@article{WernerHabachaLuetjeetal.2022,
  author    = {Werner, Rudolf A. and Habacha, Bil{\^e}l and L{\"u}tje, Susanne and Bundschuh, Lena and Higuchi, Takahiro and Hartrampf, Philipp and Serfling, Sebastian E. and Derlin, Thorsten and Lapa, Constantin and Buck, Andreas K. and Essler, Markus and Pienta, Kenneth J. and Eisenberger, Mario A. and Markowski, Mark C. and Shinehouse, Laura and AbdAllah, Rehab and Salavati, Ali and Lodge, Martin A. and Pomper, Martin G. and Gorin, Michael A. and Bundschuh, Ralph A. and Rowe, Steven P.},
  title     = {High SUVs Have More Robust Repeatability in Patients with Metastatic Prostate Cancer: Results from a Prospective Test-Retest Cohort Imaged with \(^{18}\)F-DCFPyL},
  series = {Molecular Imaging},
  volume    = {2022},
  journal   = {Molecular Imaging},
  doi       = {10.1155/2022/7056983},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300748},
  year      = {2022},
  abstract  = {No abstract available.},
  language  = {en}
}
@unpublished{WernerBundschuhBundschuhetal.2019,
  author    = {Werner, Rudolf A. and Bundschuh, Ralph A. and Bundschuh, Lena and Fanti, Stefano and Javadi, Mehrbod S. and Higuchi, Takahiro and Weich, A. and Pienta, Kenneth J. and Buck, Andreas K. and Pomper, Martin G. and Gorin, Michael A. and Herrmann, Ken and Lapa, Constantin and Rowe, Steven P.},
  title     = {Novel Structured Reporting Systems for Theranostic Radiotracers},
  series = {Journal of Nuclear Medicine},
  journal   = {Journal of Nuclear Medicine},
  issn      = {0161-5505},
  doi       = {10.2967/jnumed.118.223537},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-174629},
  year      = {2019},
  abstract  = {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.},
  subject      = {Positronen-Emissions-Tomografie},
  language  = {en}
}
@unpublished{WernerBundschuhBundschuhetal.2018,
  author    = {Werner, Rudolf A. and Bundschuh, Ralph A. and Bundschuh, Lena and Javadi, Mehrbod S. and Leal, Jeffrey P. and Higuchi, Takahiro and Pienta, Kenneth J. and Buck, Andreas K. and Pomper, Martin G. and Gorin, Michael A. and Lapa, Constantin and Rowe, Steven P.},
  title     = {Interobserver Agreement for the Standardized Reporting System PSMA-RADS 1.0 on \(^{18}\)F-DCFPyL PET/CT Imaging},
  series = {Journal of Nuclear Medicine},
  journal   = {Journal of Nuclear Medicine},
  issn      = {0161-5505},
  doi       = {10.2967/jnumed.118.217588},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-167788},
  year      = {2018},
  abstract  = {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.},
  subject      = {Positronen-Emissions-Tomografie},
  language  = {en}
}
@article{WernerBundschuhBundschuhetal.2018,
  author    = {Werner, Rudolf A. and Bundschuh, Ralph A. and Bundschuh, Lena and Javadi, Mehrbod S. and Higuchi, Takahiro and Weich, Alexander and Sheikhbahaei, Sara and Pienta, Kenneth J. and Buck, Andreas K. and Pomper, Martin G. and Gorin, Michael A. and Lapa, Constantin and Rowe, Steven P.},
  title     = {MI-RADS: Molecular Imaging Reporting and Data Systems - A Generalizable Framework for Targeted Radiotracers with Theranostic Implications},
  series = {Annals of Nuclear Medicine},
  journal   = {Annals of Nuclear Medicine},
  issn      = {0914-7187},
  doi       = {10.1007/s12149-018-1291-7},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-166995},
  year      = {2018},
  abstract  = {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.},
  subject      = {Positronen-Emissions-Tomografie},
  language  = {en}
}
@unpublished{WernerIlhanLehneretal.2018,
  author    = {Werner, Rudolf A. and Ilhan, Harun and Lehner, Sebastian and Papp, L{\´a}szl{\´o} and Zs{\´o}t{\´e}r, Norbert and Schatka, Imke and Muegge, Dirk O. and Javadi, Mehrbod S. and Higuchi, Takahiro and Buck, Andreas K. and Bartenstein, Peter and Bengel, Frank and Essler, Markus and Lapa, Constantin and Bundschuh, Ralph A.},
