@phdthesis{Stratmann2013,
  author    = {Stratmann, Jana-Teresa},
  title     = {Untersuchung zur Expression zellul{\"a}rer Marker beim metastasierenden Kopf-Hals-Karzinom im Prim{\"a}rtumor und in den Metastasen},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-76557},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2013},
  abstract  = {In der vorliegenden Arbeit wurde das Expressionsverhalten f{\"u}nf zellul{\"a}rer Marker beim metastasierenden Plattenepithelkarzinom des Kopf- und Halsbereiches untersucht. Bei den getesteten Markern handelte es sich um einen MAGE-A, zwei verschiedenen VEGF, einen EGFR und einen C-Src-Tyrosinkinase Antik{\"o}rper. Im Einzelnen sollte hinterfragt werden, ob ein Zusammenhang zwischen der Antik{\"o}rperexpression und verschiedenen, klinischen und histopathologischen Parametern (pT-Stadium, pN-Stadium, histologisches Grading, Tumorverhornung, Patientenalter, Geschlecht des Patienten) besteht. Weiterhin war von Interesse, ob Parallelen zwischen dem Expressionsverhalten der verschiedenen Antik{\"o}rper untereinander zu erkennen sind. Die Ergebnisse wurden anschließend mit Erkenntnissen aus anderen Studien und Literaturangaben verglichen.},
  subject      = {Mundh�hlentumor},
  language  = {de}
}
@phdthesis{Hellinger2003,
  author    = {Hellinger, Michaela},
  title     = {Untersuchung der Lebensqualit{\"a}t nach operativer Behandlung von Oropharynx- und Mundh{\"o}hlenkarzinomen},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-6543},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2003},
  abstract  = {Die Ergebnisse dieser Studie geben einen {\"U}berblick {\"u}ber den Gesundheitszustand und die Lebensqualit{\"a}t der Patienten nach der operativen Therapie eines Oropharynx- oder Mundh{\"o}hlenkarzinomes. Die Lebensqualit{\"a}t des Einzelnen ist ein komplexes Konstrukt und von den individuellen Werten und Einsch{\"a}tzungen des Patienten abh{\"a}ngig. Die Gesamtwerte des Patientenkollektives k{\"o}nnen nur gemeinsame Tendenzen beschreiben. Insgesamt wurde die Lebensqualit{\"a}t als wenig beeintr{\"a}chtigt eingesch{\"a}tzt. Die Betrachtung der Einzelwerte ergaben jedoch f{\"u}r 50\% der Befragten eine m{\"a}ßige Reduktion der Lebensqualit{\"a}t und des Gesundheitsstatus. Die epidemiologischen und {\"a}tiologischen Faktoren konnten best{\"a}tigt werden. Die Patienten reagierten nach der Operation in Bezug auf die Risikofaktoren einsichtig und verneinten den Alkohol- und Zigarettenkonsum oder schr{\"a}nkten ihn stark ein. Die Aufkl{\"a}rung und die Wiederentscheidung f{\"u}r die einzelnen Therapiearten wurde von den Patienten positiv beurteilt. Hier zeigte die Studie ein hohes Maß an Akzeptanz der postoperativ auftretenden somatischen Einschr{\"a}nkungen, wodurch die subjektive Bewertung der Lebensqualit{\"a}t positiv beeinflusst wurde. Zu den stark lebensqualit{\"a}tsmindernden Symptomen geh{\"o}rten die Xerostomie und die Dysphagie. Die Speisen mussten stark zerkleinert und verfl{\"u}ssigt werden, damit ein Schlucken m{\"o}glich war. Die erschwerte Nahrungsaufnahme kann die Anwendung von oraler Zusatzern{\"a}hrung und den Gebrauch einer Ern{\"a}hrungssonde erfordern, um einen ausreichenden Ern{\"a}hrungszustand zu gew{\"a}hrleisten. Der Gebrauch einer Ern{\"a}hrungssonde wirkte eher lebensqualit{\"a}tsmindernd, als die regelm{\"a}ßige orale Einnahme von kommerziellen fl{\"u}ssigen Formulardi{\"a}ten. Auch die Einschr{\"a}nkung der Bewegungsfreiheit des Kopfes und des Armes als Folge der Neck-dissection geh{\"o}rte mit zu den st{\"a}rker mindernden Faktoren. Der Vergleich h{\"o}herer zu niedrigerer subjektiv empfundener Lebensqualit{\"a}t und Gesundheitsstatus l{\"a}ßt die Annahme zu, dass Patienten, die durch allgemeine Schw{\"a}che und Schmerzen, sowie einer dauerhaften Schmerzmitteleinnahme t{\"a}glich an ihre Erkrankung erinnert werden, ihren Gesundheitsstatus und ihre Lebensqualit{\"a}t als st{\"a}rker vermindert einsch{\"a}tzen.},
  language  = {de}
}
@article{BoschertKlenkAbtetal.2020,
