Detection of ROSI rearrangement in non-small cell lung cancer: Current and future perspectives

ROS1 rearrangement characterizes a small subset (1%–2%) of non-small cell lung cancer and is associated with slight/never smoking patients and adenocarcinoma histology. Identification of ROS1 rearrangement is mandatory to permit targeted therapy with specific inhibitors, demonstrating a significantly better survival when compared with conventional chemotherapy. Detection of ROS1 rearrangement is based on in situ (immunohistochemistry, fluorescence in situ hybridization) and extractive non-in situ assays. While fluorescence in situ hybridization still represents the gold standard in clinical trials, this technique may fail to recognize rearrangements of ROS1 with some gene fusion partner. On the other hand, immunohistochemistry is the most cost-effective screening technique, but it seems to be characterized by low specificity. Extractive molecular assays are expensive and laborious methods, but they specifically recognize almost all ROS1 fusions using a limited amount of mRNA even from formalin-fixed, paraffin-embedded tumor tissues. This review is a discussion on the present and futuristic diagnostic scenario of ROS1 identification in lung cancer

Does V600E BRAF mutation predict vinorelbine efficacy? A proof-of-concept from a lung micropapillary adenocarcinoma metastatic to the breast

BRAF mutations occur in about 3% of all lung adenocarcinomas and V600E missense mutation characterizes about half of BRAFmutated lung adenocarcinomas and is significantly associated with micropapillary pattern and shorter disease-free and overall survival rates. In this report, we report a challenging case of a patient with a metastatic micropapillary adenocarcinoma of the lung harbouring V600E BRAF mutation who experienced a surprising protracted clinical response to metronomic vinorelbine. The possible association between the V600E BRAF mutation pathway and the effective use of vinca alkaloid is discussed

ROS1 rearrangements are uncommon in biliary tract cancers

Biliary tract cancers (BTCs) are a pool of diseases with poor prognosis and there is no orphan drug available. Currently, no molecular targets have been tested as druggable oncogenic drivers. C‑ros oncogene 1 (ROS1) rearrangements have been previously described in various tumors, including BTCs; however, data regarding their incidence and biological significance are controversial. Therefore, a retrospective multi‑ center study was performed to assess the incidence of ROS1 rearrangements in BTCs by means of immunohistochemistry and fluorescence in situ hybridization (FISH). The present study failed to demonstrate ROS1 expression in a multicenter series of 150 cases with BTCs and revealed that D4D6 was the most specific clone compared with other ROS1 primary antibodies, namely PA1‑30318 and EPMGHR2. Notably, nega‑ tive results obtained with D4D6 completely matched to data sorted out by FISH analysis, thus confirming a lack of ROS1 gene rearrangements in BTCs and false positive results when PA1‑30318 and EPMGHR2 clones were used. These results suggest that ROS1 rearrangements may not be targets for molecular therapy of BTCs with specific inhibitors

Correction to: Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial (Journal of Translational Medicine, (2020), 18, 1, (405), 10.1186/s12967-020-02573-9)

Following publication of the original article [1] the authors identified that the collaborators of the TOCIVID-19 investigators, Italy were only available in the supplementary file. The original article has been updated so that the collaborators are correctly acknowledged. For clarity, all collaborators are listed in this correction article

Tocilizumab for patients with COVID-19 pneumonia. The single-arm TOCIVID-19 prospective trial

BackgroundTocilizumab blocks pro-inflammatory activity of interleukin-6 (IL-6), involved in pathogenesis of pneumonia the most frequent cause of death in COVID-19 patients.MethodsA multicenter, single-arm, hypothesis-driven trial was planned, according to a phase 2 design, to study the effect of tocilizumab on lethality rates at 14 and 30 days (co-primary endpoints, a priori expected rates being 20 and 35%, respectively). A further prospective cohort of patients, consecutively enrolled after the first cohort was accomplished, was used as a secondary validation dataset. The two cohorts were evaluated jointly in an exploratory multivariable logistic regression model to assess prognostic variables on survival.ResultsIn the primary intention-to-treat (ITT) phase 2 population, 180/301 (59.8%) subjects received tocilizumab, and 67 deaths were observed overall. Lethality rates were equal to 18.4% (97.5% CI: 13.6-24.0, P=0.52) and 22.4% (97.5% CI: 17.2-28.3, P<0.001) at 14 and 30 days, respectively. Lethality rates were lower in the validation dataset, that included 920 patients. No signal of specific drug toxicity was reported. In the exploratory multivariable logistic regression analysis, older age and lower PaO2/FiO2 ratio negatively affected survival, while the concurrent use of steroids was associated with greater survival. A statistically significant interaction was found between tocilizumab and respiratory support, suggesting that tocilizumab might be more effective in patients not requiring mechanical respiratory support at baseline.ConclusionsTocilizumab reduced lethality rate at 30 days compared with null hypothesis, without significant toxicity. Possibly, this effect could be limited to patients not requiring mechanical respiratory support at baseline.Registration EudraCT (2020-001110-38); clinicaltrials.gov (NCT04317092)