@phdthesis{Kosmala2014,
  author    = {Kosmala, Aleksander},
  title     = {Pr{\"a}diktoren der Inanspruchnahme von Alternativmedizin bei Krebserkrankten},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-109933},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2014},
  abstract  = {Hintergrund: Dank der modernen Medizin werden Krebserkrankungen immer h{\"a}ufiger und fr{\"u}her entdeckt. Immer mehr onkologische Patienten leben {\"u}ber einen langen Zeitraum mit ihrer Krebserkrankung, sodass Krebs mehr und mehr zur chronischen Erkrankung wird. Von diesen Patienten nimmt ein sehr hoher Anteil Alternativmedizin in Anspruch, oft Wissen der behandelnden {\"A}rzte. Dabei sind sich viele Patienten der Tatsache nicht bewusst, dass zahlreiche vermeintlich nat{\"u}rliche alternative Heilmittel durchaus relevante Neben- und Wechselwirkungen haben k{\"o}nnen. Ziel der vorliegenden Arbeit war es, aktuelle Pr{\"a}valenzwerte f{\"u}r die Inanspruchnahme von Alternativmedizin durch Krebspatienten zu erfassen und Patientenmerkmale zu finden, die in Zusammenhang mit der Nutzung alternativmedizinischer Methoden stehen. Methoden: Es wurden Patientendaten verwendet, die im Rahmen der multizentrischen, von der Deutschen Krebshilfe gef{\"o}rderten Studie „Pr{\"a}valenz psychosozialer Belastungen, psychischer St{\"o}rungen und ihr Behandlungsbedarf bei Tumorpatienten" im Studienzentrum W{\"u}rzburg erhoben wurden. Neben Angaben zur Nutzung von Alternativmedizin wurden mit Hilfe eines vom Patienten auszuf{\"u}llenden Fragebogenheftes verschiedene soziodemographische und psychosoziale Variablen erfasst und durch medizinische Daten aus Krankenakten erg{\"a}nzt. M{\"o}gliche Pr{\"a}diktoren wurden mittels stufenweiser logistischer Regression ermittelt. Ergebnisse: Von den 770 W{\"u}rzburger Studienteilnehmern konnten 699 im Alter zwischen 21 und 75 Jahren f{\"u}r die vorliegende Arbeit zur Analyse herangezogen werden. Insgesamt nutzte etwa jeder dritte Patient (33,6\%) Alternativmedizin im Zusammen-hang mit der Krebserkrankung, was sich gut mit Daten aus der aktuellen Forschung deckt. 71,5\% der Nutzer waren weiblich. Am h{\"a}ufigsten wurden Mittel aus den Kategorien „Vitamine, Mineralien, Spurenelemente" (24\% aller Patienten), „Hom{\"o}opathie" (11,6\%) und „Misteltherapie" (6,4\%) angewandt. Als Bezugsquelle der alternativmedizinischen Mittel diente in der Mehrzahl der F{\"a}lle (62,5\%) ein Arzt. Alle alternativmedizinischen Angebote wurden von den Anwendern hoch in ihrer N{\"u}tzlichkeit bewertet. Dar{\"u}ber hinaus wurden soziodemographische, medizinische und psychosoziale Variablen auf einen Zusammenhang mit der Inanspruchnahme von Alternativmedizin untersucht. Entsprechend dem aktuellen Forschungsstand erwiesen sich dabei weibliches Geschlecht und h{\"o}herer Bildungsstand als unabh{\"a}ngige Pr{\"a}diktoren f{\"u}r die Nutzung von Alternativmedizin. Ein Zusammenhang mit dem Alter konnte hingegen nicht best{\"a}tigt werden. Im Hinblick auf krankheits- und therapieassoziierte Variablen waren der Abschluss einer Strahlentherapie und die Angabe von krebsbedingten Schmerzen von unabh{\"a}ngigem pr{\"a}diktiven Wert, w{\"a}hrend f{\"u}r den Abschluss einer Chemotherapie und die Tumorlokalisation lediglich bivariate Zusammenh{\"a}nge bestanden. Ein solcher Zusammenhang mit der Inanspruchnahme von Alternativmedizin konnte auch f{\"u}r die psychosozialen Variablen h{\"o}here psychische Belastung und geringere Lebensqualit{\"a}t nachgewiesen werden, die sich jedoch in der logistischen Regression nicht als unabh{\"a}ngige Pr{\"a}diktoren best{\"a}tigten. Von den psychosozialen Variablen stellte der Wunsch nach aktiver Partizipation am Therapieprozess den einzigen unabh{\"a}ngigen Pr{\"a}diktor f{\"u}r die Nutzung alternativmedizinischer Angebote dar. Schlussfolgerungen: Ein Drittel aller Krebspatienten wendet Alternativmedizin im Zusammenhang mit der Krebserkrankung an. Daher sollte die medizinische Wissenschaft es als wichtige Aufgabe sehen, fundierte Daten zu Nutzen und Sicherheit alternativmedizinischer Mittel bereitzustellen, um dieses weite Feld nicht unseri{\"o}sen Anbietern zu {\"u}berlassen. Auch der rein konventionell t{\"a}tige Arzt sollte sich der großen Beliebtheit von Alternativ-medizin bei bestimmten Patientengruppen bewusst sein und seinen Patienten Auskunft zu alternativmedizinischen Angeboten geben k{\"o}nnen.},