  author    = {Boschert, Verena and Klenk, Nicola and Abt, Alexander and Raman, Sudha Janaki and Fischer, Markus and Brands, Roman C. and Seher, Axel and Linz, Christian and M{\"u}ller-Richter, Urs D. A. and Bischler, Thorsten and Hartmann, Stefan},
  title     = {The influence of Met receptor level on HGF-induced glycolytic reprogramming in head and neck squamous cell carcinoma},
  series = {International Journal of Molecular Sciences},
  volume    = {21},
  journal   = {International Journal of Molecular Sciences},
  number    = {2},
  issn      = {1422-0067},
  doi       = {10.3390/ijms21020471},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-235995},
  year      = {2020},
  abstract  = {Head and neck squamous cell carcinoma (HNSCC) is known to overexpress a variety of receptor tyrosine kinases, such as the HGF receptor Met. Like other malignancies, HNSCC involves a mutual interaction between the tumor cells and surrounding tissues and cells. We hypothesized that activation of HGF/Met signaling in HNSCC influences glucose metabolism and therefore substantially changes the tumor microenvironment. To determine the effect of HGF, we submitted three established HNSCC cell lines to mRNA sequencing. Dynamic changes in glucose metabolism were measured in real time by an extracellular flux analyzer. As expected, the cell lines exhibited different levels of Met and responded differently to HGF stimulation. As confirmed by mRNA sequencing, the level of Met expression was associated with the number of upregulated HGF-dependent genes. Overall, Met stimulation by HGF leads to increased glycolysis, presumably mediated by higher expression of three key enzymes of glycolysis. These effects appear to be stronger in Met\(^{high}\)-expressing HNSCC cells. Collectively, our data support the hypothesized role of HGF/Met signaling in metabolic reprogramming of HNSCC.},
  language  = {en}
}
@article{LinzBrandsKertelsetal.2021,
  author    = {Linz, Christian and Brands, Roman C. and Kertels, Olivia and Dierks, Alexander and Brumberg, Joachim and Gerhard-Hartmann, Elena and Hartmann, Stefan and Schirbel, Andreas and Serfling, Sebastian and Zhi, Yingjun and Buck, Andreas K. and K{\"u}bler, Alexander and Hohm, Julian and Lapa, Constantin and Kircher, Malte},
  title     = {Targeting fibroblast activation protein in newly diagnosed squamous cell carcinoma of the oral cavity - initial experience and comparison to [\(^{18}\)F]FDG PET/CT and MRI},
  series = {European Journal of Nuclear Medicine and Molecular Imaging},
  volume    = {48},
  journal   = {European Journal of Nuclear Medicine and Molecular Imaging},
  number    = {12},
  issn      = {1619-7070},
  doi       = {10.1007/s00259-021-05422-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-307246},
  pages     = {3951-3960},
  year      = {2021},
  abstract  = {Purpose While [\(^{18}\)F]-fluorodeoxyglucose ([\(^{18}\)F]FDG) is the standard for positron emission tomography/computed tomography (PET/CT) imaging of oral squamous cell carcinoma (OSCC), diagnostic specificity is hampered by uptake in inflammatory cells such as neutrophils or macrophages. Recently, molecular imaging probes targeting fibroblast activation protein α (FAP), which is overexpressed in a variety of cancer-associated fibroblasts, have become available and might constitute a feasible alternative to FDG PET/CT. Methods Ten consecutive, treatment-na{\"i}ve patients (8 males, 2 females; mean age, 62 ± 9 years) with biopsy-proven OSCC underwent both whole-body [\(^{18}\)F]FDG and [\(^{68}\)Ga]FAPI-04 (FAP-directed) PET/CT for primary staging prior to tumor resection and cervical lymph node dissection. Detection of the primary tumor, as well as the presence and number of lymph node and distant metastases was analysed. Intensity of tracer accumulation was assessed by means of maximum (SUV\(_{max}\)) and peak (SUV\(_{peak}\) standardized uptake values. Histological work-up including immunohistochemical staining for FAP served as standard of reference. Results [\(^{18}\)F]FDG and FAP-directed PET/CT detected all primary tumors with a SUVmax of 25.5 ± 13.2 (FDG) and 20.5 ± 6.4 (FAP-directed) and a SUVpeak of 16.1 ± 10.3 ([\(^{18}\)F]FDG) and 13.8 ± 3.9 (FAP-directed), respectively. Regarding cervical lymph node metastases, FAP-directed PET/CT demonstrated comparable sensitivity (81.3\% vs. 87.5\%; P = 0.32) and specificity (93.3\% vs. 81.3\%; P = 0.16) to [\(^{18}\)F]FDG PET/CT. FAP expression on the cell surface of cancer-associated fibroblasts in both primary lesions as well as lymph nodes metastases was confirmed in all samples. Conclusion FAP-directed PET/CT in OSCC seems feasible. Future research to investigate its potential to improve patient staging is highly warranted.},
