@article{MantelMuellerKleineetal.2021, author = {Mantel, Frederick and M{\"u}ller, Elena and Kleine, Philip and Zimmermann, Marcus and Exner, Florian and Richter, Anne and Weick, Stefan and Str{\"o}hle, Serge and Polat, B{\"u}lent and H{\"o}cht, Stefan and Flentje, Michael}, title = {Chemoradiotherapy by intensity-modulated radiation therapy with simultaneous integrated boost in locally advanced or oligometastatic non-small-cell lung cancer-a two center experience}, series = {Strahlentherapie und Onkologie}, volume = {197}, journal = {Strahlentherapie und Onkologie}, number = {5}, issn = {1439-099X}, doi = {10.1007/s00066-021-01756-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-264821}, pages = {405-415}, year = {2021}, abstract = {Purpose Integrating moderate hypofractionation to the macroscopic tumor with elective nodal irradiation while sparing the organs at risk (OAR) in chemoradiotherapy of locally advanced non-small-cell lung cancer. Methods From 2010-2018, treatment, patient and tumor characteristics of 138 patients from two radiation therapy centers were assessed. Chemoradiotherapy by intensity-modulated radiation therapy (IMRT) with a simultaneous integrated boost (SIB) to the primary tumor and macroscopic lymph node metastases was used. Results A total of 124 (90\%) patients received concurrent chemotherapy. 106 (76\%) patients had UICC (Union for International Cancer Control) stage ≥IIIB and 21 (15\%) patients had an oligometastatic disease (UICC stage IV). Median SIB and elective total dose was 61.6 and 50.4 Gy in 28 fractions, respectively. Furthermore, 64 patients (46\%) had an additional sequential boost to the primary tumor after the SIB-IMRT main series: median 6.6 Gy in median 3 fractions. The median cumulative mean lung dose was 15.6 Gy (range 6.2-29.5 Gy). Median follow-up and radiological follow-up for all patients was 18.0 months (range 0.6-86.9) and 16.0 months (range 0.2-86.9), respectively. Actuarial local control rates at 1, 2 and 3 years were 80.4, 68.4 and 57.8\%. Median overall survival and progression-free survival was 30.0 months (95\% confidence interval [CI] 23.5-36.4) and 12.1 months (95\% CI 8.2-16.0), respectively. Treatment-related toxicity was moderate. Radiation-induced pneumonitis grade 2 and grade 3 occurred in 13 (9.8\%) and 3 (2.3\%) patients. Conclusions Chemoradiotherapy using SIB-IMRT showed promising local tumor control rates and acceptable toxicity in patients with locally advanced and in part oligometastatic lung cancer. The SIB concept, resulting in a relatively low mean lung dose, was associated with low numbers of clinically relevant pneumonitis. The overall survival appears promising in the presence of a majority of patients with UICC stage ≥IIIB disease.}, language = {en} } @article{RichterPolatLawrenzetal.2016, author = {Richter, Anne and Polat, B{\"u}lent and Lawrenz, Ingulf and Weick, Stefan and Sauer, Otto and Flentje, Michael and Mantel, Frederick}, title = {Initial results for patient setup verification using transperineal ultrasound and cone beam CT in external beam radiation therapy of prostate cancer}, series = {Radiation Oncology}, volume = {11}, journal = {Radiation Oncology}, number = {147}, doi = {10.1186/s13014-016-0722-7}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-147677}, year = {2016}, abstract = {Evaluation of set up error detection by a transperineal ultrasound in comparison with a cone beam CT (CBCT) based system in external beam radiation therapy (EBRT) of prostate cancer. Methods: Setup verification was performed with transperineal ultrasound (TPUS) and CBCT for 10 patients treated with EBRT for prostate cancer. In total, 150 ultrasound and CBCT scans were acquired in rapid succession and analyzed for setup errors. The deviation between setup errors of the two modalities was evaluated separately for each dimension. Results: A moderate correlation in lateral, vertical and longitudinal direction was observed comparing the setup errors. Mean differences between TPUS and CBCT were (-2.7 ± 2.3) mm, (3.0 ± 2.4) mm and (3.2 ± 2.7) mm in lateral, vertical and longitudinal direction, respectively. The mean Euclidean difference between TPUS and CBCT was (6.0 ± 3.1) mm. Differences up to 19.2 mm were observed between the two imaging modalities. Discrepancies between TPUS and CBCT of at least 5 mm occurred in 58 \% of monitored treatment sessions. Conclusion: Setup differences between TPUS and CBCT are 6 mm on average. Although the correlation of the setup errors determined by the two different image modalities is rather week, the combination of setup verification by CBCT and intrafraction motion monitoring by TPUS imaging can use the benefits of both imaging modalities.