  subject      = {Alternative Medizin},
  language  = {de}
}
@article{KappKosmalaKircheretal.2016,
  author    = {Kapp, Markus and Kosmala, Aleksander and Kircher, Stefan and Luber, Verena and Kunzmann, Volker},
  title     = {Exceptional Response to Nanoparticle Albumin-Bound Paclitaxel and Gemcitabine in a Patient with a Refractory Adenocarcinoma of the Ampulla of Vater},
  series = {Case Reports in Oncology},
  volume    = {9},
  journal   = {Case Reports in Oncology},
  number    = {1},
  doi       = {10.1159/000443304},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-168358},
  pages     = {15-24},
  year      = {2016},
  abstract  = {Ampullary carcinoma is a rare tumor and evidence on the treatment of recurrent metastatic disease is scarce. We report the case of a 60-year-old patient with an R0-resected node-positive adenocarcinoma of the papilla of Vater of an initially diagnosed intestinal subtype who developed pulmonary metastases 2 months after adjuvant gemcitabine chemotherapy and, subsequently, liver metastases. Palliative combination chemotherapy with standard regimens for intestinal-type adenocarcinoma (FOLFOX and FOLFIRI) failed. However, subsequent combination chemotherapy with nanoparticle albumin-bound paclitaxel and gemcitabine, a regimen with proven efficacy in metastatic adenocarcinoma of the pancreas, resulted in a durable, very good partial remission. Treatment was manageable and well tolerated. Primary tumor and metastatic tissue were reassessed by immunohistochemistry and had to be reclassified to a mixed phenotype containing predominant elements of the pancreatobiliary subtype. Our case suggests that combination chemotherapy with nanoparticle albumin-bound paclitaxel and gemcitabine could represent a promising option for the treatment of this rare disease and warrants further investigation within controlled clinical trials. Moreover, thorough characterization of ampullary carcinomas by histomorphology and additional immunohistochemistry should become mandatory in order to start a chemotherapeutic regimen tailored for the definitive subtype.},
  language  = {en}
}
@article{PetritschKosmalaWengetal.2019,
  author    = {Petritsch, Berhard and Kosmala, Aleksander and Weng, Andreas Max and Bley, Thorsten Alexander},
  title     = {Tin-filtered 100kV ultra-low-dose CT of the paranasal sinus: initial clinical results},
  series = {PLoS ONE},
  volume    = {14},
  journal   = {PLoS ONE},
  number    = {5},
  doi       = {10.1371/ journal.pone.0216295},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-204127},
  pages     = {e0216295},
  year      = {2019},
  abstract  = {Objectives To investigate the feasibility, diagnostic image quality and radiation dose of 3\(^{rd}\) generation dual-source computed tomography (CT) using a tin-filtered 100 kV protocol in patients with suspected acute inflammatory sinus disease. Methods We retrospectively evaluated 109 consecutive patients who underwent CT (Siemens SOMATOM Force, Erlangen, Germany) of the paranasal sinus with a new tin-filtered scanprotocol (Sn100 kV; tube current 35 mAs) using iterative reconstruction. Two readers independently assessed subjective image quality using a five-point Likert scale (1 = excellent, 5 = non-diagnostic). Inter-observer agreement was