Gender-Related Factors Influence the Subjective Perception of Deformity in Patients Undergoing Surgery for Idiopathic Scoliosis.

The present study aims to depict the importance of gender-related factors in the subjective perception of spine deformity in adolescents undergoing posterior instrumented fusion for scoliosis. Patients undergoing posterior spinal instrumentation and fusion (PSF) for idiopathic adolescent scoliosis (AIS) were recruited. The following data were recorded: gender, age, parents' civil status, Tegner Activity Scale (TAS), body mass index (BMI), concomitant diseases, and history of neuropsychological disorders. Each patient underwent clinical and radiological evaluations according to the protocol used at our institution. All the patients were assessed before surgery using the following Patient-Reported Outcome Measures (PROMs): the Italian version of the revised Scoliosis Research Society-22 patient questionnaire (SRS-22R), the Quality-of-Life Profile for Spinal Deformities (QLPSDs) questionnaire, and the Spinal Appearance Questionnaire (SAQ). The present study recruited 80 patients (male: 19, female: 61). A significant correlation was observed between BMI, TAS, and subjective perception scores. A worse deformity perception was observed in female patients and patients with divorced parents. Gender-related factors impact the subjective perception of spine deformity in patients undergoing PSF for AIS. Specific assessment and correction are needed to improve postoperative outcomes in these patients.

Gender-Related Issues in the Management of Low-Back Pain: A Current Concepts Review.

BACKGROUND: Low back pain (LBP) is an emerging disease. This review aims to investigate the role of gender-related factors in the diagnosis, clinical, and surgical management of LBP. METHODS: From January 2002 to March 2023, EMBASE, SCOPUS, OVID-MEDLINE, Google Scholar, PubMed, and Web of Science were searched to identify relevant papers for further analysis. RESULTS: Fifteen papers were included in this review. Sex- and gender-related differences were analyzed regarding the following points: (1) LBP epidemiology; (2) LBP physiopathology; (3) conservative management of LBP; (4) major vertebral surgery for LBP. The conservative treatment of LBP highlights that women claim services later in terms of poorer health status than men. In the postoperative phase, female patients show worse LBP, quality of life, and disability, but equal or greater interval change, compared with male patients complaining of lumbar degenerative disease. CONCLUSIONS: LBP epidemiology and clinical outcomes, following conservative and surgical management of patients complaining of back pain, might depend on both sex- and gender-related factors. It is mandatory to assess gender-related indicators in patients referred to LBP and address them to improve their clinical outcomes and quality of life.

Host-Related Factors in the Interplay among Inflammation, Immunity and Dormancy in Breast Cancer Recurrence and Prognosis: An Overview for Clinicians.

A significant proportion of patients treated for early breast cancer develop medium-term and late distant recurrence. The delayed manifestation of metastatic disease is defined as "dormancy". This model describes the aspects of the clinical latency of isolated metastatic cancer cells. Dormancy is regulated by extremely complex interactions between disseminated cancer cells and the microenvironment where they reside, the latter in turn influenced directly by the host. Among these entangled mechanisms, inflammation and immunity may play leading roles. This review is divided into two parts: the first describes the biological underpinnings of cancer dormancy and the role of the immune response, in particular, for breast cancer; the second provides an overview of the host-related factors that may influence systemic inflammation and immune response, subsequently impacting the dynamics of breast cancer dormancy. The aim of this review is to provide physicians and medical oncologists a useful tool to understand the clinical implications of this relevant topic.

Sex and Gender-Related Differences in the Outcome of Total Hip Arthroplasty: A Current Concepts Review.

