Correlation of Degree of Hypothyroidism With Survival Outcomes in Patients With Metastatic Renal Cell Carcinoma Receiving Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitors

Bailey, Erin; Tantravahi, Srinivas K.; Poole, Austin; Agarwal, Archana; Straubhar, Alli M.; Batten, Julia; Patel, Shiven B.; Wells, Chesley E.; Stenehjem, David D.; Agarwal, Neeraj

doi:10.1016/j.clgc.2014.11.002

Cited by 15 publications

(12 citation statements)

References 29 publications

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“…In these studies, a significant association between sunitinib or pazopanib-induced proteinuria and OS was observed in RCC patients [18], and bevacizumab-induced proteinuria was associated with response rate in patients with metastatic colorectal cancer [31]. Additionally, RCC patients with sunitinib-induced or sorafenib-induced hypothyroidism showed increased response rates [32], improved PFS [19,33] and improved OS [19,32]. Furthermore, the occurrence of other sunitinib-induced or sorafenib-induced toxicities, such as hypertension, skin toxicity and diarrhea, was significantly associated with an increase in response rate [12][13][14], improved PFS [12,14,15] and improved OS [12,[14][15][16][17]34,35].…”

Section: Discussionmentioning

confidence: 96%

“…The hypothesis that the occurrence of toxicity is related to the anti-tumor activity of the drug, and that toxicity therefore can be used as a biomarker of efficacy has been tested in multiple combinations of various types of drugs and different types of cancer and for different toxicities. Examples include the occurrence of sunitinib-induced hypertension in renal cell carcinoma (RCC) [12,13] or gastrointestinal stromal tumors (GIST) [14,15], sorafenib-induced diarrhea or hand-foot syndrome in hepatocellular cancer [16,17], pazopanib or sunitinib-induced proteinuria in RCC [18], and VEGF TKI-induced hypothyroidism in RCC [19]. In these studies, the occurrence of VEGF TKI-induced toxicity was associated with an improved response rate and/or survival.…”

Section: Introductionmentioning

confidence: 99%

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Association of pazopanib-induced toxicities with outcome of patients with advanced soft tissue sarcoma; a retrospective analysis based on the European Organisation for Research and Treatment of Cancer (EORTC) 62043 and 62072 clinical trials

et al. 2019

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Association of pazopanib-induced toxicities with outcome of patients with advanced soft tissue sarcoma; a retrospective analysis based on the European Organisation for Research and Treatment of Cancer (EORTC) 62043 and 62072 clinical trials

et al. 2019

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“…whereas, hypothyroidism is associated with longer progression-free survival (PFS) in sunitinib and sorafenib treatments (25,28). The severity of vascular endothelial growth factor receptor tyrosine kinase inhibitor (TKI) therapy-associated hypothyroidism (TSH >10 mIU/l) is associated with improved treatment efficacy and survival outcomes in patients with metastatic RCC (52). This year meta-analysis suggested that development of hypothyroidism during TKI therapy is not clearly predictive of efficacy in patients with metastatic RCC or advantage in overall survival (OS) (53).…”

Section: Thyroid-stimulating Hormone (Tsh)mentioning

confidence: 99%

Hormone signaling pathways as treatment targets in renal cell cancer (Review)