  language  = {en}
}
@phdthesis{Jung2010,
  author    = {Jung, Susanne},
  title     = {Retrospektive Nachuntersuchung zum Vergleich verschiedener kn{\"o}cherner Unterkieferrekonstruktionen nach ablativer Kieferchirurgie : eine Untersuchung der Jahre 1998 - 2008},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-48594},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2010},
  abstract  = {Im Zeitraum von 1998 bis 2008 wurden in der Klinik und Poliklinik f{\"u}r Mund- Kiefer und Plastische Gesichtschirurgie in W{\"u}rzburg 124 Patienten einer Kontinuit{\"a}tsresektion des Unterkiefer unterzogen und mit verschiedenen autologen oss{\"a}ren Transplantaten rekonstruiert. 103 der 124 Patienten leiden an Plattenepithelkarzinomen der Mundh{\"o}hle, 8 an Osteomyelitiden, den restlichen Patienten musste wegen Traumata, Fehlbildungen oder sonstigen Gr{\"u}nden ein Teil des Unterkiefers entfernt werden. Die Komplikationsraten betrugen f{\"u}r Wundheilungsst{\"o}rungen im Sinne von Lokalinfektionen 69\%, Pseudarthrosen 25\%, Anastomoseninsuffizienz 5\% und Lappenexplantation 16\%. Bemerkenswert ist die Tatsache, dass eine pr{\"a}operativ durchgef{\"u}hrte neoadjuvante Bestrahlung mit 40 Gray keine negativen Konsequenzen f{\"u}r den Rekonstruktionserfolg mit einem mikrovaskul{\"a}r anastomosierten Transplantat hat. Diese Erkenntnis hat sicher auch Bedeutung f{\"u}r die Bewertung alternativer Therapiekonzepte, wie die postoperative Radiochemotherapie. In 18\% der untersuchten F{\"a}lle ergab die postoperative histopathologische Untersuchung keine kn{\"o}cherne Invasion des diagnostizierten Tumors. Im Hinblick auf die Option einem Teil der Patienten eine schwere und entstellende Operation zu ersparen, wird in Zukunft ein spezielles Augenmerk auf die pr{\"a}zise pr{\"a}operative Knochenbeurteilung zu richten sein. In Zusammenschau mit analogen Arbeiten in der Literatur, f{\"u}gen sich die Resultate der Klinik und Poliklinik f{\"u}r Mund- Kiefer- und Plastische Gesichtschirurgie weitestgehend ein. F{\"u}r die nahe Zukunft stehen interessante Entwicklungen auf diesem Gebiet an. Die Etablierung von Perforatorlappen wird die M{\"o}glichkeiten der Rekonstruktion sicher um einige funktionell und {\"a}sthetisch vorteilhafte Varianten bereichern.},
  subject      = {Unterkiefer},
  language  = {de}
}
@article{BoschertTeuschMuellerRichteretal.2022,
  author    = {Boschert, Verena and Teusch, Jonas and M{\"u}ller-Richter, Urs D. A. and Brands, Roman C. and Hartmann, Stefan},
  title     = {PKM2 modulation in head and neck squamous cell carcinoma},
  series = {International Journal of Molecular Sciences},
  volume    = {23},
  journal   = {International Journal of Molecular Sciences},
  number    = {2},
  issn      = {1422-0067},
  doi       = {10.3390/ijms23020775},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-284458},
  year      = {2022},
  abstract  = {The enzyme pyruvate kinase M2 (PKM2) plays a major role in the switch of tumor cells from oxidative phosphorylation to aerobic glycolysis, one of the hallmarks of cancer. Different allosteric inhibitors or activators and several posttranslational modifications regulate its activity. Head and neck squamous cell carcinoma (HNSCC) is a common disease with a high rate of recurrence. To find out more about PKM2 and its modulation in HNSCC, we examined a panel of HNSCC cells using real-time cell metabolic analysis and Western blotting with an emphasis on phosphorylation variant Tyr105 and two reagents known to impair PKM2 