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Background: Scalp melanomas are usually thicker and show worse prognosis than other sites and other head and neck melanomas. One hypothesis to explain this aggressive behavior could be diagnosis delay attributed to hair concealment of lesions. Methods: Primary melanomas of the scalp diagnosed over two decades at four reference centers in Australia and Italy were included. Hair coverage and visibility of the lesions were assessed on preoperative photographic documentation by two investigators and correlated with some prognostic factors (Breslow thickness, mitotic rate, and ulceration). Patients records and pathology reports provided clinical and histological data. Results: The majority of 113 melanomas included were located on easily visible areas of the scalp – hairless scalp (49%) or hairline (15%). The remaining ones (36%), considered to be hair-covered, showed more frequently thinning of hair (63%) than a dense hair coverage (37%). Melanomas of “hairy scalps” were more frequently invasive (81%) and had higher median Breslow (0.8±1.3mm) than those arising on bald scalps or areas with thinning of hair (43%; 0±0.6mm), P=0.004. However, when considering only the invasive cases (n=55), Breslow thickness and mitotic rate were not statistically different between concealed and easily visible areas. Melanomas detected by a doctor were thinner than those first noticed by the patient, relatives, or a hairdresser (P&nbsp

Immunotherapy has greatly improved outcomes for subgroups of patients with cancer. As indications keep expanding, there is an unmet need to gain a better understanding of the effect of these therapies on pregnancy and fertility. During pregnancy, substantial adaptations occur in the maternal immune system to maintain protection against pathogens while avoiding detrimental reactions to the semi-allogeneic fetus. The pathways involved in the establishment of this fetomaternal tolerance can be hijacked by cancers. Immunotherapies that target these inhibitory pathways, or that directly interact with the regulatory immune cells involved in tolerance mechanisms, might therefore result in complications during pregnancy. Similarly, by activating the patient's immune system with immunotherapy, a broad range of immune-related adverse events can occur that could negatively affect the fetus or impede a future desired pregnancy. This Review summarises preclinical and clinical data related to the use of immunotherapy during pregnancy, including all approved immune checkpoint inhibitors, recombinant cytokines, cell therapies, vaccines, and immunomodulatory drugs.

Symptoms of treatment-induced menopause negatively affect quality of life and adherence to endocrine therapy of breast cancer (BC) survivors. Nevertheless, the use of systemic hormone replacement therapy (HRT) to mitigate these symptoms may be associated with an increased risk of disease recurrence in these patients. This systematic review and meta-analysis aimed to assess the safety of systemic HRT on risk of disease recurrence in BC survivors. A systematic search of PubMed up to April 20, 2021 was conducted to identify randomized controlled trials (RCTs) that investigated the risk of disease recurrence with the use of HRT in BC survivors. A random-effect model was applied to calculate the risk of recurrence, reported as pooled hazard ratio (HR) with 95% confidence intervals (CI). A subgroup analysis was performed to estimate the risk of recurrence according to hormone receptor status. Four RCTs were included in the meta-analysis (n = 4050 patients). Overall, 2022 patients were randomized to receive HRT (estrogen/progestogen combination or tibolone) and 2023 to the control group with placebo or no HRT. HRT significantly increased the risk of BC recurrence compared to placebo (HR 1.46, 95% CI 1.12–1.91, p = 0.006). At the subgroup analysis, the risk of BC recurrence with the use of HRT was significantly increased in patients with hormone receptor-positive disease (HR 1.8, 95% CI 1.15–2.82, p = 0.010) but not in those with hormone receptor-negative tumors (HR 1.19, 95% CI 0.80–1.77, p = 0.390). Use of HRT was associated with a detrimental prognostic effect in BC survivors, particularly in those with hormone receptor-positive disease. Alternative interventions to mitigate menopause-related symptoms should be proposed.

Anthracyclines are among the most active chemotherapies (CT) in breast cancer (BC). However, cardiotoxicity is a risk and peculiar side effect that has been limiting their use in clinical practice, especially after the introduction of taxanes. Non‐pegylated liposomal doxorubicin (NPLD) has been developed to optimize the toxicity profile induced by anthracyclines, while maintaining its unquestionable therapeutic index, thanks to its delivering characteristics that increase its diffusion in tumor tissues and reduce it in normal tissues. This feature allows NPLD to be safely administered beyond the standard doxorubicin maximum cumulative dose of 450–480 mg/m2. Following three pivotal first‐line phase III trials in HER2‐negative metastatic BC (MBC), this drug was finally approved in combination with cyclophosphamide in this specific setting. Given the increasing complexity of the therapeutic scenario of HER2‐negative MBC, we have carefully revised the most updated literature on the topic and dissected the potential role of NPLD in the evolving therapeutic algorithms., SCOPUS: re.j, info:eu-repo/semantics/published

s Introduction During the COVID-19 pandemic, teleconsultation was implemented in clinical practice to limit patient exposure to COVID-19 while monitoring their treatment and follow-up. We sought to examine the satisfaction of patients with breast cancer (BC) who underwent teleconsultations during this period. Methods Eighteen centres in France and Italy invited patients with BC who had at least one teleconsultation during the first wave of the COVID-19 pandemic to participate in a web-based survey that evaluated their satisfaction (EORTC OUT-PATSAT 35 and Telemedicine Satisfaction Questionnaire [TSQ] scores) with teleconsultation. Results Among the 1299 participants eligible for this analysis, 53% of participants were undergoing standard post-treatment follow-up while 22 and 17% were currently receiving active anticancer therapy for metastatic and localised cancers, respectively. The mean satisfaction scores were 77.4 and 73.3 for the EORTC OUT-PATSAT 35 and TSQ scores, respectively. In all, 52.6% of participants had low/no anxiety. Multivariable analysis showed that the EORTC OUT-PATSAT 35 score correlated to age, anxiety score and teleconsultation modality. The TSQ score correlated to disease status and anxiety score. Conclusion Patients with BC were satisfied with oncology teleconsultations during the COVID-19 pandemic. Teleconsultation may be an acceptable alternative follow-up modality in specific circumstances.

The GIM2 phase III trial demonstrated the benefit of dose-dense chemotherapy in node-positive early breast cancer (eBC). To better define the dose-dense effect in the hormone receptor-positive subgroup, we evaluated its benefit through a composite measure of recurrence risk. We conducted an ancillary analysis of the GIM2 trial evaluating the absolute treatment effect through a composite measure of recurrence risk (CPRS) in patients with hormone receptor-positive HER2-negative eBC. CPRS was estimated through Cox proportional hazards models applied to the different clinicopathological features. The treatment effect was compared to the values of CPRS by using the Sub-population Treatment Effect Pattern Plot (STEPP) process. The Disease-Free Survival (DFS)-oriented STEPP analysis showed distinct patterns of relative treatment effect with respect to CPRS. Overall, 5-year DFS differed across CPRS quartiles ranging from 95.2 to 66.4%. Each CPRS quartile was characterized by a different patients’ composition, especially for age, lymph node involvement, tumor size, estrogen and progesterone receptor expression, and Ki-67. A number needed to treat of 154 and 6 was associated with the lowest and the highest CPRS quartile, respectively. Dose-dense adjuvant chemotherapy showed a consistent benefit in node-positive eBC patients with hormone receptor-positive HER2-negative disease, but its effect varied according to CPRS.

The paper reports the case of a 5-year-old boy who presented with Perthes’ Disease with a long and underhand history of persistent coxalgia, which later became bilateral. Therefore, the main clinical data were reviewed with a particular focus on the diagnostic process and on those elements of pathogenesis and epidemiology that constitute suspicion index. While it is not a matter of urgency, early diagnosis is a priority. Magnetic resonance imaging represents the diagnostic test, since the radiography in the initial stages of the disease could be negative and the ultrasound can be confusing because it often looks like benign coxalgia. Therapeutic intervention based on severity varies from the use of orthopedic braces to surgery.

Children with Beckwith-Wiedemann syndrome (BWs) have an increased risk of developing embryonic tumours during the first few years of life. Predisposition to the development of tumours is closely related to molecular subtype and therefore the cancer screening programme should be individualized on the basis of the genotype. Among the most common tumours, those with adrenal origin even if they show benign characteristics should be evaluated to rule out the hypothesis of severe tumours such as neuroblastoma. The paper reports the case of a newborn with BWs who showed an adrenal mass shortly after birth. To evaluate the lesion, though there is little available literature on the subject, one of the few existing algorithm for the diagnosis and follow-up was used. In case of ultrasound detection of an adrenal mass the algorithm first considers age, size and type of consistency (cystic or solid).