calculated and expressed as percentage of agreement. Noise was determined for calculation of signal-to-noise-ratio (SNR). Effective radiation dose (ED) was calculated from the dose-length-product (DLP). Results All examinations showed diagnostic image quality regarding evaluation of inflammatory sinus disease. On average, subjective general image quality was rated moderate (= 3) with a percentage of agreement between the observers of 81\%. The mean image noise was 14.3 HU. The calculated median SNR was 6.0 for intraorbital fat, and 3.6 for the vitreous body, respectively. The median DLP was 2.1 mGy*cm, resulting in a median ED of 0.012 mSv. Conclusions Taking the study limitations into account, ultra-low-dose tin-filtered CT of the paranasal sinus at a tube voltage of 100 kV utilizing an iterative reconstruction algorithm provides for reliable exclusion of suspected acute inflammatory sinus disease in 100\% of the cases.},
  language  = {en}
}
@article{GrunzPennigFieberetal.2021,
  author    = {Grunz, Jan-Peter and Pennig, Lenhard and Fieber, Tabea and Gietzen, Carsten Herbert and Heidenreich, Julius Frederik and Huflage, Henner and Gruschwitz, Philipp and Kuhl, Philipp Josef and Petritsch, Bernhard and Kosmala, Aleksander and Bley, Thorsten Alexander and Gassenmaier, Tobias},
  title     = {Twin robotic x-ray system in small bone and joint trauma: Impact of cone-beam computed tomography on treatment decisions},
  series = {European Radiology},
  volume    = {31},
  journal   = {European Radiology},
  issn      = {0938-7994},
  doi       = {10.1007/s00330-020-07563-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235233},
  pages     = {3600-3609},
  year      = {2021},
  abstract  = {Objectives Trauma evaluation of extremities can be challenging in conventional radiography. A multi-use x-ray system with cone-beam CT (CBCT) option facilitates ancillary 3-D imaging without repositioning. We assessed the clinical value of CBCT scans by analyzing the influence of additional findings on therapy. Methods Ninety-two patients underwent radiography and subsequent CBCT imaging with the twin robotic scanner (76 wrist/hand/finger and 16 ankle/foot/toe trauma scans). Reports by on-call radiologists before and after CBCT were compared regarding fracture detection, joint affliction, comminuted injuries, and diagnostic confidence. An orthopedic surgeon recommended therapy based on reported findings. Surgical reports (N = 52) and clinical follow-up (N = 85) were used as reference standard. Results CBCT detected more fractures (83/64 of 85), joint involvements (69/53 of 71), and multi-fragment situations (68/50 of 70) than radiography (all p < 0.001). Six fractures suspected in radiographs were ruled out by CBCT. Treatment changes based on additional information from CBCT were recommended in 29 patients (31.5\%). While agreement between advised therapy before CBCT and actual treatment was moderate (κ = 0.41 [95\% confidence interval 0.35-0.47]; p < 0.001), agreement after CBCT was almost perfect (κ = 0.88 [0.83-0.93]; p < 0.001). Diagnostic confidence increased considerably for CBCT studies (p < 0.001). Median effective dose for CBCT was 4.3 μSv [3.3-5.3 μSv] compared to 0.2 μSv [0.1-0.2 μSv] for radiography. Conclusions CBCT provides advantages for the evaluation of acute small bone and joint trauma by detecting and excluding extremity fractures and fracture-related findings more reliably than radiographs. Additional findings induced therapy change in one third of patients, suggesting substantial clinical impact.},
  language  = {en}
}
@article{HockTerekhovStefanescuetal.2021,
  author    = {Hock, Michael and Terekhov, Maxim and Stefanescu, Maria Roxana and Lohr, David and Herz, Stefan and Reiter, Theresa and Ankenbrand, Markus and Kosmala, Aleksander and Gassenmaier, Tobias and Juchem, Christoph and Schreiber, Laura Maria},
