Refine
Has Fulltext
- yes (33)
Is part of the Bibliography
- yes (33)
Year of publication
Document Type
- Journal article (30)
- Preprint (3)
Language
- English (33) (remove)
Keywords
- prostate cancer (33) (remove)
Institute
- Klinik und Poliklinik für Nuklearmedizin (19)
- Urologische Klinik und Poliklinik (13)
- Klinik und Poliklinik für Strahlentherapie (6)
- Medizinische Klinik und Poliklinik II (4)
- Theodor-Boveri-Institut für Biowissenschaften (3)
- Institut für diagnostische und interventionelle Radiologie (Institut für Röntgendiagnostik) (2)
- Comprehensive Cancer Center Mainfranken (1)
- Deutsches Zentrum für Herzinsuffizienz (DZHI) (1)
- Institut für Klinische Biochemie und Pathobiochemie (1)
- Lehrstuhl für Biochemie (1)
Sonstige beteiligte Institutionen
EU-Project number / Contract (GA) number
- 701983 (4)
Purpose: Prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) imaging has become commonly utilized in patients with prostate cancer (PCa). The PSMA reporting and data system version 1.0 (PSMA-RADS version 1.0) categorizes lesions on the basis of the likelihood of PCa involvement, with PSMA-RADS-3A (soft tissue) and PSMA-RADS-3B (bone) lesions being indeterminate for the presence of disease. We retrospectively reviewed the imaging follow-up of such lesions to determine the rate at which they underwent changes suggestive of underlying PCa.
Methods: PET/CT imaging with \(^{18}\)F-DCFPyL was carried out in 110 patients with PCa and lesions were categorized according to PSMA-RADS Version 1.0. 56/110 (50.9%) patients were determined to have indeterminate PSMA-RADS-3A or PSMA-RADS-3B lesions and 22/56 (39.3%) patients had adequate follow-up to be included in the analysis. The maximum standardized uptake values (SUV\(_{max}\)) of the lesions were obtained and the ratios of SUV\(_{max}\) of the lesions to SUV\(_{mean}\) of blood pool (SUV\(_{max}\)-lesion/SUV\(_{mean}\)-bloodpool) were calculated. Pre-determined criteria were used to evaluate the PSMA-RADS-3A and PSMA-RADS-3B lesions on follow-up imaging to determine if they demonstrated evidence of underlying malignancy.
Results: A total of 46 lesions in 22 patients were considered indeterminate for PCa (i.e. PSMA-RADS-3A (32 lesions) or PSMA-RADS-3B (14 lesions)) and were evaluable on follow-up imaging. 27/46 (58.7%) lesions demonstrated changes on follow-up imaging consistent with the presence of underlying PCa at baseline. These lesions included 24/32 (75.0%) PSMA-RADS-3A lesions and 3/14 (21.4%) lesions categorized as PSMA-RADS-3B. The ranges of SUVmax and SUVmax-lesion/SUVmean-bloodpool overlapped between those lesions demonstrating changes consistent with malignancy on follow-up imaging and those lesions that remained unchanged on follow-up.
Conclusion: PSMA-RADS-3A and PSMA-RADS-3B lesions are truly indeterminate in that proportions of findings in both categories demonstrate evidence of malignancy on follow-up imaging. Overall, PSMA-RADS-3A lesions are more likely than PSMA-RADS-3B lesions to represent sites of PCa and this information should be taken into when guiding patient therapy.
Tracing its roots back to the 1940s, theranostics in nuclear oncology has proved successful mainly due to the beneficial effects of image-guided therapeutic concepts for patients afflicted with a variety of different cancers. The majority of these treatments are not only characterized by substantial prolongation of progression-free and overall survival, but are also generally safe, rendering theranostic agents as an attractive treatment option in various clinical scenarios in oncology. In this Special Issue Novel Theranostic Agents, nine original articles from around the globe provide further evidence on the use of the theranostic concept for neuroendocrine neoplasm (NEN), prostate cancer (PC), meningioma, and neuroblastoma. The investigated diagnostic and therapeutic radiotracers target not only established structures, such as somatostatin receptor, prostate-specific membrane antigen or norepinephrine transporter, but also recently emerging targets such as the C-X-C motif chemokine receptor 4. Moreover, the presented original articles also combine the concept of theranostics with in-depth read-out techniques such as radiomics or novel reconstruction algorithms on pretherapeutic scans, e.g., for outcome prediction. Even 80 years after its initial clinical introduction, theranostics in oncology continues to thrive, now more than ever.
