Giulia Alberti

Scopus Publications

A New Era, New Risks: The Cardio-Oncology Perspective on Immunotherapy in Non-Small Cell Lung Cancer
Luigi Tarantini, Giuseppina Gallucci, Alessandro Inno, Andrea Camerini, Maria Laura Canale, Mario Larocca, Francesca Zanelli, Maria Pagano, Giulia Alberti, Patrizia Ciammella, Nicola Maurea, Stefania Gori, Alessandro Navazio, Carmine Pinto
Cancers, 2025
Lung cancer (LC) remains the leading cause of cancer-related mortality worldwide. In recent years, mortality rates have declined due to antismoking policies, earlier detection, and the advent of targeted therapies and immunotherapy, particularly for non-small cell lung cancer (NSCLC), which accounts for 85% of all cases. With improved survival, however, LC patients are increasingly exposed to competing causes of mortality, among which cardiovascular disease (CVD) is highly prevalent, affecting 30–50% of patients and contributing to nearly 30% of deaths. This burden reflects both shared risk factors and the cardiotoxic potential of radiotherapy, chemotherapy, and immunotherapy. Beyond acute adverse cardiovascular events during treatment, real-world data indicate that immune checkpoint inhibitors (ICIs) may also exert chronic cardiovascular effects, significantly accelerating the atherosclerotic process in multimorbid patients. These findings underscore the importance of accurate baseline assessment and aggressive management of cardiovascular risk factors in LC patients—particularly in the adjuvant and neoadjuvant settings, where longer survival is anticipated. Moreover, long-term monitoring should be implemented through a tailored, multiparametric strategy that integrates novel biomarkers and advanced artificial intelligence–assisted imaging techniques. Achieving this ambitious goal requires the close collaboration of a multidisciplinary team, with cardiologists playing a pivotal role. This review will address the complexity of LC patients, focusing on the interplay of cardio-immuno-metabolic factors, summarizing the cardiovascular impact of immunotherapy across metastatic, locally advanced, and perioperative settings, and outlining practical strategies for the management of these vulnerable patients.
Successful percutaneous treatment of complex heart disease in a stage IV non-small cell lung cancer survivor
Davide Bosi, P. Demola, Giulia Alberti, S. Musto d'Amore, Mario Larocca, Vincenzo Guiducci, Carmine Pinto, A. Navazio, Luigi Tarantini
Giornale Italiano Di Cardiologia, 2024
The presence of metastatic cancer represents a high-risk condition for the treatment of heart disease requiring surgical or percutaneous procedures. We present the case of a 58-year-old man with pulmonary adenocarcinoma and renal metastases surviving more than 3 years after chemotherapy and immunotherapy suffering dyspnea and chest pain on minimal exertion due to 99% anterior coronary artery stenosis associated with severe aortic stenosis of a bicuspid valve. We treated the cardiac lesions in two steps by coronary angioplasty with drug-eluting stent implantation followed by percutaneous prosthetic aortic valve replacement. The procedures were successful with resolution of the symptoms and recovery of the usual ECOG-PS 0-1 functional capacity which persists 24 months after cardiac procedures. This case demonstrates that the multidisciplinary collaboration between oncologists and cardiologists with a personalized patient-centered approach allows to treat complex clinical situations successfully in the emerging category of patients surviving with metastatic cancer.
