Cell line. NCI-H295R cell line was obtained from the American Type Culture Collection (ATCC) and ... more Cell line. NCI-H295R cell line was obtained from the American Type Culture Collection (ATCC) and cultured as suggested. Primary cell cultures. Human ACC primary cells were derived from surgical specimens of ACC patients after obtaining a written informed consent. They were identified by a sequential number, based on the date of surgery. The project was approved by the local Ethical Committee. ACC02 cell culture derived from a steroid-secreting ACC; whereas ACC03, ACC06 and ACC08 cell cultures derived from non-secreting ACC. After surgical removal, cells were enzymatically digested with collagenase and cultured in the same medium of NCI-H295R cells. Quantitative RT-PCR (qRT-PCR). Gene expression was evaluated by qRT-PCR (ViiA7, Applied Biosystems), using the SYBR Green as fluorochrome, as described [7]. Primer sequences are shown in Fig.1 (panel A). Cell viability assay. ACC cells were treated up to for 4 days with palbociclib (1 nM-1 µM), solubilized in water. Cell viability was determined by 3-(4,5-Dimethyl-2-thiazol)-2,5-diphenyl-2H-tetrazolium bromide (MTT) dye reduction assay [8]. Absorbance was determined by a spectrophotometer at 540/620 nm (GDV).
Naunyn-Schmiedeberg's Archives of Pharmacology, 2019
To study the capability of the CYP17A1 inhibitor abiraterone acetate (AER) to antagonize the andr... more To study the capability of the CYP17A1 inhibitor abiraterone acetate (AER) to antagonize the androgen receptor (AR) activation in human prostate cancer (PCa) cell lines. T877A-AR-LNCaP, WT-AR-VCaP, AR-negative DU145, and PC3 PCa cell lines were used by MTT and cell count to study the ability of AER and enzalutamide (ENZ) to modify cell viability. The role of ARs in LNCaP was demonstrated through a gene-silencing experiment. The mechanism of AER cytotoxicity in LNCaP cells was studied, as well as the ability of AER to modulate AR gene expression. The in silico docking approach was applied to study the interaction of AER and ENZ with T877A-AR. Through high-performance liquid chromatography, the production of the AER main metabolite Δ4A was studied. AER bound AR in an almost identical manner to that of dihydrotestosterone (DHT). The higher binding energy for AER in T877A-AR could explain the major cytotoxic effect observed in LNCaP cells. The capability of LNCaP cells to synthesize Δ4A could mediate, at least in part, this effect. AER cytotoxicity in LNCaP cells was mainly due to the activation of apoptosis. Further, AER induced modification of AR target gene expression, suggesting a direct effect on AR activity. AER-induced cytotoxicity on PCa cell lines seemed to be mediated by binding with AR. The higher affinity of AER for T877A-AR may suggest a potential role of AER in the management of CRPC carrying this mutation; however, T877A-AR expressing CRPC patients developed AER resistance, probably due to the increase of progesterone. Keywords Abiraterone acetate. Prostate cancer. Cell lines. Cytotoxicity Abbreviations ADT Androgen-deprivation therapy AER Abiraterone acetate AR Androgen receptor CRPC Castration-resistant prostate cancer Δ4A Δ4-abiraterone DHT Dihydrotestosterone ENZ Enzalutamide LBD Ligand-binding domain MTT 3-(4,5-Dimethyl-2-thiazol)-2,5-diphenyl-2H-tetrazolium bromide PCa Prostate cancer si-AR siRNA targeting a region of an isoform of the AR gene si-ctrl Non-targeting negative control siRNA
Des marqueurs pleuraux pouvant discriminer les pleurésies bénignes et malignes sont nécessaires. ... more Des marqueurs pleuraux pouvant discriminer les pleurésies bénignes et malignes sont nécessaires. Parmi les possibles biomarqueurs, les microparticules (MPs) ont été décrites dans les compartiments biologiques humains ; mais peu de données existent sur leur existence dans le liquide pleural. Etant donné que les cellules tumorales produisent un grand nombre de MPs, nous avons fait l’hypothèse de la présence de MPs tumoraux (TMPs) dans les pleurésies et de leur implication dans la carcinogénèse.Donc, pour la première fois nous avons montré de nombreuses MPs pleurales produites par des cellules normales et malignes et nous avons caractérisé leur cellule d’origine.De plus, nous avons montré des TMPs pleurales exprimant l’antigène EpCAM : ce travail donne les bases pour l’utilisation de ce prometteur biomarqueur pour classifier les pleurésies. Nous avons décrit des cas cliniques de patients avec cytologie négative, mais positifs à la présence de MPs pleurales EpCAM+ : donc, les MPs EpCAM+...
