Gender and cystectomy for bladder cancer: A high-volume tertiary urologic care center experience.

BACKGROUND: Differences have often been reported in the outcomes of bladder cancer (BC) patients according to gender. OBJECTIVE: This study aims to provide data on patients undergoing radical cystectomy (RC) in a high-volume tertiary urologic center and to assess whether gender discrepancies do exist in terms of surgical options and clinical outcomes. MATERIALS AND METHODS: Consecutive BC patients treated between 2016 and 2020 at a single center (Careggi University Hospital, Florence, Italy) were included in the study. The impact of gender on disease stage at diagnosis, overall survival (OS), and type of surgery was analyzed. RESULTS: The study series comprised 447 patients (85 females and 362 males). At a median follow-up of 28.3 months (IQR: 33.5), OS was 52.6% and cancer-specific survival was 67.6%. Significant differences in OS emerged for age, acute myocardial infarction (AMI), Charlson Comorbidity Index (CCI), pT, and pN. OS rates were higher in patients undergoing robot-assisted surgery and in those receiving open orthotopic neobladder (ONB) (p = 0.0001). No statistically significant differences were found between male and female patients regarding surgical offer in any age group, surgical time, early postoperative complications, pathologic stage, and OS. CONCLUSIONS: After adjustment for pathologic tumor stage and treatment modalities, female and male patients showed similar oncologic outcomes. Further studies should be undertaken to evaluate functional results in women subjected to RC.

Inflammatory marker changes in a 24-month dietary and physical activity randomised intervention trial in postmenopausal women.

Chronic low-grade inflammation plays a role in the pathogenesis of several chronic diseases including cancer. Physical activity (PA) and diet have been supposed to modulate inflammatory markers. We evaluated the effects of a 24-month dietary and/or PA intervention on plasma levels of pro-inflammatory cytokines, a secondary analysis in the DAMA factorial trial. The 234 study participants (healthy postmenopausal women with high breast density, 50-69 years, non smokers, no hormone therapy) were randomised to four arms: (1) isocaloric dietary intervention mainly based on plant-foods; (2) moderate-intensity PA intervention with at least 1 h/week of supervised strenuous activity; (3) both interventions; (4) general recommendations on healthy dietary and PA patterns. Interleukins (IL)-1α, -1ß, -6, tumor necrosis factor-α and C-reactive protein were measured at baseline and at the end of the intervention. Intention-to-treat-analyses were carried out using Tobit regression. Although all cytokines tended to increase over time, after 24 months women in the PA intervention (arms 2 + 3) showed lower levels of IL-1α (exp(ß) = 0.66; p = 0.04) and IL-6 (exp(ß) = 0.70; p = 0.01) in comparison with women in the control group (arms 1 + 4). No effects of the dietary intervention emerged. In healthy postmenopausal women with high breast density a moderate-intensity PA appears to slow the age-related increase of pro-inflammatory cytokines.

Does a 6-point scale approach to post-treatment 18F-FDG PET-CT allow to improve response assessment in head and neck squamous cell carcinoma? A multicenter study.