Rare Driver Mutations in Advanced, Oncogene-Addicted Non-Small Cell Lung Cancer: A North Italian, Real-World, Registry Experience
Kalliopi Andrikou, Paola Ulivi, Elisabetta Petracci, Irene Azzali, Federica Bertolini, Giulia Alberti, Stefania Bettelli, Daniele Calistri, Elisa Chiadini, Laura Capelli, Paola Cravero, Giorgia Guaitoli, Francesca Zanelli, Marco Angelo Burgio, Maria Pagano, Alberto Verlicchi, Enrica Martinelli, Katia Di Emidio, Massimo Dominici, Carmine Pinto, Angelo Delmonte
Diagnostics, 2024
The real-world, retrospective, NEROnE registry investigated the impact of next-generation sequencing (NGS) in advanced non-small-cell lung cancer (NSCLC) patients (pts) at three oncology units in the north of Italy between January 2020 and December 2022. We focused on the clinical characterization and outcomes of NSCLC with rare molecular alterations: EGFR exon 20 insertion, non-activating EGFR mutations, BRAF V600E and non-V600, ROS1 and RET rearrangements, MET, ErbB2, and FGFR mutations. Overall, these represented 6.4% (62/970) of the pts analysed with NGS in the daily practice. The most heavily represented rare alterations were ROS1 rearrangement (15 pts—24%) and MET exon 14 skipping mutation (11 pts—18%). No associations were found with the demographic and clinical features. Forty-nine pts received targeted therapies, of which 38.8% were first- and 9.8% were second-line. The remaining pts received chemotherapy and/or immunotherapy. In terms of the clinical outcomes, although not statistically significant, a tendency toward shorter OS was seen when therapies other than specific targeted therapies were used (HR: 1.84, 95% CI: 0.79–4.33, p = 0.158). The pts with co-mutations (19.4%) seemed to receive an advantage from the front-line chemotherapy-based regimen. Finally, an NLR score (a well-known inflammatory index) ≥ 4 seemed to be related to shorter OS among the pts treated with immunotherapy alone or in combination with chemotherapy (HR: 2.83, 95% CI: 1.08–7.40, p = 0.033). Prospective evaluations need to be performed to clarify whether these indexes may help to identify patients with oncogene-addicted NSCLC who could benefit from immunotherapy.
Changes in the Histology of Lung Cancer in Northern Italy: Impact on Incidence and Mortality
Lucia Mangone, Francesco Marinelli, Isabella Bisceglia, Alessandro Zambelli, Francesca Zanelli, Maria Pagano, Giulia Alberti, Fortunato Morabito, Carmine Pinto
Cancers, 2023
This study assessed the incidence, mortality, and survival of lung cancer subtypes of NSCSLC (non-small-cell lung cancer), SCLC (small-cell lung cancer), and other morphologies. It is an observational epidemiological study using 7197 cases from the Reggio Emilia Cancer Registry recorded between 2001 and 2020 in males and females. The incidence of NSCLC in 5104 males indicates a significant 3% annual increase until 2013 and then a decline of −3.2% that is not statistically significant; until 2014, mortality increased significantly (3.2%), but it then decreased non-significantly (−12.1%), especially squamous cell cancer. In 2093 females, the incidence and mortality trends continued to rise significantly through 2012, and then they began to slightly decline (not statistically significant). The two-year relative survival of NSCLC increased from 32% to 38% in males and from 42% to 56% in females. SCLC in males decreased significantly both in incidence and mortality, while in women, it showed a slight increase (significantly for incidence but not for mortality). This study is important because it analyzes the decrease in lung cancer in males and the increase in females in relation to the different histotypes. Our study’s findings confirmed a decline in male incidence and death beginning in 2013. We were unable to determine if the drop in cigarette smoking and the introduction of new drugs such as EGFR in first-line therapy were responsible for the lower incidence.