Valentino Martelli,1,2 Maria Maddalena Latocca,1,2 Tommaso Ruelle,1,2 Marta Perachino,1,2 Luca Arecco,1,2 Kristi Beshiri,1,2 Maria Grazia Razeti,1,2 Marco Tagliamento,1,2 Maurizio Cosso,3 Piero Fregatti,4,5 Matteo Lambertini1,2 1Department of Medical Oncology, U.O.C Clinica Di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, Italy; 2Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Genova, Italy; 3Department of Radiology, IRCCS Ospedale Policlinico San Martino, Genova, Italy; 4U.O.C. Clinica Di Chirurgia Senologica, Department of Surgery, IRCCS Ospedale Policlinico San Martino, Genova, Italy; 5Department of Integrated Diagnostic Surgical Sciences, School of Medicine, University of Genova, Genova, ItalyCorrespondence: Matteo LambertiniIRCCS Ospedale Policlinico San Martino, University of Genova, Largo Rosanna Benzi 10, Genova, 16132, ItalyTel +39 010 555 4254Fax + 39 010 555 6536Email matteo.lambertini@unige.itAbstract: Over the last several decades, improvements in breast cancer treatment have contributed to increased cure rates for women diagnosed with this malignancy. Consequently, great importance should be paid to the long-term side effects of systemic therapies. For young women (defined as per guideline ≤ 40 years at diagnosis) who undergo chemotherapy, one of the most impactful side effects on their quality of life is premature ovarian insufficiency (POI) leading to fertility-related problems and the side effects of early menopause. Regimens, type, and doses of chemotherapy, as well as the age of patients and their ovarian reserve at the time of treatment are major risk factors for treatment-induced POI. For these reasons, childbearing desire and preservation of ovarian function and/or fertility should be discussed with all premenopausal patients before planning the treatments. This manuscript summarizes the available fertility preservation techniques in breast cancer patients, the risk of treatment-induced POI with different anticancer treatments, and the possible procedures to prevent it. A special focus is paid to the role of oncofertility counseling, as a central part of the visit in this setting, during which the patient should receive all the information about the potential consequences of the disease and of the proposed treatment on her future life.Keywords: breast cancer, fertility, young patient, oncofertility, premature ovarian insufficiency, anti-Mullerian hormone

IMPORTANCE Whether the severity and mortality of COVID-19 in patients with cancer have improved in terms of disease management and capacity is yet to be defined. OBJECTIVE To test whether severity and mortality from COVID-19 among patients with cancer have improved during the course of the pandemic. DESIGN, SETTING, AND PARTICIPANTS OnCovid is a European registry that collects data on consecutive patients with solid or hematologic cancer and COVID-19. This multicenter case series study included real-world data from 35 institutions across 6 countries (UK, Italy, Spain, France, Belgium, and Germany). This update included patients diagnosed between February 27, 2020, and February, 14, 2021. Inclusion criteria were confirmed diagnosis of SARS-CoV-2 infection and a history of solid or hematologic cancer. EXPOSURES SARS-CoV-2 infection. MAIN OUTCOMES AND MEASURES Deaths were differentiated at 14 days and 3 months as the 2 landmark end points. Patient characteristics and outcomes were compared by stratifying patients across 5 phases (February to March 2020, April to June 2020, July to September 2020, October to December 2020, and January to February 2021) and across 2 major outbreaks (February to June 2020 and July 2020 to February 2021). RESULTS At data cutoff, 2795 consecutive patients were included, with 2634 patients eligible for analysis (median [IQR] age, 68 [18-77] years ; 52.8% men). Eligible patients demonstrated significant time-dependent improvement in 14-day case-fatality rate (CFR) with estimates of 29.8% (95% CI, 0.26-0.33) for February to March 2020; 20.3% (95% CI, 0.17-0.23) for April to June 2020;12.5% (95% Cl, 0.06-22.90) for July to September 2020; 17.2% (95% CI, 0.15-0.21) for October to December 2020; and 14.5% (95% CI, 0.09-0.21) for January to February 2021(all P < .001) across the predefined phases. Compared with the second major outbreak, patients diagnosed in the first outbreak were more likely to be 65 years or older (974 of 1626 [60.3%] vs 564 of 1008 [56.1%]; P = .03), have at least 2 comorbidities (793 of 1626 [48.8%) vs 427 of 1008 [42.4%); P = .001), and have advanced tumors (708 of 1626 [46.4%) vs 536 of 1008 [56.1%]: P < .001). Complications of COVID-19 were more likely to be seen (738 of 1626 [45.4%) vs 342 of 1008 [33.9%]; P < .001) and require hospitalization (969 of 1626 [59.8%) vs 418 of 1008 [42.1%); P < .001) and anti-COVID-19 therapy (1004 of 1626 [61.7%) vs 501of 1008 [49.7%); P < .001) during the first major outbreak. The 14-day CFRs for the first and second major outbreaks were 25.6% (95% CI, 0.23-0.28) vs 16.2% (95% CI, 0.13-0.19; P < .001), respectively. After adjusting for country, sex, age, comorbidities, tumor stage and status, anti-COVID-19 and anticancer therapy, and COVID-19 complications, patients diagnosed in the first outbreak had an increased risk of death at 14 days (hazard ratio [HR], 1.85; 95% CI, 1.47-2.32) and 3 months (HR, 1.28; 95% CI, 1.08-1.51) compared with those diagnosed in the second outbreak. CONCLUSIONS AND RELEVANCE The findings of this registry-based study suggest that mortality in patients with cancer diagnosed with COVID-19 has improved in Europe; this improvement may be associated with earlier diagnosis, improved management, and dynamic changes in community transmission over time.

Background: The medium-term and long-term impact of COVID-19 in patients with cancer is not yet known. In this study, we aimed to describe the prevalence of COVID-19 sequelae and their impact on the survival of patients with cancer. We also aimed to describe patterns of resumption and modifications of systemic anti-cancer therapy following recovery from SARS-CoV-2 infection. Methods: OnCovid is an active European registry study enrolling consecutive patients aged 18 years or older with a history of solid or haematological malignancy and who had a diagnosis of RT-PCR confirmed SARS-CoV-2 infection. For this retrospective study, patients were enrolled from 35 institutions across Belgium, France, Germany, Italy, Spain, and the UK. Patients who were diagnosed with SARS-CoV-2 infection between Feb 27, 2020, and Feb 14, 2021, and entered into the registry at the point of data lock (March 1, 2021), were eligible for analysis. The present analysis was focused on COVID-19 survivors who underwent clinical reassessment at each participating institution. We documented prevalence of COVID-19 sequelae and described factors associated with their development and their association with post-COVID-19 survival, which was defined as the interval from post-COVID-19 reassessment to the patients’ death or last follow-up. We also evaluated resumption of systemic anti-cancer therapy in patients treated within 4 weeks of COVID-19 diagnosis. The OnCovid study is registered in ClinicalTrials.gov, NCT04393974. Findings: 2795 patients diagnosed with SARS-CoV-2 infection between Feb 27, 2020, and Feb 14, 2021, were entered into the study by the time of the data lock on March 1, 2021. After the exclusion of ineligible patients, the final study population consisted of 2634 patients. 1557 COVID-19 survivors underwent a formal clinical reassessment after a median of 22·1 months (IQR 8·4–57·8) from cancer diagnosis and 44 days (28–329) from COVID-19 diagnosis. 234 (15·0%) patients reported COVID-19 sequelae, including respiratory symptoms (116 [49·6%]) and residual fatigue (96 [41·0%]). Sequelae were more common in men (vs women; p=0·041), patients aged 65 years or older (vs other age groups; p=0·048), patients with two or more comorbidities (vs one or none; p=0·0006), and patients with a history of smoking (vs no smoking history; p=0·0004). Sequelae were associated with hospitalisation for COVID-19 (p

Introduction how best to manage patients with colorectal cancer and synchronous liver metastasis is still controversial, with specific concerns of increased risk of postoperative complications following combined resection. We aimed at analyzing the influence of combined liver resection on the risk of anastomotic leak (AL) following colorectal resection. Methods we reviewed the iCral prospectively maintained database to compare the relative risk of AL of patients undergoing colorectal resection for cancer to that of patients receiving simultaneous liver and colorectal resection for cancer with isolated hepatic metastases. The incidence of AL was the primary outcome of the analysis. Perioperative details and postoperative complications were also appraised. Results out of a total of 996 patients who underwent colorectal resection for cancer, 206 receiving isolated colorectal resection were compared with a matched group of 53 patients undergoing simultaneous liver and colorectal resection. Combined surgery had greater operative time and resulted in longer postoperative hospitalization compared to colorectal resection alone. The proportion of overall morbidity following combined resection was significantly higher than after isolated colorectal resection (56.6% vs. 37.9%, p = 0.021). Overall, the two groups of patients did not differ neither on the rate of major postoperative complications, nor in terms of AL (9.4% vs. 6.3%, p = 0.381). At specific multivariate analysis, the duration of surgery was the only risk factor independently associated with the likelihood of AL. Conclusions combining hepatic with colorectal resection for the treatment of synchronous liver metastasis from colorectal cancer does not increase significantly the incidence of AL.

