Publications by authors named "Alessandra Prete"

21 Publications

  • Page 1 of 1

The Pan-Immune-Inflammation Value in microsatellite instability-high metastatic colorectal cancer patients treated with immune checkpoint inhibitors.

Eur J Cancer 2021 Apr 23;150:155-167. Epub 2021 Apr 23.

Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Via Giacomo Venezian 1, 20133, Milan, Italy; Oncology and Hemato-oncology Department, University of Milan, via Festa del Perdono 7, 20122, Milan, Italy. Electronic address:

Background: Immune checkpoint inhibitors (ICIs) yielded unprecedented efficacy in patients with microsatellite instability (MSI)-high metastatic colorectal cancer (mCRC). Since the Pan-Immune-Inflammation Value (PIV) is a blood-based biomarker with prognostic usefulness in mCRC, it might predict clinical outcomes and primary resistance to ICIs.

Methods: We retrospectively analysed the association of PIV and its early modulation at 3/4 weeks after treatment initiation with the outcomes of MSI-high mCRC patients receiving anti-programmed death-(ligand)1 (PD-[L]1) +/- anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) agents. PIV was calculated as follows: (neutrophil count × platelet count × monocyte count)/lymphocyte count. PIV cut-offs were determined using the maximally selected rank statistics.

Results: A total of 163 patients were included. In the multivariable models for overall survival (OS) and progression-free survival (PFS), both high (>492) baseline PIV (OS: adjusted [a] HR, 3.00; 95% CI, 1.49-6.04, p = 0.002; PFS: aHR, 1.91; 95% CI, 1.06-3.44, p = 0.031) and early PIV increase ≥+30% (OS: aHR, 3.21; 95% CI, 1.65-6.23, p < 0.001; PFS: aHR, 2.25; 95% CI, 1.30-3.89, p = 0.003) confirmed an independent prognostic impact. After stratifying patients according to baseline PIV and ICI regimen, OS and PFS were significantly worse in subjects with high PIV receiving anti-PD-1/PD-L1 monotherapy. Early PIV increase was an independent predictor of clinical benefit (aOR, 0.23; 95% CI, 0.08-0.66; p = 0.007), whereas a trend was observed for baseline PIV (aOR, 0.33; 95% CI, 0.10-1.07; p = 0.065).

Conclusion: PIV is a strong predictor of outcomes in MSI-high mCRC patients receiving ICIs. Prospective validation of these results is required to establish its role as a stratification factor for personalised combination strategies.
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http://dx.doi.org/10.1016/j.ejca.2021.03.043DOI Listing
April 2021

Prediction of Benefit from Checkpoint Inhibitors in Mismatch Repair Deficient Metastatic Colorectal Cancer: Role of Tumor Infiltrating Lymphocytes.

Oncologist 2020 06 22;25(6):481-487. Epub 2020 Jan 22.

Surgical Pathology and Cytopathology Unit, Department of Medicine (DIMED), University of Padua, Padua University Hospital, Padua, Italy.

Background: Immunotherapy with immune checkpoint inhibitors (ICIs) is highly effective in microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC); however, specific predictive biomarkers are lacking.

Patients And Methods: Data and samples from 85 patients with MSI-H mCRC treated with ICIs were gathered. Tumor infiltrating lymphocytes (TILs) and tumor mutational burden (TMB) were analyzed in an exploratory cohort of "super" responders and "clearly" refractory patients; TILs were then evaluated in the whole cohort of patients. Primary objectives were the correlation between the number of TILs and TMB and their role as biomarkers of ICI efficacy. Main endpoints included response rate (RR), progression-free survival (PFS), and overall survival (OS).

Results: In the exploratory cohort, an increasing number of TILs correlated to higher TMB (Pearson's test, p = .0429). In the whole cohort, median number of TILs was 3.6 in responders compared with 1.8 in nonresponders (Mann-Whitney test, p = .0448). RR was 70.6% in patients with high number of TILs (TILs-H) compared with 42.9% in patients with low number of TILs (odds ratio = 3.20, p = .0291). Survival outcomes differed significantly in favor of TILs-H (PFS: hazard ratio [HR] = 0.42, p = .0278; OS: HR = 0.41, p = .0463).

Conclusion: A significant correlation between higher TMB and increased number of TILs was shown. A significantly higher activity and better PFS and OS with ICI in MSI-H mCRC were reported in cases with high number of TILs, thus supporting further studies of TIL count as predictive biomarker of ICI efficacy.

