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PURPOSE: To assess outcomes between salvage radiation therapy (SRT) with curative intent and stereotactic radiotherapy for macroscopic prostate recurrence (SSRT) after radical prostatectomy (RP). In order to compare these two different options, we compared their outcomes with a propensity score-based matched analysis. METHODS: Data from 185 patients in seven Italian centres treated for macroscopic prostate bed recurrence after RP were retrospectively collected. To make a comparison between the two treatment groups, propensity matching was applied to create comparable cohorts. RESULTS: After matching, 90 patients in the SRT and SSRT groups were selected (45 in each arm). Kaplan-Meier analysis did not show any significant differences in terms of BRFS and PFS between matched populations (p = 0.08 and p = 0.8, respectively). Multivariate models show that treatment was not associated with BRFS, neither in the whole or matched cohort, with HR of 2.15 (95%CI 0.63-7.25, p = 0.21) and 2.65 (95%CI 0.59-11.97, p = 0.21), respectively. In the matched cohort, lower rate of toxicity was confirmed for patients undergoing SSRT, with acute GI and GU adverse events reported in 4.4 versus 44.4% (p < 0.001) and 28.9 versus 46.7% (p = 0.08) of patients, and late GI and GU adverse events reported in 0 versus 13.3% (p = 0.04) and 6.7 versus 22.2% (p = 0.03) of patients, respectively. CONCLUSION: Considering the favourable therapeutic ratio of this approach and the lower number of fractions needed, SSRT should be considered as an attractive alternative to conventional SRT in this setting.
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Próstata , Neoplasias de la Próstata , Humanos , Masculino , Recurrencia Local de Neoplasia/radioterapia , Recurrencia Local de Neoplasia/cirugía , Puntaje de Propensión , Próstata/cirugía , Antígeno Prostático Específico , Prostatectomía/efectos adversos , Neoplasias de la Próstata/radioterapia , Neoplasias de la Próstata/cirugía , Estudios Retrospectivos , Terapia RecuperativaRESUMEN
PURPOSE: Laryngeal dysplasia represents a series of precancerous lesions, observed as laryngeal leukoplakia. General agreement has been lacking for their management and treatment ranging from simple biopsy to complete excision with cold blade/laser. In this work, we aim at providing the oncological outcomes of patients affected by laryngeal dysplasia, treated with a single modality, and at identifying clinical parameters predictive of malignant transformation. MATERIALS AND METHODS: We performed a retrospective analysis of patients treated with transoral laser microsurgery between January 2005 and December 2015 in a tertiary comprehensive cancer centre. Data were collected about smoke and alcohol habits, site of the laryngeal lesion, surgical outcomes and progression to invasive squamous cell carcinoma. RESULTS: The grade of dysplasia, margins' status and smoke habit were not associated with a significantly worse DFS and a higher risk of invasive SCC. We identified three parameters (supraglottic involvement, multifocality and history of more than one recurrence of dysplasia) that have a significant prognostic value. CONCLUSIONS: On the base of these clinical parameters, a more intensive follow-up might be warranted for high-risk patients.
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Instituciones Oncológicas/estadística & datos numéricos , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/terapia , Transformación Celular Neoplásica , Neoplasias Laríngeas/patología , Neoplasias Laríngeas/terapia , Lesiones Precancerosas , Centros de Atención Terciaria/estadística & datos numéricos , Carcinoma de Células Escamosas/epidemiología , Carcinoma de Células Escamosas/etiología , Progresión de la Enfermedad , Femenino , Humanos , Neoplasias Laríngeas/epidemiología , Neoplasias Laríngeas/etiología , Masculino , Oportunidad Relativa , Estudios Retrospectivos , Riesgo , Fumar/efectos adversos , Resultado del TratamientoRESUMEN
E-cadherin protein (CDH1 gene) integrity is fundamental to the process of epithelial polarization and differentiation. Deregulation of the E-cadherin function plays a crucial role in breast cancer metastases, with worse prognosis and shorter overall survival. In this narrative review, we describe the inactivating mechanisms underlying CDH1 gene activity and its possible translation to clinical practice as a prognostic biomarker and as a potential targeted therapy.
