Publications by authors named "Elisa Roca"

51 Publications

SCLC Treatment in the Immuno-Oncology Era: Current Evidence and Unmet Needs.

Front Oncol 2022 14;12:840783. Epub 2022 Apr 14.

Medical Oncology, Department of Medicine, University of Verona, Verona, Italy.

Small cell lung cancer (SCLC) represents about 13%-15% of all lung cancers. It has a particularly unfavorable prognosis and in about 70% of cases occurs in the advanced stage (extended disease). Three phase III studies tested the combination of immunotherapy (atezolizumab, durvalumab with or without tremelimumab, and pembrolizumab) with double platinum chemotherapy, with practice-changing results. However, despite the high tumor mutational load and the chronic pro-inflammatory state induced by prolonged exposure to cigarette smoke, the benefit observed with immunotherapy is very modest and most patients experience disease recurrence. Unfortunately, biological, clinical, or molecular factors that can predict this risk have not yet been identified. Thanks to these clinically meaningful steps forward, SCLC is no longer considered an "orphan" disease. Innovative treatment strategies and combinations are currently under investigation to further improve the expected prognosis of patients with SCLC. Following the recent therapeutic innovations, we have reviewed the available literature data about SCLC management, with a focus on current unmet needs and potential predictive factors. In detail, the role of radiotherapy; fragile populations, such as elderly or low-performance status patients (ECOG PS 2), usually excluded from randomized studies; predictive factors of response useful to optimize and guide therapeutic choices; and new molecular targets and future combinations have been explored and revised.
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http://dx.doi.org/10.3389/fonc.2022.840783DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9047718PMC
April 2022

A Definitive Prognostication System for Patients With Thoracic Malignancies Diagnosed With Coronavirus Disease 2019: An Update From the TERAVOLT Registry.

J Thorac Oncol 2022 05 1;17(5):661-674. Epub 2022 Feb 1.

Cancer Trials Ireland, Dublin, Ireland; Mid-Western Cancer Centre, University Hospital Limerick, Limerick, Ireland.

Introduction: Patients with thoracic malignancies are at increased risk for mortality from coronavirus disease 2019 (COVID-19), and a large number of intertwined prognostic variables have been identified so far.

Methods: Capitalizing data from the Thoracic Cancers International COVID-19 Collaboration (TERAVOLT) registry, a global study created with the aim of describing the impact of COVID-19 in patients with thoracic malignancies, we used a clustering approach, a fast-backward step-down selection procedure, and a tree-based model to screen and optimize a broad panel of demographics and clinical COVID-19 and cancer characteristics.

Results: As of April 15, 2021, a total of 1491 consecutive eligible patients from 18 countries were included in the analysis. With a mean observation period of 42 days, 361 events were reported with an all-cause case fatality rate of 24.2%. The clustering procedure screened 73 covariates in 13 clusters. A further multivariable logistic regression for the association between clusters and death was performed, resulting in five clusters significantly associated with the outcome. The fast-backward step-down selection procedure then identified the following seven major determinants of death: Eastern Cooperative Oncology Group-performance status (ECOG-PS) (OR = 2.47, 1.87-3.26), neutrophil count (OR = 2.46, 1.76-3.44), serum procalcitonin (OR = 2.37, 1.64-3.43), development of pneumonia (OR = 1.95, 1.48-2.58), C-reactive protein (OR = 1.90, 1.43-2.51), tumor stage at COVID-19 diagnosis (OR = 1.97, 1.46-2.66), and age (OR = 1.71, 1.29-2.26). The receiver operating characteristic analysis for death of the selected model confirmed its diagnostic ability (area under the receiver operating curve = 0.78, 95% confidence interval: 0.75-0.81). The nomogram was able to classify the COVID-19 mortality in an interval ranging from 8% to 90%, and the tree-based model recognized ECOG-PS, neutrophil count, and c-reactive protein as the major determinants of prognosis.

Conclusions: From 73 variables analyzed, seven major determinants of death have been identified. Poor ECOG-PS was found to have the strongest association with poor outcome from COVID-19. With our analysis, we provide clinicians with a definitive prognostication system to help determine the risk of mortality for patients with thoracic malignancies and COVID-19.
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http://dx.doi.org/10.1016/j.jtho.2021.12.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8804493PMC
May 2022

CT texture analysis for prediction of EGFR mutational status and ALK rearrangement in patients with non-small cell lung cancer.

Radiol Med 2021 Jun 29;126(6):786-794. Epub 2021 Jan 29.

Department of Radiology, University of Brescia, Piazzale Spedali Civili 1, 25123, Brescia, Italy.

Purpose: To develop a CT texture-based model able to predict epidermal growth factor receptor (EGFR)-mutated, anaplastic lymphoma kinase (ALK)-rearranged lung adenocarcinomas and distinguish them from wild-type tumors on pre-treatment CT scans.

Materials And Methods: Texture analysis was performed using proprietary software TexRAD (TexRAD Ltd, Cambridge, UK) on pre-treatment contrast-enhanced CT scans of 84 patients with metastatic primary lung adenocarcinoma. Textural features were quantified using the filtration-histogram approach with different spatial scale filters on a single 5-mm-thick central slice considered representative of the whole tumor. In order to deal with class imbalance regarding mutational status percentages in our population, the dataset was optimized using the synthetic minority over-sampling technique (SMOTE) and correlations with textural features were investigated using a generalized boosted regression model (GBM) with a nested cross-validation approach (performance averaged over 1000 resampling episodes).

Results: ALK rearrangements, EGFR mutations and wild-type tumors were observed in 19, 28 and 37 patients, respectively, in the original dataset. The balanced dataset was composed of 171 observations. Among the 29 original texture variables, 17 were employed for model building. Skewness on unfiltered images and on fine texture was the most important features. EGFR-mutated tumors showed the highest skewness while ALK-rearranged tumors had the lowest values with wild-type tumors showing intermediate values. The average accuracy of the model calculated on the independent nested validation set was 81.76% (95% CI 81.45-82.06).

Conclusion: Texture analysis, in particular skewness values, could be promising for noninvasive characterization of lung adenocarcinoma with respect to EGFR and ALK mutations.
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http://dx.doi.org/10.1007/s11547-020-01323-7DOI Listing
June 2021

The appropriate use of circulating EBV-DNA in nasopharyngeal carcinoma: Comprehensive clinical practice guidelines evaluation.

