Publications by authors named "Flavia Longo"

73 Publications

Combination of chemotherapy and PD-1 blockade induces T cell responses to tumor non-mutated neoantigens.

Commun Biol 2020 02 25;3(1):85. Epub 2020 Feb 25.

Dipartimento di Medicina Interna e Specialità Mediche, Sapienza Università di Roma, 00161, Rome, Italy.

Here, we developed an unbiased, functional target-discovery platform to identify immunogenic proteins from primary non-small cell lung cancer (NSCLC) cells that had been induced to apoptosis by cisplatin (CDDP) treatment in vitro, as compared with their live counterparts. Among the multitude of proteins identified, some of them were represented as fragmented proteins in apoptotic tumor cells, and acted as non-mutated neoantigens (NM-neoAgs). Indeed, only the fragmented proteins elicited effective multi-specific CD4 and CD8 T cell responses, upon a chemotherapy protocol including CDDP. Importantly, these responses further increased upon anti-PD-1 therapy, and correlated with patients' survival and decreased PD-1 expression. Cross-presentation assays showed that NM-neoAgs were unveiled in apoptotic tumor cells as the result of caspase-dependent proteolytic activity of cellular proteins. Our study demonstrates that apoptotic tumor cells generate a repertoire of immunogenic NM-neoAgs that could be potentially used for developing effective T cell-based immunotherapy across multiple cancer patients.
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http://dx.doi.org/10.1038/s42003-020-0811-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7042341PMC
February 2020

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

Analysis of CT features and quantitative texture analysis in patients with thymic tumors: correlation with grading and staging.

Radiol Med 2018 May 6;123(5):345-350. Epub 2018 Jan 6.

Department of Radiological, Oncological and Anatomopathological Sciences - Radiology, "Sapienza" University of Rome, Rome, Italy.

Objectives: To evaluate potential relationship between qualitative CT features, quantitative texture analysis (QTA), histology, WHO staging, Masaoka classification and myasthenic syndrome in patients with thymic tumors.

Materials And Methods: Sixteen patients affected by histologically proven thymic tumors were retrospectively included in the study population. Clinical information, with special regard to myasthenic syndrome and serological positivity of anti-AchR antibodies, were recorded. Qualitative CT evaluation included the following parameters: (a) location; (b) tumor edges; (c) necrosis; (d) pleural effusion; (e) metastases; (f) chest wall infiltration; (g) tumor margins. QTA included evaluation of "Mean" (M), "Standard Deviation" (SD), "Kurtosis" (K), "Skewness" (S), "Entropy" (E), "Shape from Texture" (TX_sigma) and "average of positive pixels" (MPP). Pearson-Rho test was used to evaluate the relationship of continuous non-dichotomic parameters, whereas Mann-Whitney test was used for dichotomic parameters.

Results: Histological evaluation demonstrated thymoma in 12 cases and thymic carcinoma in 4 cases. Tumor necrosis was significantly correlated with QTA Mean (p = 0.0253), MPP (p = 0.0417), S (p = 0.0488) and K (p = 0.0178). WHO staging was correlated with Mean (p = 0.0193), SD (p = 0.0191) and MPP (p = 0.0195). Masaoka classification was correlated with Mean (p = 0.0322), MPP (p = 0.0315), skewness (p = 0.0433) and Kurtosis (p = 0.0083). Myasthenic syndrome was significantly associated with Mean (p = 0.0211) and MPP (p = 0.0261), whereas tumor size was correlated with Mean (p = 0.0241), entropy (p = 0.0177), MPP (p = 0.0468), skewness (p = 0.009) and Kurtosis (p = 0.006).

Conclusion: Our study demonstrates significant relationship between radiomics parameters, histology, grading and clinical manifestations of thymic tumors.
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http://dx.doi.org/10.1007/s11547-017-0845-4DOI Listing
May 2018

Multimodality treatment of stage II thymic tumours.

J Thorac Dis 2017 Aug;9(8):2369-2374

Department of Thoracic Surgery, University of Rome Sapienza, Rome, Italy.

Background: Complete resection for stage II thymic tumors can be easily accomplished even if the capsula and adjacent mediastinal tissue are macroscopically involved; however, also at this stage, recurrence may occur, particularly for B2, B3 and thymic carcinoma. The criteria for the administration of adjuvant therapy remain controversial and it is unclear whether patients at this stage may benefit from it. We reviewed a series of patients at this stage receiving adjuvant chemo-radiotherapy (chemo-RT) based on histology.

Methods: Eighty-eight consecutive patients with stage II thymic tumors were reviewed; 59 patients (67%) with B thymoma or thymic carcinoma received adjuvant treatment with mediastinal irradiation (40-55 Gy), chemotherapy (CH) (PAC regimen) or a combination of both.

Results: Complete resection was achieved in all patients. Fifty-four patients (61%) received post-operative chemo-RT, 2 (2%) patients received adjuvant CH only and 3 (3%) post-operative RT only; they all had B2, B3 histology or thymic carcinoma. The median follow up was 107±83 months. 5-year and 10-year survival were 96%±2% and 83.4%±5%. Recurrence was observed in 5 patients (5.7%). Disease-free 5 and 10-year survival was 94%±2% and 92%±3% respectively. Five patients (5.7%) had recurrence.

Conclusions: The administration of adjuvant chemo-RT to patients with stage II type B thymoma and thymic carcinoma contributes to reduce the recurrence rate and to increase long-term survival.
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http://dx.doi.org/10.21037/jtd.2017.06.116DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5594157PMC
August 2017

IL-18 receptor marks functional CD8 T cells in non-small cell lung cancer.

Oncoimmunology 2017;6(7):e1328337. Epub 2017 May 12.