Implications For Practice: Microsatellite instability is the result of mismatch repair protein deficiency, caused by germline mutations or somatic modifications in mismatch repair genes. In metastatic colorectal cancer (mCRC), immunotherapy (with immune checkpoint inhibitors [ICIs]) demonstrated remarkable clinical benefit in microsatellite instability-high (MSI-H) patients. ICI primary resistance has been observed in approximately 25% of patients with MSI-H mCRC, underlining the need for predictive biomarkers. In this study, tumor mutational burden (TMB) and tumor infiltrating lymphocyte (TIL) analyses were performed in an exploratory cohort of patients with MSI-H mCRC treated with ICIs, demonstrating a significant correlation between higher TMB and increased number of TILs. Results also demonstrated a significant correlation between high number of TILs and clinical responses and survival benefit in a large data set of patients with MSI-H mCRC treated with ICI. TMB and TILs could represent predictive biomarkers of ICI efficacy in MSI-H mCRC and should be incorporated in future trials testing checkpoint inhibitors in colorectal cancer.
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http://dx.doi.org/10.1634/theoncologist.2019-0611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288636PMC
June 2020

CK7 and consensus molecular subtypes as major prognosticators in BRAF mutated metastatic colorectal cancer.

Br J Cancer 2019 10 2;121(7):593-599. Epub 2019 Sep 2.

Department of Oncology, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy.

Background: BRAF mutated metastatic colorectal cancer (mCRC) is a subtype (10%) with overall poor prognosis, but the clinical experience suggests a great heterogeneity in survival. It is still unexplored the real distribution of traditional and innovative biomarkers among BRAF mutated mCRC and which is their role in the improvement of clinical prediction of survival outcomes.

Methods: Data and tissue specimens from 155 BRAF mutated mCRC patients treated at eight Italian Units of Oncology were collected. Specimens were analysed by means of immunohistochemistry profiling performed on tissue microarrays. Primary endpoint was overall survival (OS).

Results: CDX2 loss conferred worse OS (HR = 1.72, 95%CI 1.03-2.86, p = 0.036), as well as high CK7 expression (HR = 2.17, 95%CI 1.10-4.29, p = 0.026). According to Consensus Molecular Subtypes (CMS), CMS1 patients had better OS compared to CMS2-3/CMS4 (HR = 0.37, 95%CI 0.19-0.71, p = 0.003). Samples showing less TILs had worse OS (HR = 1.72, 95%CI 1.16-2.56, p = 0.007). Progression-free survival analyses led to similar results. At multivariate analysis, CK7 and CMS subgrouping retained their significant correlation with OS.

Conclusion: The present study provides new evidence on how several well-established biomarkers perform in a homogenousBRAF mutated mCRC population, with important and independent information added to standard clinical prognosticators. These data could be useful to inform further translational research, for patients' stratification in clinical trials and in routine clinical practice to better estimate patients' prognosis.
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http://dx.doi.org/10.1038/s41416-019-0560-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6889398PMC
October 2019

A validated prognostic classifier for BRAF-mutated metastatic colorectal cancer: the 'BRAF BeCool' study.

Eur J Cancer 2019 09 19;118:121-130. Epub 2019 Jul 19.

Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milan, Italy; Department of Oncology and Hemato-oncology, Università Degli Studi di Milano, Milan, Italy.

Background: Despite the well-known negative prognostic value of the BRAF mutation in patients with metastatic colorectal cancer (mCRC), its outcome is quite heterogeneous, and the basis for this prognostic heterogeneity should be better defined.

Methods: Two large retrospective series of BRAF-mutated mCRC from 22 institutions served as an exploratory and validation set to develop a prognostic score. The model was internally and externally validated.

Results: A total of 395 BRAF-mutated mCRCs were included in the exploratory set. Performance status, CA19.9, lactate dehydrogenase, neutrophil/lymphocyte ratio, grading and liver, lung and nodal involvement emerged as independent prognostic factors for overall survival (OS). Two different scoring systems were built: a 'complete' score (0-16) including all significant covariates and a 'simplified' score (0-9), based only on clinicopathological covariates, and excluding laboratory values. Adopting the complete score, proportions of patients with a low (0-4), intermediate (5-8) and high (9-16) score were 44.7%, 42.6% and 12.6%, respectively. The median OS was 29.6, 15.5 (hazard ratio [HR] for intermediate vs low risk: 2.16, 95% confidence interval [CI]: 1.44-3.22, p < .001) and 6.6 months (HR for high vs low risk: 4.72, 95% CI: 2.72-8.20, p < .001). Similar results were observed also after adjusting for the type of first-line treatment and adopting the simplified score. The simplified prognostic score derived from the exploratory set was then applied to the validation set for external confirmation.

