@article{LisowskiLutyjAbazarietal.2023,
  author    = {Lisowski, Dominik and Lutyj, Paul and Abazari, Arya and Weick, Stefan and Traub, Jan and Polat, B{\"u}lent and Flentje, Michael and Kraft, Johannes},
  title     = {Impact of Radiotherapy on Malfunctions and Battery Life of Cardiac Implantable Electronic Devices in Cancer Patients},
  series = {Cancers},
  volume    = {15},
  journal   = {Cancers},
  number    = {19},
  issn      = {2072-6694},
  doi       = {10.3390/cancers15194830},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-358008},
  year      = {2023},
  abstract  = {Purpose: This study analyses a large number of cancer patients with CIEDs for device malfunction and premature battery depletion by device interrogation after each radiotherapy fraction and compares different guidelines in regard to patient safety. Methods: From 2007 to 2022, a cohort of 255 patients was analyzed for CIED malfunctions via immediate device interrogation after every RT fraction. Results: Out of 324 series of radiotherapy treatments, with a total number of 5742 CIED interrogations, nine device malfunctions (2.8\%) occurred. Switching into back-up/safety mode and software errors occurred four times each. Once, automatic read-out could not be performed. The median prescribed cumulative dose at planning target volume (PTV) associated with CIED malfunction was 45.0 Gy (IQR 36.0-64.0 Gy), with a median dose per fraction of 2.31 Gy (IQR 2.0-3.0 Gy). The median maximum dose at the CIED at time of malfunction was 0.3 Gy (IQR 0.0-1.3 Gy). No correlation between CIED malfunction and maximum photon energy (p = 0.07), maximum dose at the CIED (p = 0.59) nor treatment localization (p = 0.41) could be detected. After excluding the nine malfunctions, premature battery depletion was only observed three times (1.2\%). Depending on the national guidelines, 1-9 CIED malfunctions in this study would have been detected on the day of occurrence and in none of the cases would patient safety have been compromised. Conclusion: Radiation-induced malfunctions of CIEDs and premature battery depletion are rare. If recommendations of national safety guidelines are followed, only a portion of the malfunctions would be detected directly after occurrence. Nevertheless, patient safety would not be compromised.},
  language  = {en}
}
@article{PinkawaAebersoldBoehmeretal.2021,
  author    = {Pinkawa, Michael and Aebersold, Daniel M. and B{\"o}hmer, Dirk and Flentje, Michael and Ghadjar, Pirus and Schmidt-Hegemann, Nina-Sophie and H{\"o}cht, Stefan and H{\"o}lscher, Tobias and M{\"u}ller, Arndt-Christian and Niehoff, Peter and Sedlmayer, Felix and Wolf, Frank and Zamboglou, Constantinos and Zips, Daniel and Wiegel, Thomas},
  title     = {Radiotherapy in nodal oligorecurrent prostate cancer},
  series = {Strahlentherapie und Onkologie},
  volume    = {197},
  journal   = {Strahlentherapie und Onkologie},
  number    = {7},
  issn      = {0179-7158},
  doi       = {10.1007/s00066-021-01778-1},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-307763},
  pages     = {575-580},
  year      = {2021},
  abstract  = {Objective The current article encompasses a literature review and recommendations for radiotherapy in nodal oligorecurrent prostate cancer. Materials and methods A literature review focused on studies comparing metastasis-directed stereotactic ablative radiotherapy (SABR) vs. external elective nodal radiotherapy (ENRT) and studies analyzing recurrence patterns after local nodal treatment was performed. The DEGRO Prostate Cancer Expert Panel discussed the results and developed treatment recommendations. Results Metastasis-directed radiotherapy results in high local control (often > 90\% within a follow-up of 1-2 years) and can be used to improve progression-free survival or defer androgen deprivation therapy (ADT) according to prospective randomized phase II data. Distant progression after involved-node SABR only occurs within a few months in the majority of patients. ENRT improves metastases-free survival rates with increased toxicity in comparison to SABR according to retrospective comparative studies. The majority of nodal recurrences after initial local treatment of pelvic nodal metastasis are detected within the true pelvis and common iliac vessels. Conclusion ENRT with or without a boost should be preferred to SABR in pelvic nodal recurrences. In oligometastatic prostate cancer with distant (extrapelvic) nodal recurrences, SABR alone can be performed in selected cases. Application of additional systemic treatments should be based on current guidelines, with ADT as first-line treatment for hormone-sensitive prostate cancer. Only in carefully selected patients can radiotherapy be initially used without additional ADT outside of the current standard recommendations. Results of (randomized) prospective studies are needed for definitive recommendations.},
  language  = {en}
}
@article{GrabenbauerFlentje2022,
