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The Barcelona clinic liver cancer (BCLC) algorithm is the most widely accepted staging system form hepatocellular carcinoma (HCC). Liver resection is traditionally proposed to early stage HCC (BCLC-0/A), even if recent reports have shown that surgical resection could provide a safe and effective treatment also for intermediate-stage HCC (BCLC-B). In this study, we focused on surgical and oncological outcomes of hepatic resection in BLCB-B patients. Patients who received hepatic resection for early- (BCLC-0/A) or intermediate-stage (BCLC-B) HCC in two tertiary hepatobiliary centers between January 2003 and December 2016 were included in study. Four-hundred and twenty-nine patients were included in the analysis. At the time of resection, 298 patients were classified as BCLC-A/0 and 131 as BCLC-B. Despite a higher complication rate in BCLC-B group (49.6% vs 32.9%; p = 0.001), the incidence of clinically relevant complications did not differ significantly between the two groups (16.0% vs 10.1%; p = 0.079); moreover, postoperative mortality (4.6% vs 2.7%; p = 0.309) and relapse-free survival (RFS) were similar between BCLC-0/A and BCLC-B group (1-, 3-, and 5-year RFS: 74, 43, and 31% vs 59, 38, and 34%; p = 0.180). Overall survival was slightly worse in BCLC-B group (1-, 3-, and 5-year overall survival of 89, 70, and 52% vs. 77, 51, and 44%; p = 0.004). Focusing on BCLC-B group, a Child–Pugh score B (HR 2.47; p = 0.003), growing number of nodules (HR 3.04; p = 0.003), and R1 resection (HR 2.43; p = 0.005) beard a higher risk of tumor recurrence, while overall survival was negatively affected by the presence of more than two nodules (HR 3.66; p = 0.0001) and R1 resection (HR 3.06; p = 0.0001); patients presenting single-large HCC experienced a better overall survival (HR 0.53; p = 0.014) and lower recurrence-rate (HR 0.60; p = 0.046). Hepatic resection for intermediate-stage HCC shows acceptable results in terms of perioperative morbidity and mortality, with better oncological outcomes in patients with lower number of lesions despite of their size.

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.

The comprehensive assessment of the transplantable tumor (TT) proposed and included in the last Italian consensus meeting still deserve validation. All consecutive patients with hepatocellular carcinoma (HCC) listed for liver transplant (LT) between January 2005 and December 2015 were post-hoc classified by the tumor/patient stage as assessed at the last re-staging-time (ReS-time) before LT as follow: high-risk-class (HRC) = stages TTDR, TTPR, intermediate-risk-class (IRC) = TT0NT, TTFR, TTUT, low-risk-class (LRC) = TT1, TT0L, TT0C. Of 376 candidates, 330 received LT and 46 dropped-out. Transplanted patients were: HRC for 159 (48.2%), IRC for 63 (19.0%), LRC for 108 (32.7%). Cumulative incidence function (CIF) of tumor recurrence after LT was 21%, 12%, and 8% at 5-years and 27%, 15%, and 12% at 10-years respectively for HRC, IRC, and LRC (P = 0.011). IRC patients had significantly lower CIF of recurrence after LT if transplanted &gt, 2-months from ReS-time (28% vs 3% for &lt, 2 and &gt, 2 months, P = 0.031). HRC patients had significantly lower CIF of recurrence after-LT if transplanted &lt, 2 months from the ReS-time (10% vs 33% for &lt, 2 months, P = 0.006). The proposed TT staging system can adequately describe the post-LT recurrence, especially in the LRC and HRC patients. The intermediate-risk-class needs to be better defined and further studies on its ability in defining intention-to-treat survival (ITT) and drop-out are required.

Background: Alcohol is capable of traversing the blood-brain barrier and is thus a possible risk factor for brain cancer. Several epidemiological studies have been published on the issue, a number of those during recent years, with inconsistent findings. Materials and methods: We performed a systematic literature search in the Medline and EMBASE databases. We found a total of 19 studies providing risk estimates for total alcohol or specific alcoholic beverages. Pooled estimates of the relative risks (RR) and 95% confidence intervals (CI) were calculated using random-effects models. Results: The pooled RR of brain cancer for alcohol drinkers versus non-drinkers was 0.97 (95% CI 0.82-1.15; based on 12 studies). Moderate (

Bellocco, R Pasquali, E Rota, M Bagnardi, V Tramacere, I Scotti, L Pelucchi, C Boffetta, P Corrao, G La Vecchia, C eng Meta-Analysis England 2012/03/09 06:00 Ann Oncol. 2012 Sep;23(9):2235-44. doi: 10.1093/annonc/mds022. Epub 2012 Mar 7.; International audience; BACKGROUND: The role of alcohol consumption in relation with renal cell carcinoma is still unclear; a few studies have reported a beneficial effect of moderate levels of alcohol consumption, whereas it remains still under debate whether there is a dose-response association. MATERIALS AND METHODS: Twenty observational studies (4 cohort, 1 pooled and 15 case-control) reporting results on at least three levels of alcohol consumption were selected through a combined search with PubMed and EMBASE of articles published before November 2010. Overall relative risks (RRs) and 95% confidence intervals (CIs) were estimated using random-effects models, and both second-order fractional polynomials and random effect meta-regression models were implemented for the study of dose-risk relation. RESULTS: The estimated RRs were 0.85 (95% CI: 0.80-0.92) for any alcohol drinking, 0.90 (95% CI: 0.83-0.97) for light drinking (0.01-12.49 g/day), 0.79 (95% CI: 0.71-0.88) for moderate drinking (12.5-49.9 g/day) and 0.89 (95% CI: 0.58-1.39) for heavy drinking (>/=50 g/day), respectively. CONCLUSION: Our meta-analysis supports the hypothesis of a negative effect of moderate alcohol consumption on the risk of renal cell cancer.

Pelucchi, C Galeone, C Tramacere, I Bagnardi, V Negri, E Islami, F Scotti, L Bellocco, R Corrao, G Boffetta, P La Vecchia, C eng Meta-Analysis Research Support, Non-U.S. Gov't England 2011/11/01 06:00 Ann Oncol. 2012 Jun;23(6):1586-93. doi: 10.1093/annonc/mdr460. Epub 2011 Oct 29.; International audience; BACKGROUND: We aimed at investigating the risk of bladder cancer at different levels of alcohol consumption by conducting a meta-analysis of epidemiological studies. PATIENTS AND METHODS: In October 2010, we carried out a systematic literature search in the Medline database, using PubMed. We identified 16 case-control and 3 cohort studies, including a total of 11 219 cases of bladder cancer, satisfying the inclusion criteria for this meta-analysis. Moderate alcohol intake was defined as /=3 drinks/day. Pooled estimates of the relative risks (RR) and the corresponding 95% confidence intervals (CI) were calculated using random effects models. RESULTS: Compared with non-drinkers, the pooled RRs of bladder cancer were 1.00 (95% CI 0.92-1.09) for moderate and 1.02 (95% CI 0.78-1.33) for heavy alcohol drinkers. When we excluded four studies that did not adjust for tobacco smoking, the corresponding estimates were 0.98 (95% CI 0.89-1.07) and 0.97 (95% CI 0.72-1.31). CONCLUSIONS: This meta-analysis of epidemiological studies provides definite evidence on the absence of any material association between alcohol drinking and bladder cancer risk, even at high levels of consumption.