[68Ga]-Ga-PSMA-PET/CT (PSMA-PET) is routinely performed in many patients who have received or are receiving Androgen Deprivation Therapy (ADT). However, potentially occurring interactions of ADT on PSMA expression in men with Prostate cancer (PCa) have not been yet fully investigated nor understood. Since an influence of ADT on the expression of PSMA was observed in both in vitro and in vivo studies, relevant implications for image interpretation and PSMA-radioligand therapy (RLT) timing may arise from a better understanding of such a phenomenon. In this mini review, we analyzed the most relevant clinical literature on this topic (PubMed). We also presented a case series of two patients who underwent sequential PSMA-PET during ADT. We found a total of five studies which investigated the effect of ADT on PSMA expression on 43 patients at different stages of the natural history of the disease. Four studies investigated the effect of short-term ADT and detected an increase of PSMA expression (more or less heterogeneous). The remaining study investigated the long-term ADT effect, demonstrating a decrease in most lesions. In our case series, despite a complete PSA response, we observed a rapid up-regulation of PSMA expression in our PSMA-PET imaging immediately after ADT administration. Although clinical evidence remains inconclusive, a short-term ADT administration may seem to increase PSMA expression in some selected cases, while long-term ADT might have the opposite effect at least in castrate sensitive prostate cancer (CSPC) patients, even if potentially leading to an early selection of those lesions most at risk of becoming castrate resistant.

Background: Young breast cancer patients (pts) carrying a germline BRCA mutation (mBRCA) have similar outcomes as non-carriers. However, there is currently lack of evidence regarding the impact of mBRCA type and hormone receptor status on clinical behavior and outcomes of mBRCA breast cancer. We aim to address these questions in the largest dataset to date of young mBRCA breast cancer pts. Methods: This was an international, multicenter, hospital-based, retrospective cohort study. Women harboring deleterious germline mBRCA1 or mBRCA2 that received a diagnosis of stage I-III invasive early breast cancer at age ≤40 years between January 2000 and December 2012 were included. Baseline pts, tumor, and treatment characteristics, pattern and risk over time of disease-free survival (DFS) events, and survival outcomes (DFS, distant recurrence-free interval [DRFI] and overall survival [OS]) were compared between mBRCA1 and mBRCA2 pts overall and by hormone receptor status. Multivariate Cox proportional hazard models were used to compare hazard rates (HRs). Results: 1,236 young mBRCA breast cancer pts were included. Among 808 and 428 pts with mBRCA1 or mBRCA2, respectively, 191 (23.6%) and 356 (83.2%) had hormone receptor-positive tumors while 617 (76.4%) and 72 (16.8%) hormone receptor-negative disease (p Conclusions: In this large unique dataset, young mBRCA1 breast cancer pts had worse DFS than those with mBRCA2 mostly due to higher rates of second primary malignancies. Hormone receptor positivity had no positive prognostic value in young mBRCA breast cancer pts with a trend towards worse DRFI in those with hormone receptor-negative disease. These results provide important information for counseling young mBRCA breast cancer pts regarding treatment, prevention and follow-up care strategies. Citation Format: Matteo Lambertini, Marcello Ceppi, Anne-Sophie Hamy, Olivier Caron, Philip D. Poorvu, Estela Carrasco, Albert Grinshpun, Kevin Punie, Christine Rousset-Jablonski, Alberta Ferrari, Shani Paluch-Shimon, Angela Toss, Claire Senechal, Fabio Puglisi, Katarzyna Pogoda, Jose Alejandro Pérez-Fidalgo, Laura De Marchis, Riccardo Ponzone, Luca Livraghi, Maria Del Pilar Estevez-Diz, Cynthia Villarreal-Garza, Maria Vittoria Dieci, Florian Clatot, Francois P. Duhoux, Rossella Graffeo, Luis Teixeira, Octavi Córdoba, Amir Sonnenblick, Arlindo R. Ferreira, Ann H. Partridge, Antonio Di Meglio, Claire Saule, Fedro A. Peccatori, Marco Bruzzone, Lucia Del Mastro, Lieveke Ameye, Judith Balmaña, Hatem A. Azim, Jr. Clinical behavior and outcomes of BRCA-mutated breast cancer in young patients according to type of BRCA mutation and hormone receptor status: Results from an international cohort study [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD10-06.

Background: Pregnancy-related issues are a priority for young breast cancer (BC) patients. Increasing evidence has shown that pregnancy after prior BC diagnosis is feasible. Nevertheless, few BC survivors conceive following anticancer treatment completion and many physicians remain concerned about the potentially detrimental effects of pregnancy after BC in terms of fetal/obstetrical outcomes and maternal prognosis. This systematic review and meta-analysis aims at providing updated and solid evidence on these important issues. Methods: A systematic literature review up to January 31, 2020 with no language restriction was conducted to identify studies including patients with a pregnancy after prior BC diagnosis. Chances of pregnancy after BC, fetal and obstetrical outcomes, disease-free survival (DFS) and overall survival (OS) were assessed. Pooled relative risks (RRs), hazard ratios (HRs) or odds ratio (ORs) with 95% confidence intervals (CI) were calculated using the random effects models. The study is registered with the PROSPERO registration number CRD42020158324. Results: Overall, 39 studies were included. Out of the 8,265,713 young women included in these studies, 8,093,401 were from the general population, 57,739 had cancers other than BC, 114,573 had BC. Among the 114,573 BC patients, 7,505 had a pregnancy after BC diagnosis and 107,068 did not. Compared to women from the general population, BC patients had 60% reduced chances of having a pregnancy following anticancer treatment completion (RR 0.40, 95% CI 0.32-0.49). Among other cancer patients, only women with prior cervical cancer had lower pregnancy rates (RR 0.33, 95% CI 0.31-0.35) than BC patients. Compared to the general population, BC survivors had significantly increased risks of low birth weight (OR 1.50, 95% CI 1.31-1.73), small for gestational age (OR 1.16, 95% CI 1.01-1.33), preterm delivery (OR 1.45, 95% CI 1.11-1.88) and caesarean section (OR 1.14, 95% CI 1.04-1.25). No significant increased risk of congenital abnormalities (OR 1.63, 95% CI 0.89-2.98) or other pregnancy or delivery complications (spontaneous or induced abortion, gestosis, antepartum or postpartum hemorrhage) was observed. Prior chemotherapy exposure or short pregnancy interval (defined as Pregnancy after BC was not associated with a negative impact on patients’ outcomes. Compared to BC patients without subsequent pregnancy, those with pregnancy after BC had better OS (HR 0.56, 95% CI 0.46-0.67) and DFS (HR 0.73, 95% CI 0.56-0.94). Similar results were observed in the studies correcting for the potential “healthy mother effect” (OS: HR 0.52, 95% CI 0.42-0.65; DFS: HR 0.74, 95% CI 0.58-0.96). No detrimental prognostic effect of pregnancy after BC was observed in patients with hormone-receptor positive disease (DFS: HR 1.10, 95% CI 0.73-1.66), while better outcomes were observed for those with hormone-receptor negative disease (DFS: HR 0.72, 95% CI 0.55-0.95). The safety of pregnancy after BC was observed irrespective of BRCA status, nodal status, previous chemotherapy exposure, pregnancy interval and pregnancy outcomes. Conclusions: This large meta-analysis provides solid evidence on the safety of pregnancy after prior BC diagnosis. The increased risk of fetal and obstetrical complications (but not of congenital abnormalities) calls for ensuring a closer monitoring of these pregnancies. The significantly reduced chances of conceiving as compared to the general population and other cancer patients should raise further awareness on the need to improve the oncofertility counseling of young BC patients wishing to complete their family planning following anticancer treatment completion. Citation Format: Eva Blondeaux, Marta Perachino, Marco Bruzzone, Richard A. Anderson, Evandro De Azambuja, Philip D. Poorvu, Hee Jeong Kim, Cynthia Villarreal-Garza, Barbara Pistilli, Ines Vaz-Luis, Cristina Saura, Kathryn J. Ruddy, Maria Alice Franzoi, Chiara Sertoli, Marcello Ceppi, Hatem A. Azim, Jr., Frederic Amant, Isabelle Demeestere, Lucia Del Mastro, Ann H. Partridge, Olivia Pagani, Fedro A. Peccatori, Matteo Lambertini. Chances of pregnancy after breast cancer, reproductive and disease outcomes: A systematic review and meta-analysis [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr GS3-09.

