Emanuele Vita
@medical oncologist
UOSD Oncologia Toraco-Polmonare
Fondazione Policlinico Universitario A Gemelli
RESEARCH, TEACHING, or OTHER INTERESTS
Oncology
Scopus Publications
Scopus Publications
Alessandro Leonetti, Fabiana Perrone, Matteo Puntoni, Giuseppe Maglietta, Paola Bordi, Emilio Bria, Emanuele Vita, Francesco Gelsomino, Andrea De Giglio, Alain Gelibter,et al.
Elsevier BV
Arsela Prelaj, Monica Ganzinelli, Leonardo Provenzano, Laura Mazzeo, Giuseppe Viscardi, Giulio Metro, Giulia Galli, Francesco Agustoni, Carminia Maria Della Corte, Andrea Spagnoletti,et al.
Elsevier BV
Emanuele Vita, Federico Monaca, Domenico Milardi, Luca Mastrantoni, Alessio Stefani, Edoardo Vergani, Jacopo Russo, Diletta Barone, Ileana Sparagna, Antonio Vitale,et al.
Wiley
ABSTRACTBackgroundIt is reported that treatment with anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) induces hypogonadism both in male patients with ALK‐positive cancer and in murine models.MethodsIn this study, three groups, including an experimental group of male patients with ALK‐positive, advanced nonsmall cell lung cancer (ANSCLC) who were receiving alectinib (cohort A), a control group of female patients with ALK‐positive ANSCLC who were receiving alectinib (cohort B), and a control group of male patients with ALK‐negative ANSCLC (cohort C), prospectively underwent a full hormone assessment for androgen deficiency at 8 weeks after the start of treatment and in case of reported suspected symptoms. Patients with major sexual dysfunctions were referred to an endocrinologist.ResultsNinety‐five patients were consecutively enrolled onto the study. Among sixty‐eight male patients, both median total testosterone levels (2.93 vs. 4.92 ng/ml; p = .0001) and free testosterone levels (0.11 vs. 0.17 pg/ml; p = .0002) were significantly lower in ALK‐positive ANSCLC patients in cohort A compared with ALK‐negative patients in cohort C; conversely, median FSH (10.32 vs. 17.52 mUI/ml; p = .0059) and LH levels (4.72 vs. 7.49 mUI/ml; p = .0131) were significantly higher in cohort C compared to cohort A. Median inhibin B levels were higher in ALK‐positive male patients (74.3 vs. 44.24 pg/ml; p = .0038), but all patients had inhibin B values within the normal range. The percentage of male patients who had positive scores on the Androgen Deficiency in Aging Males (ADAM) questionnaire was 62% in cohort A and 26.8% in cohort C, including eight patients who reported at least one major symptom and were referred to Andrology Unit. No significant differences in the endocrine assessment were reported between cohorts A and B.ConclusionsSymptoms of androgen deficiency should be tracked in male patients with ALK‐positive ANSCLC who are receiving alectinib, and testosterone replacement should be considered, as appropriate.
Eleonora De Luca, Pietro Sollena, Lucia Di Nardo, Ettore D’Argento, Emanuele Vita, Giampaolo Tortora, and Ketty Peris
Hindawi Limited
Papulopustular rash (PPR) is the most frequent cutaneous adverse event during treatment with epidermal growth factor receptor inhibitors (EGFRis). Although often mild in severity, it can impair patients’ quality of life and may also be a reason for discontinuing or changing the dose of the antineoplastic treatment. During COVID-19 pandemics, the use of surgical masks drastically increased and it had an impact on the face skin microenvironment, favoring the worsening of dermatological pathologies. We reported the relapse of PPR in patients treated with EGFR inhibitors who consistently wore face masks (>6 hours/day). All the patients developed the PPR within 6 months of starting mask use. Compared to the PPR occurred previously, after mask use, the skin eruption was more severe and affected mainly those regions of the face which came into contact with the mask. Patients received topical or systemic treatment, obtaining complete response in 65.7% of the cases. The establishment of an early treatment for the PPR allows continuing the oncologic treatment, without any suspension which could result in a decreased oncologic outcome. In conclusion, when using these devices, it is recommended to use special precautions, particularly in oncologic patients, by using a daily prophylactic skincare and replacing masks regularly with regular and frequent breaks.
