Grazia Palomba

@article{pmid38280995,

title = {Combination of mutations in genes controlling DNA repair and high mutational load plays a prognostic role in pancreatic ductal adenocarcinoma (PDAC): a retrospective real-life study in Sardinian population},

author = {Maria Cristina Sini and Maria Grazia Doro and Laura Frogheri and Angelo Zinellu and Panagiotis Paliogiannis and Alberto Porcu and Fabrizio Scognamillo and Daniele Delogu and Davide Adriano Santeufemia and Ivana Persico and Grazia Palomba and Giovanni Battista Maestrale and Antonio Cossu and Giuseppe Palmieri},

doi = {10.1186/s12967-024-04923-3},

issn = {1479-5876},

year  = {2024},

date = {2024-01-27},

urldate = {2024-01-27},

journal = {J Transl Med},

volume = {22},

number = {1},

pages = {108},

abstract = {BACKGROUND: Patients with pancreatic ductal adenocarcinoma (PDCA) carrying impaired mismatch repair mechanisms seem to have an outcome advantage under treatment with conventional chemotherapy, whereas the role for the tumor mutation burden on prognosis is controversial. In this study, we evaluated the prognostic role of the mutated genes involved in genome damage repair in a real-life series of PDAC patients in a hospital-based manner from the main Institution deputed to surgically treat such a disease in North Sardinia.



METHODS: A cohort of fifty-five consecutive PDAC patients with potentially resectable/border line resectable PDAC (stage IIB-III) or oligometastatic disease (stage IV) and tumor tissue availability underwent next-generation sequencing (NGS)-based analysis using a panel containing driver oncogenes and tumor suppressor genes as well as genes controlling DNA repair mechanisms.



RESULTS: Genes involved in the both genome damage repair (DR) and DNA mismatch repair (MMR) were found mutated in 17 (31%) and 15 (27%) cases, respectively. One fourth of PDAC cases (14/55; 25.5%) carried tumors presenting a combination of mutations in repair genes (DR and MMR) and the highest mutation load rates (MLR-H). After correction for confounders (surgery, adjuvant therapy, stage T, and metastasis), multivariate Cox regression analysis indicated that mutations in DR genes (HR = 3.0126, 95% CI 1.0707 to 8.4764, p = 0.0367) and the MLR (HR = 1.0018, 95%CI 1.0005 to 1.0032, p = 0.009) were significantly related to worse survival.



CONCLUSIONS: The combination of mutated repair genes and MLR-H, which is associated with a worse survival in our series of PDAC patients treated with conventional chemotherapy protocols, might become a predictive biomarker of response to immunotherapy in addition to its prognostic role in predicting survival.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@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}

}

@article{pmid35012520,

title = {Global prognostic impact of driver genetic alterations in patients with lung adenocarcinoma: a real-life study},

author = {Panagiotis Paliogiannis and Maria Colombino and Maria Cristina Sini and Antonella Manca and Milena Casula and Grazia Palomba and Marina Pisano and Valentina Doneddu and Angelo Zinellu and Davide Santeufemia and and Giovanni Sotgiu and Antonio Cossu and Giuseppe Palmieri},

doi = {10.1186/s12890-021-01803-0},

issn = {1471-2466},

year  = {2022},

date = {2022-01-10},

journal = {BMC Pulm Med},

volume = {22},

number = {1},

pages = {32},

abstract = {BACKGROUND: Advanced lung adenocarcinoma (LAC) is one of the most lethal malignancies worldwide. The aim of this study was to evaluate the global survival in a real-life cohort of patients with LAC harboring driver genetic alterations.



METHODS: A series of 1282 consecutive Sardinian LAC patients who underwent genetic testing from January 2011 through July 2016 was collected. Molecular tests were based on the clinical needs of each single case (EGFR-exon18/19/21, ALK, and, more recently, BRAF-exon15), and the availability of tissue (KRAS, MET, and presence of low-frequency EGFR-T790M mutated alleles at baseline).



RESULTS: The mean follow-up time of the patients was 46 months. EGFR, KRAS, and BRAF mutations were detected in 13.7%, 21.3%, and 3% of tested cases, respectively; ALK rearrangements and MET amplifications were found respectively in 4.7% and 2% of tested cases. As expected, cases with mutations in exons 18-21 of EGFR, sensitizing to anti-EGFR tyrosine kinase inhibitors (TKIs) agents, had a significantly longer survival in comparison to those without (p < 0.0001); conversely, KRAS mutations were associated with a significantly lower survival (p = 0.0058). Among LAC patients with additional tissue section available for next-generation sequencing (NGS)-based analysis, 26/193 (13.5%) patients found positive for even low-rate EGFR-T790M mutated alleles at baseline were associated with a highly significant lower survival in comparison to those without (8.7 vs. 47.4 months, p < 0.0001).



