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Cardiac sarcoidosis is associated with a high mortality rate. Given multiple barriers to obtaining cardiac PET imaging, we suspect individuals with access to this imaging modality are not representative of the Sarcoid patient population, which in the United States are predominantly Black females.To evaluate the demographics of patients with cardiac PET access and the cost-effectiveness of cardiac PET/MR imaging relative to standard of care.This is a retrospective, observational study. The demographic information of patients with suspected cardiac sarcoidosis and cardiac PET/CT imaging within a national registry of sarcoidosis were reviewed (n = 4561). An individual-level, continuous, time-state transition model was used for the evaluation of long-term cost-effectiveness for the combined cardiac PET/MR compared to standard of care cardiac MR followed by cardiac PET/CT.Patients who underwent cardiac PET in the national registry had 88.35% higher odds of being male (p 0.001) and 43.82% higher odds of being White (p = 0.003) than their counterparts who did not have cardiac PET imaging. Combined cardiac PET/MR had overall lower total lifetime costs ($8761 vs $10,777) and overall improved expected quality of life-years compared to the standard of care (0.77 vs 0.69).The findings suggest that patients with access to cardiac PET/CT are not representative of the patient population most likely to have cardiac sarcoidosis in this limited study evaluation. Universal insurance coverage should be considered for Cardiac PET imaging as same day cardiac PET and MR imaging has potential long-term cost and quality of life benefit.

Guided by the Theory of Racial Socialization in Action (TRSA; Smith-Bynum in press), this study examined observed caregiver-provided ethnic-racial socialization in response to a school-based discriminatory dilemma. Forty-five Black and 36 Latinx caregivers (88% mothers) with low-income and their children (M

Prostate-specific membrane antigen (PSMA) is expressed by the majority of clinically significant prostate adenocarcinomas, and patients with target-positive disease can easily be identified by PSMA PET imaging. Promising results with PSMA-targeted radiopharmaceutical therapy have already been obtained in early-phase studies using various combinations of targeting molecules and radiolabels. Definitive evidence of the safety and efficacy of [177Lu]Lu-PSMA-617 in combination with standard-of-care has been demonstrated in patients with metastatic castration-resistant prostate cancer, whose disease had progressed after or during at least one taxane regimen and at least one novel androgen-axis drug. Preliminary data suggest that 177Lu-PSMA-radioligand therapy (RLT) also has high potential in additional clinical situations. Hence, the radiopharmaceuticals [177Lu]Lu-PSMA-617 and [177Lu]Lu-PSMA-I&T are currently being evaluated in ongoing phase 3 trials. The purpose of this guideline is to assist nuclear medicine personnel, to select patients with highest potential to benefit from 177Lu-PSMA-RLT, to perform the procedure in accordance with current best practice, and to prepare for possible side effects and their clinical management. We also provide expert advice, to identify those clinical situations which may justify the off-label use of [177Lu]Lu-PSMA-617 or other emerging ligands on an individual patient basis.

Prostate cancer (PC) staging with conventional imaging often includes multiparametric magnetic resonance (MR) of the prostate, computed tomography (CT) of the chest, abdomen, and pelvis, and whole-body bone scintigraphy. The recent development of highly sensitive and specific prostate specific membrane antigen (PSMA) positron emission tomography (PET) has suggested that prior imaging techniques may be insufficiently sensitive or specific, particularly when evaluating small pathologic lesions. As PSMA PET/CT is considered to be superior for multiple clinical indications, it is being deployed as the new multidisciplinary standard-of-care. Given this, we performed a cost-effectiveness analysis of [18F]DCFPyL PSMA PET/CT imaging in the evaluation of PC relative to conventional imaging and anti-3-[18F]FACBC (18F-Fluciclovine) PET/CT. We also conducted a single institution review of PSMA PET/CT scans performed primarily for research indications from January 2018 to October 2021. Our snapshot of this period of time in our catchment demonstrated that PSMA PET/CT imaging was disproportionately accessed by men of European ancestry (EA) and those residing in zip codes associated with a higher median household income. The cost-effectiveness analysis demonstrated that [18F]DCFPyL PET/CT should be considered as an alternative to anti-3-[18F]FACBC PET/CT and standard of care imaging for prostate cancer staging. [18F]DCFPyL PET/CT is a new imaging modality to evaluate PC patients with higher sensitivity and specificity in detecting disease than other prostate specific imaging studies. Despite this, access may be inequitable. This discrepancy will need to be addressed proactively as the distribution network of the radiotracer includes both academic and non-academic sites nationwide.

