for treatment of non-small cell lung cancer. JAMA Oncol 6:1952–1956

    Article  PubMed  Google Scholar 

  7. Zhou X, Yao Z, Yang H et al (2020) Are immune-related adverse events associated with the efficacy of immune checkpoint inhibitors in patients with cancer? A systematic review and meta-analysis. BMC Med 18:87

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Hussaini S, Chehade R, Boldt RG et al (2020) Association between immune-related side effects and efficacy and benefit of immune checkpoint inhibitors: a systematic review and meta-analysis. Cancer Treat Rev 92:102134

    Article  PubMed  CAS  Google Scholar 

  9. Cortellini A, Buti S, Agostinelli V et al (2019) A systematic review on the emerging association between the occurrence of immune-related adverse events and clinical outcomes with checkpoint inhibitors in advanced cancer patients. Semin Oncol 45:362–371

    Article  CAS  Google Scholar 

  10. Fujii T, Naing A, Rolfo C et al (2018) Biomarkers of response to immune checkpoint blockade in cancer treatment. Crit Rev Oncol Hematol 130:108–120

    Article  PubMed  Google Scholar 

  11. Gleiss A, Oberbauer R, Heinze G (2018) An unjustified benefit: immortal time bias in the analysis of time-dependent events. Transpl Int 31:125–213

    Article  PubMed  Google Scholar 

  12. Sterne JAC, Hernán MA, Reeves BC et al (2016) ROBINS-I: a tool for assessing risk of bias in non-randomized studies of interventions. BMJ 355:i4919. https://doi.org/10.1136/bmj.i4919

    Article  PubMed  PubMed Central  Google Scholar 

  13. Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558

    Article  PubMed  Google Scholar 

  14. Higgins JP, Thompson SG, Deeks JJ et al (2003) Measuring inconsistency in meta-analyses. BMJ 327:557–560

    Article  PubMed  PubMed Central  Google Scholar 

  15. DerSimonian R, Kacker R (2007) Random-effects model for meta-analysis of clinical trials: an update. Contemp Clin Trials 28:105–114

    Article  PubMed  Google Scholar 

  16. Begg CB, Mazumdar M (1994) Operating characteristics of a rank correlation test for publication bias. Biometrics 50:1088–1101

    Article  CAS  PubMed  Google Scholar 

  17. Egger M, Davey Smith G, Schneider M et al (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Kim HI, Kim M, Lee SH et al (2017) Development of thyroid dysfunction is associated with clinical response to PD-1 blockade treatment in patients with advanced non-small cell lung cancer. Oncoimmunology 7:e1375642

    Article  PubMed  PubMed Central  Google Scholar 

  19. Fujisawa Y, Yoshino K, Otsuka A et al (2017) Fluctuations in routine blood count might signal severe immune-related adverse events in melanoma patients treated with nivolumab. J Dermatol Sci 88:225–231

    Article  CAS  PubMed  Google Scholar 

  20. Osorio JC, Ni A, Chaft JE et al (2017) Antibody-mediated thyroid dysfunction during T-cell checkpoint blockade in patients with non-small-cell lung cancer. Ann Oncol 28:583–589

    Article  CAS  PubMed  Google Scholar 

  21. Grangeon M, Tomasini P, Chaleat S et al (2019) Association between immune-related adverse events and efficacy of immune checkpoint inhibitors in non-small-cell lung cancer. Clin Lung Cancer 30:201–207

    Article  CAS  Google Scholar 

  22. Haratani K, Hayashi H, Chiba Y et al (2018) Association of immune-related adverse events with nivolumab efficacy in non-small-cell lung cancer. JAMA Oncol 4:374–378

    Article  PubMed  Google Scholar 

  23. Owen DH, Wei L, Bertino EM et al (2018) Incidence, risk factors, and effect on survival of immune-related adverse events in patients with non-small-cell lung cancer. Clin Lung Cancer 19:e893–e900

    Article  PubMed  PubMed Central  Google Scholar 

  24. Ricciuti B, Genova C, De Giglio A et al (2019) Impact of immune-related adverse events on survival in patients with advanced non-small cell lung cancer treated with nivolumab: long-term outcomes from a multi-institutional analysis. J Cancer Res Clin Oncol 145:479–485

