Biosfera, l’ambiente che abitiamo. Crisi climatica e neoliberismo

La Biosfera è quel luogo singolare dell’Universo dove è nata e si è sviluppata la vita. È un prodotto del Sole. Noi, insieme a tutte le altre specie viventi, siamo l’esito di una sua lunga evoluzione durata milioni di anni nel corso dei quali sono nate e poi si sono estinte diverse specie di animali e vegetali, creando la meravigliosa biodiversità che ci circonda. L’equilibrio delicato di questo ecosistema è oggi a rischio e con esso la sopravvivenza della nostra specie, a causa dei cambiamenti climatici prodotti dall’eccesso di gas serra che stanno alterando equilibri millenari. Occorre invertire rapidamente i presupposti di questo sviluppo, se non vogliamo che la Terra torni a essere quell’ambiente inospitale precedente alla comparsa della vita. Per farlo occorre imboccare da subito la via della riconversione ecologica del nostro modello di sviluppo. Un cambiamento che presuppone di mettere in discussione i modelli di vita e il modo di pensare alla natura; in sostanza l’intera civiltà occidentale, fondata sul dominio della natura e delle sue leggi. Ma in ecologia non esistono scorciatoie: la tecnologia non può risolvere quei problemi che la tecnologia stessa ha creato. È infatti l’entropia a insegnarci che più consumiamo, più l’energia libera che ci resta a disposizione diminuisce. Un principio inesorabile destinato a prevalere su qualunque altro indicatore economico e sull’economia stessa, e dal quale ripensare il nostro modo di abitare questo pianeta

Real world data in the era of Immune Checkpoint Inhibitors (ICIs): Increasing evidence and future applications in lung cancer.

Immune checkpoint inhibitors (ICIs) targeting programmed death 1 (PD-1) and PD-ligand 1 (PD-L1) quickly subverted the standard of treatment in Non-Small Cell Lung Cancer (NSCLC), where they were first introduced in all comers previously treated advanced/metastatic NSCLC patients and subsequently in the first line of PD-L1 selected cases of metastatic and locally advanced disease. Treatment algorithm is an evolving landscape, where the introduction of front-line ICIs, with or without chemotherapy, unavoidably influences the following treatment lines. In this context, medical oncologists are currently facing many unclear issues, which have been not clarified so far by available data. Effectiveness and safety in special populations underrepresented in clinical trials - such as elderly, poor PS, hepatitis or human immunodeficiency virus-affected patients - are only a part of the unexplored side of ICIs in the real world. Indeed, pivotal randomized clinical trials (RCTs) often lack of external validity because eligibility criteria exclude some patient subgroups commonly treated in real-world clinical practice. Similarly, cost-effectiveness and sustainability of these innovative agents are important issues to be considered in the real-world. Though affected by several limitations, real-world evidence (RWE) studies allow to collect data regarding overall treated patients in clinical practice according to local authority regulations, overcoming the intrinsic limits of RCTs. The present review focuses on RWE about ICIs in lung cancer treatment, with particular reference to special patient populations, and discusses potential application of real-world data in a potential innovative drug development model

Immune-related adverse events (irAEs) in advanced non-small cell lung cancer (aNSCLC): Platelet-to-lymphocyte ratio (PLR) predicts the risk of development and relapse

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Fears and perception of the impact of COVID-19 on patients with lung cancer. A mono-institutional survey

In February 2020, Italy became one of the first countries to be plagued by the SARS-CoV-2 pandemic, COVID-19. In March 2020, the Italian government decreed a lockdown for the whole country, which overturned communication systems, hospital organization, and access to patients and their relatives and carers. This issue had a particular regard for cancer patients. Our Thoracic Oncology Division therefore reorganized patient access in order to reduce the risk of contagion and, at the same time, encourage the continuation of treatment. Our staff contacted all patients to inform them of any changes in treatment planning, check that they were taking safety measures, and ascertain their feelings and whether they had any COVID-19 symptoms. To better understand patients’ fears and expectations of during the pandemic period, we created a nine-question interview, administered from April to May 2020 to 156 patients with lung cancer. Patients were classified by age, sex, comorbidity, disease stage, prior treatment, and treatment type. The survey showed that during the pandemic period some patients experienced fear of COVID-19, in particular: women (55% vs. 33%), patients with comorbidities (24% vs. 9%), and patients who had already received prior insult (radiotherapy or surgery) on the lung (30% vs. 11%). In addition, the patients who received oral treatment at home or for whom intravenous treatment was delayed, experienced a sense of relief (90% and 72% respectively). However, only 21% of the patients were more afraid of COVID-19 than of their cancer, in particular patients with long-term (> 12 months) vs. short-term cancer diagnosis (28% vs. 12.5%, respectively). Furthermore, the quarantine period or even just the lockdown period alone, worsened the quality of life of some patients (40%), especially those in oral treatment (47%). Our data demonstrate how lung cancer patients are more afraid of their disease than of a world pandemic. Also this interview indirectly highlights the clinician’s major guiding principle in correctly and appropriately managing not just the patient’s expectations of their illness and its treatment, but also and especially of the patient’s fears