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Neoplasias de la Mama/genética , Cadherinas/genética , Regulación Neoplásica de la Expresión Génica , Biomarcadores de Tumor/genética , Cadherinas/metabolismo , Femenino , Humanos , Terapia Molecular Dirigida , PronósticoRESUMEN
BACKGROUND: The breast cancer genome dynamically evolves during malignant progression and recurrence. We investigated the genomic profiles of primary early-stage breast cancers and matched relapses to elucidate the molecular underpinnings of the metastatic process, focusing on potentially actionable alterations in the recurrences. METHODS: A mono-institutional cohort of 128 patients with breast cancers (n = 68 luminal B HER2, n = 6 luminal B HER2+, n = 1 HER2+ non-luminal, n = 56 triple negative) and at least one recurrence in a timeframe of 17 years was evaluated. Next-generation sequencing comprehensive genomic profiling was performed on 289 formalin-fixed paraffin-embedded (FFPE) samples, including primary tumors and matched relapses. Correlations of genomic aberrations with clinicopathologic factors and time to breast cancer relapse were analyzed. RESULTS: Genomic data were available for 188 of 289 FFPE samples that achieved the sequencing quality parameters (failure rate 34.9%), including 106 primary tumors and 82 relapses. All primary and relapse samples harbored at least one genomic alteration, with a median number of six alterations per sample (range 1-16). The most frequent somatic genomic alterations were mutations of TP53 (primary tumors = 49%, relapses = 49%) and PIK3CA (primary tumors = 33%, relapses = 30%). Distinctive genomic alterations of primary tumors were significantly associated with molecular subtypes. TP53, PIK3R1, and NF1 somatic alterations were more frequently detected in triple negative tumors (p value < 0.05); CCND1, FGF3, and FGFR1 copy number gains were recurrently identified in luminal cases (p value < 0.05). Moreover, TP53 mutations and MYC amplification were significantly and independently associated with a shorter time to relapse (p value < 0.05). Molecular subtype changes between primary tumors and relapses were seen in 10 of 128 (7.8%) cases. Most driver genomic alterations (55.8%) were shared between primary tumors and matched recurrences. However, in 39 of 61 cases (63.9%), additional private alterations were detected in the relapse samples only, including 12 patients with potentially actionable aberrations. CONCLUSIONS: Specific genomic aberrations of primary breast cancers were associated with time to relapse. Primary tumors and matched recurrences showed a core of shared driver genomic aberrations but private actionable alterations have been identified in the relapses.
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Biomarcadores de Tumor/genética , Neoplasias de la Mama/genética , Genómica/métodos , Terapia Molecular Dirigida/métodos , Mutación , Recurrencia Local de Neoplasia/genética , Adulto , Anciano , Neoplasias de la Mama/patología , Neoplasias de la Mama/terapia , Fosfatidilinositol 3-Quinasa Clase I/genética , Resistencia a Antineoplásicos , Femenino , Secuenciación de Nucleótidos de Alto Rendimiento/métodos , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/terapia , Estadificación de Neoplasias , Pronóstico , Proteínas Proto-Oncogénicas c-myc/genética , Tasa de Supervivencia , Proteína p53 Supresora de Tumor/genética , Adulto JovenRESUMEN
Increasing scientific evidence supports the link between vitamin D and cancer risk. The active metabolite 1,25(OH)2D exerts its activity by binding to the vitamin D receptor (VDR), an intracellular receptor that mediates transcriptional activation and repression of target genes. The binding of 1,25(OH)2D to VDR is able to regulate hundreds of different genes. VDR is active in virtually all tissues including the colon, breast, lung, ovary, bone, kidney, parathyroid gland, pancreatic b-cells, monocytes, T lymphocytes, melanocytes, keratinocytes, and also cancer cells.The relevance of VDR gene restriction fragment length polymorphisms for various types of cancer has been investigated by