Personalized [177Lu]Lutetium-PSMA Therapy for Patients with Pre-Treated Castration-Resistant Prostate Cancer: A Single Institution Experience from a Comprehensive Cancer Centre.

Castration resistant prostate cancer (CRPC) is characterized by an aggressive biological behavior with a relatively short survival time, especially in progressive tumors pretreated with new hormonal agents and taxane chemotherapy. [177Lu]-Lutetium-PSMA (Lu-PSMA) treatment has proven efficacy in these patients. However, around 30% of the CRPC patients do not benefit from Lu-PSMA treatment, and little is known about predictive factors for treatment success if Lu-PSMA is offered in an individualized approach based on clinical and laboratory features. In this monocentric retrospective study, 86 CRPC patients receiving Lu-PSMA treatment were evaluated. The focus of the study was to describe clinical factors at baseline and during early treatment that are related to overall survival (OS). In addition, PSMA PET/CT-, PSA-response, and safety and tolerability (CTCAE adverse event reporting) were assessed. Efficacy endpoints were calculated using stratified Kaplan-Meier methods and Cox regression models. Mean applied dose was 17.7 GBq (mean 5.3 ± 1.1 GBq per cycle) with an average of 3.6 (range 1-8) therapy cycles. Patients were followed up for a mean of 12.4 months (range 1-39). The median OS was 15 months (95% CI 12.8-17.2). The best overall response rate in patients assessed with PSMA PET/CT and PSA response was 27.9%, and 50.0% had at least stable disease. Nine patients had a ≥grade 3 adverse event with anemia being the most frequent adverse event. Positive predictors for prolonged OS from baseline parameters were pre-treatment hemoglobin level of ≥10 g/dL and a lower PSA values at treatment start, while the presence of visceral or liver metastases were not significantly associated with worse prognoses in this cohort. With careful patient selection, an individualized Lu-PSMA treatment approach is feasible and patients with dose-limiting factors or visceral metastases should be included in prospective trials.

Dynamic 18F-FET PET/CT to differentiate recurrent primary brain tumor and brain metastases from radiation necrosis after single-session robotic radiosurgery.

OBJECTIVE: Cyberknife robotic radiosurgery (RRS) provides single-session high-dose radiotherapy of brain tumors with a steep dose gradient and precise real-time image-guided motion correction. Although RRS appears to cause more radiation necrosis (RN), the radiometabolic changes after RRS have not been fully clarified. 18F-FET-PET/CT is used to differentiate recurrent tumor (RT) from RN after radiosurgery when MRI findings are indecisive. We explored the usefulness of dynamic parameters derived from 18F-FET PET in differentiating RT from RN after Cyberknife treatment in a single-center study population. METHODS: We retrospectively identified brain tumor patients with static and dynamic 18F-FET-PET/CT for suspected RN after Cyberknife. Static (tumor-to-background ratio) and dynamic PET parameters (time-activity curve, time-to-peak) were quantified. Analyses were performed for all lesions taken together (TOTAL) and for brain metastases only (METS). Diagnostic accuracy of PET parameters (using mean tumor-to-background ratio >1.95 and time-to-peak of 20 min for RT as cut-offs) and their respective improvement of diagnostic probability were analyzed. RESULTS: Fourteen patients with 28 brain tumors were included in quantitative analysis. Time-activity curves alone provided the highest sensitivities (TOTAL: 95%, METS: 100%) at the cost of specificity (TOTAL: 50%, METS: 57%). Combined mean tumor-to-background ratio and time-activity curve had the highest specificities (TOTAL: 63%, METS: 71%) and led to the highest increase in diagnosis probability of up to 16% p. - versus 5% p. when only static parameters were used. CONCLUSIONS: This preliminary study shows that combined dynamic and static 18F-FET PET/CT parameters can be used in differentiating RT from RN after RRS.

In Comparison to PSA, Interim Ga-68-PSMA PET/CT Response Evaluation Based on Modified RECIST 1.1 After 2nd Cycle Is Better Predictor of Overall Survival of Prostate Cancer Patients Treated With 177Lu-PSMA.