Conclusions: These scoring systems are based on easy-to-collect data and defined specific subgroups with relevant differences in their life expectancy. These tools could be useful in clinical practice, would allow better stratification of patients in clinical trials and may be adopted for proper adjustments in exploratory translational analyses.
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http://dx.doi.org/10.1016/j.ejca.2019.06.008DOI Listing
September 2019

Immune inflammation indicators in anal cancer patients treated with concurrent chemoradiation: training and validation cohort with online calculator (ARC: Anal Cancer Response Classifier).

Cancer Manag Res 2019 26;11:3631-3642. Epub 2019 Apr 26.

Medical Oncology Unit, Cancer Institute Giovanni Paolo II, Bari, Italy.

In anal cancer, there are no markers nor other laboratory indexes that can predict prognosis and guide clinical practice for patients treated with concurrent chemoradiation. In this study, we retrospectively investigated the influence of immune inflammation indicators on treatment outcome of anal cancer patients undergoing concurrent chemoradiotherapy. All patients had a histologically proven diagnosis of squamous cell carcinoma of the anal canal/margin treated with chemoradiotherapy according to the Nigro's regimen. Impact on prognosis of pre-treatment systemic index of inflammation (SII) (platelet x neutrophil/lymphocyte), neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) were analyzed. A total of 161 consecutive patients were available for the analysis. Response to treatment was the single most important factor for progression-free survival (PFS) and overall survival (OS). At univariate analysis, higher SII level was significantly correlated to lower PFS (<0.01) and OS (=0.046). NLR level was significantly correlated to PFS (=0.05), but not to OS (=0.06). PLR level significantly affected both PFS (<0.01) and OS (=0.02). On multivariate analysis pre-treatment, SII level was significantly correlated to PFS (=0.0079), but not to OS (=0.15). We developed and externally validated on a cohort of 147 patients a logistic nomogram using SII, nodal status and pre-treatment Hb levels. Results showed a good predictive ability with C-index of 0.74. An online available calculator has also been developed. The low cost and easy profile in terms of determination and reproducibility make SII a promising tool for prognostic assessment in this oncological setting.
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http://dx.doi.org/10.2147/CMAR.S197349DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6506779PMC
April 2019

Combined surgery and radiotherapy as curative treatment for tracheal adenoid cystic carcinoma: a case report.

J Med Case Rep 2019 Mar 6;13(1):52. Epub 2019 Mar 6.

UOC of Oncology - ASL Latina - Distretto 1, University of Rome "Sapienza", Aprilia, LT, Italy.

Background: Adenoid cystic carcinoma of the trachea is a rare tumor, characterized by slow growth and low rate of local and distant metastasis. When achievable, complete surgical resection represents the optimal treatment approach, with the highest results in terms of overall survival. Radiation therapy is a reasonable alternative in cases of inoperable disease.

Case Presentation: We report a case of an 82-year-old white man affected by primary adenoid cystic carcinoma of the trachea, treated with debulking surgery and radiotherapy on the residual disease. A three-dimensional conformal radiation therapy was conducted. The total dose amounted to 70 Gy, administered in 35 fractions of 2 Gy. The medium doses given to the esophagus and lungs were 23 Gy and 4.2 Gy respectively. The maximum dose delivered to the spinal cord was 31 Gy with satisfactory results in terms of local control of the disease.

Conclusion: A combined approach of surgical resection followed by radiotherapy on the residual disease provided an excellent result in terms of disease control, quality of life, and overall survival in a patient with locally advanced tracheal adenoid cystic carcinoma.
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http://dx.doi.org/10.1186/s13256-019-1996-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6402121PMC
March 2019

A Simplified Genomic Profiling Approach Predicts Outcome in Metastatic Colorectal Cancer.

Cancers (Basel) 2019 01 27;11(2). Epub 2019 Jan 27.

Department of Molecular Medicine, University La Sapienza, 00161 Rome, Italy.

The response of metastatic colorectal cancer (mCRC) to the first-line conventional combination therapy is highly variable, reflecting the elevated heterogeneity of the disease. The genetic alterations underlying this heterogeneity have been thoroughly characterized through omic approaches requiring elevated efforts and costs. In order to translate the knowledge of CRC molecular heterogeneity into a practical clinical approach, we utilized a simplified Next Generation Sequencing (NGS) based platform to screen a cohort of 77 patients treated with first-line conventional therapy. Samples were sequenced using a panel of hotspots and targeted regions of 22 genes commonly involved in CRC. This revealed 51 patients carrying actionable gene mutations, 22 of which carried druggable alterations. These mutations were frequently associated with additional genetic alterations. To take into account this molecular complexity and assisted by an unbiased bioinformatic analysis, we defined three subgroups of patients carrying distinct molecular patterns. We demonstrated these three molecular subgroups are associated with a different response to first-line conventional combination therapies. The best outcome was achieved in patients exclusively carrying mutations on and/or genes. By contrast, in patients carrying mutations in any of the other genes, alone or associated with mutations of , the expected response is much worse compared to patients with exclusive mutations. Additionally, our data indicate that the standard approach has limited efficacy in patients without any mutations in the genes included in the panel. In conclusion, we identified a reliable and easy-to-use approach for a simplified molecular-based stratification of mCRC patients that predicts the efficacy of the first-line conventional combination therapy.
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http://dx.doi.org/10.3390/cancers11020147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6406354PMC
January 2019