Oral Oncol 2021 03 11;114:105128. Epub 2021 Jan 11.

Medical Oncology, Department of Medical & Surgical Specialties, Radiological Sciences & Public Health, University of Brescia, ASST Spedali Civili, 25123 Brescia, Italy.

Background: In EBV-related nasopharyngeal carcinoma (NPC), quantitative determination of circulating EBV-DNA (cEBV-DNA) can potentially be applied as disease marker. The aim of the study was to investigate if the clinical utility of cEBV-DNA is established in clinical practice guidelines and if recommendations are provided to standardize the quantitative cEBV-DNA determination.

Methods: A systematic literature search for NPC guidelines published since 2011 was performed. Information for cEBV-DNA detection method and use in clinical practice was synthesized in consecutive steps of increasing simplification.

Results: From 570 titles and abstracts identified by the search, 16 guidelines were included. The selected documents were further clustered as either being based on a systematic literature revision to generate recommendations (4/16) or not (12/16). cEBV-DNA was evaluated in only one guideline based on a systematic revision and in 8 guidelines without systematic revision. Half of available guidelines provide recommendation for its clinical use. Methodological issues on cEBV-DNA determination are discussed by 31% of guidelines, without providing any recommendation on method standardization.

Conclusions: Due to its prognostic value, cEBV-DNA is suggested in the pre-treatment work-up and in the follow-up. Guideline producers need to take into more consideration methodological aspects impacting the actual reliability and generalizability of laboratory results.
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http://dx.doi.org/10.1016/j.oraloncology.2020.105128DOI Listing
March 2021

Rate of venous thromboembolism and atrial fibrillation in a real-world case series of advanced cancer patients: the CaTEV Study.

J Cardiovasc Med (Hagerstown) 2021 06;22(6):444-452

Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, Institute of Cardiology, ASST Spedali Civili di Brescia.

Background: Venous thromboembolism is the second leading cause of death in cancer patients and its incidence seems underestimated. In addition, cancer patients have an increased risk of developing atrial fibrillation, which may be the first presentation of cancer itself. The primary aim of this study was to define the incidence of venous thromboembolism (VTE) and atrial fibrillation in a real-word series of advanced cancer patients.

Methods: We performed a retrospective single-institution study on patients diagnosed with stage IV solid neoplasia at the outpatient clinic of the Medical Oncology Unit (Spedali Civili Brescia, Italy), from January to December 2018.

Results: A total of 403 patients were enrolled, with a mean age at presentation of 63 years (range 18-85 years). A VTE was observed in 24% of cases, half of which occurred after diagnosis of metastatic neoplasia, with a median time of onset of 5.5 months (range 0-84). About 3% of patients developed atrial fibrillation after cancer diagnosis. In this patient series, no statistically significant differences were found when comparing Khorana and PROTECHT thromboembolic risk scores, both before and after the start of chemotherapy. Overall, about 25% of the patients received anticoagulant therapy; in most cases, the drug of choice was low-molecular-weight heparin (LMWH).

Conclusion: This study showed for cancer patients a considerably higher incidence of VTE and a comparable incidence of atrial fibrillation than reported in literature. Validated thromboembolic risk scores appear to be poorly predictive, and LMWH remains the most widely used anticoagulant drug.
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http://dx.doi.org/10.2459/JCM.0000000000001124DOI Listing
June 2021

High Prevalence and Early Occurrence of Skeletal Complications in EGFR Mutated NSCLC Patients With Bone Metastases.

Front Oncol 2020 12;10:588862. Epub 2020 Nov 12.

Medical Oncology, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health University of Brescia, ASST-Spedali Civili, Brescia, Italy.

Objectives: The prevalence of Skeletal Related Adverse Events (SREs) in EGFR mutated non-small cell lung cancer (NSCLC) patients with bone metastases, treated with modern tyrosine kinase inhibitors (TKIs), has been scarcely investigated.

Materials And Methods: We retrospectively evaluated the data of EGFR mutated NSCLC patients with bone metastases treated with TKIs in 12 Italian centers from 2014 to 2019, with the primary aim to explore type and frequency of SREs.

Results: Seventy-seven out of 274 patients enrolled (28%) developed at least one major SRE: 55/274 (20%) bone fractures, 30/274 (11%) spinal cord compression, 5/274 (2%) hypercalcemia. Median time to the onset of SRE was 3.63 months. Nine patients (3%) underwent bone surgery and 150 (55%) radiation therapy on bone. SREs were more frequently observed within the 12 months from TKI start than afterwards (71 29%, p 0.000). Patient Performance Status and liver metastases where independently associated with the risk of developing SREs. Median TKI exposure and overall survival were 11 and 28 months, respectively. Bone resorption inhibitors were associated with a lower risk of death (HR 0.722, 95% CI: 0.504-1.033, p = 0.075) although not statistically significant at multivariate analysis.

Conclusion: Bone metastatic NSCLC patients with EGFR mutated disease, treated with EGFR TKIs, have a relatively long survival expectancy and are at high risk to develop SREs. The early SRE occurrence after the TKI start provides the rationale to administer bone resorption inhibitors.
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http://dx.doi.org/10.3389/fonc.2020.588862DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7689017PMC
November 2020

Is DNA repair a potential target for effective therapies against malignant mesothelioma?

Cancer Treat Rev 2020 Nov 25;90:102101. Epub 2020 Aug 25.

Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy. Electronic address:

Malignant pleural mesothelioma (MPM) is a rare malignancy mainly caused by asbestos exposure. Germinal and acquired mutations in genes of DNA repair pathways, in particular of homologous recombination repair, are frequent in MPM. Here we overview the available experimental data suggesting that an impaired DNA repair system affects MPM pathogenesis by leaving lesions through the genome unresolved. DNA repair defects represent a vulnerability of MPM, and it seems plausible to propose that leveraging these deficiencies could have therapeutic potential for patients with MPM, for whom there is an urgent need of more effective therapies.
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http://dx.doi.org/10.1016/j.ctrv.2020.102101DOI Listing
November 2020

Gene Expression Clustering and Selected Head and Neck Cancer Gene Signatures Highlight Risk Probability Differences in Oral Premalignant Lesions.

Cells 2020 08 3;9(8). Epub 2020 Aug 3.