Background: The role of alcohol consumption as an independent risk factor for lung cancer is controversial. Since drinking and smoking are strongly associated, residual confounding by smoking may bias the estimation of alcohol consumption and lung cancer risk relation. Therefore, we undertook a meta-analysis to quantitatively assess the association between alcohol and risk of lung cancer in never smokers.Methods: After a literature search in Medline, we included all case-control and cohort studies published up to January 2010 that reported an estimate of the association between alcohol intake and lung cancer risk in never smokers.Results: We selected 10 articles, including 1913 never smoker lung cancer cases. The random-effects pooled relative risk (RR) for drinkers versus nondrinkers was 1.21 [95% confidence interval (CI) 0.95-1.55]. The same figure was 1.05 (95% CI 0.89-1.23) after the exclusion of one outlier study. At the dose-response analysis, RR for an increase in alcohol intake of 10 g/day was 1.01 (95% CI 0.92-1.10).Conclusions: Alcohol consumption was not associated with lung cancer risk in never smokers. Even if the synergistic effect of smoking and alcohol cannot be ruled out, our results suggest that alcohol does not play an independent role in lung cancer etiology. © The Author 2011. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Background: The International Agency for Research on Cancer (IARC) concluded that alcohol consumption is related to colorectal cancer (CRC). However, several issues remain unresolved, including quantification of the association for light (=1 drink/day) and moderate (2-3 drinks/day) alcohol drinking, investigation of the dose-response relationship, and potential heterogeneity of effects by sex, colorectal site, and geographical region. Methods: Twenty-seven cohort and 34 case-control studies presenting results for at least three categories of alcohol intake were identified from a PubMed search of articles published before May 2010. The summary relative risks (RRs) were estimated by the random effects model. Second-order fractional polynomials and random effects metaregression models were used for modeling the dose-risk relation. Results: The RRs were 1.21 [95% confidence interval (CI) 1.13-1.28] for moderate and 1.52 (95% CI 1.27-1.81) for heavy (=4 drinks/day) alcohol drinking. The RR for moderate drinkers, compared with non-/occasional drinkers, was stronger for men (RR = 1.24, 95% CI 1.13-1.37) than for women (RR = 1.08, 95% CI 1.03-1.13; Pheterogeneity = 0.02). For heavy drinkers, the association was stronger in Asian studies (RR = 1.81, 95% CI 1.33-2.46; Pheterogeneity = 0.04). The dose-risk analysis estimated RRs of 1.07 (95% CI 1.04-1.10), 1.38 (95% CI 1.28-1.50), and 1.82 (95% CI 1.41-2.35) for 10, 50, and 100 g/day of alcohol, respectively. Conclusions: This meta-analysis provides strong evidence for an association between alcohol drinking of >1 drink/day and colorectal cancer risk. © The Author 2011. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Quantification of the association between alcohol drinking and risk of esophageal squamous cell carcinoma (ESCC) is an open issue, particularly among light alcohol drinkers, never-smokers, and Asian populations, in which some high-risk polymorphisms in alcohol metabolizing genes are more prevalent. To address these issues, we conducted a systematic review and meta-analysis using 40 case-control and 13 cohort studies that reported on the risk associated with alcohol drinking for at least three levels of consumption. In studies adjusted for age, sex, and tobacco smoking, the relative risk (RR) and 95% confidence interval (CI) for the association between light alcohol drinking (=12.5 g/d) and risk of ESCC was 1.38 (1.14-1.67). The association was slightly stronger in Asian countries than in other populations. The adjusted RRs (95% CIs) were 2.62 (2.07-3.31) for moderate drinking (>12.5->50 g/d) and 5.54 (3.92-7.28) for high alcohol intake (=50 g/d); the RRs were slightly higher in non-Asian populations. In prospective studies, the RR (95% CI) was 1.35 (0.92-1.98) for light, 2.15 (1.55-2.98) for moderate, and 3.35 (2.06-5.46) for high alcohol intakes; light drinking showed an association with ESCC in Asia (five studies) but not in other regions (three studies). Among never-smokers (nine studies), the RR (95% CI) was 0.74 (0.47-1.16) for light, 1.54 (1.09-2.17) for moderate, and 3.09 (1.75-5.46) for high intakes. This meta-analysis further corroborates the association of moderate and high alcohol intake with risk of ESCC and provides risk estimates based on multiple prospective studies. Light alcohol intake appears to be associated to ESCC mainly in studies in Asia, which suggests a possible role of genetic susceptibility factors. © 2011 UICC.

The association between alcohol and leukemia risk has been addressed in several studies in the past two decades, but results have been inconsistent. Therefore, we conducted a systematic review and meta-analysis to quantify the dose-risk relation. Through the literature search up to August 2013, we identified 18 studies, 10 case-control and 8 cohorts, carried out in a total of 7142 leukemia cases. We derived pooled meta-analytic estimates using random-effects models, taking into account the correlation between estimates, and we performed a dose-risk analysis using a class of nonlinear random-effects meta-regression models. Stratified analyses were carried out on leukemia subtypes and groups, in order to identify possible etiologic differences. Compared with nondrinkers, the relative risks (RRs) for all leukemia were 0.94 [95% confidence interval (CI), 0.85-1.03], 0.90 (95% CI, 0.80-1.01) and 0.91 (95% CI, 0.81-1.02) for any, light (=1 drink/day) and moderate to heavy (>1 drink/day) alcohol drinking, respectively. The summary RRs for any alcohol drinking were 1.47 (95% CI, 0.47-4.62) for acute lymphoblastic leukemia, 0.94 (95% CI 0.77-1.15) for chronic lymphocytic leukemia, 1.02 (95% CI, 0.86-1.21) for acute myeloid leukemia and 0.93 (95% CI 0.75-1.14) for chronic myeloid leukemia. The subgroup analysis on geographical area for all leukemia combined showed RRs of 0.84 (95% CI, 0.76-0.93), 0.92 (95% CI, 0.83-1.01) and 1.32 (95% CI, 1.02-1.70) for studies conducted in America, Europe and Asia, respectively. We did not find an increased risk of leukemia among alcohol drinkers. If any, a modest favorable effect emerged for light alcohol drinking, with a model-based risk reduction of approximately 10% in regular drinkers. © 2014 Elsevier Ltd.

The role of alcohol intake in the risk for multiple myeloma (MM) is unclear, although some recent findings suggest an inverse relationship. To summarize the information on the topic, we carried out a systematic review and a dose-risk meta-analysis of published data. Through the literature search until August 2013, we identified 18 studies, eight case-control and 10 cohort studies, carried out in a total of 5694 MM patients. We derived pooled meta-analytic estimates using random-effects models, taking into account the correlation between estimates, and we carried out a dose-risk analysis using a class of nonlinear random-effects meta-regression models. The relative risk for alcohol drinkers versus non/occasional drinkers was 0.97 [95% confidence interval (CI), 0.85-1.10] overall, 0.96 (95% CI, 0.74-1.24) among case-control studies, and 1.00 (95% CI, 0.89-1.13) among cohort studies. Compared with nondrinkers, the pooled relative risks were 0.96 (95% CI, 0.81-1.13) for light (i.e. ≤1 drink/day) and 0.89 (95% CI, 0.74-1.07) for moderate-to-heavy (i.e. >1 drink/day) alcohol drinkers. The dose-risk analysis revealed a model-based MM risk reduction of about 15% at two to four drinks/day (i.e. 25-50 g of ethanol). The present meta-analysis of published data found no strong association between alcohol drinking and MM risk, although a modest favorable effect emerged for moderate-to-heavy alcohol drinkers. © 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins.

Background: There is convincing evidence that alcohol consumption increases the risk of cancer of the colorectum, breast, larynx, liver, esophagus, oral cavity and pharynx. Most of the data derive from studies that focused on the effect of moderate/high alcohol intakes, while little is known about light alcohol drinking (up to 1 drink/day). Patients and methods: We evaluated the association between light drinking and cancer of the colorectum, breast, larynx, liver, esophagus, oral cavity and pharynx, through a meta-analytic approach. We searched epidemiological studies using PubMed, ISI Web of Science and EMBASE, published before December 2010. Results: We included 222 articles comprising ~92 000 light drinkers and 60 000 non-drinkers with cancer. Light drinking was associated with the risk of oropharyngeal cancer [relative risk, RR = 1.17; 95% confidence interval (CI) 1.06-1.29], esophageal squamous cell carcinoma (SCC) (RR = 1.30; 95% CI 1.09-1.56) and female breast cancer (RR = 1.05; 95% CI 1.02-1.08). We estimated that ~5000 deaths from oropharyngeal cancer, 24 000 from esophageal SCC and 5000 from breast cancer were attributable to light drinking in 2004 worldwide. No association was found for colorectum, liver and larynx tumors. Conclusions: Light drinking increases the risk of cancer of oral cavity and pharynx, esophagus and female breast. © The Author 2012. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Background Postmastectomy radiotherapy (PMRT) with TomoHelical™ (TH) or TomoDirect™ (TD) allows a uniform target coverage. In this study, we compare treatment plans using TD and TH in the setting of hypofractionated PMRT and immediate breast reconstruction. Material and methods The TD-treatment plans of breast cancer patients treated between May 2016 and August 2019 were retrospectively selected. All the TD plans were re-planned on TH with the same prescription dose (40.05 Gy/15 fractions) and according to our dose/volume constraints. Data about the 2 treatment plans were compared with a focus on PTV coverage and all the organs at risk (OARs) constraints. Results Fifty patients for a total number of 100 treatment plans (50 with TD and 50 re-planned with TH) were analyzed. All the median value in the TD PTV CHEST WALL plans fulfilled the predefined planning objectives, even though TH emerged as best for target coverage with statistically significant difference for V90%. TD provided the lowest V95% for the PTV SVC, but the median value was near to the recommended value of 90% (89.8 % vs 98.6% for TD and TH, respectively). Overall, TD reached the best OARs sparing. The main statistically significant differences with TH were for contralateral breast, ipsilateral and contralateral lung. All the other dose values for TH were higher than TD, but they fulfilled the recommended/acceptable predefined planning objectives. Conclusions In the setting of PMRT, TD compared to TH reached an acceptable target volume coverage, with an optimal sparing of OARs.

Objective: In order to provide an updated quantification of the association between alcohol drinking and epithelial ovarian cancer risk, we conducted a meta-analysis of published observational studies. Methods: Using PubMed, we performed a literature search of all case-control and cohort studies published as original articles in English up to September 2011. We included 27 observational studies, of which 23 were case-control studies, 3 cohort studies and one pooled analysis of prospective cohort studies, including a total of 16,554 epithelial ovarian cancer cases. We derived pooled meta-analytic estimates using random-effects models. Results: The pooled relative risk (RR) for any alcohol drinking compared with non/occasional drinking was 1.00 [95% confidence interval (CI), 0.95-1.05]. The RRs were 0.97 (95% CI, 0.92-1.02), 1.03 (95% CI, 0.96-1.11) and 1.09 (95% CI, 0.80-1.50) for light (= 1 drink/day), moderate (> 1 to < 3 drinks) and heavy drinking (= 3 drinks/day), respectively. In particular, the pooled RR for invasive epithelial ovarian cancers was 1.00 (95% CI, 0.95-1.06), while for borderline cancers was 0.96 (95% CI, 0.74-1.26). Stratified analyses across cancer histotypes revealed a modest protective effect of alcohol on endometrioid epithelial ovarian tumors (RR = 0.82, 95% CI, 0.70-0.96), while no association was found for serous (RR = 1.00, 95% CI, 0.84-1.19), mucinous (RR = 0.91, 95% CI, 0.78-1.08) and clear cell (RR = 0.93, 95% CI, 0.76-1.14) cancers. There was no evidence of publication bias. Conclusions: This comprehensive meta-analysis provided no evidence of a material association between alcohol drinking and epithelial ovarian cancer risk. © 2012 Elsevier Inc. All rights reserved.