a great number of studies.We have carried out a systematic review of the literature to analyze the relevance of more VDR polymorphisms (Fok1, Bsm1, Taq1, Apa1, and Cdx2) for individual malignancies considering ethnicity as a key factor for heterogeneity.Up to December 2018, we identified 176 independent studies with data to assess the risk of breast, prostate, colorectal, skin (melanoma and non-melanoma skin cancer), lung, ovarian, kidney, bladder, gallbladder, esophageal, thyroid, head and neck, liver and pancreatic cancer, oral squamous cell carcinoma, non-Hodgkin lymphoma, multiple myeloma and sarcoma.Significant associations with VDR polymorphisms have been reported for prostate (Fok1, Bsm1, Taq1, Apa1, Cdx2), breast (Fok1, Bsm1, Taq1, Apa1, CdX2), colorectal (Fok1, Bsm1, Taq1, Apa1), and skin cancer (Fok1, Bsm1, Taq1). Very few studies reported risk estimates for the other cancer sites.Conflicting data have been reported for most malignancies, and at present, it is still not possible to make any definitive statements about the importance of the VDR genotype for cancer risk. It seems probable that other factors such as ethnicity, phenotype, 25(OH)D plasma levels, and UV radiation exposure play a role as confounding factors and introduce heterogeneity.To conclude, there is some indication that VDR polymorphisms may modulate the risk of some cancer sites and in future studies VDR genetic variation should be integrated also with assessment of vitamin D status and stratified by ethnicity.
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Neoplasias/genética , Polimorfismo Genético , Receptores de Calcitriol/genética , Humanos , Neoplasias/sangre , Vitamina D/sangreRESUMEN
We reviewed the diagnostic accuracy of SARS-CoV-2 serological tests. Random-effects models yielded a summary sensitivity of 82% for IgM, and 85% for IgG and total antibodies. For specificity, the pooled estimate were 98% for IgM and 99% for IgG and total antibodies. In populations with ≤ 5% of seroconverted individuals, unless the assays have perfect (i.e. 100%) specificity, the positive predictive value would be ≤ 88%. Serological tests should be used for prevalence surveys only in hard-hit areas.
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Anticuerpos Antivirales/sangre , Técnicas de Laboratorio Clínico/métodos , Infecciones por Coronaviridae/diagnóstico , Infecciones por Coronavirus/diagnóstico , Coronavirus/inmunología , Neumonía Viral/diagnóstico , Pruebas Serológicas/normas , Síndrome Respiratorio Agudo Grave/inmunología , Betacoronavirus , COVID-19 , Prueba de COVID-19 , Técnicas de Laboratorio Clínico/normas , Coronavirus/aislamiento & purificación , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/inmunología , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Pandemias , Neumonía Viral/epidemiología , Neumonía Viral/inmunología , Valor Predictivo de las Pruebas , SARS-CoV-2 , Sensibilidad y Especificidad , Pruebas Serológicas/métodos , Síndrome Respiratorio Agudo Grave/sangreRESUMEN
BACKGROUND: A multicentric study was conducted on technical reproducibility of compartmental tongue surgery (CTS) in advanced tongue cancers (OTSCC) and comparison to standard wide margin surgery (SWMS). METHODS: We studied 551 patients with OTSCC treated by CTS and 50 by SWMS. Oncological outcomes were analyzed. A propensity score was performed to compare survival endpoints for the two cohorts. RESULTS: In the CTS group, survival and prognosis were significantly associated with positive lymph-nodes, extranodal extension, depth of invasion and involvement of the soft tissue connecting the tongue primary tumor to neck lymph nodes (T-N tract), independently from the center performing the surgery. SWMS versus CTS showed a HR Cause-Specific Survival (CSS) of 3.24 (95% CI: 1.71-6.11; p < 0.001); HR Loco-Regional Recurrence Free Survival (LRRFS) of 2.54 (95% CI: 1.47-4.40; p < 0.001); HR Overall Survival (OS) of 0.11 (95% CI: 0.01-0.77; p = 0.03). CONCLUSION: Performing the CTS could provide better CSS and LRRFS than SWMS regardless of the center performing the surgery, in advanced OTSSC.