Department of Medical & Surgical Specialties, Radiological Sciences & Public Health, University of Brescia, ASST Spedali Civili, 25123 Brescia, Italy.

Background: Oral premalignant lesions (OPLs) represent the most common oral precancerous conditions. One of the major challenges in this field is the identification of OPLs at higher risk for oral squamous cell cancer (OSCC) development, by discovering molecular pathways deregulated in the early steps of malignant transformation. Analysis of deregulated levels of single genes and pathways has been successfully applied to head and neck squamous cell cancers (HNSCC) and OSCC with prognostic/predictive implications. Exploiting the availability of gene expression profile and clinical follow-up information of a well-characterized cohort of OPL patients, we aim to dissect tissue OPL gene expression to identify molecular clusters/signatures associated with oral cancer free survival (OCFS).

Materials And Methods: The gene expression data of 86 OPL patients were challenged with: an HNSCC specific 6 molecular subtypes model (Immune related: HPV related, Defense Response and Immunoreactive; Mesenchymal, Hypoxia and Classical); one OSCC-specific signature (13 genes); two metabolism-related signatures (3 genes and signatures raised from 6 metabolic pathways associated with prognosis in HNSCC and OSCC, respectively); a hypoxia gene signature. The molecular stratification and high versus low expression of the signatures were correlated with OCFS by Kaplan-Meier analyses. The association of gene expression profiles among the tested biological models and clinical covariates was tested through variance partition analysis.

Results: Patients with Mesenchymal, Hypoxia and Classical clusters showed an higher risk of malignant transformation in comparison with immune-related ones (log-rank test, = 0.0052) and they expressed four enriched hallmarks: "TGF beta signaling" "angiogenesis", "unfolded protein response", "apical junction". Overall, 54 cases entered in the immune related clusters, while the remaining 32 cases belonged to the other clusters. No other signatures showed association with OCFS. Our variance partition analysis proved that clinical and molecular features are able to explain only 21% of gene expression data variability, while the remaining 79% refers to residuals independent of known parameters.

Conclusions: Applying the existing signatures derived from HNSCC to OPL, we identified only a protective effect for immune-related signatures. Other gene expression profiles derived from overt cancers were not able to identify the risk of malignant transformation, possibly because they are linked to later stages of cancer progression. The availability of a new well-characterized set of OPL patients and further research is needed to improve the identification of adequate prognosticators in OPLs.
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http://dx.doi.org/10.3390/cells9081828DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7466020PMC
August 2020

Ki-67 Index of 55% Distinguishes Two Groups of Bronchopulmonary Pure and Composite Large Cell Neuroendocrine Carcinomas with Distinct Prognosis.

Neuroendocrinology 2021 4;111(5):475-489. Epub 2020 May 4.

Unit of Pathology, Department of Medicine and Surgery and Research Center for the Study of Hereditary and Familial tumors, University of Insubria, Varese, Italy.

Background: Little information is available concerning prognostic factors for bronchopulmonary large cell neuroendocrine carcinomas (BP-LCNECs) and even less is known about combined LCNECs (Co-LCNECs). We investigated whether an integrated morphological, immunohistochemical, and molecular approach could be used for their prognostic evaluation.

Methods: Morphological (including combined features), proliferative (mitotic count/Ki-67 index), immunohistochemical (napsin A, p40, TTF-1, CD44, OTP, SSTR2A, SSTR5, mASH1, p53, RB1, and MDM2), and genomic (TP53, RB1, ATM, JAK2, KRAS, and STK11) findings were analyzed in BP-LCNECs from 5 Italian centers, and correlated with overall survival (OS). The Ki-67 index was expressed as the percentage of positive cells in hot spots as indicated in the WHO 2019 Digestive System Tumors and, for Co-LCNECs, the Ki-67 index was evaluated only in the LCNEC component.

Results: A total of 111 LCNECs were distinguished into 70 pure LCNECs, 35 Co-LCNECs (27 with adenocarcinoma [ADC] and 8 with squamous cell carcinoma [SqCC]), and 6 LCNECs with only napsin A immunoreactivity. The Ki-67 index cutoff at 55% evaluated in the neuroendocrine component was the most powerful predictor of OS (log-rank p = 0.0001) in all LCNECs; 34 cases had a Ki-67 index <55% (LCNEC-A) and 77 had a Ki-67 index ≥55% (LCNEC-B). Statistically significant differences in OS (log-rank p = 0.0001) were also observed between pure and Co-LCNECs. A significant difference in OS was found between pure LCNECs-A and Co-LCNECs-A (p < 0.05) but not between pure LCNECs-B and Co-LCNECs-B. Co-LCNEC-ADC and LCNEC napsin A+ cases had longer OS than pure LCNEC and Co-LCNEC-SqCC cases (log-rank p = 0.0001). On multivariable analysis, tumor location, pure versus combined features, and napsin A, but no single gene mutation, were significantly associated with OS after adjustment for Ki-67 index and study center (p < 0.05).

Conclusions: The Ki-67 proliferation index and the morphological characterization of combined features in LCNECs seem to be important tools for predicting clinical outcome in BP-LCNECs.
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http://dx.doi.org/10.1159/000508376DOI Listing
November 2021

Prognostic clinical factors in patients affected by non-small-cell lung cancer receiving Nivolumab.

Expert Opin Biol Ther 2020 03 6;20(3):319-326. Epub 2020 Feb 6.

Unit of Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.

: Immune-checkpoint inhibitors have radically changed the treatment landscape of Non-Small-Cell Lung Cancer (NSCLC). It is still unclear whether specific clinical characteristics might identify those patients benefiting from immunotherapy more than others. The aim of this study was to identify clinical characteristics associated with disease-specific survival (DSS), time-to-treatment failure (TTF), objective responses (OR) and progressive disease (PD) in NSCLC patients treated with Nivolumab.: This was a multicenter retrospective study conducted on 294 patients treated with Nivolumab for advanced NSCLC.: Of the more than 50 variables analyzed, five showed a significant correlation with DSS: ECOG PS, size of the biggest brain metastasis, number of metastatic sites, toxicity, and malignant pleural effusion. Three variables significantly correlated with TTF: malignant pleural effusion, number of metastatic sites, number of liver metastases. Malignant pleural effusion was the only variable showing a significant correlation with OR, as well as the only one correlating with all the endpoints of the study.: This study identified clinical characteristics associated with survival and response during treatment with Nivolumab in NSCLC patients. The unfavorable association between malignant pleural effusion and objective response is a novel finding with important translational implications.
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http://dx.doi.org/10.1080/14712598.2020.1724953DOI Listing
March 2020

Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), and Outcomes with Nivolumab in Pretreated Non-Small Cell Lung Cancer (NSCLC): A Large Retrospective Multicenter Study.