  author    = {Grabenbauer, Felix and Flentje, Michael},
  title     = {Salvage-Bestrahlung der Prostataloge: Mitbestrahlung der regionalen LK und Bedeutung der ADT},
  series = {Strahlentherapie und Onkologie},
  volume    = {198},
  journal   = {Strahlentherapie und Onkologie},
  number    = {12},
  doi       = {10.1007/s00066-022-02001-5},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-325047},
  pages     = {1119-1121},
  year      = {2022},
  abstract  = {No abstract available.},
  language  = {de}
}
@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}
}
@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{LisowskiTroemelLutyjetal.2022,
  author    = {Lisowski, Dominik and Tr{\"o}mel, Jannik and Lutyj, Paul and Lewitzki, Victor and Hartrampf, Philipp E. and Polat, B{\"u}lent and Flentje, Michael and Tamihardja, J{\"o}rg},
  title     = {Health-related quality of life and clinical outcome after radiotherapy of patients with intracranial meningioma},
  series = {Scientific Reports},
  volume    = {12},
  journal   = {Scientific Reports},
  doi       = {10.1038/s41598-022-24192-8},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-301233},
  year      = {2022},
  abstract  = {This retrospective, single-institutional study investigated long-term outcome, toxicity and health-related quality of life (HRQoL) in meningioma patients after radiotherapy. We analyzed the data of 119 patients who received radiotherapy at our department from 1997 to 2014 for intracranial WHO grade I-III meningioma. Fractionated stereotactic radiotherapy (FSRT), intensity modulated radiotherapy (IMRT) or radiosurgery radiation was applied. The EORTC QLQ-C30 and QLQ-BN20 questionnaires were completed for assessment of HRQoL. Overall survival (OS) for the entire study group was 89.6\% at 5 years and 75.9\% at 10 years. Local control (LC) at 5 and 10 years was 82.4\% and 73.4\%, respectively. Local recurrence was observed in 22 patients (18.5\%). Higher grade acute and chronic toxicities were observed in seven patients (5.9\%) and five patients (4.2\%), respectively. Global health status was rated with a mean of 59.9 points (SD 22.3) on QLQ-C30. In conclusion, radiotherapy resulted in very good long-term survival and tumor control rates with low rates of severe toxicities but with a deterioration of long-term HRQoL.},
  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{FischerHartmannReisslandetal.2022,
  author    = {Fischer, Thomas and Hartmann, Oliver and Reissland, Michaela and Prieto-Garcia, Cristian and Klann, Kevin and Pahor, Nikolett and Sch{\"u}lein-V{\"o}lk, Christina and Baluapuri, Apoorva and Polat, B{\"u}lent and Abazari, Arya and Gerhard-Hartmann, Elena and Kopp, Hans-Georg and Essmann, Frank and Rosenfeldt, Mathias and M{\"u}nch, Christian and Flentje, Michael and Diefenbacher, Markus E.},
  title     = {PTEN mutant non-small cell lung cancer require ATM to suppress pro-apoptotic signalling and evade radiotherapy},
  series = {Cell \& Bioscience},
  volume    = {12},
  journal   = {Cell \& Bioscience},
  issn      = {2045-3701},
  doi       = {10.1186/s13578-022-00778-7},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-299865},
  year      = {2022},
  abstract  = {Background Despite advances in treatment of patients with non-small cell lung cancer, carriers of certain genetic alterations are prone to failure. One such factor frequently mutated, is the tumor suppressor PTEN. These tumors are supposed to be more resistant to radiation, chemo- and immunotherapy. Results We demonstrate that loss of PTEN led to altered expression of transcriptional programs which directly regulate therapy resistance, resulting in establishment of radiation resistance. While PTEN-deficient tumor cells were not dependent on DNA-PK for IR resistance nor activated ATR during IR, they showed a significant dependence for the DNA damage kinase ATM. Pharmacologic inhibition of ATM, via KU-60019 and AZD1390 at non-toxic doses, restored and even synergized with IR in PTEN-deficient human and murine NSCLC cells as well in a multicellular organotypic ex vivo tumor model. Conclusion PTEN tumors are addicted to ATM to detect and repair radiation induced DNA damage. This creates an exploitable bottleneck. At least in cellulo and ex vivo we show that low concentration of ATM inhibitor is able to synergise with IR to treat PTEN-deficient tumors in genetically well-defined IR resistant lung cancer models.},
  language  = {en}
}
@article{PolatWohllebenKosmalaetal.2022,
  author    = {Polat, B{\"u}lent and Wohlleben, Gisela and Kosmala, Rebekka and Lisowski, Dominik and Mantel, Frederick and Lewitzki, Victor and L{\"o}hr, Mario and Blum, Robert and Herud, Petra and Flentje, Michael and Monoranu, Camelia-Maria},
  title     = {Differences in stem cell marker and osteopontin expression in primary and recurrent glioblastoma},
  series = {Cancer Cell International},
  volume    = {22},
  journal   = {Cancer Cell International},
  issn      = {1475-2867},
