VALERIO GRISTINA
@unipa.it
Universita di Palermo
Scopus Publications
- Late endocrine-metabolic complications in survivors of young adult and adult-onset cancers: comprehensive evaluation and strategies for management. An Italian Association of Medical Oncology (AIOM), Italian Association of Medical Diabetologists (AMD), Italian Society of Diabetology (SID), Italian Society of Endocrinology (SIE), Italian Society of Pharmacology (SIF) multidisciplinary critical review
Francesco Felicetti, Rossella Mazzilli, Stefania Gori, Marco Gallo, Alessio Cortellini, et al.
Journal of Endocrinological Investigation, 2026
Background Cancer survivors have been considered individuals who have completed anti-tumor treatment and are in “remission”. However, the definition is increasingly seen as insufficient due to a significant number of patients living with chronic or stable disease, as a result of advanced therapies, and according to a recent definition, “survivors” are all people living with and beyond cancer. Breast, prostate, lung and colorectal cancers are the most frequent tumors diagnosed in Europe with an increasing population of survivors. The longer life expectancy has made it necessary to assess the health status, comorbidities, and complications in cancer patients, mainly in the age range of 20–50 years. In particular, the long-lasting hormonal therapies in hormone-sensitive tumors and the immunotherapies, that are changing the cancer clinical scenario, have opened a broad landscape of late endocrine/metabolic toxicities. Purpose The aim of the present manuscript is to evaluate the late endocrine-metabolic complications in survivors of young adult or adult-onset cancers in the most prevalent tumors, analyzing risk factors for endocrine/metabolic disease, attempting to provide a indications for long-term surveillance and treatment strategies. Conclusions This paper highlights the importance of recognizing endocrine and metabolic complications, as well as identifying key risk factors that can suggest a more effective surveillance and management. - Liquid biopsy in Oncology: Results of a Delphi consensus study endorsed by the AIOM-SIAPEC/IAP-SIBioC-SIF Italian scientific societies
Valerio Gristina, Umberto Malapelle, Gennaro Daniele, Giovanni Maria Iannantuono, Tancredi Didier Bazan Russo, et al.
Journal of Liquid Biopsy, 2026 - Real-world description of patients with resected epidermal growth factor receptor mutation positive non-small cell lung carcinoma treated with adjuvant osimertinib in an early access program in Italy: the ELBA observational study
Giulia Pasello, Claudia Proto, Carlo Genova, Alberto Pavan, Elisa Roca, et al.
Frontiers in Oncology, 2026
Background Following the ADAURA study results, showing that adjuvant osimertinib was associated with significant improvement in disease-free survival among patients with stage IB-IIIA epidermal growth factor receptor mutation positive (EGFRm+) non-small cell lung carcinoma (NSCLC), an Early Access Program (EAP) was activated in Italy to provide preapproval access to osimertinib. Methods The ELBA observational retrospective cohort study aims to describe the characteristics, diagnostic workup, mutation testing, and treatment patterns of the patients included in the ADAURA EAP. The retrospective observation period was from the day of the first procedure leading to the pathological diagnosis of NSCLC (index date) to osimertinib initiation and data were obtained from medical records or other original documents available at the sites. Results Overall, 71 patients were evaluable, mainly females (73.2%), with mean (SD) age of 67.5 (8.7) years. Age-adjusted Charlson Comorbidity Index scored 2 or 3 for 74.7% of patients without considering lung cancer. Forty-six (66.7%) out of 69 evaluable patients with available data were discussed at the multi-disciplinary team meeting. The median (25 th -75 th percentiles) time from the initial diagnostic suspicion to the index date was 52.0 (30.0-67.0) days and from index date to EGFR test prescription 20.0 (0.0-42.0) days. Among patients with available data (N = 69), the tests were mostly single-gene polymerase chain reaction mutation-specific test (63.8%) and next-generation sequencing (33.3%). Primary tumor surgery was mostly lobectomy (n/N=63/71, 88.7%). Pathological staging was IB for 21.1% of patients, II for 43.7% and III for 35.2%. Adjuvant chemotherapy prior to osimertinib was administered in 32.4% of patients. Osimertinib was started after a median (25 th -75 th percentiles) time from tumor resection of 2.9 (2.1-4.9) months. Conclusions The ELBA Study showed an evolving landscape in biomarker-driven and molecular targeted therapies in early-stage NSCLC management towards the integration of mutational testing into clinical practice, with a growing focus on an optimal definition of adjuvant treatment. - Homologous recombination repair genetic testing variables and diagnostic paths for prostate cancer patients: a multicenter cohort study
Lorena Incorvaia, Mattia Puglisi, Marco Maruzzo, Giulia Mammone, Orazio Caffo, et al.