  title     = {Pre-therapy Somatostatin-Receptor-Based Heterogeneity Predicts Overall Survival in Pancreatic Neuroendocrine Tumor Patients Undergoing Peptide Receptor Radionuclide Therapy},
  series = {Molecular Imaging and Biology},
  journal   = {Molecular Imaging and Biology},
  issn      = {1536-1632},
  doi       = {https://doi.org/10.1007/s11307-018-1252-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-164624},
  year      = {2018},
  abstract  = {Purpose: Early identification of aggressive disease could improve decision-support in pancreatic neuroendocrine tumor (pNET) patients prior to peptide receptor radionuclide therapy (PRRT). The prognostic value of intratumoral textural features (TF) determined by baseline somatostatin receptor (SSTR)-PET before PRRT was analyzed. Procedures: 31 patients with G1/G2 pNET were enrolled (G2, n=23/31). Prior to PRRT with [\(^{177}\)Lu]DOTATATE (mean, 3.6 cycles), baseline SSTR-PET/CT was performed. By segmentation of 162 (median per patient, 5) metastases, intratumoral TF were computed. The impact of conventional PET parameters (SUV\(_{mean/max}\)), imaging-based TF as well as clinical parameters (Ki67, CgA) for prediction of both progression-free (PFS) and overall survival (OS) after PRRT was evaluated. Results: Within a median follow-up of 3.7y, tumor progression was detected in 21 patients (median, 1.5y) and 13/31 deceased (median, 1.9y). In ROC analysis, the TF Entropy, reflecting derangement on a voxel-by-voxel level, demonstrated predictive capability for OS (cutoff=6.7, AUC=0.71, p=0.02). Of note, increasing Entropy could predict a longer survival (>6.7, OS=2.5y, 17/31), whereas less voxel-based derangement portended inferior outcome (<6.7, OS=1.9y, 14/31). These findings were supported in a G2 subanalysis (>6.9, OS=2.8y, 9/23 vs. <6.9, OS=1.9y, 14/23). Kaplan-Meier analysis revealed a significant distinction between high- and low-risk groups using Entropy (n=31, p<0.05). For those patients below the ROC-derived threshold, the relative risk of death after PRRT was 2.73 (n=31, p=0.04). Ki67 was negatively associated with PFS (p=0.002); however, SUVmean/max failed in prognostication (n.s.). Conclusions: In contrast to conventional PET parameters, assessment of intratumoral heterogeneity demonstrated superior prognostic performance in pNET patients undergoing PRRT. This novel PET-based strategy of outcome prediction prior to PRRT might be useful for patient risk stratification.},
  subject      = {Positronen-Emissions-Tomografie},
  language  = {en}
}
@article{LapaReiterKircheretal.2016,
  author    = {Lapa, Constantin and Reiter, Theresa and Kircher, Malte and Schirbel, Andreas and Werner, Rudolf A. and Pelzer, Theo and Pizarro, Carmen and Skowasch, Dirk and Thomas, Lena and Schlesinger-Irsch, Ulrike and Thomas, Daniel and Bundschuh, Ralph A. and Bauer, Wolfgang R. and Gartner, Florian C.},
  title     = {Somatostatin receptor based PET/CT in patients with the suspicion of cardiac sarcoidosis: an initial comparison to cardiac MRI},
  series = {Oncotarget},
  volume    = {7},
  journal   = {Oncotarget},
  number    = {47},
  doi       = {10.18632/oncotarget.12799},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-175423},
  pages     = {77807-77814},
  year      = {2016},
  abstract  = {Diagnosis of cardiac sarcoidosis is often challenging. Whereas cardiac magnetic resonance imaging (CMR) and positron emission tomography/computed tomography (PET/CT) with \(^{18}\)F-fluorodeoxyglucose (FDG) are most commonly used to evaluate patients, PET/CT using radiolabeled somatostatin receptor (SSTR) ligands for visualization of inflammation might represent a more specific alternative. This study aimed to investigate the feasibility of SSTR-PET/CT for detecting cardiac sarcoidosis in comparison to CMR. 15 patients (6 males, 9 females) with sarcoidosis and suspicion on cardiac involvement underwent SSTR-PET/CT imaging and CMR. Images were visually scored. The AHA 17-segment model of the left myocardium was used for localization and