PURPOSE: Response assessment to definitive non-surgical treatment for head and neck squamous cell carcinoma (HNSCC) is centered on the role of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET-CT) 12 weeks after treatment. The 5-point Hopkins score is the only qualitative system available for standardized reporting, albeit limited by suboptimal positive predictive value (PPV). The aim of our study was to explore the feasibility and assess the diagnostic accuracy of an experimental 6-point scale ("Cuneo score"). METHODS: We performed a retrospective, multicenter study on HNSCC patients who received a curatively-intended, radiation-based treatment. A centralized, independent qualitative evaluation of post-treatment FDG-PET/CT scans was undertaken by 3 experienced nuclear medicine physicians who were blinded to patients' information, clinical data, and all other imaging examinations. Response to treatment was evaluated according to Hopkins, Cuneo, and Deauville criteria. The primary endpoint of the study was to evaluate the PPV of Cuneo score in assessing locoregional control (LRC). We also correlated semi-quantitative metabolic factors as included in PERCIST and EORTC criteria with disease outcome. RESULTS: Out of a total sample of 350 patients from 11 centers, 119 subjects (oropharynx, 57.1%; HPV negative, 73.1%) had baseline and post-treatment FDG-PET/CT scans fully compliant with EANM 1.0 guidelines and were therefore included in our analysis. At a median follow-up of 42 months (range 5-98), the median locoregional control was 35 months (95% CI, 32-43), with a 74.5% 3-year rate. Cuneo score had the highest diagnostic accuracy (76.5%), with a positive predictive value for primary tumor (Tref), nodal disease (Nref), and composite TNref of 42.9%, 100%, and 50%, respectively. A Cuneo score of 5-6 (indicative of residual disease) was associated with poor overall survival at multivariate analysis (HR 6.0; 95% CI, 1.88-19.18; p = 0.002). In addition, nodal progressive disease according to PERCIST criteria was associated with worse LRC (OR for LR failure, 5.65; 95% CI, 1.26-25.46; p = 0.024) and overall survival (OR for death, 4.81; 1.07-21.53; p = 0.04). CONCLUSIONS: In the frame of a strictly blinded methodology for response assessment, the feasibility of Cuneo score was preliminarily validated. Prospective investigations are warranted to further evaluate its reproducibility and diagnostic accuracy.

The risk of extra-ovarian malignancies among women with endometriosis: A systematic literature review and meta-analysis.

We conducted a meta-analysis of studies reporting on the risk of extra-ovarian malignancies among women with endometriosis. Summary relative risk (SRR) and 95% confidence intervals (CI) were calculated through random effect models. We explored causes of between-studies heterogeneity and assessed the presence of publication bias. We included 32 studies published between 1989 and 2018. We found an increased risk of endometrial (SRR 1.38, 95%CI 1.10-1.74) and thyroid cancer (SRR 1.38, 95%CI 1.17-1.63), and inverse association with cervical cancer (SRR 0.78, 95%CI 0.60-0.95). No association emerged for breast cancer (SRR 1.04, 95%CI 0.99-1.09) and melanoma (SRR 1.31, 95%CI 0.86-1.96). Between-study heterogeneity was large for breast and endometrial cancer and melanoma. Associations were generally stronger in case-control, cross-sectional, and cohort studies with internal control group, compared to cohort studies with external control group. No indication for publication bias was found. Our conclusions need to be confirmed in properly designed cohort studies with clinical confirmation of endometriosis.

A priori dietary patterns and blood pressure in the EPIC Florence cohort: a cross-sectional study.

PURPOSE: Several foods and nutrients have been independently associated with systolic (SBP) and diastolic (DBP) blood pressure values. This study aimed to evaluate the effects of combined dietary habits on SBP and DBP values in a large cohort of healthy adults, with a cross-sectional design. Adherence of participants to four a priori dietary patterns was considered: the Healthy Eating Index 2010 (HEI-2010); the Dietary Approaches to Stop Hypertension (DASH); the Greek Mediterranean Diet Score (MDS); and the Italian Mediterranean Index (IMI). METHODS: Overall, 13,597 volunteers (35-64 years) were enrolled in 1993-1998 in the EPIC-Florence cohort. Information on dietary habits, anthropometry, smoking status, education, physical activity habits, previous diagnosis of hypertension and SBP and DBP measurements were collected at baseline. Multivariate regression models were performed on 10,163 individuals (7551 women) after excluding subjects with prevalent hypertension. RESULTS: IMI, DASH and HEI-2010 were significantly and inversely associated with SBP and DBP values in the total population. The strongest association emerged between IMI and SBP (ß - 1.80 excellent adherence vs low adherence, 95% CI - 2.99; - 0.61, p trend 0.001) and DBP (ß - 1.12, 95% CI - 1.869; - 0.39, p trend 0.001) values. In sub-group analyses, an inverse association also emerged between IMI and SBP and DBP values among females and between DASH and DBP among males. MDS was not associated with SBP or DBP. CONCLUSION: Overall, this study, carried out in a large cohort of healthy adults from Tuscany (Central Italy), showed inverse significant associations between specific a priori dietary patterns, identifying general models of health-conscious diet, and blood pressure values.