activity. Our results show that in HNSCC, PKM2 is commonly phosphorylated at Tyrosine 105. Its levels depended on tyrosine kinase activity, emphasizing the importance of growth factors such as EGF (epidermal growth factor) on HNSCC metabolism. Furthermore, its correlation with the expression of CD44 indicates a role in cancer stemness. Cells generally reacted with higher glycolysis to PKM2 activator DASA-58 and lower glycolysis to PKM2 inhibitor Compound 3k, but some were more susceptible to activation and others to inhibition. Our findings emphasize the need to further investigate the role of PKM2 in HNSCC, as it could aid understanding and treatment of the disease.},
  language  = {en}
}
@article{PolatKaiserWohllebenetal.2017,
  author    = {Polat, B{\"u}lent and Kaiser, Philipp and Wohlleben, Gisela and Gehrke, Thomas and Scherzad, Agmal and Scheich, Matthias and Malzahn, Uwe and Fischer, Thomas and Vordermark, Dirk and Flentje, Michael},
  title     = {Perioperative changes in osteopontin and TGFβ1 plasma levels and their prognostic impact for radiotherapy in head and neck cancer},
  series = {BMC Cancer},
  volume    = {17},
  journal   = {BMC Cancer},
  number    = {6},
  doi       = {10.1186/s12885-016-3024-4},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-157529},
  year      = {2017},
  abstract  = {Background: In head and neck cancer little is known about the kinetics of osteopontin (OPN) expression after tumor resection. In this study we evaluated the time course of OPN plasma levels before and after surgery. Methods: Between 2011 and 2013 41 consecutive head and neck cancer patients were enrolled in a prospective study (group A). At different time points plasma samples were collected: T0) before, T1) 1 day, T2) 1 week and T3) 4 weeks after surgery. Osteopontin and TGFβ1 plasma concentrations were measured with a commercial ELISA system. Data were compared to 131 head and neck cancer patients treated with primary (n = 42) or postoperative radiotherapy (n = 89; group B1 and B2). Results: A significant OPN increase was seen as early as 1 day after surgery (T0 to T1, p < 0.01). OPN levels decreased to base line 3-4 weeks after surgery. OPN values were correlated with postoperative TGFβ1 expression suggesting a relation to wound healing. Survival analysis showed a significant benefit for patients with lower OPN levels both in the primary and postoperative radiotherapy group (B1: 33 vs 11.5 months, p = 0.017, B2: median not reached vs 33.4, p = 0.031). TGFβ1 was also of prognostic significance in group B1 (33.0 vs 10.7 months, p = 0.003). Conclusions: Patients with head and neck cancer showed an increase in osteopontin plasma levels directly after surgery. Four weeks later OPN concentration decreased to pre-surgery levels. This long lasting increase was presumably associated to wound healing. Both pretherapeutic osteopontin and TGFβ1 had prognostic impact.},
  language  = {en}
}
@article{VollmerNaglerHoerneretal.2023,
  author    = {Vollmer, Andreas and Nagler, Simon and H{\"o}rner, Marius and Hartmann, Stefan and Brands, Roman C. and Breitenb{\"u}cher, Niko and Straub, Anton and K{\"u}bler, Alexander and Vollmer, Michael and Gubik, Sebastian and Lang, Gernot and Wollborn, Jakob and Saravi, Babak},
  title     = {Performance of artificial intelligence-based algorithms to predict prolonged length of stay after head and neck cancer surgery},
  series = {Heliyon},
  volume    = {9},
  journal   = {Heliyon},
  number    = {11},
  issn      = {2405-8440},
  doi       = {10.1016/j.heliyon.2023.e20752},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-350416},
  year      = {2023},