Adv Ther 2020 03 30;37(3):1145-1155. Epub 2020 Jan 30.

Department of Medical Oncology, Campus Bio-Medico University of Rome, Rome, Italy.

Introduction: Immune checkpoint inhibitors have provided substantial benefit in non-small cell lung cancer (NSCLC) with unprecedented results in terms of survival. However, the identification of reliable predictive biomarkers to these agents is lacking and multiple clinicopathological factors have been evaluated. The aim of this study was to analyze the potential role of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lactate dehydrogenase (LDH) levels in patients with pretreated NSCLC receiving nivolumab.

Methods: This was a retrospective multicenter study involving 14 Italian centers, evaluating the role of some laboratory results in patients with NSCLC treated with nivolumab in the second or later lines of therapy for at least four doses and with a disease re-staging.

Results: A total of 187 patients with available pretreatment laboratory results were included. NLR levels below 5 were associated with an improvement in terms of both progression-free survival (PFS) (p = 0.028) and overall survival (OS) (p = 0.001), but not in terms of overall response rate (ORR) or disease control rate (DCR). Moreover, PLR levels below 200 were associated with longer PFS (p = 0.0267) and OS (p = 0.05), as well as higher ORR (p = 0.04) and DCR (p = 0.001). In contrast, LDH levels above the upper normal limit (UNL) were not associated with significant impact on patient outcomes.

Conclusions: Patients with pretreated NSCLC and high pretreatment levels of NLR and PLR may experience inferior outcomes with nivolumab. Therefore, in this subgroup of patients with poor prognosis the use of alternative therapeutic strategies may be a valuable option, especially in programmed cell death ligand 1 (PD-L1)-negative patients and/or in the presence of other additional poor prognostic factors.
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http://dx.doi.org/10.1007/s12325-020-01229-wDOI Listing
March 2020

Tumor Infiltrating Neutrophils Are Enriched in Basal-Type Urothelial Bladder Cancer.

Cells 2020 01 25;9(2). Epub 2020 Jan 25.

Department of Molecular and Translational Medicine, School of Medicine, University of Brescia, 25125 Brescia, Italy.

Background: Urothelial bladder cancers (UBCs) are distinct in two main molecular subtypes, namely basal and luminal type. Subtypes are also diverse in term of immune contexture, providing a rationale for patient selection to immunotherapy.

Methods: By digital microscopy analysis of a muscle-invasive BC (MIBC) cohort, we explored the density and clinical significance of CD66b tumor-associated-neutrophils (TAN) and CD3 T cells. Bioinformatics analysis of UBC datasets and gene expression analysis of UBC cell lines were additionally performed.

Results: Basal type BC contained a significantly higher density of CD66b TAN compared to the luminal type. This finding was validated on TCGA, GSE32894 and GSE124305 datasets by computing a neutrophil signature. Of note, basal-type MIBC display a significantly higher level of chemokines (CKs) attracting neutrophils. Moreover, pro-inflammatory stimuli significantly up-regulate CXCL1, CXCL2 and CXCL8 in 5637 and RT4 UBC cell lines and induce neutrophil chemotaxis. In term of survival, a high density of T celsl and TAN was significantly associated to a better outcome, with TAN density showing a more limited statistical power and following a non-linear predicting model.

Conclusions: TAN are recruited in basal type MIBC by pro-inflammatory CKs. This finding establishes a groundwork for a better understanding of the UBC immunity and its relevance.
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http://dx.doi.org/10.3390/cells9020291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072276PMC
January 2020

Clinical Features and Progression Pattern of Acquired T790M-positive Compared With T790M-negative EGFR Mutant Non-small-cell Lung Cancer: Catching Tumor and Clinical Heterogeneity Over Time Through Liquid Biopsy.

Clin Lung Cancer 2020 01 5;21(1):1-14.e3. Epub 2019 Aug 5.

Department of Oncology 2, Istituto Oncologico Veneto - IRCCS, Padova, Italy. Electronic address:

Background: Clinical-pathologic predictors of acquired T790M epidermal growth factor receptor (EGFR) mutation in Caucasian patients with non-small-cell lung cancer (NSCLC) progressing after first-/second-generation tyrosine kinase inhibitors (TKIs) is an open field for research. Similarly, the best time point for T790M detection by liquid or tissue biopsy after disease progression is currently matter of debate.

Patients And Methods: This is an observational study at 7 Italian centers enrolling patients with EGFR-mutant NSCLC progressing after first-/second-generation EGFR TKIs, between 2014 and 2018, aiming at comparing baseline clinical-pathologic features and progression patterns in acquired T790M-positive compared with T790M-negative cases.

Results: A total of 235 patients received first-line treatment with gefitinib (N = 126; 53%), erlotinib (N = 51; 22%), or afatinib (N = 58; 25%). In 120 (51%) cases, T790M was detected in liquid biopsy, tissue biopsy, or both. Age younger than 65 years (P = .037), the presence of common mutations (P = .004), and better response to first-line TKI (P = .023) were correlated with T790M positivity. T790M detection was associated with higher number of new progressing sites (P = .04), liver progression (P = .002), and a lower frequency of lung metastases (P = .027). When serial liquid biopsies were performed (N = 15), an oligoprogressive disease was correlated with a negative test outcome, whereas systemic progression was observed at the time of T790M positivity.

Conclusion: This study on a Caucasian population showed that age, type of EGFR mutation at diagnosis, response to first-line treatment, and peculiar progression pattern are associated with T790M status. Serial liquid biopsy might be useful for treatment selection, especially when tissue rebiopsy is not feasible.
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http://dx.doi.org/10.1016/j.cllc.2019.07.009DOI Listing
January 2020

Prognostic and predictive value of histogram analysis in patients with non-small cell lung cancer refractory to platinum treated by nivolumab: A multicentre retrospective study.

Eur J Radiol 2019 Sep 17;118:251-256. Epub 2019 Jul 17.

