Marina Pisano
Researcher
Area of interest:
Dr. Marina Pisano graduated in Biological Sciences at the University of Sassari and, after a post doctoral experience in the USA, at present she works as researcher in the CNR since 1994. Her research activity has always been related to the study of the cellular and molecular biology of tumors. Initially she followed the molecular-genetic study of breast cancer with the identification of predisposing genetic alterations through mutational analysis on genomic DNA. Later her interests focused on the cellular and molecular biology of malignant melanoma using primary cell lines derived from biopsy samples of patients as a model for malignant melanoma study. The main goal was the identification and characterization of molecules (natural or synthetic) as potential broad-spectrum antitumor agents for targeted therapies, highlighting the molecular mechanisms underlying their antitumor activity. Starting from 2018, the research activity of Dr. Pisano is aimed at the genetic analysis and molecular diagnostics in the oncology field. In particular her research involve clinical-translational and basic research, molecular diagnostics in support of personalized therapy for patients with malignant tumor (Agreement with AOU of Sassari: “Diagnostic analysis of gene mutations on tumor tissues”), and the development of clinical trials in multidisciplinary groups for the study of specific tumor pathologies.
Most significant publications:
2024
Ascierto, Paolo A.; Casula, Milena; Bulgarelli, Jenny; Pisano, Marina; Piccinini, Claudia; Piccin, Luisa; Cossu, Antonio; Mandalà, Mario; Ferrucci, Pier Francesco; Guidoboni, Massimo; Rutkowski, Piotr; Ferraresi, Virginia; Arance, Ana; Guida, Michele; Maiello, Evaristo; Gogas, Helen; Richtig, Erika; Fierro, Maria Teresa; Lebbe, Celeste; Helgadottir, Hildur; Queirolo, Paola; Spagnolo, Francesco; Tucci, Marco; Vecchio, Michele Del; Cao, Maria Gonzales; Minisini, Alessandro Marco; Placido, Sabino De; Sanmamed, Miguel F.; Mallardo, Domenico; Paone, Miriam; Vitale, Maria Grazia; Melero, Ignacio; Grimaldi, Antonio M.; Giannarelli, Diana; Dummer, Reinhard; Sileni, Vanna Chiarion; Palmieri., Giuseppe
In: Nature Communications, 15 (146), 2024.
@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}
}
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.
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.
2023
Mario, Mandalà; Giuseppe, Palmieri; Vienna, Ludovini; Sara, Baglivo; Francesca, Marasciulo; Francesca, Castiglione; Alessio, Gili; Simona, Osella Abate; Marco, Rubatto; Rebecca, Senetta; Gianluca, Avallone; Simone, Ribero; Luca, Romano; Nicola, Pimpinelli; de Giorgi Vincenzo,; Fausto, Roila; Marina, Pisano; Milena, Casula; Antonella, Manca; Cristina, Sini Maria
BRAFV600 variant allele frequency predicts outcome in metastatic melanoma patients treated with BRAF and MEK inhibitors. Journal Article
In: Journal of the European Academy of Dermatology & Venereology, 2023.
@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}
}
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.
Milena, Casula; Marina, Pisano; Panagiotis, Paliogiannis; Maria, Colombino; Cristina, Sini Maria; Angelo, Zinellu
Comparison between Three Different Techniques for the Detection of EGFR Mutations in Liquid Biopsies of Patients with Advanced Stage Lung Adenocarcinoma Journal Article
In: International Journal of Molecular Sciences, 24 (6410), 2023.