Background: The association between obesity and prognosis in HER2-positive early breast cancer remains unclear, with limited data available. This study aimed to determine the impact of body mass index (BMI) at baseline and weight change after 2 years on outcomes of patients with HER2-positive early breast cancer. Methods: ALTTO was a randomized phase III trial in patients with HER2-positive early breast cancer. BMI was collected at randomization and 2 years after. WHO BMI categories were used: underweight, 2; normal weight, 18.5 to 2; overweight, ≥25 to 2; and obese ≥30 kg/m2. A weight change from baseline of ≥5.0% and ≤5.0% was categorized as weight gain and weight loss. The impact of BMI at randomization and of weight change on disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS) were investigated with multivariate analyses, adjusting for baseline patients and tumor characteristics. Results: A total of 8,381 patients were included: 187 (2.2%), 3,797 (45.3%), 2,690 (32.1%), and 1,707 (20.4%) were underweight, normal weight, overweight, and obese at baseline, respectively. Compared with normal weight, being obese at randomization was associated with a significantly worse DDFS (adjusted hazard ratio [aHR], 1.25; 95% CI, 1.04–1.50) and OS (aHR, 1.27; 95% CI, 1.01–1.60), but no significant difference in DFS (aHR, 1.14; 95% CI, 0.97–1.32). Weight loss ≥5.0% at 2 years after randomization was associated with significantly poorer DFS (aHR, 1.34; 95% CI, 1.05–1.71), DDFS (aHR, 1.46; 95% CI, 1.07–1.98), and OS (aHR, 1.83; 95% CI, 1.18–2.84). Hormone receptor and menopausal status but not anti-HER2 treatment type influenced outcomes. Toxicities were more frequent in obese patients. Conclusions: In patients with HER2-positive early breast cancer, obesity at baseline is a poor prognostic factor. Weight loss during treatment and follow-up negatively impacts clinical outcomes. Dietary counseling should be part of survivorship care programs.

Oral (OP) and nail (NP) pigmentations may occur simultaneously in physiological or pathological conditions, and may be a sign of underlying syndromic conditions that necessitate further investigation and treatment. Interestingly, the nail unit and oral cavity show a clinical parallelism that may help the clinician to conduct a correct examination and reach a prompt diagnosis. Both OP and NP can manifest clinically with focal or diffuse involvement and are due to external factors (exogenous pigmentation, drug-induced pigmentation) or endogenous factors (racial pigmentation, post-inflammatory pigmentation, nevi, genetic conditions and other disorders). The most concerning differential diagnosis is melanoma. Here we report the pathogenetic basis of OP and NP, together with the description of similar clinical features. To the best of our knowledge this is the first paper to summarize and describe the causes of pigmentation of both the oral cavity and the nail unit.

Orale und Nagelpigmentierungen: eine für den Kliniker nützliche Parallelität.

68Ga-labeled urea-based inhibitors of the prostate-specific membrane antigen (PSMA), such as 68Ga-PSMA-11, are promising small molecules for targeting prostate cancer (PCa). Although this radiopharmaceutical was produced mostly by means of manual synthesis and automated synthesis modules, a sterile cold kit was recently introduced. The aim of our study was to evaluate the image quality of 68Ga-PSMA-11 PET/CT (PSMA-PET) in a population of PCa patients after the injection of comparable activities of 68Ga-PSMA-11 obtained with the 2 different synthetic procedures. A secondary aim was to identify secondary factors that may have an impact on image quality and, thus, final interpretation. Methods: Two different groups of 100 consecutive PCa patients who underwent PSMA-PET were included in the study. The first group of patients was imaged with 68Ga-PSMA-11 obtained using synthesis modules, whereas the second group's tracer activity was synthesized using a sterile cold kit. All PET images were independently reviewed by 2 nuclear medicine diagnosticians with at least 2 y of experience in PSMA-based imaging and unaware of the patients' clinical history. The 2 reviewers independently rated the quality of each PSMA-PET scan using a 3-point Likert-type scale. In cases of discordance, the operators together reviewed the images and reached a consensus. Performance was evaluated on the basis of the expected biodistribution, lesion detection rate, and physiologic background uptake. Results: Overall, 104 of 200 (52%) PSMA-PET scans were positive for PCa-related findings. No significant differences in image quality between cold kits and synthesis modules were found (P = 0.13), although a higher proportion of images was rated as excellent by the observers for kits than for modules (45% vs. 34%). Furthermore, after image quality had been dichotomized as excellent or not excellent, multivariate regression analysis found several factors to be significantly associated with a not-excellent quality: an increase in patient age (+5 y: odds ratio [OR], 1.40; 95% confidence interval [CI], 1.12-1.75), an increase in patient weight (+5 kg: OR, 1.89; 95% CI, 1.53-2.32), an increase in 68Ga-PSMA-11 uptake time (+10 min: OR, 1.45; 95% CI, 1.08-1.96), and a decrease in injected activity (-10 MBq: OR, 1.28; 95% CI, 1.07-1.52). Conclusion: No significant differences were identified between the 2 groups of patients undergoing PSMA-PET; therefore, we were not able to ascertain any significant influences of tracer production methodology on final scan quality. However, increased patient age, increased patient weight, decreased injected activity, and increased 68Ga-PSMA-11 uptake time were significantly associated with an overall poorer image quality.

Purpose: To evaluate the role of F-18-Fluorothymidine (FLT) PET/CT in lymphoma patients with suspected recurrent or residual disease. Methods: Adult lymphoma patients presenting with positive or equivocal F-18-FDG PET/CT at end-treatment or follow-up were prospectively addressed to an additional F-18-FLT-PET/CT. SUV max and tumour-to-background ratios (TBRs) were recorded for the most avid lesion. Biopsy or, when not available, clinical or imaging assessment were employed as standard of reference. Results: Overall 52 patients were recruited. Histology was available in 20/52 patients (38%), proliferation-index (Ki-67) in 14/20. Disease was excluded in 13/52 patients (25%) (one reactive follicular hyperplasia, five reactive-inflammatory tissues, four reactive nodes, two nodal sarcoid-like and one non-specific peri-caecal finding). FDG and FLT scans were concordant in disease restaging in 34/52 patients (65%), whereas in 18/52 cases (35%) relevant discrepancies were recorded. SUV max and TBR were significantly higher in the disease versus the disease-free group, with both tracers (p = 0.0231 and 0.0219 for FDG; p = 0.0008 and 0.0016 for FLT). FLT-SUVmax demonstrated slightly better performance in discriminating benign from malignant lesions (ROC-AUC: 0.8116 and 0.7949 for FLT-SUV max and TBR; 0.7120 and 0.7140 for FDG). Optimal FLT-SUV max cut-offs were searched: three would lead to 95% sensitivity, 81% accuracy, and 39% specificity, whereas seven led to 100%, 41%, and 56% respectively. No statistically significant correlation was observed between the two FLT indices and Ki-67. Conclusions: According to our results in a clinical setting of recurrent or residual lymphoma, FLT is not significantly superior to FDG and it is unlikely that it will be employed independently. FLT may be restricted to a few specific cases, as complementary to standard FDG imaging, to confirm a diagnosis or to define a better target to biopsy. However, due to FLT suboptimal performance, many findings would remain inconclusive, requiring further diagnostic procedures and reducing the effectiveness of performing an additional FLT scan.