Background and Objectives: Sex and gender-related differences may influence the outcome of patients undergoing total hip arthroplasty (THA). The present paper aims to depict the importance of sex and gender-related issues in the perioperative management of patients undergoing THA to improve clinical outcomes and prevent postoperative complications. Materials and Methods: From January 2002 to August 2022, OVID-MEDLINE, EMBASE, SCOPU S, Web of Science, Google Scholar, and PubMed were searched to identify relevant studies for further analysis. The search strategy included the following terms: (("gender-related differences" [MeSH Terms] OR "sex-related differences" [All Fields]) OR ("gender indicators" [MeSH Terms] OR "sex" [All Fields])) AND ("total hip arthroplasty" [MeSH Terms] OR (total hip replacement [All Fields])). Results: Twenty-eight papers were included in this current concepts review. Sex and gender-related differences were analyzed with regard to the following points: (1) surgical approach, robotic surgery, scar cosmesis, and implant choice; (2) postoperative clinical outcome and complications; (3) sexual activity after THA; and (4) psychological status and daily functional requirements. The data analysis showed that female patients need more specific attention in the preoperative, intraoperative, and postoperative phases to improve clinical and functional outcomes, reduce complications risk, and manage patient satisfaction. Conclusions: THA outcomes may be influenced by sex and gender-related factors which should be carefully assessed and addressed in patients undergoing surgery to improve the postoperative outcomes of patients' satisfaction and reduce postoperative complications that can differ between the two sexes.

Tolerability of Eribulin and correlation between polymorphisms and neuropathy in an unselected population of female patients with metastatic breast cancer: results of the multicenter, single arm, phase IV PAINTER study.

BACKGROUND: Metastatic breast cancer (MBC) is an incurable disease and its treatment focuses on prolonging patients' (pts) overall survival (OS) and improving their quality of life. Eribulin is a microtubule inhibitor that increases OS in pre-treated MBC pts. The most common adverse events (AEs) are asthenia, neutropenia and peripheral neuropathy (PN). METHODS: PAINTER is a single arm, phase IV study, aimed at evaluating the tolerability of eribulin in MBC pts. Secondary objectives were the description of treatment efficacy and safety, the assessment of the incidence and severity of PN and its association with genetic polymorphisms. Genomic DNA was isolated from blood samples and 15 Single Nucleotide Polymorphisms (SNPs) were genotyped by Taqman specific assays. The association between PN and SNPs were evaluated by Fisher exact test. RESULTS: Starting from May 2014 until June 2018 180 pts were enrolled in this study by 20 Italian centers. 170 of these pts could be evaluated for efficacy and toxicity and 159 for polymorphisms analysis. The median age of pts was 60 years old and the biological subtypes were luminal type (64.7%), Her2 positive (18.3%) and triple negative (17%). Pts were pretreated with a median of 5 lines for MBC. The median follow up of this study was 15.4 months with a median number of 4.5 cycles administered (minimum-maximum 1-23). The median overall survival was 12 months. 48.8% of pts experienced a dose reduction, mainly for neutropenia (23.9%) and liver toxicity (12%). 65 pts (38.2%) reported at least one severe toxicity. Neutropenia and neurotoxicity were the most frequent severe AEs (15.3% and 14.7%, respectively); other reported toxicities were osteo-muscular, abdominal or tumor site pain (19.4%), liver toxicity (6.6%), pulmonary toxicity (6.5%) and dermatological toxicity (3.6%). Among the 15 evaluated SNPs, an association with PN was found for rs2233335 and rs7214723. CONCLUSIONS: Eribulin is a well-tolerated treatment option in MBC. Schedule and dosage modifications were common, but toxicity rarely led to treatment discontinuation. SNPs rs2233335 (G/T and T/T) in the NDRG1 gene and rs7214723 (CC and CT) in the CAMKK1 gene were associated with PN. These findings, if validated, could allow a tailored treatment with eribulin in cancer patients. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02864030.

Impact of Baseline and On-Treatment Glycemia on Everolimus-Exemestane Efficacy in Patients with Hormone Receptor-Positive Advanced Breast Cancer (EVERMET).

