Coexistence of three EGFR mutations in an NSCLC patient: A brief report

The epidermal growth factor receptor (EGFR) represents a molecular target for tyrosine kinase inhibitors for non-small cell lung cancer (NSCLC) patients with a mutation in the EGFR gene. Mutations of the EGFR gene that occur at a single position in NSCLC tissue are found as single, whereas two or more mutations on the same allele are poorly detected and investigated

Status of correlation between BMI and response to immunocheck-point inhibitor in advanced non-small-cell lung cancer

Recently, clinical evidence has raised BMI as an emerging prognostic factor for immunotherapy, regardless of cancer types. In this article we rewirw current data about correlation between BMI and response to immunocheck-point inhibitor in advanced non-small-cell lung cance

Ten Years of Severe Vitreomacular Traction Syndrome without Functional Damage Demonstrated by Optical Coherence Tomography

Introduction. To describe anatomical and functional features in one patient with 10 years of severe vitreomacular traction syndrome (VTS) without functional damage demonstrated by optical coherence tomography (OCT). Patient and Methods. One patient with a history of 10 years VTS, with best-corrected visual acuity of 20/32, was followed up with OCT. Follow-up examinations, 3 months for the first year after diagnosis and every 6 months for the subsequent years, were performed. Results. Follow-up examinations showed no change anatomically and functionally. Far and near visual acuity was unchanged. OCT by Heidelberg Spectralis did not evidence differences from Stratus OCT images. Conclusion. VTS can be stable anatomically and functionally for 10 years. OCT is a valuable diagnostic tool in understanding the configuration of vitreomacular adhesion, followup, and eventually planning the surgical approach for operating on VTS

Degradation rate of 5-fluorouracil in metastatic colorectal cancer. A new predictive outcome biomarker?

BACKGROUND: 5-FU based chemotherapy is the most common first line regimen used for metastatic colorectal cancer (mCRC). Identification of predictive markers of response to chemotherapy is a challenging approach for drug selection. The present study analyzes the predictive role of 5-FU degradation rate (5-FUDR) and genetic polymorphisms (MTHFR, TSER, DPYD) on survival. MATERIALS AND METHODS: Genetic polymorphisms of MTHFR, TSER and DPYD, and the 5-FUDR of homogenous patients with mCRC were retrospectively studied. Genetic markers and the 5-FUDR were correlated with clinical outcome. RESULTS: 133 patients affected by mCRC, treated with fluoropyrimidine-based chemotherapy from 2009 to 2014, were evaluated. Patients were classified into three metabolic classes, according to normal distribution of 5-FUDR in more than 1000 patients, as previously published: poor-metabolizer (PM) with 5-FU-DR ≤ 0,85 ng/ml/106 cells/min (8 pts); normal metabolizer with 0,85 < 5-FU-DR < 2,2 ng/ml/106 cells/min (119 pts); ultra-rapid metabolizer (UM) with 5-FU-DR ≥ 2,2 ng/ml/106 cells/min (6 pts). PM and UM groups showed a longer PFS respect to normal metabolizer group (14.5 and 11 months respectively vs 8 months; p = 0.029). A higher G3-4 toxicity rate was observed in PM and UM, respect to normal metabolizer (50% in both PM and UM vs 18%; p = 0.019). No significant associations between genes polymorphisms and outcomes or toxicities were observed. CONCLUSION: 5-FUDR seems to be significantly involved in predicting survival of patients who underwent 5-FU based CHT for mCRC. Although our findings require confirmation in large prospective studies, they reinforce the concept that individual genetic variation may allow personalized selection of chemotherapy to optimize clinical outcomes

Is hyperprogressive disease a specific phenomenom of immunotherapy?