Dipartimento di Medicina Interna e Specialità Mediche, "Sapienza" Università di Roma, Rome, Italy.

IL-18 is an inflammasome-related cytokine, member of the IL-1 family, produced by a wide range of cells in response to signals by several pathogen- or damage-associated molecular patterns. It can be highly represented in tumor patients, but its relevance in human cancer development is not clear. In this study, we provide evidence that IL-18 is principally expressed in tumor cells and, in concert with other conventional Th1 cell-driven cytokines, has a pivotal role in establishing a pro-inflammatory milieu in the tumor microenvironment of human non-small cell lung cancer (NSCLC). Interestingly, the analysis of tumor-infiltrating CD8 T cell populations showed that (i) the relative IL-18 receptor (IL-18R) is significantly more expressed by the minority of cells with a functional phenotype (T-betEomes), than by the majority of those with the dysfunctional phenotype T-betEomes generally resident within tumors; (ii) as a consequence, the former are significantly more responsive than the latter to IL-18 stimulus in terms of IFNγ production ; (iii) PD-1 expression does not discriminate these two populations. These data indicate that IL-18R may represent a biomarker of the minority of functional tumor-infiltrating CD8 T cells in adenocarcinoma NSCLC patients. In addition, our results lead to envisage the possible therapeutic usage of IL-18 in NSCLC, even in combination with other checkpoint inhibitor approaches.
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http://dx.doi.org/10.1080/2162402X.2017.1328337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5543928PMC
May 2017

Vascular Endothelial Growth Factor Inhibitor Therapy and Cardiovascular and Renal Damage in Renal Cell Carcinoma.

Curr Vasc Pharmacol 2018 01;16(2):190-196

Department of Dynamic and Clinic Psychology, Sapienza University of Rome, Rome, Italy.

Background: Sunitinib, a tyrosine kinase inhibitor of vascular endothelial growth factor (VEGF), is approved for first and second line treatment of advanced renal cell carcinoma (RCC). Knowledge on the effects of sunitinib on cardiovascular (CV) risk and renal damage is limited.

Aim: To evaluate possible renal and CV damage in patients with RCC treated with sunitinib.

Materials And Methods: Patients with metastatic RCC treated with sunitinib were enrolled. This population was evaluated before starting treatment (T0) and after 3 months (T1). Laboratory and instrumental parameters, including interventricular septum (IVS) and left ventricular mass index (LVMI) were recorded before and after treatment.

Results: Thirty-two patients (13 female, 19 male, mean age 62.7±9.9 years) were enrolled. We observed overtime, a significant reduction in estimated glomerular filtration rate (eGFR) (p=0.01), hemoglobin (Hb) (p=0.04) and 25-hydroxyvitamin D (25-OH-VitD) (p=0.002), in association with a significant increase in serum phosphorus (p<0.001), systolic blood pressure (SBP) (p<0.001), diastolic blood pressure (DBP) (p<0.001), IVS (p=0.03) and proteinuria (p<0.001), while we showed no significant differences in glycosuria, phosphaturia, serum uric acid, intact parathormone, and LVMI.

Conclusion: We observed the development of renal damage and worsening of CV indices in patients treated with sunitinib. We suggest to consider a careful assessment of renal function and CV risk factors, before initiation and during administration of this drug.
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http://dx.doi.org/10.2174/1570161115666170621073715DOI Listing
January 2018

Mineral metabolism abnormalities in patients with prostate cancer: a systematic case controlled study.

Endocrine 2018 02 28;59(2):338-343. Epub 2017 Jun 28.

Department of Internal Medicine and Medical Disciplines, Sapienza University of Rome, Rome, Italy.

Purpose: Prostate cancer is the most common tumor in men. To the best of our knowledge a systematic assessment of bone and mineral abnormalities has not been performed in prostatic cancer patients consecutively enrolled.

Methods: This study was therefore carried out to investigate changes of skeletal and mineral metabolism in patients with prostate cancer (n  = 69). A population of patients with cancer of various origin was also investigated as a control group (n  = 53), since a comparison with non-prostate cancer patients has not been previously reported.

Results: In the prostatic cancer group, one patient had extremely high values of C-terminal Fibroblast Growth Factor 23, low values of tubular reabsorption of phosphate and very high values of bone alkaline phosphatase, suggesting the diagnosis of oncogenic osteomalacia. We found nine patients with primary hyperparathyroidism in the group of prostate cancer vs. only one in cancer patients group (p  <  0.026). We stratified the population on the basis of Gleason score, prostate specific antigen and hormonal therapy. Using a generalized linear model with a logit link to predict the probability of developing primary hyperparathyroidism, only Gleason score, C-terminal fibroblast growth factor 23 and hormonal therapy had a significant effect (p  < 0.05). Controlling for other covariates, a rise in fibroblast growth factor 23 increases the odds of developing primary hyperparathyroidism by 2% (p  = 0.017), while patients with higher values of Gleason score have a much greater probability of developing primary hyperparathyroidism (log-odds  =  3.6, p  <  0.01). The probability decreases with higher values of Gleason score while on hormonal therapy; a further decrease was observed in patients on hormonal treatment and lower values of GS. Finally, lower grade of Gleason score without hormonal therapy have a significant protective factor (p  <  0.01) decreasing the odds of developing primary hyperparathyroidism by 8%.

Conclusion: We showed a remarkable prevalence of primary hyperparathyroidism in men with prostate cancer; the multivariate analysis demonstrates that higher aggressiveness of prostate cancer, as determined by Gleason score, is a significant predictor of increased risk of developing primary hyperparathyroidism.
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http://dx.doi.org/10.1007/s12020-017-1351-0DOI Listing
February 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

Economic burden of patients affected by non-small cell lung cancer (NSCLC): the LIFE study.

