Lorena Gurrieri - Academia.edu (original) (raw)

Papers by Lorena Gurrieri

Cancer letters, Feb 1, 2024

Frontiers in Bioengineering and Biotechnology, Oct 17, 2022

Tumori Journal, 2015

Bone metastasis below the knee from primary lung cancer is rare. Discussion of such cases in a mu... more Bone metastasis below the knee from primary lung cancer is rare. Discussion of such cases in a multidisciplinary team is important to establish the correct treatment approach. We analyzed the diagnostic pathway of a 53-year-old female patient with a 5-month history of pain in the right foot. The patient underwent several radiological examinations for the pain. An initial diagnosis of osteoporotic syndrome was made, followed by a diagnosis of primary sarcoma. Only when the patient continued to have pain were other radiological examinations performed and a biopsy of the right ankle taken. This revealed a metastasis from undifferentiated pulmonary adenocarcinoma. A total-body computed tomography scan did not show any tumor locations apart from the primary lung cancer. The patient underwent chemotherapy and palliative therapies. This case has been reported for its rarity.

Annals of Oncology, Sep 1, 2012

ABSTRACT Background Non Small Cell Lung Cancer (NSCLC) diagnosis and treatment is a highly comple... more ABSTRACT Background Non Small Cell Lung Cancer (NSCLC) diagnosis and treatment is a highly complex process, requiring managerial skills merged with clinical knowledge and experience. Integrated Care Pathways (ICP) might be a good strategy to overview and improve patient's management. The aim of our study was to review our NSCLC patient's ICP in order to provide evidence of clinical or organizational inappropriateness. Methods We retrospectively reviewed the electronic medical records of 169 NSCLC patients who had had a first access at the Oncology Department of the University Hospital Santa Maria della Misericordia (Udine, Italy) during 2010. The ICP mapping and few quality indicators had already been settled by a previous study on the 2008 population and were integrated with new uptodate indicators selected from scientific literature and discussed at the weekly MDT. Results 146 patients were considered eligible; median age was 67 years old. Patients were mainly males (65%), had adenocarcinoma histology and advanced disease at the time of diagnosis (52.7%). Distant from benchmark were the percentage of diagnostic bronchoscopic procedures (60.7 vs 80-85%), the number of surgical candidates who underwent mediastinoscopy for positive PET for mediastinal nodes (0 vs 100%), median time from diagnosis to surgery and to chemotherapy (58.5 vs 21 and 34 vs 21 days; p Conclusion Our analysis has highlighted a good adherence to current national and intenational guidelines and scientific literature as far as medical oncology treatment and pathological diagnosis are concerned. There is still room for improvement, most of all regarding the pre-surgical procedures and timing for surgery. The ICP study has proven to be a feasible ad efficacious methodology to point out the patient's health management. Disclosure All authors have declared no conflicts of interest.

Annals of Oncology, Sep 1, 2016

Journal of Neuro-oncology, Aug 16, 2023

Purpose The aims of our retrospective study investigated the role of immune system in glioblastom... more Purpose The aims of our retrospective study investigated the role of immune system in glioblastoma (GBM), which is the most aggressive primary brain tumor in adults characterized by a poor prognosis. The recurrence rate remains high, probably due to "immune-desert" tumor microenvironment (TME) making GBM hidden from the anti-tumoral immune clearance. Considering this, we aimed to create a panel of prognostic markers from blood and tumor tissue correlating with overall survival (OS) and progression-free survival (PFS). Methods Firstly, we analyzed the inflammatory markers NLR and PLR as the ratio of the absolute neutrophil count and absolute platelet count by the absolute lymphocyte count respectively, collected at different time points in the peripheral blood of 95 patients. Furthermore, in 31 patients of the same cohort, we analyzed the formalin-fixed paraffin embedded samples to further compare the impact of circulating and inflammatory markers within the TME. Results Patients aged < 60 years and with methylated MGMT showed better OS. While, pre-chemotherapy Systemic Inflammatory Index (SII) < 480 was related to a better OS and PFS, we observed that only CD68+macrophage and CD66b+neutrophils expressed in vascular/perivascular area (V) showed a statistically significant prognostic role in median OS and PFS. Conclusions Thus, we underscored a role of SII as predictive value of response to STUPP protocol. Regarding the TMErelated markers, we suggested to take into consideration for future studies with new immunotherapy combinations, each component relating to expression of immune infiltrating subsets.