Purpose The pituitary gland has the fourth highest physiologic avidity of [68Ga]-DOTATATE. In order to guide our understanding of [68Ga]-DOTATATE PET in clinical contexts, accurate characterization of the normal pituitary gland is first required. This study aimed to characterize the normal pituitary gland using dedicated brain [68Ga]-DOTATATE PET/MRI as a function of age and sex.Methods A total of 95 patients with a normal pituitary gland underwent brain [68Ga]-DOTATATE PET examinations for the purpose of diagnosing CNS SSTR2 positive tumors (mean age: 58.9, 73% female). Maximum SUV of the pituitary gland was obtained in each patient. SUV of superior sagittal sinus was obtained to calculate normalized SUV score (SUVR) of the gland. The anatomic size of the gland was collected as maximum sagittal height (MSH). Correlations with age and sex were analyzed.Results The mean SUV and SUVR of the pituitary gland were 17.6 (range: 7-59.5, SD = 7.1) and 13.8 (range: 3.3–52.6, SD = 7.2), respectively. Older females had significantly higher SUV of the pituitary gland compared to younger females. When stratified by age and sex, both older and younger females had significantly higher pituitary SUV than older males. SUVR did not differ significantly by age or sex. MSH of the pituitary gland in younger females was significantly greater than in younger males at all age cutoffs.Conclusion This study provides an empiric profiling of the physiological [68Ga]-DOTATATE avidity of the pituitary gland. The findings suggest that SUV may vary by age and sex and can help guide the use of [68Ga]-DOTATATE PET/MRI in clinical and research settings. Future studies can build on these findings to investigate further the relationship between pituitary biology and demographic factors.

DESTINY-Breast01 (NCT03248492) evaluated trastuzumab deruxtecan (T-DXd; DS-8201) in patients with heavily pretreated HER2-positive metastatic breast cancer (mBC). We present a subgroup of 24 patients with a history of treated brain metastases (BM), a population with limited treatment options. In patients with BMs, the confirmed objective response rate (cORR) was 58.3% [95% confidence interval (CI), 36.6%–77.9%], and the median progression-free survival (mPFS) was 18.1 months (95% CI, 6.7–18.1 months). In patients without BMs (n = 160), cORR was 61.3% and mPFS was 16.4 months. Eight patients (47.1%) experienced a best overall intracranial response of partial response or complete response. Seven patients (41.2%) had a best percentage change in brain lesion diameter from baseline consistent with stable disease. Two patients (8.3%) with BMs and two (1.3%) without BMs experienced progression in the brain. The safety profile of T-DXd was consistent with previous studies. The durable clinical activity of T-DXd in this population warrants further investigation.Significance:Advances in treating HER2-positive metastatic breast cancer have greatly improved patient outcomes, but intracranial progression remains an important risk for which few therapeutic options are currently available. T-DXd demonstrated durable efficacy in patients with stable, treated BMs.This article is highlighted in the In This Issue feature, p. 2711

Supplementary Data from Trastuzumab Deruxtecan in HER2-Positive Metastatic Breast Cancer Patients with Brain Metastases: A DESTINY-Breast01 Subgroup Analysis

XLSX file - 23K, Mapping statistics for genome sequencing of tumor and germline DNA from mTNBC

XLSX file - 45K, Genes containing breakpoint from translocation in mTNBC

XLSX file - 273K, Somatic genic focal copy number changes in mTNBC

XLSX file - 598K, edgeR differential expression results in mTNBC for select cancer related genes