Inconsistent results on the relationship between alcohol drinking and prostate cancer have been found. In order to provide a definite quantification of the dose-risk relation, we investigated the risk of prostate cancer at different levels of alcohol consumption, by conducting a meta-analysis of epidemiological studies. We performed a literature search using PubMed of all case-control and cohort studies published as original articles in English up to December 2010. We identified 50 case-control and 22 cohort studies, including a total of 52 899 prostate cancer cases. We derived pooled meta-analytic estimates using random-effects models, taking into account the correlation between estimates. We performed a dose-risk analysis using nonlinear random-effects meta-regression models. The overall relative risk for any alcohol drinking compared with non/occasional drinking was 1.06 [95% confidence interval (CI), 1.01-1.10]. The relative risks were 1.05 (95% CI, 1.02-1.08), 1.06 (95% CI, 1.01-1.11), and 1.08 (95% CI, 0.97-1.20) for light (=1 drink/day), moderate (>1 to

Tramacere, I Negri, E Pelucchi, C Bagnardi, V Rota, M Scotti, L Islami, F Corrao, G La Vecchia, C Boffetta, P eng Meta-Analysis Research Support, Non-U.S. Gov't England 2011/05/04 06:00 Ann Oncol. 2012 Jan;23(1):28-36. doi: 10.1093/annonc/mdr135. Epub 2011 May 2.; International audience; BACKGROUND: Whether an association between alcohol drinking and gastric cancer risk exists is an open question. In order to provide a definite quantification of the association between alcohol drinking and gastric cancer risk, we conducted a meta-analysis of available data. PATIENTS AND METHODS: We carried out a PubMed search of articles published up to June 2010 and identified 44 case-control and 15 cohort studies, including a total of 34 557 gastric cancer cases. We derived meta-analytic estimates using random-effects models, taking into account correlation between estimates. We carried out a dose-risk analysis using nonlinear random-effects meta-regression models. RESULTS: Compared with nondrinkers, the pooled relative risk (RR) was 1.07 [95% confidence interval (CI) 1.01-1.13] for alcohol drinkers and 1.20 (95% CI 1.01-1.44) for heavy alcohol drinkers (>/=4 drinks per day). The pooled estimates were apparently higher for gastric noncardia (RR for heavy drinkers=1.17, 95% CI 0.78-1.75) than for gastric cardia (RR=0.99, 95% CI 0.67-1.47) adenocarcinoma. The dose-risk model estimated a RR of 0.95 (95% CI 0.91-0.99) for 10 g/day and 1.14 (95% CI 1.08-1.21) for 50 g/day. CONCLUSIONS: This meta-analysis provides definite evidence of a lack of association between moderate alcohol drinking and gastric cancer risk. There was, however, a positive association with heavy alcohol drinking.

Alcohol drinking is a known risk factor for laryngeal cancer. However, little information is available on the risk associated with light alcohol drinking. To address this issue, we conducted a meta-analysis using two methods: (i) random-effects models with reconstruction of alcohol consumption categories and calculation of risk estimates associated with predefined consumption levels using Hamling method and (ii) random-effects meta-regression models. The PubMed database was searched for all case-control or cohort studies published in the English language on the association between alcohol consumption and risk of laryngeal cancer. Forty studies (38 case-control, 2 cohort) reporting on at least three levels of consumption were included. Overall, alcohol drinking versus non-drinking was associated with an approximately 2-fold increase in risk of laryngeal cancer (RR = 1.90; 95% CI: 1.59-2.28). While light alcohol drinking (=1 drink/day) did not show any significant association with risk of laryngeal cancer (12 studies. RR = 0.88; 95% CI: 0.71-1.08), moderate drinking (>1 to

Oral and pharyngeal cancers are strongly related to alcohol drinking. We combined findings from all case-control and cohort studies published up to September 2009 and presented analyses by subsites, using a meta-analytic approach. Summary measures were obtained using random-effects models, and taking into account the correlation between estimates from the same study. We also performed a dose-risk analysis, using a random-effects meta-regression model. Compared to non- or occasional drinkers, the overall relative risks (RR) for light drinkers were 1.17 (95% confidence interval, CI, 1.01-1.35) for oral (nine studies) and 1.23 (95% CI, 0.87-1.73) for pharyngeal (five studies) cancer, with no significant heterogeneity between the two sites (p = 0.793). RRs for heavy drinkers were 4.64 (95% CI, 3.78-5.70) for oral (17 studies) and 6.62 (95% CI, 4.72-9.29) for pharyngeal (17 studies) cancer (p of heterogeneity between the two sites = 0.075). The summary RRs for heavy drinkers were 4.11 (95% CI, 2.46-6.87) for tongue (five studies), 7.76 (95% CI, 4.77-12.62) for oropharyngeal (four studies), and 9.03 (95% CI, 4.46-18.27) for hypopharyngeal (four studies) cancer. In conclusion, the alcohol-related RRs are higher for pharyngeal than for oral cancer, particularly at higher doses, while the association with cancer of the tongue was similar to that for oral cancer. © 2010 Elsevier Ltd. All rights reserved.

Background Specific data regarding coronavirus disease 2019 (COVID-19) in patients with neuroendocrine neoplasms (NENs) are lacking. The aim of this study is to describe the characteristics of patients with NENs who tested severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive. Material and methods This is a worldwide study collecting cases of patients with NENs along with a positive nasopharyngeal swab reverse transcriptase-polymerase chain reaction (RT-PCR) test for SARS-CoV-2 between June 1, 2020, and March 31, 2021. Centres treating patients with NENs were directly contacted by the principal investigator. Patients with NENs of any primary site, grade and stage were included, excluding small-cell lung carcinoma and mixed adenoneuroendocrine carcinoma. Results Among 81 centres directly contacted, 88.8% responded and 48.6% of them declined due to lack of cases or interest. On March 31st, 2021, eight recruiting centres enrolled 89 patients. The median age was 64 years at the time of COVID-19 diagnosis. Most patients had metastatic, non-functioning, low-/intermediate-grade gastroenteropancreatic NENs on treatment with somatostatin analogues and radioligand therapy. Most of them had comorbidities. Only 8% of patients had high-grade NENs and 12% were receiving chemotherapy. Most patients had symptoms or signs of COVID-19, mainly fever and cough. Only 3 patients underwent sub-intensive treatment, whereas most of them received medical therapies, mostly antibiotics. In two third of cases, no changes occurred for the anti-NEN therapy. More than 80% of patients completely recovered without sequelae, whereas 7.8% patients died due to COVID-19. Conclusions Patients included in this study reflect the typical NEN population regardless of SARS-CoV-2. In most cases, they overcome COVID-19 without need of intensive care, short-term sequelae and discontinuation of systemic oncological therapy.

Introduction The aim of this study was to provide the most comprehensive and up-to-date evidence on the association between cigarette smoking and colorectal cancer (CRC) risk. Methods We conducted a systematic review and meta-analysis of epidemiological studies on the association between cigarette smoking and CRC risk published up to September 2018. We calculated relative risk (RR) of CRC according to smoking status, intensity, duration, pack-years, and time since quitting, with a focus on molecular subtypes of CRC. Results The meta-analysis summarizes the evidence from 188 original studies. Compared with never smokers, the pooled RR for CRC was 1.14 (95% confidence interval [CI] 1.10-1.18) for current smokers and 1.17 (95% CI 1.15-1.20) for former smokers. CRC risk increased linearly with smoking intensity and duration. Former smokers who had quit smoking for more than 25 years had significantly decreased risk of CRC compared with current smokers. Smoking was strongly associated with the risk of CRC, characterized by high CpG island methylator phenotype (RR 1.42; 95% CI 1.20-1.67; number of studies [n] = 4), BRAF mutation (RR 1.63; 95% CI 1.23-2.16; n = 4), or high microsatellite instability (RR 1.56; 95% CI 1.32-1.85; n = 8), but not characterized by KRAS (RR 1.04; 95% CI 0.90-1.20; n = 5) or TP53 (RR 1.13; 95% CI 0.99-1.29; n = 5) mutations. Discussion Cigarette smoking increases the risk of CRC in a dose-dependent manner with intensity and duration, and quitting smoking reduces CRC risk. Smoking greatly increases the risk of CRC that develops through the microsatellite instability pathway, characterized by microsatellite instability-high, CpG island methylator phenotype positive, and BRAF mutation.