    Article  CAS  PubMed  Google Scholar 

  25. Cortellini A, Chiari R, Ricciuti B et al (2019) Correlations between the immune-related adverse events spectrum and efficacy of anti-PD1 immunotherapy in NSCLC patients. Clin Lung Cancer 20:237-247.e1

    Article  CAS  PubMed  Google Scholar 

  26. Funazo TY, Nomizo T, Ozasa H et al (2019) Clinical impact of low serum free T4 in patients with non-small cell lung cancer treated with nivolumab. Sci Rep 9:17085

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Koyama J, Horiike A, Yoshizawa T et al (2019) Correlation between thyroid transcription factor-1 expression, immune-related thyroid dysfunction, and efficacy of anti-programmed cell death protein-1 treatment in non-small cell lung cancer. J Thorac Dis 11:1919–1928

    Article  PubMed  PubMed Central  Google Scholar 

  28. Lei M, Michael A, Patel S et al (2019) Evaluation of the impact of thyroiditis development in patients receiving immunotherapy with programmed cell death-1 inhibitors. J Oncol Pharm Pract 25:1402–1411

    Article  CAS  PubMed  Google Scholar 

  29. Maeda T, Yoshino K, Nagai K et al (2019) Development of endocrine immune-related adverse events and improved survival in advanced melanoma patients treated with nivolumab monotherapy. Eur J Cancer 115:13–16

    Article  PubMed  Google Scholar 

  30. Peiró I, Palmero R, Iglesias P et al (2019) Thyroid dysfunction induced by nivolumab: searching for disease patterns and outcomes. Endocrine 64:605–613

    Article  PubMed  CAS  Google Scholar 

  31. Sakakida T, Ishikawa T, Uchino J et al (2019) Clinical features of immune-related thyroid dysfunction and its association with outcomes in patients with advanced malignancies treated by PD-1 blockade. Oncol Lett 18:2140–2147

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Verzoni E, Cartenì G, Cortesi E et al (2019) Real-world efficacy and safety of nivolumab in previously-treated metastatic renal cell carcinoma, and association between immune-related adverse events and survival: the Italian expanded access program. J Immunother Cancer 7:99

    Article  PubMed  PubMed Central  Google Scholar 

  33. Basak EA, van der Meer JWM, Hurkmans DP et al (2020) Overt thyroid dysfunction and anti-thyroid antibodies predict response to anti-PD-1 immunotherapy in cancer patients. Thyroid 30(7):966–973

    Article  CAS  PubMed  Google Scholar 

  34. Cortellini A, Friedlaender A, Banna GL et al (2020) Immune-related adverse events of pembrolizumab in a large real-world cohort of patients With NSCLC with a PD-L1 expression ≥ 50% and their relationship with clinical outcomes. Clin Lung Cancer 21:498-508.e2

    Article  CAS  PubMed  Google Scholar 

  35. Economopoulou P, Kotsantis I, Papaxoinis G et al (2020) Association of autoimmunity with survival in patients with recurrent/metastatic head and neck squamous cell carcinoma treated with nivolumab. Oral Oncol 111:105013

    Article  CAS  PubMed  Google Scholar 

  36. Eggermont AMM, Kicinski M, Blank CU et al (2020) Association between immune-related adverse events and recurrence-free survival among patients with stage III melanoma randomized to receive pembrolizumab or placebo: a secondary analysis of a randomized clinical trial. JAMA Oncol 6:519–527

    Article  PubMed  PubMed Central  Google Scholar 

  37. España S, Montes Pérez, de Oca A, Marques-Pamies M et al (2020) Endocrine adverse events related to immune-oncology agents: retrospective experience of a single institution. Transl Lung Cancer Res 9:103–110

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Lima Ferreira J, Costa C, Marques B et al (2020) Improved survival in patients with thyroid function test abnormalities secondary to immune-checkpoint inhibitors. Cancer Immunol Immunother. https://doi.org/10.1007/s00262-020-02664-y