printing supported by . Visit Chiesi at Stand B2.10 WEDNESDAY, SEPTEMBER 5TH 2012 P4619 Serum thi... more printing supported by . Visit Chiesi at Stand B2.10 WEDNESDAY, SEPTEMBER 5TH 2012 P4619 Serum thioredoxin-1 as a diagnostic marker for malignant peritoneal mesothelioma Chiharu Tabata1, Takayuki Terada1, Rie Tabata2, Takashi Nakano1. 1Division of Respiratory Medicine, Department of Internal Medicine, Hyogo College of Medicine, Nishinimiya, Japan; 2Department of Internal Medicine, Hyogo Prefectural Tsukaguchi Hospital, Amagasaki, Japan Background: Diffuse malignant peritoneal mesothelioma (DMPM) is an aggressive malignant tumor of mesothelial origin that shows a limited response to cytoreductive surgery along with intra-peritoneal chemotherapy. Therefore, diagnosing DMPM early is very important. Reactive oxygen species (ROS) play an important role in asbestos toxicity, which is associated with the pathogenesis of DMPM growing. Thioredoxin-1 (TRX) is a small redox-active protein that demonstrates anti-oxidative activity associated with tumor growth. Here, we investigated the serum lev...
Introduction Coronavirus disease 2019 (COVID-19) has disrupted the global health care system sinc... more Introduction Coronavirus disease 2019 (COVID-19) has disrupted the global health care system since March 2020. Lung cancer (LC) patients (pts) represent a vulnerable population highly affected by the pandemic. This multicenter Italian study aimed to evaluate whether the COVID-19 outbreak impacted on access to cancer diagnosis and treatment for LC pts compared to pre-pandemic time. Methods Consecutive newly diagnosed LC pts referred to 25 Italian Oncology Departments between March and December 2020 were included. Access rate and temporal intervals between date of symptoms onset and diagnostic and therapeutic services were compared to the same period in 2019. Differences between the two years were analyzed using chi-square test for categorical variables and Mann-Whitney U test for continuous variables. Results A slight reduction (-6.9%) in newly diagnosed LC cases was observed in 2020 compared with 2019 (1523 vs 1637, p=0.09). Newly LC pts in 2020 were more likely to be diagnosed with stage IV disease (p<0.01) and to be current smokers (p<0.01). The drop in terms of new diagnoses was greater in the lockdown period (percentage drop -12% vs -3.2%) compared to the other months included. More LC pts referred to low/medium volume hospital in 2020 compared to 2019 (p=0.01). No differences emerged in terms of interval between symptoms onset and radiological diagnosis (p=0.94), symptoms onset and cytohistological diagnosis (p=0.92), symptoms onset and treatment start (p=0.40), treatment start and first radiological revaluation (p=0.36). Conclusions Our study pointed out a reduction of new diagnoses with a shift towards higher stage at diagnosis for LC pts in 2020. Despite this, the measures adopted by Italian Oncology Departments ensured the maintenance of the diagnostic-therapeutic pathways of LC pts.
Considering the frequent expression of somatostatine receptors, we designed the G04.2011 trial to... more Considering the frequent expression of somatostatine receptors, we designed the G04.2011 trial to investigate the efficacy of the somatostatine analogue lanreotide in maintenance for SCLC patients after response to standard treatment. Materials and Methods: A multicenter, randomized, phase 3 trial was conducted in SCLC expressing somatostatine receptors at baseline Octreoscan, responding after platinum-based chemotherapy with/without radiotherapy. Patients were randomized 1:1 to receive maintenance lanreotide 120 mg subcutaneously every 28 days, up to 1 year or progression versus observation. Randomization was stratified according to stage (limited/extended, LD/ED). The primary end-point was progression-free survival (PFS). Secondary endpoints were overall survival (OS) and safety. Results: Seventy-one patients were randomly assigned (39 to lanreotide, 32 to observation) in 9 Italian institutions. Median PFS was 3.6 (95% CI 3.2-3.9) with lanreotide versus 2.3 months (95% CI 1.7-2.9) with observation (HR 1.51, 95% CI 0.90-2.50; P = 0.11). Stage was an independent predictor for PFS (HR 3.14, 95%
Introduction: Poorly differentiated neuroendocrine carcinomas (NECs) are characterized by aggress... more Introduction: Poorly differentiated neuroendocrine carcinomas (NECs) are characterized by aggressive clinical course and poor prognosis. No reliable prognostic markers have been validated to date; thus, the definition of a specific NEC prognostic algorithm represents a clinical need. This study aimed to analyze a large NEC case series to validate the specific prognostic factors identified in previous studies on gastro-entero-pancreatic and lung NECs and to assess if further prognostic parameters can be isolated. Methods: A pooled analysis of four NEC retrospective studies was performed to evaluate the prognostic role of Ki-67 cut-off, the overall survival (OS) according to primary cancer site, and further prognostic parameters using multivariable Cox proportional hazards model and machine learning random survival forest (RSF). Results: 422 NECs were analyzed. The most represented tumor site was the colorectum (n = 156, 37%), followed by the lungs (n = 111, 26%), gastroesophageal sit...