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Carcinoma de Células Escamosas , Neoplasias de la Lengua , Humanos , Reproducibilidad de los Resultados , Estadificación de Neoplasias , Lengua/cirugía , Carcinoma de Células Escamosas/patología , Neoplasias de la Lengua/patología , Pronóstico , Estudios Retrospectivos , Recurrencia Local de Neoplasia/patologíaRESUMEN
BACKGROUND: Radiomics represents an emerging field of precision-medicine. Its application in head and neck is still at the beginning. METHODS: Retrospective study about magnetic resonance imaging (MRI) based radiomics in oral tongue squamous cell carcinoma (OTSCC) surgically treated (2010-2019; 79 patients). All preoperative MRIs include different sequences (T1, T2, DWI, ADC). Tumor volume was manually segmented and exported to radiomic-software, to perform feature extraction. Statistically significant variables were included in multivariable analysis and related to survival endpoints. Predictive models were elaborated (clinical, radiomic, clinical-radiomic models) and compared using C-index. RESULTS: In almost all clinical-radiomic models radiomic-score maintained statistical significance. In all cases C-index was higher in clinical-radiomic models than in clinical ones. ADC provided the best fit to the models (C-index 0.98, 0.86, 0.84 in loco-regional recurrence, cause-specific mortality, overall survival, respectively). CONCLUSION: MRI-based radiomics in OTSCC represents a promising noninvasive method of precision medicine, improving prognosis prediction before surgery.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Lengua , Humanos , Estudios Retrospectivos , Neoplasias de la Lengua/diagnóstico por imagen , Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/terapia , Pronóstico , Imagen por Resonancia Magnética/métodos , Carcinoma de Células Escamosas de Cabeza y CuelloRESUMEN
BACKGROUND: Several studies suggest a role of gut microbiota in colorectal cancer (CRC) initiation and progression. Vitamin D (vitD) blood levels are also inversely correlated with CRC risk and prognosis. However, these factors' interplay remains unknown. METHODS: 74 CRC patients after standard treatment were randomized to 1-year 2000 IU/day vitD or placebo. Baseline and post-treatment fecal microbiota for shotgun metagenomics sequencing was collected. Coda-lasso and Principal Component Analysis were used to select and summarize treatment-associated taxa and pathways. Associations between vitD and taxa/pathways were investigated with logistic regression. Mediation analysis was performed to study if treatment-associated taxa mediated the effect of supplementation on 25(OH)D levels. Cox proportional-hazards model was used for disease-free survival (DFS). RESULTS: 60 patients were analyzed. Change in alpha diversity (Shannon: p = 0.77; Simpson: p = 0.63) and post-treatment beta diversity (p = 0.70) were comparable between arms. Post-treatment abundances of 63 taxa and 32 pathways differed between arms. The 63 taxa also mediated the effect of supplementation on 25(OH)D (p = 0.02). There were sex differences in vitD levels, microbiota and pathways. Pathways of essential amino acids' biosynthesis were more abundant in supplemented women. Fusobacterium nucleatum presence at baseline was associated with worse DFS (p = 0.02). Those achieving vitD sufficiency (25(OH)D≥30 ng/ml) had lower post-treatment abundances (p = 0.05). Women were more likely to have F. nucleatum post-treatment (p = 0.02). CONCLUSIONS: VitD supplementation may contribute shaping the gut microbiota and the microbiota may partially mediate the effect of supplementation on 25(OH)D. The observed sex-specific differences highlight the necessity of including sex/gender as a variable in microbiome studies.