Filippo Lococo, Luca Boldrini, Charles-Davies Diepriye, Jessica Evangelista, Camilla Nero, Sara Flamini, Angelo Minucci, Elisa De Paolis, Emanuele Vita, Alfredo Cesario,et al.
Springer Science and Business Media LLC
Filippo Lococo, Luca Boldrini, Charles-Davies Diepriye, Jessica Evangelista, Camilla Nero, Sara Flamini, Angelo Minucci, Elisa De Paolis, Emanuele Vita, Alfredo Cesario,et al.
Springer Science and Business Media LLC
Abstract Background The current management of lung cancer patients has reached a high level of complexity. Indeed, besides the traditional clinical variables (e.g., age, sex, TNM stage), new omics data have recently been introduced in clinical practice, thereby making more complex the decision-making process. With the advent of Artificial intelligence (AI) techniques, various omics datasets may be used to create more accurate predictive models paving the way for a better care in lung cancer patients. Methods The LANTERN study is a multi-center observational clinical trial involving a multidisciplinary consortium of five institutions from different European countries. The aim of this trial is to develop accurate several predictive models for lung cancer patients, through the creation of Digital Human Avatars (DHA), defined as digital representations of patients using various omics-based variables and integrating well-established clinical factors with genomic data, quantitative imaging data etc. A total of 600 lung cancer patients will be prospectively enrolled by the recruiting centers and multi-omics data will be collected. Data will then be modelled and parameterized in an experimental context of cutting-edge big data analysis. All data variables will be recorded according to a shared common ontology based on variable-specific domains in order to enhance their direct actionability. An exploratory analysis will then initiate the biomarker identification process. The second phase of the project will focus on creating multiple multivariate models trained though advanced machine learning (ML) and AI techniques for the specific areas of interest. Finally, the developed models will be validated in order to test their robustness, transferability and generalizability, leading to the development of the DHA. All the potential clinical and scientific stakeholders will be involved in the DHA development process. The main goals aim of LANTERN project are: i) To develop predictive models for lung cancer diagnosis and histological characterization; (ii) to set up personalized predictive models for individual-specific treatments; iii) to enable feedback data loops for preventive healthcare strategies and quality of life management. Discussion The LANTERN project will develop a predictive platform based on integration of multi-omics data. This will enhance the generation of important and valuable information assets, in order to identify new biomarkers that can be used for early detection, improved tumor diagnosis and personalization of treatment protocols. Ethics Committee approval number 5420 − 0002485/23 from Fondazione Policlinico Universitario Agostino Gemelli IRCCS – Università Cattolica del Sacro Cuore Ethics Committee. Trial registration clinicaltrial.gov - NCT05802771.
Emanuele Vita, Alessio Stefani, Geny Piro, Luca Mastrantoni, Marco Cintoni, Giuseppe Cicchetti, Ileana Sparagna, Federico Monaca, Guido Horn, Jacopo Russo,et al.
Springer Science and Business Media LLC
Abstract Background Only few ES-SCLC patients experience long-term survival benefit by maintenance IT. Adipokines-induced metabolic meta-inflammation has been related to enhanced responsiveness to IT in obese patients; however, their prognostic role in SCLC is currently controversial. Methods Pre-treatment CT scan was used for determining distribution of abdominal adiposity, and blood samples were collected at fasting for measuring glycemia, insulin, ghrelin, leptin and adipokines (TNF-α, IFN-γ, IL-6 and MCP-1). Patients with known history of DM type II or metabolic syndrome with HOMA index > 2.5 were considered insulin resistant (IR). Results In ES-SCLC pts receiving maintenance IT, increased leptin concentration and higher leptin/visceral adipose tissue (VAT) ratio were significantly associated with prolonged PFS. By applying a hierarchical clustering algorithm, we identified a cluster of patients characterized by higher leptin values and lower pro-inflammatory cytokines (TNF-α, IFN-γ and IL-6) who experienced longer PFS (13.2 vs 8.05 months; HR: 0.42 [0.18–0.93] p = 0.02) and OS (18.04 vs 12.09 mo; HR: 0.53 [0.25–1.29] p = 0.07). Conclusions Adipokines can play a crucial role to determining effectiveness of anti-cancer immunotherapy. The role of metabolic immune dysfunctions needs further pre-clinical validation and is currently investigated in the larger prospective cohort.
Filippo Lococo, Alessandra Cancellieri, Marco Chiappetta, Alessandro Leonetti, Giuseppe Cardillo, Francesca Zanelli, Giuseppe Mangiameli, Luca Toschi, Gianluca Guggino, Francesco Jacopo Romano,et al.