@article{nokey,
title = {Comparison between Three Different Techniques for the Detection of EGFR Mutations in Liquid Biopsies of Patients with Advanced Stage Lung Adenocarcinoma},
author = {Casula Milena and Pisano Marina and Paliogiannis Panagiotis and Colombino Maria and Sini Maria Cristina and Zinellu Angelo},
year = {2023},
date = {2023-03-29},
urldate = {2023-03-29},
journal = {International Journal of Molecular Sciences},
volume = {24},
number = {6410},
abstract = {Oncogenic mutations in the EGFR gene are targets of tyrosine kinase inhibitors (TKIs) in lung adenocarcinoma (LC) patients and their search is mandatory to make decisions on treatment strategies. Liquid biopsy of circulating tumour DNA (ctDNA) is increasingly used to detect EGFR mutations including main activating alterations (exon 19 deletions and exon 21 L858R mutation) and T790M mutation which is the most common mechanism of acquired resistance to first- and second-generation TKIs. In this study we prospectively compared three different techniques for EGFR mutation detection in liquid biopsies of such patients. Fifty-four ctDNA samples from 48 consecutive advanced LC patients treated with TKIs were tested for relevant EGFR mutations with Therascreen® EGFR Plasma RGQ-PCR Kit (Qiagen). Samples were subsequently tested with two different technologies with the aim to compare the EGFR detection rates: real-time PCR based Idylla™ ctEGFR mutation assay (Biocartis) and next-generation sequencing (NGS) system with Ion AmpliSeq Cancer Hotspot panel (ThermoFisher). A high concordance rate for main druggable EGFR alterations was observed with the two real-time PCR-based assays ranging from 100% for T790M mutation to 94% for L858R variant and 85% for exon 19 deletions. Conversely lower concordance rates were found between real-time PCR approaches and the NGS method (L858R: 88%; exon19-dels: 74%; T790M: 37.5%). Our results evidenced an equivalent detection ability between PCR-based techniques for circulating EGFR mutations. The NGS assay allowed detection of a wider range of EGFR mutations but showed a poor ability to detect T790M.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Oncogenic mutations in the EGFR gene are targets of tyrosine kinase inhibitors (TKIs) in lung adenocarcinoma (LC) patients and their search is mandatory to make decisions on treatment strategies. Liquid biopsy of circulating tumour DNA (ctDNA) is increasingly used to detect EGFR mutations including main activating alterations (exon 19 deletions and exon 21 L858R mutation) and T790M mutation which is the most common mechanism of acquired resistance to first- and second-generation TKIs. In this study we prospectively compared three different techniques for EGFR mutation detection in liquid biopsies of such patients. Fifty-four ctDNA samples from 48 consecutive advanced LC patients treated with TKIs were tested for relevant EGFR mutations with Therascreen® EGFR Plasma RGQ-PCR Kit (Qiagen). Samples were subsequently tested with two different technologies with the aim to compare the EGFR detection rates: real-time PCR based Idylla™ ctEGFR mutation assay (Biocartis) and next-generation sequencing (NGS) system with Ion AmpliSeq Cancer Hotspot panel (ThermoFisher). A high concordance rate for main druggable EGFR alterations was observed with the two real-time PCR-based assays ranging from 100% for T790M mutation to 94% for L858R variant and 85% for exon 19 deletions. Conversely lower concordance rates were found between real-time PCR approaches and the NGS method (L858R: 88%; exon19-dels: 74%; T790M: 37.5%). Our results evidenced an equivalent detection ability between PCR-based techniques for circulating EGFR mutations. The NGS assay allowed detection of a wider range of EGFR mutations but showed a poor ability to detect T790M.
2022
Andrea, Anichini; Alessandra, Molla; Gabriella, Nicolini; Eleonora, Perotti Valentina; Francesco, Sgambelluri; Alessia, Covre; Carolina, Fazio; Fortunata, Lofiego Maria; Maria, Di Giacomo Anna; Sandra, Coral; Antonella, Manca; Cristina, Sini Maria; Marina, Pisano; Teresa, Noviello; Francesca, Caruso; Silvia, Brich; Giancarlo, Pruneri; Andrea, Maurichi; Mario, Santinami; Michele, Ceccarelli; Giuseppe, Palmieri; Michele, Maio; Roberta, Mortarini
Landscape of immune-related signatures induced by targeting of different epigenetic regulators in melanoma: implications for immunotherapy Journal Article
In: JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH, 41 (325), 2022.