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Neoplasias Colorrectales , Microbiota , Humanos , Femenino , Masculino , Vitamina D , Vitaminas/uso terapéutico , Suplementos Dietéticos , Neoplasias Colorrectales/tratamiento farmacológicoRESUMEN
Non-melanoma skin cancers (NMSC) are more frequent among men, but women (especially those aged < 40 years) have experienced steeper growth in their incidence rates in recent years. Hormonal factors were hypothesized to be playing a role in modulating NMSC risk, but the studies published to date provided conflicting results. We systematically reviewed and meta-analysed the studies focusing on the association between hormone-related characteristics (use of exogenous sex hormones, and aspects of menstrual and reproductive history) and the risk of NMSC among women. We included observational and experimental studies published in PubMed and EMBASE until February 2020. We calculated summary relative risk (SRR) and 95% confidence intervals (CI) by applying random effects models with maximum likelihood estimation, and used the I2 statistics to quantify the degree of heterogeneity of risk estimates across studies. Eleven independent studies encompassing a total of over 30,000 NMSC cases were included in quantitative analyses. No evidence of an increased NMSC risk emerged among ever vs. never users of oral contraceptives (SRR 1.13, 95% CI 0.88-1.45) or hormones for menopause (SRR 1.09, 95% CI 0.87-1.37). Likewise, age at menarche or at menopause and parity were not associated with NMSC risk. Heterogeneity across studies was low, and pooled results were comparable between NMSC subtypes. We found no evidence that hormonal factors play a role in the pathogenesis of NMSC among women.
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Hormonas Esteroides Gonadales/metabolismo , Melanoma/etiología , Melanoma/metabolismo , Menstruación/fisiología , Neoplasias Cutáneas/etiología , Neoplasias Cutáneas/metabolismo , Femenino , Humanos , Menopausia/metabolismo , Menopausia/fisiología , Historia Reproductiva , Factores de RiesgoRESUMEN
Vitamin D receptors polymorphisms are found to be associated with several cancers. Since their prevalence vary across ethnicities and ethnicity itself seems to influence the cancer risk, a comprehensive meta-analysis was performed to investigate the role of VDR Fok1, Bsm1, Taq1, Apa1, Cdx2 and cancer risk at specific organ sites. Odds ratios, calculated with random-effects models, summarized one-hundred-ninety-two independent studies for twenty-two cancer sites. Evidence was provided that Fok1, Bsm1, Cdx2, Apa1 and Taq1 are linked to cancer susceptibility for colorectal, lung, ovarian, skin, multiple myeloma and brain cancer. Stratifying by ethnicity, some differences were found, partially explained by minor allele frequency (MAF), for colorectal cancer, ovarian and prostate cancer in Caucasian and prostate cancer in Asian populations. In summary, ethnicity may be a modifier of cancer risk, in particular for hormone dependent cancers and it should be considered evaluating the effect of VDR on cancer risk.
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Neoplasias Ováricas , Neoplasias de la Próstata , Etnicidad , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Polimorfismo Genético , Receptores de Calcitriol/genética , Vitamina DRESUMEN
Hereditary diffuse gastric cancer (HDGC) is a complex and multifactorial inherited cancer predisposition syndrome caused by CDH1 germline mutations. Nevertheless, current CDH1 genetic screening recommendations disregard an unbalanced worldwide distribution of CDH1 variants, impacting testing efficacy and patient management. In this systematic review, we collected and analyzed all studies describing CDH1 variants in gastric cancer patients originating from both high- and low-prevalence countries. Selected studies were categorized as family study, series study, and unknown study, according to the implementation of HDGC clinical criteria for genetic testing. Our results indicate that CDH1 mutations are more frequently identified in gastric cancer low-incidence countries, and in the family study group that encompasses cases fulfilling criteria. Considering the type of CDH1 alterations, we verified that the relative frequency of mutation types varies within study groups and geographical areas. In the series study, the missense variant frequency is higher in high-incidence areas of gastric cancer, when compared with non-missense mutations. However, application of variant scoring for putative relevance led to a strong reduction of CDH1 variants conferring increased risk of gastric cancer. Herein, we demonstrate that criteria for CDH1 genetic screening are critical for identification of individuals carrying mutations with clinical significance. Further, we propose that future guidelines for testing should consider GC incidence across geographical regions for improved surveillance programs and early diagnosis of disease.