Elsevier BV
Marco Chiappetta, Diomira Tabacco, Amedeo Giuseppe Iaffaldano, Jessica Evangelista, Maria Teresa Congedo, Carolina Sassorossi, Elisa Meacci, Ettore D’Argento, Emilio Bria, Emanuele Vita,et al.
MDPI AG
BACKGROUND: The aim of this study is to analyze the prognostic factors in patients that underwent induction therapy and surgery for clinical stage III NSCLC. METHODS: Clinical and pathological characteristics of stage III NSCLC patients for N2 involvement that underwent neoadjuvant treatment (NAD) and surgery from 1/01/1998 to 31/12/2017 were collected and retrospectively analyzed. Tumor characteristics, yClinical, yPathological stage and lymph node characteristics were correlated to Overall Survival (OS). RESULTS: The analysis was conducted on 180 patients. Five-year OS (5YOS) was 50.9%. Univariable analysis results revealed old age (p = 0.003), clinical N2 post-NAD (p = 0.01), pneumonectomy (0.005), persistent pathological N2 (p = 0.039, HR 1.9, 95% CI 1.09–2.68) and adjuvant therapy absence (p = 0.049) as significant negative prognostic factors. Multivariable analysis confirmed pN0N1 (p = 0.02, HR 0.29, 95% CI 0.13–0.62) as a favorable independent prognostic factor and adjuvant therapy absence (p = 0.012, HR 2.61, 95% CI 1.23–5.50) as a negative prognostic factor. Patients with persistent N2 presented a 5YOS of 35.3% vs. 55.8% in pN0N1 patients. Regarding lymph node parameters, the lymph node ratio (NR) significantly correlated with OS: 5YOS of 67.6% in patients with NR < 50% vs. 29.5% in NR > 50% (p = 0.029). CONCLUSION: Clinical response aided the stratification of prognosis in patients that underwent multimodal treatment for stage III NSCLC. Adjuvant therapy seemed to be an important option in these patients, while node ratio was a strong prognosticator in patients with persistent nodal involvement.
Alessio Stefani, Geny Piro, Francesco Schietroma, Alessandro Strusi, Emanuele Vita, Simone Fiorani, Diletta Barone, Federico Monaca, Ileana Sparagna, Giustina Valente,et al.
Frontiers Media SA
Lung cancer is one of the most aggressive malignancies, classified into two major histological subtypes: non-small cell lung cancer (NSCLC), that accounts for about 85% of new diagnosis, and small cell lung cancer (SCLC), the other 15%. In the case of NSCLC, comprehensive genome sequencing has allowed the identification of an increasing number of actionable targets, which have become the cornerstone of treatment in the advanced setting. On the other hand, the concept of oncogene-addiction is lacking in SCLC, and the only innovation of the last 30 years has been the introduction of immune checkpoint inhibitors in extensive stage disease. Dysregulation of cell cycle is a fundamental step in carcinogenesis, and Aurora kinases (AURKs) are a family of serine/threonine kinases that play a crucial role in the correct advance through the steps of the cycle. Hyperexpression of Aurora kinases is a common protumorigenic pathway in many cancer types, including NSCLC and SCLC; in addition, different mechanisms of resistance to anticancer drugs rely on AURK expression. Hence, small molecule inhibitors of AURKs have been developed in recent years and tested in several malignancies, with different results. The aim of this review is to analyze the current evidences of AURK inhibition in lung cancer, starting from preclinical rationale to finish with clinical trials available up to now.
Filippo Lococo, Marco Chiappetta, Jessica Evangelista, Isabella Sperduti, Dania Nachira, Venanzio Porziella, Maria Teresa Congedo, Emilio Bria, Emanuele Vita, Alfredo Cesario,et al.