Oltre la monocoltura del turismo. Per un atlante delle resistenze e delle contro-progettualità

Questo libro risponde alla necessità di nominare un pericolo e anche, forse, ciò che salva. Il pericolo è lo stravolgimento mercificante che città e territori conoscono per effetto di una violenta colonizzazione turistica. Sappiamo che il turismo, specie nella sua pervasività monoculturale, produce impatti ed esternalità negative: al pari di una vera e propria politica industriale orienta scelte infrastrutturali, generando uno sfruttamento intensivo di risorse patrimoniali e ambientali; mina il diritto all’abitare e le tutele dei lavoratori; riduce le possibilità d’uso dello spazio pubblico. Ciò che salva è invece la capacità di resistenza che i nostri territori riescono a esprimere: una capacità che è insieme conflitto e contro- progettualità. La mappatura contenuta in questo Atlante costituisce un primo ritratto nazionale di questo potenziale salvifico. Si tratta di una partitura di frammenti indiziari, territorialmente ancorati, che tracciano possibili fuoriuscite dal paradigma estrattivo di tipo turistico. Un modo per mettere in discussione quelle logiche di reificazione territoriale per cui il consumo, la produzione e circolazione di merci costituisce l’unico orizzonte di senso che obbliga il presente a pensarsi senza alternative

Results of multilevel containment measures to better protect lung cancer patients from COVID-19. the IEO model

A novel coronavirus causing severe acute respiratory syndrome (SARS), named SARS-CoV-2, was identified at the end of 2019. The spread of coronavirus disease 2019 (COVID-19) has progressively expanded from China, involving several countries throughout the world, leading to the classification of the disease as a pandemic by the World Health Organization (WHO). According to published reports, COVID-19 severity and mortality are higher in elderly patients and those with active comorbidities. In particular, lung cancer patients were reported to be at high risk of pulmonary complications related to SARS-CoV2 infection. Therefore, the management of cancer care during the COVID-19 pandemic is a crucial issue, to which national and international oncology organizations have replied with recommendations concerning patients receiving anticancer treatments, delaying follow-up visits and limiting caregiver admission to the hospitals. In this historical moment, medical oncologists are required to consider the possibility to delay active treatment administration based on a case-by-case risk/benefit evaluation. Potential risks associated with COVID-19 infection should be considered, considering tumor histology and natural course, disease setting, clinical conditions, and disease burden, together with the expected benefit, toxicities (e.g., myelosuppression or interstitial lung disease), and response obtained from the planned or ongoing treatment. In this study, we report the results of proactive measures including social media, telemedicine, and telephone triage for screening patients with lung cancer during the COVID-19 outbreak in the European Institute of Oncology (Milan, Italy). Proactive management and containment measures, applied in a structured and daily way, has significantly aided the identification of advance patients with suspected symptoms related to COVID-19, limiting their admission to our cancer center; we have thus been more able to protect other patients from possible contamination and at the same time guarantee to the suspected patients the immediate treatment and evaluation in referral hospitals for COVID-19

Early Progression in Non-Small Cell Lung Cancer (NSCLC) with High PD-L1 Treated with Pembrolizumab in First-Line Setting: A Prognostic Scoring System Based on Clinical Features

Background: Pembrolizumab is approved in monotherapy for the first-line (1L) of advanced or metastatic NSCLC patients with high PD-L1 (≥50%). Despite a proportion of patients achieve long-term survival, about one-third of patients experience detrimental survival outcomes, including early death, hyperprogression, and fast progression. The impact of clinical factors on early progression (EP) development has not been widely explored. Methods: We designed a retrospective, multicenter study involving five Italian centers, in patients with metastatic NSCLC with PD-L1 ≥ 50%, treated with Pembrolizumab in a 1L setting. EP was defined as a progressive disease within three months from pembrolizumab initiation. Baseline clinical factors of patients with and without EP were collected and analyzed. Logistic regression was performed to identify clinical factors associated with EP and an EP prognostic score was developed based on the logistic model. Results: Overall, 321 out of 336 NSCLC patients treated with 1L pembrolizumab provided all the data for the analysis. EP occurred in 137 (42.7%) patients; the median PFS was 3.8 months (95% CI: 2.9–4.7), and median OS was not reached in the entire study population. Sex, Eastern Cooperative Oncology Group (ECOG) performance status (PS), steroids, metastatic sites ≥2, and the presence of liver/pleural metastasis were confirmed as independent factors for EP by multivariate analysis. By combining these factors, we developed an EP prognostic score ranging from 0–13, with three-risk group stratification: 0–2 (good prognosis), 3–6 (intermediate prognosis), and 7–13 (poor prognosis). The area under the curve (AUC) of the model was 0.76 (95% CI: 0.70–0.81). Conclusions: We identified six clinical factors independently associated with EP. We developed a prognostic score model for EP-risk to potentially improve clinical practice and patient selection for 1L pembrolizumab in NSCLC with high PD-L1, in the real-world clinical setting