comparison of inflamed myocardium for both imaging modalities. In semi-quantitative analysis, mean (SUV\(_{mean}\)) and maximum standardized uptake values (SUV\(_{max}\)) of affected myocardium were calculated and compared with both remote myocardium and left ventricular (LV) cavity. SSTR-PET was positive in 7/15, CMR in 10/15 patients. Of the 3 CMR+/PET- subjects, one patient with minor involvement (<25\% of wall thickness in CMR) was missed by PET. The remaining two CMR+/PET- patients displayed no adverse cardiac events during follow-up. In the 17-segment model, PET/CT yielded 27 and CMR 29 positive segments. Overall concordance of the 2 modalities was 96.1\% (245/255 segments analyzed). SUV\(_{mean}\) and SUV\(_{max}\) in inflamed areas were 2.0±1.2 and 2.6±1.2, respectively. The lesion-to-remote myocardium and lesion-to-LV cavity ratios were 1.8±0.2 and 1.9±0.2 for SUV\(_{mean}\) and 2.0±0.3 and 1.7±0.3 for SUV\(_{max}\), respectively. Detection of cardiac sarcoidosis by SSTR-PET/CT is feasible. Our data warrant further analysis in larger prospective series.},
  language  = {en}
}
@article{LapaWernerBluemeletal.2014,
  author    = {Lapa, Constantin and Werner, Rudolf A. and Bluemel, Christina and Lueckerath, Katharina and Muegge, Dirk O. and Strate, Alexander and Haenscheid, Heribert and Schirbel, Andreas and Allen-Auerbach, Martin S. and Bundschuh, Ralph A. and Buck, Andreas K. and Herrmann, Ken},
  title     = {Prediction of clinically relevant hyperkalemia in patients treated with peptide receptor radionuclide therapy},
  series = {EJNMMI Research},
  volume    = {4},
  journal   = {EJNMMI Research},
  number    = {74},
  doi       = {10.1186/s13550-014-0074-y},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-124963},
  year      = {2014},
  abstract  = {Background Peptide receptor radionuclide therapy (PRRT) is applied in patients with advanced neuroendocrine tumors. Co-infused amino acids (AA) should prevent nephrotoxicity. The aims of this study were to correlate the incidence of AA-induced hyperkalemia (HK) (≥5.0 mmol/l) and to identify predictors of AA-induced severe HK (>6.0). Methods In 38 patients, standard activity of \(^{177}Lu\)-labelled somatostatin analogs was administered. Pre-therapeutic kidney function was assessed by renal scintigraphy and laboratory tests. For kidney protection, AA was co-infused. Biochemical parameters (potassium, glomerular filtration rate, creatinine, blood urea nitrogen (BUN), sodium, phosphate, chloride, and lactate dehydrogenase (LDH)) were obtained prior to 4 and 24 h after the AA infusion. Incidence of HK (≥5.0) was correlated with pre-therapeutic kidney function and serum parameters. Formulas for the prediction of severe hyperkalemia (>6.0) were computed and prospectively validated. Results At 4 h, HK (≥5.0) was present in 94.7\% with severe HK (>6.0) in 36.1\%. Values normalized after 24 h in 84.2\%. Pre-therapeutic kidney function did not correlate with the incidence of severe HK. Increases in K+ were significantly correlated with decreases in phosphate (r = -0.444, p < 0.005) and increases in BUN (r = 0.313, p = 0.056). A baseline BUN of >28 mg/dl had a sensitivity of 84.6\% and a specificity of 60.0\% (AUC = 0.75) in predicting severe HK of >6.0 (phosphate, AUC = 0.37). Computing of five standard serum parameters (potassium, BUN, sodium, phosphate, LDH) resulted in a sensitivity of 88.9\% and a specificity of 79.3\% for the prediction of severe HK >6.0 (accuracy = 81.6\%). Conclusions A combination of serum parameters predicted prospectively the occurrence of relevant HK with an accuracy of 81.6\% underlining its potential utility for identifying 'high-risk' patients prone to PRRT.},
  language  = {en}
}
@article{HartrampfWeinzierlSeitzetal.2022,
  author    = {Hartrampf, Philipp E. and Weinzierl, Franz-Xaver and Seitz, Anna Katharina and K{\"u}bler, Hubert and Essler, Markus and Buck, Andreas K. and Werner, Rudolf A. and Bundschuh, Ralph A.},