Early modifications of circulating microRNAs levels in metastatic colorectal cancer patients treated with regorafenib.

Pharmacogenomics J 2019 10 28;19(5):455-464. Epub 2019 Jan 28.

Institute of Clinical Physiology, CNR, Pisa, Italy.

Biomarkers able to improve the cost/benefit ratio are urgently needed for metastatic colorectal cancer patients that are eligible to receive regorafenib. Here, we measured plasma levels of ten circulating microRNAs (c-miRNAs) and we investigated their early changes during treatment, as well as possible correlation with clinical outcome. Ten literature-selected c-miRNAs were quantified by qRT-PCR on plasma samples collected at baseline (d1) and after 15 days of treatment (d15). C-miRNAs showing significant changes were further analyzed to establish correlations with outcome. A decision tree-based approach was employed to define a c-miRNA signature able to predict the outcome. Results achieved in an exploratory cohort were tested in a validation group. In the exploratory cohort (n = 34), the levels of c-miR-21 (p = 0.06), c-miR-141 (p = 0.04), and c-miR-601 (p = 0.01) increased at d15 compared with d1. A c-miRNA signature involving c-miR-21, c-miR-221, and c-miR-760 predicted response to treatment (p < 0.0001) and was significantly associated to PFS (HR = 10.68; 95% CI 3.2-35.65; p < 0.0001). In the validation cohort (n = 36), the increase in c-miR-21 (p = 0.02) and c-miR-601 (p = 0.02) levels at d15 was confirmed, but the associations with outcome were not. Our data indicate that early changes of c-miRNA levels might be influenced by regorafenib treatment. However, further studies are needed to establish the predictive power of such modifications.
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http://dx.doi.org/10.1038/s41397-019-0075-3DOI Listing
October 2019

Safety and Tolerability of Anti-Angiogenic Protein Kinase Inhibitors and Vascular-Disrupting Agents in Cancer: Focus on Gastrointestinal Malignancies.

Drug Saf 2019 02;42(2):159-179

Unit of Medical Oncology 1, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy.

Angiogenesis is an essential process for tumor growth and metastasis. Inhibition of angiogenesis as an anticancer strategy has shown significant results in a plethora of tumors. Anti-angiogenic agents are currently part of many standard-of-care options for several metastatic gastrointestinal cancers. Bevacizumab, aflibercept, ramucirumab, and regorafenib have significantly improved both progression-free and overall survival in different lines of treatment in metastatic colorectal cancer. Second-line ramucirumab and third-line apatinib are effective anti-angiogenic treatments for patients with metastatic gastric cancer. Unfortunately, the anti-angiogenic strategy has major practical limitations: resistance inevitably develops through redundancy of signaling pathways and selection for subclonal populations adapted for hypoxic conditions. Anti-angiogenic agents may be more effective in combination therapies, with not only cytotoxics but also other emerging compounds in the anti-angiogenic class or in the separate class of the so-called vascular-disrupting agents. This review aims to provide an overview of the approved and "under development" anti-angiogenic compounds as well as the vascular-disrupting agents in the treatment of gastrointestinal cancers, focusing on the actual body of knowledge available on therapy challenges, pharmacodynamic and pharmacokinetic mechanisms, safety profiles, promising predictive biomarkers, and future perspectives.
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http://dx.doi.org/10.1007/s40264-018-0776-6DOI Listing
February 2019

Prognostic Value of Thyroid Hormone Ratios in Patients With Advanced Metastatic Colorectal Cancer Treated With Regorafenib: The TOREADOR Study.

Clin Colorectal Cancer 2018 09 8;17(3):e601-e615. Epub 2018 Jun 8.