Prostate-specific membrane antigen (PSMA)-targeted PET imaging for prostate cancer with \(^{68}\)Ga-labeled compounds has rapidly become adopted as part of routine clinical care in many parts of the world. However, recent years have witnessed the start of a shift from \(^{68}\)Ga- to \(^{18}\)F-labeled PSMA-targeted compounds. The latter imaging agents have several key advantages, which may lay the groundwork for an even more widespread adoption into the clinic. First, facilitated delivery from distant suppliers expands the availability of PET radiopharmaceuticals in smaller hospitals operating a PET center but lacking the patient volume to justify an onsite \(^{68}\)Ge/\(^{68}\)Ga generator. Thus, such an approach meets the increasing demand for PSMA-targeted PET imaging in areas with lower population density and may even lead to cost-savings compared to in-house production. Moreover, \(^{18}\)F-labeled radiotracers have a higher positron yield and lower positron energy, which in turn decreases image noise, improves contrast resolution, and maximizes the likelihood of detecting subtle lesions. In addition, the longer half-life of 110 min allows for improved delayed imaging protocols and flexibility in study design, which may further increase diagnostic accuracy. Moreover, such compounds can be distributed to sites which are not allowed to produce radiotracers on-site due to regulatory issues or to centers without access to a cyclotron. In light of these advantageous characteristics, \(^{18}\)F-labeled PSMA-targeted PET radiotracers may play an important role in both optimizing this transformative imaging modality and making it widely available. We have aimed to provide a concise overview of emerging \(^{18}\)F-labeled PSMA-targeted radiotracers undergoing active clinical development. Given the wide array of available radiotracers, comparative studies are needed to firmly establish the role of the available \(^{18}\)F-labeled compounds in the field of molecular PCa imaging, preferably in different clinical scenarios.
Objectives: Recently, the standardized reporting and data system for prostate-specific membrane antigen (PSMA)-targeted positron emission tomography (PET) imaging studies, termed PSMA-RADS version 1.0, was introduced. We aimed to determine the interobserver agreement for applying PSMA-RADS to imaging interpretation of 18F-DCFPyL PET examinations in a prospective setting mimicking the typical clinical work-flow at a prostate cancer referral center.
Methods: Four readers (two experienced readers (ER, > 3 years of PSMA-targeted PET interpretation experience) and two inexperienced readers (IR, < 1 year of experience)), who had all read the initial publication on PSMA-RADS 1.0, assessed 50 18F-DCFPyL PET/computed tomography (CT) studies independently. Per scan, a maximum of 5 target lesions were selected by the observers and a PSMA-RADS score for every target lesion was recorded. No specific pre-existing conditions were placed on the selection of the target lesions, although PSMA-RADS 1.0 suggests that readers focus on the most highly avid or largest lesions. An overall scan impression based on PSMA-RADS was indicated and interobserver agreement rates on a target lesion-based, on an organ-based, and on an overall PSMA-RADS score-based level were computed.
Results: The number of target lesions identified by each observer were as follows: ER 1, 123; ER 2, 134; IR 1, 123; and IR 2, 120. Among those selected target lesions, 125 were chosen by at least two individual observers (all four readers selected the same target lesion in 58/125 (46.4%) instances, three readers in 40/125 (32%) and two observers in 27/125 (21.6%) instances). The interobserver agreement for PSMA-RADS scoring among identical target lesions was good (intraclass correlation coefficient (ICC) for four, three and two identical target lesions, ≥0.60, respectively). For lymph nodes, an excellent interobserver agreement was derived (ICC=0.79). The interobserver agreement for an overall scan impression based on PSMA-RADS was also excellent (ICC=0.84), with a significant difference for ER (ICC=0.97) vs. IR (ICC=0.74, P=0.005).
Conclusions: PSMA-RADS demonstrates a high concordance rate in this study, even among readers with different levels of experience. This suggests that PSMA-RADS can be effectively used for communication with clinicians and can be implemented in the collection of data for large prospective trials.
Both prostate-specific membrane antigen (PSMA)- and somatostatin receptor (SSTR)-targeted positron emission tomography (PET) imaging agents for staging and restaging of prostate carcinoma or neuroendocrine tumors, respectively, are seeing rapidly expanding use. In addition to diagnostic applications, both classes of radiotracers can be used to triage patients for theranostic endoradiotherapy. While interpreting PSMA- or SSTR-targeted PET/computed tomography (CT) scans, the reader has to be aware of certain pitfalls. Adding to the complexity of the interpretation of those imaging agents, both normal biodistribution, and also false-positive and -negative findings differ between PSMA- and SSTR-targeted PET radiotracers. Herein summarized under the umbrella term molecular imaging reporting and data systems (MI-RADS), two novel RADS classifications for PSMA- and SSTR-targeted PET imaging are described (PSMA- and SSTR-RADS). Both framework systems may contribute to increase the level of a reader’s confidence and to navigate the imaging interpreter through indeterminate lesions, so that appropriate workup for equivocal findings can be pursued. Notably, PSMA- and SSTR-RADS are structured in a reciprocal fashion, i.e. if the reader is familiar with one system, the other system can readily be applied as well. In the present review we will discuss the most common pitfalls on PSMA- and SSTR-targeted PET/CT, briefly introduce PSMA- and SSTR-RADS, and define a future role of the umbrella framework MI-RADS compared to other harmonization systems.