  title     = {Any decline in prostate-specific antigen levels identifies survivors scheduled for prostate-specific membrane antigen-directed radioligand therapy},
  series = {The Prostate},
  volume    = {82},
  journal   = {The Prostate},
  number    = {14},
  doi       = {10.1002/pros.24414},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-318766},
  pages     = {1406 -- 1412},
  year      = {2022},
  abstract  = {Background Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) is increasingly incorporated in the therapeutic algorithm of patients with metastatic castration-resistant prostate cancer (mCRPC). We aimed to elucidate the predictive performance of early biochemical response for overall survival (OS). Materials and Methods In this bicentric analysis, we included 184 mCRPC patients treated with \(^{177}\)Lu-PSMA RLT. Response to treatment was defined as decrease in prostate-specific antigen (PSA) levels 8 weeks after the first cycle of RLT (any decline or >50\% according to Prostate Cancer Working Group 3). OS of responders and nonresponders was then compared using Kaplan-Meier curves and log-rank comparison. Results A total of 114/184 patients (62.0\%) showed any PSA decline (PSA response >50\%, 55/184 [29.9\%]). For individuals exhibiting a PSA decline >50\%, OS of 19 months was significantly longer relative to nonresponders (13 months; hazard ratio of death [HR] = 0.64, 95\% confidence interval [95\% CI] = 0.44-0.93; p = 0.02). However, the difference was even more pronounced for any PSA decline, with an OS of 19 months in responders, but only 8 months in nonresponders (HR = 0.39, 95\% CI = 0.25-0.60; p < 0.001). Conclusions In mCRPC patients scheduled for RLT, early biochemical response was tightly linked to prolonged survival, irrespective of the magnitude of PSA decline. As such, even in patients with PSA decrease of less than 50\%, RLT should be continued.},
  language  = {en}
}
@article{WernerIlhanLehneretal.2018,
  author    = {Werner, Rudolf A. and Ilhan, Harun and Lehner, Sebastian and Papp, L{\´a}szl{\´o} and Zs{\´o}t{\´e}r, Norbert and Schatka, Imke and Muegge, Dirk O. and Javadi, Mehrbod S. and Higuchi, Takahiro and Buck, Andreas K. and Bartenstein, Peter and Bengel, Frank and Essler, Markus and Lapa, Constantin and Bundschuh, Ralph A.},
  title     = {Pre-therapy Somatostatin-Receptor-Based Heterogeneity Predicts Overall Survival in Pancreatic Neuroendocrine Tumor Patients Undergoing Peptide Receptor Radionuclide Therapy},
  series = {Molecular Imaging and Biology},
  journal   = {Molecular Imaging and Biology},
  issn      = {1536-1632},
  doi       = {10.1007/s11307-018-1252-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-167168},
  year      = {2018},
  abstract  = {Purpose: Early identification of aggressive disease could improve decision-support in pancreatic neuroendocrine tumor (pNET) patients prior to peptide receptor radionuclide therapy (PRRT). The prognostic value of intratumoral textural features (TF) determined by baseline somatostatin receptor (SSTR)-PET before PRRT was analyzed. Procedures: 31 patients with G1/G2 pNET were enrolled (G2, n=23/31). Prior to PRRT with [\(^{177}\)Lu]DOTATATE (mean, 3.6 cycles), baseline SSTR-PET/CT was performed. By segmentation of 162 (median per patient, 5) metastases, intratumoral TF were computed. The impact of conventional PET parameters (SUV\(_{mean/max}\)), imaging-based TF as well as clinical parameters (Ki67, CgA) for prediction of both progression-free (PFS) and overall survival (OS) after PRRT was evaluated. Results: Within a median follow-up of 3.7y, tumor progression was detected in 21 patients (median, 1.5y) and 13/31 deceased (median, 1.9y). In ROC analysis, the TF Entropy, reflecting derangement on a voxel-by-voxel level, demonstrated predictive capability for OS (cutoff=6.7, AUC=0.71, p=0.02). Of note, increasing Entropy could predict a longer survival (>6.7, OS=2.5y, 17/31), whereas less voxel-based derangement