BACKGROUND: Prostate-specific membrane antigen (PSMA) targeting radioligands have transformed treatment of prostate cancer. Radioligand therapy (RLT) with 177Lu-PSMA in metastasized castration resistant prostate cancer (mCRPC) achieves objective response and disease stabilization in roughly two third of patients, whereas one third of patients progress. This study was performed to assess the role of interim PSMA PET/CT after the 2nd cycle of RLT for early prediction of overall survival in patients undergoing RLT with 177Lu-PSMA. METHODS: 38 mCRPC patients (68.9 ± 8.1 y) treated with at least two cycles of RLT at 8 week intervals and interim 68Ga-PSMA PET/CT (PET) at 8-10 weeks after the 2nd cycle of RLT were included in this study. Prostate-specific antigen (PSA) response was evaluated according to the Prostate Cancer Working Group 3 criteria. Radiographic response assessment of soft tissue, lymph node, and bone lesions was performed according to RECIST 1.1 including the PET component. Patients' data were collected for follow-up from the local Comprehensive Cancer Center Register. RESULTS: Median follow-up was 19.7 months (4.7-45.3). PSA response after the 2nd therapy cycle showed partial remission (PR) in 23.7%, stable disease (SD) in 50%, and progressive disease (PD) in 26.3% of patients. In comparison, 52.6, 23.7, and 23.7% of patients showed PR, SD, and PD respectively on PET/CT. The strength of agreement between PSA response and PET/CT response criteria was only fair (kappa 0.346). Median overall survival (OS) was 22.5 months (95% CI: 15.8-29.2). Median OS stratified to PSA/PET response was 25.6/25.6 months for PR, 21.7/30.6 months for SD and 19.4/13.1 months for PD (p = 0.496 for PSA and 0.013 for PET/CT response). CONCLUSIONS: Interim PSMA PET/CT based response evaluation at 8-10 weeks after the 2nd cycle of RLT is predictive of overall survival and PD in patients treated with 177Lu-PSMA. On the contrary, PSA appears to have only limited predictive value.

Cost comparison of 111In-DTPA-octreotide scintigraphy and 68Ga-DOTATOC PET/CT for staging enteropancreatic neuroendocrine tumours.

PURPOSE: Although somatostatin receptor positron emission tomography (PET)/CT is gaining increasing popularity and has shown its diagnostic superiority in several studies, (111)In-diethylenetriaminepentaacetic acid (DTPA)-octreotide is still the current standard for diagnosis of neuroendocrine tumours (NET). The aim of this study was to compare the costs for the two diagnostic tests and the respective consequential costs. METHODS: From January 2009 to July 2009, 51 consecutive patients with enteropancreatic NET who underwent contrast-enhanced (68)Ga-DOTATOC PET/CT (n = 29) or (111)In-DTPA-octreotide (mean 3 whole-body scans plus 1.6 low-dose single photon emission computed tomography/CT; n = 22) were included. For cost analysis, direct costs (equipment) and variable costs (material, labour) per examination were calculated. Additionally required CT and/or MRI examinations within the staging process were assessed as consequential costs. An additional deterministic sensitivity analysis was performed. RESULTS: A (68)Ga-DOTATOC PET/CT examination yielded total costs (equipment, personnel and material costs) of 548 euro. On the other hand, an (111)In-DTPA-octreotide examination resulted in 827 euro total costs. Costs for equipment and material had a share of 460 euro/720 euro for (68)Ga-DOTATOC/(111)In-DTPA-octreotide and labour costs of 89 euro/106 euro. With (68)Ga-DOTATOC additional MRI had to be performed in 7% of the patients resulting in a mean of 20 euro for supplementary imaging per patient; 82% of patients with (111)In-DTPA-octreotide needed additional MRI and/or CT resulting in mean additional costs of 161 euro per patient. CONCLUSION: (68)Ga-DOTATOC PET/CT was considerably cheaper than (111)In-DTPA-octreotide with respect to both material and personnel costs. Furthermore, by using (68)Ga-DOTATOC PET/CT considerably fewer additional examinations were needed reducing the consequential costs significantly.

Efficacy of indigenously developed single vial kit preparation of 99mTc-ciprofloxacin in the detection of bacterial infection: an Indian experience.

OBJECTIVE: To investigate the diagnostic efficacy of indigenously developed single vial kit preparation of Tc-ciprofloxacin (Diagnobact) for the detection of orthopedic infections. METHODS: Seventy-seven patients [25 with clinical suspicion of diabetic foot osteomyelitis (DFOM), 25 with orthopedic device-related infection (ODRI) and 27 with tubercular bone infection] underwent three-phase Tc-methylenediphosphonate bone scintigraphy followed by static Tc-ciprofloxacin imaging at 1, 4 and 24 h. Imaging (anterior and posterior views) was performed under a dual-head gamma-camera using a low-energy, high-resolution, parallel-hole collimator. The lesion-to-background ratio (LBR) of the radiotracer was calculated on the static isotime Tc-ciprofloxacin images using semiquantitative analysis. Scintigraphic (Diagnobact) results were compared with the histopathological and/or culture/PCR analysis as a gold standard. RESULTS: The mean LBR of the radiotracer (Tc-ciprofloxacin) in the positive scans (n=29; 16 ODRI, 13 DFOM) was > or =2.0 at 1 h postinjection and remained consistent till 24 h. In contrast, the mean LBR in the negative scans (n=21; 12 DFOM, nine ODRI) was < or =1.5 at 1 h and declined significantly (P<0.05) at 24 h. The observed trend in the mean LBR in positive (n=18) and negative (n=9) scans for tubercular osteomyelitis was identical to that seen in the nontubercular bacterial infections. CONCLUSION: The management protocol for patients with suspected bony infection may include a three-phase bone scan followed by Tc-ciprofloxacin scan. An LBR of > or =2.0 at 1 h that remained consistent till 24 h on Tc-ciprofloxacin scan is indicative of active bacterial infection. However, resistance to ciprofloxacin at the bacterial cell membrane may be a limitation of this technique.