Hyperprogressive disease (HPD) is a novel pattern of response during immunotherapy treatment. Several retrospective studies have evaluated its prevalence among various cancer types and, in particular, in non-small cell lung cancer patients, based on different definition criteria. If HPD is a just a typical phenomenon of immunotherapy is still an unsolved concern. This paper summarized the available data about HPD in other cancer treatments. Hyperprogressive disease (HPD) is a novel pattern of response during immunotherapy treatment. Several retrospective studies have evaluated its prevalence among various cancer types and, in particular, in non-small cell lung cancer patients, based on different definition criteria. If HPD is a just a typical phenomenon of immunotherapy is still an unsolved concern. This paper summarized the available data about HPD in other cancer treatments

Surgical and survival outcomes with perioperative or neoadjuvant immune-checkpoint inhibitors combined with platinum-based chemotherapy in resectable NSCLC: A systematic review and meta-analysis of randomised clinical trials

: The use of neoadjuvant or perioperative anti-PD(L)1 was recently tested in multiple clinical trials. We performed a systematic review and meta-analysis of randomised trials comparing neoadjuvant or perioperative chemoimmunotherapy to neoadjuvant chemotherapy in resectable NSCLC. Nine reports from 6 studies were included. Receipt of surgery was more frequent in the experimental arm (odds ratio, OR 1.39) as was pCR (OR 7.60). EFS was improved in the experimental arm (hazard ratio, HR 0.55) regardless of stage, histology, PD-L1 expression (PD-L1 negative, HR 0.74) and smoking exposure (never smokers, HR 0.67), as was OS (HR 0.67). Grade &gt;&nbsp;= 3 treatment-related adverse events were more frequent in the experimental arm (OR 1.22). The experimental treatment improved surgical outcomes, pCR rates, EFS and OS in stage II-IIIB, EGFR/ALK negative resectable NSCLC; confirmatory evidence is warranted for stage IIIB tumours and with higher maturity of the OS endpoint

Real-world data to build explainable trustworthy artificial intelligence models for prediction of immunotherapy efficacy in NSCLC patients

IntroductionArtificial Intelligence (AI) methods are being increasingly investigated as a means to generate predictive models applicable in the clinical practice. In this study, we developed a model to predict the efficacy of immunotherapy (IO) in patients with advanced non-small cell lung cancer (NSCLC) using eXplainable AI (XAI) Machine Learning (ML) methods. MethodsWe prospectively collected real-world data from patients with an advanced NSCLC condition receiving immune-checkpoint inhibitors (ICIs) either as a single agent or in combination with chemotherapy. With regards to six different outcomes - Disease Control Rate (DCR), Objective Response Rate (ORR), 6 and 24-month Overall Survival (OS6 and OS24), 3-months Progression-Free Survival (PFS3) and Time to Treatment Failure (TTF3) - we evaluated five different classification ML models: CatBoost (CB), Logistic Regression (LR), Neural Network (NN), Random Forest (RF) and Support Vector Machine (SVM). We used the Shapley Additive Explanation (SHAP) values to explain model predictions. ResultsOf 480 patients included in the study 407 received immunotherapy and 73 chemo- and immunotherapy. From all the ML models, CB performed the best for OS6 and TTF3, (accuracy 0.83 and 0.81, respectively). CB and LR reached accuracy of 0.75 and 0.73 for the outcome DCR. SHAP for CB demonstrated that the feature that strongly influences models' prediction for all three outcomes was Neutrophil to Lymphocyte Ratio (NLR). Performance Status (ECOG-PS) was an important feature for the outcomes OS6 and TTF3, while PD-L1, Line of IO and chemo-immunotherapy appeared to be more important in predicting DCR. ConclusionsIn this study we developed a ML algorithm based on real-world data, explained by SHAP techniques, and able to accurately predict the efficacy of immunotherapy in sets of NSCLC patients

Secondo Protocollo di Implementazione Misure per il contrasto e il contenimento della diffusione del virus Sars-CoV-2