@article{nokey,
title = {Landscape of immune-related signatures induced by targeting of different epigenetic regulators in melanoma: implications for immunotherapy},
author = {Anichini Andrea and Molla Alessandra and Nicolini Gabriella and Perotti Valentina Eleonora and Sgambelluri Francesco and Covre Alessia and Fazio Carolina and Lofiego Maria Fortunata and Di Giacomo Anna Maria and Coral Sandra and Manca Antonella and Sini Maria Cristina and Pisano Marina and Noviello Teresa and Caruso Francesca and Brich Silvia and Pruneri Giancarlo and Maurichi Andrea and Santinami Mario and Ceccarelli Michele and Palmieri Giuseppe and Maio Michele and Mortarini Roberta},
url = {https://jeccr.biomedcentral.com/articles/10.1186/s13046-022-02529-5},
year = {2022},
date = {2022-05-10},
urldate = {2022-05-10},
journal = {JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH},
volume = {41},
number = {325},
abstract = {Background: Improvement of efficacy of immune checkpoint blockade (ICB) remains a major clinical goal. Association of ICB with immunomodulatory epigenetic drugs is an option. However epigenetic inhibitors show a heterogeneous landscape of activities. Analysis of transcriptional programs induced in neoplastic cells by distinct classes of epigenetic drugs may foster identification of the most promising agents.Methods: Melanoma cell lines characterized for mutational and differentiation profile were treated with inhibitors of DNA methyltransferases (guadecitabine) histone deacetylases (givinostat) BET proteins (JQ1 and OTX-015) and enhancer of zeste homolog 2 (GSK126). Modulatory effects of epigenetic drugs were evaluated at the gene and protein levels. Master molecules explaining changes in gene expression were identified by Upstream Regulator (UR) analysis. Gene set enrichment and IPA were used respectively to test modulation of guadecitabine-specific gene and UR signatures in baseline and on-treatment tumor biopsies from melanoma patients in the Phase Ib NIBIT-M4 Guadecitabine + Ipilimumab Trial. Prognostic significance of drug-specific immune-related genes was tested with Timer 2.0 in TCGA tumor datasets.Results: Epigenetic drugs induced different profiles of gene expression in melanoma cell lines. Immune-related genes were frequently upregulated by guadecitabine irrespective of the mutational and differentiation profiles of the melanoma cell lines to a lesser extent by givinostat but mostly downregulated by JQ1 and OTX-015. GSK126 was the least active drug. Quantitative western blot analysis confirmed drug-specific modulatory profiles. Most of the guadecitabine-specific signature genes were upregulated in on-treatment NIBIT-M4 tumor biopsies but not in on-treatment lesions of patients treated only with ipilimumab. A guadecitabine-specific UR signature containing activated molecules of the TLR NF-kB and IFN innate immunity pathways was induced in drug-treated melanoma mesothelioma and hepatocarcinoma cell lines and in a human melanoma xenograft model. Activation of guadecitabine-specific UR signature molecules in on-treatment tumor biopsies discriminated responding from non-responding NIBIT-M4 patients. Sixty-five % of the immune-related genes upregulated by guadecitabine were prognostically significant and conferred a reduced risk in the TCGA cutaneous melanoma dataset.Conclusions: The DNMT inhibitor guadecitabine emerged as the most promising immunomodulatory agent among those tested supporting the rationale for usage of this class of epigenetic drugs in combinatorial immunotherapy approaches.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background: Improvement of efficacy of immune checkpoint blockade (ICB) remains a major clinical goal. Association of ICB with immunomodulatory epigenetic drugs is an option. However epigenetic inhibitors show a heterogeneous landscape of activities. Analysis of transcriptional programs induced in neoplastic cells by distinct classes of epigenetic drugs may foster identification of the most promising agents.Methods: Melanoma cell lines characterized for mutational and differentiation profile were treated with inhibitors of DNA methyltransferases (guadecitabine) histone deacetylases (givinostat) BET proteins (JQ1 and OTX-015) and enhancer of zeste homolog 2 (GSK126). Modulatory effects of epigenetic drugs were evaluated at the gene and protein levels. Master molecules explaining changes in gene expression were identified by Upstream Regulator (UR) analysis. Gene set enrichment and IPA were used respectively to test modulation of guadecitabine-specific gene and UR signatures in baseline and on-treatment tumor biopsies from melanoma patients in the Phase Ib NIBIT-M4 Guadecitabine + Ipilimumab Trial. Prognostic significance of drug-specific immune-related genes was tested with Timer 2.0 in TCGA tumor datasets.Results: Epigenetic drugs induced different profiles of gene expression in melanoma cell lines. Immune-related genes were frequently upregulated by guadecitabine irrespective of the mutational and differentiation profiles of the melanoma cell lines to a lesser extent by givinostat but mostly downregulated by JQ1 and OTX-015. GSK126 was the least active drug. Quantitative western blot analysis confirmed drug-specific modulatory profiles. Most of the guadecitabine-specific signature genes were upregulated in on-treatment NIBIT-M4 tumor biopsies but not in on-treatment lesions of patients treated only with ipilimumab. A guadecitabine-specific UR signature containing activated molecules of the TLR NF-kB and IFN innate immunity pathways was induced in drug-treated melanoma mesothelioma and hepatocarcinoma cell lines and in a human melanoma xenograft model. Activation of guadecitabine-specific UR signature molecules in on-treatment tumor biopsies discriminated responding from non-responding NIBIT-M4 patients. Sixty-five % of the immune-related genes upregulated by guadecitabine were prognostically significant and conferred a reduced risk in the TCGA cutaneous melanoma dataset.Conclusions: The DNMT inhibitor guadecitabine emerged as the most promising immunomodulatory agent among those tested supporting the rationale for usage of this class of epigenetic drugs in combinatorial immunotherapy approaches.
