Refine
Has Fulltext
- yes (24)
Is part of the Bibliography
- yes (24)
Document Type
- Journal article (24)
Language
- English (24)
Keywords
- adrenocortical carcinoma (5)
- CYP2W1 (2)
- Cushing’s syndrome (2)
- FGFR (2)
- SOAT1 (2)
- adrenal tumours (2)
- immunotherapy (2)
- machine learning (2)
- metabolomics (2)
- 18F-FDG (1)
- 2-deoxy-2-(18F)fluoro-D-glucose (1)
- ACTH (1)
- CRH stimulation test (1)
- CTNNB1 (1)
- CXCR4 (1)
- CXCR7 (1)
- CYP2B6 (1)
- Cushing syndrome (1)
- Cushing's disease (1)
- Cushing’s disease (1)
- EMT (1)
- FGF-pathway (1)
- NCI-H295R (1)
- NR3C1 (1)
- PD-L1 (1)
- PET (1)
- Positronen-Emissions-Tomografie (1)
- RNA Expression (1)
- RNAScope (1)
- SNP (1)
- TKI (1)
- USP8 (1)
- [18F]FDG-PET-CT (1)
- abdominal lymph node metastases (1)
- adjuvant platinum-based chemotherapy (1)
- adrenal (1)
- adrenal glands (1)
- adrenal imaging (1)
- adrenocortical carcinoma (ACC) (1)
- adrenocortical tissues (1)
- adrenocortical tumors (1)
- amphiphilic block copolymer (1)
- autonomous cortisol secretion (1)
- biomarker (1)
- biomarkers (1)
- cancer treatment (1)
- carcinomas (1)
- cardiovascular events (1)
- cardiovascular risk factors (1)
- catecholamines (1)
- chemokine receptor (1)
- cholesterol metabolism (1)
- combination (1)
- confounders (1)
- dexamethasone suppression test (1)
- diagnosis (1)
- drug therapy (1)
- ectopic (1)
- endogenous hypercortisolism (1)
- epithelial markers (1)
- feature selection (1)
- glucocorticoid excess (1)
- high dose dexamethasone suppression test (1)
- hormones (1)
- hypercortisolism (1)
- hypertension (1)
- immune check inhibitor (1)
- immune checkpoint inhibitor (ICI) (1)
- immune response (1)
- immunity (1)
- immunohistochemistry (1)
- immunohistochemistry techniques (1)
- lymphocytes (1)
- mass spectronomy (1)
- medullary thyroid cancer (1)
- medullary thyroid carcinoma (1)
- mesenchymal markers (1)
- mitotane (1)
- molecular diagnostics (1)
- morbidity (1)
- mortality (1)
- multi-tyrosine kinase inhibitor (1)
- multicenter (1)
- mutation triggers (1)
- normal adrenal glands (1)
- papillary thyroid carcinoma (PTC) (1)
- paraganglioma (1)
- parathyroid carcinoma (1)
- patient survival (1)
- pembrolizumab (1)
- personalized medicine (1)
- pheochromocytoma (1)
- pheochromocytoma/paraganglioma (1)
- phosphorylation (1)
- plasma NMR (1)
- poly(2-oxazoline) (1)
- positron emission tomography (1)
- preanalytical conditions (1)
- predictive marker (1)
- primary aldosteronism (1)
- prognosis (1)
- prognostic factors (1)
- prostate cancer (1)
- radical resection (1)
- radioiodine (1)
- radiotherapy (RT) (1)
- rearranged during transfection (1)
- recurrence-free survival (1)
- repeated surgery (1)
- selpercatinib (1)
- solubility enhancement (1)
- surgical oncology (1)
- survival (1)
- t-lymphocytes (1)
- target therapies (1)
- targeted metabolomics (1)
- thyroid carcinoma (TC) (1)
- treatment outcome (1)
- tumor microenvironment (1)
- tumor-infiltrating (1)
- tyrosine kinase inhibitor (1)
- tyrosine kinase inhibitor (TKI) (1)
- unsupervised clustering (1)
- vandetanib (1)
- variant (1)
Institute
- Medizinische Klinik und Poliklinik I (24) (remove)
Sonstige beteiligte Institutionen
Adrenocortical carcinoma (ACC) is a rare tumor and prognosis is overall poor but heterogeneous. Mitotane (MT) has been used for treatment of ACC for decades, either alone or in combination with cytotoxic chemotherapy. Even at doses up to 6 g per day, more than half of the patients do not achieve targeted plasma concentration (14–20 mg L\(^{-1}\)) even after many months of treatment due to low water solubility, bioavailability, and unfavorable pharmacokinetic profile. Here a novel MT nanoformulation with very high MT concentrations in physiological aqueous media is reported. The MT‐loaded nanoformulations are characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry, and powder X‐ray diffraction which confirms the amorphous nature of the drug. The polymer itself does not show any cytotoxicity in adrenal and liver cell lines. By using the ACC model cell line NCI‐H295 both in monolayers and tumor cell spheroids, micellar MT is demonstrated to exhibit comparable efficacy to its ethanol solution. It is postulated that this formulation will be suitable for i.v. application and rapid attainment of therapeutic plasma concentrations. In conclusion, the micellar formulation is considered a promising tool to alleviate major drawbacks of current MT treatment while retaining bioactivity toward ACC in vitro.