  abstract  = {Background Medical resource management can be improved by assessing the likelihood of prolonged length of stay (LOS) for head and neck cancer surgery patients. The objective of this study was to develop predictive models that could be used to determine whether a patient's LOS after cancer surgery falls within the normal range of the cohort. Methods We conducted a retrospective analysis of a dataset consisting of 300 consecutive patients who underwent head and neck cancer surgery between 2017 and 2022 at a single university medical center. Prolonged LOS was defined as LOS exceeding the 75th percentile of the cohort. Feature importance analysis was performed to evaluate the most important predictors for prolonged LOS. We then constructed 7 machine learning and deep learning algorithms for the prediction modeling of prolonged LOS. Results The algorithms reached accuracy values of 75.40 (radial basis function neural network) to 97.92 (Random Trees) for the training set and 64.90 (multilayer perceptron neural network) to 84.14 (Random Trees) for the testing set. The leading parameters predicting prolonged LOS were operation time, ischemia time, the graft used, the ASA score, the intensive care stay, and the pathological stages. The results revealed that patients who had a higher number of harvested lymph nodes (LN) had a lower probability of recurrence but also a greater LOS. However, patients with prolonged LOS were also at greater risk of recurrence, particularly when fewer (LN) were extracted. Further, LOS was more strongly correlated with the overall number of extracted lymph nodes than with the number of positive lymph nodes or the ratio of positive to overall extracted lymph nodes, indicating that particularly unnecessary lymph node extraction might be associated with prolonged LOS. Conclusions The results emphasize the need for a closer follow-up of patients who experience prolonged LOS. Prospective trials are warranted to validate the present results.},
  language  = {en}
}
@phdthesis{Schewe2020,
  author    = {Schewe, Victoria Kristina},
  title     = {Mikrokernbildung in Mundschleimhautzellen von Patienten mit Kopf-Hals-Tumoren w{\"a}hrend Radio-/Radiochemotherapie},
  doi       = {10.25972/OPUS-21535},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-215354},
  school      = {Universit{\"a}t W{\"u}rzburg},
  year      = {2020},
  abstract  = {Das Ziel der vorliegenden Arbeit war die Mikrokernbildung in Mundschleimhautzellen von 35 Patienten mit Kopf-Hals-Tumoren w{\"a}hrend einer sechsw{\"o}chigen Radio-/Radiochemotherapie und sechs Wochen danach darzustellen. Die Ergebnisse der vorliegenden Arbeit zeigten, dass Patienten mit Kopf-Hals-Tumoren im Vergleich zu gesunden Probanden erh{\"o}hte Mikrokernraten aufwiesen. Ebenfalls konnte gezeigt werden, dass es zu einer vermehrten Bildung von Mikrokernen w{\"a}hrend einer sechsw{\"o}chigen Radio-/Radiochemotherapie kam. Nach Therapiebeendigung sanken die Werte nach drei bis sechs Wochen und lagen unter dem Ausgangswert, in dem Bereich von spontan entstehenden Mikrokernen. In Bezug auf die Tumorgr{\"o}ße konnte nur in der zweiten Woche ein signifikanter Unterschied in der Mikrokernrate zwischen T1- und T4-Stadium beobachtet werden. Es konnte keine Korrelation zwischen einer zus{\"a}tzlich verabreichten Chemotherapie, Grading des Tumors, Alter sowie Geschlecht der Patienten und einem Anstieg der Mikrokernrate festgestellt werden.},
  subject      = {Kleinkern},
  language  = {de}
}
@article{WohllebenScherzadGuettleretal.2015,
  author    = {Wohlleben, Gisela and Scherzad, Agmal and G{\"u}ttler, Antje and Vordermark, Dirk and Kuger, Sebastian and Flentje, Michael and Polat, Buelent},
  title     = {Influence of hypoxia and irradiation on osteopontin expression in head and neck cancer and glioblastoma cell lines},
  series = {Radiation Oncology},
  volume    = {10},
  journal   = {Radiation Oncology},
  number    = {167},
  doi       = {10.1186/s13014-015-0473-x},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-125746},
  year      = {2015},