Supplemental Table 1. Overall cohort characteristics of AAPC whole exome sequencing cohort (n=102) Supplemental Table 2. Clinical and pathological characteristics of AAPC WES discovery cohort (n=102) Supplemental Table 3. Comparison of numbers of tumors by Gleason grade between the TCGA and AAPC cohorts Supplemental Table 4. Germline pathogenic variants in genes in the DNA repair pathway and list of 20 DNA repair genes assessed in targeted analysis Supplemental Table 5. Alteration file of somatic variants detected in the AAPC WES discovery cohort (n=102) Supplemental Table 6. Focal deletion and amplification peaks and genes located within peaks by GISTIC2.0 analysis of AAPC WES cohort Supplemental Table 7. ERF deletions and mutations in prostate tumors of the Weill Cornell Precision Medicine cohort Supplemental Table 8. Clinical and pathological characteristics of AAPC targeted sequencing extension cohort Supplemental Table 9. List of genes and intronic regions targeted with hybrid capture bait set used for AAPC extension cohort Supplemental Table 10. Alteration file of somatic variants detected in the AAPC extension cohort (n=90) using the targeted sequencing panel Supplemental Table 11. ERF mutation frequencies across published prostate cancer cohorts Supplemental Table 12. Germline ERF variant detected in the AAPC WES cohort Supplemental Table 13. Mutations in cytochrome P450 genes in the AAPC exome discovery cohort Supplemental Table 14. ERF oligonucleotides used for RNA in situ hybridization Supplemental Table 15. Gene sets shERF_VCAP_UP_LnCAP_UP_overlap_UP and shERF_vs_CNTRL.LHSAR_UP Supplemental Table 16. Tumor purity estimates for AAPC exome discovery cohort

Supplemental Methods

XLSX file - 607K, Outlier differential expression results in mTNBC for select cancer related genes

XLSX file - 61K, List of somatic point mutations in mTNBC detected by NGS sequencing analysis

XLSX file - 42K, Ingenuity Canonical Pathways results for mTNBC based on edgeR differential expression results

XLSX file - 40K, Characteristics of mTNBC study population

Supplemental Figure Legends

PDF file - 1635K, PET/CT images of mTNBC2 breast lesion before and after treatment on combination MEK and AKT inhibitors

XLSX file - 48K, Transcriptome sequencing (RNA-seq) run statistics for mTNBC

PDF file - 135K, Validation of RB1 39bp homozygous deletion in mTNBC1

Purpose: Standard imaging for assessing osseous metastases in advanced prostate cancer remains focused on altered bone metabolism and is inadequate for diagnostic, prognostic, or predictive purposes. We performed a first-in-human phase I/II study of 89Zr-DFO-huJ591 (89Zr-J591) PET/CT immunoscintigraphy to assess performance characteristics for detecting metastases compared with conventional imaging modalities (CIM) and pathology.Experimental Design: Fifty patients with progressive metastatic castration-resistant prostate cancers were injected with 5 mCi of 89Zr-J591. Whole-body PET/CT scans were obtained, and images were analyzed for tumor visualization. Comparison was made to contemporaneously obtained bone scintigraphy and cross-sectional imaging on a lesion-by-lesion basis and with biopsies of metastatic sites.Results: Median standardized uptake value for 89Zr-J591–positive bone lesions (n = 491) was 8.9 and for soft-tissue lesions (n = 90), it was 4.8 (P < 0.00003). 89Zr-J591 detected 491 osseous sites compared with 339 by MDP and 90 soft-tissue lesions compared with 124 by computed tomography (CT). Compared with all CIMs combined, 89Zr-J591 detected an additional 99 osseous sites. Forty-six lesions (21 bone and 25 soft tissue) were biopsied in 34 patients; 18 of 19 89Zr-J591–positive osseous sites and 14 of 16 89Zr-J591–positive soft tissue sites were positive for prostate cancer. The overall accuracy of 89Zr-J591 was 95.2% (20 of 21) for osseous lesions and 60% (15 of 25) for soft-tissue lesions.Conclusions: 89Zr-J591 imaging demonstrated superior targeting of bone lesions relative to CIMs. Targeting soft-tissue lesions was less optimal, although 89Zr-J591 had similar accuracy as individual CIMs. This study will provide benchmark data for comparing performance of proposed prostate-specific membrane antigen (PSMA) targeting agents for prostate cancer. Clin Cancer Res; 21(23); 5277–85. ©2015 AACR.

Supplementary Table S1. Patient demographics

Supplementary Figures S1-4. Figure S1. 89Zr-J591 versus bone scan comparison of lesion positivity. Figure S2. Patient with metastatic prostate cancer (PSA of 10.1) with 89Zr-J591+ lesions that were not seen on MDP. Figure S3. Patient with metastatic prostate cancer (PSA of 0.62). Figure S4. Uniform prior distribution.

Supplementary Appendix

Supplementary Figure 1 from Targeted Elimination of Prostate Cancer by Genetically Directed Human T Lymphocytes

PDF file - 256K