Thyroid hormones ratio is a major prognostic marker in advanced metastatic colorectal cancer: Results from the phase III randomised CORRECT trial
Giuseppe Pasqualetti, Marta Schirripa, Emmanuelle Dochy, Matteo Fassan, Pina Ziranu, Marco Puzzoni, Mario Scartozzi, Giulia Alberti, Sara Lonardi, Vittorina Zagonel, Fabio Monzani, Fotios Loupakis
European Journal of Cancer, 2020
BACKGROUND Free triiodothyronine (FT3)/free thyroxine (FT4) ratio is an index estimating the peripheral activity of thyroid hormones. In a previous experience, we identified a prognostic role for FT3/FT4 ratio in chemorefractory patients treated with regorafenib. Therefore, we planned this post hoc analysis of the phase III CORRECT trial of regorafenib versus placebo. METHODS Seven hundred fifty-eight out of 760 randomised patients (503 in the regorafenib and 255 in the placebo arm) were evaluable for the present analyses, based on availability of FT3 and FT4 baseline values. Co-primary objectives were to explore the predictive role of FT3/FT4 ratio in patients treated with regorafenib compared with placebo and to validate the prognostic value of FT3/FT4 ratio in the CORRECT trial. RESULTS For patients randomised to regorafenib, median overall survival (OS) was 4.0, 7.5 and 9.8 months in low, intermediate and high FT3/FT4 ratio subgroups, respectively. Hazard ratio (HR) for OS was 0.40 (p < 0.0001) when comparing intermediate versus low and 0.32 (p < 0.0001) when comparing high versus low FT3/FT4 ratio. In the placebo arm, median OS was 3.3, 5.6 and 7.7 months, in the three subgroups. HR for OS was 0.47 (p < 0.0001) when comparing intermediate versus low and 0.33 (p < 0.0001) when comparing high versus low. FT3/FT4 ratio retained its association with OS in the multivariate model in both arms. CONCLUSIONS While rejecting the predictive effect of baseline FT3/FT4 ratio, present data strengthen the prognostic role of the ratio, pave the way for direct clinical application, underline the need for a better biological understanding and suggest possible therapeutic implications for thyroid hormones.
PD-L1 expression in gastroesophageal dysplastic lesions
Matteo Fassan, Stefano Brignola, Gianmaria Pennelli, Giulia Alberti, Valentina Angerilli, Alessandra Bressan, Antonio Pellino, Cristiano Lanza, Roberta Salmaso, Sara Lonardi, Salvatore Pucciarelli, Gaya Spolverato, Marco Scarpa, Stefano Realdon, Fabio Farinati, Claudio Luchini, Massimo Rugge, Fotios Loupakis
Virchows Archiv, 2020
Immunotherapy has been recently approved for gastric (GC) and gastroesophageal-junction adenocarcinomas (GEC), and PD-L1 immunohistochemical evaluation represents a promising predictive biomarker in this oncological setting. A series of 125 gastroesophageal dysplastic lesions (52 low-grade, 73 high-grade) was investigated for PD-L1 and DNA mismatch repair proteins status. PD-L1 was positive (combined positive score (CPS) ≥ 1) in 48 (31.0%) dysplastic lesions. A higher prevalence of PD-L1–positive cases was observed among esophageal specimens compared with gastric ones ( p = 0.0003), in high-grade and adenocarcinoma samples in comparison with low-grade dysplasia ( p < 0.0001), and in lesions with mismatch repair deficiency ( p = 0.028). For 30 dysplastic samples, a synchronous matched invasive lesion (GC = 15, GEC = 15) was available and tested for PD-L1 expression; a discordant PD-L1 status was observed in 12/30 (40%) cases. A relatively high prevalence in PD-L1 positivity was observed among gastroesophageal dysplastic lesions and this should be taken into consideration for future therapeutic strategies based on this biomarker.