Standardized reporting is more and more routinely implemented in clinical practice and such structured reports have a major impact on a large variety of medical fields, e.g. laboratory medicine, pathology, and, recently, radiology. Notably, the field of nuclear medicine is constantly evolving, as novel radiotracers for numerous clinical applications are developed. Thus, framework systems for standardized reporting in this field may a) increase clinical acceptance of new radiotracers, b) allow for inter- and intra-center comparisons for quality assurance, and c) may be used in (global) multi-center studies to ensure comparable results and enable efficient data abstraction. In the last two years, several standardized framework systems for positron emission tomography (PET) radiotracers with potential theranostic applications have been proposed. These include systems for prostate-specific membrane antigen (PSMA)-targeted PET agents for the diagnosis and treatment of prostate cancer (PCa) and somatostatin receptor (SSTR)-targeted PET agents for the diagnosis and treatment of neuroendocrine neoplasias. In the present review, those standardized framework systems for PSMA- and SSTR-targeted PET will be briefly introduced followed by an overview of their advantages and limitations. In addition, potential applications will be defined, approaches to validate such concepts will be proposed, and future perspectives will be discussed.
Metastatic tumor cells in body fluids are important targets for treatment, and critical surrogate markers for evaluating cancer prognosis and therapeutic response. Here we report, for the first time, that live metastatic tumor cells in blood samples from mice bearing human tumor xenografts and in blood and cerebrospinal fluid samples from patients with cancer were successfully detected using a tumor cell-specific recombinant vaccinia virus (VACV). In contrast to the FDA-approved CellSearch system, VACV detects circulating tumor cells (CTCs) in a cancer biomarker-independent manner, thus, free of any bias related to the use of antibodies, and can be potentially a universal system for detection of live CTCs of any tumor type, not limited to CTCs of epithelial origin. Furthermore, we demonstrate for the first time that VACV was effective in preventing and reducing circulating tumor cells in mice bearing human tumor xenografts. Importantly, a single intra-peritoneal delivery of VACV resulted in a dramatic decline in the number of tumor cells in the ascitic fluid from a patient with gastric cancer. Taken together, these results suggest VACV to be a useful tool for quantitative detection of live tumor cells in liquid biopsies as well as a potentially effective treatment for reducing or eliminating live tumor cells in body fluids of patients with metastatic disease.
Simple Summary
Patients, who suffer from oligorecurrent prostate cancer with limited nodal involvement, may be offered positron emission tomography (PET)-directed salvage nodal radiotherapy to delay disease progression. This current analysis aimed to access salvage radiotherapy for nodal oligorecurrent prostate cancer with simultaneous integrated boost to PET-involved lymph nodes as metastasis-directed therapy. A long-term oncological outcome was favorable after salvage nodal radiotherapy and severe toxicity rates were low. Androgen deprivation therapy plays a major role in recurrent prostate cancer management and demonstrates a positive influence on the rate of biochemical progression in patients receiving salvage nodal radiotherapy. The present long-term analysis may help clinicians identify patients who would benefit from salvage nodal radiotherapy and androgen deprivation therapy, as a multimodal treatment strategy for oligorecurrent prostate cancer.
Abstract
Background: The study aimed to access the long-term outcome of salvage nodal radiotherapy (SNRT) in oligorecurrent prostate cancer. Methods: A total of 95 consecutive patients received SNRT for pelvic and/or extrapelvic nodal recurrence after prostate-specific membrane antigen (PSMA) or choline PET from 2010 to 2021. SNRT was applied as external beam radiotherapy with simultaneous integrated boost up to a median total dose of 62.9 Gy (EQD2\(_{1.5Gy}\)) to the recurrent lymph node metastases. The outcome was analyzed by cumulative incidence functions with death as the competing risk. Fine–Gray regression analyses were performed to estimate the relative hazards of the outcome parameters. Genitourinary (GU)/gastrointestinal (GI) toxicity evaluation utilized Common Toxicity Criteria for Adverse Events (v5.0). The results are as follows: the median follow-up was 47.1 months. The five-year biochemical progression rate (95% CI) was 50.1% (35.7–62.9%). Concomitant androgen deprivation therapy (ADT) was adminstered in 60.0% of the patients. The five-year biochemical progression rate was 75.0% (42.0–90.9%) without ADT versus 35.3% (19.6–51.4%) with ADT (p = 0.003). The cumulative five-year late grade 3 GU toxicity rate was 2.1%. No late grade 3 GI toxicity occured. Conclusions: Metastasis-directed therapy through SNRT for PET-staged oligorecurrent prostate cancer demonstrated a favorable long-term oncologic outcome. Omittance of ADT led to an increased biochemical progression.