The purpose of this study is the evaluation of clinical and surgical impact of the Z0011 trial criteria on the management of breast cancer (BC) patients undergoing breast conservative surgery (BCS) at the European Institute of Oncology (IEO). We studied 1386 patients who underwent BCS and sentinel lymph node biopsy (SLNB) from July 2016 to July 2018. Clinical evaluation, breast ultrasound, mammogram, and cyto/histological examination were performed for all patients at the time of diagnosis. Frozen sections of the sentinel lymph node (SLN) were not performed for any patient. Patients who underwent neo-adjuvant therapy were excluded. To evaluate the results before and after the introduction of Z0011 criteria, a group of 1425 patients with the same characteristics who underwent BCS and SLNB from July 2013 to July 2015 were analyzed. We studied the characteristics of the patients by nodal status, and we observed that T stage, tumor grade, and lymphovascular invasion were statistically related with the highest rate of positive SLN. Of the 1386 patients who underwent surgery after the introduction of the Z011 trial, 1156 patients (83.4%) had negative SLN, 230 patients (16.6%) had positive SLN. Subsequent axillary lymph node dissection (ALND) was performed in only 7 cases (3.0%). Of the 1425 patients operated before the introduction of the Z0011 trial, 216 patients had subsequent ALND (15%). The reduction in the number of ALND performed after the introduction of Z0011 is statistically significant, and this could result in a remarkable reduction of the comorbidities of our patients.

Objectives: To develop a novel nomogram to identify candidates for active surveillance (AS) that combines clinical, biopsy and multiparametric magnetic resonance imaging (mpMRI) findings; and to compare its predictive accuracy to, respectively: (i) Prostate Cancer Research International: Active Surveillance (PRIAS) criteria, (ii) Johns Hopkins (JH) criteria, (iii) European Association of Urology (EAU) low-risk classification, and (iv) EAU low-risk or low-volume with International Society of Urological Pathology (ISUP) Grade Group (GG) 2 classification. Patients and Methods: We selected 1837 patients with ISUP GG1 or GG2 prostate cancer (PCa), treated with radical prostatectomy (RP) between 2012 and 2018. The outcome of interest was the presence of unfavourable disease (i.e., clinically significant PCa [csPCa]) at RP, defined as: ISUP GG (Formula presented.) 3 and/or pathological T stage (pT) ≥3a and/or pathological N stage (pN) 1. First, logistic regression models including PRIAS, JH, EAU low-risk, and EAU low-risk or low-volume ISUP GG2 binary classifications (not eligible vs eligible) were used. Second, a multivariable logistic regression model including age, prostate-specific antigen density (PSA-D), ISUP GG, and the percentage of positive cores (Model 1) was fitted. Third, Prostate Imaging-Reporting and Data System (PI-RADS) score (Model 2), extracapsular extension (ECE) score (Model 3) and PI-RADS + ECE score (Model 4) were added to Model 1. Only variables associated with higher csPCa rates in Model 4 were retained in the final simplified Model 5. The area under the receiver operating characteristic curve (AUC), calibration plots and decision curve analyses were used. Results: Of the 1837 patients, 775 (42.2%) had csPCa at RP. Overall, 837 (47.5%), 986 (53.7%), 348 (18.9%), and 209 (11.4%) patients were eligible for AS according to, respectively, the EAU low-risk, EAU low-risk or low-volume ISUP GG2, PRIAS, and JH criteria. The proportion of csPCa amongst the EAU low-risk, EAU low-risk or low-volume ISUP GG2, PRIAS and JH candidates was, respectively 28.5%, 29.3%, 25.6% and 17.2%. Model 4 and Model 5 (in which only PSA-D, ISUP GG, PI-RADS and ECE score were retained) had a greater AUC (0.84), compared to the four proposed AS criteria (all P&nbsp

Background The latest National Comprehensive Cancer Network Breast Cancer Guidelines still discourage repeat sentinel node biopsy (SNB) after mastectomy, and the largest multicentric study available reports only 35 cases in the absence of previous axillary dissection (AD). Methods From January 2003 to November 2018, 89 patients of the European Institute of Oncology with local recurrence of breast cancer after mastectomy, free of distant metastases, with a clinically negative axilla and a negative axillary ultrasound, in absence of AD, underwent lymphatic mapping before wide local excision. Results During surgery, SNB was successful for 99% of the patients, with 14% being metastatic. Additional metastatic nodes removed by AD after a positive sentinel node occurred in 82% of cases. After a medium follow-up period of 3.7 years, the overall survival rate was 96.7%, and the disease-free survival rate was 84.4%. No axillary relapse after AD was recorded. One patient who refused human epidermal growth factor receptor 2 (HER2)-targeted treatment experienced ipsilateral axillary recurrence after a negative repeat SNB. The first axillary level was never directly irradiated because all the patients with positive repeat SNB underwent AD. For invasive luminal-like HER2-negative recurrences, the metastatic sentinel node was significantly associated with the choice to prescribe adjuvant chemotherapy (p = 0.003). Conclusions In specialized centers, repeat axillary SNB for patients with local recurrence after mastectomy in the absence of previous AD can represent a safe option for detection and removal of occult axillary disease that would otherwise not be excised/irradiated to achieve better local control and could possibly influence the choice of adjuvant treatments.

Purpose: Grade 3 neuroendocrine tumor (NET G3) is a novel pathologic category within gastro-entero-pancreatic (GEP) neuroendocrine neoplasms (NENs) but its clinical behavior and therapeutic management still remain challenging. Prognostic and predictive factors aiding NET G3 management are needed. Patients and methods: We performed a retrospective analysis from 2015 to 2020 of all patients with > 20% Ki-67, well-differentiated NETs evaluated within our NEN-dedicated multidisciplinary team. We divided the sample according the timing of NET G3 diagnosis, the radiotracers distribution and Ki-67. We analyzed the correlation between these NET G3 features and clinical outcomes. Results: Among 3238 multidisciplinary discussion reports, we selected 55 patients, 48 from GEP and 7 from an occult GEP origin. In 45 patients, NET G3 diagnosis occurred at the beginning of clinical history (upfront-NET G3), whereas in 10, during the NET G1-G2 clinical history (late-NET G3). Patients with ≤ 30% (34/55) vs. > 30% Ki-67 (21/55) had a better overall survival (OS) (p = 0.042); patients with a homogeneous vs. inhomogeneous/negative 68Gallium(68Ga)-DOTA-Peptide Positron Emission Tomography (PET)/computed tomography (CT) showed a trend to a better OS, and a significant better progression-free survival (PFS) (p = 0.033). A better OS was observed for negative/inhomogeneous vs. homogeneous 18-fluorodeoxyglucose (18FDG)-PET/CT (p = 0.027). A trend to a better OS was reported in late- vs. upfront-NET G3, while the latter showed a significantly better response rate (RR) (p = 0.048). Conclusion: Our findings suggested that Ki-67 cutoff, functional imaging and the timing to NET G3 diagnosis may help clinicians in more accurate selection of NET G3 management. Prospective studies are needed.

Objectives Bleomycin, etoposide, and cisplatin (BEP) is the most common and successful chemotherapy regimen for germ-cell tumor (GCT) patients, accompanied by a bleomycin-induced dose-dependent lung toxicity in certain patients. In an attempt to reduce bleomycin-toxicity, we developed a modified-BEP (mBEP) regimen. Materials and methods Between August 2008 and February 2018, 182 unselected mainly testicular GCT patients (39 with adjuvant purpose and 143 with curative purpose) received a tri-weekly 5-day hospitalization schedule with bleomycin 15 U intravenous (IV) push on day 1 and 10 U IV continuous infusion over 12 hours on days 1 to 3, cisplatin 20 mg/m IV, and etoposide 100 mg/m IV on days 1 to 5. Pulmonary toxicity was assessed through chest computed tomography scan and clinical monitoring. Results Median number of mBEP cycles was 3 (range: 1 to 4). In the curative setting, according to the International Germ Cell Cancer Collaborative Group (IGCCCG) prognostic system, 112, 21, and 9 patients had good-risk, intermediate-risk, and poor-risk class, respectively; 66 (46%) patients had complete response (CR), 67 (47%) had partial response (52 of whom became CR afterwards), 6 (4%) had stable disease (that in 3 became CR afterwards), 3 (2%) progressed, and 1 (1%) died of brain stroke. At a median follow-up of 2.67 years (interquartile range: 1.23-5.00 y), 1 and 5-year overall survival and progression-free survival were 99% and 95%, and 90% and 88%, respectively. In the entire patient population, there was grade 3/4 neutropenia in 92 patients (51%), febrile neutropenia in 11 patients (6%), grade 1/2 nausea in 74 patients (41%), and no death due to pulmonary toxicity. Conclusion In GCT patients, our mBEP-schedule would suggest an effective treatment modality without suffering meaningful pulmonary toxicity.

Objectives Tumor-associated antigens (TAAs) are frequently overexpressed in several cancer types. The aim of this study was to investigate the expression of TAAs in breast cancer. Material and methods A total of 250 selected invasive breast cancers including 50 estrogen receptor (ER)-positive (Luminal B like), 50 triple-negative (TN), 50 ER-positive lobular type, 50 ER- and progesterone receptor (PgR)-positive (Luminal A like) and 50 cerbB2-positive breast cancers, were assessed for New York esophageal squamous cell carcinoma-1 (NY-ESO-1), Wilms tumor antigen (WT-1) and PReferentially expressed Antigen of MElanoma (PRAME) antigen expression by immunohistochemistry (IHC). Results A significantly higher expression of cancer testis (CT)-antigens NY-ESO-1 and WT-1 antigen was detected in TN breast cancers compared with ER-positive tumors. NY-ESO-1 overexpression (score 2 + and 3+) assessed by monoclonal and polyclonal antibodies was detected in 9 (18%) TN cancers as compared to 2 (4%) ER-positive tumors (p = 0.002). WT1 over-expression (score 2 + and 3+) was confirmed in 27 (54%) TN tumor samples as compared to 6 (12%) ER-positive (p, Highlights • Tumor-associated antigens are frequently overexpressed in several cancer types, being also associated with poorer patients’ survival outcomes. • Our study confirmed that NY-ESO-1 and WT1 antigens are higher expressed in triple-negative than in other breast cancer subtypes. • Given the limited therapeutic options for triple-negative breast cancer patients, the assessment of WT1 and NY-ESO-1 antigens expression in breast cancer tissue at surgery may allow to identify patients potentially candidate to adjuvant peptide vaccines, alone or in combination with other systemic therapies.

