Intraoperative 3-D mapping of parathyroid adenoma using freehand SPECT

Background: Freehand single photon emission computed tomography (fSPECT) is a three-dimensional (3-D) tomographic imaging modality based on data acquisition with a handheld detector that is moved freely, in contrast to conventional, gantry-mounted gamma camera systems. In this pilot study, we evaluated the feasibility of fSPECT for intraoperative 3-D mapping in patients with parathyroid adenomas. Methods: Three patients (range 30 to 45 years) diagnosed with hyperparathyroidism (one primary and two tertiary) underwent parathyroid scintigraphy with technetium-99m sestamibi (99mTc-MIBI) to localize parathyroid adenomas. Two patients were referred with persistent hyperparathyroidism after conventional parathyroidectomy. In all three patients, a planar scintigraphy of the neck was performed 10 min after injection (p.i.) followed by SPECT/CT (Symbia T2, Siemens Healthcare) and a correlative ultrasound 2 h p.i. 99mTc-MIBI scan was performed the day before surgery in two patients and at the same day in one patient. fSPECT images were acquired intraoperatively using declipse SPECT (SurgicEyeTM). Results: A total of five parathyroid adenomas were successfully located with SPECT/CT. fSPECT allowed intraoperative detection of all adenomas, and successful parathyroidectomy was accomplished. Parathyroid hormone level decreased intraoperatively in all three patients, on average, by 79% (range 72% to 91%). Conclusion: In this preliminary study, we could demonstrate that intraoperative localization of parathyroid adenomas is feasible using the freehand SPECT technology, thus allowing an image-guided parathyroidectomy

Second line chemotherapy and visceral metastases are associated with poor survival in patients with mCRPC receiving 177Lu-PSMA-617

The purpose of this study was to identify previous treatments and biomarker profile features that prognosticate overall survival (OS) in patients with mCRPC receiving 177Lu-PSMA-617. METHODS: 109 mCRPC patients treated with a median of 3 cycles of 177Lu-PSMA-617 were included. Data were analyzed according to OS as well as PSA response patterns with regard to prior therapies, laboratory biomarkers and metastatic extent in univariate as well as multivariate Cox's proportional hazards models. PSA decline was assessed using the lowest PSA levels after the first cycle of therapy (initial PSA response) and during the entire observation period (best PSA response). RESULTS: In total, 54 patients (49.5%) died during the observation period. First and second line chemotherapy were performed in 85% and 26%, and Abiraterone and Enzalutamide were administered in 83% and 85%, respectively. Any initial PSA decline occurred in 55% while 25% showed a PSA decline of ≥50%. The median estimated OS was 9.9 months (95% CI: 7.2-12.5) for all patients. Any initial decline of PSA was associated with significantly prolonged OS (15.5 vs. 5.7 months, p = 0.002). Second line cabazitaxel chemotherapy (6.7 vs. 15.7 months, p = 0.002) and presence of visceral metastases (5.9 vs. 16.4 months, p<0.001) were associated with shorter OS. Only visceral metastases remained significant in a multivariate analysis. CONCLUSION: 177Lu-PSMA-617 is an effective therapy for patients with mCRPC. However, the present data indicate that its beneficial effects on OS are strongly influenced by pretreatment (history of second line chemotherapy with cabazitaxel) and the presence of visceral metastases at onset of 177Lu-PSMA-617 treatment

Molecular analysis of circulating tumor cells of metastatic castration-resistant Prostate Cancer Patients receiving 177Lu-PSMA-617 Radioligand Therapy