J Cancer Res Clin Oncol 2017 May 18;143(5):783-791. Epub 2017 Feb 18.

Istituto Europeo di Oncologia, Milan, Italy.

Purpose: Non-small cell lung cancer (NSCLC) is a condition with significant clinical burden for patients and relevant economic impact. Limited evidence exists on the management costs of NSCLC patients, especially in the late phases of the disease. The main objective of this analysis was to evaluate the economic impact of clinical management of NSCLC patients in the Italian population.

Methods: This evaluation was an economic analysis of the observational and multicentre study LIFE, which described the therapeutic approach in routine clinical practice for NSCLC patients, progressing after first-line treatment. This study evaluated resource consumption in different Italian hospitals, including specialist visits, hospitalizations, accesses to first aid, pharmacological treatment, laboratory tests and palliative care. The National Healthcare Service perspective was adopted.

Results: In this study, N = 191 patients enrolled in the LIFE study were included. Patients were aged 64.2 years and were predominantly males (66%). In the different line of treatments, monthly costs of patients ranged between €1471 (first line) and €1788 (third line). The overall healthcare cost over the average period of observation (16.4 months) was €25,859 per patient. Overall, oncology therapy was the cost driver, although the composition of medical costs changed across the different lines of treatment, with costs for concomitant medication and palliative care being predominant in late phase of the disease.

Conclusions: The economic burden of NSCLC is extremely high during the overall period of treatment, and a significant level of care is required in each stage of the disease.
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http://dx.doi.org/10.1007/s00432-016-2326-xDOI Listing
May 2017

Anaplastic thyroid carcinoma and foscarnet use in a multitarget treatment documented by 18F-FDG PET/CT: A case report.

Medicine (Baltimore) 2017 Feb;96(6):e5621

Department of Experimental Medicine Department of Internal Medicine and Clinical Specialities Department of Radiology, Anatomopathology and Oncology, Sapienza University of Rome, Rome Nuclear Medicine Unit, Department of Interventional Oncology, Azienda Ospedaliera Ospedale di Circolo di Busto Arsizio Varese, Busto Arsizio, Varese, Italy.

Rationale: The case reported the rapid remission of disease recurrence achieved adding foscarnet, a DNA polymerase inhibitor that interacts with fibroblast growth factor 2, to low molecular weight heparin and sunitinib for the first time in a patient with an anaplastic thyroid cancer (ATC).

Patient Concerns: A 65-year-old woman with a multinodular goiter referred for a rapid enlargement of a nodule. Histological examination revealed an ATC with a little area of papillary thyroid cancer (PTC). The patient was resistant to selective single-target treatment.

Diagnoses: Immunophenotyping and gene analyses found a significant increase in FGF2 and FGFR1 expression in the primary ATC area (FGF2 = 38.2 ± 6.2% in ATC vs 34.6 ± 6.0% in the differentiated area of PTC, P < 0.05; FGFR1: 41.7 ± 6.0% in ATC vs 34.4 ± 4.2% in PTC, P < 0.001) and in metastatic neck lymph nodes (P < 0.001 vs normal control tissues). Unlike conventional imaging, F-FDG PET/CT with PERCIST 1.0 criteria promptly and quantitatively detected disease recurrence and remission before and after multitarget therapy, combining anatomic, metabolic, and functional data.

Interventions: Foscarnet was administered given the positivity for FGF2, FGFR1 and FGFR4 in ATC. Low molecular wight heparin and Sunitinib were coadministere to limiti metastatic progression and on neck tumor masse, respectively.

Outcomes: The rationale for the clinical response to this innovative multitarget association with foscarnet is based on the histological and genetic finding that fibroblast growth factors and their receptor super-family are up-regulated in the primary anaplastic thyroid tumor and in the metastatic lymph node of our patient.

Lessons: We propose that fibroblast growth factors and their receptor super-family play a key role as potential therapeutic targets in anaplastic thyroid cancer and the positive relevance of this suggestion for patient care, especially for an individualized management.
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http://dx.doi.org/10.1097/MD.0000000000005621DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5312981PMC
February 2017

Regulatory T cells with multiple suppressive and potentially pro-tumor activities accumulate in human colorectal cancer.

Oncoimmunology 2016 Jul 25;5(7):e1175800. Epub 2016 Apr 25.

Dipartimento di Medicina Interna e Specialità Mediche, Sapienza Università di Roma, Rome, Italy; Istituto Pasteur-Fondazione Cenci Bolognetti, Rome, Italy.

Tregs can contribute to tumor progression by suppressing antitumor immunity. Exceptionally, in human colorectal cancer (CRC), Tregs are thought to exert beneficial roles in controlling pro-tumor chronic inflammation. The goal of our study was to characterize CRC-infiltrating Tregs at multiple levels, by phenotypical, molecular and functional evaluation of Tregs from the tumor site, compared to non-tumoral mucosa and peripheral blood of CRC patients. The frequency of Tregs was higher in mucosa than in blood, and further significantly increased in tumor. Ex vivo, those Tregs suppressed the proliferation of tumor-infiltrating CD8(+) and CD4(+) T cells. A differential compartmentalization was detected between Helios(high) and Helios(low) Treg subsets (thymus-derived versus peripherally induced): while Helios(low) Tregs were enriched in both sites, only Helios(high) Tregs accumulated significantly and specifically in tumors, displayed a highly demethylated TSDR region and contained high proportions of cells expressing CD39 and OX40, markers of activation and suppression. Besides the suppression of T cells, Tregs may contribute to CRC progression also through releasing IL-17, or differentiating into Tfr cells that potentially antagonize a protective Tfh response, events that were both detected in tumor-associated Tregs. Overall, our data indicate that Treg accumulation may contribute through multiple mechanisms to CRC establishment and progression.
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http://dx.doi.org/10.1080/2162402X.2016.1175800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5006916PMC
July 2016

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

Natural History of Non-Small-Cell Lung Cancer with Bone Metastases.