}, language = {en} } @phdthesis{Weick2015, author = {Weick, Stefan}, title = {Retrospektive Bewegungskorrektur zur hochaufgel{\"o}sten Darstellung der menschlichen Lunge mittels Magnetresonanztomographie}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-124084}, school = {Universit{\"a}t W{\"u}rzburg}, year = {2015}, abstract = {Ziel dieser Arbeit war es, das gesamte Lungenvolumen in hoher dreidimensionaler Aufl{\"o}sung mittels der MRT darzustellen. Um trotz der niedrigen Protonendichte der Lunge und der geforderten hohen Aufl{\"o}sung ausreichend Signal f{\"u}r eine verl{\"a}ssliche Diagnostik zu erhalten, sind Aufnahmezeiten von einigen Minuten n{\"o}tig. Um die Untersuchung f{\"u}r den Patienten angenehmer zu gestalten oder auf Grund der eingeschr{\"a}nkten F{\"a}higkeit eines Atemstopps {\"u}berhaupt erst zu erm{\"o}glichen, war eine Anforderung, die Aufnahmen in freier Atmung durchzuf{\"u}hren. Dadurch entstehen allerdings Bewegungsartefakte, die die Diagnostik stark beeintr{\"a}chtigen und daher m{\"o}glichst vermieden werden m{\"u}ssen. F{\"u}r eine Bewegungskompensation der Daten muss die auftretende Atembewegung detektiert werden. Die Bewegungsdetektion kann durch externe Messger{\"a}te (Atemgurt oder Spirometer) oder durch eine zus{\"a}tzliche Anregungen erfolgen (konventionelle Navigatoren) erfolgen. Nachteile dieser Methoden bestehen darin, dass die Bewegung w{\"a}hrend der Atmung nicht direkt verfolgt wird, dass elektronische Messger{\"a}te in die N{\"a}he des Tomographen gebracht werden und das die Patienten zus{\"a}tzlich vorbereitet und eingeschr{\"a}nkt werden. Des Weiteren erfordert eine zus{\"a}tzliche Anregung extra Messzeit und kann unter Umst{\"a}nden die Magnetisierung auf unterw{\"u}nschte Weise beeinflussen. Um die angesprochenen Schwierigkeiten der Bewegungsdetektion zu umgehen, wurden in dieser Arbeit innerhalb einer Anregung einer 3d FLASH-Sequenz sowohl Bilddaten- als auch Navigatordaten aufgenommen. Als Navigator diente dabei das nach der Rephasierung aller bildgebenden Gradienten entstehende Signal (DC Signal). Das DC Signal entspricht dabei der Summe aller Signale, die mit einem bestimmten Spulenelement detektiert werden k{\"o}nnen. Bewegt sich beispielsweise die Leber bedingt durch die Atmung in den Sensitivit{\"a}tsbereich eines Spulenelementes, wird ein st{\"a}rkeres DC Signal detektiert werden. Je nach Positionierung auf dem K{\"o}rper kann so die Atembewegung mit einzelnen r{\"a}umlich lokalisierten Spulenelementen nachverfolgt werden. Am DC Signalverlauf des f{\"u}r die Bewegungskorrektur ausgew{\"a}hlten Spulenelementes sind dann periodische Signalschwankungen zu erkennen. Zus{\"a}tzlich k{\"o}nnen aus dem Verlauf Expirations- von Inspirationszust{\"a}nden unterschieden werden, da sich Endexpirationszust{\"a}nde im Regelfall durch eine l{\"a}ngere Verweildauer auszeichnen. Grunds{\"a}tzlich kann das DC Signal vor oder nach der eigentlichen Datenaufnahme innerhalb einer Anregung aufgenommen werden. Auf Grund der kurzen Relaxationszeit T∗2 des Lungengewebes f{\"a}llt das Signal nach der RF Anregung sehr schnell ab. Um m{\"o}glichst viel Signal zu erhalten sollten, wie in dieser Arbeit gezeigt wurde, innerhalb einer Anregung zuerst die Bilddaten und danach die Navigatordaten aufgenommen werden. Dieser Ansatz f{\"u}hrt zu einer Verk{\"u}rzung der Echozeit TE um 0.3 ms und damit zu einem SNR Gewinn von etwa 20 \%. Gleichzeitig ist das verbleibende Signal nach der Datenakquisition und Rephasierung der bildgebenden Gradienten noch ausreichend um die Atembewegung zu erfassen und somit eine Bewegungskorrektur der Daten (Navigation) zu erm{\"o}glichen. Um eine retrospektive Bewegungskorrektur durchf{\"u}hren zu k{\"o}nnen, m{\"u}ssen Akzeptanzbedingungen (Schwellenwerte) f{\"u}r die Datenauswahl festgelegt werden. Bei der Wahl des Schwellenwertes ist darauf zu achten, dass weder zu wenige noch zu viele Daten akzeptiert werden. Akzeptiert man sehr wenige Daten, zeichnen sich die Rekonstruktionen durch einen scharfen {\"U}bergang zwischen Lunge und Diaphragma aus, da man sehr wenig Bewegung in den Rekonstruktionen erlaubt. Gleichzeitig erh{\"o}ht sich allerdings das Risiko, dass nach der Navigation Linien fehlen. Dies f{\"u}hrt zu Einfaltungsartefakten, die in Form von gest{\"o}rten Bildintensit{\"a}ten in den Rekonstruktionen zu sehen sind und die diagnostische Aussagekraft einschr{\"a}nken. Um Einfaltungsartefakte zu vermeiden sollte der Schwellenwert so gew{\"a}hlt werden, dass nach der Datenauswahl keine Linien fehlen. Aus dieser Anforderung l{\"a}sst sich ein maximaler Schwellenwert ableiten. Akzeptiert man dagegen sehr viele Daten, zeichnen sich die Rekonstruktionen durch erh{\"o}htes Signal und das vermehrte Auftreten von Bewegungsartefakten aus. In diesem Fall m{\"u}sste der Arzt entscheiden, ob Bewegungsartefakte die Diagnostik zu stark beeinflussen. W{\"a}hlt man den Schwellenwert so, dass weder Linien fehlen noch zu viel Bewegung erlaubt wird, erh{\"a}lt man Rekonstruktionen die sich durch einen scharfen Diaphragma{\"u}bergang auszeichnen und in denen noch kleinste Gef{\"a}ße auch in der N{\"a}he des Diaphragmas deutlich zu erkennen sind. Hierf{\"u}r haben sich Schwellenwerte, die zu einer Datenakzeptanz von ca. 40 \% f{\"u}hren als g{\"u}nstig erwiesen. Um Einfaltungsartefakte auf Grund der retrospektiven Datenauswahl zu verhindern, muss das Bildgebungsvolumen mehrfach abgetastet werden. Dadurch wird gew{\"a}hrleistet, dass f{\"u}r die letztendliche Rekonstruktion ausreichend Daten zur Verf{\"u}gung stehen, wobei mehrfach akzeptierte Daten gemittelt werden. Dies spielt auf Grund der niedrigen Protonendichte der Lunge eine wesentliche Rolle in der Rekonstruktion hochaufgel{\"o}ster Lungendatens{\"a}tze. Weiterhin f{\"u}hrt das Mitteln von mehrfach akzeptierten Daten zu einer Unterdr{\"u}ckung der sogenannten Ghost Artefakte, was am Beispiel der Herzbewegung in der Arbeit gezeigt wird. Da die Messungen unter freier