  abstract  = {Background Tumor hypoxia is a known risk factor for reduced response to radiotherapy. The evaluation of noninvasive methods for the detection of hypoxia is therefore of interest. Osteopontin (OPN) has been discussed as an endogenous hypoxia biomarker. It is overexpressed in many cancers and is involved in tumor progression and metastasis. Methods To examine the influence of hypoxia and irradiation on osteopontin expression we used different cell lines (head and neck cancer (Cal27 and FaDu) and glioblastoma multiforme (U251 and U87)). Cells were treated with hypoxia for 24 h and were then irradiated with doses of 2 and 8 Gy. Osteopontin expression was analyzed on mRNA level by quantitative real-time RT-PCR (qPCR) and on protein level by western blot. Cell culture supernatants were evaluated for secreted OPN by ELISA. Results Hypoxia caused an increase in osteopontin protein expression in all cell lines. In Cal27 a corresponding increase in OPN mRNA expression was observed. In contrast the other cell lines showed a reduced mRNA expression under hypoxic conditions. After irradiation OPN mRNA expression raised slightly in FaDu and U87 cells while it was reduced in U251 and stable in Cal27 cells under normoxia. The combined treatment (hypoxia and irradiation) led to a slight increase of OPN mRNA after 2 Gy in U251 (24 h) and in U87 (24 and 48 h) cell lines falling back to base line after 8 Gy. This effect was not seen in Cal27 or in FaDu cells. Secreted OPN was detected only in the two glioblastoma cell lines with reduced protein levels under hypoxic conditions. Again the combined treatment resulted in a minor increase in OPN secretion 48 hours after irradiation with 8 Gy. Conclusion Osteopontin expression is strongly modulated by hypoxia and only to a minor extent by irradiation. Intracellular OPN homeostasis seems to vary considerably between cell lines. This may explain the partly conflicting results concerning response prediction and prognosis in the clinical setting.},
  language  = {en}
}
@article{BoschertTeuschAljasemetal.2020,
  author    = {Boschert, Verena and Teusch, Jonas and Aljasem, Anwar and Schmucker, Philipp and Klenk, Nicola and Straub, Anton and Bittrich, Max and Seher, Axel and Linz, Christian and M{\"u}ller-Richter, Urs D. A. and Hartmann, Stefan},
  title     = {HGF-induced PD-L1 expression in head and neck cancer: preclinical and clinical findings},
  series = {International Journal of Molecular Sciences},
  volume    = {21},
  journal   = {International Journal of Molecular Sciences},
  number    = {20},
  issn      = {1422-0067},
  doi       = {10.3390/ijms21228770},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-236220},
  year      = {2020},
  abstract  = {Head and neck squamous cell carcinoma (HNSCC) is a widespread disease with a low survival rate and a high risk of recurrence. Nowadays, immune checkpoint inhibitor (ICI) treatment is approved for HNSCC as a first-line treatment in recurrent and metastatic disease. ICI treatment yields a clear survival benefit, but overall response rates are still unsatisfactory. As shown in different cancer models, hepatocyte growth factor/mesenchymal-epithelial transition (HGF/Met) signaling contributes to an immunosuppressive microenvironment. Therefore, we investigated the relationship between HGF and programmed cell death protein 1 (PD-L1) expression in HNSCC cell lines. The preclinical data show a robust PD-L1 induction upon HGF stimulation. Further analysis revealed that the HGF-mediated upregulation of PD-L1 is MAP kinase-dependent. We then hypothesized that serum levels of HGF and soluble programmed cell death protein 1 (sPD-L1) could be potential markers of ICI treatment failure. Thus, we determined serum levels of these proteins in 20 HNSCC patients before ICI treatment and correlated them with treatment outcomes. Importantly, the clinical data showed a positive correlation of both serum proteins (HGF and sPD-L1) in HNSCC patient's sera. Moreover, the serum concentration of sPD-L1 was significantly higher in ICI non-responsive patients. Our findings indicate a potential role for sPD-L1 as a prognostic marker for ICI treatment in HNSCC.},
  language  = {en}
}
@article{PollmannToussaintFlentjeetal.2022,
  author    = {Pollmann, Stephan and Toussaint, Andr{\´e} and Flentje, Michael and Wegener, Sonja and Lewitzki, Victor},
  title     = {Dosimetric evaluation of commercially available flat vs. self-produced 3D-conformal silicone boluses for the head and neck region},
  series = {Frontiers in Oncology},