Objectives: The extension of atypical melanocytes to the hair follicle, also termed melanoma folliculotropism, is poorly evaluated and its role is contradictory. We performed an observational study focusing on anatomical areas rich in follicles, such as the head and neck region. Methods: Primary head and neck melanomas diagnosed in the Melanoma Unit, Policlinic Sant'Orsola-Malpighi, University of Bologna were analyzed. Folliculotropism was evaluated with a quantitative and morphologic parameter. Statistical analyses were performed correlating patients' prognosis with folliculotropism and other clinical and histopathologic factors. Results: The study was carried out on a sample of 62 patients. The diffuse distribution (atypical melanocytes present in more than three contiguous follicular units) correlated with scalp localization, nodular subtype, higher Breslow thickness, and a poorer prognosis. Conclusions: We believe that folliculotropism should be further investigated and reported by pathologists during the histologic diagnosis of melanoma.

Background/aim The perspective validation of a selective approach in patients undergoing breast cancer surgery was performed in order to assess whether patients as well as Health Care Workers (HCWs) were exposed to any undue risk of COVD-19 infection. Patients and methods From March 9th to June 9th 2020, 207 patients were phone-triaged by a dedicated Breast Care Nurse; a patient-tailored program was adopted with the aim of avoiding hospitalization of SARS-CoV-2 symptomatic patients, with a careful prioritization of surgical procedures according to specific disease features. Results Two hundred and three out of 207 patients underwent operation; seven patients were temporarily excluded because they tested positive at phone triage (n=3), or in-hospital triage (n=3); another asymptomatic patient with negative NP swab tested IgM Ab-positive so that surgery was re-scheduled two weeks later. Four patients had no surgery; one of them was reconsidered for neoadjuvant chemotherapy (NAC) after testing positive at phone triage; three patients were excluded because they were already hospitalized for COVID-19. Overall, mean in-hospital stay was 2.2 days (±SD, 0.7) and, after hospital discharge, no patient required readmission. Conclusion This preventive program avoided any COVID-19 infection among patients and HCWs, so that an elective breast cancer surgical procedure can be safely and timely pursued without affecting the oncologic outcome.

Background Patients with coronavirus disease 2019 (COVID-19) who have underlying malignancy have a higher mortality rate compared with those without cancer, although the magnitude of such excess risk is not clearly defined. We performed a systematic review and pooled analysis to provide precise estimates of the mortality rate among patients with both cancer and COVID-19. Methods A systematic literature search involving peer-reviewed publications, preprints and conference proceedings up to July 16, 2020, was performed. The primary end-point was the case fatality rate (CFR), defined as the rate of death among patients with cancer and COVID-19. The CFR was assessed with a random effects model, which was used to derive a pooled CFR and its 95% confidence interval (CI). Results Fifty-two studies, involving a total of 18,650 patients with both COVID-19 and cancer, were selected for the pooled analysis. A total of 4243 deaths were recorded in this population. The probability of death was 25.6% (95% CI: 22.0%–29.5%; I2 = 48.9%) in this patient population. Conclusions Patients with cancer who develop COVID-19 have high probability of mortality. Appropriate and aggressive preventive measures must be taken to reduce the risk of COVID-19 in patients with cancer and to optimally manage those who do contract the infection., Highlights • Patients with both cancer and coronavirus disease 2019 (COVID-19) have a higher mortality than reported in the overall COVID-19-positive population. • We aim to provide precise mortality estimates among patients with cancer and COVID-19. • Pooled case mortality rate was 25.6% (95% CI: 22.0%–29.5%; I2 = 48.9%). • Aggressive measures must be taken to reduce risk of infection in patients with cancer.

Chemotherapy-induced ovarian damage:apoptosis and/or in vitro activation?The term‘‘ovarian reserve’’is typically used to refer to the pop-ulation ofprimordial follicles (PMFs) .This population is very sensitive to cytotoxic drugs, especially alkylating agents (cyclo-phosphamide, busulfan, ifosfamide). Among them, cyclophos-phamide (CPA) is the alkylating agent that causes the mostdamage to oocytes and granulosa cells. Alkylating-like plat-inum complexes (such as cisplatin, anthracyclanes [includingdoxorubicin]) should also be considered as ovo-toxic drugs. [...]

PURPOSE Young women with germline BRCA mutations have unique reproductive challenges. Pregnancy after breast cancer does not increase the risk of recurrence; however, very limited data are available in patients with BRCA mutations. This study investigated the impact of pregnancy on breast cancer outcomes in patients with germline BRCA mutations. PATIENTS AND METHODS This is an international, multicenter, hospital-based, retrospective cohort study. Eligible patients were diagnosed between January 2000 and December 2012 with invasive early breast cancer at age ≤ 40 years and harbored deleterious germline BRCA mutations. Primary end points were pregnancy rate, and disease-free survival (DFS) between patients with and without a pregnancy after breast cancer. Pregnancy outcomes and overall survival (OS) were secondary end points. Survival analyses were adjusted for guarantee-time bias controlling for known prognostic factors. RESULTS Of 1,252 patients with germline BRCA mutations ( BRCA1, 811 patients; BRCA2, 430 patients; BRCA1/2, 11 patients) included, 195 had at least 1 pregnancy after breast cancer (pregnancy rate at 10 years, 19%; 95% CI, 17% to 22%). Induced abortions and miscarriages occurred in 16 (8.2%) and 20 (10.3%) patients, respectively. Among the 150 patients who gave birth (76.9%; 170 babies), pregnancy complications and congenital anomalies occurred in 13 (11.6%) and 2 (1.8%) cases, respectively. Median follow-up from breast cancer diagnosis was 8.3 years. No differences in DFS (adjusted hazard ratio [HR], 0.87; 95% CI, 0.61 to 1.23; P = .41) or OS (adjusted HR, 0.88; 95% CI, 0.50 to 1.56; P = .66) were observed between the pregnancy and nonpregnancy cohorts. CONCLUSION Pregnancy after breast cancer in patients with germline BRCA mutations is safe without apparent worsening of maternal prognosis and is associated with favorable fetal outcomes. These results provide reassurance to patients with BRCA-mutated breast cancer interested in future fertility.

Risk stratification by genomic signatures has been shown to improve prognostication and guide treatment decisions among patients with hormone-sensitive breast cancer. However, their role in young women has not been fully elucidated. In this review, a systematic search was conducted for published articles and abstracts from major congresses that evaluated the use of genomic signatures in young breast cancer patients. A total of 71 studies were analyzed, including 561,188 patients of whom 27,748 (4.9%) were young. Women aged ≤40 years were subjected to genomic testing at a similar rate to older women but had a higher proportion of intermediate- to high-risk tumors when classified by EndoPredict (p = 0.04), MammaPrint (p p

Aim This study aimed to evaluate the patterns and potential risk factors associated with the occurrence of Salmonella sp. and Escherichia coli in selected United States swine feed mills. Methods and results A total of 405 samples were collected during fall 2018, spring and summer 2019 from selected sites including floors, equipment, shoes and feed in six feed mills in the US Midwest region. Each sample was analysed for the presence of Salmonella and E. coli with culture methods and confirmed by PCR. A survey regarding production volumes, hygiene practices and microbial testing capabilities was conducted in each facility All mills had at least one sampling site positive for either Salmonella or E. coli. Of the 405 samples, 4·7, and 14·1% were positive for Salmonella sp., and E. coli respectively. Sites with higher percentages of positive samples were the receiving, manufacturing, and control area floors. The survey responses indicated that the age of the mill might be a risk factor for bacterial contamination: the older the facility, the higher the number of positive samples. Other risk factors evaluated, such as the production capacity, did not appear to relate to bacterial prevalence. Conclusion The data documents the presence of E. coli and Salmonella in selected US swine feed mills, and an association between E. coli occurrence and number of ingredient suppliers to feed mill. Significance and impact of the study This information could be used to understand risk factors affecting the occurrence of Salmonella sp. and E. coli in feed mills and help implement monitoring and mitigation strategies for public health.