Atmung durchgef{\"u}hrt werden und keine zus{\"a}tzlichen externen Messger{\"a}te angeschlossen werden m{\"u}ssen, stellte die Untersuchung f{\"u}r die Patienten in dieser Arbeit kein Problem dar. Im ersten Teil dieser wurde Arbeit gezeigt, dass sich mit Hilfe des DC Signales als Navigator und einer retrospektiven Datenauswahl das gesamte Lungenvolumen in hoher dreidimensionaler Aufl{\"o}sung von beispielsweise 1.6 x 1.6 x 4 mm3 innerhalb von 13 min. darstellen l{\"a}sst. Die Anwendbarkeit der vorgestellten Methode zur Bewegungskorrektur wurde neben Probanden auch an Patienten demonstriert. Da wie bereits beschrieben das Bildgebungsvolumen mehrfach abgetastet werden muss, wiederholt sich auch die Abfolge der f{\"u}r die Bildgebung verantwortlichen Gradienten periodisch. Da sich der Atemzyklus aber auch periodisch wiederholt, kann es zu Korrelationen zwischen der Atmung und den wiederholten Messungen kommen. Dies f{\"u}hrt dazu, dass auch nach vielen wiederholten Messungen immer noch gr{\"o}ßere Bereiche fehlender Linien im k-Raum bleiben, was zu Artefakten in den Rekonstruktionen f{\"u}hrt. Dies konnte im Falle der konventionellen Bewegungskorrektur in den Gatingmasken, die die Verteilung und H{\"a}ufigkeit der einzelnen akzeptierten Phasenkodierschritte im k-Raum zeigen, beobachtet werden. Da eine vors{\"a}tzliche Unterbrechung der Atemperiodizit{\"a}t (der Patient wird dazu angehalten, seine Atemfrequenz w{\"a}hrend der Messung absichtlich zu variieren) zur Vermeidung der angesprochenen Korrelationen nicht in Frage kommt, musste die Periodizit{\"a}t in der Datenaufnahme unterbrochen werden. In dieser Arbeit wurde dies durch eine quasizuf{\"a}llige Auswahl von Phasen- und Partitionskodiergradienten erreicht, da Quasizufallszahlen so generiert werden, dass sie unabh{\"a}ngig von ihrer Anzahl einen Raum m{\"o}glichst gleichf{\"o}rmig ausf{\"u}llen. Die quasizuf{\"a}llige Datenaufnahme f{\"u}hrt deshalb dazu, das sowohl akzeptierte als auch fehlende Linien nach der Bewegungskorrektur homogen im k-Raum verteilt auftreten. Vergleicht man das auftreten von Ghosting zeichnen sich die quasizuf{\"a}lligen Rekonstruktionen im Vergleich zur konventionellen Datenaufnahme durch eine verbesserte Reduktion von Ghost Artefakten aus. Dies ist auf die homogene Verteilung mehrfach akzeptierter Linien im k-Raum zur{\"u}ckzuf{\"u}hren. Die homogenere Verteilung von fehlenden Linien im k-Raum f{\"u}hrt weiterhin zu einer wesentlich stabileren Rekonstruktion fehlender Linien mit parallelen MRT-Verfahren (z.B. iterativem Grappa). Dies wird umso deutlicher je h{\"o}her der Anteil fehlender Linien im k-Raum wird. Im Falle der konventionellen Datenaufnahme werden die zusammenh{\"a}ngenden Bereiche fehlender Linien immer gr{\"o}ßer, was eine erfolgreiche Rekonstruktion mit iterativem Grappa unm{\"o}glich macht. Im Falle der quasizuf{\"a}lligen Datenaufnahme dagegen k{\"o}nnen auch Datens{\"a}tze in denen 40\% der Linien fehlen einfaltungsartefaktfrei rekonstruiert werden. Im weiteren Verlauf der Arbeit wurde gezeigt, wie die Stabilit{\"a}t der iterativen Grappa Rekonstruktion im Falle der quasizuf{\"a}lligen Datenaufnahme f{\"u}r eine erhebliche Reduktion der gesamten Messzeit genutzt werden kann. So ist in einer Messzeit von nur 74s die Rekonstruktion eines artefaktfreien und bewegungskorrigierten dreidimensionalen Datensatzes der menschlichen Lunge mit einer Aufl{\"o}sung von 2 x 2 x 5 mm3 m{\"o}glich. Des Weiteren erlaubt die quasizuf{\"a}llige Datenaufnahme in Kombination mit iterativem Grappa die Rekonstruktion von Datens{\"a}tzen unterschiedlicher Atemphasen von Inspiration bis Expiration (4D Bildgebung). Nach einer Messzeit von 15min. wurden 19 unterschiedliche Atemzust{\"a}nde rekonstruiert, wobei sich der Anteil der fehlenden Linien zwischen 0 und 20 \% lag. Im Falle der konventionellen Datenaufnahme w{\"a}re eine wesentlich l{\"a}ngere Messzeit n{\"o}tig gewesen, um {\"a}hnliche Ergebnisse zu erhalten. Zum Schluss soll noch ein Ausblick {\"u}ber m{\"o}gliche Weiterentwicklungen und Anwendungsm{\"o}glichkeiten, die sich aus den Erkenntnissen dieser Arbeit ergeben haben, gegeben werden. So k{\"o}nnte das quasizuf{\"a}llige Aufnahmeschema um eine Dichtegewichtung erweitert werden. Hierbei w{\"u}rde der zentrale k-Raum Bereich etwas h{\"a}ufiger als die peripheren Bereiche akquiriert werden. Dadurch sollte die iterative Grappa Rekonstruktion noch stabiler funktionieren und Ghost Artefakte besser reduziert werden. Die Verteilung der Linien sollte allerdings nicht zu inhomogen werden, um gr{\"o}ßere L{\"u}cken im k-Raum zu vermeiden. Dar{\"u}ber hinaus k{\"o}nnte die vorgestellte Methode der Bewegungskompensation auch f{\"u}r die Untersuchung anderer Organe oder K{\"o}rperteile verwendet werden. Voraussetzung w{\"a}re lediglich das Vorhandensein dezidierter Spulenanordnungen, mit denen die Bewegung nachverfolgt werden kann. So ist beispielsweise eine dynamische Bildgebung des frei und aktiv bewegten Knies m{\"o}glich, wobei zwischen Beugung und Streckung durch die erste Ableitung des zentralen k-Raum Signales unterschieden werden kann. Dies kann zus{\"a}tzliche Diagnoseinformationen liefern oder f{\"u}r Verlaufskontrollen nach Operationen benutzt werden [15]. Eine Weiterentwicklung mit hohem klinischen Potential k{\"o}nnte die Kombination der in dieser Arbeit vorgestellten