BACKGROUND In EBV-related nasopharyngeal carcinoma (NPC), quantitative determination of circulati... more BACKGROUND In EBV-related nasopharyngeal carcinoma (NPC), quantitative determination of circulating EBV-DNA (cEBV-DNA) can potentially be applied as disease marker. The aim of the study was to investigate if the clinical utility of cEBV-DNA is established in clinical practice guidelines and if recommendations are provided to standardize the quantitative cEBV-DNA determination. METHODS A systematic literature search for NPC guidelines published since 2011 was performed. Information for cEBV-DNA detection method and use in clinical practice was synthesized in consecutive steps of increasing simplification. RESULTS From 570 titles and abstracts identified by the search, 16 guidelines were included. The selected documents were further clustered as either being based on a systematic literature revision to generate recommendations (4/16) or not (12/16). cEBV-DNA was evaluated in only one guideline based on a systematic revision and in 8 guidelines without systematic revision. Half of available guidelines provide recommendation for its clinical use. Methodological issues on cEBV-DNA determination are discussed by 31% of guidelines, without providing any recommendation on method standardization. CONCLUSIONS Due to its prognostic value, cEBV-DNA is suggested in the pre-treatment work-up and in the follow-up. Guideline producers need to take into more consideration methodological aspects impacting the actual reliability and generalizability of laboratory results.
To develop a CT texture-based model able to predict epidermal growth factor receptor (EGFR)-mutat... more To develop a CT texture-based model able to predict epidermal growth factor receptor (EGFR)-mutated, anaplastic lymphoma kinase (ALK)-rearranged lung adenocarcinomas and distinguish them from wild-type tumors on pre-treatment CT scans. Texture analysis was performed using proprietary software TexRAD (TexRAD Ltd, Cambridge, UK) on pre-treatment contrast-enhanced CT scans of 84 patients with metastatic primary lung adenocarcinoma. Textural features were quantified using the filtration-histogram approach with different spatial scale filters on a single 5-mm-thick central slice considered representative of the whole tumor. In order to deal with class imbalance regarding mutational status percentages in our population, the dataset was optimized using the synthetic minority over-sampling technique (SMOTE) and correlations with textural features were investigated using a generalized boosted regression model (GBM) with a nested cross-validation approach (performance averaged over 1000 resampling episodes). ALK rearrangements, EGFR mutations and wild-type tumors were observed in 19, 28 and 37 patients, respectively, in the original dataset. The balanced dataset was composed of 171 observations. Among the 29 original texture variables, 17 were employed for model building. Skewness on unfiltered images and on fine texture was the most important features. EGFR-mutated tumors showed the highest skewness while ALK-rearranged tumors had the lowest values with wild-type tumors showing intermediate values. The average accuracy of the model calculated on the independent nested validation set was 81.76% (95% CI 81.45–82.06). Texture analysis, in particular skewness values, could be promising for noninvasive characterization of lung adenocarcinoma with respect to EGFR and ALK mutations.
e12504Background: Aromatase-inhibitors (AIs) decrease the bone mineral density (BMD) and increase... more e12504Background: Aromatase-inhibitors (AIs) decrease the bone mineral density (BMD) and increase the risk of clinical fractures but the mechanism underlying the increased fracture risk (FR) is not fully elucidated. In healthy post menopausal women obesity is associated with lower FR due the protective effect of elevated estrogen levels. However this mechanism cannot be extended to AI treated pts since estrogens are deeply inhibited. We designed a cross sectional study to explore the effect of Fat body mass (FBM) on the risk of morphometric vertebral fracture (VF) in postmenopausal estrogen receptor positive breast carcinoma (BC) submitted to adjuvant AI therapy. Methods: From October 2013 to May 2017 315 EBC patients (pts) were recruited. All pts underwent a dual-energy X-ray absorptiometry (DXA) for the assessment of BMD, morphometric evaluation of VFs and body composition at baseline and after at least one year of AI therapy. Results: 187 pts were AI naive and 128 AI treated, and the prevalence of VFs ...