Czarnecka

Niedzwiedzka

Porta

et al. 2016

International Journal of Oncology

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Abstract. Epidemiological, clinical, biochemical and genetic research has revealed that renal cell cancer (RCC) etiology is hormone-related. It was shown that hormone receptors are abnormally expressed in RCC cells. Abnormal endocrine stimulation also plays a significant role in RCC pathophysiology. Cellular proliferation, migration, angiogenesis, and drug resistance in RCC is modulated by para-and autocrine hormonal stimulation. In particular, RCC overexpression of gonadotropin-releasing hormone and its receptor was reported. On the contrary, corticotropin releasing hormone was reported to inhibit RCC cell proliferation and regulate angiogenesis. Overexpression of luteinizing hormone also promotes RCC tumor angiogenesis. Estrogen receptor α overexpression increases the transcriptional factor activity of hypoxia inducible factor HIF-1α, but estrogen receptor β has a cancer suppressive role. Glucocorticoid receptors and androgen receptor are markers of indolent RCC and assigned tumor suppressive activity. Proopiomelanocortin is upregulated in VHL-mutated renal cell carcinoma via Nur77 transcription factor signaling. In RCC, follicle-stimulating hormone receptor promotes angiogenesis and metastatic formation via VEGF release. Mineralocorticoid receptor overexpression promotes cell survival and increases RCC cell proliferation. Vitamin D receptor expression is downregulated or absent in RCC and differentiate subtypes of renal cell tumors. RAR-β promotes tumorigenesis but retinoic acid receptor γ expression correlates negatively with the TNM stage at diagnosis. Finally, progesterone receptor expression is negatively correlated with the cancer stage. Molecular data analysis revealed the possibility of renal cancer cell proliferation induction via hormone activated pathways. Inhibition of hormonal signaling may thus play a putative role in supportive therapies against this cancer type.

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“…It was reported to be associated with a higher incidence of breast cancer and prostate cancer and also as a side effect among patients with neck cancer, breast cancer and renal cancer receiving radiotherapy or molecular‐targeted therapy . Moreover, the development of secondary hypothyroidism was observed to be associated with better survival . In HCC patients, we have previously found hypothyroidism to be significantly more prevalent in patients with HCC of unknown etiology .…”

Section: Introductionmentioning

confidence: 92%

Hypothyroidism is associated with worse outcomes of hepatocellular carcinoma patients after liver transplantation

et al. 2018

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Background/AimsHypothyroidism has been associated with hepatocellular carcinoma (HCC) incidence; however, the relationship between hypothyroidism and HCC patient outcomes is unclear. We investigated the impact of hypothyroidism on outcomes after liver transplantation for HCC.Materials and MethodsWe retrospectively studied HCC patients transplanted between January 2000 and December 2015. Hypothyroidism was defined as a thyroid‐stimulating hormone (TSH) level continuously greater than 5 mIU/L, a documented history of hypothyroidism, or treatment with thyroid hormone replacement therapy. Multivariate Cox regression was used to assess the impact of hypothyroidism on overall survival (OS) and recurrence‐free survival (RFS) adjusting for potential confounders. Subgroup analyses and interaction tests were conducted to compare the impact of hypothyroidism in different subgroups and assess for possible synergistic effects. Sensitivity analyses were performed among different cohorts to verify the stability of the results.ResultsA total of 343 HCC patients who underwent liver transplantation were included in the analysis. The primary analysis was conducted among 288 patients diagnosed with HCC prior to transplantation. Hypothyroidism was independently associated with worse OS and RFS, as was elevated TSH. The adjusted hazard ratio (AHR) of hypothyroidism was 2.45 (95% confidence interval [CI], 1.44‐4.18) for OS and 5.54 (2.36, 13.01) for RFS. The AHR of TSH for OS was 1.05 (1.02, 1.09) and 1.08 (1.03, 1.13) for RFS. No interaction was found among different subgroups categorized by etiology and comorbidity. The results were stable to sensitivity analyses.ConclusionHypothyroidism is associated with poorer overall and recurrence‐free survival of HCC patients receiving liver transplantation. These results require validation.

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Correlation of Degree of Hypothyroidism With Survival Outcomes in Patients With Metastatic Renal Cell Carcinoma Receiving Vascular Endothelial Growth Factor Receptor Tyrosine Kinase Inhibitors

Cited by 15 publications

References 29 publications

Association of pazopanib-induced toxicities with outcome of patients with advanced soft tissue sarcoma; a retrospective analysis based on the European Organisation for Research and Treatment of Cancer (EORTC) 62043 and 62072 clinical trials

Association of pazopanib-induced toxicities with outcome of patients with advanced soft tissue sarcoma; a retrospective analysis based on the European Organisation for Research and Treatment of Cancer (EORTC) 62043 and 62072 clinical trials

Hormone signaling pathways as treatment targets in renal cell cancer (Review)

Hypothyroidism is associated with worse outcomes of hepatocellular carcinoma patients after liver transplantation

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