Annals of Oncology, Oct 1, 2016

Annals of Oncology, Mar 1, 2013

International Journal of Molecular Sciences, Apr 8, 2023

Unveiling the Genomic Basis of Chemosensitivity in Sarcomas of the Extremities: An Integrated App... more Unveiling the Genomic Basis of Chemosensitivity in Sarcomas of the Extremities: An Integrated Approach for an Unmet Clinical Need. Int. J.

Therapeutic Advances in Medical Oncology, 2022

Myxofibrosarcoma (MFS) is a common entity of adult soft tissue sarcomas (STS) characterized by a ... more Myxofibrosarcoma (MFS) is a common entity of adult soft tissue sarcomas (STS) characterized by a predilection of the extremities and a high local recurrence rate. Originally classified as a myxoid variant of malignant fibrous histiocytoma, this musculoskeletal tumor has been recognized since 2002 as a distinct histotype showing a spectrum of malignant fibroblastic lesions with myxoid stroma, pleomorphism and curvilinear vessels. Currently, the molecular pathogenesis of MFS is still poorly understood and its genomic profile exhibits a complex karyotype with a number of aberrations including amplifications, deletions and loss of function. The diagnosis is challenging due to the unavailability of specific immunohistochemical markers and is based on the analysis of cytomorphologic features. The mainstay of treatment for localized disease is represented by surgical resection, with (neo)-adjuvant radio- and chemotherapy. In the metastatic setting, chemotherapy represents the backbone of treatments, however its role is still controversial and the outcome is very poor. Recent advent of genomic profiling, targeted therapies and larger enrollment of patients in translational and clinical studies, have improved the understanding of biological behavior and clinical outcome of such a disease. This review will provide an overview of current diagnostic pitfalls and clinical management of MFS. Finally, a look at future directions will be discussed.