portended inferior outcome (<6.7, OS=1.9y, 14/31). These findings were supported in a G2 subanalysis (>6.9, OS=2.8y, 9/23 vs. <6.9, OS=1.9y, 14/23). Kaplan-Meier analysis revealed a significant distinction between high- and low-risk groups using Entropy (n=31, p<0.05). For those patients below the ROC-derived threshold, the relative risk of death after PRRT was 2.73 (n=31, p=0.04). Ki67 was negatively associated with PFS (p=0.002); however, SUVmean/max failed in prognostication (n.s.). Conclusions: In contrast to conventional PET parameters, assessment of intratumoral heterogeneity demonstrated superior prognostic performance in pNET patients undergoing PRRT. This novel PET-based strategy of outcome prediction prior to PRRT might be useful for patient risk stratification.},
  subject      = {Positronen-Emissions-Tomografie},
  language  = {en}
}
@article{WernerBundschuhHiguchietal.2018,
  author    = {Werner, Rudolf A. and Bundschuh, Ralph A. and Higuchi, Takahiro and Javadi, Mehrbod S. and Rowe, Steven P. and Zs{\´o}t{\´e}r, Norbert and Kroiss, Matthias and Fassnacht, Martin and Buck, Andreas K. and Kreissl, Michael C. and Lapa, Constantin},
  title     = {Volumetric and Texture Analysis of Pretherapeutic \(^{18}\)F-FDG PET can Predict Overall Survival in Medullary Thyroid Cancer Patients Treated with Vandetanib},
  series = {Endocrine},
  journal   = {Endocrine},
  issn      = {1355-008X},
  doi       = {10.1007/s12020-018-1749-3},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-167910},
  year      = {2018},
  abstract  = {Purpose: The metabolically most active lesion in 2-deoxy-2-(\(^{18}\)F)fluoro-D-glucose (\(^{18}\)F-FDG) PET/CT can predict progression-free survival (PFS) in patients with medullary thyroid carcinoma (MTC) starting treatment with the tyrosine kinase inhibitor (TKI) vandetanib. However, this metric failed in overall survival (OS) prediction. In the present proof of concept study, we aimed to explore the prognostic value of intratumoral textural features (TF) as well as volumetric parameters (total lesion glycolysis, TLG) derived by pre-therapeutic \(^{18}\)F-FDG PET. Methods: Eighteen patients with progressive MTC underwent baseline \(^{18}\)F-FDG PET/CT prior to and 3 months after vandetanib initiation. By manual segmentation of the tumor burden at baseline and follow-up PET, intratumoral TF and TLG were computed. The ability of TLG, imaging-based TF, and clinical parameters (including age, tumor marker doubling times, prior therapies and RET (rearranged during transfection) mutational status) for prediction of both PFS and OS were evaluated. Results: The TF Complexity and the volumetric parameter TLG obtained at baseline prior to TKI initiation successfully differentiated between low- and high-risk patients. Complexity allocated 10/18 patients to the high-risk group with an OS of 3.3y (vs. low-risk group, OS=5.3y, 8/18, AUC=0.78, P=0.03). Baseline TLG designated 11/18 patients to the high-risk group (OS=3.5y vs. low-risk group, OS=5y, 7/18, AUC=0.83, P=0.005). The Hazard Ratio for cancer-related death was 6.1 for Complexity (TLG, 9.5). Among investigated clinical parameters, the age at initiation of TKI treatment reached significance for PFS prediction (P=0.02, OS, n.s.). Conclusions: The TF Complexity and the volumetric parameter TLG are both independent parameters for OS prediction.},
  subject      = {Positronen-Emissions-Tomografie},
  language  = {en}
}
@article{WeichHiguchiBundschuhetal.2022,
  author    = {Weich, Alexander and Higuchi, Takahiro and Bundschuh, Ralph A. and Lapa, Constantin and Serfling, Sebastian E. and Rowe, Steven P. and Pomper, Martin G. and Herrmann, Ken and Buck, Andreas K. and Derlin, Thorsten and Werner, Rudolf A.},
  title     = {Training on reporting and data system (RADS) for somatostatin-receptor targeted molecular imaging can reduce the test anxiety of inexperienced readers},
  series = {Molecular Imaging and Biology},
  volume    = {24},