retrospektiven Bewegungskorrektur mit einer Multi- Gradienten-Echo Sequenz darstellen. Hierzu musste die bestehende Sequenz lediglich um eine mehrfache Abfolge von Auslesegradienten innerhalb einer Anregung erweitert werden. Dies erm{\"o}glicht eine bewegungskorrigierte voxelweise Bestimmung der transversalen Relaxationszeit T∗2 in hoher r{\"a}umlicher Aufl{\"o}sung. Unter zus{\"a}tzlicher Sauerstoffgabe kann es zu einer Ver{\"a}nderung von T∗2 kommen, die auf den sogenannten BOLD Effekt (Blood Oxygen Level Dependent) zur{\"u}ckzuf{\"u}hren ist. Aus dieser {\"A}nderung k{\"o}nnten R{\"u}ckschl{\"u}sse auf hypoxische Tumorareale gezogen werden. Da diese eine erh{\"o}hte Strahlenresistenz aufweisen, k{\"o}nnte auf diese Bereiche innerhalb des Tumors eine erh{\"o}hte Strahlendosis appliziert und so m{\"o}glicherweise Behandlungsmisserfolge reduziert werden. Gleichzeitig kann durch die 4D Bildgebung eine m{\"o}gliche Tumorbewegung durch die Atmung erfasst und diese Information ebenfalls in der Bestrahlungsplanung benutzt werden. Die Lungen MRT k{\"o}nnte somit um eine hochaufgel{\"o}ste dreidimensionale funktionelle Bildgebung erweitert werden.}, subject = {Kernspintomografie}, language = {de} } @article{TamihardjaLutyjKraftetal.2021, author = {Tamihardja, J{\"o}rg and Lutyj, Paul and Kraft, Johannes and Lisowski, Dominik and Weick, Stefan and Flentje, Michael and Polat, B{\"u}lent}, title = {Two-Weekly High-Dose-Rate Brachytherapy Boost After External Beam Radiotherapy for Localized Prostate Cancer: Long-Term Outcome and Toxicity Analysis}, series = {Frontiers in Oncology}, volume = {11}, journal = {Frontiers in Oncology}, issn = {2234-943X}, doi = {10.3389/fonc.2021.764536}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-250992}, year = {2021}, abstract = {Purpose Evaluation of clinical outcome of two-weekly high-dose-rate brachytherapy boost after external beam radiotherapy (EBRT) for localized prostate cancer. Methods 338 patients with localized prostate cancer receiving definitive EBRT followed by a two-weekly high-dose-rate brachytherapy boost (HDR-BT boost) in the period of 2002 to 2019 were analyzed. EBRT, delivered in 46 Gy (DMean) in conventional fractionation, was followed by two fractions HDR-BT boost with 9 Gy (D90\%) two and four weeks after EBRT. Androgen deprivation therapy (ADT) was added in 176 (52.1\%) patients. Genitourinary (GU)/gastrointestinal (GI) toxicity was evaluated utilizing the Common Toxicity Criteria for Adverse Events (version 5.0) and biochemical failure was defined according to the Phoenix definition. Results Median follow-up was 101.8 months. 15 (4.4\%)/115 (34.0\%)/208 (61.5\%) patients had low-/intermediate-/high-risk cancer according to the D`Amico risk classification. Estimated 5-year and 10-year biochemical relapse-free survival (bRFS) was 84.7\% and 75.9\% for all patients. The estimated 5-year bRFS was 93.3\%, 93.4\% and 79.5\% for low-, intermediate- and high-risk disease, respectively. The estimated 10-year freedom from distant metastasis (FFM) and overall survival (OS) rates were 86.5\% and 70.0\%. Cumulative 5-year late GU toxicity and late GI toxicity grade ≥ 2 was observed in 19.3\% and 5.0\% of the patients, respectively. Cumulative 5-year late grade 3 GU/GI toxicity occurred in 3.6\%/0.3\%. Conclusions Two-weekly HDR-BT boost after EBRT for localized prostate cancer showed an excellent toxicity profile with low GU/GI toxicity rates and effective long-term biochemical control.}, language = {en} } @article{TamihardjaRazinskasExneretal.2021, author = {Tamihardja, J{\"o}rg and Razinskas, Gary and Exner, Florian and Richter, Anne and Kessler, Patrick and Weick, Stefan and Kraft, Johannes and Mantel, Frederick and Flentje, Michael and Polat, B{\"u}lent}, title = {Comparison of treatment plans for hypofractionated high-dose prostate cancer radiotherapy using the Varian Halcyon and the Elekta Synergy platforms}, series = {Journal of Applied Clinical Medical Physics}, volume = {22}, journal = {Journal of Applied Clinical Medical Physics}, number = {9}, doi = {10.1002/acm2.13380}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-260722}, pages = {262-270}, year = {2021}, abstract = {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.}, language = {en} } @article{KraftWeickBreueretal.2022, author = {Kraft, Johannes and Weick, Stefan and Breuer, Kathrin and Lutyj, Paul and Bratengeier, Klaus and Exner, Florian and Richter, Anne and Tamihardja, J{\"o}rg and Lisowski, Dominik and Polat, B{\"u}lent and Flentje, Michael}, title = {Treatment plan comparison for irradiation of multiple brain metastases with hippocampal avoidance whole brain radiotherapy and simultaneous integrated boost using the Varian Halcyon and the Elekta Synergy platforms}, series = {Radiation Oncology}, volume = {17}, journal = {Radiation Oncology}, doi = {10.1186/s13014-022-02156-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-301221}, year = {2022}, abstract = {No abstract available.