BACKGROUND/AIM A retrospective study was performed in 246 breast cancer patients to define whether tumor-to-nipple distance (TND) assessment by breast MRI may select patients eligible to nipple-sparing mastectomy (NSM) as compared to permanent section assessment of retroareolar margin. PATIENTS AND METHODS Pre- and post-operative parameters including imaging data, histology of the primary tumor, biologic prognostic factors, and adjuvant regimens were retrieved; patients with close/positive retroareolar margins underwent nipple or NAC excision. The primary endpoint was loco-regional recurrence (LRR). RESULTS Patients with TND ≤2 cm had a significantly higher rate of invasive ductal carcinoma (p

The loss of skeletal muscle mass is widely considered a predictor of poor survival and toxicity in breast cancer patients. The aim of this study is to evaluate if there is pectoralis muscle area (PMA) variation, reflecting loss of skeletal muscle mass, on consecutive MRI examinations after neoadjuvant chemotherapy. The retrospective study protocol was approved by our institutional review board. A total of n = 110 consecutive patients (mean age 56 ± 11 years) who were treated with neoadjuvant chemotherapy (NAC) for histologically proven primary breast cancer between January 2017 and January 2019 and in whom tumor response was checked with standard breast MRI were included. Two radiologists calculated the pectoralis muscle cross-sectional area before and after NAC. Time between the MRI examinations, before starting NAC and after completing NAC, was 166.8 ± 50 days. PMA calculated pre-NAC (8.14 cm2) was larger than PMA calculated post-NAC (7.03 cm2) (p

Background The purpose of this study was to test use of the Dutch leakage score (DLS), serum C‐reactive protein (CRP) and serum procalcitonin (PCT) in the diagnosis of anastomotic leakage (AL) after elective colorectal resection in a prospective observational study. Methods Patients undergoing elective colorectal resection with anastomosis in 19 centres were enrolled over a 1‐year period from September 2017. The DLS and CRP and PCT levels were evaluated on postoperative day (POD) 2, POD3 and POD6. Statistical analysis, including determination of the area under the receiver operating characteristic (ROC) curve (AUC), was performed for the primary endpoint of AL; secondary endpoints were morbidity and mortality rates ( http://clinicaltrials.gov identifier: NCT03560180). Results Among 1546 patients enrolled, the AL rate was 4·9 per cent. Morbidity and mortality rates were 30·2 and 1·3 per cent respectively. With respect to AL, DLS performed better than CRP and PTC levels on POD2 and POD3 (AUC 0·75 and 0·84), whereas CRP levels were documented with better AUC values on POD6 (AUC 0·81). Morbidity was poorly predicted, whereas mortality was best predicted by PCT on POD2 (AUC 0·83) and by DLS on POD3 and POD6 (AUC 0·87 and 0·98 respectively). Overall, the combination of positive PCT, CRP and DLS values resulted in a probability of AL of 21·3 per cent on POD2, 33·4 per cent on POD3, and 47·1 per cent on POD6. However, the combination of their negative values excluded AL in 99·0 per cent of cases on POD2, 99·3 per cent on POD3, and 99·2 per cent on POD6. Conclusion DLS and CRP level are good positive and excellent negative predictors of AL; the addition of PCT improved the predictive value for diagnosis of AL., Early diagnosis and treatment of anastomotic leakage (AL) is crucial to limit related mortality. In this prospective 1‐year multicentre study of 1546 patients who had an elective colorectal resection with anastomosis, the AL rate was 4·9 per cent. The Dutch leakage score was the best predictor of AL on days 2 and 3 after surgery. Colorectal surgery and markers for leakage

Introduction: P and trastuzumab (T) are approved for the treatment of early and advanced breast cancer (BC) pts. Skin rash and diarrhea are frequent adverse events (AE) with P. With the use of lapatinib, we demonstrated that early development of rash correlates with pathologic complete response in the NeoALTTO trial and is both a prognostic and predictive marker in the ALTTO trial. In this subanalysis of the CLEOPATRA trial, we investigated if incidence of rash and diarrhea associates with progression free survival (PFS) or overall survival (OS) and if it can predict the benefit of P+T. Methods: In the CLEOPATRA phase III trial, advanced HER2-positive BC pts where randomized between first-line T vs P+T with at least 6 cycles of docetaxel. We evaluated whether rash (any grade) and/or diarrhea (any grade or grade ≥3) were prognostic in pts receiving P+T and/or predictive of benefit from P+T vs T. To deal with immortal-time bias, we performed a landmark analysis removing pts progressing/dying before a minimum of 46 days (median time to rash/diarrhea occurrence) after treatment initiation (cohort 1), and after end of docetaxel treatment (cohort 2). Survival endpoints were PFS and OS according to study definition. We also investigated if age ( Incidence and Impact of Diarrhea and/or Rash on PFS and OS in cohort 1Patients, n (%)PFS, % at 2 yrsOS, % at 2 yrsPrognostic role (pertuzumab treated)RashYes, any grade169 (42.5)48.587.3No, any grade229 (57.5)37.478.0HR (95% CI), p-value (any grade vs. no)NA0.71 (0.56-0.91), p Citation Format: Arlindo R. Ferreira, Noam Pondé, Matteo Lambertini, Christian Maurer, Samuel Martel, Luis Costa, Evandro De Azambuja. Association between pertuzumab (P) induced diarrhea and skin rash and survival outcomes in patients (pts) with HER2-positive metastatic breast cancer enrolled in the CLEOPATRA trial [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-10-09.

Background: The number of people living with HIV is increasing worldwide thanks to the use of effective antiretroviral therapy. As these individuals get older, their risk of being diagnosed with cancer increases, including non-AIDS defining cancers such as breast cancer (BC). Most reports reveal that HIV+ patients (pts) with BC tend to be younger than HIV-uninfected (HIV-) pts. However, epidemiological data is yet conflicting regarding tumor stage at diagnosis, distribution of BC subtypes and overall survival (OS) of HIV+ pts as compared to HIV- pts. This meta-analysis aims to assess differences of baseline clinicopathological characteristics and OS of HIV+ vs HIV- BC pts. Methods: We performed a systematic review using MEDLINE, Scielo, and conference abstracts up to June 10, 2019, with no language restrictions. Cohort studies and consecutive series comparing baseline characteristics (age, stage at diagnosis or BC subtypes) and/or OS of HIV+ vs HIV- BC pts were included. BC subtypes were defined according to 2 classifications: 1) “classic” immunohistochemical (IHC) subtypes (ER+/HER2-; HER2+; triple-negative BC); 2) surrogate intrinsic subtypes as per the St. Gallen Consensus (luminal A-like, luminal B-like, HER2-enriched and basal-like). Summary risk estimates (pooled mean ratios [pMR] and odds ratios [pOR]) and 95% confidence intervals (CI) were calculated using random effects models. OS data were pooled as hazard ratios (HR) and 95% CI and modeled using a random effects model. The main endpoints were age (as a continuous variable), stage at diagnosis (early [0-II] vs late [III-IV]), distribution of BC subtypes and OS (using both adjusted and unadjusted HR). Subgroup analysis of each endpoint was performed according to region of the world. Results: A total of 16 studies (4 from North America and 12 from Sub-Saharan Africa [SSA]) published from 2005-2019 were included in this meta-analysis (with 1,764 HIV+ and 1,330,122 HIV- pts). HIV+ pts were younger than HIV- pts (pooled mean age of 41.1 vs 50.5 years, respectively; pMR 0.82, 95% CI 0.76-0.90, p < 0.001) and had a 45% increased risk of presenting with late stage disease (pOR 1.45, 95% CI 1.25-1.68, p < 0.001). There were no differences regarding distribution of BC subtypes, both by the “classic” IHC or by the St. Gallen classification. Overall, HIV+ pts had a 91% increased risk of dying as compared to HIV- pts (adjusted HR for OS: 1.91, 95% CI 1.06-3.45, p = 0.031 and unadjusted HR for OS: HR 1.47, 95% CI 1.10-1.95, p = 0.008). Subgroup analysis of OS according to region of the world showed that, in North America, HIV+ pts had a significantly increased risk of dying as compared to HIV- pts (adjusted HR 2.96, 95% CI 1.06-8.25, p = 0.038). In SSA, the increased mortality risk among HIV+ pts was also significant (adjusted HR 1.59, 95% CI 1.26-2.00, p < 0.001). Sensitivity analysis showed similar findings. Conclusion: This meta-analysis provides for the first time a comprehensive comparison of baseline characteristics and survival outcomes between HIV+ vs HIV- BC pts. Our results consistently demonstrate that HIV+ pts are diagnosed with BC at a younger age and at a more advanced stage. Additionally, even after adjusting for known prognostic factors, HIV+ pts have a worse OS as compared to HIV- pts, not only in developing countries (SSA) but also and particularly in developed countries (North America). There were no apparent differences in terms of distribution of BC subtypes. These results should raise the awareness of clinicians and policy makers regarding the detection and survival gap among HIV+ BC pts. This underserved population should be the focus of more research efforts, in order to better understand the reasons behind these disparities, which can be related to the HIV infection itself, to a more aggressive BC biology, and/or to a lower access to timely diagnosis and effective treatment. Citation Format: Mariana Brandão, Marco Bruzzone, Maria Alice Franzoi, Claudia De Angelis, Daniel Eiger, Rafael Caparica, Martine Piccart-Gebhart, Laurence Buisseret, Marcello Ceppi, Evandro de Azambuja, Matteo Lambertini. Characteristics and survival outcomes of HIV-positive breast cancer patients: A systematic review and meta-analysis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-11-03.