Correction to: A priori dietary patterns and blood pressure in the EPIC Florence cohort: a cross-sectional study.

In the original publication of the article have been published in an incorrect form. The correct form is given below.

Physical activity and blood pressure in 10,000 Mediterranean adults: The EPIC-Florence cohort.

BACKGROUND AND AIMS: The relevant role of physical activity (PA) in cardiovascular risk prevention is widely agreed. We aimed to evaluate, in a large Mediterranean population, the influence of PA on systolic (SBP) and diastolic blood pressure (DBP), taking into account individual characteristics and lifestyle habits. METHODS AND RESULTS: In the Florence section of the European Prospective Investigation into Cancer and Nutrition 10,163 individuals, 35-64 years, without a previous diagnosis of hypertension were recruited. Information on occupational and leisure-time PA and blood pressure were collected at recruitment, together with data on lifestyle, dietary habits and anthropometry. Multivariate regression models were applied to evaluate the effect of total, occupational and leisure-time PA on SBP and DBP. Mean values of SBP and DBP in the study subjects were 124.4 (SD 15.6) and 79.7 mmHg (SD 9.4), respectively. Overall, a total PA index and an index including cycling, fitness and occupational PA (Cambridge index) were inversely associated with DBP (beta -0.87, p-value 0.02 actives vs inactives, p for trend 0.02 and beta -0.84, p value 0.003 actives vs inactives, p for trend 0.002, respectively), while SBP was associated only with the latter index (beta -1.14, p-value 0.01 actives vs inactives, p for trend 0.006). An inverse association emerged between manual/heavy manual occupation and DBP (p 0.02, ref sedentary/standing occupation) and between increasing cycling activity and SBP (p for trend 0.04). CONCLUSIONS: In this large cohort of Mediterranean adults without a diagnosis of hypertension we confirm the role of overall PA in modulating SBP and DBP values. Cycling and manual occupations were associated with lower DBP values.

Alcohol consumption and the risk of renal cancers in the European Prospective Investigation into Cancer and Nutrition (EPIC). Wozniak MB, Brennan P, Brenner DR, Overvad K, Olsen A, Tjønneland A, Boutron-Ruault MC, Clavel-Chapelon F, Fagherazzi G, Katzke V, Kühn T, Boeing H, Bergmann MM, Steffen A, Naska A, Trichopoulou A, Trichopoulos D, Saieva C, Grioni S, Panico S, Tumino R, Vineis P, Bueno-de-Mesquita HB, Peeters PH, Hjartåker A, Weiderpass E, Arriola L, Molina-Montes E, Duell EJ, Santiuste C, Alonso de la Torre R, Barricarte Gurrea A, Stocks T, Johansson M, Ljungberg B, Wareham N, Khaw KT, Travis RC, Cross AJ, Murphy N, Riboli E, Scelo G.Int J Cancer. 2015 Oct 15;137(8):1953-66. [Epub 2015 Apr 28]. doi: 10.1002/ijc.29559.