PURPOSE: The mTOR complex C1 (mTORC1) inhibitor everolimus in combination with the aromatase inhibitor exemestane is an effective treatment for patients with hormone receptor-positive (HR+), HER2-negative (HER2-), advanced breast cancer (HR+/HER2- aBC). However, everolimus can cause hyperglycemia and hyperinsulinemia, which could reactivate the PI3K/protein kinase B (AKT)/mTORC1 pathway and induce tumor resistance to everolimus. EXPERIMENTAL DESIGN: We conducted a multicenter, retrospective, Italian study to investigate the impact of baseline and on-treatment (i.e., during first 3 months of therapy) blood glucose levels on progression-free survival (PFS) in patients with HR+/HER2- aBC treated with everolimus-exemestane. RESULTS: We evaluated 809 patients with HR+/HER2- aBC treated with everolimus-exemestane as any line of therapy for advanced disease. When evaluated as dichotomous variables, baseline and on-treatment glycemia were not significantly associated with PFS. However, when blood glucose concentration was evaluated as a continuous variable, a multivariable model accounting for clinically relevant patient- and tumor-related variables revealed that both baseline and on-treatment glycemia are associated with PFS, and this association is largely attributable to their interaction. In particular, patients who are normoglycemic at baseline and experience on-treatment diabetes have lower PFS compared with patients who are already hyperglycemic at baseline and experience diabetes during everolimus-exemestane therapy (median PFS, 6.34 vs. 10.32 months; HR, 1.76; 95% confidence interval, 1.15-2.69; P = 0.008). CONCLUSIONS: The impact of on-treatment glycemia on the efficacy of everolimus-exemestane therapy in patients with HR+/HER2- aBC depends on baseline glycemia. This study lays the foundations for investigating novel therapeutic approaches to target the glucose/insulin axis in combination with PI3K/AKT/mTORC1 inhibitors in patients with HR+/HER2- aBC.

Overall Survival in Metastatic Breast Cancer Patients in the Third Millennium: Results of the COSMO Study.

INTRODUCTION: Metastatic breast cancer (MBC) is a life-threatening disease, and although some data suggest a trend in survival improvement, it has not yet been unequivocally demonstrated. This study aimed to evaluate the overall survival (OS) of MBC patients, assessing its correlation with prognostic factors. PATIENTS AND METHODS: COSMO (Checking Overall Survival in a MBC Observational study) is an Italian longitudinal retrospective multicenter study that enrolled patients with MBC diagnosed between 2000 and 2008. The primary objective was to detect a temporal difference in OS; the secondary objective was to identify prognostic factors as causal factors of the temporal variation in OS. RESULTS: A total of 3721 of 3930 patients from 31 centers were distributed in 3 periods: 886 (23.8%), 1302 (35.0%), and 1533 (41.2%) in 2000-2002, 2003-2005, and 2006-2008, respectively. With a median follow-up of 9.3 years, median OS was 2.8 years (95% confidence interval, 2.6-2.9). No difference in OS was found in the 3 cohorts (P for trend = .563). The worst prognosis was observed for patients with triple-negative MBC (OS, 1.5 years) and for those with central nervous system metastases (1.7 years); the best prognosis was observed in those with bone metastases or nonvisceral disease (3.4 and 3.2 years, respectively) and in patients with a disease-free interval, defined as the time between resection of the primary malignancy and diagnosis of MBC, of > 2 years (3 years). CONCLUSIONS: The COSMO study found improvement in OS between 2000 and 2008. Molecular subtype remained the strongest prognostic factor, and the role of other prognostic factors was confirmed, in particular disease-free interval, site of metastasis, and age.

Gender differences in treatment of Coronavirus Disease-2019.