Introduction: Although HER2+ breast cancer (BC) is considered a moderately immunogenic tumor, several studies have shown a role of pre-existing immunity associated with favorable long-term prognosis and better response to treatment. In this study, we performed exploratory analyses to assess whether the efficacy of HER2 targeted treatment in the MARIANNE trial correlated with immune gene expression. Methods: MARIANNE (NCT01120184) is a phase 3 study in patients (pts) with centrally confirmed HER2+ local advanced/metastatic BC naïve to prior treatments in the advanced disease. Pts were randomized (1:1:1) to trastuzumab+taxane (HT), T-DM1, or T-DM1+Petuzumab (P) and the trial showed noninferior PFS of T-DM1 and T-DM1+P vs HT. Gene expression (RNA) analysis was performed on tumor samples by a custom 800-gene codeset on the nCounter platform. PD-L1, CD8 expressions and immune gene signatures (sign) analyses were assessed by multivariate Cox regression models using median (cut-off) as categorical variable and adjusted by prior HT, presence of visceral disease, world region, baseline ECOG, measureable disease at baseline, therapy setting, HER2 mRNA expression, PIK3CA mutation status. Results: MARIANNE randomized 1095 pts (HT, n=365; T-DM1, n=367; T-DM1+P, n=363). Gene expression results were available for 671 pts (61.3% of the intent-to-treat [ITT] population) which was representative of ITT. In ITT, HR below 1 was observed when comparing pts with high (>median) vs low (≤median) immune gene expression by clinical outcome suggesting a potential association of high immune marker expression with improved PFS (Table 1) and to some extent with OS (data not shown). This association was primarily observed in the T-DM1 arm where the HR suggested a risk reduction of disease progression(PD)/death especially in the high Teff, high PD-L1 and high CD8 subgroups, and to some extent in the HT arm (Table 1). When assessing the predictive impact on PFS by comparing T-DM1 vs HT, HR below 1 was observed especially in pts with high Teff signature, high PD-L1 and high CD8 expressions (HR 0.67 (95% CI (0.47-0.95)), HR 0.68 (95% CI (0.48-0.97), and HR 0.64 (95%CI 0.44-0.93), respectively). When comparing T-DM1+P vs. HT, HR below 1 was observed especially in pts with low Teff signature and low PD-L1 expression (HR 0.70 (95% CI (0.50-0.99), and HR 0.68 (95% CI (0.48-0.96) respectively). No clear differences between immune gene expression subgroups was observed when comparing treatment arms in regards to OS (data not shown). Conclusions: In the exploratory analysis from the MARIANNE study, high immune gene expression, especially in the high PD-L1, CD8 and Teff subgroups, showed an association with improved clinical benefit with HRs reflecting for a risk reduction of PD/death for PFS and partially for OS. This association was less obvious in the T-DM1+P arm. When comparing the treatments effect, the data showed a potential impact of high Teff signature, and high CD8 and PD-L1 expressions on T-DM1 and less on HT. The potential opposite association of low Teff signature and low PD-L1 expression with improved benefit in the T-DM1+P arm was unexpected and needs further investigation. Table 1: Prognostic biomarker effect on PFSBiomarker by categories (>Median vs ≤Median)HR (95% CI) ITT n=671HR (95% CI) HT n=220HR (95% CI) T-DM1 n=227HR (95% CI) T-DM1+P n=224Teff sign0.89 (0.73-1.09)0.97 (0.68-1.38)0.64 (0.45-0.91)1.09 (0.75-1.58)Th1 cytokine sign0.91 (0.74-1.11)0.92 (0.64-1.31)0.78 (0.55-1.11)0.96 (0.67-1.36)Checkpoint inhibitor sign0.95 (0.78-1.15)0.91 (0.64-1.29)0.90 (0.64-1.26)1.02 (0.71-1.47)PD-L10.80 (0.66-0.98)0.79 (0.55-1.13)0.62 (0.44-0.87)1.07 (0.74-1.55)CD80.91 (0.75-1.11)1.10 (0.77-1.57)0.66 (0.46-0.93)0.98 (0.68-1.41) Citation Format: Edith A Perez, Sanne Lysbet de Haas, Carlos H Barrios, Wolfgang Eiermann, Masakazu Toi, Young-Hyuck Im, Pier Franco Conte, Miguel Martin, Tadeusz Pienkowski, Xavier B Pivot, Howard A Burris III, Chiara Lambertini, Silke Hoersch, Monika Patre, Paul Anthony Ellis. Association of immune gene expression with outcome in the MARIANNE phase 3 clinical trial in HER2-positive metastatic breast cancer (MBC) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD5-11.

Summary Background The benefit of extending aromatase inhibitor therapy beyond 5 years in the context of previous aromatase inhibitors remains controversial. We aimed to compare extended therapy with letrozole for 5 years versus the standard duration of 2–3 years of letrozole in postmenopausal patients with breast cancer who have already received 2–3 years of tamoxifen. Methods This multicentre, open-label, randomised, phase 3 trial was done at 69 hospitals in Italy. Women were eligible if they were postmenopausal at the time of study entry, had stage I–III histologically proven and operable invasive hormone receptor-positive breast cancer, had received adjuvant tamoxifen therapy for at least 2 years but no longer than 3 years and 3 months, had no signs of disease recurrence, and had an Eastern Cooperative Oncology Group performance status of 2 or lower. Patients were randomly assigned (1:1) to receive 2–3 years (control group) or 5 years (extended group) of letrozole (2·5 mg orally once a day). Randomisation, with stratification by centre, with permuted blocks of size 12, was done with a centralised, interactive, internet-based system that randomly generated the treatment allocation. Participants and investigators were not masked to treatment assignment. The primary endpoint was invasive disease-free survival in the intention-to-treat population. Safety analysis was done for patients who received at least 1 month of study treatment. This trial was registered with EudraCT, 2005-001212-44, and ClinicalTrials.gov, NCT01064635. Findings Between Aug 1, 2005, and Oct 24, 2010, 2056 patients were enrolled and randomly assigned to receive letrozole for 2–3 years (n=1030; control group) or for 5 years (n=1026; extended group). After a median follow-up of 11·7 years (IQR 9·5–13·1), disease-free survival events occurred in 262 (25·4%) of 1030 patients in the control group and 212 (20·7%) of 1026 in the extended group. 12-year disease-free survival was 62% (95% CI 57–66) in the control group and 67% (62–71) in the extended group (hazard ratio 0·78, 95% CI 0·65–0·93; p=0·0064). The most common grade 3 and 4 adverse events were arthralgia (22 [2·2%] of 983 patients in the control group vs 29 [3·0%] of 977 in the extended group) and myalgia (seven [0·7%] vs nine [0·9%]). There were three (0·3%) serious treatment-related adverse events in the control group and eight (0·8%) in the extended group. No deaths related to toxic effects were observed. Interpretation In postmenopausal patients with breast cancer who received 2–3 years of tamoxifen, extended treatment with 5 years of letrozole resulted in a significant improvement in disease-free survival compared with the standard 2–3 years of letrozole. Sequential endocrine therapy with tamoxifen for 2–3 years followed by letrozole for 5 years should be considered as one of the optimal standard endocrine treatments for postmenopausal patients with hormone receptor-positive breast cancer. Funding Novartis and the Italian Ministry of Health. Translation For the Italian translation of the abstract see Supplementary Materials section.