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Purpose: To assess the predictive and prognostic value of pre-treatment CT texture features in lu... more Purpose: To assess the predictive and prognostic value of pre-treatment CT texture features in lung adenocarcinoma treated with tyrosine kinase inhibitors (TKI). Materials and Methods: Texture analysis was performed using commercially available software (TexRAD Ltd, Cambridge, UK) on pre-treatment contrast-enhanced CT studies from 50 patients with metastatic lung adenocarcinoma treated by TKI. Texture features were quantified on a 5-mm-thick central slice of the primary tumor and were correlated with progression-free and overall survival (PFS and OS) using an internally cross-validated machine learning approach then validated on a bootstrapped sample. Results: Median PFS and OS were 10.5 and 20.7 months, respectively. A noninvasive signature based on five texture parameters predicted 6-month progression with Area Under the Curve (AUC) of 0.8 (95%CI) and 1-year progression with AUC of 0.76. A high-risk group had hazard ratios for progression of 4.63 and 5.78 when divided by median and best cutoff points, respectively. Texture signature did not correlate with OS. Available clinical variables did not correlate with PFS or with OS. Conclusion: Texture features seem to be associated with PFS in lung adenocarcinoma treated with TKI.
Malignant pleural mesothelioma (MPM) is a rare malignancy mainly caused by asbestos exposure. Ger... more Malignant pleural mesothelioma (MPM) is a rare malignancy mainly caused by asbestos exposure. Germinal and acquired mutations in genes of DNA repair pathways, in particular of homologous recombination repair, are frequent in MPM. Here we overview the available experimental data suggesting that an impaired DNA repair system affects MPM pathogenesis by leaving lesions through the genome unresolved. DNA repair defects represent a vulnerability of MPM, and it seems plausible to propose that leveraging these deficiencies could have therapeutic potential for patients with MPM, for whom there is an urgent need of more effective therapies.
Objectives To assess whether tumour heterogeneity, quantified by texture analysis (TA) on contras... more Objectives To assess whether tumour heterogeneity, quantified by texture analysis (TA) on contrast-enhanced computed tomography (CECT), can predict response to chemotherapy in advanced non-small cell lung cancer (NSCLC). Methods Fifty-three CECT studies of patients with advanced NSCLC who had undergone first-line chemotherapy were retrospectively reviewed. Response to chemotherapy was evaluated according to RECIST1.1. Tumour uniformity was assessed by a TA method based on Laplacian of Gaussian filtering. The resulting parameters were correlated with treatment response and overall survival by multivariate analysis. Results Thirty-one out of 53 patients were non-responders and 22 were responders. Average overall survival was 13 months (4-35), minimum follow-up was 12 months. In the adenocarcinoma group (n=31), the product of tumour uniformity and grey level (GL*U) was the unique independent variable correlating with treatment response. Dividing the GL*U (range 8.5-46.6) into tertiles, lesions belonging to the second and the third tertiles had an 8.3-fold higher probability of treatment response compared with those in the first tertile. No association between texture features and response to treatment was observed in the non-adenocarcinoma group (n=22). GL*U did not correlate with overall survival. Conclusions TA on CECT images in advanced lung adenocarcinoma provides an independent predictive indicator of response to first-line chemotherapy. Key Points • Contrast enhanced computed tomography is currently used to stage lung cancer. • Texture analysis allows tumour heterogeneity to be quantified on CT images. • Texture parameters seem to predict chemotherapy response in advanced NSCLC.
Small cell lung cancer (SCLC) represents about 13%–15% of all lung cancers. It has a particularly... more Small cell lung cancer (SCLC) represents about 13%–15% of all lung cancers. It has a particularly unfavorable prognosis and in about 70% of cases occurs in the advanced stage (extended disease). Three phase III studies tested the combination of immunotherapy (atezolizumab, durvalumab with or without tremelimumab, and pembrolizumab) with double platinum chemotherapy, with practice-changing results. However, despite the high tumor mutational load and the chronic pro-inflammatory state induced by prolonged exposure to cigarette smoke, the benefit observed with immunotherapy is very modest and most patients experience disease recurrence. Unfortunately, biological, clinical, or molecular factors that can predict this risk have not yet been identified. Thanks to these clinically meaningful steps forward, SCLC is no longer considered an “orphan” disease. Innovative treatment strategies and combinations are currently under investigation to further improve the expected prognosis of patients ...