    Article  PubMed  Google Scholar 

  39. Kelly K, Manitz J, Patel MR et al (2020) Efficacy and immune-related adverse event associations in avelumab-treated patients. J Immunother Cancer 8:e001427

    Article  PubMed  PubMed Central  Google Scholar 

  40. Kijima T, Fukushima H, Kusuhara S et al (2020) Association between the occurrence and spectrum of immune-related adverse events and efficacy of pembrolizumab in Asian patients with advanced urothelial cancer: multicenter retrospective analyses and systematic literature review. Clin Genitourin Cancer S1558–7673:30163–30164

    Google Scholar 

  41. Kotwal A, Kottschade L, Ryder M (2020) PD-l1 inhibitor-induced thyroiditis is associated with better overall survival in cancer patients. Thyroid 30:177–184

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Maillet D, Corbaux P, Stelmes JJ et al (2020) Association between immune-related adverse events and long-term survival outcomes in patients treated with immune checkpoint inhibitors. Eur J Cancer 132:61–70

    Article  CAS  PubMed  Google Scholar 

  43. Bai R, Li L, Chen X et al (2021) Correlation of peripheral blood parameters and immune-related adverse events with the efficacy of immune checkpoint inhibitors. J Oncol 10:9935076

    Google Scholar 

  44. Frelau A, Jali E, Campillo-Gimenez B et al (2021) Prognostic impact of thyroid dysfunctions on progression-free survival in patients with metastatic melanoma treated with anti-PD-1 antibodies. Melanoma Res 31:208–217

    Article  CAS  PubMed  Google Scholar 

  45. Luongo C, Morra R, Gambale C et al (2021) Higher baseline TSH levels predict early hypothyroidism during cancer immunotherapy. J Endocrinol Invest 44:1927–1933

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Muir CA, Clifton-Bligh RJ, Long GV et al (2021) Thyroid immune-related adverse events following immune checkpoint inhibitor treatment. J Clin Endocrinol Metab. https://doi.org/10.1210/clinem/dgab263

    Article  PubMed  Google Scholar 

  47. Street S, Chute D, Strohbehn I et al (2021) The positive effect of immune checkpoint inhibitor-induced thyroiditis on overall survival accounting for immortal time bias: a retrospective cohort study of 6596 patients. Ann Oncol 32:1050–1051

    Article  CAS  PubMed  Google Scholar 

  48. Thuillier P, Joly C, Alavi Z et al (2021) Thyroid dysfunction induced by immune checkpoint inhibitors is associated with a better progression-free survival and overall survival in non-small cell lung cancer: an original cohort study. Cancer Immunol Immunother. https://doi.org/10.1007/s00262-020-02802-6

    Article  PubMed  Google Scholar 

  49. Zhou Y, Xia R, Xiao H et al (2020) Thyroid function abnormality induced by PD-1 inhibitors have a positive impact on survival in patients with non-small cell lung cancer. Int Immunopharmacol 91:107296

    Article  PubMed  CAS  Google Scholar 

  50. Al Ashi SI, Thapa B, Flores M et al (2021) Endocrine toxicity and outcomes in patients with metastatic malignancies treated with immune checkpoint inhibitors. J Endocr Soc 5:bvab100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Ahn BC, Pyo KH, Xin CF et al (2019) Comprehensive analysis of the characteristics and treatment outcomes of patients with non-small cell lung cancer treated with anti-PD-1 therapy in real-world practice. J Cancer Res Clin Oncol 145:1613–1623

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Campredon P, Mouly C, Lusque A et al (2019) Incidence of thyroid dysfunctions during treatment with nivolumab for non-small cell lung cancer: retrospective study of 105 patients. Presse Med 48:e199–e207

    Article  PubMed  Google Scholar 

  53. Ksienski D, Wai ES, Croteau N et al (2019) Efficacy of nivolumab and pembrolizumab in patients with advanced non-small-cell lung cancer needing treatment interruption because of adverse events: a retrospective multicenter analysis. Clin Lung Cancer 20:e97–e106