Background: Limited evidence is available on effectiveness of clinicoradiological follow-up of early-stage NSCLC patients. MAGRIT was a phase III adjuvant RCT conducted in surgically resected stage IB-IIIA NSCLC patients, in which all participants had a prospectively defined intensive clinicoradiological follow-up. Methods: At patient-level data, we analyzed detection modality of disease recurrences and new primary lung cancer (i.e. detected by clinicoradiological scheduled exams versus by interim unscheduled exams), features associated with higher risk of locoregional and/or distant recurrence, and recurrence rates over time. Results: In the 2261 patients studied, there was a significant association between the type of recurrence and the modality of detection: 88.4% (95% CI, 84%–91%) of the locoregional recurrences and 93.2% (95% CI, 84%–99%) of the new primary lung cancers were detected by scheduled exams, whereas this was only 68.7% (95% CI, 65%–73%) for distant metastases (p < 0.001). Survival of patients with locoregional recurrence or new primary lung cancer detected by scheduled exams was significantly better as compared with those detected by unscheduled exams (HR 0.56, 95% CI 0.36–0.87; p = 0.01). Survival was similarly poor in patients with distant recurrences, both with scheduled and unscheduled detection (3-year survival after recurrence 22.0% and 21.8%, respectively). Recurrence rate was the highest in the first 18 months after surgery—with a peak between month 6 and 12—decreasing thereafter. The hazard of a second primary lung cancer was constant over time. Conclusion: Intensive follow-up is effective in detecting locoregional recurrences and second primary lung cancers, with impact on patients’ survival but did not influence the detection of distant recurrences.

Background: To assess the clinical usefulness of serum tumor markers for early detection of distant breast cancer recurrence using FDG-PET/CT. Methods: We retrospectively analyzed 561 consecutive patients who underwent surgery for invasive primary breast cancer and had increased tumor markers (CA 15-3 and CEA) after completion of locoregional therapy. FDG-PET/CT data were reviewed for all cases. CA 15-3 and CEA were evaluated both in a continuous and in a quartile (Q) distribution. The Wilcoxon rank-sum test and logistic regression models were used to evaluate the association between increased tumor marker values and the presence (and type) of distant metastases. Results: The median value of CA 15-3 was 35.0 U/mL (IQR, 29.5–43.0) in cases where no distant metastases were detected, and it was 58.9 U/mL (IQR, 40.0–108.0) in cases where metastases were detected (p < 0.001). The median value of CEA was 6.6 U/mL (IQR, 4.4–10.0) in cases of no metastases and 12.4 U/mL (IQR, 6.9–30.0) in cases of metastases (p < 0.001). Increased levels of both tumor markers (Q3 and Q4) were strongly associated with the presence of distant metastases. The association between CA 15-3 and bone/liver metastases was stronger compared with other types of metastases (p heterogeneity between odds ratios [ORs] = 0.03 for Q3 and Conclusion: Increased tumor marker levels detected in asymptomatic breast cancer patients during adjuvant therapies and follow-up are significantly predictive of distant metastases identified on FDG-PET/CT.

Obesity correlates with hematologic malignancies including leukemias, but risk of specific leukemia subtypes like acute promyelocytic leukemia and underlying molecular mechanisms are poorly understood. We explored multiple datasets for correlation between leukemia, body mass index (BMI) and molecular features. In a population-based study (n=5.2 million), we correlated BMI with promyelocytic leukemia, and other acute myeloid, lymphoid or other leukemias. In cross-sectional studies, we tested BMI deviation in promyelocytic leukemia trial cohorts from that expected based on national surveys. We explored The Cancer Genome Atlas for transcriptional signatures and mutations enriched in promyelocytic leukemia and/or obesity, and confirmed a correlation between body mass and FLT3 mutations in promyelocytic leukemia cohorts by logistic regression. In the population-based study, hazard ratio per 5 kg/m2 increase was: promyelocytic leukemia 1.44 (95%CI: 1.0-2.08), non-promyelocytic acute myeloid leukemias 1.17 (95%CI: 1.10-1.26), lymphoid leukemias 1.04 (95%CI: 1.0-1.09), other 1.10 (95%CI: 1.04-1.15). In cross-sectional studies, body mass deviated significantly from that expected (Italy: P

Background: The aim of this work is to evaluate pattern of care and clinical outcome in a large series of patients with in-breast recurrence (IBR), after quadrantectomy and intraoperative radiation therapy with electrons (IOERT) as partial breast irradiation. Patients and Methods: Patients with IBR after IOERT, treated with salvage surgery ± adjuvant reirradiation (re-RT), were selected from a multiinstitution database. Disease-free survival (DFS), overall survival (OS), cumulative incidence of second IBR, and distant metastases (DM) were estimated. Results: A total of 224/267 patients from seven institutions were included. Primary tumors received 21 Gy. Median time to first IBR was 4.3 years (range 2.6–6.1 years). Salvage mastectomy and repeat quadrantectomy were performed in 135 (60.3%) and 89 (39.7%) patients, followed by adjuvant re-RT in 21/135 (15.5%) and 63/89 (70.8%), respectively. Median follow-up after salvage treatment was 4.1 years. Overall, 5- and 8-year outcomes were as follows: cumulative incidence of second IBR: 8.4% and 14.8%; cumulative incidence of DM: 17.1% and 22.5%; DFS: 67.4% and 52.5%; OS: 89.3% and 74.7%. The risk of second IBR was similar in the salvage mastectomy and repeat quadrantectomy + RT groups [hazard ratio (HR) 1.41, p = 0.566], while salvage mastectomy patients had greater risk of DM (HR 3.15, p = 0.019), as well as poorer DFS (HR 2.13, p = 0.016) and a trend towards worse OS (HR 3.27, p = 0.059). Patients who underwent repeat quadrantectomy alone had worse outcomes (second IBR, HR 5.63, p = 0.006; DFS, HR 3.21, p = 0.003; OS, HR 4.38, p = 0.044) than those adding re-RT. Conclusions: Repeat quadrantectomy + RT represents an effective salvage approach and achieved local control comparable to that of salvage mastectomy.

Objectives Most research addressing needs and concerns of young patients with breast cancer (≤40 years) is retrospective. The HOHO European protocol is a prospective multicenter cohort study of young women with newly diagnosed breast cancer, about fertility, psychosocial and quality of life concerns. Here we report the baseline data and focus on predictors of fertility concerns. Materials and methods Patient surveys and medical record review were used. The baseline survey included sociodemographic, medical and treatment data as well as questions on fertility concerns and preservation strategies. Subscales from the CAncer Rehabilitation Evaluation System-Short Form (CARES-SF) were administered to measure specific quality of life aspects. Uni- and multivariable modeling were used to investigate predictors of greater fertility concern. Results Among 297 eligible respondents, 67% discussed fertility issues before starting therapy, 64% were concerned about becoming infertile after treatment, and 15% decided not to follow prescribed therapies. Fifty-four percent of women wished future children before diagnosis; of these, 71% still desired biologic children afterwards. In multivariable analysis, not having children was the only patient characteristic significantly associated with fertility concerns at diagnosis. Twenty-seven percent used fertility preservation strategies. Women who received chemotherapy reported greater physical (p = 0.021) and sexual difficulties (p = 0.039) than women who did not. Women who were married or had a partner reported less psychosocial problems than single women (p = 0.039). Conclusions Young women with newly diagnosed breast cancer have several concerns, including, but not limited to, fertility. The HOHO European study provides valuable information to develop targeted interventions.

Neoadjuvant chemotherapy (NAC) significantly improved the prognosis of patients with locally advanced resectable gastric cancer but, despite important progresses, relapse-related death remains a major challenge. Therefore, it appears crucial to understand which patients will benefit from peri-operative treatment. Biomarkers such as human epidermal growth factor receptor-2 (HER2), microsatellite instability (MSI), and Epstein-Barr Virus (EBV) have been widely studied; however, they do not yet guide the choice of perioperative treatment in clinical practice. We performed a narrative review, including 23 studies, addressing the value of tissue- or blood-based biomarkers in the neoadjuvant setting. Ten studies (43.5%) were prospective, and more than half were conducted in East-Asia. Biomarkers were evaluated only post-NAC (on surgical samples or blood) in seven studies (30.4%), only pre-NAC (on endoscopic specimens or blood) in 10 studies (43.5%), and both pre- and post-NAC (26.1%) in six studies. Among the high variety of investigated biomarkers, some of these including MSI-H or enzymatic profile (as TS, UGT1A1, MTHFR, ERCC or XRCC) showed promising results and deserve to be assessed in methodologically sound clinical trials. The identification of molecular biomarkers in patients treated with NAC for locally advanced resectable gastric or EGJ cancer remains crucial.