Sci Rep 2015 Dec 22;5:18670. Epub 2015 Dec 22.

Department of Medical Oncology, Institute for Cancer Research &Treatment (IRCC), Candiolo, Torino, Italy.

We conducted a large, multicenter, retrospective survey aimed to explore the impact of tumor bone involvement in Non-Small Cell Lung Cancer.Data on clinical-pathology, skeletal outcomes and bone-directed therapies for 661 deceased patients with evidence of bone metastasis were collected and statistically analyzed. Bone metastases were evident at diagnosis in 57.5% of patients. In the remaining cases median time to bone metastases appearance was 9 months. Biphosphonates were administered in 59.6% of patients. Skeletal-related events were experienced by 57.7% of patients; the most common was the need for radiotherapy. Median time to first skeletal-related event was 6 months. Median survival after bone metastases diagnosis was 9.5 months and after the first skeletal-related event was 7 months. We created a score based on four factors used to predict the overall survival from the diagnosis of bone metastases: age >65 years, non-adenocarcinoma histology, ECOG Performance Status >2, concomitant presence of visceral metastases at the bone metastases diagnosis. The presence of more than two of these factors is associated with a worse prognosis.This study demonstrates that patients affected by Non-Small Cell Lung Cancer with bone metastases represent a heterogeneous population in terms of risk of skeletal events and survival.
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http://dx.doi.org/10.1038/srep18670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4687045PMC
December 2015

Circulating miR-21-5p and miR-148a-3p as emerging non-invasive biomarkers in thymic epithelial tumors.

Cancer Biol Ther 2016 ;17(1):79-82

a Department of Anatomical, Histological , Forensic and orthopedic Sciences, Section of Histology & Medical Embryology, Sapienza University of Rome , Rome , Italy.

Thymic epithelial cells give rise to both thymoma and thymic carcinoma. A crucial advance in thymic epithelial tumors (TET) management may derive from the identification of novel molecular biomarkers able to improve diagnosis, prognosis and treatment planning.In a previous study, we identified microRNAs that were differentially expressed in tumor vs normal thymic tissues. Among the microRNAs resulted up-regulated in TET tissues, we evaluated miR-21-5p, miR-148a-3p, miR-141-3p, miR-34b-5p, miR-34c-5p, miR-455-5p as blood plasma circulating non-invasive biomarkers for TET management.We firstly report that the expression levels of specific onco-miRNAs, that we found upregulated in the blood plasma collected from TET patients at surgery, resulted significantly reduced in follow-up samples.This pilot study suggests that circulating miR-21-5p and miR-148a-3p could represent novel non-invasive biomarkers to evaluate the efficacy of therapy and the prognosis of TET.
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http://dx.doi.org/10.1080/15384047.2015.1108493DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4847810PMC
October 2016

Role of KRAS-LCS6 polymorphism in advanced NSCLC patients treated with erlotinib or docetaxel in second line treatment (TAILOR).

Sci Rep 2015 Nov 17;5:16331. Epub 2015 Nov 17.

Oncology Department, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Italy.

MicroRNAs were described to target mRNA and regulate the transcription of genes involved in processes de-regulated in tumorigenesis, such as proliferation, differentiation and survival. In particular, the miRNA let-7 has been suggested to regulate the expression of the KRAS gene, a common mutated gene in non-small cell lung cancer (NSCLC), through a let-7 complementary site (LCS) in 3'UTR of KRAS mRNA. We have reported the analysis performed on the role of the polymorphism located in the KRAS-LCS (rs61764370) which is involved in the disruption of the let-7 complementary site in NSCLC patients enrolled within the TAILOR trial, a randomised trial comparing erlotinib versus docetaxel in second line treatment. In our cohort of patients, KRAS-LCS6 polymorphism did not have any impact on both overall survival (OS) and progression free survival (PFS) and was not associated with any patient's baseline characteristics included in the study. Overall, patients had a better prognosis when treated with docetaxel instead of erlotinib for both OS and PFS. Considering KRAS-LCS6 status, the TG/GG patients had a benefit from docetaxel treatment (HR(docetaxel vs erlotinib) = 0.35, 95% CI 0.15-0.79, p = 0.011) compared with the TT patients (HR(docetaxel vs erlotinib) = 0.72, 95% CI 0.52-1.01, p = 0.056) in terms of PFS.
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http://dx.doi.org/10.1038/srep16331DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4648064PMC
November 2015

KRAS mutations affect prognosis of non-small-cell lung cancer patients treated with first-line platinum containing chemotherapy.

Oncotarget 2015 Oct;6(32):34014-22

Oncology Department, IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.

Unlabelled: KRAS mutations seem to indicate a poor outcome in Non-Small-Cell Lung Cancer (NSCLC) but such evidence is still debated. The aim of this planned ancillary study within the TAILOR trial was to assess the prognostic value of KRAS mutations in advanced NSCLC patients treated with platinum-based first-line chemotherapy. Patients (N = 540), enrolled in the study in 52 Italian hospitals, were centrally genotyped twice in two independent laboratories for EGFR and KRAS mutational status.Of these, 247 patients were eligible and included in the present study. The primary endpoint was overall survival (OS) according to KRAS mutational status in patients harboring EGFR wild-type.Sixty (24.3%) out of 247 patients harbored KRAS mutations. Median OS was 14.3 months and 10.6 months in wild-type and mutated KRAS patients, respectively (unadjusted Hazard Ratio [HR]=1.41, 95%Confidence Interval [CI]: 1.03-1.94 P = 0.032; adjusted HR=1.39, 95%CI: 1.00-1.94 P = 0.050). This study, with all consecutive patients genotyped, indicates that the presence of KRAS mutations has a mild negative impact on OS in advanced NSCLC patient treated with a first-line platinum-containing regimen.