Fadda, Giovanni M.; Lobrano, Renato; Casula, Milena; Pisano, Marina; Pazzola, Antonio; Cossu, Antonio; Palmieri, Giuseppe; Paliogiannis, Panagiotis
Liquid Biopsy in the Oncological Management of a Histologically Undiagnosed Lung Carcinoma: A Case Report Journal Article
In: Journal of Personalized Medicine , 12 (1874 ), 2022.
@article{nokey,
title = {Liquid Biopsy in the Oncological Management of a Histologically Undiagnosed Lung Carcinoma: A Case Report},
author = {Giovanni M. Fadda and Renato Lobrano and Milena Casula and Marina Pisano and Antonio Pazzola and Antonio Cossu and Giuseppe Palmieri and Panagiotis Paliogiannis},
year = {2022},
date = {2022-05-10},
urldate = {2022-05-10},
journal = {Journal of Personalized Medicine },
volume = {12},
number = {1874 },
abstract = {Lung cancer is one of the most common and lethal cancers worldwide. Numerous medications targeting specific molecular alterations in non-small cell lung cancer have been introduced in the last decade and have revolutionized the clinical management of the disease. Their use has brought to a parallel evolution of molecular testing techniques to identify alterations in druggable molecular targets within the genetic material of the tumors. To perform molecular testing biopsy or surgery tissue specimens are needed which in addition allow the histological characterization of the tumors. Unfortunately in real-life practice not all the patients are suitable for biopsy or surgery procedures. The use of liquid biopsy for blood extracted tumoral DNA analysis is a promising approach in unbiopsied cases but it is also weighted by several methodological and technical limitations. We report here a case of histologically undiagnosed lung cancer managed with a liquid biopsy and subsequently with anti-EGFR treatment. Our report highlights that the use of liquid biopsy molecular testing in specific clinical situations can offer treatment opportunities for fragile patients affected by lung cancer.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Lung cancer is one of the most common and lethal cancers worldwide. Numerous medications targeting specific molecular alterations in non-small cell lung cancer have been introduced in the last decade and have revolutionized the clinical management of the disease. Their use has brought to a parallel evolution of molecular testing techniques to identify alterations in druggable molecular targets within the genetic material of the tumors. To perform molecular testing biopsy or surgery tissue specimens are needed which in addition allow the histological characterization of the tumors. Unfortunately in real-life practice not all the patients are suitable for biopsy or surgery procedures. The use of liquid biopsy for blood extracted tumoral DNA analysis is a promising approach in unbiopsied cases but it is also weighted by several methodological and technical limitations. We report here a case of histologically undiagnosed lung cancer managed with a liquid biopsy and subsequently with anti-EGFR treatment. Our report highlights that the use of liquid biopsy molecular testing in specific clinical situations can offer treatment opportunities for fragile patients affected by lung cancer.
Mariani, Stefano; Puzzoni, Marco; Giampieri, Riccardo; Ziranu, Pina; Pusceddu, Valeria; Donisi, Clelia; Persano, Mara; Pinna, Giovanna; Cimbro, Erika; Parrino, Alissa; Spanu, Dario; Pretta, Andrea; Lai, Eleonora; Liscia, Nicole; Lupi, Alessio; Giglio, Enrica; Palomba, Grazia; Casula, Milena; Pisano, Marina; Palmieri, Giuseppe; Scartozzi, Mario
Liquid Biopsy-Driven Cetuximab Rechallenge Strategy in Molecularly Selected Metastatic Colorectal Cancer Patients Journal Article
In: Frontiers in Oncology, 12 (852583), 2022.
