Johnson, Geoffrey

Purpose: The purpose was to evaluate the pathological nature of focal thyroid uptake seen in 11C-Choline PET/CT performed for prostate cancer. Material and methods: The study was IRB-approved. All 11C-Choline PET/CT exam reports for studies performed between January 01, 2018, and July 30, 2021, in male patients with prostate cancer in our institution were retrospectively reviewed. Exams with “focal thyroid uptake” on their final report were selected. Patients with surgery or ablation in the thyroid prior to the PET/CT, proven parathyroid adenomas or absent thyroid ultrasound were excluded. Repeated PET/CT exams of same patient were excluded. PET images were analyzed visually and semi-quantitatively by measuring the maximum standardized uptake value (SUVmax) of the focal thyroid uptake. Available thyroid ultrasound images, cytology and pathology reports were reviewed. Statistical analyses were performed. Results: Out of 10,047 sequential 11C-Choline PET/CT studies, 318 reports included “focal thyroid uptake.” About 128 of these studies were repeat exams and were excluded. Additional 87 patients were excluded, because the uptake was determined to be adjacent, rather than confined to the thyroid gland. Out of the remaining 103 patients, 74 patients had focal thyroid uptake and concurrent thyroid sonographic evaluation. Out of the 74 focal uptakes evaluated with ultrasound, 21 were presumed benign thyroid nodules based on the ultrasound and 53 had further evaluation with biopsy. Sixty three nodules were benign (21 presumed benign on ultrasound and 42 cytology or surgical pathology-proven), 9 nodules were malignant and 2 remained indeterminate. There was no significant difference between the SUVs of the benign and malignant groups (P > .3). Conclusion: In this retrospective study of patients with prostate cancer who underwent 11C-Choline PET/CT, we identified a group of patients who underwent thyroid ultrasound for incidental finding of focal 11C-Choline thyroid uptake. Incidence of malignancy in this group was 12%. Therefore, further investigation with ultrasound and possibly ultrasound-guided biopsy may be warranted when a choline avid thyroid nodule is found incidentally on choline PET.

220 Background: There is a critical need to identify biomarkers of response and resistance to 177Lu-PSMA-617. Post-hoc analyses of VISION have explored the prognostic and predictive value of select clinical parameters. However, we are still in the early stages of deciphering which molecular changes are associated with favorable or adverse treatment outcomes. Methods: We conducted a retrospective analysis of patients with metastatic castration-resistant prostate cancer (mCRPC), who received 177Lu-PSMA-617 at Mayo Clinic in Rochester, Minnesota, in the interval of March 2022 to March 2023. We included patients who provided research authorization, had a baseline PSA of at least 2 ng/mL, received at least 2 cycles of treatment, and had circulating tumor DNA (ctDNA) genomic profiling performed by Guardant (83 gene panel) within 60 days of treatment initiation. Clinical, laboratory, genomic, and radiomic parameters were abstracted by trained research personnel. Two independent analyses of “response” and “resistance” were performed. Response to treatment was defined as 50% or greater decrease in PSA from baseline (PSA50 response: dichotomized yes versus no), and resistance was defined as non-decreasing or rising PSA during treatment (PSA non-response: dichotomized yes versus no). Associations between gene alterations and response and resistance were evaluated via Fisher’s exact tests. Results: Between March 2022 and March 2023, 273 patients received cycle 1 of 177Lu-PSMA-617. A total of 108 patients met the inclusion criteria. The median number of cycles at data cutoff was 6 (IQR: 4,6) with 57 (53%) patients receiving all 6 planned cycles. The median PSA at baseline was 16.65 ng/ml (IQR: 5.20, 66.12). A total of 65 patients (60%) experienced a PSA50 response. No molecular alterations were associated with a higher rate of PSA50 response; however, alterations in ARID1A, AR, and CHEK2 were associated with lack of PSA50 response (Fisher’s exact p < 0.05). Of the 108 evaluable patients, 20 (19%) met criteria for PSA non-response. Alterations in AR, ARID1A, MYC, TP53, CHEK2, ATM, EGFR, and NOTCH1 were significantly associated with PSA non-response (Fisher’s exact p < 0.05); in each case, the presence of the alteration was positively associated with resistance (i.e., more instance of PSA non-response). No biomarkers were found to be inversely associated with PSA non-response. Conclusions: ctDNA assessed by commercially available, targeted sequencing panels prior to treatment may be useful in identifying the patients least likely to benefit from 177Lu-PSMA-617. Further work is ongoing to integrate ctDNA findings with clinical parameters in the hopes of understanding the factors mediating response and resistance to therapy.