  volume    = {12},
  journal   = {Frontiers in Oncology},
  issn      = {2234-943X},
  doi       = {10.3389/fonc.2022.881439},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-283156},
  year      = {2022},
  abstract  = {Background Boluses are routinely used in radiotherapy to modify surface doses. Nevertheless, considerable dose discrepancies may occur in some cases due to fit inaccuracy of commercially available standard flat boluses. Moreover, due to the simple geometric design of conventional boluses, also surrounding healthy skin areas may be unintentionally covered, resulting in the unwanted dose buildup. With the fused deposition modeling (FDM) technique, there is a simple and possibly cost-effective way to solve these problems in routine clinical practice. This paper presents a procedure of self-manufacturing bespoke patient-specific silicone boluses and the evaluation of buildup and fit accuracy in comparison to standard rectangular commercially available silicone boluses. Methods 3D-conformal silicone boluses were custom-built to cover the surgical scar region of 25 patients who received adjuvant radiotherapy of head and neck cancer at the University Hospital W{\"u}rzburg. During a standard CT-based planning procedure, a 5-mm-thick 3D bolus contour was generated to cover the radiopaque marked surgical scar with an additional safety margin. From these digital contours, molds were 3D printed and poured with silicone. Dose measurements for both types of boluses were performed with radiochromic films (EBT3) at three points per patient—at least one aimed to be in the high-dose area (scar) and one in the lower-dose area (spared healthy skin). Surface-bolus distance, which ideally should not be present, was determined from cone-beam CT performed for positioning control. The dosimetric influence of surface-bolus distance was also determined on slab phantom for different field sizes. The trial was performed with hardware that may be routinely available in every radiotherapy department, with the exception of the 3D printer. The required number of patients was determined based on the results of preparatory measurements with the help of the statistical consultancy of the University of W{\"u}rzburg. The number of measuring points represents the total number of patients. Results In the high-dose area of the scar, there was a significantly better intended dose buildup of 2.45\% (95\%CI 0.0014-0.0477, p = 0.038, N = 30) in favor of a 3D-conformal bolus. Median distances between the body surface and bolus differed significantly between 3D-conformal and commercially available boluses (3.5 vs. 7.9 mm, p = 0.001). The surface dose at the slab phantom did not differ between commercially available and 3D-conformal boluses. Increasing the surface-bolus distance from 5 to 10 mm decreased the surface dose by approximately 2\% and 11\% in the 6 × 6- and 3 × 3-cm2 fields, respectively. In comparison to the commercially available bolus, an unintended dose buildup in the healthy skin areas was reduced by 25.9\% (95\%CI 19.5-32.3, p < 0.01, N = 37) using the 3D-conformal bolus limited to the region surrounding the surgical scar. Conclusions Using 3D-conformal boluses allows a comparison to the commercially available boluses' dose buildup in the covered areas. Smaller field size is prone to a larger surface-bolus distance effect. Higher conformity of 3D-conformal boluses reduces this effect. This may be especially relevant for volumetric modulated arc therapy (VMAT) and intensity-modulated radiotherapy (IMRT) techniques with a huge number of smaller fields. High conformity of 3D-conformal boluses reduces an unintended dose buildup in healthy skin. The limiting factor in the conformity of 3D-conformal boluses in our setting was the immobilization mask, which was produced primarily for the 3D boluses. The mask itself limited tight contact of subsequently produced 3D-conformal boluses to the mask-covered body areas. In this respect, bolus adjustment before mask fabrication will be done in the future setting.},
  language  = {en}
}