@article{KandelsPietschBisonetal.2020, author = {Kandels, Daniela and Pietsch, Torsten and Bison, Brigitte and Warmuth-Metz, Monika and Thomale, Ulrich-Wilhelm and Kortmann, Rolf-Dieter and Timmermann, Beate and Hern{\´a}iz Driever, Pablo and Witt, Olaf and Schmidt, Ren{\´e} and Gnekow, Astrid K.}, title = {Loss of efficacy of subsequent nonsurgical therapy after primary treatment failure in pediatric low-grade glioma patients—Report from the German SIOP-LGG 2004 cohort}, series = {International Journal of Cancer}, volume = {147}, journal = {International Journal of Cancer}, number = {12}, doi = {10.1002/ijc.33170}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-216130}, pages = {3471 -- 3489}, year = {2020}, abstract = {First-line treatment of pediatric low-grade glioma using surgery, radio- or chemotherapy fails in a relevant proportion of patients. We analyzed efficacy of subsequent surgical and nonsurgical therapies of the German cohort of the SIOP-LGG 2004 study (2004-2012, 1558 registered patients; median age at diagnosis 7.6 years, median observation time 9.2 years, overall survival 98\%/96\% at 5/10 years, 15\% neurofibromatosis type 1 [NF1]). During follow-up, 1078/1558 patients remained observed without (n = 217), with 1 (n = 707), 2 (n = 124) or 3 to 6 (n = 30) tumor volume reductions; 480/1558 had 1 (n = 332), 2 (n = 80), 3 or more (n = 68) nonsurgical treatment-lines, accompanied by up to 4 tumor-reductive surgeries in 215/480; 265/480 patients never underwent any neurosurgical tumor volume reduction (163/265 optic pathway glioma). Patients with progressing tumors after first-line adjuvant treatment were at increased risk of suffering further progressions. Risk factors were young age (<1 year) at start of treatment, tumor dissemination or progression within 18 months after start of chemotherapy. Progression-free survival rates declined with subsequent treatment-lines, yet remaining higher for patients with NF1. In non-NF1-associated tumors, vinblastine monotherapy vs platinum-based chemotherapy was noticeably less effective when used as second-line treatment. Yet, for the entire cohort, results did not favor a certain sequence of specific treatment options. Rather, all can be aligned as a portfolio of choices which need careful balancing of risks and benefits. Future molecular data may predict long-term tumor biology.}, language = {en} } @article{HenkeNandigamaErguen2020, author = {Henke, Erik and Nandigama, Rajender and Erg{\"u}n, S{\"u}leyman}, title = {Extracellular matrix in the tumor microenvironment and its impact on cancer therapy}, series = {Frontiers in Molecular Biosciences}, volume = {6}, journal = {Frontiers in Molecular Biosciences}, number = {160}, issn = {2296-889X}, doi = {10.3389/fmolb.2019.00160}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-199341}, year = {2020}, abstract = {Solid tumors are complex organ-like structures that consist not only of tumor cells but also of vasculature, extracellular matrix (ECM), stromal, and immune cells. Often, this tumor microenvironment (TME) comprises the larger part of the overall tumor mass. Like the other components of the TME, the ECM in solid tumors differs significantly from that in normal organs. Intratumoral signaling, transport mechanisms, metabolisms, oxygenation, and immunogenicity are strongly affected if not controlled by the ECM. Exerting this regulatory control, the ECM does not only influence malignancy and growth of the tumor but also its response toward therapy. Understanding the particularities of the ECM in solid tumor is necessary to develop approaches to interfere with its negative effect. In this review, we will also highlight the current understanding of the physical, cellular, and molecular mechanisms by which the pathological tumor ECM affects the efficiency of radio-, chemo-, and immunotherapy. Finally, we will discuss the various strategies to target and modify the tumor ECM and how they could be utilized to improve response to therapy.}, language = {en} }