Milena Casula

@article{Nam2025,

title = {Genomic landscape of virus-associated cancers},

author = {Yoonhee Nam and Karen Gomez and Jean-Baptiste Reynier and Cole Khamnei and Michael Aitken and Vivian Zheng and Tenzin Lhakhang and Milena Casula and Giuseppe Palmieri and Antonio Cossu and Arnold Levine and Enrico Tiacci and Raul Rabadan},

doi = {10.1038/s41467-025-60836-9},

issn = {2041-1723},

year  = {2025},

date = {2025-12-00},

journal = {Nat Commun},

volume = {16},

number = {1},

publisher = {Springer Science and Business Media LLC},

abstract = {Abstract

          It has been estimated that 15%-20% of human cancers are attributable to infections, mostly by carcinogenic viruses. The incidence varies worldwide, with a majority affecting developing countries. Here, we conduct a comparative analysis of virus-positive and virus-negative tumors in nine cancers linked to five viruses. We observe a higher frequency of virus-positive tumors in males, with notable geographic differences in incidence. Our genomic analysis of 1971 tumors reveals a lower somatic burden, distinct mutation signatures, and driver gene mutations in virus-positive tumors. Compared to virus-negative cases, virus-positive cases have fewer mutations of TP53, CDKN2A, and deletions of 9p21.3/CDKN2A-CDKN1A while exhibiting more mutations in RNA helicases DDX3X and EIF4A1. Furthermore, an analysis of clinical trials of PD-(L)1 inhibitors suggests an association of virus-positivity with higher treatment response rate, particularly evident in gastric cancer and head and neck squamous cell carcinoma. Both cancer types also show evidence of increased CD8 + T cell infiltration and T cell receptor clonal selection in virus-positive tumors. These results illustrate the epidemiological, genetic, and therapeutic trends across virus-associated malignancies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ascierto2024,

title = {Sequencing of Checkpoint or BRAF/MEK Inhibitors on Brain Metastases in Melanoma},

author = {Paolo A. Ascierto and Mario Mandalà and Pier Francesco Ferrucci and Massimo Guidoboni and Piotr Rutkowski and Virginia Ferraresi and Ana Arance and Michele Guida and Evaristo Maiello and Helen Gogas and Erika Richtig and Pietro Quaglino and Céleste Lebbé and Hildur Helgadottir and Paola Queirolo and Francesco Spagnolo and Marco Tucci and Michele Del Vecchio and Maria Gonzalez-Cao and Alessandro Marco Minisini and Sabino De Placido and Miguel F. Sanmamed and Milena Casula and Jenny Bulgarelli and Marina Pisano and Claudia Piccinini and Luisa Piccin and Antonio Cossu and Domenico Mallardo and Miriam Paone and Maria Grazia Vitale and Ignacio Melero and Antonio M. Grimaldi and Diana Giannarelli and Giuseppe Palmieri and Reinhard Dummer and Vanna Chiarion Sileni},

doi = {10.1056/evidoa2400087},

issn = {2766-5526},

year  = {2024},

date = {2024-09-24},

journal = {NEJM Evidence},

volume = {3},

number = {10},

publisher = {Massachusetts Medical Society},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Sequential immunotherapy and targeted therapy for metastatic BRAF V600 mutated melanoma: 4-year survival and biomarkers evaluation from the phase II SECOMBIT trial},

author = {Paolo A. Ascierto and Milena Casula and Jenny Bulgarelli and Marina Pisano and Claudia Piccinini and Luisa Piccin and Antonio Cossu and Mario Mandalà and Pier Francesco Ferrucci and Massimo Guidoboni and Piotr Rutkowski and Virginia Ferraresi and Ana Arance and Michele Guida and Evaristo Maiello and Helen Gogas and Erika Richtig and Maria Teresa Fierro and Celeste Lebbe and Hildur Helgadottir and Paola Queirolo and Francesco Spagnolo and Marco Tucci and Michele Del Vecchio and Maria Gonzales Cao and Alessandro Marco Minisini and Sabino De Placido and Miguel F. Sanmamed and Domenico Mallardo and Miriam Paone and Maria Grazia Vitale and Ignacio Melero and Antonio M. Grimaldi and Diana Giannarelli and Reinhard Dummer and Vanna Chiarion Sileni and Giuseppe Palmieri.},

url = {https://irgb.cnr.it/wp-content/uploads/2024/05/Ascierto-et-al-2024-Nat-Comm.pdf},