Questo documento è da intendersi come protocollo di implementazione delle attività nel corso della attuale fase dell’emergenza pandemica e, con lo “Addendum al Documento di Valutazione dei Rischi dedicato al rischio biologico derivante da Sars-CoV-2, protocollo di sicurezza anti contagio, misure di prevenzione e protezione, formazione e informazione”, le Linee guida operative per i lavoratori e le lavoratrici dello “Istituto Nazionale di Astrofisica” Misure per il contrasto e il contenimento della diffusione del virus Sars-CoV-2 e il Protocollo di implementazione MAB (Musei Archivi Biblioteche) dell’INAF, Misure per il contrasto e il contenimento della diffusione del virus Sars-CoV-2, dei quali costituisce parte integrante, contiene misure per il contrasto e il contenimento della diffusione del virus Sars-CoV-2 per ogni Struttura di Ricerca INAF - Istituto Nazionale di Astrofisica e per la sede della Amministrazione Centrale, e sostituisce integralmente il “Protocollo di Implementazione Fase 2, Misure per il contrasto e il contenimento della diffusione del virus Sars-CoV-2” adottato con nota Circolare del Direttore Generale del 15 maggio 2020, numero 2482. Le disposizioni contenute nel Decreto del Presidente del Consiglio dei Ministri del 5 Agosto 2020 non si concretano in una totale “ripresa” delle attività di ricerca, ma semplicemente in un “ampliamento”, peraltro assai limitato e condizionato, delle stesse. È quindi necessario, in questa “Fase”, adottare misure che consentano, ove possibile, di svolgere le attività lavorative nella massima sicurezza. Pertanto, il Direttore Generale, d'intesa con il Presidente, il Direttore Scientifico e il Collegio dei Direttori di Struttura, ha avviato un processo volto a definire le azioni propedeutiche all’aggiornamento del “processo di implementazione” delle attività di ricerca e di laboratorio che potranno essere svolte in questa nuova “Fase”, nella consapevolezza che le stesse non devono arrecare alcun nocumento alla salute dei dipendenti dell'Ente e non devono, in alcun modo, favorire, direttamente o indirettamente, una recrudescenza della pandemia in atto, salvaguardando il bene supremo della salute pubblica, costituzionalmente tutelato, e che facciano, quindi, prevalere l'interesse generale sulle logiche puramente individualistiche (Circolare 2 maggio 2020, n. 2083, Allegato 9). Il presente documento tiene conto delle indicazioni contenute nei vari aggiornamenti dei provvedimenti Governativi e delle raccomandazioni delle Autorità Sanitarie Nazionali ed Internazionali, individua e definisce, per tutte le Strutture di Ricerca, le misure di sicurezza che dovranno essere adottate e i dispositivi da utilizzare, suscettibili di ulteriori e/o diverse implementazioni a livello locale, in ragione delle diverse peculiarità delle singole Strutture della specificità dei luoghi, delle esigenze logistiche, delle misure organizzative adottate e di eventuali aggiornamenti delle disposizioni normative. Resta inteso che in base all’evoluzione dello scenario epidemiologico, e nell’ottica della tutela della pubblica sicurezza, le misure indicate potranno essere rimodulate, anche in senso più restrittivo, e dovranno essere immediatamente applicate eventuali, future e più restrittive disposizioni governative Regionali e/o locali. Il Direttore Generale, il Direttore Scientifico e i Direttori di Struttura, ciascuno nell'ambito delle rispettive competenze, individuano idonee procedure di controllo dell'applicazione delle predette misure di sicurezza, con la collaborazione di RSPP, RLS e Medico Competente. I contenuti del documento saranno aggiornati ad ogni variazione della valutazione del rischio e delle misure di contrasto alla diffusione del Sars-CoV-19 da parte degli organi competenti. Ogni sede integra con eventuali indicazioni del Responsabile della Prevenzione e Protezione, del Medico Competente, del Rappresentante dei Lavoratori per la Sicurezza, anche in relazione all’ambiente specifico