    Article  CAS  PubMed  Google Scholar 

  54. Freeman-Keller M, Kim Y, Cronin H et al (2016) Nivolumab in resected and unresectable metastatic melanoma: characteristics of immune-related adverse events and association with outcomes. Clin Cancer Res 22:886–894

    Article  CAS  PubMed  Google Scholar 

  55. Matsuo M, Yasumatsu R, Masuda M et al (2020) Relationship between immune-related adverse events and the long-term outcomes in recurrent/metastatic head and neck squamous cell carcinoma treated with nivolumab. Oral Oncol 101:104525

    Article  CAS  PubMed  Google Scholar 

  56. Al Mushref M, Guido PA, Collichio FA et al (2020) Thyroid dysfunction, recovery, and prognosis in melanoma patients treated with immune checkpoint inhibitors: a retrospective review. Endocr Pract 26:36–42

    Article  PubMed  Google Scholar 

  57. D’Aiello A, Lin J, Gucalp R et al (2021) Thyroid dysfunction in lung cancer patients treated with immune checkpoint inhibitors (ICIs): outcomes in a multiethnic urban cohort. Cancers (Basel) 13:1464

    Article  CAS  Google Scholar 

  58. Rubino R, Marini A, Roviello G et al (2021) Endocrine-related adverse events in a large series of cancer patients treated with anti-PD1 therapy. Endocrine. https://doi.org/10.1007/s12020-021-02750-w

    Article  PubMed  PubMed Central  Google Scholar 

  59. Paderi A, Giorgione R, Giommoni E et al (2021) Association between immune related adverse events and outcome in patients with metastatic renal cell carcinoma treated with immune checkpoint inhibitors. Cancers (Basel) 13:860

    Article  CAS  Google Scholar 

  60. Morimoto K, Yamada T, Takumi C et al (2021) Immune-related adverse events are associated with clinical benefit in patients with non-small-cell lung cancer treated with immunotherapy plus chemotherapy: a retrospective study. Front Oncol. https://doi.org/10.3389/fonc.2021.630136

    Article  PubMed  PubMed Central  Google Scholar 

  61. Lui DTW, Lee CH, Tang V, et al (2021) Thyroid immune-related adverse events in patients with cancer treated with anti-PD1/anti-CTLA4 immune checkpoint inhibitor combination: clinical course and outcomes. Endocr Pract S1530-891X(21)00030-6

  62. Holstead RG, Kartolo BA, Hopman WM et al (2021) Impact of the development of immune related adverse events in metastatic melanoma treated with PD -1 inhibitors. Melanoma Res 31:258–263

    Article  CAS  PubMed  Google Scholar 

  63. Fujisawa Y, Yoshino K, Otsuka A et al (2018) Retrospective study of advanced melanoma patients treated with ipilimumab after nivolumab: Analysis of 60 Japanese patients. J Dermatol Sci 89:60–66

    Article  CAS  PubMed  Google Scholar 

  64. Cortellini A, Friedlaender A, Banna GL et al (2020) Immune-related adverse events of pembrolizumab in a large real-world cohort of patients with NSCLC with a PD-L1 expression ≥ 50% and their relationship with clinical outcomes. Clin Lung Cancer 21:498.e2-508

    Article  CAS  Google Scholar 

  65. Paderi A, Giorgione R, Giommoni E et al (2021) Association between immune related adverse events and outcome in patients with metastatic renal cell carcinoma treated with immune checkpoint inhibitors. Cancers (Basel) 13:860

    Article  CAS  Google Scholar 

  66. Lisberg A, Tucker DA, Goldman JW et al (2018) Treatment-related adverse events predict improved clinical outcome in NSCLC patients on KEYNOTE-001 at a single center. Cancer Immunol Res 6:288–294

    Article  PubMed  PubMed Central  Google Scholar 

  67. de Filette J, Andreescu CE, Cools F et al (2019) A systematic review and meta-analysis of endocrine-related adverse events associated with immune checkpoint inhibitors. Horm Metab Res 51:145–156

    Article  PubMed  CAS  Google Scholar 

  68. Park R, Lopes L, Saeed A (2021) Anti-PD-1/L1-associated immune-related adverse events as harbinger of favorable clinical outcome: systematic review and meta-analysis. Clin Transl Oncol 23:100–109