Oncologist, 2025
Background Evidence on homologous recombination repair (HRR) mutation prevalence in prostate cancer (PC) patients and the diagnostic testing path to guide treatment remains limited outside of clinical trials. The objective of this study was to investigate the DNA source, type of tumor tissue, timing for testing in the patient’s disease course, and rate of conclusive results in a real-world population. Patients and Methods This was an observational, cohort study, involving 20 Italian cancer centers. The study population included consecutive PC patients undergoing germline, tumor, and/or plasma circulating tumor DNA (ctDNA) to profile HRR genes between January 1, 2020 and January 31, 2025. Results Among 1400 PC patients included, 248 (17.7%) showed (likely)pathogenic variants (PVs) in the HRR genes. Most HRR testing was conducted during the metastatic castration-resistant PC (mCRPC)(779, 62.8%). The rate of conclusive results was 89.7% and varied widely according to the type of tumor tissue. The prevalence of HRR alterations was 18.1% in the mCRPC and 13.8% in the hormone-sensitive PC (P = .06). The concordance between tumor testing and ctDNA was 83.9%. Interestingly, 4.6% reported ctDNA testing positive but tumor testing negative, leading to important therapeutic implications. The prevalence of positive ctDNA testing was 47.4% vs 10.5%, for testing within 1 month or over 3 months, respectively, from the initiation of a new line of therapy. Conclusion This large real-world study, through the workflow adopted by clinicians for HRR genomic testing, provides novel insights into the variables influencing the success rate of genomic testing. - Predictive role of functional respiratory tests in LUng toxicity in stage III NSCLC treated with chemo-, raDIO- and immuno-therapy: PRELUDIO TRIAL
P.M. Medusa, N. Carro, F. Morgillo, G.Di Guida, V. Nardone, et al.
Lung Cancer, 2025 - Potential Applications of PRP-Enhanced Polybutylene Succinate Graft as Vascular Access for Chemotherapy in Oncological Patients: A Systematic Review
Andrea Gottardo, Giulia Bonventre, Tancredi Didier Bazan Russo, Pietro Zanatta, Giulia Lo Monte, et al.
Journal of Functional Biomaterials, 2025
This systematic review aimed to evaluate the potential of combining platelet-rich plasma (PRP) and polybutylene succinate (PBS) for the development of vascular grafts in patients undergoing chemotherapy. Relevant articles published in English or Italian were selected through a comprehensive search of MEDLINE (via PubMed) and the Cochrane Library. A total of ten screened articles and two additional relevant studies were included. The synthesis of results was conducted using digital tools, thoroughly reviewed by the authors. The quality assessment of the included studies revealed a medium-to-high risk of bias, with frequent limitations such as small sample sizes, experimental designs, and overall moderate to low methodological quality. Despite the heterogeneity of the findings, the available evidence suggests that radiocephalic graft placement and the use of PBS as a scaffold material, in combination with the growth factors contained in PRP, may improve clinical outcomes and reduce complications related to arteriovenous graft implantation. While promising, the current literature on this topic remains scarce and fragmented, underscoring the need for additional preclinical and clinical research. The proposed approach appears to hold potential for improving vascular access in oncology, but further in vivo validation is essential. This study received no external funding. Registration: PROSPERO ID CRD42025646724. - Pregnancy and miscarriage before epithelial ovarian cancer (EOC) diagnosis in patients carrying germline BRCA1/BRCA2 pathogenic variants.
