Ricciuti B, Genova C, Crinò L, Libra M, Leonardi GC.Onco Targets Ther. 2019;12:3171-3179. Lucio Crinò has advised that affiliation 3 is incorrect. Thecorrect affiliation 3 should be as ...follows:Department of Medical Oncology, Istituto ScientificoRomagnolo per lo Studio e la Cura dei Tumori (IRSTIRCCS), Meldola, Italy.Read the original article
Due to the bad state of conservation, “Palazzo Governi”, a seventeenth-century building located in the old town district of “Stampace” in Cagliari (Sardinia, Italy), was subjected to restoration. ...Thus, according to the Italian Law n. 1089, the main façade colour must be reproduced, and therefore, its identification was required. The available samples looked fairly degraded, in particular as an easy plaster to crumble; so, some other analyses able to identify the degradation cause were performed. Two different approaches were adopted to attain the first goal, the visual colour assessment by a sensory panel (subjective) and the instrumental measurement by colorimetry (objective). Ion chromatography and inductively coupled plasma–optical emission spectroscopy analyses, as well as conductivity and pH measurements, were performed to evaluate the presence of water-soluble salts inside the plaster, as possible cause of degradation; the binder/aggregate ratio was also evaluated. A full mineralogical and petrographic characterisation of the materials constituting the samples, as well as the identification of their stratigraphy and some other morphologic and structural features suitable to highlight eventual forms of degradation, were performed by optical microscopy. Scanning electron microscopy coupled to X-ray microanalysis was been also used in order to confirm and/or to integrate data obtained by optical microscopy. The samples have been compared with two samples coming from two other buildings, also located in Sardinia, that looked in good conservation state. The results evidenced that the causes of degradation come from a high salt (especially sulphate) content and a scarce presence of binder in the plaster that can be imputed to a wrong initial composition and/ or to a leaching by acidic rain.
Preclinical studies have suggested that combining cytotoxic agents with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) to treat EGFR‐mutated tumors may increase their ...inhibitory effect depending on the order of drug administration. The antitumor efficacy of different treatment sequences using vinorelbine (VNB) and gefitinib (GEF) was investigated both in vitro and in vivo in non‐small cell lung cancer (NSCLC) cell lines with the rationale of potentially translating these findings into the clinical setting. The EGFR‐wild‐type A549 and the EGFR‐mutated (exon 21 L858R/exon 20 T790M) H1975 cell lines were treated as follows: GEF followed by VNB, VNB followed by GEF and the two drugs applied individually or concurrently. Results in vitro demonstrated that the sequence of VNB followed by GEF was significantly more active than single‐agent treatments. The expression of activated EGFR and its downstream pathway genes indicated that the increased cytotoxic effect of the VNB and GEF treatment sequence was accompanied by inhibition of EGFR, AKT and ERK1/2. Moreover, the increased inhibition of tumor growth after treatment with VNB followed by GEF was also confirmed in CD1‐nude mice that were xenotransplanted with H1975 cells (p < 0.0001). This effect was paralleled by a corresponding decrease in cancer glucose consumption, as assessed by micro‐positron emission tomography scans (p < 0.05). These preclinical findings in NSCLC cell lines, which are poorly responsive to EGFR‐TKIs, demonstrated that the sequential treatment of VNB followed by GEF induced a significant antitumor effect, which supports the translation of this treatment schedule into a clinical setting.
What's new?
Chemotherapy and EGFR‐TKIs may produce enhanced effect when combined together, but this is influenced by the choice of the drug and the sequence of administration. This study reports that NSCLC cell line carrying the EGFR‐L858R/T790M mutations showed increased sensitivity to the sequential schedule of vinorelbine followed by gefitinib in vitro and in vivo. These preclinical findings support the application of this treatment scheme in lung tumors poorly responsive to reversible EGFR‐TKIs.