Unit of Medical Oncology 1, Department of Clinical and Experimental Oncology, Istituto Oncologico Veneto, IRCCS, Padova, Italy. Electronic address:

Background: The impact of free triiodothyronine (FT)/free thyroxine (FT) ratio on survival in hospitalized geriatric patients was recently described. Up today, there are no data regarding the prognostic role of FT/FT ratio in patients with advanced cancer. We evaluated the impact of FT/FT ratio on survival in patients with refractory colorectal cancer (CRC) treated with regorafenib.

Methods: Patients with metastatic CRC treated with regorafenib with available clinical data and baseline measurement of FT, FT, and thyroid-stimulating hormone (TSH) were considered eligible. Exploratory analyses included subjects treated at Istituto Oncologico Veneto. A confirmatory analysis was planned based on FT/FT ratio tertile results, and a validation cohort was built on data retrieved from University of Cagliari.

Results: In an exploratory cohort, the median overall survival in patients with low, intermediate, and high FT/FT ratios, according to tertiles' value, was 4.8, 5.0, and 7.6 months, respectively (P = .003). The differences were significant in the multivariate model (hazard ratio, 0.43; 95% confidence interval, 0.28-0.68; P = .0003). Confirmatory results were obtained in a validation cohort, both in univariate (P = .0002) and in multivariate (hazard ratio, 0.56; 95% confidence interval, 0.36-0.88; P = .0118) models.

Conclusions: High baseline FT/FT ratio is strongly associated to better outcome in patients with progressive metastatic CRC treated with regorafenib. Further investigations are ongoing to draw definitive conclusions regarding a potential predictive effect.
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http://dx.doi.org/10.1016/j.clcc.2018.05.013DOI Listing
September 2018

Mandatory Reporting of Coronary Artery Calcifications Incidentally Noted on Chest Multi-Detector Computed Tomography: A Multicentre Experience.

Curr Vasc Pharmacol 2019 ;17(1):92-98

Department of Clinical and Experimental Medicine, "F. Magrassi-A. Lanzara", University of Campania "Luigi Vanvitelli", 80131, Naples, Italy.

Background: Coronary Artery Calcifications (CACs) are associated with coronary atherosclerosis and Cardiovascular (CV) events. In "non-cardiovascular" settings, CACs can be easily detected on chest Multi-Detector Computed Tomography (MDCT). Their evaluation may help to better stratify CV risk in the general population, especially for primary prevention.

Aims: We retrospectively evaluated the relationship between CAC distribution and CV risk, determined by Framingham Risk Score (FRS), in a cohort of patients who underwent chest MDCT performed for several clinical indications.

Method: We retrospectively recruited 305 patients (194 men, 111 women; mean age 70.5 years) from 3 different Italian centres. Patients with coronary stent, pacemaker and/or CV devices were excluded from the study. Circumflex Artery (LCX), Left Main Coronary Artery (LMCA), left Anterior Descending artery (LAD) and right coronary artery (RCA) were analysed.

Results: From a total population of 305 patients, 119 (39%) had low FRS (<10%), 115 (38%) had intermediate FRS (10-20%), and 71 (23%) had high FRS (>20%). The study identified 842 CACs located in decreasing order as follows: RCA (34.5%), LAD (32.3%), LCX (28%) and LMCA (13%). Statistical two-step analysis subdivided patients into two clusters according to FRS (risk threshold = 12.38%): cluster I (mean 9.34) and cluster II (mean 15.09). A significant association between CAC distribution and cluster II was demonstrated. CACs were mostly detected in patients with intermediate FRS. All patients (100%) with the highest CV risk showed intermediate RCA and LMCA involvement.

Conclusion: Radiologists can note the distribution of CACs on a chest MDCT and should mandatorily record them in their reports. Depending on CAC presence and location, these findings may have important clinical implications, mostly in asymptomatic patients with intermediate FRS. This information may reclassify a patients' CV risk and improve clinical management.
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http://dx.doi.org/10.2174/1570161116666180117111856DOI Listing
January 2020

Immunotherapy in Gastrointestinal Cancers.

Biomed Res Int 2017 3;2017:4346576. Epub 2017 Jul 3.

Division of Medical Oncology 1, Istituto Oncologico Veneto, IRCCS, Padova, Italy.