Springer Science and Business Media LLC
Anastasios Gkountakos, Giovanni Centonze, Emanuele Vita, Lorenzo Belluomini, Michele Milella, Emilio Bria, Massimo Milione, Aldo Scarpa, and Michele Simbolo
MDPI AG
The use of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) as first-line treatment in patients with lung adenocarcinoma (LUAD) harboring EGFR-activating mutations has resulted in a dramatic improvement in the management of the disease. However, the long-term clinical benefit is inevitably compromised by multiple resistance mechanisms. Accumulating evidence suggests that metabolic landscape remodeling is one of the mechanisms that EGFR-mutant LUAD cells activate, thus acquiring higher plasticity, tolerating EGFR TKI-mediated cytotoxic stress, and sustaining their oncogenic phenotype. Several metabolic pathways are upregulated in EGFR TKI-resistant models modulating the levels of numerous metabolites such as lipids, carbohydrates, and metabolic enzymes which have been suggested as potential mediators of resistance to EGFR TKIs. Moreover, metabolites have been shown to carry signals and stimulate oncogenic pathways and tumor microenvironment (TME) components such as fibroblasts, facilitating resistance to EGFR TKIs in various ways. Interestingly, metabolic signatures could function as predictive biomarkers of EGFR TKI efficacy, accurately classifying patients with EGFR-mutant LUAD. In this review, we present the identified metabolic rewiring mechanisms and how these act either independently or in concert with epigenetic or TME elements to orchestrate EGFR TKI resistance. Moreover, we discuss potential nutrient dependencies that emerge, highlighting them as candidate druggable metabolic vulnerabilities with already approved drugs which, in combination with EGFR TKIs, might counteract the solid challenge of resistance, hopefully prolonging the clinical benefit.
Miriam Grazia Ferrara, Alessio Stefani, Sara Pilotto, Carmine Carbone, Emanuele Vita, Mariantonietta Di Salvatore, Ettore D’Argento, Ileana Sparagna, Federico Monaca, Giustina Valente,et al.
Frontiers Media SA
Non-small cell lung cancer (NSCLC) represents the perfect paradigm of ‘precision medicine’ due to its complex intratumoral heterogeneity. It is truly characterized by a range of molecular alterations that can deeply influence the natural history of this disease. Several molecular alterations have been found over time, paving the road to biomarker-driven therapy and radically changing the prognosis of ‘oncogene addicted’ NSCLC patients. Kirsten rat sarcoma (KRAS) mutations are present in up to 30% of NSCLC (especially in adenocarcinoma histotype) and have been identified decades ago. Since its discovery, its molecular characteristics and its marked affinity to a specific substrate have led to define KRAS as an undruggable alteration. Despite that, many attempts have been made to develop drugs capable of targeting KRAS signaling but, until a few years ago, these efforts have been unsuccessful. Comprehensive genomic profiling and wide-spectrum analysis of genetic alterations have only recently allowed to identify different types of KRAS mutations. This tricky step has finally opened new frontiers in the treatment approach of KRAS-mutant patients and might hopefully increase their prognosis and quality of life. In this review, we aim to highlight the most interesting aspects of (epi)genetic KRAS features, hoping to light the way to the state of art of targeting KRAS in NSCLC.
Miriam Grazia Ferrara, Maurizio Martini, Ettore D’Argento, Chiara Forcella, Emanuele Vita, Vincenzo Di Noia, Isabella Sperduti, Mirna Bilotta, Marta Ribelli, Paola Damiano,et al.
Elsevier BV
Antonio Passaro, Silvia Novello, Diana Giannarelli, Emilio Bria, Domenico Galetta, Alain Gelibter, Maria Lucia Reale, Simona Carnio, Emanuele Vita, Alessio Stefani,et al.
MDPI AG
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.
Emanuele Vita, Alessio Stefani, Mariantonietta Di Salvatore, Marco Chiappetta, Filippo Lococo, Stefano Margaritora, Giampaolo Tortora, and Emilio Bria
MDPI AG
Malignant pleural mesothelioma (MPM) is a rare malignancy characterized by very poor prognosis and lack of treatment options. Immunotherapy has rapidly emerged as an effective tool for MPM, particularly for tumors of non-epithelioid histology. At the same time, comprehensive genomic sequencing may open the way to new-generation targeted-drugs able to hit specific MPM molecular vulnerabilities. These innovations will possibly enrich, but also dramatically complicate, the elucidation of treatment algorithms. Multidisciplinary integration is urgently needed.
Vincenzo Di Noia, Ettore D’Argento, Sara Pilotto, Emanuele Vita, Miriam Grazia Ferrara, Paola Damiano, Marta Ribelli, Antonella Cannella, Antonella Virtuoso, Andrea Fattorossi,et al.