}, language = {en} } @article{RichterWeickKriegeretal.2017, author = {Richter, Anne and Weick, Stefan and Krieger, Thomas and Exner, Florian and Kellner, Sonja and Polat, B{\"u}lent and Flentje, Michael}, title = {Evaluation of a software module for adaptive treatment planning and re-irradiation}, series = {Radiation Oncology}, volume = {12}, journal = {Radiation Oncology}, number = {205}, doi = {10.1186/s13014-017-0943-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-158711}, year = {2017}, abstract = {Background: The aim of this work is to validate the Dynamic Planning Module in terms of usability and acceptance in the treatment planning workflow. Methods: The Dynamic Planning Module was used for decision making whether a plan adaptation was necessary within one course of radiation therapy. The Module was also used for patients scheduled for re-irradiation to estimate the dose in the pretreated region and calculate the accumulated dose to critical organs at risk. During one year, 370 patients were scheduled for plan adaptation or re-irradiation. All patient cases were classified according to their treated body region. For a sub-group of 20 patients treated with RT for lung cancer, the dosimetric effect of plan adaptation during the main treatment course was evaluated in detail. Changes in tumor volume, frequency of re-planning and the time interval between treatment start and plan adaptation were assessed. Results: The Dynamic Planning Tool was used in 20\% of treated patients per year for both approaches nearly equally (42\% plan adaptation and 58\% re-irradiation). Most cases were assessed for the thoracic body region (51\%) followed by pelvis (21\%) and head and neck cases (10\%). The sub-group evaluation showed that unintended plan adaptation was performed in 38\% of the scheduled cases. A median time span between first day of treatment and necessity of adaptation of 17 days (range 4-35 days) was observed. PTV changed by 12 ± 12\% on average (maximum change 42\%). PTV decreased in 18 of 20 cases due to tumor shrinkage and increased in 2 of 20 cases. Re-planning resulted in a reduction of the mean lung dose of the ipsilateral side in 15 of 20 cases. Conclusion: The experience of one year showed high acceptance of the Dynamic Planning Module in our department for both physicians and medical physicists. The re-planning can potentially reduce the accumulated dose to the organs at risk and ensure a better target volume coverage. In the re-irradiation situation, the Dynamic Planning Tool was used to consider the pretreatment dose, to adapt the actual treatment schema more specifically and to review the accumulated dose.}, language = {en} } @article{TamihardjaSchortmannLawrenzetal.2021, author = {Tamihardja, J{\"o}rg and Schortmann, Max and Lawrenz, Ingulf and Weick, Stefan and Bratengeier, Klaus and Flentje, Michael and Guckenberger, Matthias and Polat, B{\"u}lent}, title = {Moderately hypofractionated radiotherapy for localized prostate cancer: updated long-term outcome and toxicity analysis}, series = {Strahlentherapie und Onkologie}, volume = {197}, journal = {Strahlentherapie und Onkologie}, issn = {0179-7158}, doi = {10.1007/s00066-020-01678-w}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-232509}, pages = {124-132}, year = {2021}, abstract = {Purpose Evaluation of long-term outcome and toxicity of moderately hypofractionated radiotherapy using intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost treatment planning and cone beam CT-based image guidance for localized prostate cancer. Methods Between 2005 and 2015, 346 consecutive patients with localized prostate cancer received primary radiotherapy using cone beam CT-based image-guided intensity-modulated radiotherapy (IG-IMRT) and volumetric modulated arc therapy (IG-VMAT) with a simultaneous integrated boost (SIB). Total doses of 73.9 Gy (n = 44) and 76.2 Gy (n = 302) to the high-dose PTV were delivered in 32 and 33 fractions, respectively. The low-dose PTV received a dose (D95) of 60.06 Gy in single doses of 1.82 Gy. The pelvic lymph nodes were treated in 91 high-risk patients to 45.5 Gy (D95). Results Median follow-up was 61.8 months. The 5‑year biochemical relapse-free survival (bRFS) was 85.4\% for all patients and 93.3, 87.4, and 79.4\% for low-, intermediate-, and high-risk disease, respectively. The 5‑year prostate cancer-specific survival (PSS) was 94.8\% for all patients and 98.7, 98.9, 89.3\% for low-, intermediate-, and high-risk disease, respectively. The 5‑year and 10-year overall survival rates were 83.8 and 66.3\% and the 5‑year and 10-year freedom from distant metastasis rates were 92.2 and 88.0\%, respectively. Cumulative 5‑year late GU toxicity and late GI toxicity grade ≥2 was observed in 26.3 and 12.1\% of the patients, respectively. Cumulative 5‑year late grade 3 GU/GI toxicity occurred in 4.0/1.2\%. Conclusion Moderately hypofractionated radiotherapy using SIB treatment planning and cone beam CT image guidance resulted in high biochemical control and survival with low rates of late toxicity.