Trial Registration: clinicaltrials.gov identifierNCT00637910.
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http://dx.doi.org/10.18632/oncotarget.5607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4741822PMC
October 2015

Development of a prediction model and risk score for procedure-related complications in patients undergoing percutaneous computed tomography-guided lung biopsy.

Eur J Cardiothorac Surg 2015 Jul 16;48(1):e1-6. Epub 2015 May 16.

Department of Radiological, Oncological and Anatomopathological Sciences - Radiology, 'Sapienza' University of Rome, Rome, Italy.

Objectives: To propose a risk score predicting the potential occurrence of procedure-related complications in patients undergoing computed tomography (CT)-guided lung biopsy.

Methods: Institution review board approval was obtained. A total of 342 CT-guided lung biopsies were retrospectively evaluated taking into account procedure-related complications and associated risk factors, including patient gender and age, previous radiation therapy (RT) and/or chemotherapy (CHT), lesion size, depth and location, incomplete pulmonary fissures, associated diffuse lung diseases, previous pneumothorax (PNX), lung volumes, punctured fissures, thoracic access, needle size and operator experience. Complications were assessed on chest X-ray and/or CT scans. Stepwise logistic regression was used to identify risk factors, to evaluate their correlation with procedure-related complications and to calculate models of risk (MoRs).

Results: PNX requiring chest tube placement occurred in 39 patients (11.4%), high-grade pulmonary parenchymal haemorrhage occurred in 62 patients (18.1%) and haemothorax occurred in 12 patients (3.5%). Risk factors increasing the incidence of complications were lesion size (P = 0.01), lesion depth (P = 0.01) and incomplete pulmonary fissures (P = 0.01); previous chemo-radiation therapy was correlated to a lower incidence of complications (P = 0.01). MoR for PNX was as follows: risk base line = 60%; age = +0.15%/year; punctured fissures = +20%; incomplete fissures = +9%; previous CHT/RT = -10%. MoR for parenchymal haemorrhage was as follows: risk base line = 20%, lesion depth = +0.8%/mm; age = +0.25%/year; incomplete fissures = +15%. MoR for haemothorax was as follows: risk base line = 1%; previous PNX = +20%; incomplete fissures = 7%; both previous PNX and incomplete fissures = +67%.

Conclusion: This study provides MoRs to predict the risk of complications in patients undergoing CT-guided percutaneous lung biopsies.
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http://dx.doi.org/10.1093/ejcts/ezv172DOI Listing
July 2015

HE4 in the differential diagnosis of ovarian masses.

Clin Chim Acta 2015 Jun 16;446:147-55. Epub 2015 Apr 16.

Department of Molecular Medicine, "Sapienza" University of Rome, Policlinico Umberto I, Viale Regina Elena 324, 00161 Rome, Italy. Electronic address:

Ovarian masses, a common finding among pre- and post-menopausal women, can be benign or malignant. Ovarian cancer is the leading cause of death from gynecologic malignancy among women living in industrialized countries. According to the current guidelines, measurement of CA125 tumor marker remains the gold standard in the management of ovarian cancer. Recently, HE4 has been proposed as emerging biomarker in the differential diagnosis of adnexal masses and in the early diagnosis of ovarian cancer. Discrimination of benign and malignant ovarian tumors is very important for correct patient referral to institutions specialized in care and management of ovarian cancer. Tumor markers CA125 and HE4 are currently incorporated into the "Risk of Ovarian Malignancy Algorithm" (ROMA) with menopausal status for discerning malignant from benign pelvic masses. The availability of a good biomarker such as HE4, closely associated with the differential and early diagnosis of ovarian cancer, could reduce medical costs related to more expensive diagnostic procedures. Finally, it is important to note that HE4 identifies platinum non-responders thus enabling a switch to second line chemotherapy and improved survival.
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http://dx.doi.org/10.1016/j.cca.2015.03.047DOI Listing
June 2015

Identification of subgroups of early breast cancer patients at high risk of nonadherence to adjuvant hormone therapy: results of an Italian survey.

Clin Breast Cancer 2015 Apr 22;15(2):e131-7. Epub 2014 Oct 22.

Department of Experimental and Clinical Sciences, University 'G. d'Annunzio,' Chieti, Italy.

Background: Adherence to adjuvant endocrine therapy (HT) is suboptimal among breast cancer patients. A high rate of nonadherence might explain differences in survival between clinical trial and clinical practice. Tailored interventions aimed at improving adherence can only be implemented if subgroups of patients at higher risk of poor adherence are identified. Because no data are available for Italy, we undertook a large survey on adherence among women taking adjuvant HT for breast cancer.

Patients And Methods: Patients were recruited from 10 cancer clinics in central Italy. All patients taking HT for at least 1 year were invited, during one of their follow-up visit, to fill a confidential questionnaire. The association of sociodemographic and clinical characteristics of participants with adherence was assessed using logistic regression. The RECPAM method was used to evaluate interactions among variables and to identify subgroups of patients at different risk of nonadherence.