Cancer Research, Apr 4, 2023

Background: Liposarcoma (LPS) encompass one of most common soft tissue sarcoma (STS) histological... more Background: Liposarcoma (LPS) encompass one of most common soft tissue sarcoma (STS) histological subtypes accounting for 15% of all cases. They can be divided into four entities including atypical lipomatous tumor or well-differentiated LPS (ALT/WDLPS), dedifferentiated LPS (DDLPS), myxoid LPS (MLPS) and pleomorphic LPS (PLS). Their heterogeneity is reflected in their morphology, molecular landscape, prognosis and clinical behavior. Current treatment options for localized disease include surgery, (neo)adjuvant radiotherapy and chemotherapy; for the metastatic setting chemotherapy represents the cornerstone but its role needs to be elucidated. The unavailability of predictive biomarkers makes the management of these mesenchymal diseases even more challenging. Recent evidences have shed light on the key role of cyclin-dependent kinase 4 (CDK4) in cancer cells proliferation. Methods: This study involved 21 adult patients affected by liposarcoma (n= 5 ALT/WDLPS and n= 16 DDLPS). IHC analyses of CDK4 and MDM2 were performed on FFPE surgically resected specimens by experienced sarcoma pathologists. Moreover, a patient-derived DDLPS cell line was established and pharmacological profiling was performed. Next, standard and innovative drugs currently used for LPS management were assessed in both 2D and 3D culture systems. Finally, in silico analyses based on public repositories on STS were carried out including 260 sarcoma patients. Results: IHC results highlighted an higher expression of CDK4 and MDM2 biomarkers in DDLPS compared to ALT/WDLSP. Moreover, although CDK4 and MDM2 are codified by the same genomic region, their expression did not correlate (e.g. 100% of CDK4 and 2% of MDM2 in the same patient). Therefore we hypothesized that even exhibiting a low MDM2 expression, a patient could benefit from CDK4 inhibition. Furthermore, our data showed that in DDLPS cases CDK4 expression ranged from 90% to 100% in spermatic cord, skin and abdomen while it ranged from 5% to 50% in the retroperitoneum. The above observations prompted us to hypothesize a correlation of CDK4 expression with specific anatomical sites. Moreover, pharmacological profiling showed a synergistic effect exerted by sequential treatment with palbociclib and some chemotherapeutics including trabectedin, dacarbazine, eribulin and lenvatinib. Indeed we observed a 10% increase in cell proliferation inhibition compared to standard treatment. In addition, in silico analyses revealed the role of CDK4 as negative prognostic biomarker for PFS and OS in STS. Conclusions: Our study highlighted the promising role of CDK4 in the management of LPS patients. In particular, we pointed out encouraging results of sequential treatment combining CDK4 inhibitor palbociclib and chemotherapy. Furthermore, preliminary analyses highlighted the involvement of this biomarker as a potential prognostic tool for STS. Citation Format: Silvia Vanni, Graziana Gallo, Valentina Fausti, Giacomo Miserocchi, Chiara Liverani, Chiara Spadazzi, Claudia Cocchi, Chiara Calabrese, Giovanni De Luca, Massimo Bassi, Manlio Gessaroli, Angelo Campobassi, Federica Pieri, Giorgio Ercolani, Davide Cavaliere, Lorena Gurrieri, Nada Riva, Giovanni Martinelli, Laura Mercatali, Alessandro De Vita. Dissecting the role of CDK4 in liposarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5993.

Journal of Clinical Oncology, May 20, 2015

e13003 Background: the efficacy of TMZ plus RT in elderly patients (PTS) with glioblastoma (GBM) ... more e13003 Background: the efficacy of TMZ plus RT in elderly patients (PTS) with glioblastoma (GBM) is unclear. We performed a multicenter retrospective study to analyze prognostic factors and clinica...

Journal of Clinical Oncology, May 20, 2017

2048 Background: The methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) prom... more 2048 Background: The methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) promoter has been associated with improved outcome in glioblastoma (GBM) patients (pts). Pyrosequencing (PSQ) has been reported to be an accurate method for quantitative detection of CpG islands (CpGs) methylation, but the role of methylation heterogeneity among different CpGs sites is still unclear. Aim of this study was to evaluate on a large multicentric cohort a novel prognostic score based on the evaluation of the MGMT promoter methylation at 10 different CpGs sites. Methods: We retrospectively analyzed a series of 185 pts with GBM treated at the University Hospital of Udine and Istituto Oncologico Veneto in Padua between 2006 and 2015. The methylation level of 10 CpGs (74 – 83) was determined by PSQ. The cut-off point of 9% was used to define a CpG as methylated. One point was assigned to each methylated CpG, with a total score from 0 (all CpGs &amp;amp;amp;amp;amp;amp;amp;amp;lt; 9%) to 10 (all CpGs ≥ 9%). A threshold capable to detect a favorable outcome (Overall Survival, OS &amp;amp;amp;amp;amp;amp;amp;amp;gt; 24 months) has been identified through ROC analysis as 6 by a previous study conducted at our center. The prognostic impact was explored through Cox regression. Results: After a median follow-up of 59 months, the median OS and Progression Free Survival (PFS) in the whole population were 16.41 and 9.67 months, respectively. A score ≥ 6 identified pts with a considerably better median OS (24.85 vs 12.99 months, p &amp;amp;amp;amp;amp;amp;amp;amp;lt; .0001) and PFS (11.44 vs 8.22 months, p &amp;amp;amp;amp;amp;amp;amp;amp;lt; .0001). On multivariate analysis, it remained independently associated with a favorable prognosis (HR 0.38, 95% CI 0.27-0.55, p &amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.0001) after adjustment for IDH1 mutational status (HR 0.42, 95% CI 0.20-0.87, p = .02), age ( &amp;amp;amp;amp;amp;amp;amp;amp;gt; 70 vs ≤ 70 years HR 2.20, 95% CI 1.48-3.28, p = .0001) and ECOG performance status (2-3 vs 0-1 HR 2.35, 95% CI 1.59-3.49, p &amp;amp;amp;amp;amp;amp;amp;amp;lt; .0001). The score’s prognostic value was maintained in all the explored subgroups. Conclusions: Combining methylation data from multiple CpGs increases the prognostic value of the MGMT promoter methylation assessment. The study confirmed the independent prognostic value of a novel score system based on the evaluation of the MGMT promoter methylation at 10 different CpGi sites.