Epidemiologic studies have reported that moderate alcohol consumption is inversely associated with the risk of renal cancer. However, there is no information available on the associations in renal cancer subsites. From 1992 to 2010, 477,325 men and women in the European Prospective Investigation into Cancer and Nutrition cohort were followed for incident renal cancers (n = 931). Baseline and lifetime alcohol consumption was assessed by country-specific, validated dietary questionnaires. Information on past alcohol consumption was collected by lifestyle questionnaires. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated from Cox proportional hazard models. In multivariate analysis, total alcohol consumption at baseline was inversely associated with renal cancer; the HR and 95% CI for the increasing categories of total alcohol consumption at recruitment vs. the light drinkers category were 0.78 (0.62-0.99), 0.82 (0.64-1.04), 0.70 (0.55-0.90), and 0.91 (0.63-1.30), respectively, (ptrend = 0.001). A similar relationship was observed for average lifetime alcohol consumption and for all renal cancer subsites combined or for renal parenchyma subsite. The trend was not observed in hypertensive individuals and not significant in smokers. In conclusion, moderate alcohol consumption was associated with a decreased risk of renal cancer.

Impact of molecular subtypes classification concordance between preoperative core needle biopsy and surgical specimen on early breast cancer management: Single-institution experience and review of published literature.

BACKGROUND: Core needle biopsy (CNB) plays a crucial role as diagnostic tool for breast cancer (BC). The characterization of biomarkers status before surgical treatment is crucial when primary systemic therapy is a therapeutic option. The aim of this analysis was to report concordance between preoperative CNB and surgical specimen (SS) in evaluating biomarkers and molecular subtypes. METHODS: Data have been collected from a cohort of 101 patients affected by early BC treated at Careggi Florence University Hospital, between January 2014 and March 2015. The conformity between molecular subtype classification was tested using kappa (κ) test. RESULTS: Mean age was 57.5 years (range 29-86). There was concordance between the estrogen receptor (ER) assessment on CNB and SS in 95 cases (94.1%). Concordance of the progesterone receptor (PgR) assessment was observed in 89 cases (88.1%). Concordance for detecting immunohistochemistry-assessed BC molecular subtypes was 87.1% (κ = 0.78). Concerning Ki-67 evaluation, we report a concordance rate of 88.1% (κ = 0.68). The evaluation of luminal A plus luminal B/HER negative subgroup showed a κ-value of 0.65. CONCLUSIONS: CNB showed good accuracy in evaluating hormonal receptors status, HER2, and BC molecular subtypes. Evaluation of Ki67 status was less accurate than other biomarkers; therefore, we recommend that it should be detected both on CNB and SS samples, especially in hormonal positive HER2 negative tumors, in order to avoid a misclassification of tumor subtypes that could lead to an omission of potential effective systemic therapy.

Accuracy and Reproducibility of HER2 Status in Breast Cancer Using Immunohistochemistry: A Quality Control Study in Tuscany Evaluating the Impact of Updated 2013 ASCO/CAP Recommendations.

The correct identification of HER2-positive cases is a key point to provide the most appropriate therapy to breast cancer (BC) patients. We aimed at investigating the reproducibility and accuracy of HER2 expression by immunohistochemistry (IHC) in a selected series of 35 invasive BC cases across the pathological anatomy laboratories in Tuscany, Italy. Unstained sections of each BC case were sent to 12 participating laboratories. Pathologists were required to score according to the Food and Drug Administration (FDA) four-tier scoring system (0, 1+, 2+, 3+). Sixteen and nineteen cases were HER2 non-amplified and amplified respectively on fluorescence in situ hybridization. Among 192 readings of the 16 HER2 non-amplified samples, 153 (79.7%) were coded as 0 or 1+, 39 (20.3%) were 2+, and none was 3+ (false positive rate 0%). Among 228 readings of the 19 HER2 amplified samples, 56 (24.6%) were scored 0 or 1+, 79 (34.6%) were 2+, and 93 (40.8%) were 3+. The average sensitivity was 75.4%, ranging between 47% and 100%, and the overall false negative rate was 24.6%. Participation of pathological anatomy laboratories performing HER2 testing by IHC in external quality assurance programs should be made mandatory, as the system is able to identify laboratories with suboptimal performance that may need technical advice. Updated 2013 ASCO/CAP recommendations should be adopted as the widening of IHC 2+ "equivocal" category would improve overall accuracy of HER2 testing, as more cases would be classified in this category and, consequently, tested with an in situ hybridisation method.