Coronavirus Disease-2019 (COVID-19) is the worst worldwide pandemic with more than 12,000,000 cases and 560,000 deaths until 14th July 2020. Men were more infected by COVID-19 than women, and male subjects with underlying conditions, including diabetes, hypertension, and cardiovascular diseases developed a severe form of the affection, with increased mortality rate. Many factors can contribute to the disparity in disease outcomes, such as hormone-specific reaction and activity of X-linked genes, which modulate the innate and adaptive immune response to virus infection. Until now, only the Remdesivir was approved by FDA (Food Drug Administration) for COVID-19 treatment, although several clinical trials are ongoing worldwide also on other drugs. In this review, we analyzed published studies on several drugs (chloroquine or hydroxychloroquine, remdesivir, favipiravir, lopinavir-ritonavir in combination, tocilizumab, plasma, and immunoglobulins) with some efficacy to COVID-19 in humans, and evaluated if there were a gender analysis of the available data. In our opinion, it is essential to report data about COVID-19 disaggregated by sex, age, and race, because the knowledge of gender differences is fundamental to identify effective and customized treatments to reduce hospitalizations, admissions to intensive care units, and mortality.

Gender differences in patients with COVID-19: a narrative review.

In December 2019 a novel coronavirus emerged in Wuhan, China causing many cases of severe pneumonia. World Health Organization (WHO) named this disease Coronavirus Disease 2019 (COVID-19). The infection has rapidly spread across China to many other countries, and on March 12, 2020 the WHO declared pandemic outbreak of COVID-19. As of May 16, 2020, COVID-19 has been diagnosed in more than 4,490,000 patients, associated to 305,976 deaths worldwide; in Italy 224,760 COVID-19 cases have been reported with 31,763 deaths. The main routes of transmission are respiratory droplets and direct contact with infected people, so numerous prevention strategies are employed to mitigate the spread of disease, including social distancing and isolation. The aim of this narrative review is to underline gender differences in epidemiology, etiopathogenesis, risk factors, clinical presentation, diagnosis, prognosis and mortality of patients infected with SARS-CoV-2. Currently data on the sex indicators for admitted or deceased patients are only available, but there is no analysis about other gender indicators. The data considered in our study are the only currently available in the literature, but it is appropriate to implement a specific analysis with all gender indicators to identify appropriate strategies. Moreover, the evaluation of a health service efficiency is a key element to define gender outcomes. Knowing the gender differences in COVID-19 outbreak would be a fundamental tool to understand the effects of a health emergency on individuals and communities as well as to carry out effective and equitable policies, public health measures and targeted solutions.

Neoadjuvant eribulin mesylate following anthracycline and taxane in triple negative breast cancer: Results from the HOPE study.

BACKGROUND: Eribulin mesylate (E) is indicated for metastatic breast cancer patients previously treated with anthracycline and taxane. We argued that E could also benefit patients eligible for neoadjuvant chemotherapy. METHODS: Patients with primary triple negative breast cancer ≥2 cm received doxorubicin 60 mg/m2 and paclitaxel 200 mg/m2 x 4 cycles (AT) followed by E 1.4 mg/m2 x 4 cycles. Primary endpoint was pathological complete response (pCR) rate; secondary and explorative endpoints included clinical/metabolic response rates and safety, and biomarker analysis, respectively. Using a two-stage Simon design, 43 patients were to be included provided that 4 of 13 patients had achieved pCR in the first stage of the study. RESULTS: In stage I of the study 13 women were enrolled, median age 43 years, tumor size 2-5 cm in 9/13 (69%), positive nodal status in 8/13 (61%). Main grade 3 adverse event was neutropenia (related to AT and E in 4 and 2 cases, respectively). AT followed by E induced clinical complete + partial responses in 11/13 patients (85%), pCR in 3/13 (23%). Median measurements of maximum standardized uptake value (SUVmax) resulted 13, 3, and 1.9 at baseline, after AT and E, respectively. Complete metabolic response (CMR) occurred after AT and after E in 2 and 3 cases, respectively. Notably, 2 of the 5 (40%) patients with CMR achieved pCR at surgery. Immunostaining of paired pre-/post-treatment tumor specimens showed a reduction of ß-catenin, CyclinD1, Zeb-1, and c-myc expression, in the absence of N-cadherin modulation. The study was interrupted at stage I due to the lack of the required patients with pCR. CONCLUSIONS: Despite the early study closure, preoperative E following AT showed clinical and biological activity in triple negative breast cancer patients. Furthermore, the modulation of ß-catenin pathway core proteins, supposedly outside the domain of epithelial-mesenchymal transition, claims for further investigation. TRIAL REGISTRATION: EU Clinical Trial Register, EudraCT number 2012-004956-12.