Cell line. NCI-H295R cell line was obtained from the American Type Culture Collection (ATCC) and ... more Cell line. NCI-H295R cell line was obtained from the American Type Culture Collection (ATCC) and cultured as suggested. Primary cell cultures. Human ACC primary cells were derived from surgical specimens of ACC patients after obtaining a written informed consent. They were identified by a sequential number, based on the date of surgery. The project was approved by the local Ethical Committee. ACC02 cell culture derived from a steroid-secreting ACC; whereas ACC03, ACC06 and ACC08 cell cultures derived from non-secreting ACC. After surgical removal, cells were enzymatically digested with collagenase and cultured in the same medium of NCI-H295R cells. Quantitative RT-PCR (qRT-PCR). Gene expression was evaluated by qRT-PCR (ViiA7, Applied Biosystems), using the SYBR Green as fluorochrome, as described [7]. Primer sequences are shown in Fig.1 (panel A). Cell viability assay. ACC cells were treated up to for 4 days with palbociclib (1 nM-1 µM), solubilized in water. Cell viability was determined by 3-(4,5-Dimethyl-2-thiazol)-2,5-diphenyl-2H-tetrazolium bromide (MTT) dye reduction assay [8]. Absorbance was determined by a spectrophotometer at 540/620 nm (GDV).
Naunyn-Schmiedeberg's Archives of Pharmacology, 2019
To study the capability of the CYP17A1 inhibitor abiraterone acetate (AER) to antagonize the andr... more To study the capability of the CYP17A1 inhibitor abiraterone acetate (AER) to antagonize the androgen receptor (AR) activation in human prostate cancer (PCa) cell lines. T877A-AR-LNCaP, WT-AR-VCaP, AR-negative DU145, and PC3 PCa cell lines were used by MTT and cell count to study the ability of AER and enzalutamide (ENZ) to modify cell viability. The role of ARs in LNCaP was demonstrated through a gene-silencing experiment. The mechanism of AER cytotoxicity in LNCaP cells was studied, as well as the ability of AER to modulate AR gene expression. The in silico docking approach was applied to study the interaction of AER and ENZ with T877A-AR. Through high-performance liquid chromatography, the production of the AER main metabolite Δ4A was studied. AER bound AR in an almost identical manner to that of dihydrotestosterone (DHT). The higher binding energy for AER in T877A-AR could explain the major cytotoxic effect observed in LNCaP cells. The capability of LNCaP cells to synthesize Δ4A could mediate, at least in part, this effect. AER cytotoxicity in LNCaP cells was mainly due to the activation of apoptosis. Further, AER induced modification of AR target gene expression, suggesting a direct effect on AR activity. AER-induced cytotoxicity on PCa cell lines seemed to be mediated by binding with AR. The higher affinity of AER for T877A-AR may suggest a potential role of AER in the management of CRPC carrying this mutation; however, T877A-AR expressing CRPC patients developed AER resistance, probably due to the increase of progesterone. Keywords Abiraterone acetate. Prostate cancer. Cell lines. Cytotoxicity Abbreviations ADT Androgen-deprivation therapy AER Abiraterone acetate AR Androgen receptor CRPC Castration-resistant prostate cancer Δ4A Δ4-abiraterone DHT Dihydrotestosterone ENZ Enzalutamide LBD Ligand-binding domain MTT 3-(4,5-Dimethyl-2-thiazol)-2,5-diphenyl-2H-tetrazolium bromide PCa Prostate cancer si-AR siRNA targeting a region of an isoform of the AR gene si-ctrl Non-targeting negative control siRNA
Des marqueurs pleuraux pouvant discriminer les pleurésies bénignes et malignes sont nécessaires. ... more Des marqueurs pleuraux pouvant discriminer les pleurésies bénignes et malignes sont nécessaires. Parmi les possibles biomarqueurs, les microparticules (MPs) ont été décrites dans les compartiments biologiques humains ; mais peu de données existent sur leur existence dans le liquide pleural. Etant donné que les cellules tumorales produisent un grand nombre de MPs, nous avons fait l’hypothèse de la présence de MPs tumoraux (TMPs) dans les pleurésies et de leur implication dans la carcinogénèse.Donc, pour la première fois nous avons montré de nombreuses MPs pleurales produites par des cellules normales et malignes et nous avons caractérisé leur cellule d’origine.De plus, nous avons montré des TMPs pleurales exprimant l’antigène EpCAM : ce travail donne les bases pour l’utilisation de ce prometteur biomarqueur pour classifier les pleurésies. Nous avons décrit des cas cliniques de patients avec cytologie négative, mais positifs à la présence de MPs pleurales EpCAM+ : donc, les MPs EpCAM+...