Journal of Neuro-oncology, Aug 21, 2018

Purpose Epigenetic variations in the O6-methylguanine-methyltransferase gene had been widely asso... more Purpose Epigenetic variations in the O6-methylguanine-methyltransferase gene had been widely associated with a favorable impact on survival in patients affected by glioblastoma multiforme (GBM). Aim of this study is to explore a scoring system based on the gene promoter methylation in order to predict patients' prognosis. Methods A series of 128 patients with GBM was retrospectively analyzed. A training set and a validations set were then generated. The methylation level of CpGi from 74 to 83 was determined by pyrosequencing. In accordance to previous literature, each island was assigned with 1 point if the corresponding methylation level was higher than 9%. The sum consisted in a score that went from 0 (all CpGi < 9%) to 10 (all CpGi ≥ 9%). A threshold capable to detect a favorable outcome (overall survival, OS > 24 months) was identified by ROC analysis. Results Median OS and follow-up were 14 and 32.6 months respectively. Among the total population, 35% of the pts had a score of 0, while 29% had a score of 10. A score ≥ 6 was associated with a favorable prognosis also when corrected for age (> 70 vs. ≤ 70 years) and ECOG performance status (0-1 vs. 2-3). Similar results were observed also in terms of PFS. Results were consistent in the training and in the validation set. Conclusions The present manuscript explored a novel scoring system capable to take into consideration the methylation status of each single CpGi, capable to better predict prognosis in GBM patients.

Future Oncology, Apr 1, 2018

MGMT promoter methylation has been associated with improved survival in glioblastoma multiforme t... more MGMT promoter methylation has been associated with improved survival in glioblastoma multiforme treated with temozolomide. However, there is no consensus on specific cutoff levels of methylation. The aims of the study were to explore the prognostic impact of MGMT methylation status and to analyze the role of specific cutoff values. Materials & methods: We analyzed 108 glioblastoma multiforme patients treated between 2008 and 2013 stratified according to three pyrosequencing-based quantitative methylation in: unmethylated (methylation <9%), intermediate (9-29%) and highly methylated (>29%). Results: The three-class stratification has a prognostic impact (median progression-free survival: 7.97, 11.6 and 15 months respectively; p = 0.004; median OS: 13.2, 15.8 and 19.5 months, respectively; p = 0.0002), especially in patients exposed to temozolomide. Conclusion: Our study confirmed that the independent prognostic role of MGMT methylation status. An average level of methylation between all investigated CpGs of 9% may help discriminating between methylated and unmethylated tumors.