doi = {https://doi.org/10.1038/s41467-023-44475-6},

year  = {2024},

date = {2024-01-15},

urldate = {2024-01-15},

journal = {Nature Communications},

volume = {15},

number = {146},

abstract = {No prospective data were available prior to 2021 to inform selection between combination BRAF and MEK inhibition versus dual blockade of programmed cell death protein-1 (PD-1) and cytotoxic T lymphocyte antigen-4 (CTLA-4) as first-line treatment options for BRAFV600-mutant melanoma. SECOMBIT (NCT02631447) was a randomized, three-arm, non comparative phase II trial in which patients were randomized to one of two sequences with immunotherapy or targeted therapy first, with a third arm in which an 8-week induction course of targeted therapy followed by a planned switch to immunotherapy was the first treatment. BRAF/MEK inhibitors were encorafenib plus binimetinib and checkpoint inhibitors ipilimumab plus nivolumab. Primary outcome of overall survival was previously reported, demonstrating improved survival with immunotherapy administered until progression and followed by BRAF/MEK inhibition. Here we report 4-year survival outcomes, confirming long term benefit with first-line immunotherapy. We also describe preliminary results of predefined biomarkers analyses that identify a trend toward improved 4-year overall survival and total progression-free survival in patients

with loss-of-function mutations affecting JAK or low baseline levels of serum interferon gamma (IFNy). These long-term survival outcomes confirm immunotherapy as the preferred first-line treatment approach for most patients with BRAFV600-mutant metastatic melanoma, and the biomarker analyses are hypothesis-generating for future investigations of predictors of durable benefit with dual checkpoint blockade and targeted therapy.

},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {BRAFV600 variant allele frequency predicts outcome in metastatic melanoma patients treated with BRAF and MEK inhibitors.},

author = {Mandalà Mario and Palmieri Giuseppe and Ludovini Vienna and Baglivo Sara and Marasciulo Francesca and Castiglione Francesca and Gili Alessio and Osella Abate Simona and Rubatto Marco and Senetta Rebecca and Avallone Gianluca and Ribero Simone and Romano Luca and Pimpinelli Nicola and de Giorgi Vincenzo and Roila Fausto and Pisano Marina and Casula Milena and Manca Antonella and Sini Maria Cristina},

doi = {10.1111/jdv.19281},

year  = {2023},

date = {2023-06-27},

urldate = {2023-06-27},

journal = {Journal of the European Academy of Dermatology & Venereology},

abstract = {Background: The prognostic impact of variant allele frequency (VAF) on clinical outcome in BRAFV600 mutated metastatic melanoma patients (MMPs) receiving BRAF (BRAFi) and MEK inhibitors (MEKi) is unclear. Materials and methods: A cohort of MMPs receiving first line BRAFi and MEKi was identified by inspecting dedicated databases of three Italian Melanoma Intergroup centres. VAF was determined by next generation sequencing in pre-treatment baseline tissue samples. Correlation between VAF and BRAF copy number variation was analysed in an ancillary study by using a training and a validation cohort of melanoma tissue samples and cell lines.Results: Overall, 107 MMPs were included in the study. The VAF cut-off determined by ROC curve was 41.3%. At multivariate analysis, progression-free survival (PFS) was significantly shorter in patients with M1c/M1d [HR 2.25 (95% CI 1.41-3.6, p < 0.01)], in those with VAF >41.3% [HR 1.62 (95% CI 1.04-2.54, p < 0.05)] and in those with ECOG PS ≥1 [HR 1.82 (95% CI 1.15-2.88, p < 0.05)]. Overall survival (OS) was significantly shorter in patients with M1c/M1d [HR 2.01 (95% CI 1.25-3.25, p < 0.01)]. Furthermore, OS was shorter in patients with VAF >41.3% [HR 1.46 (95% CI 0.93-2.29, p = 0.06)] and in patients with ECOG PS ≥1 [HR 1.52 (95% CI 0.94-2.87, p = 0.14)]. BRAF gene amplification was found in 11% and 7% of samples in the training and validation cohort, respectively. Conclusions: High VAF is an independent poor prognostic factor in MMP receiving BRAFi and MEKi. High VAF and BRAF amplification coexist in 7%-11% of patients. },

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Calabrò2021,

title = {Tremelimumab plus durvalumab retreatment and 4-year outcomes in patients with mesothelioma: a follow-up of the open label, non-randomised, phase 2 NIBIT-MESO-1 study},

author = {Luana Calabrò and Giulia Rossi and Aldo Morra and Claudio Rosati and Ornella Cutaia and Maria Grazia Daffinà and Maresa Altomonte and Anna Maria Di Giacomo and Milena Casula and Carolina Fazio and Giuseppe Palmieri and Diana Giannarelli and Alessia Covre and Michele Maio},

doi = {10.1016/s2213-2600(21)00043-6},

issn = {2213-2600},

year  = {2021},

date = {2021-09-00},

journal = {The Lancet Respiratory Medicine},

volume = {9},

number = {9},

pages = {969--976},

publisher = {Elsevier BV},

keywords = {},

pubstate = {published},

tppubtype = {article}

}