Objective Metronomic chemotherapy is a treatment option for metastatic breast cancer (MBC) patients who require prolonged disease control without cumulative toxicity. Data available on the efficacy and tolerability of prolonged usage of metronomic therapy are limited. Methods We analyzed patients with MBC, enrolled in a clinical trial, who obtained a prolonged clinical benefit for a duration of at least 12 months with vinorelbine 30 or 40 mg orally three times a week, cyclophosphamide 50 mg daily and capecitabine 500 mg three times a day (VEX regimen). The patients were treated at the European Institute of Oncology, Milan. Results We identified 67 MBC patients. The median age before starting the VEX regimen was 53 years. There were 59 patients (88%) who had hormone-receptors positive and HER2 negative BC. We had 37 patients who received VEX as the first-line treatment for MBC, while 30 patients were pretreated. The objective response rate was 49% (95% CI, 37-62). The median duration of VEX treatment after the first year was 14 months (min-max range 0.3-81.3 months). The progression-free survival at 3 years was 25.4% (95% CI, 15.7-36.2) and at 4 years was 18.5% (95% CI, 10.1-28.8 time 0 corresponds to 1 year after starting VEX). A total of 25 patients required a dose reduction, 7% of patients experienced G3 hand and foot syndrome. Conclusions Metronomic VEX regimen can induce prolonged clinical benefit in MBC. On the basis of this long-term safety evaluation, there is no evidence of specific cumulative or delayed toxicities with metronomic chemotherapy.

Although the diagnostic value of Liver Imaging Reporting and Data System (LI-RADS) protocol is well recognized in clinical practice, its role in liver transplant (LT) setting is under-explored. We sought to evaluate the oncological impact of LI-RADS classification applied to Metroticket 2.0 calculator in a single-centre retrospective cohort of transplanted hepatocellular carcinoma (HCC) patients, exploring which LI-RADS subclasses need to be considered in order to grant the best Metroticket 2.0 performance. The most recent pre-LT imaging of 245 patients undergoing LT for HCC between 2005 and 2015 was retrospectively and blindly reviewed, classifying all nodules according to LI-RADS protocol. Metroticket 2.0 accuracy was subsequently tested incorporating all vital nodules identified during multi-disciplinary team (MDT) meetings attended before LI-RADS reclassification of the latest pre-LT imaging, LR-5 and LR-treatment-viable (LR-TR-V), LR-4/5 and LR-TR-V, and LR-3/4/5 and LR-TR-V nodules respectively. Considering their extremely low probability for harbouring HCC, LR-1 and LR-2 nodules were not considered in this analysis. Incorporation of all HCCs identified during MDT meetings attended before LI-RADS reclassification of the latest pre-LT imaging resulted in a Metroticket 2.0 c-index of 0.72, [95% confidence interval (CI) 0.64–0.80]. Metroticket 2.0 c-index dropped to 0.60 [95% CI: 0.48–0.72] when LI-RADS-5 and LI-RADS-TR-V (P=0.0089) or LI-RADS-5, LI-RADS-4 and LI-RADS-TR-V (P=0.0068) nodules were entered in the calculator. Conversely, addition of LI-RADS-3 HCCs raised the Metroticket 2.0 c-index to 0.65 [95% CI: 0.54–0.86], resulting in a not statistically significant diversion from the original performance (0.72 vs. 0.65; P=0.08). Exclusion of LR-3 and LR-4 nodules from Metroticket 2.0 calculator resulted in a significant drop in its accuracy. Every nodule with an intermediate-to-high probability of harbouring HCC according to LI-RADS protocol seems to contribute to tumour burden and should be entered in the Metroticket 2.0 calculator in order to grant appropriate performance.

(1) Background: to evaluate which factors can reduce the upgrade rate of atypical ductal hyperplasia (ADH) to in situ or invasive carcinoma in patients who underwent vacuum-assisted breast biopsy (VABB) and subsequent surgical excision. (2) Methods: 2955 VABBs were reviewed, 141 patients with a diagnosis of ADH were selected for subsequent surgical excision. The association between patients’ characteristics and the upgrade rate to breast cancer was evaluated in both univariate and multivariate analyses. (3) Results: the upgrade rates to ductal carcinoma in situ (DCIS) and invasive carcinoma (IC) were, respectively, 29.1% and 7.8%. The pooled upgrade rate to DCIS or IC was statistically lower at univariate analysis, considering the following parameters: complete removal of the lesion (p-value &lt, 0.001), BIRADS ≤ 4a (p-value &lt, size of the lesion ≤15 mm (p-value: 0.002), age of the patients &lt, 50 years (p-value: 0.035). (4) Conclusions: the overall upgrade rate of ADH to DCIS or IC is high and, as already known, surgery should be recommended. However, ADH cases should always be discussed in multidisciplinary meetings: some parameters appear to be related to a lower upgrade rate. Patients presenting these parameters could be strictly followed up to avoid overtreatment.

Aims Risk stratification of patients with long QT syndrome (LQTS) represents a difficult task. In 2018, we proposed a granular estimate of the baseline 5-year risk of life-threatening arrhythmias (LAE) for patients with LQTS, based on the genotype (long QT syndrome Type 1, long QT syndrome Type 2, and long QT syndrome Type 3) and the duration of the QTc interval. We sought to externally validate a novel risk score model (1-2-3-LQTS-Risk model) in a geographically diverse cohort from the USA and to evaluate its performance and assess potential clinical implication of this novel model. Methods and results The prognostic model (1-2-3-LQTS-Risk model) was derived using data from a prospective, single-centre longitudinal cohort study published in 2018 (discovery cohort) and was validated using an independent cohort of 1689 patients enrolled in the International LQTS Registry (Rochester NY, USA). The validation study revealed a C-index of 0.69 [95% confidence interval (CI): 0.61–0.77] in the validation cohort, when compared with C-index of 0.79 (95% CI: 0.70–0.88) in the discovery cohort. Adopting a 5-year risk ≥5%, as suggested by the ROC curve analysis as the most balanced threshold for implantable cardioverter-defibrillator (ICD) implantation, would result in a number needed to treat (NNT) of nine (NNT = 9; 95% CI: 6.3–13.6). Conclusion The 1-2-3-LQTS-Risk model, the first validated 5-year risk score model for patients with LQTS, can be used to aid clinicians to identify patients at the highest risk of LAE who could benefit most from an ICD implant and avoid unnecessary implants.

Background Oncoplastic surgery is a well-established approach that combines breast-conserving treatment for breast cancer and plastic surgery techniques. Although this approach already has been described for multicentric and multifocal tumors, no long-term oncologic follow-up evaluation and no comparison with patients undergoing mastectomy have been published. This study aimed to evaluate whether oncoplastic surgery is a safe and reliable treatment for managing invasive primary multicentric and multifocal breast cancer. Methods The study compared a consecutive series of 100 patients with multicentric or multifocal tumors who had undergone oncoplastic surgery (study group) with 100 patients who had multicentric or multifocal tumors and had undergone mastectomy (control group) during a prolonged period. The end points evaluated were disease-free survival (DFS), overall survival (OS), cumulative incidence of local recurrence (CI-L), regional recurrence (CI-R), and distant recurrence (CI-D), all measured from the date of surgery. Results The OS and DFS were similar between the two groups. The incidence of local events was higher in the oncoplastic group, whereas the incidence of regional events was slightly higher in the mastectomy group. These differences were not statistically significant. The cumulative incidence of distant events was similar between the two groups. Conclusions To the authors’ knowledge, the current study provides the best available evidence suggesting that the oncoplastic approach is a safe and reliable treatment for managing invasive multifocal and multicentric breast cancers.

Simple Summary Li-RADS classification has recently emerged as an accurate tool for hepatocellular carcinoma diagnosis in the setting of liver cirrhosis, but its prognostic value has never been investigated so far. Single HCC benefits from both surgical resection and percutaneous ablation, although several studies support the superiority of surgery in terms of oncological results. We retrospectively and blindly classified 140 treatment-naïve single HCC according to Li-RADS protocol, comparing the oncological outcomes of surgical resection and percutaneous ablation for each Li-RADS subclass. Our analysis highlighted better overall survival, recurrence free survival and lower incidence of local recurrence after surgical resection in Li-RADS-5 nodules, while Li-RADS-3/4 subclasses showed similar outcomes after the two treatments. These results confirm the superiority of surgical approach for single HCC and suggest a potential prognostic role of Li-RADS classification, supporting liver resection especially for Li-RADS-5 subclass. Abstract Background: Single hepatocellular carcinoma (HCC) benefits from surgical resection (SR) or US-guided percutaneous ablation (PA), although the best approach is still debated. We evaluated the impact of Li-RADS classification on the oncological outcomes of SR vs. PA as single HCC first-line treatment. Methods: We retrospectively and blindly classified treatment-naïve single HCC that underwent SR or PA between 2010 and 2016 according to Li-RADS protocol. Overall survival (OS), recurrence free survival (RFS) and local recurrence after SR and PA were compared for each Li-RADS subclass before and after propensity-score matching (PS-M). Results: Considering the general population, SR showed better 5-year OS (68.3% vs. 52.2%; p = 0.049) and RFS (42.5% vs. 29.8%; p = 0.002), with lower incidence of local recurrence (8.2% vs. 44.4%; p < 0.001), despite a significantly higher frequency of clinically-relevant complications (12.8% vs. 1.9%; p = 0.002) and a higher Comprehensive Complication Index (12.1 vs. 2.2; p < 0.001). Focusing on different Li-RADS subclasses, we highlighted better 5-year OS (67.1% vs. 46.2%; p = 0.035), RFS (45.0% vs. 27.0% RFS; p < 0.001) and lower incidence of local recurrence (9.7% vs. 48.6%; p < 0.001) after SR for Li-RADS-5 HCCs, while these outcomes did not differ for Li-RADS-3/4 subclasses; such results were confirmed after PS-M. Conclusions: Our analysis suggests a potential prognostic role of Li-RADS classification, supporting SR over PA especially for Li-RADS-5 single HCC.

