Objective: The aim of this study was to analyze the incidence of and risk factors for adrenocortical carcinoma (ACC) in adrenal incidentaloma (AI). Summary of Background Data: AI guidelines are based on data obtained with old-generation imaging and predominantly use tumor size to stratify risk for ACC. There is a need to analyze the incidence and risk factors from a contemporary series. Methods: This is a retrospective review of 2219 AIs that were either surgically removed or nonoperatively monitored for ≥12 months between 2000 and 2017. Multivariate logistic regression was performed to define risk factors. ROC curves constructed to determine optimal size and attenuation cut-offs for ACC. Results: 16.8% of AIs underwent upfront surgery and rest initial nonoperative management. Of conservatively managed patients, an additional 7.7% subsequently required adrenalectomy. Overall, ACC incidence in AI was 1.7%. ACC rates by size were 0.1%, 2.4%, and 19.5% for AIs of <4, 4 to 6, and >6 cm, respectively. The optimal size cut-off for ACC in AI was 4.6 cm. ACC risks by Hounsfield density were 0%, 0.5%, and 6.3% for lesions of <10, 10 to 20, and >20 HU, with an optimal cut-off of 20 HU to diagnose ACC. 15.5% of all AIs and 19.2% of ACCs were hormonally active. Male sex, large tumor size, high Hounsfield density, and >0.6 cm/year growth were independent risk factors for ACC. Conclusion: This contemporary analysis demonstrates that ACC risk per size in AI is less than previously reported. Given these findings, modern management of AIs should not be based just on size, but a combination of thorough hormonal evaluation and imaging characteristics.
Isolated, primary extranodal Hodgkin's disease of the spine is extremely rare. Seven other cases were reported in 1954. Although the Hodgkin's disease in these cases may arise in the bone of the spine, the possibility of origin in the paraspinous soft tissues also cannot be excluded.
5048 Background: Sorafenib is an orally bioavailable VEGF receptor inhibitor with anti-tumor activity in metastatic RCC. Sunitinib, another VEGF receptor inhibitor, induces biochemical hypothyroidism in 85% of metastatic RCC pts, the majority of whom have signs or symptoms of hypothyroidism (Rini BI et al. JNCI 2007 99(1):81–83). Thus, the incidence of TFT abnormalities in pts with metastatic RCC receiving sorafenib was investigated. Methods: The medical records of pts with metastatic RCC receiving sorafenib in one of five clinical trials at the Cleveland Clinic Taussig Cancer Center were reviewed. TFTs (TSH, T4, FTI and T3), patient demographics and clinical outcomes were recorded. Results: Between February 2004 and November 2006, 71 pts (49 males, 22 females) were treated with sorafenib. Baseline pt characteristics included a median age of 62 years (range, 35–87), 87% of pts had clear cell histology and 97% had prior nephrectomy. Forty-two pts had TFTs measured while receiving sorafenib and 19/42 pts (45%; 95% CI: 30–61%) had abnormal TFTs. The TFT abnormalities were consistent with hypothyroidism (13 pts), euthyroid sick syndrome (2 pts) or hyperthyroidism (4 pts). The median values in pts with abnormal TFTs were: TSH-7 μU/ml, T3–79 ng/dl, T4–12.7 μg/dl, FTI- 5.4; these values are just outside the normal laboratory ranges. The majority of pts did not have clinical signs or symptoms that could be attributed solely to thyroid dysfunction; only one pt (2%) received thyroid hormone replacement. The estimated progression free survival for pts with normal TFTs is 7.5 months vs. 6.1 months for pts with abnormal TFTs (p=0.79). Conclusion: Mild biochemical TFTs abnormalities are common in pts with metastatic RCC treated with sorafenib. However, severe TFT abnormalities and/or clinical signs/symptoms of thyroid dysfunction are not seen, and thyroid replacement therapy is not often indicated. In contrast to sunitinib, where the high incidence and clinical relevance of thyroid dysfunction requires routine monitoring, pts with metastatic RCC receiving sorafenib should have TFTs monitored only if clinically indicated. [Table: see text]
Background The common HSD3B1 (1245C) germline variant encodes for a 3βHSD1 missense that increases enzyme activity that allows tumors to utilize extragonadal androgens and is a predictive biomarker of resistance to ADT and sensitivity to CYP17A1 inhibition by the nonsteroidal drug ketoconazole. However, 3βHSD is also the first enzyme necessary in the conversion from abiraterone, a steroidal CYP17A1 inhibitor, to 5α-abiraterone, which stimulates the androgen receptor (AR) and prostate cancer progression. The HSD3B1 (1245C) variant might therefore increase 5α-abiraterone synthesis in patients on abiraterone therapy, possibly limiting clinical benefit. Significance This work aims to characterize the pharmacokinetics of steroidal metabolites of abiraterone and to determine the association between HSD3B1 genotype and the generation of 5α-abiraterone metabolites. Patients and Methods Part 1: 15 healthy male volunteers received a single oral dose of 1000 mg abiraterone acetate plus 240 mg of the AR antagonist apalutamide, steroidal metabolites of abiraterone were quantitated at 12 time points from 0.5-96 hours post-dose. Part 2: 5α-abiraterone metabolites and HSD3B1 genotype was determine in 30 patients with castration-resistant prostate cancer (CRPC) on abiraterone therapy. Metabolite concentrations were normalized to the 8 hour time point of the pharmacokinetic study and the association between HSD3B1 genotype and 5α-abiraterone metabolites was determined. Results There were 8, 19, and 3 pts with homozygous wild-type, heterozygous, and homozygous variant HSD3B1 genotypes. Patients who inherit 0, 1 and 2 copies of the HSD3B1 (1245C) variant have a stepwise increase in serum concentrations of 5α-abiraterone metabolites (p=0.002). Conclusion The generation of 5α-abiraterone preferentially in patients with the HSD3B1 (1245C) variant might negate the benefits of abiraterone specifically in a patient subset that is otherwise more likely to benefit from CYP17A1 inhibition by the nonsteroidal drug ketoconazole. Citation Format: Mohammad Alyamani, Hamid Emamekhoo, Sunho Park, Jennifer Taylor, Nima Almassi, Sunil Upadhyay, Allison Tyler, Michael P. Berk, Tae Hyun Hwang, Petros Grivas, Brian Rini, Jorge Garcia, Richard J. Auchus, Nima Sharifi. HSD3B1 genotype and abiraterone metabolism in patients with prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2572.
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