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OBJECTIVES: We aimed to determine whether radiomic features extracted from a highly homogeneous database of breast MRI could non-invasively predict pathological complete responses (pCR) to neoadjuvant chemotherapy (NACT) in patients with breast cancer. METHODS: One hundred patients with breast cancer receiving NACT in a single center (01/2017-06/2019) and undergoing breast MRI were retrospectively evaluated. For each patient, radiomic features were extracted within the biopsy-proven tumor on T1-weighted (T1-w) contrast-enhanced MRI performed before NACT. The pCR to NACT was determined based on the final surgical specimen. The association of clinical/biological and radiomic features with response to NACT was evaluated by univariate and multivariable analysis by using random forest and logistic regression. The performances of all models were assessed using the areas under the receiver operating characteristic curves (AUC) with 95% confidence intervals (CI). RESULTS: Eighty-three patients (mean (SD) age, 47.26 (8.6) years) were included. Patients with HER2+, basal-like molecular subtypes and Ki67 ≥ 20% presented a pCR to NACT more frequently; the clinical/biological model's AUC (95% CI) was 0.81 (0.71-0.90). Using 136 representative radiomics features selected through cluster analysis from the 1037 extracted features, a radiomic score was calculated to predict the response to NACT, with AUC (95% CI): 0.64 (0.51-0.75). After combining the clinical/biological and radiomics models, the AUC (95% CI) was 0.83 (0.73-0.92). CONCLUSIONS: MRI-based radiomic features slightly improved the pre-treatment prediction of pCR to NACT, in addiction to biological characteristics. If confirmed on larger cohorts, it could be helpful to identify such patients, to avoid unnecessary treatment.
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We conducted a systematic review and meta-analysis of the association between somatic mutations of the TERT gene promoter and melanoma survival. Data from nineteen independent studies (>2,500 melanoma overall) were pooled using random effects meta-analysis models. TERT-mutated melanoma patients had a significantly worse overall survival (OS) (summary hazard ratio 1.43, 95 % confidence intervals (CI) 1.05-1.95) compared to wild-type ones. The association became stronger when combining risk estimates for overall and melanoma-specific survival (MSS) (1.52, 95 % CI 1.14-2.02), and when restricting the analysis to studies mostly based on invasive non-acral cutaneous melanomas (1.77, 95 % CI 1.00-3.15). Limited, yet suggestive evidence of a detrimental effect of TERT promoter mutations on melanoma prognosis emerged also for other survival measures (e.g. disease-free and distant metastasis-free survival). We found suggestive evidence of a detrimental effect of TERT mutations on melanoma patients' survival.
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Melanoma , Neoplasias Cutáneas , Telomerasa , Humanos , Melanoma/genética , Mutación , Pronóstico , Neoplasias Cutáneas/genética , Telomerasa/genéticaRESUMEN
OBJECTIVE: The prognostic role of age among patients affected by Oral Tongue Squamous Cell Carcinoma (OTSCC) is a topic of debate. Recent cohort studies have found that patients diagnosed at 40 years of age or younger have a better prognosis. The aim of this cohort study was to clarify whether age is an independent prognostic factor and discuss heterogeneity of outcomes by stage and treatments in different age groups. METHODS: We performed a study on 577 consecutive patients affected by primary tongue cancer and treated with surgery and adjuvant therapy according to stage, at European Institute of Oncology, IRCCS. Patients with age at diagnosis below 40 years totaled 109 (19%). Overall survival (OS), disease-free survival (DFS), tongue specific free survival (TSFS) and cause-specific survival (CSS) were compared by age groups. Multivariate Cox proportional hazards models were used to assess the independent role of age. RESULTS: The median follow-up time was 5.01 years (range 0-18.68) years with follow-up recorded up to February 2020. After adjustment for all the significant confounding and prognostic factors, age remained independently associated with OS and DSF (respectively, p = 0.002 and p = 0.02). In CSS and TSFS curves, the role of age seems less evident (respectively, p = 0.14 and p = 0.0.37). In the advanced stage sub-group (stages III-IV), age was significantly associated with OS and CSS with almost double increased risk of dying (OS) and dying from tongue cancer (CSS) in elderly compared to younger groups (OS: HR = 2.16 95%, CI: 1.33-3.51, p= 0.001; CSS: HR = 1.76 95%, CI: 1.03-3.01, p = 0.02, respectively). In our study, young patients were more likely to be treated with intensified therapies (glossectomies types III-V and adjuvant radio-chemotherapy). Age was found as a prognostic factor, independently of other significant factors and treatment. Also the T-N tract involved by disease and neutrophil-to-lymphocyte ratio ≥3 were independent prognostic factors. CONCLUSIONS: Young age at diagnosis is associated with a better overall survival. Fewer younger people than older people died from tongue cancer in advanced stages.