High Circulating Methylated DNA Is a Negative Predictive and Prognostic Marker in Metastatic Colorectal Cancer Patients Treated With Regorafenib
Alessio Amatu, Marta Schirripa, Federica Tosi, Sara Lonardi, Katia Bencardino, Erica Bonazzina, Laura Palmeri, Damiano Alfio Patanè, Elio Gregory Pizzutilo, Benedetta Mussolin, Francesca Bergamo, Giulia Alberti, Rossana Intini, Letizia Procaccio, Marco Arese, Silvia Marsoni, Michele Nichelatti, Vittorina Zagonel, Salvatore Siena, Alberto Bardelli, Fotios Loupakis, Federica Di Nicolantonio, Andrea Sartore-Bianchi, Ludovic Barault
Frontiers in Oncology, 2019
Background: Regorafenib improves progression free survival (PFS) in a subset of metastatic colorectal cancer (mCRC) patients, although no biomarkers of efficacy are available. Circulating methylated DNA (cmDNA) assessed by a five-gene panel was previously associated with outcome in chemotherapy treated mCRC patients. We hypothesized that cmDNA could be used to identify cases most likely to benefit from regorafenib (i.e., patients with PFS longer than 4 months). Methods: Plasma samples from mCRC patients were collected prior to (baseline samples N = 60) and/or during regorafenib treatment (N = 62) for the assessment of cmDNA and total amount of cell free DNA (cfDNA). Results: In almost all patients, treatment with regorafenib increased the total cfDNA, but decreased cmDNA warranting the normalization of cmDNA to the total amount of circulating DNA (i.e., cmDNA/ml). We report that cmDNA/ml dynamics reflects clinical response with an increase in cmDNA/ml associated with higher risk of progression (HR for progression = 1.78 [95%CI: 1.01–3.13], p = 0.028). Taken individually, high baseline cmDNA/ml (above median) was associated with worst prognosis (HR for death = 3.471 [95%CI: 1.83–6.57], p < 0.0001) and also predicted shorter PFS (<16 weeks with PPV 86%). In addition, high cmDNA/ml values during regorafenib treatment predicted with higher accuracy shorter PFS (<16 weeks with a PPV of 96%), therefore associated with increased risk of progression (HR for progression = 2.985; [95%CI: 1.63–5.46; p < 0.0001). Conclusions: Our data highlight the predictive and prognostic value of cmDNA/ml in mCRC patients treated with regorafenib.
Ramucirumab: the long and winding road toward being an option for mCRC treatment
Celine Debeuckelaere, Sabina Murgioni, Sara Lonardi, Noemi Girardi, Giulia Alberti, Carolina Fano, Sara Gallimberti, Cristina Magro, Selma Ahcene-Djaballah, Francesca Daniel, Matteo Fassan, Hans Prenen, Fotios Loupakis
Expert Opinion on Biological Therapy, 2019
Introduction: Colorectal cancer (CRC) is one of the main causes of cancer-related morbidity and mortality worldwide. Mortality is most often attributable to metastatic disease. Despite the progress achieved so far, life expectancy continues to be limited in most patients. Ramucirumab, a most recent antiangiogenic drug, is vying in the race to metastatic CRC (mCRC) treatment since its approval by the Food and Drug Administration (FDA), based on the results of the RAISE study. Areas covered: This article reviews the role of ramucirumab in mCRC, including clinical indication, safety issues, and future perspectives. Expert opinion: The use of Ramucirumab in clinical practice is still limited, probably due to economic burden and the lack of specific biomarkers. Future efforts will be addressed to improve our knowledge in the use of this drug and better guide us in patients’ care.
Prognostic Value of Thyroid Hormone Ratios in Patients With Advanced Metastatic Colorectal Cancer Treated With Regorafenib: The TOREADOR Study
Marta Schirripa, Giuseppe Pasqualetti, Riccardo Giampieri, Mario Scartozzi, Sara Lonardi, Laura Rumanò, Francesca Bergamo, Silvia Stragliotto, Sabina Murgioni, Giulia Alberti, Mario Domenico Rizzato, Alessandra Anna Prete, Marco Puzzoni, Valeria Pusceddu, Pina Ziranu, Fabiana Pani, Stefano Mariotti, Vittorina Zagonel, Fabio Monzani, Fotios Loupakis
Clinical Colorectal Cancer, 2018