University of Brescia, Department of Radiology, P.le Spedali Civili 1, 25123, Brescia, Italy. Electronic address:

Purpose: The aim of this study was to assess computed-tomography histogram analysis (CTHA) as prognostic and predictive factor in platinum-refractory non-small cell lung carcinoma (NSCLC) treated with immune checkpoint inhibitor Nivolumab.

Method: One hundred and four patients were enrolled from 3 different centers. CT was performed using similar parameters among different scanners. CTHA was performed with the proprietary software TexRAD, which extracts histogram features at different spatial scale (spatial scale filters, SSF) producing 30 CTHA features per patients. Cross-validated Least Absolute Shrinkage and Selection Operator LASSO was used to select those features which were related to overall and progression-free survival (OS and PFS, respectively). High- and low-risk subgroups were identified using the best cutoff.

Results: Median follow-up was 13.8 weeks. Median OS and PFS were 7.3 and 3 months, respectively. LASSO selected kurtosis obtained by SSF = 4 mm as the single feature related to OS, leading to an hazard ratio (HR) of 0.476 (95%CI 0.29-0.77). PFS was related with kurtosis SSF = 6 mm, with HR of 0.556 (95%CI 0.36-0.86).

Conclusion: Despite its limitations, this study is the first which suggests that CTHA could play a role in stratifying prognosis and treatment response in patients with NSCLC treated with Nivolumab.
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http://dx.doi.org/10.1016/j.ejrad.2019.07.019DOI Listing
September 2019

Maintenance with lanreotide in small-cell lung cancer expressing somatostatine receptors: A multicenter, randomized, phase 3 trial.

Lung Cancer 2019 08 11;134:121-126. Epub 2019 Jun 11.

Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; Università Cattolica Del Sacro Cuore, Rome, Italy. Electronic address:

Objectives: Considering the frequent expression of somatostatine receptors, we designed the G04.2011 trial to investigate the efficacy of the somatostatine analogue lanreotide in maintenance for SCLC patients after response to standard treatment.

Materials And Methods: A multicenter, randomized, phase 3 trial was conducted in SCLC expressing somatostatine receptors at baseline Octreoscan, responding after platinum-based chemotherapy with/without radiotherapy. Patients were randomized 1:1 to receive maintenance lanreotide 120 mg subcutaneously every 28 days, up to 1 year or progression versus observation. Randomization was stratified according to stage (limited/extended, LD/ED). The primary end-point was progression-free survival (PFS). Secondary endpoints were overall survival (OS) and safety.

Results: Seventy-one patients were randomly assigned (39 to lanreotide, 32 to observation) in 9 Italian institutions. Median PFS was 3.6 (95% CI 3.2-3.9) with lanreotide versus 2.3 months (95% CI 1.7-2.9) with observation (HR 1.51, 95% CI 0.90-2.50; P = 0.11). Stage was an independent predictor for PFS (HR 3.14, 95% CI 1.77-5.57; P < 0.0001). Median PFS was 7.0 (95% CI <1-13.5) with lanreotide versus 3.8 months (95% CI <1-8.6) with observation in LD (P = 0.21), and 3.0 (95% CI 2.2-3.8) versus 2.2 (95% 1.7-2.7) in ED (P = 0.19). Median OS was 9.5 (95% CI 4.8-14.3) with lanreotide versus 4.7 months (95% CI <1-16.6) with observation (P = 0.47). Treatment-related adverse events occurred in 28% of patients with lanreotide (grade 3 in two patients).

Conclusion: Although survival outcomes were not significantly prolonged with lanreotide as a maintenance in SCLC expressing somatostatin receptors after response to standard treatment, lanreotide showed a slight PFS benefit in LD SCLC deserving further investigations.
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http://dx.doi.org/10.1016/j.lungcan.2019.06.011DOI Listing
August 2019

Texture features of colorectal liver metastases on pretreatment contrast-enhanced CT may predict response and prognosis in patients treated with bevacizumab-containing chemotherapy: a pilot study including comparison with standard chemotherapy.

Radiol Med 2019 Sep 6;124(9):877-886. Epub 2019 Jun 6.

Department of Radiology, University of Brescia, P.le Spedali Civili 1, 25123, Brescia, Italy.

Purpose: Bevacizumab added to chemotherapy can improve survival in patients with metastatic colorectal cancer, but no predictive factors of efficacy are available in clinical practice. The aim of this study is to assess the predictive and prognostic value of texture analysis on pretreatment contrast-enhanced CT in patients affected by colorectal liver metastases.

Materials And Methods: Forty-three patients with colorectal liver metastases were retrospectively included in the study: 23 treated with bevacizumab-containing chemotherapy (group A), and 20 with standard chemotherapy (group B). Target liver lesions were analyzed by texture analysis of pretreatment contrast-enhanced CT. Texture analysis produced the parameter uniformity, describing lesion heterogeneity. Radiological response was classified after 3 months according to RECIST-1.1. Overall survival (OS) and progression-free survival (PFS) were considered to be outcome indicators. Multivariable logistic regression and survival analysis were performed.

Results: Uniformity was lower in responders than in nonresponders (p < 0.001) in group A but not in group B. Lesion CT density was lower in nonresponders in both groups (p = 0.03 and 0.02, respectively). In group A, uniformity was independently correlated with radiological response (odds ratio = 20, p = 0.01), OS and PFS (relative risks 6.94 and 5.05, respectively; p = 0.005 and p = 0.004, respectively). In group B, no variables were correlated with radiological response, OS or PFS.

Conclusion: Texture analysis on contrast-enhanced CT stratified response probability and prognosis in patients with colorectal liver metastases treated with bevacizumab-containing therapy. This result was specific for the bevacizumab group.
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http://dx.doi.org/10.1007/s11547-019-01046-4DOI Listing
September 2019

Abiraterone and prednisone therapy may cause severe hypoglycemia when administered to prostate cancer patients with type 2 diabetes receiving glucose-lowering agents.

Endocrine 2019 06 7;64(3):724-726. Epub 2019 May 7.

Medical Oncology, ASST-Spedali Civili, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Piazzale Spedali Civili 1, 25123, Brescia, Italy.

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http://dx.doi.org/10.1007/s12020-019-01947-4DOI Listing
June 2019

Abiraterone acetate exerts a cytotoxic effect in human prostate cancer cell lines.

Naunyn Schmiedebergs Arch Pharmacol 2019 06 15;392(6):729-742. Epub 2019 Feb 15.