Association of SULT1A1 Arg²¹³His polymorphism with male breast cancer risk: results from a multicenter study in Italy.

Male breast cancer (MBC) is rare and poorly understood. Like female breast cancer (FBC), MBCs are highly sensitive to hormonal changes, and hyperestrogenism, specifically, represents a major risk factor for MBC. MBC is considered similar to late-onset, post-menopausal estrogen/progesteron receptors positive FBC (ER+/PR+). Sulfotransferase 1A1 (SULT1A1) is an enzyme involved in the metabolism of estrogens. Recently, SULT1A1 common functional polymorphism Arg(213)His (638G>A) variant has been found to be associated with increased breast cancer (BC) risk, particularly in post-menopausal women. For this reason, we decided to explore whether SULT1A1 Arg(213)His could exert an effect on MBC development. The primary aim of this study was to evaluate the influence of the SULT1A1 Arg(213)His polymorphism on MBC risk. The secondary aim was to investigate possible associations with relevant clinical-pathologic features of MBC. A total of 394 MBC cases and 786 healthy male controls were genotyped for SULT1A1 Arg(213)His polymorphism by PCR-RFLP and high-resolution melting analysis. All MBC cases were characterized for relevant clinical-pathologic features. A significant difference in the distribution of SULT1A1 Arg(213)His genotypes was found between MBC cases and controls (P < 0.0001). The analysis of genotype-specific risk showed a significant increased MBC risk in individuals with G/A (OR 1.97, 95% CI 1.50-2.59; P < 0.0001) and A/A (OR 3.09, 95% CI 1.83-5.23; P < 0.0001) genotypes in comparison to wild-type genotype, under co-dominant model. A significant association between SULT1A1 risk genotypes and HER2 status emerged. Results indicate that SULT1A1 Arg(213)His may act as a low-penetrance risk allele for developing MBC and could be associated with a specific tumor subtype associated with HER2 overexpression.

Impact of sentinel node tumor burden on outcome of invasive breast cancer patients.

BACKGROUND: The tumor status of the axillary lymph nodes is one of the most important prognostic factors in women with early breast cancer (BC). Sentinel lymph node (SLN) biopsy has become the standard staging procedure for patients with invasive BC, largely replacing axillary lymph nodes dissection (ALND). The exact impact on prognosis of SLN tumor burden is still object of controversy. The aim of this study was to correlate the tumor burden in the SLN with the outcome in a large cohort of women. PATIENTS AND METHODS: 1040 consecutive patients with clinical stage I-III invasive BC were prospectively collected on our Institutional BC database from January 2001 to January 2007. Patients were stratified into the following four groups based on the tumor burden of the SLN: macrometastases, tumor deposit ≥2 mm; micrometastases, tumor deposit ≥0.2 mm and <2 mm; isolated tumor cells (ITC), isolated tumor cells or tumor deposit <0.2 mm; negative, in case of patients with no evidence of tumor. RESULTS: At a median follow-up of 8.5 years, the tumor burden of SLN metastases resulted significant predictor of DFS (P < 0.0001) and OS (P = 0.042). Multivariate analysis showed that the tumor burden of SLN metastases and Ki 67 proliferative index maintained the statistical significance. CONCLUSION: Patients with SLN micrometastases or ITC, do not seem to have a worse DFS or OS compared with SLN negative cases. There is a significant decrease in DFS and OS in patients with macrometastatic disease in the SLN.

Dietary intake of acrylamide and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort.