Gastrointestinal cancers represent a major public health problem worldwide. Immunotherapeutic strategies are currently under investigation in this setting and preliminary results of ongoing trials adopting checkpoint inhibitors are striking. Indeed, although a poor immunogenicity for GI has been reported, a strong biological rationale supports the development of immunotherapy in this field. The clinical and translational research on immunotherapy for the treatment of GI cancers started firstly with the identification of immune-related mechanisms possibly relevant to GI tumours and secondly with the development of immunotherapy-based agents in clinical trials. In the present review a general overview is firstly provided followed by a focus on major findings on gastric, colorectal, and hepatocellular carcinomas. Finally, pathological and molecular perspectives are provided since many efforts are ongoing in order to identify possible predictive biomarkers and to improve patients' selection. Many issues are still unsolved in this field; however, we strongly believe that immunotherapy might positively affect the natural history of a subgroup of GI cancer patients improving outcome and the overall quality of life.
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http://dx.doi.org/10.1155/2017/4346576DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5512095PMC
April 2018

Evaluation of the efficacy of cisplatin-etoposide and the role of thoracic radiotherapy and prophylactic cranial irradiation in LCNEC.

ERJ Open Res 2017 Jan 29;3(1). Epub 2017 Mar 29.

Dept of Medical Oncology Unit A, Policlinico Umberto I, "Sapienza" University of Rome, Rome, Italy.

In small-cell lung cancer (SCLC), the role of chemotherapy and radiotherapy is well established. Large-cell neuroendocrine carcinoma (LCNEC) shares several clinicopathological features with SCLC, but its optimal therapy is not defined. We evaluated clinical response and survival outcomes of advanced LCNEC treated in first-line therapy compared with SCLC. 72 patients with stage III-IV LCNEC (n=28) and extensive-stage SCLC (ES-SCLC) (n=44) received cisplatin-etoposide with/without thoracic radiotherapy (TRT) and prophylactic cranial irradiation (PCI). Comparing LCNEC with SCLC, we observed similar response rates (64.2% 59.1%), disease control rates (82.1% 88.6%), progression-free survival (mPFS) (7.4 6.1 months) and overall survival (mOS) (10.4 10.9 months). TRT and PCI in both histologies showed a benefit in mOS (34 7.8 months and 34 8.6 months, both p=0.0001). LCNEC patients receiving TRT showed an improvement in mPFS and mOS (12.5 5 months, p=0.02 and 28.3 5 months, p=0.004), similarly to ES-SCLC. PCI in LCNEC showed an increase in mPFS (20.5 6.4 months, p=0.09) and mOS (33.4 8.6 months, p=0.05), as in ES-SCLC. Advanced LCNEC treated with SCLC first-line therapy has a similar clinical response and survival outcomes to ES-SCLC.
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http://dx.doi.org/10.1183/23120541.00128-2016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5370316PMC
January 2017

Monitoring PD-L1 positive circulating tumor cells in non-small cell lung cancer patients treated with the PD-1 inhibitor Nivolumab.

Sci Rep 2016 08 24;6:31726. Epub 2016 Aug 24.

Department of Molecular Medicine, Circulating tumor cells Unit, Sapienza University of Rome.

Controversial results on the predictive value of programmed death ligand 1 (PD-L1) status in lung tumor tissue for response to immune checkpoint inhibitors do not allow for any conclusive consideration. Liquid biopsy might allow real-time sampling of patients for PD-L1 through the course of the disease. Twenty-four stage IV NSCLC patients included in the Expanded Access Program with Nivolumab were enrolled. Circulating tumor cells (CTCs) were analyzed by CellSearch with anti-human B7-H1/PD-L1 PE-conjugated antibody. PD-L1 expressing CTCs were assessed at baseline, at 3 and 6 months after starting therapy, and correlated with outcome. At baseline and at 3 months of treatment, the presence of CTCs and the expression of PD-L1 on their surface were found associated to poor patients outcome. Nevertheless, the high frequency of PD-L1 expressing CTCs hampered to discriminate the role of PD-L1 in defining prognosis. Conversely although CTCs were found in all patients 6 months after treatment, at this time patients could be dichotomized into two groups based PD-L1 expression on CTCs. Patients with PD-L1 negative CTCs all obtained a clinical benefit, while patients with PD-L1 (+) CTCs all experienced progressive disease. This suggests that the persistence of PD-L1(+) CTCs might mirror a mechanism of therapy escape.
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http://dx.doi.org/10.1038/srep31726DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4995431PMC
August 2016

Sharp penetrating wounds: spectrum of imaging findings and legal aspects in the emergency setting.

Radiol Med 2015 Sep 2;120(9):856-65. Epub 2015 Jun 2.