  journal   = {Molecular Imaging and Biology},
  number    = {4},
  doi       = {10.1007/s11307-022-01712-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324645},
  pages     = {631-640},
  year      = {2022},
  abstract  = {Purpose For somatostatin receptor (SSTR)-positron emission tomography/computed tomography (PET/CT), a standardized framework termed SSTR-reporting and data system (RADS) has been proposed. We aimed to elucidate the impact of a RADS-focused training on reader's anxiety to report on SSTR-PET/CT, the motivational beliefs in learning such a system, whether it increases reader's confidence, and its implementation in clinical routine. Procedures A 3-day training course focusing on SSTR-RADS was conducted. Self-report questionnaires were handed out prior to the course (Pre) and thereafter (Post). The impact of the training on the following categories was evaluated: (1) test anxiety to report on SSTR-PET/CT, (2) motivational beliefs, (3) increase in reader's confidence, and (4) clinical implementation. To assess the effect size of the course, Cohen's d was calculated (small, d = 0.20; large effect, d = 0.80). Results Of 22 participants, Pre and Post were returned by 21/22 (95.5\%). In total, 14/21 (66.7\%) were considered inexperienced (IR, < 1 year experience in reading SSTR-PET/CTs) and 7/21 (33.3\%) as experienced readers (ER, > 1 year). Applying SSTR-RADS, a large decrease in anxiety to report on SSTR-PET/CT was noted for IR (d =  - 0.74, P = 0.02), but not for ER (d = 0.11, P = 0.78). For the other three categories motivational beliefs, reader's confidence, and clinical implementation, agreement rates were already high prior to the training and persisted throughout the course (P ≥ 0.21). Conclusions A framework-focused reader training can reduce anxiety to report on SSTR-PET/CTs, in particular for inexperienced readers. This may allow for a more widespread adoption of this system, e.g., in multicenter trials for better intra- and interindividual comparison of scan results.},
  language  = {en}
}
@article{HartrampfBundschuhWeinzierletal.2022,
  author    = {Hartrampf, Philipp E. and Bundschuh, Ralph A. and Weinzierl, Franz-Xaver and Serfling, Sebastian E. and Kosmala, Aleksander and Seitz, Anna Katharina and K{\"u}bler, Hubert and Buck, Andreas K. and Essler, Markus and Werner, Rudolf A.},
  title     = {mCRPC patients with PSA fluctuations under radioligand therapy have comparable survival benefits relative to patients with sustained PSA decrease},
  series = {European Journal of Nuclear Medicine and Molecular Imaging},
  volume    = {49},
  journal   = {European Journal of Nuclear Medicine and Molecular Imaging},
  number    = {13},
  doi       = {10.1007/s00259-022-05910-w},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324562},
  pages     = {4727-4735},
  year      = {2022},
  abstract  = {Introduction In men with metastatic castration-resistant prostate cancer (mCRPC) scheduled for prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT), biochemical response is assessed based on repeated measurements of prostate-specific antigen (PSA) levels. We aimed to determine overall survival (OS) in patients experiencing sustained PSA increase, decrease, or fluctuations during therapy. Materials and methods In this bicentric study, we included 176 mCRPC patients treated with PSMA-directed RLT. PSA levels were determined using blood samples prior to the first RLT and on the admission days for the following cycles. We calculated relative changes in PSA levels compared to baseline. Kaplan-Meier curves as well as log-rank test were used to compare OS of different subgroups, including patients with sustained PSA increase, decrease, or fluctuations (defined as change after initial decrease or increase after the first cycle). Results Sixty-one out of one hundred seventy-six (34.7\%) patients showed a sustained increase and 86/176 (48.8\%) a sustained decrease in PSA levels. PSA