BACKGROUND: Three prospective studies have evaluated the association between dietary acrylamide intake and endometrial cancer (EC) risk with inconsistent results. The objective of this study was to evaluate the association between acrylamide intake and EC risk: for overall EC, for type-I EC, and in never smokers and never users of oral contraceptives (OCs). Smoking is a source of acrylamide, and OC use is a protective factor for EC risk. METHODS: Cox regression was used to estimate hazard ratios (HRs) for the association between acrylamide intake and EC risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Acrylamide intake was estimated from the EU acrylamide monitoring database, which was matched with EPIC questionnaire-based food consumption data. Acrylamide intake was energy adjusted using the residual method. RESULTS: No associations were observed between acrylamide intake and overall EC (n=1382) or type-I EC risk (n=627). We observed increasing relative risks for type-I EC with increasing acrylamide intake among women who both never smoked and were non-users of OCs (HRQ5vsQ1: 1.97, 95% CI: 1.08-3.62; likelihood ratio test (LRT) P-value: 0.01, n=203). CONCLUSIONS: Dietary intake of acrylamide was not associated with overall or type-I EC risk; however, positive associations with type I were observed in women who were both non-users of OCs and never smokers.

The impact of method of biopsy on the incidence of breast cancer sentinel lymph node metastases.

BACKGROUND: The dislocation of the malignant cells along the needle tract during breast cancer (BC) diagnosis has been demonstrated by several studies. However, the published experiences that relate the diagnostic technique with sentinel node (SN) involvement are few and controversial. The aim of our analysis was to evaluate the impact of different techniques for preoperative BC biopsy among prognostic factors of metastases occurrence in SN. MATERIALS AND METHODS: We reviewed the institutional clinical database of our Center. A total of 674 patients were diagnosed between February 1999 and December 2006 with invasive BC. SN metastases classification followed the 2002 American Joint Committee on Cancer (AJCC) TNM pathological staging: macrometastases, micrometastases, isolated tumor cells or negative. Only macrometastases and micrometastases were considered positive. Concerning fine-needle aspiration cytology, we used disposable needles of the size of 21-27 G. For percutaneous biopsy we used cutting needle type "tru-cut"; the Gauge needle ranged between 14 and 20. RESULTS: At univariate analysis of specific parameters using positive SN as outcome, percutaneous diagnostic technique did not affect significantly the SN positivity (p = 0.60). At multivariate models only central quadrant lesion (p = 0.005) and lymph vascular invasion (LVI) presence (p < 0.0001) maintained the statistical significance as risk factor for positive SN status. Polytomic logistics models showed that only LVI maintained the statistical significance both for prediction of micrometastases and macrometastases. CONCLUSIONS: Our analysis showed that different techniques used for BC diagnosis did not influence SN status.

Dietary vitamin D intake and risk of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition: the EPIC-InterAct study.

BACKGROUND/OBJECTIVES: Prospective cohort studies have indicated that serum vitamin D levels are inversely related to risk of type 2 diabetes. However, such studies cannot determine the source of vitamin D. Therefore, we examined the association of dietary vitamin D intake with incident type 2 diabetes within the European Prospective Investigation into Cancer and Nutrition (EPIC)-InterAct study in a heterogeneous European population including eight countries with large geographical variation. SUBJECTS/METHODS: Using a case-cohort design, 11,245 incident cases of type 2 diabetes and a representative subcohort (N=15,798) were included in the analyses. Hazard ratios (HR) and 95% confidence intervals (CIs) for type 2 diabetes were calculated using a Prentice-weighted Cox regression adjusted for potential confounders. Twenty-four-hour diet-recall data from a subsample (N=2347) were used to calibrate habitual intake data derived from dietary questionnaires. RESULTS: Median follow-up time was 10.8 years. Dietary vitamin D intake was not significantly associated with the risk of type 2 diabetes. HR and 95% CIs for the highest compared to the lowest quintile of uncalibrated vitamin D intake was 1.09 (0.97-1.22) (Ptrend=0.17). No associations were observed in a sex-specific analysis. The overall pooled effect (HR (95% CI)) using the continuous calibrated variable was 1.00 (0.97-1.03) per increase of 1 µg/day dietary vitamin D. CONCLUSIONS: This observational study does not support an association between higher dietary vitamin D intake and type 2 diabetes incidence. This result has to be interpreted in light of the limited contribution of dietary vitamin D on the overall vitamin D status of a person.