Purpose: The metabolically most active lesion in 2-deoxy-2-(\(^{18}\)F)fluoro-D-glucose (\(^{18}\)F-FDG) PET/CT can predict progression-free survival (PFS) in patients with medullary thyroid carcinoma (MTC) starting treatment with the tyrosine kinase inhibitor (TKI) vandetanib. However, this metric failed in overall survival (OS) prediction. In the present proof of concept study, we aimed to explore the prognostic value of intratumoral textural features (TF) as well as volumetric parameters (total lesion glycolysis, TLG) derived by pre-therapeutic \(^{18}\)F-FDG PET.
Methods: Eighteen patients with progressive MTC underwent baseline \(^{18}\)F-FDG PET/CT prior to and 3 months after vandetanib initiation. By manual segmentation of the tumor burden at baseline and follow-up PET, intratumoral TF and TLG were computed. The ability of TLG, imaging-based TF, and clinical parameters (including age, tumor marker doubling times, prior therapies and RET (rearranged during transfection) mutational status) for prediction of both PFS and OS were evaluated.
Results: The TF Complexity and the volumetric parameter TLG obtained at baseline prior to TKI initiation successfully differentiated between low- and high-risk patients. Complexity allocated 10/18 patients to the high-risk group with an OS of 3.3y (vs. low-risk group, OS=5.3y, 8/18, AUC=0.78, P=0.03). Baseline TLG designated 11/18 patients to the high-risk group (OS=3.5y vs. low-risk group, OS=5y, 7/18, AUC=0.83, P=0.005). The Hazard Ratio for cancer-related death was 6.1 for Complexity (TLG, 9.5). Among investigated clinical parameters, the age at initiation of TKI treatment reached significance for PFS prediction (P=0.02, OS, n.s.).
Conclusions: The TF Complexity and the volumetric parameter TLG are both independent parameters for OS prediction.
Background
Adrenocortical tumors comprise frequent adenomas (ACA) and rare carcinomas (ACC). Human cytochrome P450 2W1 (CYP2W1) is highly expressed in some cancers holding the potential to activate certain drugs into tumor cytotoxins.
Objective
To investigate the CYP2W1 expression in adrenal samples and its relationship with clinical outcome in ACC.
Material and Methods
CYP2W1 expression was investigated by qRT-PCR in 13 normal adrenal glands, 32 ACA, 25 ACC, and 9 different non-adrenal normal tissue samples and by immunohistochemistry in 352 specimens (23 normal adrenal glands, 33 ACA, 239 ACC, 67 non-adrenal normal or neoplastic samples).
Results
CYP2W1 mRNA expression was absent/low in normal non-adrenal tissues, but high in normal and neoplastic adrenal glands (all P<0.01 vs non-adrenal normal tissues). Accordingly, CYP2W1 immunoreactivity was absent/low (H-score 0–1) in 72% of non-adrenal normal tissues, but high (H-score 2–3) in 44% of non-adrenal cancers, in 65% of normal adrenal glands, in 62% of ACAs and in 50% of ACCs (all P<0.001 vs non-adrenal normal tissues), being significantly increased in steroid-secreting compared to non-secreting tumors. In ACC patients treated with mitotane only, high CYP2W1 immunoreactivity adjusted for ENSAT stage was associated with longer overall survival and time to progression (P<0.05 and P<0.01, respectively), and with a better response to therapy both as palliative (response/stable disease in 42% vs 6%, P<0.01) or adjuvant option (absence of disease recurrence in 69% vs 45%, P<0.01).
Conclusion
CYP2W1 is highly expressed in both normal and neoplastic adrenal glands making it a promising tool for targeted therapy in ACC. Furthermore, CYP2W1 may represent a new predictive marker for the response to mitotane treatment.
Background: Adrenocortical carcinoma (ACC) is a rare tumor with a poor prognosis. Often, the physicians who first treat patients with ACC have no prior experience with the disease. The aim of our study was to evaluate the quality of medical care for patients with ACC in Germany.
Methods: Data from the German ACC registry were analyzed with regard to the patients’ preoperative diagnostic evaluation, histopathological reporting, and clinical followup. The findings were compared with the recommendations of the European Network for the Study of Adrenal Tumors (ENSAT).
Results: Data were analyzed from 387 patients who had been given an initial diagnosis of ACC in the years 1998 to 2009. 21% of them underwent no hormonal evaluation before surgery, and 59% underwent an inadequate hormonal evaluation. This exposed the patients to unnecessary perioperative risks and impaired their follow-up. 48% did not undergo CT scanning of the chest, even though the lungs are the most frequent site of metastases of ACC. For 13% of the patients, the diagnosis of ACC was later revised by a reference pathologist. For 11% of the patients, the histopathology report contained no information about resection status, even though this is an important determinant of further treatment and prognosis. Optimal management requires re-staging at three-month intervals, yet some patients underwent re-staging only after a longer delay, or not at all.
Conclusion: We have identified significant deficits in the care of patients with ACC in Germany. We suspect that the situation is similar for other rare diseases. The prerequisite to better care is close and early cooperation of the treating physicians with specialized centers.