CONCLUSIONS: In addition to its predictive value for addressing targeted therapy approaches, the assessment of as more inclusive mutation analysis at baseline may provide clues about factors significantly impacting on global survival in advanced LAC patients.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32091431,

title = {KIT and PDGFRa mutational patterns in Sardinian patients with gastrointestinal stromal tumors},

author = {Grazia Palomba and Panagiotis Paliogiannis and Maria C Sini and Maria Colombino and Milena Casula and Antonella Manca and Marina Pisano and Giovanni Sotgiu and Valentina Doneddu and Giuseppe Palmieri and Antonio Cossu},

doi = {10.1097/CEJ.0000000000000581},

issn = {1473-5709},

year  = {2021},

date = {2021-01-30},

journal = {Eur J Cancer Prev},

volume = {30},

number = {1},

pages = {53--58},

abstract = {Gastrointestinal stromal tumor (GIST) is the most common mesenchymal malignancy of the gastrointestinal tract. We provide in the present article the molecular characterization of a series of primary GISTs in a cohort of Sardinian patients (Italy), with the aim to describe the patterns of KIT and PDGFRa mutations and the corresponding clinical features. Ninety-nine Sardinian patients with histologically-proven diagnosis of GIST were included in the study. Medical records and pathology reports were used to assess the demographic and clinical features of the patients and the disease at the time of the diagnosis. Formalin-fixed, paraffin-embedded tissue samples were retrieved for each case, and mutation analysis of the KIT and PDGFRa genes was performed. KIT and PDGFRa mutations were detected in 81.8% and 5% of the cases, respectively. The most common KIT mutation was W557_K558del in exon 11, while D842V in exon 18 was the most common PDGFRa genetic alteration; V561D was the only PDGFRa mutation found in exon 12. The global "wild-type" cases, with no mutations in either the KIT or PDGFRa genes, were 13 (13.1%). The mean survival of those patients was approximately 46.9 (±43.9) months. Globally, 86.9% of Sardinian patients with GIST had a KIT or PDGFRa mutation; the former were more frequent in comparison with other Italian cohorts, while PDGFRa mutations were rare. No statistical differences in survival between mutated and wild-type cases, and between KIT and PDGFRa mutated cases were detected in our study.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32751423,

title = {Comparison of BRAF Mutation Screening Strategies in a Large Real-Life Series of Advanced Melanoma Patients},

author = {Colombino, M. and Rozzo, C. and Paliogiannis, P. and Casula, M. and Manca, A. and Doneddu, V. and Fedeli, M. A. and Sini, M. C. and Palomba, G. and Pisano, M. and Ascierto, P. A. and Caracò, C. and Lissia, A. and Cossu, A. and Palmieri, G.},

year  = {2020},

date = {2020-07-01},

urldate = {2020-07-01},

journal = {J Clin Med},

volume = {9},

number = {8},

abstract = {Malignant melanoma (MM) is one of the deadliest skin cancers. BRAF mutation status plays a predominant role in the management of MM patients. The aim of this study was to compare BRAF mutational testing performed by conventional nucleotide sequencing approaches with either real-time polymerase chain reaction (rtPCR) or next-generation sequencing (NGS) assays in a real-life, hospital-based series of advanced MM patients. Consecutive patients with AJCC (American Joint Committee on Cancer) stage IIIC and IV MM from Sardinia, Italy, who were referred for molecular testing, were enrolled into the study. Initial screening was performed to assess the mutational status of the BRAF and NRAS genes, using the conventional methodologies recognized by the nationwide guidelines, at the time of the molecular classification, required by clinicians: at the beginning, Sanger-based sequencing (SS) and, after, pyrosequencing. The present study was then focused on BRAF mutation detecting approaches only. BRAF wild-type cases with available tissue and adequate DNA were further tested with rtPCR (Idyllaâ„¢) and NGS assays. Globally, 319 patients were included in the study; pathogenic BRAF mutations were found in 144 (45.1%) cases examined with initial screening. The rtPCR detected 11 (16.2%) and 3 (4.8%) additional BRAF mutations after SS and pyrosequencing, respectively. NGS detected one additional BRAF-mutated case (2.1%) among 48 wild-type cases previously tested with pyrosequencing and rtPCR. Our study evidenced that rtPCR and NGS were able to detect additional BRAF mutant cases in comparison with conventional sequencing methods; therefore, we argue for the preferential utilization of the aforementioned assays (NGS and rtPCR) in clinical practice, to eradicate false-negative cases and improve the accuracy of BRAF detection.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}