printing supported by . Visit Chiesi at Stand B2.10 WEDNESDAY, SEPTEMBER 5TH 2012 P4619 Serum thi... more printing supported by . Visit Chiesi at Stand B2.10 WEDNESDAY, SEPTEMBER 5TH 2012 P4619 Serum thioredoxin-1 as a diagnostic marker for malignant peritoneal mesothelioma Chiharu Tabata1, Takayuki Terada1, Rie Tabata2, Takashi Nakano1. 1Division of Respiratory Medicine, Department of Internal Medicine, Hyogo College of Medicine, Nishinimiya, Japan; 2Department of Internal Medicine, Hyogo Prefectural Tsukaguchi Hospital, Amagasaki, Japan Background: Diffuse malignant peritoneal mesothelioma (DMPM) is an aggressive malignant tumor of mesothelial origin that shows a limited response to cytoreductive surgery along with intra-peritoneal chemotherapy. Therefore, diagnosing DMPM early is very important. Reactive oxygen species (ROS) play an important role in asbestos toxicity, which is associated with the pathogenesis of DMPM growing. Thioredoxin-1 (TRX) is a small redox-active protein that demonstrates anti-oxidative activity associated with tumor growth. Here, we investigated the serum lev...
Introduction Coronavirus disease 2019 (COVID-19) has disrupted the global health care system sinc... more Introduction Coronavirus disease 2019 (COVID-19) has disrupted the global health care system since March 2020. Lung cancer (LC) patients (pts) represent a vulnerable population highly affected by the pandemic. This multicenter Italian study aimed to evaluate whether the COVID-19 outbreak impacted on access to cancer diagnosis and treatment for LC pts compared to pre-pandemic time. Methods Consecutive newly diagnosed LC pts referred to 25 Italian Oncology Departments between March and December 2020 were included. Access rate and temporal intervals between date of symptoms onset and diagnostic and therapeutic services were compared to the same period in 2019. Differences between the two years were analyzed using chi-square test for categorical variables and Mann-Whitney U test for continuous variables. Results A slight reduction (-6.9%) in newly diagnosed LC cases was observed in 2020 compared with 2019 (1523 vs 1637, p=0.09). Newly LC pts in 2020 were more likely to be diagnosed with stage IV disease (p<0.01) and to be current smokers (p<0.01). The drop in terms of new diagnoses was greater in the lockdown period (percentage drop -12% vs -3.2%) compared to the other months included. More LC pts referred to low/medium volume hospital in 2020 compared to 2019 (p=0.01). No differences emerged in terms of interval between symptoms onset and radiological diagnosis (p=0.94), symptoms onset and cytohistological diagnosis (p=0.92), symptoms onset and treatment start (p=0.40), treatment start and first radiological revaluation (p=0.36). Conclusions Our study pointed out a reduction of new diagnoses with a shift towards higher stage at diagnosis for LC pts in 2020. Despite this, the measures adopted by Italian Oncology Departments ensured the maintenance of the diagnostic-therapeutic pathways of LC pts.
Considering the frequent expression of somatostatine receptors, we designed the G04.2011 trial to... more Considering the frequent expression of somatostatine receptors, we designed the G04.2011 trial to investigate the efficacy of the somatostatine analogue lanreotide in maintenance for SCLC patients after response to standard treatment. Materials and Methods: A multicenter, randomized, phase 3 trial was conducted in SCLC expressing somatostatine receptors at baseline Octreoscan, responding after platinum-based chemotherapy with/without radiotherapy. Patients were randomized 1:1 to receive maintenance lanreotide 120 mg subcutaneously every 28 days, up to 1 year or progression versus observation. Randomization was stratified according to stage (limited/extended, LD/ED). The primary end-point was progression-free survival (PFS). Secondary endpoints were overall survival (OS) and safety. Results: Seventy-one patients were randomly assigned (39 to lanreotide, 32 to observation) in 9 Italian institutions. Median PFS was 3.6 (95% CI 3.2-3.9) with lanreotide versus 2.3 months (95% CI 1.7-2.9) with observation (HR 1.51, 95% CI 0.90-2.50; P = 0.11). Stage was an independent predictor for PFS (HR 3.14, 95%
Introduction: Poorly differentiated neuroendocrine carcinomas (NECs) are characterized by aggress... more Introduction: Poorly differentiated neuroendocrine carcinomas (NECs) are characterized by aggressive clinical course and poor prognosis. No reliable prognostic markers have been validated to date; thus, the definition of a specific NEC prognostic algorithm represents a clinical need. This study aimed to analyze a large NEC case series to validate the specific prognostic factors identified in previous studies on gastro-entero-pancreatic and lung NECs and to assess if further prognostic parameters can be isolated. Methods: A pooled analysis of four NEC retrospective studies was performed to evaluate the prognostic role of Ki-67 cut-off, the overall survival (OS) according to primary cancer site, and further prognostic parameters using multivariable Cox proportional hazards model and machine learning random survival forest (RSF). Results: 422 NECs were analyzed. The most represented tumor site was the colorectum (n = 156, 37%), followed by the lungs (n = 111, 26%), gastroesophageal sit...