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Radiomics uses high-dimensional sets of imaging features to predict biological characteristics of tumors and clinical outcomes. The choice of the algorithm used to analyze radiomic features and perform predictions has a high impact on the results, thus the identification of adequate machine learning methods for radiomic applications is crucial. In this study we aim to identify suitable approaches of analysis for radiomic-based binary predictions, according to sample size, outcome balancing and the features-outcome association strength. Simulated data were obtained reproducing the correlation structure among 168 radiomic features extracted from Computed Tomography images of 270 Non-Small-Cell Lung Cancer (NSCLC) patients and the associated to lymph node status. Performances of six classifiers combined with six feature selection (FS) methods were assessed on the simulated data using AUC (Area Under the Receiver Operating Characteristics Curves), sensitivity, and specificity. For all the FS methods and regardless of the association strength, the tree-based classifiers Random Forest and Extreme Gradient Boosting obtained good performances (AUC ≥ 0.73), showing the best trade-off between sensitivity and specificity. On small samples, performances were generally lower than in large-medium samples and with larger variations. FS methods generally did not improve performances. Thus, in radiomic studies, we suggest evaluating the choice of FS and classifiers, considering specific sample size, balancing, and association strength.
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Obesity and diet are associated with colorectal cancer (CRC) risk, and microbiome could mediate this risk factor. To investigate this interaction, we performed a case-control study (34 CRC cases and 32 controls) and analyzed fecal microbiota composition using 16S rRNA metabarcoding and sub-sequential shotgun analyses of genomic bacterial DNA to evaluate the role of microbiome and diet in CRC etiology, taking into account vitamin D and other risk biomarkers. Dietary habits were evaluated using a short questionnaire. Multivariate methods for data integration and mediation analysis models were used to investigate causal relationships. CRC cases were significantly more often deficient in vitamin D than controls (p = 0.04); FokI and CYP24A1 polymorphism frequency were different between cases and controls (p = 0.03 and p = 0.02, respectively). A diet poor in fatty fish and rich in carbohydrates was found to be significantly associated with CRC risk (p = 0.011). The mediation analysis confirmed the significant role of the microbiome in mediating CRC risk-increasing levels of Bifidobacteria/Escherichia genera ratio, an indicator of "healthy" intestinal microbiome, can overcome the effect of diet on CRC risk (p = 0.03). This study suggests that microbiome mediates the diet effect on CRC risk, and that vitamin D, markers of inflammation, and adipokines are other factors to consider in order to achieve a better knowledge of the whole carcinogenic process.