Educational level, marital status and sex as social gender discharge determinants in chronic obstructive pulmonary disease exacerbations: a time-to-event analysis.

The aim of this study is to evaluate, in patients hospitalized for COPD exacerbation, how educational level, marital status and sex (social gender indicators) affect the prognosis (main effects) and how interact with each other in affecting prognosis (effect modification). Data for all patients discharged with a principal diagnosis of COPD with exacerbation (ICD-9 491.21) by Apulian facilities between 2013 and 2017 were retrieved from the National Hospital Discharge Register Database. A multivariable multi-stratified frailty cox proportional-hazard regression with interaction terms was fitted in order to assess the effect of sex, educational level and marital status on the time-to-event for home discharge through the estimation of hazard ratios. Adjusting for several hospitalization characteristics and for healthcare facilities, low educational level (<8 years of schooling) seems to be a risk factor in both sexes and in all marital status categories (HR 0.92, 95%CI 0.87-0.97, p=0.0020). Female sex seems to be a risk factor only in married patients (HR 0.83, 95%CI 0.78-0.88, p<0.0001). Marital status different from married seems to be a risk factor only in male patients, in particular single patients (HR 0.82, 95%CI 0.74-0.92, p=0.0009), separated or divorced patients (HR 0.71, 95%CI 0.58-0.86, p=0.0005) and widowed patients (HR 0.87, 95%CI 0.80-0.95, p=0.0018). Differently from findings about protective effect of education, the evidence of different effects of sex among civil statuses and of different effect of civil status among sexes is supposed to be a proxy for social gender health and healthcare inequalities.

HER2-Positive Lobular Versus Ductal Carcinoma of the Breast: Pattern of First Recurrence and Molecular Insights.

BACKGROUND: Infiltrating lobular carcinoma (ILC) represents about 10% of breast cancer and rarely shows overexpression of human epidermal growth factor receptor 2 (HER2). We compared biological and clinical characteristics of HER2-positive ILC versus HER2-positive infiltrating ductal carcinoma (IDC). PATIENTS AND METHODS: We retrospectively analyzed the data of 328 patients with HER2-positive pure ductal or lobular breast carcinoma, comparing clinical and biological data at diagnosis as well as outcome between the 2 histologies. A gene-mutation analysis was performed in a subset of patients. RESULTS: Two hundred ninety-one patients (88.7%) had IDC and 37 patients (11.3%) ILC. ILC resulted more frequently in multicenter (24.3% vs. 6.5%, P < .0001) and node-positive (54.1% vs. 45%, P = .013) disease of lower proliferative activity (Mib1 < 20%: 51.4% vs. 22.3%, P < .0001) and lower histologic grade (grade 3: 32.4% vs. 57.4%, P = .038). Disease recurred in 57 patients (17.4%) and involved the bone in 40% of ILC patients (vs. 17% of IDC patients) and the viscera in 30% of ILC patients (vs. 59.6% of IDC patients). No difference in the recurrence rate between the 2 histologies was observed in patients treated with adjuvant trastuzumab (12.5% of ILC patients and 8.3% of IDC patients). Exploratory molecular analysis revealed a higher frequency of mutations in ILC, with more cases of multiple mutations. CONCLUSION: HER2-positive ILC shows different biological behavior than IDC, with a possible higher mutation load. Despite lower proliferation activity and estrogen receptor expression in ILC breast cancer, trastuzumab is clearly an effective therapy for this histologic subtype.

High-sensitivity assay for monitoring ESR1 mutations in circulating cell-free DNA of breast cancer patients receiving endocrine therapy.