Section of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, V.le Europa 11, 25123, Brescia, Italy.

To study the capability of the CYP17A1 inhibitor abiraterone acetate (AER) to antagonize the androgen receptor (AR) activation in human prostate cancer (PCa) cell lines. T877A-AR-LNCaP, WT-AR-VCaP, AR-negative DU145, and PC3 PCa cell lines were used by MTT and cell count to study the ability of AER and enzalutamide (ENZ) to modify cell viability. The role of ARs in LNCaP was demonstrated through a gene-silencing experiment. The mechanism of AER cytotoxicity in LNCaP cells was studied, as well as the ability of AER to modulate AR gene expression. The in silico docking approach was applied to study the interaction of AER and ENZ with T877A-AR. Through high-performance liquid chromatography, the production of the AER main metabolite Δ4A was studied. AER bound AR in an almost identical manner to that of dihydrotestosterone (DHT). The higher binding energy for AER in T877A-AR could explain the major cytotoxic effect observed in LNCaP cells. The capability of LNCaP cells to synthesize Δ4A could mediate, at least in part, this effect. AER cytotoxicity in LNCaP cells was mainly due to the activation of apoptosis. Further, AER induced modification of AR target gene expression, suggesting a direct effect on AR activity. AER-induced cytotoxicity on PCa cell lines seemed to be mediated by binding with AR. The higher affinity of AER for T877A-AR may suggest a potential role of AER in the management of CRPC carrying this mutation; however, T877A-AR expressing CRPC patients developed AER resistance, probably due to the increase of progesterone.
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http://dx.doi.org/10.1007/s00210-019-01622-5DOI Listing
June 2019

Outcome of EGFR-mutated adenocarcinoma NSCLC patients with changed phenotype to squamous cell carcinoma after tyrosine kinase inhibitors: A pooled analysis with an additional case.

Lung Cancer 2019 01 13;127:12-18. Epub 2018 Nov 13.

Department of Medical & Surgical Specialties, Radiological Sciences & Public Health, Medical Oncology Unit, University of Brescia at ASST Spedali Civili, Brescia, 25123, Italy. Electronic address:

The onset of a new histology is a resistant mechanism to tyrosine kinase inhibitors (TKI) in lung adenocarcinoma (ADK), but this phenomenon has not yet been fully clarified. We present a pooled analysis of the outcomes of EGFR-mutated ADK patients with changed phenotype to squamous cell carcinoma (SqCC) following TKI, along with the description of an additional case. A 67-year-old woman with EGFR-mutated NSCLC received gefitinib and subsequently osimertinib, due to the presence of T790 M at progression. The re-biopsy after third-generation TKI revealed SqCC histology along with the basal EGFR mutation, while T790 M disappeared. The patient rapidly progressed and died despite two chemotherapy cycles. Since this first description of SqCC transformation appearing after treatment with the third-generation TKI osimertinib, other 16 patients, with EGFR-mutated ADK developing a transformation to SqCC histology after treatment with TKIs, were up to now published. From our pooled analysis emerged that most patients were female (82%), 41% were former smokers and no current smokers were identified. Median time to SqCC onset was 11.5 months. In all cases, basal EGFR mutation was maintained, and 11 patients (65%) developed an acquired mutation on exon 20. Interestingly also 790 M mutation appeared in 8 patients (47%). The median survival after SqCC diagnosis was 3.5 months regardless the treatments received. Therefore, EGFR-mutated lung ADK destined to develop a squamous phenotype were often smokers and maintained the baseline genomic alterations. The prognosis after SqCC diagnosis was extremely poor and current treatments largely inefficacious.
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http://dx.doi.org/10.1016/j.lungcan.2018.11.016DOI Listing
January 2019

Listening understanding and acting (lung): focus on communicational issue in thoracic oncology.

Transl Cancer Res 2019 Jan;8(Suppl 1):S16-S22

Oncologia Medica, Spedali Civili di Brescia, Brescia, Italy.

Background: In the field of oncological assistance, nowadays we have to deal with a complex scenario where patients got used to obtain a huge amount of information through internet or social media and to apply them in performing their health-related decisions. This landscape requires that clinicians become able to handle therapeutical approaches and adequate skills in communication tools to satisfy the current needs. Our project aimed to build a communication model based on clinical oncologists' real experiences in order to find a simple way to share with patients all the innovative therapeutical opportunities today available in lung cancer. The final goal is to design a flexible and personalized model adaptable to clinician's personal characteristics and to the specific patient he is facing. We applied both traditional educational tools and innovative techniques in order to make the results effective and applicable to support peer learning.

Methods: The first step consisted in a Board synthesized the definition of the diagnostic process, the identification of treatment strategies and any potential communication barrier clinicians may face dealing with patients. The second step consisted in teamwork including a theoretical part and a training part. In the third step we produce five training videos and video interviews regarding communication praxis and a "Small communication manual". The last step consisted in the publication of the produced material on website and its diffusion through the social media.

Results: In medicine, the universal application of a single model of communication does not represent the optimal solution. By contrary, the availability of simple and practical suggestions to improve the communicative style could allow clinicians to abandon stereotyped formulas identically repurposed to all patients. The "from bottom to top" training, starting from real-life to take advantage of the clinician's experience, give the clinicians the possibility to meditate about their own communicative style and to train in the context of a protected environment. Applying these rules, we design an effective communication model, based on healthcare humanization, which could represent a fundamental support for the patient in order to be gently driven by the clinician to the most appropriate therapeutical choice, balancing efficacy and quality of life. The relational training may improve the quality of clinician-patient communication and could be widespread to other clinicians through the media.

Conclusions: Considering the innovative therapeutical options available, particularly for lung cancer patients, and the increasing access of health-related information through internet or social media the clinician-patient communication has become crucial to support the achievement of the most appropriate therapeutical choice for the patient, facing the intricate illness experience. Building a shareable and easy-to-apply communication model represents a challenge aimed to help clinicians and including technology not as a threat, but as a positive tool.
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http://dx.doi.org/10.21037/tcr.2018.12.32DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8798889PMC
January 2019

CT texture analysis as predictive factor in metastatic lung adenocarcinoma treated with tyrosine kinase inhibitors (TKIs).

Eur J Radiol 2018 Dec 24;109:130-135. Epub 2018 Oct 24.