Common Co-activation of AXL and CDCP1 in EGFR-mutation-positive Non-smallcell Lung Cancer Associated With Poor Prognosis.

Epidermal growth factor receptor (EGFR)-mutation-positive non-smallcell lung cancer (NSCLC) is incurable, despite high rates of response to EGFR tyrosine kinase inhibitors (TKIs). We investigated receptor tyrosine kinases (RTKs), Src family kinases and focal adhesion kinase (FAK) as genetic modifiers of innate resistance in EGFR-mutation-positive NSCLC. We performed gene expression analysis in two cohorts (Cohort 1 and Cohort 2) of EGFR-mutation-positive NSCLC patients treated with EGFR TKI. We evaluated the efficacy of gefitinib or osimertinib with the Src/FAK/Janus kinase 2 (JAK2) inhibitor, TPX0005 in vitro and in vivo. In Cohort 1, CUB domain-containing protein-1 (CDCP1) was an independent negative prognostic factor for progression-free survival (hazard ratio of 1.79, p=0.0407) and overall survival (hazard ratio of 2.23, p=0.0192). A two-gene model based on AXL and CDCP1 expression was strongly associated with the clinical outcome to EGFR TKIs, in both cohorts of patients. Our preclinical experiments revealed that several RTKs and non-RTKs, were up-regulated at baseline or after treatment with gefitinib or osimertinib. TPX-0005 plus EGFR TKI suppressed expression and activation of RTKs and downstream signaling intermediates. Co-expression of CDCP1 and AXL is often observed in EGFR-mutation-positive tumors, limiting the efficacy of EGFR TKIs. Co-treatment with EGFR TKI and TPX-0005 warrants testing

Introduzione

C\u2019\ue8 un "Popolo Nuovo" che preme ai confini d\u2019Europa. Un popolo che non torner\ue0 pi\uf9 indietro: ha tagliato i ponti alle proprie spalle; iniziato la lunga marcia verso l\u2019Impero di cui preme alle porte. Chiede conto e accoglienza a chi lo ha derubato nel corso dei secoli e ora cerca di ignorarlo. Sono gli abitanti di tutte le citt\ue0 coloniali della sponda sud del nostro mare, un tempo ponte; sono i figli delle \u201cmagnifiche sorti e progressive\u201d dell\u2019Occidente, faro della pi\uf9 grande civilt\ue0 del mondo e ora madre di un\u2019economia che divora l\u2019umanit\ue0. L\u2019accoglienza dei profughi \ue8 una delle sfide principali delle citt\ue0 contemporanee europee, la questione su cui si gioca il destino stesso della civilt\ue0 europea

La città e l'accoglienza

Un Popolo Nuovo arriva alla frontiera della civilissima Europa. Un Popolo composto dai “dannati della Terra”; da coloro che non hanno più nulla da perdere perché hanno perso tutto. Parte da lontano: dalla sponda sud del Mediterraneo e, prima ancora, dai paesi dell’Africa. Attraversa deserti, fiumi e mari; abbandona alle proprie spalle luoghi di morte: rovine in fiamme, terre desertificate dal furore predatorio del modello occidentale. All’Europa presenta il conto da pagare per gli anni di benessere da essa goduto estraendo ricchezze dai loro territori. Nelle città europee, un tempo luoghi di accoglienza e di ibridazioni etniche, sociali, religiose, si alzano muri per fermarne il cammino, per arrestarne la marcia silenziosa. Così la Fortezza-Europa pensa di difendere se stessa dall’“invasione”. Fuori da quei muri ci sono loro, i nuovi barbari, che fuggono da terre devastate; dentro quei muri i cittadini che hanno goduto dei dividendi provenienti dalle loro terre. Solo governi miopi e terrorizzati di perdere i loro antichi (e attuali) privilegi possono pensare di fermarli. L’Europa rischia la barbarie poiché si mostra incapace di affrontare la crisi da essa stessa provocata, il nuovo disordine mondiale prodotto dalla sua politica coloniale. I governi degli stati nazionali sono divisi e imbelli, tenacemente decisi a difendere una identità nazionale figlia di “mille letti” e spazzata via dalla Globalizzazione