Simple Summary
Prostate cancer often relapses after initial radical prostatectomy, and salvage radiotherapy offers a second chance of cure for relapsed patients. Modern imaging techniques, especially prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT), enable radiation oncologists to target radiotherapy at the involved sites of disease. In a group of patients, PSMA PET/CT imaging can detect a macroscopic local recurrence with or without locoregional lymph node metastasis. In these cases, an escalation of the radiotherapy dose is often considered for controlling the visible tumor mass. As the evidence for dose-escalated salvage radiotherapy for macroscopic recurrent prostate cancer after PSMA PET/CT imaging is still limited, we address this topic in the current analysis. We found that the outcome of patients with dose-escalated salvage radiotherapy for macroscopic prostate cancer recurrence is encouragingly favorable, while the toxicity is very limited.
Abstract
Background: The purpose of this study was to access the oncological outcome of prostate-specific membrane antigen positron emission tomography (PSMA PET/CT)-guided salvage radiotherapy (SRT) for localized macroscopic prostate cancer recurrence. Methods: Between February 2010 and June 2021, 367 patients received SRT after radical prostatectomy. Out of the 367 screened patients, 111 patients were staged by PSMA PET/CT before SRT. A total of 59 out of these 111 (53.2%) patients were treated for PSMA PET-positive macroscopic prostatic fossa recurrence. Dose-escalated SRT was applied with a simultaneous integrated boost at a median prescribed dose of 69.3 Gy (IQR 69.3–72.6 Gy). The oncological outcome was investigated using Kaplan-Meier and Cox regression analyses. The genitourinary (GU)/gastrointestinal (GI) toxicity evaluation utilized Common Toxicity Criteria for Adverse Events (version 5.0). Results: The median follow-up was 38.2 months. The three-year biochemical progression-free survival rate was 89.1% (95% CI: 81.1–97.8%) and the three-year metastasis-free survival rate reached 96.2% (95% CI: 91.2–100.0%). The cumulative three-year late grade 3 GU toxicity rate was 3.4%. No late grade 3 GI toxicity occurred. Conclusions: Dose-escalated PSMA PET/CT-guided salvage radiotherapy for macroscopic prostatic fossa recurrence resulted in favorable survival and toxicity rates.
Purpose
To compare radiotherapy plans between an O-ring and a conventional C-arm linac for hypofractionated high-dose prostate radiotherapy in terms of plan quality, dose distribution, and quality assurance in a multi-vendor environment.
Methods
Twenty prostate cancer treatment plans were irradiated on the O-ring Varian Halcyon linac and were re-optimized for the C-arm Elekta Synergy Agility linac. Dose-volume histogram metrics for target coverage and organ at risk dose, quality assurance, and monitor units were retrospectively compared. Patient-specific quality assurance with ion chamber measurements, gamma index analysis, and portal dosimetry was performed using the Varian Portal Dosimetry system and the ArcCHECK® phantom (Sun Nuclear Corporation). Prostate-only radiotherapy was delivered with simultaneous integrated boost (SIB) volumetric modulated arc therapy (VMAT) in 20 fractions of 2.5/3.0 Gy each.
Results
For both linacs, target coverage was excellent and plan quality comparable. Homogeneity in PTVBoost was high for Synergy as well as Halcyon with a mean homogeneity index of 0.07 ± 0.01 and 0.05 ± 0.01, respectively. Mean dose for the organs at risk rectum and bladder differed not significantly between the linacs but were higher for the femoral heads and penile bulb for Halcyon. Quality assurance showed no significant differences in terms of ArcCHECK gamma pass rates. Median pass rate for 3%/2 mm was 99.3% (96.7 to 99.8%) for Synergy and 99.8% (95.6 to 100%) for Halcyon. Agreement between calculated and measured dose was high with a median deviation of −0.6% (−1.7 to 0.8%) for Synergy and 0.2% (−0.6 to 2.3%) for Halcyon. Monitor units were higher for the Halcyon by approximately 20% (p < 0.001).
Conclusion
Hypofractionated high-dose prostate cancer SIB VMAT on the Halcyon system is feasible with comparable plan quality in reference to a standard C-arm Elekta Synergy linac.