Background and objectives The American College of Surgeons Oncology Group (ACOSOG) Z0011 trial demonstrated that in clinically node-negative women undergoing breast-conserving therapy (BCT) and found to have metastases to 1 or 2 sentinel nodes, sentinel lymph node biopsy (SLNB) alone resulted in rates of local control, disease-free survival, and overall survival equivalent to those seen after axillary lymph node dissection (ALND), but with significantly lower morbidity. Application of the Z0011 guidelines resulted in fewer ALNDs without affecting locoregional recurrence or survival. Changes in practice inevitably affect health care costs. The current study investigated the actual impact of applying the Z0011 guidelines to eligible patients and determined the costs of care at a single institution. Patients and methods We compared axillary nodal management and cost data in breast cancer patients who met the Z0011 criteria and were treated with BCT and SLNB. Patients were allocated into two mutually exclusive cohorts based on the date of surgery: pre-Z0011 (June 2013 to December 2015) and post-Z0011 (June 2016 to December 2018). Results Of 3912 patients, 433 (23%) and 357 (17.6%) patients in the pre- and post-Z0011 era had positive lymph nodes. ALND decreased from 15.3% to 1.57% in the post-Z0011 era. The mean overall cost of SLNB in the pre-Z0011 cohort was €1312 per patient, while that for SLNB with completion ALND was €2613. Intraoperative frozen section (FS) use decreased from 100% to 12%. Omitting the FS decreased mean costs from €247 to €176. The mean total cost in the pre-Z0011 cohort was €1807 per patient, while in the post-Z0011 cohort it was €1498. The application of Z0011 resulted in an overall mean cost savings of €309 for each patient. Conclusions Application of the Z0011 criteria to patients undergoing BCT at our institution results in more than half a million Euro cost savings.

Introduction In patients with positive lymph nodes (cN+) prior to neoadjuvant treatment (NAT), which convert to a clinically negative axilla (cN0) after treatment, the use of sentinel node biopsy (SNB) is still debatable, since the false-negative rate (FNR) is significantly high (12.6–14.2%). The objective of this retrospective mono-institutional study, with a long follow-up, aimed to evaluate the outcome in patients undergoing NAT who remained or converted to cN0 and received SNB independent of target axillary dissection (TAD) or the removal of at least 3 sentinel nodes (SNs). Methods This study analyzed 688 consecutive cT1-3, cN0/1/2 patients, operated at the European Institute of Oncology, Milan, from 2000 to 2015 who became or remained cN0 after NAT and underwent SNB with a least one SN found. Axillary dissection (AD) was not performed if the SN was negative. Nodal radiotherapy (RT) was not mandatory. Results Axillary failure occurred in 1.8% of the initially cN1/2 patients and in 1.5% of the initially cN0 patients. After a median follow-up of 9.2 years (IQR 5.3–12.3), the 5- and 10-year overall survival (OS) were 91.3% (95% CI, 88.8–93.2) and 81.0% (95% CI, 77.2–84.2) in the whole cohort, 92.0% (95% CI, 89.0–94.2) and 81.5% (95% CI, 76.9–85.2) in those initially cN0, 89.8% (95% CI, 85.0–93.2) and 80.1% (95% CI, 72.8–85.7) in those initially cN1/2. Conclusion The 10-year follow-up confirmed our preliminary data that the use of standard SNB is acceptable in cN1/2 patients who become cN0 after NAT and will not translate into a worse outcome.

Introduction: Magnetic Resonance Imaging (MRI) is routinely used in preoperative rectal cancer staging. The concordance of MRI staging with final pathologic exam, albeit improved, has not yet reached perfection. The aim of this study is to analyze the agreement between MRI and pathologic exam in patients operated on for mid-low rectal cancer. Material and Method: Patients undergoing neoadjuvant chemoradiation therapy (nCRT) or upfront surgery were analyzed. Between January 2019 to December 2019, 140 patients enrolled in the AIMS Academy rectal cancer registry were analyzed. Sixty-two patients received nCRT and 78 underwent upfront surgery. Results: Overall, the agreement between MRI and pathologic exam on T stage and N stage were 64.7% and 69.2%, respectively. The agreement between MRI and pathologic exam on T stage was 62.7% for patients who did not receive nCRT and 67.4% for patients who received nCRT (p = 0.62). The agreement on N stage was 76.3% for patients who did not receive nCRT and 60.0% for patients who received nCRT (p = 0.075). Conclusions: Real-world data shows MRI is still far from being able to correlate with the pathology findings which raises questions about the accuracy of the real-life decision-making process during cancer boards.

Background and objectives cT4 breast cancer (BC) is classified as noninflammatory breast cancer (non-IBC) or inflammatory breast cancer (IBC). The outcome often is considered worse. The purpose of this study was to determine recurrence and outcomes in overall survival (OS), invasive disease-free survival (IDFS), distant disease-free survival (DDFS) according to pathological complete response (pCR), and inflammatory status. Methods From 2000 to 2015 we selected 634 nonmetastatic cT4 BC patients treated with neoadjuvant therapy followed by surgery at the European Institute of Oncology. OS, IDFS, and DDFS were estimated with the Kaplan-Meier method. Results The median follow-up was 9.0 years. Twenty patients underwent only sentinel node biopsy (SNB), 13 SNB + AD, and 601 only AD. Considering the 614 patients with AD, only 2.5% of non-IBC patients reported pCR compared to 15% of IBC cases. Only two axillary recurrences were reported. Ten-year results were 52.3% (95% confidence interval [CI]: 47.8-56.5) for OS, 37.0% (95% CI: 32.6-41.3) for IDFS, and 49.8% (95% CI: 45.0-54.4) for DDFS. OS, IDFS, and DDFS were better in all BC with pCR (irrespective of inflammatory status). Conclusion Our long-term results demonstrated that pCR significantly improves survival, reducing locoregional and distant recurrence risk in cT4 tumors with respect to patients with no pCR and according to inflammatory status of cT4 BC.

Background Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors and endocrine therapy (ET) deeply transformed the treatment landscape of hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2−) advanced breast cancer. Randomized clinical trials suggest that second progression-free survival (PFS2) was not compromised and time to subsequent chemotherapy (TTC) may be delayed. We carried out a meta-analysis to assess the benefit on PFS2 and on delaying the TTC. Methods We conducted a systematic literature search of randomized clinical trials with CDK4/6 inhibitors and ET reporting PFS2 or TTC of HR+/HER2− pre- or postmenopausal metastatic breast cancer. We also reviewed abstracts and presentations from all major conference proceedings. We calculated the pooled hazard ratios (HR) for PFS2 and TTC using random-effects models with 95% confidence intervals (CI). I2 was used to quantify heterogeneity between results of the studies. Results Eight studies (MONALEESA-2/3/7, MONARCH-2/3, PALOMA-1/2/3) were included in this analysis (N = 4580 patients). PFS2 benefit was observed in patients who received CDK4/6 inhibitors plus ET (pooled HR = 0.68, 95% CI = 0.62-0.74, I2 = 0%) and also a delay in subsequent TTC (pooled HR = 0.65, 95% CI = 0.60-0.71, I2 = 0%). A benefit in terms of PFS (pooled HR = 0.55, 95% CI = 0.51-0.59, I2 = 0%) and overall survival (pooled HR = 0.76, 95% CI = 0.69-0.84, I2 = 0%) was also observed. Conclusions CDK4/6 inhibitors plus ET compared with ET alone improve PFS2 and TTC. The delay of chemotherapy may postpone the start of a more toxic treatment option, delaying related toxicities and potentially maintaining a better quality of life for patients, for a longer time. The benefit in PFS2 may postpone the onset of endocrine resistance and help further validate this treatment approach., Highlights • Eight RCTs (MONALEESA-2/3/7, MONARCH-2/3, PALOMA-1/2/3) were included in this analysis on pooled HR for PFS2 and TTC. • Patients who received CDK4/6 inhibitors plus ET had a clear PFS2 benefit and a delay in subsequent TTC. • CDK4/6 inhibitors plus ET compared with ET alone improve PFS2 and TTC.

Purpose: To develop a novel risk tool that allows the prediction of lymph node invasion (LNI) among patients with prostate cancer (PCa) treated with robot-assisted radical prostatectomy (RARP) and extended pelvic lymph node dissection (ePLND). Methods: We retrospectively identified 742 patients treated with RARP + ePLND at a single center between 2012 and 2018. All patients underwent multiparametric magnetic resonance imaging (mpMRI) and were diagnosed with targeted biopsies. First, the nomogram published by Briganti et al. was validated in our cohort. Second, three novel multivariable logistic regression models predicting LNI were developed: (1) a complete model fitted with PSA, ISUP grade groups, percentage of positive cores (PCP), extracapsular extension (ECE), and Prostate Imaging Reporting and Data System (PI-RADS) score; (2) a simplified model where ECE score was not included (model 1); and (3) a simplified model where PI-RADS score was not included (model 2). The predictive accuracy of the models was assessed with the receiver operating characteristic-derived area under the curve (AUC). Calibration plots and decision curve analyses were used. Results: Overall, 149 patients (20%) had LNI. In multivariable logistic regression models, PSA (OR: 1.03; P= 0.001), ISUP grade groups (OR: 1.33; P= 0.001), PCP (OR: 1.01; P= 0.01), and ECE score (ECE 4 vs. 3 OR: 2.99; ECE 5 vs. 3 OR: 6.97; P< 0.001) were associated with higher rates of LNI. The AUC of the Briganti et al. model was 74%. Conversely, the AUC of model 1 vs. model 2 vs. complete model was, respectively, 78% vs. 81% vs. 81%. Simplified model 1 (ECE score only) was then chosen as the best performing model. A nomogram to calculate the individual probability of LNI, based on model 1 was created. Setting our cut-off at 5% we missed only 2.6% of LNI patients. Conclusions: We developed a novel nomogram that combines PSA, ISUP grade groups, PCP, and mpMRI-derived ECE score to predict the probability of LNI at final pathology in RARP candidates. The application of a nomogram derived cut-off of 5% allows to avoid a consistent number of ePLND procedures, missing only 2.6% of LNI patients. External validation of our model is needed.