BACKGROUND In EBV-related nasopharyngeal carcinoma (NPC), quantitative determination of circulati... more BACKGROUND In EBV-related nasopharyngeal carcinoma (NPC), quantitative determination of circulating EBV-DNA (cEBV-DNA) can potentially be applied as disease marker. The aim of the study was to investigate if the clinical utility of cEBV-DNA is established in clinical practice guidelines and if recommendations are provided to standardize the quantitative cEBV-DNA determination. METHODS A systematic literature search for NPC guidelines published since 2011 was performed. Information for cEBV-DNA detection method and use in clinical practice was synthesized in consecutive steps of increasing simplification. RESULTS From 570 titles and abstracts identified by the search, 16 guidelines were included. The selected documents were further clustered as either being based on a systematic literature revision to generate recommendations (4/16) or not (12/16). cEBV-DNA was evaluated in only one guideline based on a systematic revision and in 8 guidelines without systematic revision. Half of available guidelines provide recommendation for its clinical use. Methodological issues on cEBV-DNA determination are discussed by 31% of guidelines, without providing any recommendation on method standardization. CONCLUSIONS Due to its prognostic value, cEBV-DNA is suggested in the pre-treatment work-up and in the follow-up. Guideline producers need to take into more consideration methodological aspects impacting the actual reliability and generalizability of laboratory results.
To develop a CT texture-based model able to predict epidermal growth factor receptor (EGFR)-mutat... more To develop a CT texture-based model able to predict epidermal growth factor receptor (EGFR)-mutated, anaplastic lymphoma kinase (ALK)-rearranged lung adenocarcinomas and distinguish them from wild-type tumors on pre-treatment CT scans. Texture analysis was performed using proprietary software TexRAD (TexRAD Ltd, Cambridge, UK) on pre-treatment contrast-enhanced CT scans of 84 patients with metastatic primary lung adenocarcinoma. Textural features were quantified using the filtration-histogram approach with different spatial scale filters on a single 5-mm-thick central slice considered representative of the whole tumor. In order to deal with class imbalance regarding mutational status percentages in our population, the dataset was optimized using the synthetic minority over-sampling technique (SMOTE) and correlations with textural features were investigated using a generalized boosted regression model (GBM) with a nested cross-validation approach (performance averaged over 1000 resampling episodes). ALK rearrangements, EGFR mutations and wild-type tumors were observed in 19, 28 and 37 patients, respectively, in the original dataset. The balanced dataset was composed of 171 observations. Among the 29 original texture variables, 17 were employed for model building. Skewness on unfiltered images and on fine texture was the most important features. EGFR-mutated tumors showed the highest skewness while ALK-rearranged tumors had the lowest values with wild-type tumors showing intermediate values. The average accuracy of the model calculated on the independent nested validation set was 81.76% (95% CI 81.45–82.06). Texture analysis, in particular skewness values, could be promising for noninvasive characterization of lung adenocarcinoma with respect to EGFR and ALK mutations.
e12504Background: Aromatase-inhibitors (AIs) decrease the bone mineral density (BMD) and increase... more e12504Background: Aromatase-inhibitors (AIs) decrease the bone mineral density (BMD) and increase the risk of clinical fractures but the mechanism underlying the increased fracture risk (FR) is not fully elucidated. In healthy post menopausal women obesity is associated with lower FR due the protective effect of elevated estrogen levels. However this mechanism cannot be extended to AI treated pts since estrogens are deeply inhibited. We designed a cross sectional study to explore the effect of Fat body mass (FBM) on the risk of morphometric vertebral fracture (VF) in postmenopausal estrogen receptor positive breast carcinoma (BC) submitted to adjuvant AI therapy. Methods: From October 2013 to May 2017 315 EBC patients (pts) were recruited. All pts underwent a dual-energy X-ray absorptiometry (DXA) for the assessment of BMD, morphometric evaluation of VFs and body composition at baseline and after at least one year of AI therapy. Results: 187 pts were AI naive and 128 AI treated, and the prevalence of VFs ...