Springer Science and Business Media LLC
AbstractBackgroundIdentifying the patients who may benefit the most from immune checkpoints inhibitors remains a great challenge for clinicians. Here we investigate on blood serum amyloid A (SAA) as biomarker of response to upfront pembrolizumab in patients with advanced non-small-cell lung cancer (NSCLC).MethodsPatients with PD-L1 ≥ 50% receiving upfront pembrolizumab (P cohort) and with PD-L1 0–49% treated with chemotherapy (CT cohort) were evaluated for blood SAA and radiological response at baseline and every 9 weeks. Endpoints were response rate (RR) according to RECIST1.1, progression-free (PFS) and overall survival (OS). The most accurate SAA cut-off to predict response was established with ROC analysis in the P cohort.ResultsIn the P Cohort (n = 42), the overall RR was 38%. After a median follow-up of 18.5 months (mo), baseline SAA ≤ the ROC-derived cut-off (29.9 mg/L;n = 28/42.67%) was significantly associated with higher RR (53.6 versus 7.1%; OR15, 95% CI 1.72–130.7,p = 0.009), longer PFS (17.4 versus 2.1 mo;p < 0.0001) and OS (not reached versus 7.2mo;p < 0.0001) compared with SAA > 29.9 mg/L. In multivariate analysis, low SAA positively affects PFS (p = 0.001) and OS (p = 0.048) irrespective of ECOG PS, number of metastatic sites and pleural effusion. SAA monitoring (n = 40) was also significantly associated with survival endpoints: median PFS 17.4 versus 2.1 mo and median OS not reached versus 7.2 mo when SAA remained low (n = 14) and high (n = 12), respectively. In the CT Cohort (n = 30), RR was not affected by SAA level (p > 0.05) while low SAA at baseline (n = 17) was associated with better PFS (HR 0.38, 95% CI 0.16–0.90,p = 0.006) and OS (HR 0.25, 95% CI 0.09–0.67,p < 0.001).ConclusionLow SAA predicts good survival outcomes irrespective of treatment for advanced NSCLC patients and higher likelihood of response to upfront pembrolizumab only. The strong prognostic value might be exploited to easily identify patients most likely to benefit from immunotherapy. A further study (FoRECATT-2) is ongoing to confirm results in a larger sample size and to investigate the effect of SAA on immune response in vitro assays.
Miriam Grazia Ferrara, Alessio Stefani, Michele Simbolo, Sara Pilotto, Maurizio Martini, Filippo Lococo, Emanuele Vita, Marco Chiappetta, Alessandra Cancellieri, Ettore D’Argento,et al.
Frontiers Media SA
Large-cell neuroendocrine carcinomas of the lung (LCNECs) are rare tumors representing 1–3% of all primary lung cancers. Patients with LCNEC are predominantly male, older, and heavy smokers. Histologically, these tumors are characterized by large cells with abundant cytoplasm, high mitotic rate, and neuroendocrine immunohistochemistry-detected markers (chromogranin-A, synaptophysin, and CD56). In 2015 the World Health Organization classified LCNEC as a distinct subtype of pulmonary large-cell carcinoma and, therefore, as a subtype of non-small cell lung carcinoma (NSCLC). Because of the small-sized tissue samples and the likeness to other neuroendocrine tumors, the histological diagnosis of LCNEC remains difficult. Clinically, the prognosis of metastatic LCNECs is poor, with high rates of recurrence after surgery alone and overall survival of approximately 35% at 5 years, even for patients with early stage disease that is dramatically shorter compared with other NSCLC subtypes. First-line treatment options have been largely discussed but with limited data based on phase II studies with small sample sizes, and there are no second-line well defined treatments. To date, no standard treatment regimen has been developed, and how to treat LCNEC is still on debate. In the immunotherapy and targeted therapy era, in which NSCLC treatment strategies have been radically reshaped, a few data are available regarding these opportunities in LCNEC. Due to lack of knowledge in this field, many efforts have been done for a deeper understanding of the biological and molecular characteristics of LCNEC. Next generation sequencing analyses have identified subtypes of LCNEC that may be relevant for prognosis and response to therapy, but further studies are needed to better define the clinical impact of these results. Moreover, scarce data exist about PD-L1 expression in LCNEC and its predictive value in this histotype with regard to immunotherapy efficacy. In the literature some cases are reported concerning LCNEC metastatic patients carrying driver mutations, especially EGFR alterations, showing targeted therapy efficacy in this setting of disease. Due to the rarity and the challenging understanding of LCNEC, in this review we aim to summarize the management options currently available for treatment of LCNEC.