Introduction Metaplastic breast cancer (MBC) is a rare condition of breast tumor with different subtypes, considered a disease with worse prognosis; treatments and survival are often unclear and conflicting. Methods We consecutively collected 153 primary MBCs of different subtypes. Breast surgery, neoadjuvant or adjuvant treatment, clinic-pathological factors, number and type of events during follow-up were considered to evaluate overall survival (OS) and invasive disease-free survival (IDFS). Results The majority of MBC was triple-negative (TN) subtype (88.7%), G3 (95.3%), pN0 (70.6%), and with high levels of Ki-67 (93.5%). For OS and IDFS, no significant associations were seen between the different MBC subtypes. The matched triple-negative MBC (TNMBC) and ductal TNBC cohorts had similar prognosis both in terms of OS (p = .411) and IDFS (p = .981). We observed a positive trend for TNMBC patients treated in the adjuvant setting with the cyclofosfamide, methotrexate, 5-fluorouracil protocol for better OS (p = .090) and IDFS (p = .087). A poor or absent response rate was observed in the neoadjuvant setting. Conclusion Our results demonstrate that metaplastic and ductal breast cancers with TN phenotype are similar in terms of overall and disease-free survival. Metaplastic cancers are poorly responsive to neoadjuvant treatment, and in the absence of novel targeted therapies, surgical treatment remains the first choice.

Mechanical circulatory support (MCS) refers to a range of rescue devices to assist circulation for the treatment of heart failure, including venoarterial extracorporeal membrane oxygenation (VA-ECMO) and ventricular assist devices (VADs). This review aims at evaluating the transplant outcome of the livers procured from brain-dead donors on MCS, who are currently considered as having extended criteria. We identified 22 records (17 on VA-ECMO and 5 on VADs), most of which (68.2%) were case reports. We performed a meta-analysis only when the outcome was reported homogeneously among studies; otherwise, we illustrated the results with narrative synthesis. A total of 156 liver transplants (LTs) have been reported, where VA-ECMO was initiated in the donor with resuscitative intent or as a bridge to donation. Early graft survival approached 100% in most studies. The pooled rate of primary nonfunction was 1% (95% CI: 0-3%). Only three successful LTs from VAD donors have been reported. Particular attention should be paid to cardiological history, biochemical tests, and imaging, as well as MCS parameters, to determine graft eligibility for transplantation. Although further analysis is needed in this field, the results of this review advocate a more systematic consideration of brain-dead patients on MCS as potential liver donors.

Background and Aims: The standard treatment of non-metastatic anal squamous cell carcinoma (ASCC) consists of chemotherapy with mitomycin (MMC) plus 5-fluorouracil (5FU) for 1–2 cycles concomitant with pelvic radiotherapy. Subsequent studies introduced cisplatin (CDDP) combined with 5FU, with unclear results. We evaluated the doublet capecitabine (C) and CDDP as a possible alternative to MMC-5FU regimen concomitant with intensity-modulated radiation therapy (IMRT). Patients and Methods: We carried out a retrospective study on 67 patients affected by stage I–III ASCC, treated with CDDP (60–70 mg/m2 every 21 days for two courses) plus C (825 mg/m2 twice daily for 5 days/week) chemotherapy concomitant with IMRT for curative intent. Results: At a median follow up of 41 months, the clinical complete response calculated at the 6-month time-point (6-moCR), the 6-month objective response rate and the 6-month disease control rate were 93%, 94%, and 99%, respectively. Disease-free survival rates at 1, 2, and 3 years were 89%, 87%, and 85%, while the overall survival rates at 1 and 2 years were 100% and 95%. The colostomy-free survival rates were 90% at 1 year and 88% at 2 years. Grade 3–4 acute adverse events were reported in 61% of patients; predominantly skin toxicity (46%) and limited hematological toxicity (12%). Conclusion: In this retrospective study, chemotherapy with C plus CDDP concomitant with IMRT proved safe and effective, and may represent a possible alternative option to standard MMC-containing regimen for curative intent.

BackgroundMicroinvasive breast cancer is an uncommon pathological entity. Owing to the rarity of this condition, its surgical axillary management and overall prognosis remain controversial.MethodsA database was analysed to identify patients with microinvasive ductal carcinoma in situ (DCIS) who had surgery for invasive breast cancer at the European Institute of Oncology, Milan, between 1998 and 2010. Women who had undergone axillary staging by sentinel lymph node biopsy were included in the study.ResultsOf 257 women with microinvasive breast cancer who underwent sentinel lymph node biopsy (SLNB), 226 (87·9 per cent) had negative sentinel lymph nodes (SLNs) and 31 had metastatic SLNs. Twelve patients had isolated tumour cells (ITCs), 14 had micrometastases and five had macrometastases in sentinel nodes. Axillary lymph node dissection was performed in 16 of the 31 patients with positive SLNs. After a median follow-up of 11 years, only one regional first event was observed in the 15 patients with positive SLNs who did not undergo axillary lymph node dissection. There were no regional first events in the 16 patients with positive SLNs who had axillary dissection.ConclusionGood disease-free and overall survival were found in women with positive SLNs and microinvasive DCIS. This study is in line with studies showing that SLNB in microinvasive DCIS may not be useful, and supports the evidence that less surgery can provide the same level of overall survival with better quality of life.

Purpose To analyse the survival outcomes and toxicity profile of patients treated with pulsed-dose-rate (PDR) brachytherapy (BT) after intensity-modulated radiation therapy (IMRT) for uterine cervical cancer in a single institution. Material and methods Between March 2011 and December 2014, 50 patients with histologically proven stages IB1-IVB cervical cancer were treated with IMRT followed by PDR-BT boost. Radiation treatment consisted of IMRT to pelvic with or without paraaortic lymph nodes to a total dose of 45-50.4 Gy. Weekly concomitant chemotherapy was administered to 45 patients. PDR-BT boost was delivered with a median dose of 30 Gy to the high-risk clinical target volume (HR-CTV) after a median time of 14 days since IMRT. Acute and late toxicity were evaluated by Radiation Therapy Oncology Group (RTOG) - European Organization for Research and Treatment of Cancer (EORTC) scoring criteria and Subjective Objective Management Analytic-Late Effects of Normal Tissues (SOMA-LENT) criteria. Results Two patients had tumour persistence at 6 months after the end of BT. After a median follow-up of 33 months, 6 distant metastases with or without regional relapse were observed. The 1- and 5-year progression-free survival was 83% (95% CI: 69-91%) and 76% (95% CI: 61-86%), whereas the 3- and 5-year overall survival was 91% (95% CI: 78-97%) and 76% (95% CI: 56-88%), respectively. Urinary and rectal toxicity higher than grade 2 was observed in 6.3% and 17% of patients, respectively. Five patients (10.6%) had grade 4 gastrointestinal toxicity requiring colostomy. Conclusions Our study confirms that the combination of IMRT and PDR-BT can be considered an effective treatment for cervical cancer, ensuring high local control, despite the high percentage of locally advanced disease.

Background: Nipple-sparing mastectomy (NSM) is increasingly used in women with breast cancer who are not eligible for conservative surgery, but extensive outcome data are lacking and indications have not been established. Objective: The aim of this study was to assess the oncological outcomes of NSM in a large series of patients with invasive or in situ breast cancer treated at a single center. Methods: We analyzed 1989 consecutive women who had an NSM in 2003–2011, for invasive (1711 patients) or in situ cancer (278 patients) at the European Institute of Oncology, Italy, and followed-up to December 2016. Endpoints were local recurrences, recurrences in the nipple-areola complex (NAC), NAC necrosis, and overall survival (OS). Results: After a median follow-up of 94 months (interquartile range 70–117), 91/1711 (5.3%) patients with invasive cancer had local recurrence (4.8% invasive disease, 0.5% in situ disease), and 11/278 (4.0%) patients with in situ disease had local recurrence (1.8% invasive disease, 2.2% in situ disease). Thirty-six (1.8%) patients had NAC recurrence, 9 with in situ disease (4 invasive and 5 in situ recurrences), and 27 with invasive disease (18 invasive and 9 in situ recurrences). NAC loss for necrosis occurred in 66 (3.3%) patients. There were 131 (6.6%) deaths, 109 (5.5%) as a result of breast cancer. OS at 5 years was 96.1% in women with invasive cancer and 99.2% in women with in situ disease. Conclusions: The findings in this large series, with a median follow-up of nearly 8 years, indicate that NSM is oncologically safe for selected patients. The rate of NAC loss was acceptably low.