Tancredi Didier Bazan Russo, Mattia Puglisi, Elga Adriana Cipolla, Giovanni Colletta, Karen Carobene, et al.
Journal of Clinical Oncology, 2025
e22516 Background: Several case-control studies have been performed to understand the prognostic impact of pregnancy after breast cancer in patients carrying germline BRCA1/2 (g BRCA1/2 ) pathogenic/likely pathogenic variants (PVs). The median age of onset of epithelial ovarian cancer (EOC) diagnosis is higher than breast cancer. Clinical data on fertility, pregnancy outcomes, and abortion rates before the EOC onset are still missing. Previous research showed that g BRCA PV carriers may have a reduced ovarian reserve, earlier menopause than the general population, and defective homologous recombination repair of DNA double-strand breaks in human trophoblast, potentially leading to spontaneous miscarriage. Methods: This was a real-world, hospital-based cohort study to assess the cumulative incidence of pregnancy and miscarriage in a consecutive series of EOC patients who underwent g BRCA1/2 between May 2015 and December 2024. EOC patients carrying PVs in no- BRCA1/2 genes or tumor BRCA1/2 PVs were excluded from the current analysis. Results: From May 2015 to December 2024, 731 EOC patients were included in the analysis: 138 were carriers of g BRCA1/2 PVs (18.9%): 93 in BRCA1 (67.4%), and 45 in BRCA2 (32.6%). The number of patients with at least 1 pregnancy, abortion included, was 91 in the g BRCA carriers vs 192 in the g BRCA non-carriers. Notably, when the incidence of miscarriage between BRCA carriers and non-carriers was compared, the reduced incidence of spontaneous miscarriage was in the group of patients carrying g BRCA PVs [ BRCA carriers vs non-carriers: 11/92 (12.1%) vs 51/192 (26.6%)]. The total number of full-term pregnancies was 205 for g BRCA carriers vs 192 for non-carrier patients. Also, the median number of full-term pregnancies for single patients was higher in the patients harboring g BRCA PVs vs BRCA wild type (2.25 vs 1.5). The total number of miscarriages was 20 among g BRCA carriers vs 70 among non-carriers, with a lower miscarriage rate for individual patients in the BRCA -mutated patients (1.8 vs 1.3). The genetic characteristics and the EOC clinical behavior between parous and nulliparous women, according to BRCA mutational status, were also collected. Conclusions: Genetic diagnosis of constitutional BRCA1/2 PVs mutation raises concerns about the future fertility of female carriers. Interestingly, our data suggested that pregnancy in EOC women carriers of g BRCA1/2 PVs was associated with a reduced incidence of miscarriage than non-carriers. Prospective validation of these findings is required to improve understanding of fetal and obstetric outcomes and to guide counseling for BRCA carrier patients. - Germline evaluation of mismatch repair (MMR) genes in breast cancer patients missing Lynch syndrome criteria: Clinical behavior, preventive paths and therapeutic implications.
Lorena Incorvaia, Laura Cortesi, Tancredi Didier Bazan Russo, Clarissa Mujacic, Emma Zattarin, et al.