Filippo Lococo, Carolina Sassorossi, Dania Nachira, Marco Chiappetta, Leonardo Petracca Ciavarella, Emanuele Vita, Luca Boldrini, Jessica Evangelista, Alfredo Cesario, Emilio Bria,et al.
MDPI AG
Background: Outcomes for locally advanced NSCLC with pathological complete response (pCR), i.e., pT0N0 after induction chemoradiotherapy (IT), have been seldom investigated. Herein, long-term results, in this highly selected group of patients, have been evaluated with the aim to identify prognostic predictive factors. Methods: Patients affected by locally advanced NSCLC (cT1-T4/N0-2/M0) who underwent IT, possibly following surgery, from January 1992 to December 2019, were considered for this retrospective analysis. Survival rates and prognostic factors have been studied with Kaplan-Meier analysis, log-rank and Cox regression analysis. Results: Three-hundred and forty-three consecutive patients underwent IT in the considered period. Out of them, 279 were addressed to surgery; among them, pCR has been observed in 62 patients (18% of the total and 22% of the operated patients). In the pCR-group, clinical staging was IIb in 3 (5%) patients, IIIa in 28 (45%) patients and IIIb in 31 (50%). Surgery consisted of (bi)lobectomy in the majority of cases (80.7%), followed by pneumonectomy (19.3%). Adjuvant therapy was administered in 33 (53.2%) patients. Five-year overall survival and disease-free survival have been respectively 56.18% and 48.84%. The relative risk of death, observed with the Cox regression analysis, was 4.4 times higher (95% confidence interval (CI): 1.632–11.695, p = 0.03) for patients with N2 multi-station disease, 2.6 times higher (95% CI: 1.066–6.407, p = 0.036) for patients treated with pneumonectomy and 3 times higher (95% CI: 1.302–6.809, p = 0.01) for patients who did not receive adjuvant therapy. Conclusions: Rewarding long-term results could be expected in locally advanced NSCLC patients with pCR after IT followed by surgery. Baseline N2 single-station disease and adjuvant therapy after surgery seem to be associated with better prognosis, while pneumonectomy is associated with poorer outcomes.
Melissa Bersanelli, Sebastiano Buti, Diana Giannarelli, Alessandro Leonetti, Alessio Cortellini, Giuseppe Lo Russo, Diego Signorelli, Luca Toschi, Michele Milella, Sara Pilotto,et al.
Elsevier BV
Emanuele Vita, Alessio Stefani, Ettore D’Argento, Giampaolo Tortora, and Emilio Bria
Informa UK Limited
The discovery of ALK and ROS1 gene rearrangements in nonsmall-cell lung cancer (NSCLC) patients 2007 identified two new genetically distinct tumor populations with the potential to be effectively t...
Andrea Di Giorgio, Carlo Alberto Schena, Miriam Attalla El Halabieh, Carlo Abatini, Emanuele Vita, Antonia Strippoli, Frediano Inzani, Elena Rodolfino, Bruno Romanò, Fabio Pacelli,et al.
Elsevier BV
BACKGROUND
Few patients affected by gastric cancer peritoneal metastasis (GCPM) are offered locoregional treatment, despite several proof-of-efficacy trials. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) has emerged in recent years as a promising tool to control peritoneal carcinomatosis. The combination of PIPAC with systemic chemotherapy may offer a greater clinical benefit than standard treatment alone.
METHODS
A single-center cohort of 28 consecutive patients affected by GCPM was scheduled for bidirectional treatment, comprising PIPAC and systemic chemotherapy, from September 2017 to September 2019. Data recorded included safety, efficacy and survival outcomes. Ascite volumes, the Peritoneal Cancer Index (PCI) and pathological response through the Peritoneal Regression Grading Score (PRGS) were compared in those patients who underwent more than one PIPAC procedure.
RESULTS
Forty-six PIPAC procedures were administered, with a mean of 1.7 PIPAC procedures per patient. The median time to resume systemic chemotherapy after PIPAC was 6 days (range 4-7). Concerning safety, two grade 3-4 CTCAE (Common Terminology Criteria for Adverse Events v4.0) toxicity events and one intraoperative complication were recorded. Thirteen patients repeated PIPAC. A pathological response was recorded in 61.5% of patients (one with complete and seven with partial regression). The median overall survival was 12.3 months in the overall population and 15.0 months in patients undergoing more than one PIPAC procedure.
