Molecular Imaging of Steroid Receptors in Breast Cancer.

ABSTRACT: Steroid receptors regulate gene expression for many important physiologic functions and pathologic processes. Receptors for estrogen, progesterone, and androgen have been extensively studied in breast cancer, and their expression provides prognostic information as well as targets for therapy. Noninvasive imaging utilizing positron emission tomography and radiolabeled ligands targeting these receptors can provide valuable insight into predicting treatment efficacy, staging whole-body disease burden, and identifying heterogeneity in receptor expression across different metastatic sites. This review provides an overview of steroid receptor imaging with a focus on breast cancer and radioligands for estrogen, progesterone, and androgen receptors.

Models using comprehensive, lesion-level, longitudinal [68Ga]Ga-DOTA-TATE PET-derived features lead to superior outcome prediction in neuroendocrine tumor patients treated with [177Lu]Lu-DOTA-TATE.

PURPOSE: Somatostatin receptor (SSTR) imaging features are predictive of treatment outcome for neuroendocrine tumor (NET) patients receiving peptide receptor radionuclide therapy (PRRT). However, comprehensive (all metastatic lesions), longitudinal (temporal variation), and lesion-level measured features have never been explored. Such features allow for capturing the heterogeneity in disease response to treatment. Furthermore, models combining these features are lacking. In this work we evaluated the predictive power of comprehensive, longitudinal, lesion-level 68GA-SSTR-PET features combined with a multivariate linear regression (MLR) model. METHODS: This retrospective study enrolled NET patients treated with [177Lu]Lu-DOTA-TATE and imaged with [68Ga]Ga-DOTA-TATE at baseline and post-therapy. All lesions were segmented, anatomically labeled, and longitudinally matched. Lesion-level uptake and variation in uptake were measured. Patient-level features were engineered and selected for modeling of progression-free survival (PFS). The model was validated via concordance index, patient classification (ROC analysis), and survival analysis (Kaplan-Meier and Cox proportional hazards). The MLR was benchmarked against single feature predictions. RESULTS: Thirty-six NET patients were enrolled and stratified into poor and good responders (PFS ≥ 25 months). Four patient-level features were selected, the MLR concordance index was 0.826, and the AUC was 0.88 (0.85 specificity, 0.81 sensitivity). Survival analysis led to significant patient stratification (p<.001) and hazard ratio (3⨯10-5). Lastly, in a benchmark study, the MLR modeling approach outperformed all the single feature predictors. CONCLUSION: Comprehensive, lesion-level, longitudinal 68GA-SSTR-PET analysis, combined with MLR modeling, leads to excellent predictions of PRRT outcome in NET patients, outperforming non-comprehensive, patient-level, and single time-point feature predictions. MESSAGE: Neuroendocrine tumor, peptide receptor radionuclide therapy, Somatostatin Receptor Imaging, Outcome Prediction, Treatment Response Assessment.

Nonspecific pain is a marker for hypovitaminosis D in patients undergoing evaluation for sleep disorders: a pilot study.

BACKGROUND: The purpose of this cross-sectional study was to test the hypothesis that serum vitamin D levels are abnormally low in sleep clinic patients admitting to chronic nonspecific musculoskeletal pain and to assess the associated risk factors. A secondary purpose was to identify a clinical biomarker for vitamin D deficiency. METHODS: We enrolled 153 consecutive patients who admitted to the presence of chronic nonspecific musculoskeletal pain during a comprehensive sleep evaluation at a specialist sleep medicine clinic within an academic center. Venous blood sampling was performed for determination of serum 25-hydroxyvitamin D. Risk factors for vitamin D deficiency (25-hydroxyvitamin D < 20 ng/mL) were identified by odds ratios. Receiver-operating characteristic curve analysis was performed with 10-fold cross-validation to identify a biomarker for vitamin D deficiency calculated by linear discriminant analysis. RESULTS: The mean serum 25-hydroxyvitamin D level was 19.8 ± 11.1, with 54% of the study population having vitamin D deficiency. This mean 25-hydroxyvitamin D level was lower than that observed historically in healthy controls, and was either similar or lower than in all but one representative historical cohort formed on the basis of chronic nonspecific musculoskeletal pain. Risk factors for vitamin D deficiency were black ethnicity, age < 60 years, and obesity. These risk factors were identified both in the entire cohort and separately in subgroups with and without obstructive sleep apnea. The biomarker (based on race, age, and body mass index) had a sensitivity and specificity for predicting vitamin D deficiency of 0.73 and 0.74, respectively. CONCLUSION: Vitamin D deficiency was prevalent in patients with sleep disorders and chronic nonspecific musculoskeletal pain on evaluation in a sleep medicine clinic. Vitamin D deficiency was reliably estimated in the study population using a biomarker derived from common demographic characteristics.

Vitamin D, race, and excessive daytime sleepiness.

STUDY OBJECTIVES: First, to determine whether serum vitamin D levels were correlated with excessive daytime sleepiness (EDS) in patients with or without vitamin D deficiency (VitDd). Second, to assess whether race affected the relation between vitamin D levels and EDS. METHODS: Serum 25-hydroxyvitamin D (25OHD) was measured by immunoassay in a consecutive series of 81 sleep clinic patients who complained of sleep problems and nonspecific pain (25OHD < 20 ng/mL ' VitDd). Sleepiness was determined using the Epworth Sleepiness Scale score ([ESSs] ESSs ≥ 10 ≡ EDS). Correlations were assessed using Pearson r. RESULTS: In patients without VitDd (25OHD ≥ 20 ng/mL), ESSs was inversely correlated with vitamin D concentration (r = 0.45, p < 0.05). The group consisted of 6% black patients, compared with 35% for the entire cohort. Among the patients who had VitDd (25OHD < 20 ng/mL), ESSs was directly correlated with 25OHD in black (r = 0.48, p < 0.05) but not white patients. In black patients, mean ESSs in patients with VitDd were higher and 25OHD levels were lower p < 0.05). CONCLUSIONS: The results suggested the novel possibility that VitDd-related disease has a yet-to-be-identified mechanistic role in the presentation of sleepiness, sleep disorders, or both. Further research is needed to clarify the mechanism(s) involved in producing the complex relationships noted.