Journal of Clinical Oncology, 2025
e22507 Background: Currently,Breast Cancer (BC) is not considered a mismatch repair (MMR)-deficiency (MMRd)–spectrum tumor. The BC patients carrying constitutional MMR pathogenic variants (PVs) are not eligible for dedicated screening programs and risk-reducing strategies, which are addressed only to the BC individual carriers of specific Homologous Recombination Repair (HRR) variants. The MMRd status, as well as the high levels of microsatellite instability (MSI-H) that occur upon loss of the expression of MMR genes, may have direct therapeutic implications for the patients, who may benefit from the treatment with immune-checkpoint inhibitors (ICIs). Methods: This was an observational, hospital-based, cohort study to investigate the prevalence of germline MMR PVs in BC patients who were appropriate candidates for hereditary breast and/or ovarian cancer (HBOC) predisposition evaluation. BC patients were tested through NGS-based multigene panel testing including MMR-associated genes, according to clinical established criteria. Results: Between January 2016 and December 2024, 6.020 BC patients were referred for genetic counseling and HBOC predisposition evaluation. In the cohort of consecutive 5.595 BC patients tested with multigene panel testing, a subgroup of 26 patients resulted carriers of germline MMR PVs. Interestingly, 6 of 26 MMR-mutated patients (23.1%) had also a personal bilateral BC history. The median age at BC diagnosis was 55 (range 31-82). Mutation prevalence showed that PMS2 was the most mutated MMR gene (10 PVs, 38.5%), followed by MLH1 (6 PVs, 23.1%), EPCAM (5 PVs, 19.2%), MSH2 (3 PVs, 11.5%), and MSH6 (2 PVs, 7.7%). Notably, in the MMR - mutated cohort, 73.1% of BC patients (19/26) reported a family history of HRR-associated tumors (BC, ovarian/prostate and/or pancreatic tumors), predominantly BC (78.9%). Conversely, first or second-degree family members with a colorectal or endometrial cancer diagnosis, that represents the main Lynch Syndrome-associate tumors, were reported only for 3 patients (11.5%). The genetic characteristics and the clinical behavior of BC in MMR-, BRCA - and HRR non- BRCA -carriers were also collected. The variant of uncertain significance (VUS) prevalence was described. Conclusions: Our results suggested that, in women who met hereditary BC testing criteria but missed the established Lynch Syndrome clinical or testing criteria, the use of panel testing including MMR genes could lead to the identification of a subgroup of BC patients who are carriers of MMR constitutional PVs, with potential important preventive and therapeutic implications. - On-treatment dynamics of circulating extracellular vesicles in the first-line setting of patients with advanced non-small cell lung cancer: the LEXOVE prospective study
Valerio Gristina, Viviana Bazan, Nadia Barraco, Simona Taverna, Mauro Manno, et al.
Molecular Oncology, 2025
Extracellular vesicle (EV) monitoring can complement clinical assessment of cancer response. In this study, patients with advanced non‐small cell lung cancer (NSCLC) undergoing osimertinib, alectinib, pembrolizumab or platinum‐based chemotherapy ± pembrolizumab were enrolled. EVs were characterized using Bradford assay to quantify the circulating cell‐free EV protein content (cfEV), and dynamic light scattering to assess Rayleigh ratio excess at 90°, z‐averaged hydrodynamic diameter and polydispersity index. A total of 135 plasma samples from 27 patients were collected at baseline (T0) and at the first radiological restaging (T1). A ∆cfEV < 20% was associated with improved median progression‐free survival (mPFS) in responders versus non‐responders. Specifically, cfEV responders on pembrolizumab had a significantly better mPFS (25.2 months) compared to those on chemotherapy plus pembrolizumab (6.1 months). EGFR‐positive cfEV responders also experienced longer mPFS compared to cfEV non‐responders (35.1 months, 95% CI: 14.9–35.5 vs. 20.8 months, 95% CI: 11.2–30.4). This study suggested that monitoring circulating EV could provide valuable insights into treatment efficacy in NSCLC, particularly for patients receiving pembrolizumab or osimertinib. - BRCA functional domains associated with high risk of multiple primary tumors and domain-related sensitivity to olaparib: the Prometheus Study
L. Incorvaia, C. Marchetti, C. Brando, T.D. Bazan Russo, M. Bono, et al.
ESMO Open, 2025 - Genomics and the early diagnosis of lung cancer
Francesco Pepe, Tancredi Didier Bazan Russo, Valerio Gristina, Andrea Gottardo, Giulia Busuito, et al.