Micro‐Abstract: In 2 distinct series of patients with metastatic colorectal cancer treated with regorafenib, we demonstrated an independent association between higher baseline free triiodothyronine/free thyroxine ratio and better overall survival. Future studies aimed to better clarify details on reduced peripheral conversion of thyroid hormone are warranted to understand whether free triiodothyronine/free thyroxine ratio is a marker of progression or a metabolic alteration with potential therapeutic implications. Background: The impact of free triiodothyronine (FT3)/free thyroxine (FT4) ratio on survival in hospitalized geriatric patients was recently described. Up today, there are no data regarding the prognostic role of FT3/FT4 ratio in patients with advanced cancer. We evaluated the impact of FT3/FT4 ratio on survival in patients with refractory colorectal cancer (CRC) treated with regorafenib. Methods: Patients with metastatic CRC treated with regorafenib with available clinical data and baseline measurement of FT3, FT4, and thyroid‐stimulating hormone (TSH) were considered eligible. Exploratory analyses included subjects treated at Istituto Oncologico Veneto. A confirmatory analysis was planned based on FT3/FT4 ratio tertile results, and a validation cohort was built on data retrieved from University of Cagliari. Results: In an exploratory cohort, the median overall survival in patients with low, intermediate, and high FT3/FT4 ratios, according to tertiles' value, was 4.8, 5.0, and 7.6 months, respectively (P = .003). The differences were significant in the multivariate model (hazard ratio, 0.43; 95% confidence interval, 0.28–0.68; P = .0003). Confirmatory results were obtained in a validation cohort, both in univariate (P = .0002) and in multivariate (hazard ratio, 0.56; 95% confidence interval, 0.36–0.88; P = .0118) models. Conclusions: High baseline FT3/FT4 ratio is strongly associated to better outcome in patients with progressive metastatic CRC treated with regorafenib. Further investigations are ongoing to draw definitive conclusions regarding a potential predictive effect.
NOS2 polymorphisms in prediction of benefit from first-line chemotherapy in metastatic colorectal cancer patients
Marta Schirripa, Wu Zhang, Dongyun Yang, Shu Cao, Satoshi Okazaki, Fotios Loupakis, Martin D. Berger, Yan Ning, Yuji Miyamoto, Mitsukuni Suenaga, Giulia Alberti, Jordan D. West, Sara Lonardi, Taline Khoukaz, Francesca Bergamo, Francesca Battaglin, Carlotta Antoniotti, Alfredo Falcone, Sebastian Stintzing, Volker Heinemann, Heinz-Josef Lenz
Plos One, 2018
Background Macrophages play a crucial role in the interaction between tumor and immune system, and iNOS is known as a surrogate marker of M1 macrophages activation. The goal of the study was to investigate the role of iNOS polymorphisms as prognostic marker in mCRC patients. Materials and methods Functional significant polymorphisms in the promoter of INOS gene were analyzed by PCR-based and direct DNA sequencing in 4 cohorts of patients receiving bevacizumab based first-line chemotherapy: two evaluation cohorts (TRIBE ARM A and ARM B) and two validation cohorts (FIRE 3 arm A and MOMA). The relation of the SNPs with PFS and OS was evaluated through Kaplan-Meier method and log-rank test. Subgroup analyses according to RAS status were preplanned. Results In the exploratory cohort 1 (TRIBE A), patients with CCTTT any>13repeats (N = 57) showed improved median PFS compared with patients carrying the ≤13/≤13 repeats variant (N = 152) (HR, 0.64; 95%CI 0.44–0.92, p = 0.010). Similar results were shown adopting the >26repeats/≤26 repeats (HR, 0.56; 95%CI 0.36–0.87, p = 0.005). In RAS mutant, patient with any>13 repeats (N = 24) had improved PFS results compared with those carrying the ≤13/≤13 repeats variant (N = 81) (HR, 0.51; 95%CI 0.30–0.87, p = 30.009). Similar results were found adopting the >26 repeats/≤26 repeats cut off: (HR, 0.52; 95%CI 0.27–0.98, p = 0.035). These data were partially confirmed in the exploratory cohort 2 (TRIBE B): a better median PFS was observed in patients with >26 repeats vs ≤26 repeats (N = 205) patients. However, these data were not confirmed in the two validation cohorts. Conclusion We failed to replicate the exploratory findings in both validation sets. The CCTTT polymorphic region of the INOS gene does not predict outcome in mCRC receiving bevacizumab based first line chemotherapy. Further investigations are needed to reveal mechanisms between tumor, immune system and chemotherapy response.