Osimertinib represents the standard of care for the treatment of advanced non-small-cell lung cancer (NSCLC) harboring classical epidermal growth factor receptor (EGFR) mutations, constituting ...80%-90% of all EGFR alterations. In the remaining cases, an assorted group of uncommon alterations of EGFR (uEGFR) can be detected, which confer variable sensitivity to previous generations of EGFR inhibitors, overall with lower therapeutic activity. Data on osimertinib in this setting are limited and strongly warranted.
The ARTICUNO study retrospectively evaluated data on osimertinib activity from patients with advanced NSCLC harboring uEGFR treated in 21 clinical centers between August 2017 and March 2023. Data analysis was carried out with a descriptive aim. Investigators collected response data according to RECIST version 1.1 criteria. The median duration of response, progression-free survival (mPFS), and overall survival were estimated by the Kaplan–Meier method.
Eighty-six patients harboring uEGFR and treated with osimertinib were identified. Patients with ‘major’ uEGFR, that is, G719X, L861X, and S768I mutations (n = 51), had an overall response rate (ORR) and mPFS of 50% and 9 months, respectively. Variable outcomes were registered in cases with rarer ‘minor’ mutations (n = 27), with ORR and mPFS of 31% and 4 months, respectively. Among seven patients with exon 20 insertions, ORR was 14%, while the best outcome was registered among patients with compound mutations including at least one classical EGFR mutation (n = 13). Thirty patients presented brain metastases (BMs) and intracranial ORR and mPFS were 58% and 9 months, respectively. Amplification of EGFR or MET, TP53 mutations, and EGFR E709K emerged after osimertinib failure in a dataset of 18 patients with available rebiopsy.
The ARTICUNO study confirms the activity of osimertinib in patients with uEGFR, especially in those with compound uncommon–common mutations, or major uEGFR, even in the presence of BMs. Alterations at the E709 residue of EGFR are associated with resistance to osimertinib.
•Largest dataset of NSCLC with uncommon EGFR alterations treated with osimertinib.•Best outcomes with compound uncommon–common EGFR mutations and with G719X, L861X, or S768I.•Heterogeneous activity with rarer mutations; no response with alterations at E709 residue.•Confirmed activity in the central nervous system, with intracranial ORR of 58%.•Amplification of EGFR or MET, TP53 mutations, and EGFR E709K are putative mechanisms of resistance.
Bioenergy has the unique potential to provide a dispatchable and carbon-negative component to renewable energy portfolios. However, the sustainability, spatial distribution, and capacity for ...bioenergy are critically dependent on highly uncertain land-use impacts of biomass agriculture. Biomass cultivation on abandoned agriculture lands is thought to reduce land-use impacts relative to biomass production on currently used croplands. While coarse global estimates of abandoned agriculture lands have been used for large-scale bioenergy assessments, more practical technological and policy applications will require regional, high-resolution information on land availability. Here, we present US county-level estimates of the magnitude and distribution of abandoned cropland and potential bioenergy production on this land using remote sensing data, agriculture inventories, and land-use modeling. These abandoned land estimates are 61% larger than previous estimates for the US, mainly due to the coarse resolution of data applied in previous studies. We apply the land availability results to consider the capacity of biomass electricity to meet the seasonal energy storage requirement in a national energy system that is dominated by wind and solar electricity production. Bioenergy from abandoned croplands can supply most of the seasonal storage needs for a range of energy production scenarios, regions, and biomass yield estimates. These data provide the basis for further down-scaling using models of spatially gridded land-use areas as well as a range of applications for the exploration of bioenergy sustainability.
Purpose
Since the role of resistin was evaluated only in patients with non-small cell lung cancer (NSCLC) not treated with immunotherapy, we aimed to evaluate levels of resistin during immunotherapy ...(nivolumab) and its prognostic role with regard to OS.
Methods/patients
From a cohort of 78 patients with advanced NSCLC enrolled in a prospective study at Ospedale Policlinico San Martino in Genoa (Italy), 43 patients have been considered for this sub-analysis because of the availability of samples. Before and during nivolumab administration, clinical information and blood samples were collected and resistin, matrix metalloproteinase (MMP)-8, MMP-9, and myeloperoxidase were evaluated by enzyme-linked immunosorbent assay (ELISA).