}, language = {en} } @article{RichterWegenerBreueretal.2021, author = {Richter, Anne and Wegener, Sonja and Breuer, Kathrin and Razinskas, Gary and Weick, Stefan and Exner, Florian and Bratengeier, Klaus and Flentje, Michael and Sauer, Otto and Polat, B{\"u}lent}, title = {Comparison of sliding window and field-in-field techniques for tangential whole breast irradiation using the Halcyon and Synergy Agility systems}, series = {Radiation Oncology}, volume = {16}, journal = {Radiation Oncology}, doi = {10.1186/s13014-021-01942-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-265704}, year = {2021}, abstract = {Background To implement a tangential treatment technique for whole breast irradiation using the Varian Halcyon and to compare it with Elekta Synergy Agility plans. Methods For 20 patients two comparable treatment plans with respect to dose coverage and normal tissue sparing were generated. Tangential field-in-field treatment plans (Pinnacle/Synergy) were replanned using the sliding window technique (Eclipse/Halcyon). Plan specific QA was performed using the portal Dosimetry and the ArcCHECK phantom. Imaging and treatment dose were evaluated for treatment delivery on both systems using a modified CIRS Phantom. Results The mean number of monitor units for a fraction dose of 2.67 Gy was 515 MUs and 260 MUs for Halcyon and Synergy Agility plans, respectively. The homogeneity index and dose coverage were similar for both treatment units. The plan specific QA showed good agreement between measured and calculated plans. All Halcyon plans passed portal dosimetry QA (3\%/2 mm) with 100\% points passing and ArcCheck QA (3\%/2 mm) with 99.5\%. Measurement of the cumulated treatment and imaging dose with the CIRS phantom resulted in lower dose to the contralateral breast for the Halcyon plans. Conclusions For the Varian Halcyon a plan quality similar to the Elekta Synergy device was achieved. For the Halcyon plans the dose contribution from the treatment fields to the contralateral breast was even lower due to less interleaf transmission of the Halcyon MLC and a lower contribution of scattered dose from the collimator system.}, language = {en} } @article{RichterExnerBratengeieretal.2019, author = {Richter, Anne and Exner, Florian and Bratengeier, Klaus and Polat, B{\"u}lent and Flentje, Michael and Weick, Stefan}, title = {Impact of beam configuration on VMAT plan quality for Pinnacle\(^3\)Auto-Planning for head and neck cases}, series = {Radiation Oncology}, volume = {14}, journal = {Radiation Oncology}, doi = {10.1186/s13014-019-1211-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-200301}, pages = {12}, year = {2019}, abstract = {Background The purpose of this study was to compare automatically generated VMAT plans to find the superior beam configurations for Pinnacle3 Auto-Planning and share "best practices". Methods VMAT plans for 20 patients with head and neck cancer were generated using Pinnacle3 Auto-Planning Module (Pinnacle3 Version 9.10) with different beam setup parameters. VMAT plans for single (V1) or double arc (V2) and partial or full gantry rotation were optimized. Beam configurations with different collimator positions were defined. Target coverage and sparing of organs at risk were evaluated based on scoring of an evaluation parameter set. Furthermore, dosimetric evaluation was performed based on the composite objective value (COV) and a new cross comparison method was applied using the COVs. Results The evaluation showed a superior plan quality for double arcs compared to one single arc or two single arcs for all cases. Plan quality was superior if a full gantry rotation was allowed during optimization for unilateral target volumes. A double arc technique with collimator setting of 15° was superior to a double arc with collimator 60° and a two single arcs with collimator setting of 15° and 345°. Conclusion The evaluation showed that double and full arcs are superior to single and partial arcs in terms of organs at risk sparing even for unilateral target volumes. The collimator position was found as an additional setup parameter, which can further improve the target coverage and sparing of organs at risk.}, language = {en} } @article{WeickBreuerRichteretal.2020, author = {Weick, Stefan and Breuer, Kathrin and Richter, Anne and Exner, Florian and Str{\"o}hle, Serge-Peer and Lutyj, Paul and Tamihardja, J{\"o}rg and Veldhoen, Simon and Flentje, Michael and Polat, B{\"u}lent}, title = {Non-rigid image registration of 4D-MRI data for improved delineation of moving tumors}, series = {BMC Medical Imaging}, volume = {20}, journal = {BMC Medical Imaging}, doi = {10.1186/s12880-020-00439-6}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-229271}, year = {2020}, abstract = {Background To increase the image quality of end-expiratory and end-inspiratory phases of retrospective respiratory self-gated 4D MRI data sets using non-rigid image registration for improved target delineation of moving tumors. Methods End-expiratory and end-inspiratory phases of volunteer and patient 4D MRI data sets are used as targets for non-rigid image registration of all other phases using two different registration schemes: In the first, all phases are registered directly (dir-Reg) while next neighbors are successively registered until the target is reached in the second (nn-Reg). Resulting data sets are quantitatively compared using diaphragm and tumor sharpness and the coefficient of variation of regions of interest in the lung, liver, and heart. Qualitative assessment of the patient data regarding noise level, tumor delineation, and overall image quality was performed by blinded reading based on a 4 point Likert scale. Results The median coefficient of variation was lower for both registration schemes compared to the target. Median dir-Reg coefficient of variation of all ROIs was 5.6\% lower for expiration and 7.0\% lower for inspiration compared with nn-Reg. Statistical significant