Department of Internal and Experimental Medicine, Magrassi-Lanzara, Institute of Radiology, Second University of Naples, Piazza Miraglia 12, 80138, Naples, Italy,

The main cause of severe civilian trauma is not the same all over the world; while in Europe the majority of cases are due to blunt traumatic injury, in the United States, penetrating gunshot wounds are the most common. Penetrating wounds can be classified into two different entities: gunshot wounds, or more technically ballistic traumas, and sharp penetrating traumas, also identifiable with non-ballistic traumas. Sharp penetrating injuries are mainly caused by sharp pointed objects such as spears, nails, daggers, knives, and arrows. The type of injuries caused by sharp pointed objects depends on the nature and shape of the weapon, the amount of energy in the weapon or implement when it strikes the body, whether it is inflicted upon a moving or a still body, and the nature of the tissue injured. In the assessment of hemodynamically stable patients with sharp penetrating wounds, the main imaging procedure is Multidetector Computed Tomography (MDCT), especially used in complicated cases of penetrating injuries with an important impact on the final therapeutic choice. The diagnostic approach has been changed by MDCT due to its technical improvements, in particular, faster data acquiring and upgraded image reconstructions.
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http://dx.doi.org/10.1007/s11547-015-0553-xDOI Listing
September 2015

Situs inversus with levocardia, infrahepatic interruption of the inferior vena cava, and azygos continuation: a case report.

Surg Radiol Anat 2016 Apr 4;38(3):369-71. Epub 2015 Mar 4.

Department of Radiology, AORN Cardarelli, Naples, Italy.

Situs inversus incompletus is a rare congenital condition in which the major abdominal organs are reversed or mirrored from their normal positions. It is often associated with multiple congenital anomalies. We present the case of a 38-year-old woman with dyspnea and a clinical history of chronic kidney disease and kidney transplantation. Echocardiography showed a right atrial mass, and analysis of multidetector computed tomography angiography revealed the interruption of the inferior vena cava with an increase of the azygos vein and azygos continuation. These congenital malformations are often associated with deep vein thrombosis and/or pulmonary thromboembolism and explained the occurrence of dyspnea. Cardiac magnetic resonance with contrast medium confirmed the presence of the right atrial mass, the characteristics of which were attributed to interatrial thrombus, which was further confirmed by the success of thrombolytic therapy and the remission of symptoms. In conclusion, we described a case of situs inversus with levocardia in association with infrahepatic interruption of the inferior vena cava, and azygos continuation with cardiac thrombus and chronic renal failure.
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http://dx.doi.org/10.1007/s00276-015-1454-3DOI Listing
April 2016

Dual-source dual-energy CT: dose reduction after endovascular abdominal aortic aneurysm repair.

Radiol Med 2014 Dec 2;119(12):934-941. Epub 2014 Jul 2.

UOC Radiologia Cardiovascolare e d'Urgenza, AO San Camillo Forlanini, Rome, Italy.

Purpose: This study was done to evaluate the possibility of reducing the dose of ionising radiation by using dual-source dual-energy computed tomography (CT) in patients undergoing CT angiography of the aorta to search for endoleaks after endovascular aneurysm repair (EVAR).

Materials And Methods: One hundred and forty-eight patients (117 M, 31 F; mean age 75 ± 6.5) underwent 171 CT angiography scans for follow-up after EVAR. For each patient we performed a triple-phase acquisition protocol consisting of a nonenhanced phase, an arterial phase and a delayed phase; the latter acquired in dual energy. Two radiologists jointly evaluated the nonenhanced, arterial and delayed phase, and a third radiologist evaluated only the delayed phase and its virtual noncontrast (VNC) reconstruction. Moreover, we compared the cumulative effective doses of the triple-phase acquisition with the dual-energy acquisition.

Results: We detected 34 endoleaks (19.8 %), with 100 % agreement between the triple-phase and dual-energy acquisitions. The effective dose of dual-energy acquisition performed during the delayed phase was 61.7 % lower than that of the triple-phase acquisition.

Conclusions: A dual-energy CT scan acquired during the delayed phase and its VNC reconstruction allow detection of endoleaks with a substantial reduction of effective dose and a complete diagnostic agreement with a triple-phase acquisition protocol.
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http://dx.doi.org/10.1007/s11547-014-0420-1DOI Listing
December 2014

Fertility drugs, reproductive strategies and ovarian cancer risk.

J Ovarian Res 2014 8;7:51. Epub 2014 May 8.

Department of Medico-Surgical Sciences and Biotechnologies, University of Rome "Sapienza," Corso della Repubblica, 04100 Latina, Italy.

Several adverse effects have been related to infertility treatments, such as cancer development. In particular, the relationship between infertility, reproductive strategies, and risk of gynecological cancers has aroused much interest in recent years. The evaluation of cancer risk among women treated for infertility is very complex, mainly because of many factors that can contribute to occurrence of cancer in these patients (including parity status). This article addresses the possible association between the use of fertility treatments and the risk of ovarian cancer, through a scrupulous search of the literature published thus far in this field. Our principal objective was to give more conclusive answers on the question whether the use of fertility drug significantly increases ovarian cancer risk. Our analysis focused on the different types of drugs and different treatment schedules used. This study provides additional insights regarding the long-term relationships between fertility drugs and risk of ovarian cancer.
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http://dx.doi.org/10.1186/1757-2215-7-51DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4020377PMC
October 2015

Factors influencing choice of chemotherapy in metastatic colorectal cancer (mCRC).