Approximately 70% of breast cancers (BCs) express estrogen receptor alpha (ERα) and are treated with endocrine therapy. However, the effectiveness of this therapy is limited by innate or acquired resistance in approximately one-third of patients. Activating mutations in the ESR1 gene that encodes ERα promote critical resistance mechanisms. Here, we developed a high sensitivity approach based on enhanced-ice-COLD-PCR for detecting ESR1 mutations. The method produced an enrichment up to 100-fold and allowed the unambiguous detection of ESR1 mutations even when they consisted of only 0.01% of the total ESR1 allelic fraction. After COLD-PCR enrichment, methods based on next-generation sequencing or droplet-digital PCR were employed to detect and quantify ESR1 mutations. We applied the method to detect ESR1 mutations in circulating free DNA from the plasma of 56 patients with metastatic ER-positive BC. Fifteen of these patients were found to have ESR1 mutations at codons 536-538. This study demonstrates the utility of the enhanced-ice-COLD-PCR approach for simplifying and improving the detection of ESR1 tumor mutations in liquid biopsies. Because of its high sensitivity, the approach may potentially be applicable to patients with non-metastatic disease.

Final data of an Italian multicentric survey about counseling for smoking cessation in patients with diagnosis of a respiratory disease.

INTRODUCTION: Smoking is the major risk factor for cancer and several respiratory diseases. Quitting smoking at any point of life may increase the effectiveness of treatments and improve prognosis of patients with any pulmonary disease, including lung cancer. However, few institutions in Europe offer to patients adequate counseling for smoking cessation. OBJECTIVES: Aim of this study was to investigate the level of counseling for smoking cessation offered by healthcare professionals to patients and their appreciation towards the intervention itself. METHODS: Between January 2013 and February 2016, 490 patients, diagnosed with a respiratory diseases, were prospectively evaluated with an anonymous survey developed by WALCE (Women Against Lung Cancer in Europe). RESULTS: The majority of patients enrolled (76%) declared to have stopped smoking after the diagnosis of a respiratory disease, 17% to smoke less, 7% to continue smoking. Patients who reported to have never received any counseling for smoking cessation were 38%. Almost 73% of the other patients reported a positive judgment about the quality of healthcare's intervention. Despite these favorable considerations, 83% of patients have disclosed they simply quit smoking overnight without help, 5% have used electronic cigarettes, 5% nicotine replacement treatments, 4% dedicated books, 3% have attended a referral clinic. CONCLUSIONS: Considering all the smoking-related side effects, greater efforts should be made in order to better support patients in smoking cessation. Smoking should be considered as a real physical disorder and similar surveys should be encouraged with the aim to fight the 'stigma' of smoking that still exists among patients.

The prognostic role of tumor size in early breast cancer in the era of molecular biology.

BACKGROUND: The prognosis of early breast cancer (EBC) depends on patient and tumor characteristics. The association between tumor size, the largest diameter in TNM staging, and prognosis is well recognized. According to TNM, tumors classified as T2, could have very different volumes; e.g. a tumor of 2.1 cm has a volume of 4500 mm3, while a tumor of 4.9 cm has a volume of 60.000 mm3 even belonging to the same class. The aim of the study is to establish if the prognostic role of tumor size, expressed as diameter and volume, has been overshadowed by other factors. METHODS: The primary objective is to evaluate the association between tumor dimensions and overall survival (OS) / disease free survival (DFS), in our institution from January 1st 2005 to September 30th 2013 in a surgical T1-T2 population. Volume was evaluated with the measurement of three half-diameters of the tumor (a, b and c), and calculated using the following formula: 4/3π x a x b x c. RESULTS: 341 patients with T1-T2 EBC were included. 86.5% were treated with conservative surgery. 85.1% had a Luminal subtype, 9.1% were Triple negative and 7.4% were HER2 positive. Median volume was 942 mm3 (range 0.52-31.651.2). 44 patients (12.9%) relapsed and 23 patients died. With a median follow-up of 6.5 years, the univariate analysis for DFS showed an association between age, tumor size, volume, histological grading and molecular subtype. The multivariate analysis confirmed the statistically significant association only for molecular subtype (p 0.005), with a worse prognosis for Triple negative and HER2 positive subtypes compared with Luminal (HR: 2.65; 95%CI: 1.34-5.22). Likewise for OS, an association was shown by the multivariate analysis solely for molecular subtype (HER2 and Triple negative vs. Luminal. HR: 2.83; 95% CI:1.46-5.49; p 0.002). CONCLUSIONS: In our study, the only parameter that strongly influences survival is molecular subtype. These findings encourage clinicians to choose adjuvant treatment not based on dimensional criteria but on biological features.