@article{nokey,
title = {Liquid Biopsy-Driven Cetuximab Rechallenge Strategy in Molecularly Selected Metastatic Colorectal Cancer Patients},
author = {Stefano Mariani and Marco Puzzoni and Riccardo Giampieri and Pina Ziranu and Valeria Pusceddu and Clelia Donisi and Mara Persano and Giovanna Pinna and Erika Cimbro and Alissa Parrino and Dario Spanu and Andrea Pretta and Eleonora Lai and Nicole Liscia and Alessio Lupi and Enrica Giglio and Grazia Palomba and Milena Casula and Marina Pisano and Giuseppe Palmieri and Mario Scartozzi},
year = {2022},
date = {2022-04-21},
urldate = {2022-04-21},
journal = {Frontiers in Oncology},
volume = {12},
number = {852583},
abstract = {Background: Rechallenge with EGFR inhibitors represents a promising strategy for patients with RAS wild type (WT) colorectal cancer (CRC) but definitive selection criteria are lacking. Recently the RAS WT status on circulating tumor DNA (ct-DNA) emerged as a potential watershed for this strategy. Our study explored the liquid biopsy-driven cetuximab rechallenge in a RAS and BRAF WT selected population. Methods: CRC patients with RAS and BRAF WT both on tumor tissue and on ct-DNA at baseline receiving rechallenge with cetuximab were eligible for our analysis. Ct-DNA was analyzed for RAS-BRAF mutations with pyro-sequencing and nucleotide sequencing assays. Real-time PCR and droplet digital PCR were performed to confirm the RAS-BRAF mutational status. Results: A total of 26 patients were included in our analysis. In the global population RR was 25.0% median overall survival (mOS) was 5.0 months and median progression-free survival (mPFS) was 3.5 months. Previous response to anti-EGFR was associated with improved mPFS (5.0 vs. 2.0 months HR: 0.26 p = 0.048) and anti-EGFR free interval > 14 months and anti-EGFR free interval > 16 months were associated with improved mPFS (respectively 7.0 vs. 3.0 months HR: 0.27 p = 0.013 and not reached vs. 3.0 months HR: 0.20 p = 0.002) and with improved mOS (respectively 13.0 vs. 5.0 months HR: 0.27 p = 0.013 and 13.0 vs. 5.0 months HR: 0.20 p = 0.002). Previous lines >2 were correlated with improved mPFS (4.0 vs. 1.0 month HR: 0.05 p = 0.041) and with improved mOS (7.0 vs. 1.0 month HR: 0.045 p = 0.034). In a multiple logistic regression model only the anti-EGFR free interval was confirmed to be a significant predictor for mOS and mPFS. Conclusions: Liquid biopsy-driven cetuximab rechallenge was confirmed to be effective. The clinical outcome was consistent with available results from phase II studies. In addition to the molecular selection through the analysis of ct-DNA for RAS the long anti-EGFR free interval is confirmed as a prospective selection criterion for this therapeutic option.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Background: Rechallenge with EGFR inhibitors represents a promising strategy for patients with RAS wild type (WT) colorectal cancer (CRC) but definitive selection criteria are lacking. Recently the RAS WT status on circulating tumor DNA (ct-DNA) emerged as a potential watershed for this strategy. Our study explored the liquid biopsy-driven cetuximab rechallenge in a RAS and BRAF WT selected population. Methods: CRC patients with RAS and BRAF WT both on tumor tissue and on ct-DNA at baseline receiving rechallenge with cetuximab were eligible for our analysis. Ct-DNA was analyzed for RAS-BRAF mutations with pyro-sequencing and nucleotide sequencing assays. Real-time PCR and droplet digital PCR were performed to confirm the RAS-BRAF mutational status. Results: A total of 26 patients were included in our analysis. In the global population RR was 25.0% median overall survival (mOS) was 5.0 months and median progression-free survival (mPFS) was 3.5 months. Previous response to anti-EGFR was associated with improved mPFS (5.0 vs. 2.0 months HR: 0.26 p = 0.048) and anti-EGFR free interval > 14 months and anti-EGFR free interval > 16 months were associated with improved mPFS (respectively 7.0 vs. 3.0 months HR: 0.27 p = 0.013 and not reached vs. 3.0 months HR: 0.20 p = 0.002) and with improved mOS (respectively 13.0 vs. 5.0 months HR: 0.27 p = 0.013 and 13.0 vs. 5.0 months HR: 0.20 p = 0.002). Previous lines >2 were correlated with improved mPFS (4.0 vs. 1.0 month HR: 0.05 p = 0.041) and with improved mOS (7.0 vs. 1.0 month HR: 0.045 p = 0.034). In a multiple logistic regression model only the anti-EGFR free interval was confirmed to be a significant predictor for mOS and mPFS. Conclusions: Liquid biopsy-driven cetuximab rechallenge was confirmed to be effective. The clinical outcome was consistent with available results from phase II studies. In addition to the molecular selection through the analysis of ct-DNA for RAS the long anti-EGFR free interval is confirmed as a prospective selection criterion for this therapeutic option.
- Traversa la Crucca, 3 – Regione Baldinca, Sassari
- 079 2841228
ORCID ID: https://orcid.org/0000-0002-0649-1010