CONCLUSIONS
A bidirectional approach for GCPM was feasible and safe, as the PIPAC procedure integrates well with several systemic chemotherapy regimens. The pathological response demonstrated the antitumoral efficacy of PIPAC. The proposed bidirectional approach may be further investigated in the first-line treatment of metastatic gastric cancer.
Giulia Sartori, Lorenzo Belluomini, Fiorella Lombardo, Alice Avancini, Ilaria Trestini, Emanuele Vita, Daniela Tregnago, Jessica Menis, Emilio Bria, Michele Milella,et al.
Informa UK Limited
ABSTRACT Introduction Afatinib is a second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, acting as an irreversible and multitarget blocker of ErbB family members. Afatinib is currently approved for advanced non-small-cell lung cancer (NSCLC) harboring common and uncommon sensitizing EGFR mutations and for squamous NSCLC patients progressing after first-line platinum-based chemotherapy. Areas covered This review summarizes the efficacy and safety profile of afatinib compared with chemotherapy and other EGFR TKIs, in order to evaluate its characteristics and potential role in the increasingly complex treatment landscape of EGFR-mutant lung cancer. Future perspectives and innovative drug combinations are also discussed. Expert opinion Afatinib has been demonstrated to improve efficacy and quality of life compared with chemotherapy with a managed toxicity profile. However, in recent years, the increasing availability of different treatment options for advanced EGFR-mutant NSCLC has made the current treatment scenario more complicated, with an increasing need of new and deeper scientific data. In this light, the identification and validation of potential clinicopathological and/or molecular predictors of benefit, as well as the clarification of resistance mechanisms, may help to clarify the most appropriate treatment strategies and sequences for EGFR-mutant patients.
Miriam Grazia Ferrara, Vincenzo Di Noia, Ettore D’Argento, Emanuele Vita, Paola Damiano, Antonella Cannella, Marta Ribelli, Sara Pilotto, Michele Milella, Giampaolo Tortora,et al.
MDPI AG
Before the introduction of tyrosine kinase inhibitors (TKIs) for a particular subgroup of patients, despite platinum-based combination chemotherapy, the majority of patients affected by non-small-cell lung cancer (NSCLC) did not live longer than one year. With deeper understanding of tumor molecular biology, treatment of NSCLC has progressively entered the era of treatment customization according to tumor molecular characteristics, as well as histology. All this information allowed the development of personalized molecular targeted therapies. A series of studies have shown that, in some cases, cancer cells can grow and survive as result of the presence of a single driver genomic abnormality. This phenomenon, called oncogene-addiction, more often occurs in adenocarcinoma histology, in non-smokers (except BRAF mutations, also frequent in smoking patients), young, and female patients. Several different driver mutations have been identified and many studies have clearly shown that upfront TKI monotherapy may improve the overall outcome of these patients. The greater efficacy of these drugs is also associated with a better tolerability and safety than chemotherapy, with fewer side effects and an extremely good compliance to treatment. The most frequent oncogene-addicted disease is represented by those tumors carrying a mutation of the epidermal growth factor receptor (EGFR). The development of first, second and third generation TKIs against EGFR mutations have dramatically changed the prognosis of these patients. Currently, osimertinib (which demonstrated to improve efficacy with a better tolerability in comparison with first-generation TKIs) is considered the best treatment option for patients affected by NSCLC harboring a common EGFR mutation. EML4-ALK-driven disease (which gene re-arrangement occurs in 3–7% of NSCLC), has demonstrated to be significantly targeted by specific TKIs, which have improved outcome in comparison with chemotherapy. To date, alectinib is considered the best treatment option for these patients, with other newer agents upcoming. Other additional driver abnormalities, such as ROS1, BRAF, MET, RET and NTRK, have been identified as a target mirroring peculiar vulnerability to specific agents. Oncogene-addicted disease typically has a low early resistance rate, but late acquired resistance always develops and therefore therapy needs to be changed when progression occurs. In this narrative review, the state of art of scientific literature about targeted therapy options in oncogene-addicted disease is summarized and critically discussed. We also aim to analyze future perspectives to maximize benefits for this subgroup of patients.
Francesco Facchinetti, Giulia Mazzaschi, Fausto Barbieri, Francesco Passiglia, Francesca Mazzoni, Rossana Berardi, Claudia Proto, Fabiana Letizia Cecere, Sara Pilotto, Vieri Scotti,et al.
Elsevier BV