Journal of Neuro-oncology, Sep 30, 2015

The efficacy of temozolomide (TMZ) plus radiation therapy (RT) in elderly patients with glioblast... more The efficacy of temozolomide (TMZ) plus radiation therapy (RT) in elderly patients with glioblastoma is unclear. We performed a large multicenter retrospective study to analyze prognostic factors and clinical outcome in these patients. Inclusion criteria were age ≥65 years, newly histologically confirmed glioblastoma, ECOG PS 0-2, adjuvant treatment with RT plus TMZ. We enrolled 237 patients; the average age was 71 and ECOG PS was 0-1 in 196 patients; gross total resection was performed in 174 cases. MGMT was analyzed in 151 persons and was methylated in 56 %. IDH1 was assessed in 100 patients and was mutated in 6 %. Seventy-one patients were treated with RT 40 Gy and 166 with RT 60 Gy. Progression-free survival and overall survival (OS) were 11.3 and 17.3 months, respectively. Overall survival was 19.4 vs 13.8 months for patients treated with RT 60 Gy and 40 Gy (p = 0.02); OS was 17.7 versus 16.1 months for patients treated with gross total resection vs partial surgery (p = 0.02); OS was 21.2 versus 13.6 months for methylated and unmethylated MGMT (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). On multivariate analysis, gross total resection, RT 60 Gy, methylated MGMT and ECOG PS 0-1 were independent predictors of longer survival. Twenty-five patients (10 %) had grade 3-4 haematological toxicity during the concomitant treatment. We showed that, in elderly patients in good clinical condition treated with concomitant treatment, standard-course irradiation might be more effective than short-course irradiation. Methylated MGMT remains the most important prognostic factor.

Frontiers in Oncology, Oct 20, 2020

Glioblastoma is the most aggressive tumor of the central nervous system. Prognosis is poor, even ... more Glioblastoma is the most aggressive tumor of the central nervous system. Prognosis is poor, even in the presence of a methylated state of MGMT gene promoter, which represents the biomarker with the highest prognostic/predictive value for the standard treatment of patients. Among patients with a methylated MGMT status, we identified an intermediate range of methylation above the standard 9% cutoff (gray zone) in which the predictive strength of the marker was lost. In an effort to improve the evaluation of the biomarker in clinical decision-making, we are carrying out a retrospective study, performing an in-depth analysis of samples used for diagnosis to understand how molecular heterogeneity, a hallmark of glioblastoma, impacts the evaluation of MGMT gene promoter methylation. Preliminary data from samples belonging to the "gray zone" tend to confirm the hypothesis of a mismatch between methylation values used for clinical decision-making and those included in our in-depth analysis. Confirmation of these data would help to better define the predictive power of MGMT promoter methylation status and greatly facilitate clinical decision-making.

Research Square (Research Square), Feb 17, 2021

Background: In ammatory myo broblastic tumor (IMT) is a rare mesenchymal tumor and is prevalent a... more Background: In ammatory myo broblastic tumor (IMT) is a rare mesenchymal tumor and is prevalent among children and adolescents. Surgery is the most important therapeutic approach for IMT and complete resection is recommended. Although 50% of IMTs present anaplastic lymphoma kinase (ALK) rearrangements, an e cacy has been shown by the use of Crizotinib. However the genetic landscape of this tumor is not fully understood and the therapeutic options are limited in particular for the remaining percentage of negative ALK tumors. Case presentation: In our case, we detail the clinical history of 18-year-old female patient diagnosed with pulmonary IMT negative for ALK, subjected to surgery and subsequently to follow-up. The initial pathology report oriented for a salivary gland lung cancer. Afterwards due to a second look by another pathologist an ALK negative IMT of the lung was diagnosed. We also perform a literature review based on IMT and other kinase fusions found in addition to ALK such as ROS proto-oncogene 1 (ROS1), rearranged during transfection (RET), neurotrophic receptor tyrosine kinases (NTRKs) and platelet derived growth factor receptor (PDGFR beta). Conclusions: IMT is a very rare disease involving children and adolescents. Little is known about the clinical and molecular characteristics, pathological diagnosis, prognosis and optimal management strategy of IMT. Since there is no "standard of care" therapy for IMT, identifying feasible genomic alterations could rede ne the management of patients with negative ALK disease.