Dietary intake of acrylamide and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

BACKGROUND: In 1994, acrylamide (AA) was classified as a probable human carcinogen by the International Agency for Research on Cancer. In 2002, AA was discovered at relatively high concentrations in some starchy, plant-based foods cooked at high temperatures. PATIENTS AND METHODS: A prospective analysis was conducted to evaluate the association between the dietary intake of AA and ductal adenocarcinoma of the exocrine pancreatic cancer (PC) risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort using Cox regression modeling. EPIC includes >500,000 men and women aged 35-75 at enrollment from 10 European countries. AA intake was estimated for each participant by combining questionnaire-based food consumption data with a harmonized AA database derived from the EU monitoring database of AA levels in foods, and evaluated in quintiles and continuously. RESULTS: After a mean follow-up of 11 years, 865 first incident adenocarcinomas of the exocrine pancreas were observed and included in the present analysis. At baseline, the mean dietary AA intake in EPIC was 26.22 µg/day. No overall association was found between continuous or quintiles of dietary AA intake and PC risk in EPIC (HR:0.95, 95%CI:0.89-1.01 per 10 µg/day). There was no effect measure modification by smoking status, sex, diabetes, alcohol intake or geographic region. However, there was an inverse association (HR: 0.73, 95% CI: 0.61-0.88 per 10 µg/day) between AA intake and PC risk in obese persons as defined using the body mass index (BMI, ≥ 30 kg/m(2)), but not when body fatness was defined using waist and hip circumference or their ratio. CONCLUSIONS: Dietary intake of AA was not associated with an increased risk of PC in the EPIC cohort.

Role of radiotherapy boost in women with ductal carcinoma in situ: a single-center experience in a series of 389 patients.

BACKGROUND: The use of adjuvant radiotherapy in ductal carcinoma in situ is accepted by most radiation oncologists worldwide; the role of a boost on the tumor bed is however more controversial. MATERIALS AND METHODS: We reviewed our Institute experience in DCIS treatment, focusing on main prognostic factors and impact of radiation boost on local relapse. A total of 389 patients treated between 1990 and 2007 were retrospectively analyzed. All patients received adjuvant radiotherapy after breast-conserving surgery for a median dose of 50 Gy; 190 patients (48.8%) received and additional radiation boost on the tumor bed. RESULTS: At a mean follow up of 7.7 years, we recorded 26 local recurrence (6.7%). Concerning local relapse-free survival, at Cox regression univariate analyses <1 mm surgical margins (p < 0.0001) and young age (p = 0.01) emerged as significant unfavorable prognostic factors. At multivariate analysis Cox regression model, surgical margins (p < 0.001) and radiation boost (p = 0.014) resulted as the significant independent predictors of recurrence. CONCLUSIONS: Our experience showed the negative prognostic impact of surgical margins <1 mm and the protective role of radiation boost on LR rate. Anyway, results from ongoing prospective Phase III studies are strongly necessary to better identify high-risk DCIS patients.

Association of low-penetrance alleles with male breast cancer risk and clinicopathological characteristics: results from a multicenter study in Italy.