  doi       = {10.1186/s12935-022-02510-4},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-301240},
  year      = {2022},
  abstract  = {Background Despite of a multimodal approach, recurrences can hardly be prevented in glioblastoma. This may be in part due to so called glioma stem cells. However, there is no established marker to identify these stem cells. Methods Paired samples from glioma patients were analyzed by immunohistochemistry for expression of the following stem cell markers: CD133, Musashi, Nanog, Nestin, octamer-binding transcription factor 4 (Oct4), and sex determining region Y-box 2 (Sox2). In addition, the expression of osteopontin (OPN) was investigated. The relative number of positively stained cells was determined. By means of Kaplan-Meier analysis, a possible association with overall survival by marker expression was investigated. Results Sixty tissue samples from 30 patients (17 male, 13 female) were available for analysis. For Nestin, Musashi and OPN a significant increase was seen. There was also an increase (not significant) for CD133 and Oct4. Patients with mutated Isocitrate Dehydrogenase-1/2 (IDH-1/2) status had a reduced expression for CD133 and Nestin in their recurrent tumors. Significant correlations were seen for CD133 and Nanog between OPN in the primary and recurrent tumor and between CD133 and Nestin in recurrent tumors. By confocal imaging we could demonstrate a co-expression of CD133 and Nestin within recurrent glioma cells. Patients with high CD133 expression had a worse prognosis (22.6 vs 41.1 months, p = 0.013). A similar trend was seen for elevated Nestin levels (24.9 vs 41.1 months, p = 0.08). Conclusions Most of the evaluated markers showed an increased expression in their recurrent tumor. CD133 and Nestin were associated with survival and are candidate markers for further clinical investigation.},
  language  = {en}
}
@article{TamihardjaZehnerHartrampfetal.2022,
  author    = {Tamihardja, J{\"o}rg and Zehner, Leonie and Hartrampf, Philipp E. and Cirsi, Sinan and Wegener, Sonja and Buck, Andreas K. and Flentje, Michael and Polat, B{\"u}lent},
  title     = {Dose-escalated salvage radiotherapy for macroscopic local recurrence of prostate cancer in the prostate-specific membrane antigen positron emission tomography era},
  series = {Cancers},
  volume    = {14},
  journal   = {Cancers},
  number    = {19},
  issn      = {2072-6694},
  doi       = {10.3390/cancers14194956},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-290302},
  year      = {2022},
  abstract  = {Simple Summary Prostate cancer often relapses after initial radical prostatectomy, and salvage radiotherapy offers a second chance of cure for relapsed patients. Modern imaging techniques, especially prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA PET/CT), enable radiation oncologists to target radiotherapy at the involved sites of disease. In a group of patients, PSMA PET/CT imaging can detect a macroscopic local recurrence with or without locoregional lymph node metastasis. In these cases, an escalation of the radiotherapy dose is often considered for controlling the visible tumor mass. As the evidence for dose-escalated salvage radiotherapy for macroscopic recurrent prostate cancer after PSMA PET/CT imaging is still limited, we address this topic in the current analysis. We found that the outcome of patients with dose-escalated salvage radiotherapy for macroscopic prostate cancer recurrence is encouragingly favorable, while the toxicity is very limited. Abstract Background: The purpose of this study was to access the oncological outcome of prostate-specific membrane antigen positron emission tomography (PSMA PET/CT)-guided salvage radiotherapy (SRT) for localized macroscopic prostate cancer recurrence. Methods: Between February 2010 and June 2021, 367 patients received SRT after radical prostatectomy. Out of the 367 screened patients, 111 patients were staged by PSMA PET/CT before SRT. A total of 59 out of these 111 (53.2\%) patients were treated for PSMA PET-positive macroscopic prostatic fossa recurrence. Dose-escalated SRT was applied with a simultaneous integrated boost at a median prescribed dose of 69.3 Gy (IQR 69.3-72.6 Gy). The oncological outcome was investigated using Kaplan-Meier and Cox regression analyses. The genitourinary (GU)/gastrointestinal (GI) toxicity evaluation utilized Common Toxicity Criteria for Adverse Events (version 5.0). Results: The median follow-up was 38.2 months. The three-year biochemical progression-free survival rate was 89.1\% (95\% CI: 81.1-97.8\%) and the three-year metastasis-free survival rate reached 96.2\% (95\% CI: 91.2-100.0\%). The cumulative three-year late grade 3 GU toxicity rate was 3.4\%. No late grade 3 GI toxicity occurred. Conclusions: Dose-escalated PSMA PET/CT-guided salvage radiotherapy for macroscopic prostatic fossa recurrence resulted in favorable survival and toxicity rates.},
  language  = {en}
}