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Purpose: To assess the predictive and prognostic value of pre-treatment CT texture features in lu... more Purpose: To assess the predictive and prognostic value of pre-treatment CT texture features in lung adenocarcinoma treated with tyrosine kinase inhibitors (TKI). Materials and Methods: Texture analysis was performed using commercially available software (TexRAD Ltd, Cambridge, UK) on pre-treatment contrast-enhanced CT studies from 50 patients with metastatic lung adenocarcinoma treated by TKI. Texture features were quantified on a 5-mm-thick central slice of the primary tumor and were correlated with progression-free and overall survival (PFS and OS) using an internally cross-validated machine learning approach then validated on a bootstrapped sample. Results: Median PFS and OS were 10.5 and 20.7 months, respectively. A noninvasive signature based on five texture parameters predicted 6-month progression with Area Under the Curve (AUC) of 0.8 (95%CI) and 1-year progression with AUC of 0.76. A high-risk group had hazard ratios for progression of 4.63 and 5.78 when divided by median and best cutoff points, respectively. Texture signature did not correlate with OS. Available clinical variables did not correlate with PFS or with OS. Conclusion: Texture features seem to be associated with PFS in lung adenocarcinoma treated with TKI.
Malignant pleural mesothelioma (MPM) is a rare malignancy mainly caused by asbestos exposure. Ger... more Malignant pleural mesothelioma (MPM) is a rare malignancy mainly caused by asbestos exposure. Germinal and acquired mutations in genes of DNA repair pathways, in particular of homologous recombination repair, are frequent in MPM. Here we overview the available experimental data suggesting that an impaired DNA repair system affects MPM pathogenesis by leaving lesions through the genome unresolved. DNA repair defects represent a vulnerability of MPM, and it seems plausible to propose that leveraging these deficiencies could have therapeutic potential for patients with MPM, for whom there is an urgent need of more effective therapies.
Objectives To assess whether tumour heterogeneity, quantified by texture analysis (TA) on contras... more Objectives To assess whether tumour heterogeneity, quantified by texture analysis (TA) on contrast-enhanced computed tomography (CECT), can predict response to chemotherapy in advanced non-small cell lung cancer (NSCLC). Methods Fifty-three CECT studies of patients with advanced NSCLC who had undergone first-line chemotherapy were retrospectively reviewed. Response to chemotherapy was evaluated according to RECIST1.1. Tumour uniformity was assessed by a TA method based on Laplacian of Gaussian filtering. The resulting parameters were correlated with treatment response and overall survival by multivariate analysis. Results Thirty-one out of 53 patients were non-responders and 22 were responders. Average overall survival was 13 months (4-35), minimum follow-up was 12 months. In the adenocarcinoma group (n=31), the product of tumour uniformity and grey level (GL*U) was the unique independent variable correlating with treatment response. Dividing the GL*U (range 8.5-46.6) into tertiles, lesions belonging to the second and the third tertiles had an 8.3-fold higher probability of treatment response compared with those in the first tertile. No association between texture features and response to treatment was observed in the non-adenocarcinoma group (n=22). GL*U did not correlate with overall survival. Conclusions TA on CECT images in advanced lung adenocarcinoma provides an independent predictive indicator of response to first-line chemotherapy. Key Points • Contrast enhanced computed tomography is currently used to stage lung cancer. • Texture analysis allows tumour heterogeneity to be quantified on CT images. • Texture parameters seem to predict chemotherapy response in advanced NSCLC.
Small cell lung cancer (SCLC) represents about 13%–15% of all lung cancers. It has a particularly... more Small cell lung cancer (SCLC) represents about 13%–15% of all lung cancers. It has a particularly unfavorable prognosis and in about 70% of cases occurs in the advanced stage (extended disease). Three phase III studies tested the combination of immunotherapy (atezolizumab, durvalumab with or without tremelimumab, and pembrolizumab) with double platinum chemotherapy, with practice-changing results. However, despite the high tumor mutational load and the chronic pro-inflammatory state induced by prolonged exposure to cigarette smoke, the benefit observed with immunotherapy is very modest and most patients experience disease recurrence. Unfortunately, biological, clinical, or molecular factors that can predict this risk have not yet been identified. Thanks to these clinically meaningful steps forward, SCLC is no longer considered an “orphan” disease. Innovative treatment strategies and combinations are currently under investigation to further improve the expected prognosis of patients ...
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Papers by Elisa Roca