  title     = {B\(_{0}\) shimming of the human heart at 7T},
  series = {Magnetic Resonance in Medicine},
  volume    = {85},
  journal   = {Magnetic Resonance in Medicine},
  number    = {1},
  doi       = {10.1002/mrm.28423},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218096},
  pages     = {182 -- 196},
  year      = {2021},
  abstract  = {Purpose Inhomogeneities of the static magnetic B\(_{0}\) field are a major limiting factor in cardiac MRI at ultrahigh field (≥ 7T), as they result in signal loss and image distortions. Different magnetic susceptibilities of the myocardium and surrounding tissue in combination with cardiac motion lead to strong spatio-temporal B\(_{0}\)-field inhomogeneities, and their homogenization (B0 shimming) is a prerequisite. Limitations of state-of-the-art shimming are described, regional B\(_{0}\) variations are measured, and a methodology for spherical harmonics shimming of the B\(_{0}\) field within the human myocardium is proposed. Methods The spatial B\(_{0}\)-field distribution in the heart was analyzed as well as temporal B\(_{0}\)-field variations in the myocardium over the cardiac cycle. Different shim region-of-interest selections were compared, and hardware limitations of spherical harmonics B\(_{0}\) shimming were evaluated by calibration-based B0-field modeling. The role of third-order spherical harmonics terms was analyzed as well as potential benefits from cardiac phase-specific shimming. Results The strongest B\(_{0}\)-field inhomogeneities were observed in localized spots within the left-ventricular and right-ventricular myocardium and varied between systolic and diastolic cardiac phases. An anatomy-driven shim region-of-interest selection allowed for improved B\(_{0}\)-field homogeneity compared with a standard shim region-of-interest cuboid. Third-order spherical harmonics terms were demonstrated to be beneficial for shimming of these myocardial B\(_{0}\)-field inhomogeneities. Initial results from the in vivo implementation of a potential shim strategy were obtained. Simulated cardiac phase-specific shimming was performed, and a shim term-by-term analysis revealed periodic variations of required currents. Conclusion Challenges in state-of-the-art B\(_{0}\) shimming of the human heart at 7 T were described. Cardiac phase-specific shimming strategies were found to be superior to vendor-supplied shimming.},
  language  = {en}
}
@article{PetritschPannbeckerWengetal.2021,
  author    = {Petritsch, Bernhard and Pannbecker, Pauline and Weng, Andreas M. and Grunz, Jan-Peter and Veldhoen, Simon and Bley, Thorsten A. and Kosmala, Aleksander},
  title     = {Split-filter dual-energy CT pulmonary angiography for the diagnosis of acute pulmonary embolism: a study on image quality and radiation dose},
  series = {Quantitative Imaging in Medicine and Surgery},
  volume    = {11},
  journal   = {Quantitative Imaging in Medicine and Surgery},
  number    = {5},
  doi       = {10.21037/qims-20-740},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-231456},
  pages     = {1817-1827},
  year      = {2021},
  abstract  = {Background: Computed tomography (CT) pulmonary angiography is the diagnostic reference standard in suspected pulmonary embolism (PE). Favorable results for dual-energy CT (DECT) images have been reported for this condition. Nowadays, dual-energy data acquisition is feasible with different technical options, including a single-source split-filter approach. Therefore, the aim of this retrospective study was to investigate image quality and radiation dose of thoracic split-filter DECT in comparison to conventional single-energy CT in patients with suspected PE. Methods: A total of 110 CT pulmonary angiographies were accomplished either as standard single-energy CT with