University of Brescia, Department of Radiology, Piazzale Spedali Civili 1, 25123 Brescia, Italy.

Purpose: To assess the predictive and prognostic value of pre-treatment CT texture features in lung adenocarcinoma treated with tyrosine kinase inhibitors (TKI).

Materials And Methods: Texture analysis was performed using commercially available software (TexRAD Ltd, Cambridge, UK) on pre-treatment contrast-enhanced CT studies from 50 patients with metastatic lung adenocarcinoma treated by TKI. Texture features were quantified on a 5-mm-thick central slice of the primary tumor and were correlated with progression-free and overall survival (PFS and OS) using an internally cross-validated machine learning approach then validated on a bootstrapped sample.

Results: Median PFS and OS were 10.5 and 20.7 months, respectively. A noninvasive signature based on five texture parameters predicted 6-month progression with Area Under the Curve (AUC) of 0.8 (95% CI) and 1-year progression with AUC of 0.76. A high-risk group had hazard ratios for progression of 4.63 and 5.78 when divided by median and best cut-off points, respectively. Texture signature did not correlate with OS. Available clinical variables did not correlate with PFS or with OS.

Conclusion: Texture features seem to be associated with PFS in lung adenocarcinoma treated with TKI.
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http://dx.doi.org/10.1016/j.ejrad.2018.10.016DOI Listing
December 2018

Efficacy of nivolumab in pre-treated non-small-cell lung cancer patients harbouring KRAS mutations.

Br J Cancer 2019 01 31;120(1):57-62. Epub 2018 Oct 31.

Istituto Tumouri "Giovanni Paolo II", Bari, Italy.

Background: The present study investigated the efficacy and safety of nivolumab in pre-treated patients with advanced NSCLC harbouring KRAS mutations.

Methods: Clinical data and KRAS mutational status were analysed in patients treated with nivolumab within the Italian Expanded Access Program. Objective response rate, progression-free survival and overall survival were evaluated. Patients were monitored for adverse events using the National Cancer Institute Common Terminology Criteria for Adverse Events.

Results: Among 530 patients evaluated for KRAS mutations, 206 (39%) were positive while 324 (61%) were KRAS wild-type mutations. KRAS status did not influence nivolumab efficacy in terms of ORR (20% vs 17%, P = 0.39) and DCR (47% vs 41%, P = 0.23). The median PFS and OS were 4 vs 3 months (P = 0.5) and 11.2 vs 10 months (P = 0.8) in the KRAS-positive vs the KRAS-negative group. The 3-months PFS rate was significantly higher in the KRAS-positive group as compared to the KRAS-negative group (53% vs 42%, P = 0.01). The percentage of any grade and grade 3-4 AEs were 45% vs 33% (P = 0.003) and 11% vs 6% (P = 0.03) in KRAS-positive and KRAS-negative groups, respectively.

Conclusions: Nivolumab is an effective and safe treatment option for patients with previously treated, advanced non-squamous NSCLC regardless of KRAS mutations.
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http://dx.doi.org/10.1038/s41416-018-0234-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6325128PMC
January 2019

Cost-effectiveness of model-based eligibility for lung cancer screening in the routine clinical practice.

Ann Transl Med 2018 Sep;6(18):369

Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Medical Oncology, ASST Spedali Civili, Brescia, Italy.

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http://dx.doi.org/10.21037/atm.2018.07.24DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6186555PMC
September 2018

Decision-making for adrenocortical carcinoma: surgical, systemic, and endocrine management options.

Expert Rev Anticancer Ther 2018 11 21;18(11):1125-1133. Epub 2018 Aug 21.

a Internal Medicine, Department of Clinical and Biological Sciences, San Luigi Hospital , University of Turin , Orbassano (TO) , Italy.

Introduction: Adrenocortical carcinoma (ACC) is a rare tumor characterized by poor prognosis in most cases. Moreover, in most cases ACC produces an excess of adrenal steroid hormones with relevant clinical consequences. Areas covered: After an extensive literature search, this narrative review addresses diagnostic management, including hormonal, radiological and pathological assessment, and treatment, which should be directed toward both cancer and hormone related problems. While surgery is the first option in ACC without evidence of metastatic disease, and the only possibility of cure, the therapeutic management of metastatic patients is centered on systemic therapy including mitotane alone or in combination with chemotherapy. Mitotane is also used in the adjuvant setting, because up to 80% of patients with nonmetastatic ACC show locoregional or distant metastases after an apparent complete surgical excision. Expert commentary: Management of ACC patients is fraught with many difficulties and should be limited to experienced physicians. Each step of clinical management, such as diagnosis, prognostication, treatment (both surgical and medical) is challenging and carries the possibility of severe mistakes. For this reason, each step of the management strategy should be decided in the setting of a multidisciplinary team including different expertise (endocrinology, radiology, pathology, oncology), in expert centers.
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http://dx.doi.org/10.1080/14737140.2018.1510325DOI Listing
November 2018

Eribulin in Heavily Pretreated Metastatic Breast Cancer Patients in the Real World: A Retrospective Study.

Oncology 2018 23;94 Suppl 1:10-15. Epub 2018 Jul 23.

Oncology Department, Spedali Civili Hospital, Brescia, Italy.

Objectives: The aim of this study was to investigate efficacy and safety of eribulin in heavily pretreated patients with advanced breast cancer (BC) in a real-life setting.

Methods: This retrospective monocentric study included patients with HER-2-negative metastatic BC, pretreated with anthracyclines and taxanes, who were referred to the Oncology Department of Spedali Civili of Brescia from May 2012 to April 2017. Patients received the same dose of eribulin as that used in the EMBRACE trial: 1.4 mg/m2 on days 1 and 8 every 21 days.

Results: In a total of 53 patients, 32% obtained a partial response, 11% a stable disease, and 43% a clinical benefit (CB). After a median follow-up of 36 months, median progression-free survival (PFS) was 4.7 months and median overall survival (OS) 13.53 months. Median PFS was significantly longer in patients who reported a CB compared to those with no CB, while survival outcomes (PFS and OS) were better in patients who received > 6 cycles of eribulin. Eribulin showed a good tolerability profile with acceptable toxicities, similar to those reported in EMBRACE.

Conclusions: Our experience in a real-world setting confirms the activity, efficacy, and good tolerability profile of eribulin in heavily pretreated BC patients.
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http://dx.doi.org/10.1159/000489063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6193751PMC
July 2018

Osimertinib in EGFR Mutation–Positive Advanced NSCLC.