Results: A total of 939 patients joined the study and 18.6% of them were classified as nonadherers. Among possible predictors, only age, working status, and switching from tamoxifen to an aromatase inhibitor were predictive of nonadherence in multivariate analysis. RECPAM analysis led to the identification of 4 classes of patients with a different likelihood of nonadherence to therapy, the lowest being observed in retired women with a low level of education, the highest in the group of unmarried, employed women, or housewives.

Conclusion: The identification of these subgroups of "real life" patients with a high prevalence of nonadherers might be functional in designing intervention studies aimed at improving adherence.
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http://dx.doi.org/10.1016/j.clbc.2014.10.005DOI Listing
April 2015

Preliminary clinical experience with a dedicated interventional robotic system for CT-guided biopsies of lung lesions: a comparison with the conventional manual technique.

Eur Radiol 2015 May 23;25(5):1310-6. Epub 2014 Nov 23.

Department of Radiological, Oncological and Anatomopathological Sciences - Radiology - Sapienza, University of Rome, Viale Regina Elena 324, 00161, Rome, Italy,

Objective: Evaluate the performance of a robotic system for CT-guided lung biopsy in comparison to the conventional manual technique.

Materials And Methods: One hundred patients referred for CT-guided lung biopsy were randomly assigned to group A (robot-assisted procedure) or group B (conventional procedure). Size, distance from entry point and position in lung of target lesions were evaluated to assess homogeneity differences between the two groups. Procedure duration, dose length product (DLP), precision of needle positioning, diagnostic performance of the biopsy and rate of complications were evaluated to assess the clinical performance of the robotic system as compared to the conventional technique.

Results: All biopsies were successfully performed. The size (p = 0.41), distance from entry point (p = 0.86) and position in lung (p = 0.32) of target lesions were similar in both groups (p = 0.05). Procedure duration and radiation dose were significantly reduced in group A as compared to group B (p = 0.001). Precision of needle positioning, diagnostic performance of the biopsy and rate of complications were similar in both groups (p = 0.05).

Conclusion: Robot-assisted CT-guided lung biopsy can be performed safely and with high diagnostic accuracy, reducing procedure duration and radiation dose in comparison to the conventional manual technique.

Key Points: • CT-guided biopsy is the main procedure to obtain diagnosis in lung tumours. • The robotic device facilitates percutaneous needle placement under CT guidance. • Robot-assisted CT-guided lung biopsy reduces procedure duration and radiation dose.
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http://dx.doi.org/10.1007/s00330-014-3508-zDOI Listing
May 2015

Metastatic colorectal cancer first-line treatment with bevacizumab: the impact of K-ras mutation.

Onco Targets Ther 2013 29;6:1761-9. Epub 2013 Nov 29.

Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Rome, Italy.

Background: Bevacizumab plus chemotherapy prolongs progression-free survival (PFS) and overall survival (OS) in metastatic colorectal cancer (mCRC). Although there is strong evidence to suggest that the mutational status of the K-ras oncogene has a role as a predictive factor for activity in patients treated with cetuximab and panitumumab, few data have been obtained in patients treated with bevacizumab. We conducted an additional retrospective analysis to investigate the prognostic value of K-ras mutation relative to mCRC first-line treatment with bevacizumab.

Materials And Methods: A total of 108 patients were retrospectively reviewed. K-ras status was assessed in the overall population by sequencing. Statistical association for PFS and OS was analyzed using the Kaplan-Meier method, and the prognostic role of K-ras was determined using the logrank test.

Results: Median PFS was 10 months both for patients with wild-type (WT) K-ras and mutated (MT) K-ras (hazard ratio [HR] 0.94, P=0.75); neither difference in median OS was significant (27 months WT K-ras versus 26 months MT K-ras, HR 0.92; P=0.70). A further analysis was carried out in the two groups according to metastatic sites. No statistically significant difference in terms of PFS and OS was demonstrated between WT K-ras and MT K-ras with liver metastases only and in those with extrahepatic disease.

Conclusion: Although further study is required, our results seem to confirm that K-ras mutation does not have a prognostic role in mCRC patients receiving first-line treatment with bevacizumab.
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http://dx.doi.org/10.2147/OTT.S43828DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3848929PMC
December 2013

Merkel cell carcinoma of the retroperitoneum with no identifiable primary site.

Case Rep Oncol Med 2013 1;2013:131695. Epub 2013 Sep 1.

Department of Clinical Oncology A, Sapienza University of Rome, Policlinico Umberto Primo, Viale Regina Elena 324, 00161 Rome, Italy.

Merkel cell carcinoma (MCC) is an extremely rare primary neuroendocrine neoplasm of the skin that shows aggressive behavior and a poor prognosis. We report a case of a 67-year-old male with a Merkel cell carcinoma which initially presented itself as a large retroperitoneal mass. Pathological and immunohistochemical analysis revealed tissue consistent with neuroendocrine carcinoma. Despite complete medical workup, no other primary MCC could be detected. While being an atypical presentation, the tumor mass showed an excellent response to the combination of chemotherapy followed by radiotherapy.
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http://dx.doi.org/10.1155/2013/131695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3773894PMC
September 2013

Erlotinib versus docetaxel as second-line treatment of patients with advanced non-small-cell lung cancer and wild-type EGFR tumours (TAILOR): a randomised controlled trial.

Lancet Oncol 2013 Sep 22;14(10):981-8. Epub 2013 Jul 22.

Department of Medical Oncology, Fatebenefratelli e Oftalmico Hospital, Milan,

Background: Erlotinib is registered for treatment of all patients with advanced non-small-cell lung cancer (NSCLC). However, its efficacy for treatment of patients whose tumours are EGFR wild-type-which includes most patients-is still contentious. We assessed the efficacy of erlotinib compared with a standard second-line chemotherapy in such patients.