differences between the two schemes were found in all comparisons. Median sharpness in inspiration is lower compared to expiration sharpness in all cases. Registered data sets were rated better compared to the targets in all categories. Over all categories, mean expiration scores were 2.92 +/- 0.18 for the target, 3.19 +/- 0.22 for nn-Reg and 3.56 +/- 0.14 for dir-Reg and mean inspiration scores 2.25 +/- 0.12 for the target, 2.72 +/- 215 0.04 for nn-Reg and 3.78 +/- 0.04 for dir-Reg. Conclusions In this work, end-expiratory and inspiratory phases of a 4D MRI data sets are used as targets for non-rigid image registration of all other phases. It is qualitatively and quantitatively shown that image quality of the targets can be significantly enhanced leading to improved target delineation of moving tumors.}, language = {en} } @article{RichterWechWengetal.2020, author = {Richter, Julian A. J. and Wech, Tobias and Weng, Andreas M. and Stich, Manuel and Weick, Stefan and Breuer, Kathrin and Bley, Thorsten A. and K{\"o}stler, Herbert}, title = {Free-breathing self-gated 4D lung MRI using wave-CAIPI}, series = {Magnetic Resonance in Medicine}, volume = {84}, journal = {Magnetic Resonance in Medicine}, number = {6}, doi = {10.1002/mrm.28383}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-218075}, pages = {3223 -- 3233}, year = {2020}, abstract = {Purpose The aim of this study was to compare the wave-CAIPI (controlled aliasing in parallel imaging) trajectory to the Cartesian sampling for accelerated free-breathing 4D lung MRI. Methods The wave-CAIPI k-space trajectory was implemented in a respiratory self-gated 3D spoiled gradient echo pulse sequence. Trajectory correction applying the gradient system transfer function was used, and images were reconstructed using an iterative conjugate gradient SENSE (CG SENSE) algorithm. Five healthy volunteers and one patient with squamous cell carcinoma in the lung were examined on a clinical 3T scanner, using both sampling schemes. For quantitative comparison of wave-CAIPI and standard Cartesian imaging, the normalized mutual information and the RMS error between retrospectively accelerated acquisitions and their respective references were calculated. The SNR ratios were investigated in a phantom study. Results The obtained normalized mutual information values indicate a lower information loss due to acceleration for the wave-CAIPI approach. Average normalized mutual information values of the wave-CAIPI acquisitions were 10\% higher, compared with Cartesian sampling. Furthermore, the RMS error of the wave-CAIPI technique was lower by 19\% and the SNR was higher by 14\%. Especially for short acquisition times (down to 1 minute), the undersampled Cartesian images showed an increased artifact level, compared with wave-CAIPI. Conclusion The application of the wave-CAIPI technique to 4D lung MRI reduces undersampling artifacts, in comparison to a Cartesian acquisition of the same scan time. The benefit of wave-CAIPI sampling can therefore be traded for shorter examinations, or enhancing image quality of undersampled 4D lung acquisitions, keeping the scan time constant.}, language = {en} } @article{ZimmermannRichterWeicketal.2022, author = {Zimmermann, Marcus and Richter, Anne and Weick, Stefan and Exner, Florian and Mantel, Frederick and Diefenhardt, Markus and Fokas, Emmanouil and Kosmala, Rebekka and Flentje, Michael and Polat, B{\"u}lent}, title = {Acute toxicities of patients with locally advanced rectal cancer treated with intensified chemoradiotherapy within the CAO/ARO/AIO-12 trial: comparing conventional versus VMAT planning at a single center}, series = {Scientific Reports}, volume = {12}, journal = {Scientific Reports}, doi = {10.1038/s41598-022-25647-8}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-301255}, year = {2022}, abstract = {In locally advanced rectal cancer (LARC) neoadjuvant chemoradiotherapy is regarded as standard treatment. We assessed acute toxicities in patients receiving conventional 3D-conformal radiotherapy (3D-RT) and correlated them with dosimetric parameters after re-planning with volumetric modulated arc therapy (VMAT). Patients were randomized within the multicenter CAO/ARO/AIO-12 trial and received 50.4 Gy in 28 fractions and simultaneous chemotherapy with fluorouracil and oxaliplatin. Organs at risk (OAR) were contoured in a standardized approach. Acute toxicities and dose volume histogram parameters of 3D-RT plans were compared to retrospectively calculated VMAT plans. From 08/2015 to 01/2018, 35 patients with LARC were treated at one study center. Thirty-four patients were analyzed of whom 1 (3\%) was UICC stage II and 33 (97\%) patients were UICC stage III. Grade 3 acute toxicities occurred in 5 patients (15\%). Patients with acute grade 1 cystitis (n = 9) had significantly higher D\(_{mean}\) values for bladder (29.4 Gy vs. 25.2 Gy, p < 0.01) compared to patients without bladder toxicities. Acute diarrhea was associated with small bowel volume (grade 2: 870.1 ccm vs. grade 0-1: 647.3 ccm; p < 0.01) and with the irradiated volumes V5 to V50. Using VMAT planning, we could reduce mean doses and irradiated volumes for all OAR: D\(_{mean}\) bladder (21.9 Gy vs. 26.3 Gy, p < 0.01), small bowel volumes V5-V45 (p < 0.01), D\(_{mean}\) anal sphincter (34.6 Gy vs. 35.6 Gy, p < 0.01) and D\(_{mean}\) femoral heads (right 11.4 Gy vs. 25.9 Gy, left 12.5 Gy vs. 26.6 Gy, p < 0.01). Acute small bowel and bladder toxicities were dose and volume dependent. Dose and volume sparing for all OAR could be achieved through VMAT planning and might result in less acute toxicities.