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Adipoquinas/sangre , Neoplasias Colorrectales/sangre , Neoplasias Colorrectales/microbiología , Dieta/métodos , Microbioma Gastrointestinal/fisiología , Inflamación/sangre , Vitamina D/sangre , Biomarcadores/sangre , Femenino , Humanos , Masculino , Persona de Mediana Edad , Medición de Riesgo , Factores de Riesgo , Vitaminas/sangreRESUMEN
BACKGROUND AND PURPOSE: Between 30% and 47% of patients treated with definitive radiotherapy (RT) for prostate cancer are at risk of intraprostatic recurrence during follow-up. Re-irradiation with stereotactic body RT (SBRT) is emerging as a feasible and safe therapeutic option. However, no consensus or guidelines exist on this topic. The purpose of this ESTRO ACROP project is to investigate expert opinion on salvage SBRT for intraprostatic relapse after RT. MATERIALS AND METHODS: A 40-item questionnaire on salvage SBRT was prepared by an internal committee and reviewed by a panel of leading radiation oncologists plus a urologist expert in prostate cancer. Following the procedure of a Delphi consensus, 3 rounds of questionnaires were sent to selected experts on prostate re-irradiation. RESULTS: Among the 33 contacted experts, 18 (54.5%) agreed to participate. At the end of the final round, participants were able to find consensus on 14 out of 40 questions (35% overall) and major agreement on 13 questions (32.5% overall). Specifically, the consensus was reached regarding some selection criteria (no age limit, ECOG 0-1, satisfactory urinary flow), diagnostic procedures (exclusion of metastatic disease, SBRT target defined on the MRI) and therapeutic approach (no need for concomitant ADT, consideration of the first RT dose, validity of Phoenix criteria for salvage SBRT failure). CONCLUSION: While awaiting the results of ongoing studies, our ESTRO ACROP Delphi consensus may serve as a practical guidance for salvage SBRT. Future research should address the existing disagreements on this promising approach.
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Recurrencia Local de Neoplasia/cirugía , Guías de Práctica Clínica como Asunto/normas , Neoplasias de la Próstata/cirugía , Radiocirugia/métodos , Terapia Recuperativa/métodos , Consenso , Humanos , Masculino , Recurrencia Local de Neoplasia/patología , Neoplasias de la Próstata/patologíaRESUMEN
Background: The unprecedented impact of the COVID-19 pandemic on modern society has ignited a "gold rush" for effective treatment and diagnostic strategies, with a significant diversion of economic, scientific, and human resources toward dedicated clinical research. We aimed to describe trends in this rapidly changing landscape to inform adequate resource allocation. Methods: We developed an online repository (COVID Trial Monitor) to analyze in real time the growth rate, geographical distribution, and characteristics of COVID-19 related trials. We defined structured semantic ontologies with controlled vocabularies to categorize trial interventions, study endpoints, and study designs. Analyses are publicly available at https://bioinfo.ieo.it/shiny/app/CovidCT. Results: We observe a clear prevalence of monocentric trials with highly heterogeneous endpoints and a significant disconnect between geographic distribution and disease prevalence, implying that most countries would need to recruit unrealistic percentages of their total prevalent cases to fulfill enrolment. Conclusions: This geographically and methodologically incoherent growth casts doubts on the actual feasibility of locally reaching target sample sizes and the probability of most of these trials providing reliable and transferable results. We call for the harmonization of clinical trial design criteria for COVID-19 and the increased use of larger master protocols incorporating elements of adaptive designs. COVID Trial Monitor identifies critical issues in current COVID-19-related clinical research and represents a useful resource with which researchers and policymakers can improve the quality and efficiency of related trials.
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BACKGROUND: To evaluate whether a model based on radiomic and clinical features may be associated with lymph node (LN) status and overall survival (OS) in lung cancer (LC) patients; to evaluate whether CT reconstruction algorithms may influence the model performance. METHODS: patients operated on for LC with a pathological stage up to T3N1 were retrospectively selected and divided into training and validation sets. For the prediction of positive LNs and OS, the Least Absolute Shrinkage and Selection Operator (LASSO) logistic regression model was used; univariable and multivariable logistic regression analysis assessed the association of clinical-radiomic variables and endpoints. All tests were repeated after dividing the groups according to the CT reconstruction algorithm. p-values < 0.05 were considered significant. RESULTS: 270 patients were included and divided into training (n = 180) and validation sets (n = 90). Transfissural extension was significantly associated with positive LNs. For OS prediction, high- and low-risk groups were different according to the radiomics score, also after dividing the two groups according to reconstruction algorithms. CONCLUSIONS: a combined clinical-radiomics model was not superior to a single clinical or single radiomics model to predict positive LNs. A radiomics model was able to separate high-risk and low-risk patients for OS; CTs reconstructed with Iterative Reconstructions (IR) algorithm showed the best model performance.