automatic tube voltage selection (ATVS) (n=58), or as split-filter DECT (n=52). Objective [pulmonary artery CT attenuation, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR)] and subjective image quality [four-point Likert scale; three readers (R)] were compared among the two study groups. Size-specific dose estimates (SSDE), dose-length-product (DLP) and volume CT dose index (CTDIvol) were assessed for radiation dose analysis. Results: Split-filter DECT images yielded 67.7\% higher SNR (27.0 vs. 16.1; P<0.001) and 61.9\% higher CNR (22.5 vs. 13.9; P<0.001) over conventional single-energy images, whereas CT attenuation was significantly lower (344.5 vs. 428.2 HU; P=0.013). Subjective image quality was rated good or excellent in 93.0\%/98.3\%/77.6\% (R1/R2/R3) of the single-energy CT scans, and 84.6\%/82.7\%/80.8\% (R1/R2/R3) of the split-filter DECT scans. SSDE, DLP and CTDIvol were significantly lower for conventional single-energy CT compared to split-filter DECT (all P<0.05), which was associated with 26.7\% higher SSDE. Conclusions: In the diagnostic workup of acute PE, the split-filter allows for dual-energy data acquisition from single-source single-layer CT scanners. The existing opportunity to assess pulmonary "perfusion" based on analysis of iodine distribution maps is associated with higher radiation dose in terms of increased SSDE than conventional single-energy CT with ATVS. Moreover, a proportion of up to 3.8\% non-diagnostic examinations in the current reference standard test for PE is not negligible.},
  language  = {en}
}
@article{KosmalaSerflingDreheretal.2022,
  author    = {Kosmala, Aleksander and Serfling, Sebastian E. and Dreher, Niklas and Lindner, Thomas and Schirbel, Andreas and Lapa, Constantin and Higuchi, Takahiro and Buck, Andreas K. and Weich, Alexander and Werner, Rudolf A.},
  title     = {Associations between normal organs and tumor burden in patients imaged with fibroblast activation protein inhibitor-directed positron emission tomography},
  series = {Cancers},
  volume    = {14},
  journal   = {Cancers},
  number    = {11},
  issn      = {2072-6694},
  doi       = {10.3390/cancers14112609},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-275154},
  year      = {2022},
  abstract  = {(1) Background: We aimed to quantitatively investigate [\(^{68}\)Ga]Ga-FAPI-04 uptake in normal organs and to assess a relationship with the extent of FAPI-avid tumor burden. (2) Methods: In this single-center retrospective analysis, thirty-four patients with solid cancers underwent a total of 40 [\(^{68}\)Ga]Ga-FAPI-04 PET/CT scans. Mean standardized uptake values (SUV\(_{mean}\)) for normal organs were established by placing volumes of interest (VOIs) in the heart, liver, spleen, pancreas, kidneys, and bone marrow. Total tumor burden was determined by manual segmentation of tumor lesions with increased uptake. For tumor burden, quantitative assessment included maximum SUV (SUV\(_{max}\)), tumor volume (TV), and fractional tumor activity (FTA = TV × SUV\(_{mean}\)). Associations between uptake in normal organs and tumor burden were investigated by applying Spearman's rank correlation coefficient. (3) Results: Median SUV\(_{mean}\) values were 2.15 in the pancreas (range, 1.05-9.91), 1.42 in the right (range, 0.57-3.06) and 1.41 in the left kidney (range, 0.73-2.97), 1.2 in the heart (range, 0.46-2.59), 0.86 in the spleen (range, 0.55-1.58), 0.65 in the liver (range, 0.31-2.11), and 0.57 in the bone marrow (range, 0.26-0.94). We observed a trend towards significance for uptake in the myocardium and tumor-derived SUV\(_{max}\) (ρ = 0.29, p = 0.07) and TV (ρ = -0.30, p = 0.06). No significant correlation was achieved for any of the other organs: SUV\(_{max}\) (ρ ≤ 0.1, p ≥ 0.42), TV (ρ ≤ 0.11, p ≥ 0.43), and FTA (ρ ≤ 0.14, p ≥ 0.38). In a sub-analysis