Methods: We did this randomised controlled trial in 52 Italian hospitals. We enrolled patients who had metastatic NSCLC, had had platinum-based chemotherapy, and had wild-type EGFR as assessed by direct sequencing. Patients were randomly assigned centrally (1:1) to receive either erlotinib orally 150 mg/day or docetaxel intravenously 75 mg/m(2) every 21 days or 35 mg/m(2) on days 1, 8, and 15, every 28 days. Randomisation was stratified by centre, stage, type of first-line chemotherapy, and performance status. Patients and investigators who gave treatments or assessed outcomes were not masked to treatment allocation, investigators who analysed results were. The primary endpoint was overall survival in the intention-to-treat population. The study is registered at ClinicalTrials.gov, number NCT00637910.

Findings: We screened 702 patients, of whom we genotyped 540. 222 patients were enrolled (110 assigned to docetaxel vs 112 assigned to erlotinib). Median overall survival was 8·2 months (95% CI 5·8-10·9) with docetaxel versus 5·4 months (4·5-6·8) with erlotinib (adjusted hazard ratio [HR] 0·73, 95% CI 0·53-1·00; p=0·05). Progression-free survival was significantly better with docetaxel than with erlotinib: median progression-free survival was 2·9 months (95% CI 2·4-3·8) with docetaxel versus 2·4 months (2·1-2·6) with erlotinib (adjusted HR 0·71, 95% CI 0·53-0·95; p=0·02). The most common grade 3-4 toxic effects were: low absolute neutrophil count (21 [20%] of 104 in the docetaxel group vs none of 107 in the erlotinib group), skin toxic effects (none vs 15 [14%]), and asthenia (ten [10%] vs six [6%]).

Interpretation: Our results show that chemotherapy is more effective than erlotinib for second-line treatment for previously treated patients with NSCLC who have wild-type EGFR tumours.
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http://dx.doi.org/10.1016/S1470-2045(13)70310-3DOI Listing
September 2013

Evaluation of a CLEIA automated assay system for the detection of a panel of tumor markers.

Tumour Biol 2013 Oct 18;34(5):3093-100. Epub 2013 Jun 18.

Laboratory of Tumor Markers, Department of Molecular Medicine, University "Sapienza", Viale Regina Elena 324, 00161, Rome, Italy.

Tumor markers are commonly used to detect a relapse of disease in oncologic patients during follow-up. It is important to evaluate new assay systems for a better and more precise assessment, as a standardized method is currently lacking. The aim of this study was to assess the concordance between an automated chemiluminescent enzyme immunoassay system (LUMIPULSE® G1200) and our reference methods using seven tumor markers. Serum samples from 787 subjects representing a variety of diagnoses, including oncologic, were analyzed using LUMIPULSE® G1200 and our reference methods. Serum values were measured for the following analytes: prostate-specific antigen (PSA), alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), carbohydrate antigen 15-3 (CA15-3), carbohydrate antigen 19-9 (CA19-9), and cytokeratin 19 fragment (CYFRA 21-1). For the determination of CEA, AFP, and PSA, an automatic analyzer based on chemiluminescence was applied as reference method. To assess CYFRA 21-1, CA125, CA19-9, and CA15-3, an immunoradiometric manual system was employed. Method comparison by Passing-Bablok analysis resulted in slopes ranging from 0.9728 to 1.9089 and correlation coefficients from 0.9977 to 0.9335. The precision of each assay was assessed by testing six serum samples. Each sample was analyzed for all tumor biomarkers in duplicate and in three different runs. The coefficients of variation were less than 6.3 and 6.2 % for within-run and between-run variation, respectively. Our data suggest an overall good interassay agreement for all markers. The comparison with our reference methods showed good precision and reliability, highlighting its usefulness in clinical laboratory's routine.
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http://dx.doi.org/10.1007/s13277-013-0877-xDOI Listing
October 2013

Circulating tumor cells in high-risk nonmetastatic colorectal cancer.

Tumour Biol 2013 Oct 29;34(5):2507-9. Epub 2013 Mar 29.

Department of Molecular Medicine, Sapienza University of Rome, Viale Regina Elena 324, 000161, Rome, Italy,

The identification of patients at higher risk of recurrence after primary colorectal cancer resection is currently one of the challenges facing medical oncologists. Circulating tumor cell (CTC) may represent a surrogate marker of an early spread of disease in patients without overt metastases. Thirty-seven high-risk stages II-III colorectal cancer patients were evaluated for the presence of CTC. Enumeration of CTCs in 7.5 ml of blood was carried out with the FDA-cleared CellSearch system. CTC count was performed after primary tumor resection and before the start of adjuvant therapy. CTC was detected in 22 % of patients with a significant correlation with regional lymph nodes involvement and stage of disease. No significant correlation was found among the presence of CTC and other clinicopathological parameters. These data suggest that CTCs detection might help in the selection of high-risk stage II colorectal cancer patient candidates for adjuvant chemotherapy.
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http://dx.doi.org/10.1007/s13277-013-0752-9DOI Listing
October 2013

Bevacizumab plus chemotherapy in metastatic colorectal cancer patients treated in clinical practice.

Future Oncol 2012 Sep;8(9):1193-7

Oncology, S. M. Goretti Hospital, Latina, Sapienza University, Rome, Italy.

Aim: The effect of KRAS status on response to bevacizumab plus chemotherapy in metastatic colorectal cancer is still unclear. We aimed to evaluate the overall clinical response to such a therapy in clinical practice and assess the role of KRAS status on therapy response.

Patients & Methods: This was a retrospective study enrolling 108 metastatic colorectal cancer patients. KRAS mutation analysis was performed by PCR.