    Article  CAS  PubMed  Google Scholar 

  69. Barroso-Sousa R, Barry WT, Garrido-Castro AC et al (2018) Incidence of endocrine dysfunction following the use of different immune checkpoint inhibitor regimens: a systematic review and meta-analysis. JAMA Oncol 4:173–182

    Article  PubMed  Google Scholar 

  70. Hussaini S, Chehade R, Boldt RG et al (2021) Association between immune-related side effects and efficacy and benefit of immune checkpoint inhibitors: a systematic review and meta-analysis. Cancer Treat Rev 92:102134

    Article  CAS  PubMed  Google Scholar 

  71. Cortellini A, Buti S, Agostinelli V et al (2019) A systematic review on the emerging association between the occurrence of immune-related adverse events and clinical outcomes with checkpoint inhibitors in advanced cancer patients. Semin Oncol 46:362–371

    Article  CAS  PubMed  Google Scholar 

  72. Ye Y, Jing Y, Li L et al (2020) Sex-associated molecular differences for cancer immunotherapy. Nat Commun 11:1779

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Network NCC (2021) NCCN guidelines version 4.2021 management of immune checkpoint inhibitor-related toxicity https://www.nccn.org/professionals/physician_gls/pdf/immunotherapy.pdf

  74. Chang LS, Barroso-Sousa R, Tolaney SM et al (2019) Endocrine toxicity of cancer immunotherapy targeting immune checkpoints. Endocr Rev 40:17–65

    Article  PubMed  Google Scholar 

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Funding

This work was conducted with support from Harvard Catalyst | The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, National Institutes of Health Award UL1 TR002541) and financial contributions from Harvard University and its affiliated academic healthcare centers. The content is solely the responsibility of the authors and does not necessarily represent the views of Harvard Catalyst, Harvard University and its affiliated academic healthcare centers, or National Institutes of Health.

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Authors and Affiliations

  1. Division of Endocrinology, Diabetes, and Hypertension, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, 221 Longwood Ave, RFB-2, Boston, MA, 02115, USA

    Yee-Ming Melody Cheung & Ole-Petter Riksfjord Hamnvik

  2. Department of Medicine, Endocrine Unit, Austin Hospital, The University of Melbourne, Melbourne, VIC, Australia

    Yee-Ming Melody Cheung

  3. Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women’s Hospital, Boston, USA

    Wei Wang

  4. Division of Sleep Medicine, Harvard Medical School, Boston, USA

    Wei Wang

  5. Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, 02215, USA

    Bradley McGregor

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  1. Yee-Ming Melody Cheung
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  2. Wei Wang
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  4. Ole-Petter Riksfjord Hamnvik
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Contributions

Y-MMC had substantial contribution in the conception and design of the manuscript, along with its methodology. She also conducted the statistical analyses and was primarily responsible for drafting the manuscript. She was one of two reviewers responsible for the review and selection of studies for both the systematic review and meta-analysis, as well as for the extracting of data from the selected studies. WW had substantial contribution in overseeing and supervising all statistical analyses performed for the meta-analysis. She also contributed to the revisions of the manuscript. BM had substantial contribution in the drafting and revisions of the manuscript. O-PRH had substantial contribution in the conception and design of the manuscript, along with its methodology. He also contributed to the drafting and revisions of the manuscript. He was one of two reviewers responsible for the review and selection of studies for both the systematic review and meta-analysis, as well as for the extracting of data from the selected studies. He also provided supervision and oversight of the project. All authors have given approval for this version of the manuscript to be published.

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Correspondence to Ole-Petter Riksfjord Hamnvik.

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The authors (YC, BM, WW and OH) do not have any disclosures or conflicts of interest.

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Cheung, YM.M., Wang, W., McGregor, B. et al. Associations between immune-related thyroid dysfunction and efficacy of immune checkpoint inhibitors: a systematic review and meta-analysis. Cancer Immunol Immunother 71, 1795–1812 (2022). https://doi.org/10.1007/s00262-021-03128-7

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