Rationale: Lu-177-PSMA-617 radioligand therapy (RLT) is currently under approval for treatment of metastatic castration resistant prostate cancer (mCRPC) patients with late stage disease. However, previous studies demonstrated both heterogeneity of prostate specific membrane antigen (PSMA) expression, as well as response to PSMA treatment among mCRPC patients. Thus, there is an unmet need for identifying predictive parametres prior or under PSMA-RLT treatment. We therefore aimed to correlate several clinical and molecular parameters with response to PSMA treatment in a cohort of mCRPC patients undergoing PSMA RLT followed by a detailed analysis of promising candidates. Methods: Nineteen patients, median age 68.8 years (range: 56.9 - 83.3) with mCRPC were included in this study. We performed baseline analysis of clinical parameters based on PSMA PET/CT, (metabolic tumor volume (MTV), total tumor volume (TTV)), serum PSA, ALP, LDH and gene expression analysis of circulating tumor cells (expression of AR full length (AR-FL), AR splice variant 7 (AR-V7), PSA and PSMA) as well as common markers for neuroendocrine differentiation (NED). Results: Patients presented with bone, lymph node, and visceral metastases (89%, 68%, and 21%, respectively). All patients were pretreated with docetaxel, either abiraterone or enzalutamide, or both. Biochemical response in terms of PSA decline ≥50 or ≥30% was observed in 42% and 63%, respectively. There were significant correlations between PSA and PSMA mRNA expression, as well as tumor volumes (both MTV and TTV), AR-FL and AR-V7 mRNA expression. However, there was no correlation with response to PSMA treatment. Furthermore, none of these parameters was significantly correlated with baseline serum PSA values. Common NED markers were shown to be specifically high expressed and revealed impact on OS independent from AR-V7 gene expression. Conclusion: We demonstrate that AR-FL and its splice variant AR-V7 might serve as prognostic biomarkers displaying high tumor burden in mCRPC patient prior to PSMA-RLT. Contrary, PSMA, which has been discussed as a biomarker for PSMA targeted treatment, does not display strong prognostic ability – at least on the mRNA level. Surprisingly, none of these parameters correlates to response to PSMA treatment. In contrast, commom NED markers such as SYP and ENO2 as well as FOXA1 expression level seem to predict OS, but not PFS, more reliably. We admit that a limitation of our study is the focus on mRNA expression of potential biomarkers only. Further investigations analyzing the potential role of protein expression of these markers are therefore warranted

Repeated radioembolization in advanced liver cancer

Background: To evaluate safety and clinical outcome of repeated transarterial 90Y (yttrium) radioembolization (TARE) in primary and metastatic liver cancer. Methods: Between 2009 and 2018, n=288 patients underwent TARE for treatment of malignant liver disease in a tertiary care hospital. This retrospective single center study analyzed the safety and outcome of patients (n=11/288) undergoing repeated resin microsphere TARE. Included patients suffered from hepatocellular carcinoma (n=3), colorectal cancer (n=2), breast cancer (n=2), intrahepatic cholangiocarcinoma (n=3), and neuroendocrine carcinoma (n=1). All patients had shown either partial response (n=9) or stable disease (n=2) after first TARE. Lab parameters, response assessed by the Response Evaluation Criteria in Solid Tumors (mRECIST/RECIST) at 3 months and overall survival was analyzed. Additionally, patients with repeated TARE were compared to a matched control group (n=56) with single TARE therapy. Kaplan Meier analysis was performed to analyze survival. Results: Patients after repeated TARE showed similar increase in lab parameters as compared to their first TARE. No case of radioembolization induced liver disease was observed. While n=5/11 patients showed a partial response and n=4/11 patients a stable disease after repeated TARE, only n=2/11 patients suffered from progressive disease. Median overall survival was 20.9±11.9 months for the repeated TARE group while it was 5.9±16.2 months for the control group.Conclusions: Repeated 90Y TARE is safe and can be of benefit for patients yielding a comparable degree of local disease control compared to patients with singular TARE

Prostate specific membrane antigen (PSMA) expression in non-small cell lung cancer

Objectives: PSMA (prostate-specific membrane antigen) is overexpressed in prostate cancer cells and is reported to be a promising target for antibody-based radioligand therapy in patients with metastasized prostate cancer. Since PSMA expression is not restricted to prostate cancer, the underlying study investigates PSMA expression in non-small cell lung cancer (NSCLC). Material and methods: Immunohistochemistry was used to identify PSMA expression in n = 275 samples of NSCLC tissue specimens. By means of CD34 co-expression, the level of PSMA expression in tumor associated neovasculature was investigated. The impact of PSMA expression on clinicopathologic parameters and prognosis was evaluated. Results: PSMA tumor cell expression in NSCLC is as low as 6% and was predominantly found in squamous cell carcinoma (p = 0.002). Neovascular PSMA expression was found in 49% of NSCLC. High neovascular PSMA expression was associated with higher tumor grading (G3/G4) (p < 0.001). Neither for PSMA tumor cell expression, nor for PSMA neovascular cell expression prognostic effects were found for the investigated NSCLC cases. Conclusion: Here, we report on the expression of PSMA in NSCLC tissue samples. Against the background of a potential treatment with radiolabeled PSMA ligands, our data might serve for the future identification of patients who could benefit from this therapeutic option