Results: Overall, 41.7% of patients had stable disease, 39.8% a partial response, 3.7% a complete response and 14.8% disease progression. Both clinical benefit and objective response rate tended to be higher in patients with only hepatic metastases than those with extrahepatic or multiple metastases. Response to therapy would appear to be independent of KRAS status, but larger studies are needed.

Conclusion: Bevacizumab plus chemotherapy provides clinical benefit and objective response rate in patients with metastatic colorectal cancer independently of KRAS expression, especially in those patients with only liver metastases.
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http://dx.doi.org/10.2217/fon.12.108DOI Listing
September 2012

Capecitabine in elderly patients with metastatic breast cancer.

Tumori 2012 May-Jun;98(3):303-7

Department of Molecular Medicine, Polyclinic Umberto I, Sapienza University, Rome, Italy.

Aims And Background: Capecitabine is the reference treatment for anthracycline- and/or taxane-pretreated metastatic breast cancer (MBC). This study examined its efficacy, tolerability and impact on the quality of life of elderly patients with MBC.

Materials And Methods: Between January 2002 and December 2009, 75 consecutive elderly patients with MBC received first-line chemotherapy with capecitabine 1000 mg/m2 twice daily for 14 days every 3 weeks. Endpoints were efficacy, tolerability and clinical-benefit response measured every 3 cycles.

Results: Median age was 76 years (range 65-88); median ECOG performance status was 1 (range 0-2); 51 patients (68%) had received adjuvant chemotherapy and all patients had received hormonal therapy. Median exposure was 6 cycles. After 3 cycles, 11 patients (14.7%) had a partial response, one patient experienced a complete response, and 49 patients (65.3%) had stable disease, amounting to a disease control rate of 81.3%. Stable disease was maintained in 45 patients (60%) after 6 cycles, in 21 patients (28%) after 9 cycles, and in 13 patients (17.3%) after 12 cycles. A clinical-benefit response was experienced by 42 patients (56%), indicating a positive impact on quality of life. Treatment was well tolerated, the most common grade 3 events being diarrhea (12%) hand-foot syndrome (8%), and mucositis (8%). Adverse events were managed with dose adjustments and supportive therapy when required.

Conclusions: Our results indicate that capecitabine is active and well tolerated in elderly patients with MBC. This dosing regimen warrants further study in the first-line setting for patients with less aggressive MBC who are not candidates for combination therapy.
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http://dx.doi.org/10.1700/1125.12396DOI Listing
October 2012

Role of HE4, CA72.4, and CA125 in monitoring ovarian cancer.

Tumour Biol 2012 Oct 13;33(5):1335-9. Epub 2012 Apr 13.

CNR-IBPM, Consiglio Nazionale delle Ricerche, Viale Regina Elena 324, 00161, Roma, Italy.

The aim of this study was to investigate the role of biomarkers CA125, HE4, and CA72.4 at diagnosis and throughout the follow-up in patients with epithelial ovarian cancer (EOC). Thirty-nine patients with EOC were deemed eligible, and 20 were followed up. CA125, HE4, and CA72.4 serum levels were determined for all patients at initial diagnosis of EOC. Among these patients, the number of cases with an elevated level of each individual marker was CA125 77 %, HE4 85 %, and CA72.4 72 %. A statistically significant difference was observed between the level of HE4 when compared to CA72.4 (p < 0.02). In the follow-up phase, we observed tumor marker levels fluctuating according to response to chemotherapy. When combining two out of the three biomarkers together, we observed increased values of CA125 and CA72.4 in 55 % of the patients, increased values of CA125 and HE4 in 65 % of the patients, and finally increased HE4 and CA72.4 in 75 % of the patients. A statistically significant difference was observed when combining HE4 and CA72.4, but not CA125 and CA 72.4 (p < 0.002). In conclusion, our study demonstrates that the association of three biomarkers CA125, HE4, and CA72.4 provides a valuable contribution in the follow-up of EOC patients.
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http://dx.doi.org/10.1007/s13277-012-0381-8DOI Listing
October 2012

HE4 combined with MDCT imaging is a good marker in the evaluation of disease extension in advanced epithelial ovarian carcinoma.

Tumour Biol 2012 Oct 20;33(5):1291-8. Epub 2012 Mar 20.

Department of Molecular Medicine, Sapienza University, Viale Regina Elena 324, 00161, Rome, Italy.

The purpose of the study was to evaluate the expression of the biomarkers CA125 and HE4 combined with imaging, in patients with advanced epithelial ovarian cancer (EOC). Forty-six women with EOC were included in the study all affected with peritoneal carcinomatosis. Twenty-two of 46 patients (group I) had peritoneal carcinomatosis with small implants in single or in multiple sites (score 1); 24/46 patients (group II) had macro-nodular implants and omental thickening (score 2). High levels of CA125 (350 ± 11, mean ± SEM) have been observed in 21/22 patients of group I, and a similar value (370 ± 13) has been observed in all patients belonging to group II. HE4 positivity values (350 ± 9) have been observed in all group I patients, whereas all patients belonging to group II showed a higher value of HE4 (600 ± 12). Statistically significant differences were observed between the HE4 levels observed in group I patients in comparison with group II patients (p < 0.0001). In addition, we expressed the extension of lymph nodal disease in three scores: L1-L2-L3, and a statistically significant correlation was observed between high HE4 levels and severity of lymph nodal disease L3 (p < 0.0001). The availability of biomarkers, particularly HE4, together with sophisticated imaging techniques, strengthens the clinical relevance of this study, for the follow-up of patients with peritoneal carcinomatosis.
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http://dx.doi.org/10.1007/s13277-012-0376-5DOI Listing
October 2012