Results
Median age was 71 with a prevalence of males and former smokers. Median resistin levels presented a peak at cycle 2 and then dropped down until the last cycle. Resistin correlated with all neutrophil degranulation products at cycle 1 (except for MMP-9) and at cycle 2 as well as with white blood cells and neutrophils. By a ROC curve analysis, a resistin value at cycle 2 of 19 ng/mL was tested as the best cut-off point for OS. Kaplan–Meier analysis demonstrated that patients above the resistin cut-off experienced a reduced OS (median OS 242.5 vs. 470 days,
p
= 0.0073), as confirmed by Cox proportional hazards regression analysis.
Conclusions
Resistin levels > 19 ng/mL at the time of the second cycle of nivolumab treatment independently predict a reduced OS in patients with advanced NSCLC.
Immune checkpoint inhibitors (ICIs) have revolutionized the management of multiple tumors, due to improved efficacy, quality of life, and safety. While most immune-related adverse events (irAEs) are ...mild and easily managed, in rare cases such events may be life-threatening, especially those affecting the neuromuscular and cardiac system. The management of neuromuscular/cardiac irAEs is not clear due to the lack of consistent data. Therefore, we carried out a pooled analysis of collected cases from selected Italian centers and individual data from published case reports and case series, in order to improve our understanding of these irAEs.
We collected retrospective data from patients treated in six Italian centers with ICIs (programmed cell death protein 1 or programmed death-ligand 1 and/or cytotoxic T-lymphocyte antigen 4 inhibitor) for any solid tumor who experienced neuromuscular and/or cardiovascular toxicity. Then, we carried out a search of case reports and series of neuromuscular/cardiac irAEs from ICIs with any solid tumor.
This analysis includes cases from Italian institutions (n = 18) and the case reports identified in our systematic literature search (n = 120), for a total of 138 patients. Among these patients, 50 (36.2%) had complete resolution of their neuromuscular/cardiac irAEs, in 21 (15.2%) cases there was a clinical improvement with mild sequelae, and 53 (38.4%) patients died as a result of the irAEs. Factors significantly associated with worse outcomes were early irAE onset, within the first two cycles of ICI (Fisher P < 0.0001), clinical manifestation of both myositis and myocarditis when compared with patients who developed only myositis or myocarditis (chi-square P = 0.0045), and the development of arrhythmia (Fisher P = 0.0070).
To the best of our knowledge, this is the largest collection of individual cases of immune-related myocarditis/myositis. Early irAE onset, concurrent development of myositis and myocarditis, as well as occurrence of arrhythmias are associated with worse outcomes and should encourage an aggressive immunomodulatory treatment.
•Myocarditis and myositis represent rare but potentially lethal irAEs.•There is no standard management of these irAEs due to the lack of consistent data.•This is the largest pooled analysis of individual cases of myocarditis/myositis related to ICIs.•Early onset and the concurrent manifestation of myositis and myocarditis are associated with worse outcomes.
Vinflunine belongs to the class of vinca alkaloids and acts by disrupting the microtubule dynamics during cell cycle; this agent is currently available for previously treated advanced transitional ...cell carcinoma in Europe. The aim of this invited review is to evaluate the potential role of vinflunine for the treatment of non-small cell lung cancer (NSCLC). Areas covered: The potential role of vinflunine in NSCLC is discussed on the basis of the available data, including full papers and meeting abstracts. Relevant preclinical studies describing the pharmacological properties of vinflunine are also included. The review also summarizes clinical studies, including phase I trials involving NSCLC among other tumors as well as phase II/III trials specifically addressing this malignancy. Additionally, the safety profile and the current regulatory status of vinflunine is discussed. Expert opinion: Vinflunine is active as single agent and as part of platinum-based combinations in NSCLC. It results non-inferior to docetaxel in a randomized phase III trial including previously treated NSCLC patients; additionally, its safety profile is generally considered manageable. Ultimately, further studies are needed to confirm the role of vinflunine in NSCLC, in consideration of the evolving evidence regarding targeted therapies and immune check-point inhibitors.
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