1.A fully automated image analysis method to quantify lung fibrosis in the bleomycin-induced rat model.
Seger S;Stritt M;Vezzali E;Nayler O;Hess P;Groenen PMA;Stalder AK PLoS One. 2018 Mar 16;13(3):e0193057. doi: 10.1371/journal.pone.0193057. eCollection 2018.
Intratracheal administration of bleomycin induces fibrosis in the lung, which is mainly assessed by histopathological grading that is subjective. Current literature highlights the need of reproducible and quantitative pulmonary fibrosis analysis. If some quantitative studies looked at fibrosis parameters separately, none of them quantitatively assessed both aspects: lung tissue remodeling and collagenization. To ensure reliable quantification, support vector machine learning was used on digitalized images to design a fully automated method that analyzes two important aspects of lung fibrosis: (i) areas having substantial tissue remodeling with appearance of dense fibrotic masses and (ii) collagen deposition. Fibrotic masses were identified on low magnification images and collagen detection was performed at high magnification. To insure a fully automated application the tissue classifier was trained on several independent studies that were performed over a period of four years. The detection method generates two different values that can be used to quantify lung fibrosis development: (i) percent area of fibrotic masses and (ii) percent of alveolar collagen. These two parameters were validated using independent studies from bleomycin- and saline-treated animals.
2.F-fluoromisonidazole PET and Activity of Neoadjuvant Nintedanib in Early HER2-Negative Breast Cancer: A Window-of-Opportunity Randomized Trial.
Quintela-Fandino M;Lluch A;Manso L;Calvo I;Cortes J;García-Saenz JA;Gil-Gil M;Martinez-Jánez N;Gonzalez-Martin A;Adrover E;de Andres R;Viñas G;Llombart-Cussac A;Alba E;Guerra J;Bermejo B;Zamora E;Moreno-Anton F;Pernas Simon S;Carrato A;Lopez-Alonso A;Escudero MJ;Campo R;Carrasco E;Palacios J;Mulero F;Colomer R Clin Cancer Res. 2017 Mar 15;23(6):1432-1441. doi: 10.1158/1078-0432.CCR-16-0738. Epub 2016 Sep 1.
Purpose:; We previously detected promising efficacy of neoadjuvant nintedanib (a multityrosine kinase inhibitor, TKI) in early HER2-negative breast cancer. In a preclinical study, we monitored stromal hypoxia with ;18;F-fluoromisonidazole-positron emission tomography (18F-FMISO-PET); we found that reoxygenation of tumors (or lack of it) during a window-of-opportunity (WoO) treatment with TKIs correlated with the benefit (or lack of it) from TKI-plus-chemotherapy combinations. We studied the predictive role of 18F-FMISO-PET for the TKI nintedanib in the neoadjuvant setting in a phase II WoO randomized trial.;Experimental Design:; Patients were randomized to a 14-day WoO of nintedanib preceded and followed by an 18F-FMISO-PET, followed by nintedanib plus weekly paclitaxel (Arm A) or an 18F-FMISO-PET followed by weekly paclitaxel (Arm B) before surgery. The endpoint was residual cancer burden (RCB). The objective was to detect the patients with no response (RCB-III) on the basis of the baseline or evolutive 18F-FMISO-PET values/changes.;Results:; One-hundred and thirty HER2-negative patients were randomized. Seventeen (27.9%), 34 (55.7%), and 8 (13.1%) patients had an RCB of III, II, and I/0, respectively, in Arm A.
3.Emerging multitarget tyrosine kinase inhibitors in the treatment of neuroendocrine neoplasms.
Grillo F;Florio T;Ferraù F;Kara E;Fanciulli G;Faggiano A;Colao A;NIKE Group Endocr Relat Cancer. 2018 Sep;25(9):R453-R466. doi: 10.1530/ERC-17-0531. Epub 2018 May 16.
In the last few years, the therapeutic approach for neuroendocrine neoplasms (NENs) has changed dramatically following the approval of several novel targeted treatments. The multitarget tyrosine kinase inhibitor (MTKI), sunitinib malate, has been approved by Regulatory Agencies in pancreatic NENs. The MTKI class, however, includes several other molecules (approved for other conditions), which are currently being studied in NENs. An in-depth review on the studies published on the MTKIs in neuroendocrine tumors such as axitinib, cabozantinib, famitinib, lenvatinib, nintedanib, pazopanib, sorafenib and sulfatinib was performed. Furthermore, we extensively searched on the Clinical Trial Registries databases worldwide, in order to collect information on the ongoing clinical trials related to this topic. Our systematic analysis on emerging MTKIs in the treatment of gastroenteropancreatic and lung NENs identifies ;in vitro; and ;in vivo; studies, which demonstrate anti-tumor activity of diverse MTKIs on neuroendocrine cells and tumors. Moreover, for the first time in the literature, we report an updated view concerning the upcoming clinical trials in this field: presently, phase I, II and III clinical trials are ongoing and will include, overall, a staggering 1667 patients.