What Medical Oncologist Residents Think about the Italian Speciality Schools: A Survey of the Italian Association of Medical Oncology (AIOM) on Educational, Clinical and Research Activities.

BACKGROUND AND OBJECTIVES: Relevant heterogeneity exists among Postgraduate Schools in Medical Oncology, also within the same country. In order to provide a comprehensive overview of the landscape of Italian Postgraduate Schools in Medical Oncology, the Italian Association of Medical Oncology (AIOM) undertook an online survey, inviting all the residents to describe their daily activities and to express their overall satisfaction about their programs. METHODS: A team composed of five residents and three consultants in medical oncology prepared a 38 items questionnaire that was published online in a reserved section, accessible through a link sent by e-mail. Residents were invited to anonymously fill in the questionnaire that included the following sub-sections: quality of teaching, clinical and research activity, overall satisfaction. RESULTS: Three-hundred and eleven (57%) out of 547 invited residents filled in the questionnaire. Two-hundred and twenty-three (72%) participants declared that attending lessons was frequently difficult and 153 (49%) declared they did not gain substantial improvement in their knowledge from them. Fifty-five percent stated that they did not receive lessons on palliative care. Their overall judgment about didactic activity was low in 63% of the interviewed. The satisfaction for clinical activity was in 86% of cases good: 84% recognized that, during the training period, they acquired a progressive independence on patients' management. About research activity, the majority (79%) of participants in the survey was actively engaged in managing patients included in clinical trials but the satisfaction level for the involvement in research activities was quite low (54%). Overall, 246 residents (79%) gave a positive global judgment of their Medical Oncology Schools. CONCLUSIONS: The landscape of Italian Postgraduate Schools in Medical Oncology is quite heterogeneous across the country. Some improvements in the organization of teaching and in the access to research opportunity are needed; the perception about clinical activity and the overall judgment of the programs are quite satisfactory.

A targeted approach to genetic counseling in breast cancer patients: the experience of an Italian local project.

AIMS AND BACKGROUND: Patients with hereditary breast cancer (BC) may benefit from genetic counseling and testing for detection of causative mutations, definition of therapeutic and preventive strategies, and identification of at-risk relatives. Italy has few oncogenetic centers and genetic evaluation of all patients with BC is not feasible. Moreover, lack of uniformity in the selection of patients generates inappropriate referral to the geneticist. We designed a model that may represent a reproducible way to select patients at risk for hereditary BC, with the aims of rationalizing access to genetic centers and improving clinical management and surveillance. METHODS: The genetic unit of a Cancer Center and the Departments of Oncology from 2 public Hospitals in Milan were involved in the project. After training sessions at the genetic unit, operators from the 2 hospitals evaluated all patients with BC attending a first oncologic visit, through a specific interview. Patients considered at risk of hereditary BC attended counseling at the genetic unit. RESULTS: Of 419 patients, 61 (14.5%) were eligible for genetic counseling after the interview. Of these, 46 (10.9%) strictly met testing criteria. Overall, 52 (12.4%) patients underwent genetic counseling and 47 were tested for BRCA1/BRCA2 mutation. After genetic test results, the available options for treatment/surveillance were discussed by a multidisciplinary team, according to the level of genetic risk. CONCLUSIONS: It is possible to improve the process of referring patients with suspected hereditary BC for genetic risk assessment. The application of clinical screening reduced the genetics unit's workload and enabled optimization of time and resources.

Prospective, mono-institutional study of the impact of a systematic prevention program on incidence and outcome of osteonecrosis of the jaw in patients treated with bisphosphonates for bone metastases.