}, language = {en} } @article{HuflageKunzHendeletal.2023, author = {Huflage, Henner and Kunz, Andreas Steven and Hendel, Robin and Kraft, Johannes and Weick, Stefan and Razinskas, Gary and Sauer, Stephanie Tina and Pennig, Lenhard and Bley, Thorsten Alexander and Grunz, Jan-Peter}, title = {Obesity-related pitfalls of virtual versus true non-contrast imaging — an intraindividual comparison in 253 oncologic patients}, series = {Diagnostics}, volume = {13}, journal = {Diagnostics}, number = {9}, issn = {2075-4418}, doi = {10.3390/diagnostics13091558}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-313519}, year = {2023}, abstract = {Objectives: Dual-source dual-energy CT (DECT) facilitates reconstruction of virtual non-contrast images from contrast-enhanced scans within a limited field of view. This study evaluates the replacement of true non-contrast acquisition with virtual non-contrast reconstructions and investigates the limitations of dual-source DECT in obese patients. Materials and Methods: A total of 253 oncologic patients (153 women; age 64.5 ± 16.2 years; BMI 26.6 ± 5.1 kg/m\(^2\)) received both multi-phase single-energy CT (SECT) and DECT in sequential staging examinations with a third-generation dual-source scanner. Patients were allocated to one of three BMI clusters: non-obese: <25 kg/m\(^2\) (n = 110), pre-obese: 25-29.9 kg/m\(^2\) (n = 73), and obese: >30 kg/m\(^2\) (n = 70). Radiation dose and image quality were compared for each scan. DECT examinations were evaluated regarding liver coverage within the dual-energy field of view. Results: While arterial contrast phases in DECT were associated with a higher CTDI\(_{vol}\) than in SECT (11.1 vs. 8.1 mGy; p < 0.001), replacement of true with virtual non-contrast imaging resulted in a considerably lower overall dose-length product (312.6 vs. 475.3 mGy·cm; p < 0.001). The proportion of DLP variance predictable from patient BMI was substantial in DECT (R\(^2\) = 0.738) and SECT (R\(^2\) = 0.620); however, DLP of SECT showed a stronger increase in obese patients (p < 0.001). Incomplete coverage of the liver within the dual-energy field of view was most common in the obese subgroup (17.1\%) compared with non-obese (0\%) and pre-obese patients (4.1\%). Conclusion: DECT facilitates a 30.8\% dose reduction over SECT in abdominal oncologic staging examinations. Employing dual-source scanner architecture, the risk for incomplete liver coverage increases in obese patients.}, language = {en} } @article{TamihardjaLawrenzLutyjetal.2022, author = {Tamihardja, J{\"o}rg and Lawrenz, Ingulf and Lutyj, Paul and Weick, Stefan and Guckenberger, Matthias and Polat, B{\"u}lent and Flentje, Michael}, title = {Propensity score-matched analysis comparing dose-escalated intensity-modulated radiation therapy versus external beam radiation therapy plus high-dose-rate brachytherapy for localized prostate cancer}, series = {Strahlentherapie und Onkologie}, volume = {198}, journal = {Strahlentherapie und Onkologie}, number = {8}, doi = {10.1007/s00066-022-01953-y}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-325055}, pages = {735-743}, year = {2022}, abstract = {Purpose Dose-escalated external beam radiation therapy (EBRT) and EBRT + high-dose-rate brachytherapy (HDR-BT) boost are guideline-recommended treatment options for localized prostate cancer. The purpose of this study was to compare long-term outcome and toxicity of dose-escalated EBRT versus EBRT + HDR-BT boost. Methods From 2002 to 2019, 744 consecutive patients received either EBRT or EBRT + HDR-BT boost, of whom 516 patients were propensity score matched. Median follow-up was 95.3 months. Cone beam CT image-guided EBRT consisted of 33 fractions of intensity-modulated radiation therapy with simultaneous integrated boost up to 76.23 Gy (D\(_{Mean}\)). Combined treatment was delivered as 46 Gy (D\(_{Mean}\)) EBRT, followed by two fractions HDR-BT boost with 9 Gy (D\(_{90\\%}\)). Propensity score matching was applied before analysis of the primary endpoint, estimated 10-year biochemical relapse-free survival (bRFS), and the secondary endpoints metastasis-free survival (MFS) and overall survival (OS). Prognostic parameters were analyzed by Cox proportional hazard modelling. Genitourinary (GU)/gastrointestinal (GI) toxicity evaluation used the Common Toxicity Criteria for Adverse Events (v5.0). Results The estimated 10-year bRFS was 82.0\% vs. 76.4\% (p = 0.075) for EBRT alone versus combined treatment, respectively. The estimated 10-year MFS was 82.9\% vs. 87.0\% (p = 0.195) and the 10-year OS was 65.7\% vs. 68.9\% (p = 0.303), respectively. Cumulative 5‑year late GU ≥ grade 2 toxicities were seen in 23.6\% vs. 19.2\% (p = 0.086) and 5‑year late GI ≥ grade 2 toxicities in 11.1\% vs. 5.0\% of the patients (p = 0.002); cumulative 5‑year late grade 3 GU toxicity occurred in 4.2\% vs. 3.6\% (p = 0.401) and GI toxicity in 1.0\% vs. 0.3\% (p = 0.249), respectively. Conclusion Both treatment groups showed excellent long-term outcomes with low rates of severe toxicity.}, language = {en} }