fluctuations were observed in the remaining 29/176 (16.5\%). In this subgroup, 22/29 experienced initial PSA decrease followed by an increase (7/29, initial increase followed by a decrease). Median OS of patients with sustained decrease in PSA levels was significantly longer when compared to patients with sustained increase of PSA levels (19 vs. 8 months; HR 0.35, 95\% CI 0.22-0.56; P < 0.001). Patients with PSA fluctuations showed a significantly longer median OS compared to patients with sustained increase of PSA levels (18 vs. 8 months; HR 0.49, 95\% CI 0.30-0.80; P < 0.01), but no significant difference relative to men with sustained PSA decrease (18 vs. 19 months; HR 1.4, 95\% CI 0.78-2.49; P = 0.20). In addition, in men experiencing PSA fluctuations, median OS did not differ significantly between patients with initial decrease or initial increase of tumor marker levels (16 vs. 18 months; HR 1.2, 95\% CI 0.38-4.05; P = 0.68). Conclusion Initial increase or decrease of PSA levels is sustained in the majority of patients undergoing RLT. Sustained PSA decrease was linked to prolonged survival and men with PSA fluctuations under treatment experienced comparable survival benefits. As such, transient tumor marker oscillations under RLT should rather not lead to treatment discontinuation, especially in the absence of radiological progression.},
  language  = {en}
}
@article{HartrampfWeinzierlBucketal.2022,
  author    = {Hartrampf, Philipp E. and Weinzierl, Franz-Xaver and Buck, Andreas K. and Rowe, Steven P. and Higuchi, Takahiro and Seitz, Anna Katharina and K{\"u}bler, Hubert and Schirbel, Andreas and Essler, Markus and Bundschuh, Ralph A. and Werner, Rudolf A.},
  title     = {Matched-pair analysis of [\(^{177}\)Lu]Lu-PSMA I\&T and [\(^{177}\)Lu]Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer},
  series = {European Journal of Nuclear Medicine and Molecular Imaging},
  volume    = {49},
  journal   = {European Journal of Nuclear Medicine and Molecular Imaging},
  number    = {9},
  doi       = {10.1007/s00259-022-05744-6},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-324581},
  pages     = {3269-3276},
  year      = {2022},
  abstract  = {Background Labelled with lutetium-177, the urea-based small molecules PSMA I\&T and PSMA-617 are the two agents most frequently used for radioligand therapy (RLT) in patients with advanced metastatic castration-resistant and prostate-specific membrane antigen (PSMA) expressing prostate cancer (mCRPC). In this matched-pair analysis, we aimed to compare the toxicity and efficacy of both agents for PSMA-directed RLT. Materials and methods A total of 110 mCRPC patients from two centres were accrued, 55 individuals treated with [\(^{177}\)Lu]Lu-PSMA I\&T, and a matched cohort of 55 patients treated with [\(^{177}\)Lu]Lu-PSMA-617. Matching criteria included age at the first cycle, Gleason score, prostate-specific antigen (PSA) values, and previous taxane-based chemotherapy. Using common terminology criteria for adverse events (CTCAE v. 5.0), toxicity profiles were investigated (including bone marrow and renal toxicity). Overall survival (OS) between both groups was compared. Results Toxicity assessment revealed grade III anaemia in a single patient (1.8\%) for [\(^{177}\)Lu]Lu-PSMA I\&T and five (9.1\%) for [\(^{177}\)Lu]Lu-PSMA-617. In addition, one (1.9\%) grade III thrombopenia for [\(^{177}\)Lu]Lu-PSMA-617 was recorded. Apart from that, no other grade III/IV toxicities were present. A median OS of 12 months for patients treated with [\(^{177}\)Lu]Lu-PSMA I\&T did not differ significantly when compared to patients treated with [\(^{177}\)Lu]Lu-PSMA-617 (median OS, 13 months; P = 0.89). Conclusion In this matched-pair analysis of patients receiving one of the two agents most frequently applied for PSMA RLT, the rate of clinically relevant toxicities was low for both compounds. In addition, no relevant differences for OS were observed.},
  language  = {en}
}