Cancer Manag Res 2013 Nov 19;5:377-85. Epub 2013 Nov 19.

Department of Medico-Surgical Sciences and Biotechnologies, "Sapienza" University of Rome, Rome, Italy; Oncology Unit, ICOT, Latina, Italy.

Management of metastatic colorectal cancer requires a multimodal approach and must be performed by an experienced, multidisciplinary expert team. The optimal choice of the individual treatment modality, according to disease localization and extent, tumor biology, and patient clinical characteristics, will be one that can maintain quality of life and long-term survival, and even cure selected patients. This review is an overview of the different therapeutic approaches available in metastatic colorectal cancer, for the purpose of defining personalized therapeutic algorithms according to tumor biology and patient clinical features.
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http://dx.doi.org/10.2147/CMAR.S47986DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3875371PMC
November 2013

High-pitch coronary CT angiography in dual-source CT during free breathing vs. breath holding in patients with low heart rates.

Eur J Radiol 2013 Dec 12;82(12):2217-21. Epub 2013 Sep 12.

Institute for Clinical Radiology; Ludwig-Maximilians-University Hospital Munich, Germany; DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany. Electronic address:

Background: Coronary CT angiography (CCTA) is usually performed during breath holding to reduce motion artifacts caused by respiration. However, some patients are not able to follow the breathing commands adequately due to deafness, hearing impairment, agitation or pulmonary diseases. The aim of this study was to evaluate the potential of high-pitch CCTA in free breathing patients when compared to breath holding patients.

Methods: In this study we evaluated 40 patients (20 free breathing and 20 breath holding patients) with a heart rate of 60 bpm or below referred for CCTA who were examined on a 2nd generation dual-source CT system. Image quality of each coronary artery segment was rated using a 4-point grading scale (1: non diagnostic-4: excellent).

Results: Mean heart rate during image acquisition was 52 ± 5 bpm in both groups. There was no significant difference in mean image quality, slightly favoring image acquisition during breath holding (mean image quality score 3.76 ± 0.32 in breath holding patients vs. 3.61 ± 0.45 in free breathing patients; p = 0.411). Due to a smaller amount of injected contrast medium, there was a trend for signal intensity to be slightly lower in free breathing patients, but this was not statistically significant (435 ± 123 HU vs. 473 ± 117 HU; p=0.648).

Conclusion: In patients with a low heart rate who are not able to hold their breath adequately, CCTA can also be acquired during free breathing without substantial loss of image quality when using a high pitch scan mode in 2nd generation dual-source CT.
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http://dx.doi.org/10.1016/j.ejrad.2013.09.003DOI Listing
December 2013

A 68-year-old Caucasian man presenting with urinary bladder lymphoepithelioma: a case report.

J Med Case Rep 2013 Jun 20;7:161. Epub 2013 Jun 20.

UOC Oncology Aprilia - (LT), University of Rome 'Sapienza', via Giustiniano snc, 04011 Aprilia, LT, Italy.

Introduction: Lymphoepithelioma is a very rare form of malignant tumor originating from epithelial line cells. Its occurrence has potential clinical, therapeutic and prognostic implications. In the present report we describe an unusual case of bladder cancer with two different histological varieties: transition cell carcinoma and lymphoepithelioma-like carcinoma. Lymphoepithelioma-like carcinoma of the bladder has only been rarely reported in the literature to date.

Case Presentation: We present the case of a 68-year-old Caucasian man who, after occurrence of hematuria, underwent transurethral resection of a bladder tumor. The results of a histological examination confirmed a high-grade non-muscle-invasive pT1 lymphoepithelioma-like carcinoma of the urinary bladder, associated with a concurrent high-grade transition cell carcinoma. After analyzing the histological features, our patient was subjected to treatment with intra-vesical instillations of bacillus Calmette-Guérin. Our work stresses that diagnosis and therapeutic approaches can be difficult and controversial, especially in the early stages of this rare carcinoma.

Conclusions: This report emphasizes the importance of extending our knowledge and experiences regarding this uncommon carcinoma. Further studies are needed to better understand this rare disease and define more accurate diagnostic and therapeutic strategies.
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http://dx.doi.org/10.1186/1752-1947-7-161DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3700764PMC
June 2013