60 Background: Recent studies, including a post-hoc analysis of the ARCHES trial, highlight radiographic disease progression (rDP) occurring without concordant rise in prostate specific antigen (PSA). In a previous study by our group, we reported that almost 40% of patients on 2nd generation hormone therapy experience rDP with non-rising PSA and have poor survival outcomes. The current analysis more specifically focuses on the subgroup of patients with rDP occurring at low PSA (<0.5 ng/dL) and describes factors associated with poorer survival outcomes in this patient population. Methods: In a single institution study, we reviewed the prospectively maintained Mayo Clinic C-11 Choline PET registry for patients treated between 2011 and 2021, who experienced rDP at low PSA (value < 0.5 ng/mL). Disease progression on C-11 choline PET was confirmed by either tissue biopsy or subsequent response to therapy. We investigated factors associated with poor cancer-specific survival outcomes in univariable and multivariable cox regression analyses. Results: In total, 220 (16%) patients experiencing rDP at low PSA were identified. Median (IQR) age at rDP was 67.91 (61.10 – 73.87) yrs., median (IQR) primary Gleason score was 9 (7-9), and median (IQR) PSA was 0.17 (0 – 0.32) ng/ml. 75% of the patients (n=166) had CRPC disease status at time of rDP. Prior systemic treatments included 2nd generation HT in 18% (n= 40) and chemotherapy in 31% (n=70). Sites of rDP were divided into 7% local (n=16), 42% lymph nodes (n=91), 43% bone (n=95), and 8% visceral metastases (n=18). Over a median follow-up duration of 55 months, 46% of patients (n=100) reported death. Factors associated with poor survival outcomes are demonstrated in the table and include age at rDP, CRPC status, and disease location (P-value <0.05). Conclusions: We found that radiographic disease progression commonly occurs at low PSA (<0.5 ng/mL). CRPC-disease status and the development of visceral metastases are associated with particularly poor survival outcomes. To identify early progression, monitoring with imaging may be warranted, even in the patients with low PSA. [Table: see text]

269 Background: Metastatic visceral involvement in prostate cancer patients conveys a poor prognosis. Survival patterns of site-specific visceral metastasis are poorly understood. Here, we sought to investigate survival patterns in prostate cancer patients according to their first detected site of visceral metastasis. Methods: Retrospectively, we identified 200 patients with visceral metastatic prostate cancer. Patients were divided into three groups according to first site detected with visceral metastases; first-site lung metastases, first-site brain metastases, and first-site liver metastases. Visceral metastases were detected on either conventional imaging (CT/MRI), metabolic imaging (C-11 choline), or PSMA PET-CT scan. Follow up duration of our study was 80 months. Results: Clinicopathological variables are shown. The K-M curve of overall survival of the entire cohort suggests better survival patterns in patients with first-site lung metastases compared to patients with first-site brain or liver metastases (p<0.0001). In subset analysis of patients with CRPC, the K-M curve of overall survival, which demonstrates better survival outcomes in patients with first-site lung metastases in comparison with patients with first-site brain or liver metastases (p<0.0001). Conclusions: Our data suggests that prostate cancer patients with visceral metastatic disease have different survival patterns according to the first site detected with visceral metastasis. In our cohort, patients with first-site lung metastasis demonstrated better survival outcomes than patients with first-site brain or liver metastasis. Further studies are warranted. [Table: see text]

641 Background: Tumors of neuroendocrine origin are a rare, heterogenous group of neoplasms. Neuroendocrine neoplasms (NENs) are categorized by site of origin, differentiation status, and by grade (Ki-67 expression and/or mitotic rate), with prognostic variability accordingly. These tumors frequently metastasize to bone, with reported incidence between 6-12% by older SSTR imaging. Our study evaluates patients with well-differentiated tumors of neuroendocrine origin to determine the incidence of osseous metastases when evaluated with higher-sensitivity Ga68 DOTATATE PET scans. The study characterizes the clinical features. Methods: This study was performed at a single, 3-site, US tertiary-care institution. IRB approval was obtained. An automated data extraction tool was used to mine the electronic medical record by searching all positron emission tomography (PET) studies for keywords. Identified scans had to include a combination of the following keywords: “Dotatate” AND “met*” or “lesion” AND “bone” or “osse*” or “skel*”. The individual medical records from the generated report were reviewed to include only patients with 1) well-differentiated NETs of GI and pancreatic origin, lung carcinoid, paraganglioma/pheochromocytoma, or other/unknown primary site, and 2) patients with confirmed osseous metastatic disease. Patient data was entered into a database and evaluated in aggregate. Results: 1,948 PET scans of 1,473 patients were extracted from the EMR, from which 424 patients were identified for inclusion; scans were performed between 5/2018 and 5/2021. Calculated incidence of bone metastasis by Ga68 DOTATATE PET was 28.8%. Median age of included population was 61 years (range 14-92), 49.5% being male. Site of origin was 47.2% bowel NET, 18.9% pancreatic NET, 10.8% lung carcinoid, 10.6% paraganglioma/pheochromocytoma, 2.1% other site, and 10.4% unknown primary. Majority of patients were asymptomatic (64.0%), had sclerotic appearance (76.7%), Krenning 4 (71.4%), and >3 sites (68.3%) of osseous disease. 94.6% of the population had disease of the axial skeleton; 65.6% appendicular. Only 57 patients (13.4%) with osseous disease suffered a fracture, despite metastases at high-risk sites. Fracture occurred at disproportionately low rates in NETs originating in bowel (22.8% of fractures), with proportionately higher rates among pancreatic NETS and paragangliomas/pheochromocytomas (31.6% and 22.8%, respectively). Fractures occurred at proportionately higher rates in higher-grade disease compared to low-grade. Conclusions: Osseous metastatic disease in well-differentiated NENs is evident at much higher rates when imaging with Ga68 DOTATATE PET compared with previously reported data. Nevertheless, fracture occurred at a low rate, suggesting that these patients are at a relatively low risk for skeletal-related events.