N Engl J Med 2018 03;378(13):1261-2

University of Brescia, Brescia, Italy

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http://dx.doi.org/10.1056/NEJMc1801669DOI Listing
March 2018

Hepatoprotective effect of N-acetylcysteine in trabectedin-induced liver toxicity in patients with advanced soft tissue sarcoma.

Support Care Cancer 2018 Aug 15;26(8):2929-2935. Epub 2018 Mar 15.

Dipartimento di Specialità Medico-Chirurgiche, Scienze Radiologiche e Sanità Pubblica, Oncologia Medica, Università degli Studi di Brescia, ASST Spedali Civili, Brescia, Italy.

Purpose: Trabectedin is one of the few active agents in soft tissue sarcoma (STS) but hepatotoxicity is frequent and represents a dose-limiting factor. Protective strategies aiming at counteracting this important side effect have a crucial clinical impact. Due to its antioxidant properties, N-acetylcysteine (NAC) has a recognized hepatoprotective effect and this provides the rationale for testing NAC in the management of trabectedin-induced hepatotoxicity.

Methods: Patients with recurrent or metastatic soft tissue sarcoma, consecutively observed at our institution, who were considered eligible to trabectedin, received concomitant NAC if they had impaired hepatic or renal function at baseline or developed hepatotoxicity during treatment. The study aim was to retrospectively explore trabectedin administration in terms of number of cycles, mean dose, and dose intensity (DI) in patients who received NAC as compared with those who did not. Secondary end points were progression-free survival (PFS) and overall survival (OS).

Results: A total number of 18 patients were enrolled in this study. Nine received NAC and nine did not. The median number of administered trabectedin cycles, mean trabectedin dose/cycles, and median DI was comparable in the two groups (p = 0.450, p = 0.534, and p = 0.450, respectively). The PFS and OS curves overlapped.

Conclusion: This explorative study suggests that NAC can have a hepatoprotective activity in patients receiving trabectedin allowing to maintain an adequate dose intensity and continuative administration in patients with impaired liver and renal function or developing treatment-induced hepatotoxicity. A prospective randomized trial is warranted.
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http://dx.doi.org/10.1007/s00520-018-4129-xDOI Listing
August 2018

IFN-α in advanced well-differentiated neuroendocrine tumors: the neglected drug?

Future Oncol 2018 04 12;14(10):897-899. Epub 2018 Mar 12.

Department of Medical & Surgical Specialties, Radiological Sciences & Public Health, Medical Oncology Unit, University of Brescia at ASST Spedali Civili, Brescia 25123, Italy.

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http://dx.doi.org/10.2217/fon-2017-0667DOI Listing
April 2018

Testosterone Levels and Prostate Cancer Prognosis: Systematic Review and Meta-analysis.

Clin Genitourin Cancer 2018 06 2;16(3):165-175.e2. Epub 2018 Feb 2.

Medical Oncology Unit, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia at Spedali Civili Hospital, Brescia, Italy. Electronic address:

Androgen receptor is the major driver of and testosterone the natural growth factor of prostate cancer (PC). Studies exploring the relationship among circulating testosterone levels, PC aggressiveness, and patient prognosis showed contradictory results. We performed a comprehensive literature search for studies reporting the independent relationship between serum testosterone and prognosis of PC patients. Meta-analyses using random effects models were conducted to estimate pooled hazard ratios (HRs) and 95% confidence intervals (CIs). We identified 25 articles that evaluated the prognostic value of testosterone in early-stage PC (8 studies), in advanced PC either before (4 studies) or during androgen deprivation therapy (ADT) (5 studies), and in castration-resistant PC (8 studies). In early PC, serum testosterone level was not prognostic in terms of overall survival (HR = 1.03; 95% CI, 0.99-1.08; P = .19) and biochemical recurrence (HR = 0.99; 95% CI, 0.87-1.13; P = .93). In advanced PC, higher testosterone levels before ADT were associated with a reduced risk of death (HR = 0.58; 95% CI, 0.45-0.74; P < .0001). During ADT, lower levels were associated with a reduced risk of death (HR = 0.48; 95% CI, 0.28-0.81; P = .006) and progression (HR = 0.59; 95% CI, 0.46-0.77; P < .0001). In castration-resistant PC patients, higher testosterone levels predicted a reduced risk of progression (HR = 0.33; 95% CI, 0.11-0.97; P = .04) but not of death (HR = 0.86; 95% CI, 0.69-1.07; P = .18). The heterogeneity of the included studies is a major limitation of this meta-analysis. The relationship between circulating testosterone and PC prognosis varies in different clinical settings and according to ADT administration.
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http://dx.doi.org/10.1016/j.clgc.2018.01.005DOI Listing
June 2018

Radiotherapy and Tyrosine Kinase Inhibitors in Stage IV Non-small Cell Lung Cancer: Real-life Experience.

In Vivo 2018 Jan-Feb;32(1):159-164

Department of Radiation Oncology, Olindo Alberti Radiotherapy Institute, Brescia, Italy.

Aim: To investigate the role of conventional radiotherapy (RT) and stereotactic body radiotherapy (SBRT) in patients with epidermal growth factor (EGFR)-mutant or anaplastic lymphoma kinase (ALK) rearrangement-positive metastatic non-small cell lung cancer (NSCLC).

Patients And Methods: Fifty patients with EGFR-mutated or ALK rearrangement-positive NSCLC were treated at our Institution. Radiotherapy was delivered before, after or concomitantly with tyrosine kinase inhibitors (TKIs). Acute toxicities and overall survival (OS) were assessed.

Results: Radiotherapy was performed within 30 days before TKI, concomitantly with TKI and within 30 days after TKI in eight (16%), 33 (66%) and 9 (18%) cases, respectively. The median duration of TKI therapy in the whole series was 11.9 months. The median OS was 19.3 months and 1- and 2-year OS was 71.5% and 36.5%, respectively. The group treated with SBRT had a significant benefit in terms of OS (p=0.043). Only two grade 3 toxicities were reported.

Conclusion: RT concomitantly or close to TKI administration in stage IV NSCLC was shown to be feasible and safe. Intriguing data on OS were also reported.
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http://dx.doi.org/10.21873/invivo.11219DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5892641PMC
August 2018
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