Personalized Medicine, 2025 - Recent advances in liquid biopsy for precision oncology: emerging biomarkers and clinical applications in lung cancer
Tancredi Didier Bazan Russo, Francesco Pepe, Valerio Gristina, Andrea Gottardo, Gianluca Russo, et al.
Future Oncology, 2025 - Smaller, cheaper, faster: where next for liquid biopsies?
Valerio Gristina, Francesco Pepe, Francesca Rita Ogliari, Tancredi Didier Bazan Russo, Andrea Gottardo, et al.
Expert Review of Molecular Diagnostics, 2025 - Part III – Post-analytical phase
Nicola Fusco, Giancarlo Pruneri, Fabio Pagni, Umberto Malapelle
Pathologica, 2025 - Clinical utility of ctDNA by amplicon based next generation sequencing in first line non small cell lung cancer patients
Valerio Gristina, Tancredi Didier Bazan Russo, Nadia Barraco, Andrea Gottardo, Francesco Pepe, et al.
Scientific Reports, 2024 - The intersection of homologous recombination (HR) and mismatch repair (MMR) pathways in DNA repair-defective tumors
Lorena Incorvaia, Tancredi Didier Bazan Russo, Valerio Gristina, Alessandro Perez, Chiara Brando, et al.
Npj Precision Oncology, 2024 - Scientific Communication and oncology – “The bridge between knowledge and patients”
Antonio Galvano, Andrea Gottardo, Valerio Gristina, Daniele Fanale, Lidia Rita Corsini, et al.
Critical Reviews in Oncology Hematology, 2024 - Polθ: emerging synthetic lethal partner in homologous recombination-deficient tumors
Tancredi Didier Bazan Russo, Clarissa Mujacic, Emilia Di Giovanni, Maria Concetta Vitale, Carla Ferrante Bannera, et al.
Cancer Gene Therapy, 2024 - Exploring the potential of multiomics liquid biopsy testing in the clinical setting of lung cancer
Andrea Gottardo, Tancredi Didier Bazan Russo, Alessandro Perez, Marco Bono, Emilia Di Giovanni, et al.
Cytopathology, 2024 - Applications of Platelet Concentrates (PCs) in Regenerative Onco-Urology: A Systematic Review of Literature
Andrea Gottardo, Gabriele Tulone, Nicola Pavan, Fabio Fulfaro, Valerio Gristina, et al.
International Journal of Molecular Sciences, 2024 - Extracellular Vesicles in Lung Cancer: Implementation in Diagnosis and Therapeutic Perspectives
Anna Paola Carreca, Rosaria Tinnirello, Vitale Miceli, Antonio Galvano, Valerio Gristina, et al.
Cancers, 2024 - Roles of Tumor-Educated Platelets (TEPs) in the biology of Non-Small Cell Lung Cancer (NSCLC): A systematic review. “Re-discovering the neglected biosources of the liquid biopsy family”
Andrea Gottardo, Valerio Gristina, Alessandro Perez, Emilia Di Giovanni, Silvia Contino, et al.
Journal of Liquid Biopsy, 2024 - Editorial: Real-world data and real-world evidence in lung cancer
Valerio Gristina, Chukwuka Eze
Frontiers in Oncology, 2024 - Dissecting the nuances of cancer epigenomics in liquid biopsy
Valerio Gristina, Umberto Malapelle
Epigenomics, 2024 - Harnessing the potential of genomic characterization of mutational profiles to improve early diagnosis of lung cancer
Valerio Gristina, Francesco Pepe, Carlo Genova, Tancredi Didier Bazan Russo, Andrea Gottardo, et al.
Expert Review of Molecular Diagnostics, 2024