The aim of our study was to investigate the occurrence of osteonecrosis of the jaw (ONJ) after implementation of dental preventive measures before starting bisphosphonates (BPs) therapy and during treatment. All consecutive patients with bone lesions eligible for BPs treatment were prospectively evaluated. Before starting BPs, each patient underwent a strict dental preventive program with a specialized odontoiatric team. The odontoiatric evaluation identified patients with oral pathologies or inadequate oral hygiene and provided a dental preventive treatment. From April 2007 to April 2012, 254 patients were enrolled. After excluding patients due to previous BPs treatment, 212 patients with a mean age of 74 years (range 37-95) were included. On average, patients received 9.7 treatment cycles (range 1-48). No ONJ was recorded (0.0 %; 95 % confidence interval [CI] 0.0-1.4). Comparing this risk with that observed in a previous cohort who did not receive dental prevention (16/186, 8.6 %; 95 % CI 4.2-15.3 %), we observed clear efficacy in preventing ONJ (relative risk reduction: 100 %, 95 % CI 86-100 %, P < 0.0001). We developed a strict three-step prevention program that is able to decrease ONJ incidence and the need for destructive surgery with permanent sequelae. We demonstrated that ONJ could be effectively prevented. We recommend a mandatory preventive program involving a multidisciplinary team for all patients starting BPs.

Efficacy of biological agents in metastatic triple-negative breast cancer.

Metastatic triple-negative breast cancer (mTNBC) represents 15% of invasive breast cancers. Prognosis is poor, and there is no specific target therapy but biological agents combined with chemotherapy may be effective. To assess the role of biological agents in metastatic triple-negative breast cancer we performed a systematic review of phase III randomized controlled trials published from January 2006 to February 2013 and presentations at ESMO, ASCO, and SABCS congresses in 2010-2012. We consulted PubMed and ClinicalTrials.gov. Only studies comparing biological agents and chemotherapy versus chemotherapy alone were considered. Relevant statistical variables were log of the hazard ratio and relative variance for progression-free survival (PFS) and overall survival (OS). Of 353 PubMed publications and 229 studies registered on ClinicalTrials.gov, 10 trials were selected and 5293 patients were analyzed: 1546 had mTNBC. Biological agents considered were bevacizumab, sunitinib, sorafenib, lapatinib, iniparib and cetuximab. In addition, a meta analysis of the four studies containing bevacizumab was performed and it showed a PFS improvement with a relative risk reduction of 35% (95% CI: 25-43%). No effect on OS was observed. No PFS and OS benefit was detected with the other agents. No improvement of OS was detected in patients treated with biological agents plus chemotherapy, while a significant PFS improvement was observed only for bevacizumab and cetuximab. The overall impact of these agents on patient survival was not as great as expected, probably because the molecular basis of this illness needs to be better understood so that treatment can be more appropriately tailored.

Eribulin in cutaneous breast cancer metastasis treatment: clinical activity and symptom control.

AIM: This observational study evaluated the behavior and outcome of cutaneous breast cancer metastasis treated with eribulin. PATIENTS & METHODS: From November 2012 to January 2013, oncologists completed a database with patient, tumor and treatment characteristics from 14 Italian cancer centers. Skin lesions were assessed by Response Evaluation Criteria In Solid Tumors and cutaneous symptoms by present/absent criteria. RESULTS: A total of 23 metastatic breast cancer patients with skin metastasis who were treated with eribulin were analyzed. After treatment, 43% of patients exhibited a partial response, 35% stable disease and 22% progressive disease. Regarding only the skin response, 26% obtained a complete response, 22% a partial response, 39% stable disease and 13% progressive disease. We found an improvement in symptoms, infiltration and ulceration. With a median follow-up of 6 months, median progression-free survival was 4.3 months and median overall survival was 9.1 months. CONCLUSION: The response rate of skin metastasis to eribulin treatment was coherent with systemic responses. The good clinical response in most patients reflected symptom improvement.