It is well-known that male breast cancer (MBC) susceptibility is mainly due to high-penetrance BRCA1/2 mutations. Here, we investigated whether common low-penetrance breast cancer (BC) susceptibility alleles may influence MBC risk in Italian population and whether variant alleles may be associated with specific clinicopathological features of MBCs. In the frame of the Italian Multicenter Study on MBC, we genotyped 413 MBCs and 745 age-matched male controls at 9 SNPs annotating known BC susceptibility loci. By multivariate logistic regression models, we found a significant increased MBC risk for 3 SNPs, in particular, with codominant models, for rs2046210/ESR1 (OR = 1.71; 95 % CI: 1.43-2.05; p = 0.0001), rs3803662/TOX3 (OR = 1.59; 95 % CI: 1.32-1.92; p = 0.0001), and rs2981582/FGFR2 (OR = 1.26; 95 % CI: 1.05-1.50; p = 0.013). Furthermore, we showed that the prevalence of the risk genotypes of ESR1 tended to be higher in ER- tumors (p = 0.062). In a case-case multivariate analysis, a statistically significant association between ESR1 and ER- tumors was found (OR = 1.88; 95 % CI: 1.03-3.49; p = 0.039). Overall, our data, based on a large and well-characterized MBC series, support the hypothesis that common low-penetrance BC susceptibility alleles play a role in MBC susceptibility and, interestingly, indicate that ESR1 is associated with a distinct tumor subtype defined by ER-negative status.

Neoadjuvant oxaliplatin and 5-fluorouracil with concurrent radiotherapy in patients with locally advanced rectal cancer: a single-institution experience.

PURPOSE: The aim of this study was to evaluate the rate of pathological response (PR), disease control and safety of neoadjuvant chemotherapy using oxaliplatin (OX) and 5-fluorouracil (5-FU) with concurrent radiotherapy for treating locally advanced rectal cancer. MATERIALS AND METHODS: Between November 2002 and December 2010, 90 patients with locally advanced rectal cancer treated with neoadjuvant chemoradiotherapy (CRT) were retrospectively analysed. All patients underwent preoperative radiotherapy (45 Gy in 1.8-Gy fractions) with concurrent OX (80 mg/m(2) i.v., day 1) and a 120-h continuous infusion of 5-FU (1,000 mg/m(2) per day). Surgery was performed within 6 weeks after completion of CRT treatment. RESULTS: Complete pathological response was obtained in six patients (6.7%), and 39 (43.3%) had their disease downstaged. The median follow-up period was 4.7 years (6 months to 9 years). Local recurrence occurred in two patients (2.2%), one of whom developed also liver metastases. Distant metastases not associated with local relapse occurred in 23 (25.6%) patients. Overall (OS) and disease-free (DFS) survival were 62.9% and 52.8%, respectively. CRT was well tolerated, with only one grade 3 (1.2%) haematological toxicity (neutropaenia). CONCLUSIONS: Neoadjuvant systemic chemotherapy based on OX and 5-UC associated with radiotherapy is well tolerated, with good results in terms of pathological response, disease control and survival, in rectal cancer patients.

Treatment of invasive male breast cancer: a 40-year single-institution experience.

PURPOSE: We conducted a retrospective analysis to evaluate the management and outcome of invasive male breast cancer treated in a single-institution over a period of 40 years. MATERIALS AND METHODS: We reviewed the clinical and pathological features of 60 male patients affected by breast carcinoma treated at our Radiotherapy Unit between 1971 and 2011. Tumours were classified according to histological type and the updated 2010 TNM classification of malignant tumours. RESULTS: At a median follow-up of 8.9 [range, 0.6-20; standard deviation (SD), 4.98] years, 32 patients (53.3%) were alive and 16 patients died (26.7%) due to disease progression and 12 (20%) due to other causes. At univariate analysis for overall survival, pathological tumour size (p=0.031), histological subtype (p=0.013) and nodal status (p=0.006) emerged as significant predictors of death. At multivariate analysis, independent death predictors were advanced pathological tumour size (p=0.016), positive nodal status (p=0.003) and invasive cribriform histological type (p=0.0003). CONCLUSIONS: In consideration of the rarity of the disease, many issues are still being debated, and future collaborative studies are required. However, our experience confirms the prognostic role of greater pathological tumour size and positive nodal status as unfavourable features for survival in male breast cancer.