exclusively investigating patients with high tumor burden, significant correlations of myocardial uptake with tumor SUV\(_{max}\) (ρ = 0.44; p = 0.03) and tumor-derived FTA with liver uptake (ρ = 0.47; p = 0.02) were recorded. (4) Conclusions: In this proof-of-concept study, quantification of [\(^{68}\)Ga]Ga-FAPI-04 PET showed no significant correlation between normal organs and tumor burden, except for a trend in the myocardium. Those preliminary findings may trigger future studies to determine possible implications for treatment with radioactive FAP-targeted drugs, as higher tumor load or uptake may not lead to decreased doses in the majority of normal organs.},
  language  = {en}
}
@article{HerzStefanescuLohretal.2022,
  author    = {Herz, Stefan and Stefanescu, Maria R. and Lohr, David and Vogel, Patrick and Kosmala, Aleksander and Terekhov, Maxim and Weng, Andreas M. and Grunz, Jan-Peter and Bley, Thorsten A. and Schreiber, Laura M.},
  title     = {Effects of image homogeneity on stenosis visualization at 7 T in a coronary artery phantom study: With and without B1-shimming and parallel transmission},
  series = {PloS One},
  volume    = {17},
  journal   = {PloS One},
  number    = {6},
  doi       = {10.1371/journal.pone.0270689},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300129},
  year      = {2022},
  abstract  = {Background To investigate the effects of B\(_1\)-shimming and radiofrequency (RF) parallel transmission (pTX) on the visualization and quantification of the degree of stenosis in a coronary artery phantom using 7 Tesla (7 T) magnetic resonance imaging (MRI). Methods Stenosis phantoms with different grades of stenosis (0\%, 20\%, 40\%, 60\%, 80\%, and 100\%; 5 mm inner vessel diameter) were produced using 3D printing (clear resin). Phantoms were imaged with four different concentrations of diluted Gd-DOTA representing established arterial concentrations after intravenous injection in humans. Samples were centrally positioned in a thorax phantom of 30 cm diameter filled with a custom-made liquid featuring dielectric properties of muscle tissue. MRI was performed on a 7 T whole-body system. 2D-gradient-echo sequences were acquired with an 8-channel transmit 16-channel receive (8 Tx / 16 Rx) cardiac array prototype coil with and without pTX mode. Measurements were compared to those obtained with identical scan parameters using a commercially available 1 Tx / 16 Rx single transmit coil (sTX). To assess reproducibility, measurements (n = 15) were repeated at different horizontal angles with respect to the B0-field. Results B\(_1\)-shimming and pTX markedly improved flip angle homogeneity across the thorax phantom yielding a distinctly increased signal-to-noise ratio (SNR) averaged over a whole slice relative to non-manipulated RF fields. Images without B\(_1\)-shimming showed shading artifacts due to local B\(_1\)\(^+\)-field inhomogeneities, which hampered stenosis quantification in severe cases. In contrast, B\(_1\)-shimming and pTX provided superior image homogeneity. Compared with a conventional sTX coil higher grade stenoses (60\% and 80\%) were graded significantly (p<0.01) more precise. Mild to moderate grade stenoses did not show significant differences. Overall, SNR was distinctly higher with B\(_1\)-shimming and pTX than with the conventional sTX coil (inside the stenosis phantoms 14\%, outside the phantoms 32\%). Both full and half concentration (10.2 mM and 5.1 mM) of a conventional Gd-DOTA dose for humans were equally suitable for stenosis evaluation in this phantom study. Conclusions B\(_1\)-shimming and pTX at 7 T can distinctly improve image homogeneity and therefore provide considerably more accurate MR image analysis, which is beneficial for imaging of small vessel structures.},
  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}
}