Càncer de mama; Genètica del càncer Cáncer de mama; Genética del cáncer Breast cancer; Cancer genetics Young breast cancer (BC) patients carrying a germline BRCA pathogenic variant (mBRCA) have similar outcomes as non-carriers. However, the impact of the type of gene (BRCA1 vs. BRCA2) and hormone receptor status (positive [HR+] vs. negative [HR−]) on clinical behavior and outcomes of mBRCA BC remains largely unknown. This is an international, multicenter, hospital-based, retrospective cohort study that included mBRCA patients diagnosed, between January 2000 and December 2012, with stage I–III invasive early BC at age ≤40 years. From 30 centers worldwide, 1236 young mBRCA BC patients were included. Among 808 and 428 patients with mBRCA1 or mBRCA2, 191 (23.6%) and 356 (83.2%) had HR+tumors, respectively (P

Background: Phytotherapeutic agents aroused an increasing interest either as alternative or in addition to conventional therapy in the management of BPH. The aim of the article was to evaluate the clinical and functional changes after add-on treatment with Serenoa repens associated with Solanum lycopersicum, lycopene and bromelain in patients with BPH presenting with mild to moderate LUTS and previously treated only with Alfuzosin over a 6–12 months period. Materials and methods: Between January and July 2019, patients with symptomatic BPH already on treatment with Alfuzosin (Al) 10 mg for at least 6–12-month were enrolled at three academic referral centres, included in a prospective treatment group, and managed with a combination treatment of Al and 6-month daily oral single-tablet supplementation of Serenoa repens and Solanum lycopersicum + lycopene + bromelain (SeR + SL + Ly + Br). A retrospective control group with comparable baseline characteristics was obtained by performing a propensity score matching from a database of 434 patients managed with Alfuzosin 10 mg/day only over a 6–12 months period between March 2015 and December 2018. IPSS, QoL questionnaires, voiding diary assessment, postvoid residual volume (PVR), maximal (Qmax) and average (Qave) urinary flow rates were evaluated at baseline in the treatment group at the moment of patient accrual, in the control group after 6-month of treatment with alfuzosin, and thereafter at 3 and 6 months in both groups. Results: Overall, 250 patients entered the study (n = 125 treatment group, n = 125 control group). Total IPSS score significantly decreased at 6-month assessment from baseline in the treatment vs control group (17 [IQR: 12–20] vs 12 [IQR: 9–14], p = 0.02) with a significative storage symptoms improvement detected both at 3- (p = 0.03) and 6-month evaluation (p = 0.001). PVR significantly improved at each follow-up visit with the most relevant reduction at 6-month assessment (125 cc vs. 102 cc, p = 0.02). Moreover, a significative improvement in LUTS-related quality of life (QoL) was recorded at 3- and 6-month assessment with a median decrease of −1 and −2 (p = 0.05 and p = 0.001 respectively) from baseline. Conclusions: Combination treatment with AB and SeR + SL + Ly + Br led to meaningful improvements in LUTS severity compared to AB as monotherapy, after a 6-month treatment period in men with mild to moderate LUTS/BPH.

PurposeHormonal assessment (HA) and contrast-enhanced CT (ceCT) show insufficient sensitivity and specificity when staging unilateral adrenal lesions (ALs). We aimed at: 1) developing an imaging-based, i.e. ceCT and FDG-PET, diagnostic score able to discriminate adrenal tumors entailing adrenalectomy from those who need clinical monitoring, and 2) identifying a diagnostic flow-chart that allows clinicians to avoid unneeded diagnostic procedures and to address patients to the optimal management.MethodsRetrospective single-center study assessing patients with unilateral AL and the following inclusion criteria: a) a four-phase ceCT; b) FDG-PET within one month of the ceCT; c) histopathology or a clinical follow-up of at least 24 months. Firstly, multivariate logistic regression analysis was employed to identify the predictors of adrenal tumors to treat surgically (AL-to-treat) and regression-based coefficients were used to develop a diagnostic score. Secondly, using cut-offs of predictor variables, a diagnostic flow-chart was defined.ResultsForty-eight patients were enrolled (mean age 61 years), of whom 21/48 (44%) had AL-to-treat. The remaining 27/48 (56%) presented with AL to follow-up only (i.e. benign). Maximum and minimum lesion diameter, Hounsfield units (HU) before contrast media injection and HU at the delayed phase (HUdelayed), relative and absolute washout, AL SUVmax, AL SUVmean, ratio SUVmax AL/SUVmax liver (adrenal-liver ratio) were associated with the presence of AL-to-treat (all pConclusionWe developed a two-parameter imaging-based score that may be applied to predict adrenal tumors requiring adrenalectomy. Furthermore, a diagnostic flow-chart to stratify patients on the basis of the optimal management was proposed, thus guiding undefined unilateral adrenal lesions to FDG-PET imaging.

Objective: Several studies have reported about the performance of C-choline-PET/computed tomography (CT) (choline) in patients with biochemical recurrent (BCR) prostate cancer, but there is a lack of information regarding negative choline in the same clinical setting. Our aim was to retrospectively analyse negative choline in a cohort of BCR-patients with high prostate-specific antigen (PSA). Methods and results: We retrospectively analysed all choline-scans performed at two high-volume imaging centres between 2005 and 2018, selecting those of interest according to the following inclusion criteria: (1) proven prostate cancer treated either with radical prostatectomy or primary external beam radiation therapy (EBRT), (2) BCR after radical prostatectomy or EBRT, (3) PSA serum values >20 ng/mL at the time of scan and (4) scan reported as negative for active disease. Overall, among 5792 scans performed for BCR-prostate cancer, 14 matched the inclusion criteria and were classified as follows: 5/14(36%) inaccurate reports, 3/14(21%) questionable underestimation of positive findings, originally described as unclear, 6/14(43%) negatives. Choline showed a high detection rate in BCR-prostate cancer patients with PSA >20 ng/mL. Conclusions: Although negative reports can be found in this clinical setting, in our review various disease-relevant findings were identified in more than half of the cases originally reported as negative warranting a double reading in such cases to avoid false-negative reports.

A 59-year-old patient was referred to the Melanoma Unit for a dermatologic consultation due to the eruptive onset of multiple hyperpigmented nevi one-month after the beginning of their medical therapy with cetuximab for metastatic colorectal cancer. No other side-effects were reported, with the exception of a mild cutaneous xerosis.

COVID-19; SARS-CoV-2; Cáncer de mama COVID-19; SARS-CoV-2; Càncer de mama COVID-19; SARS-CoV-2; Breast cancer Background: Cancer patients are at higher risk of COVID-19 complications and mortality than the rest of the population. Breast cancer patients seem to have better prognosis when infected by SARS-CoV-2 than other cancer patients. Methods: We report a subanalysis of the OnCovid study providing more detailed information in the breast cancer population. Results: We included 495 breast cancer patients with a SARS-CoV-2 infection. Mean age was 62.6 years; 31.5% presented more than one comorbidity. The most frequent breast cancer subtype was luminal-like (n = 245, 49.5%) and 177 (35.8%) had metastatic disease. A total of 332 (67.1%) patients were receiving active treatment, with radical intent in 232 (47.6%) of them. Hospitalization rate was 58.2% and all-cause mortality rate was 20.3%. One hundred twenty-nine (26.1%) patients developed one COVID-19 complication, being acute respiratory failure the most common (n = 74, 15.0%). In the multivariable analysis, age older than 70 years, presence of COVID-19 complications, and metastatic disease were factors correlated with worse outcomes, while ongoing anticancer therapy at time of COVID-19 diagnosis appeared to be a protective factor. No particular oncological treatment was related to higher risk of complications. In the context of SARS-CoV-2 infection, 73 (18.3%) patients had some kind of modification on their oncologic treatment. At the first oncological reassessment (median time: 46.9 days ± 36.7), 255 (51.6%) patients reported to be fully recovered from the infection. There were 39 patients (7.9%) with long-term SARS-CoV-2-related complications. Conclusion: In the context of COVID-19, our data confirm that breast cancer patients appear to have lower complications and mortality rate than expected in other cancer populations. Most breast cancer patients can be safely treated for their neoplasm during SARS-CoV-2 pandemic. Oncological treatment has no impact on the risk of SARS-CoV-2 complications, and, especially in the curative setting, the treatment should be modified as little as possible. D.J. Pinato is supported by grant funding from the Wellcome Trust Strategic Fund (PS3416) and acknowledges grant support from the Cancer Treatment and Research Trust (CTRT), infrastructural and grant support by the Cancer Research UK Imperial Centre and the NIHR Imperial Biomedical Research Centre. A. Gennari is supported by the AIRC IG Grant, No. 14230, Associazione Italiana per la Ricerca sul Cancro Foundation, Milan, Italy and acknowledge also support from the UPO Aging Project.

Background The current standard first-line treatment of human epidermal growth factor receptor 2 (HER2)-positive (+) metastatic breast cancer is the combination of pertuzumab, trastuzumab and a taxane (P + T + taxane), while standard second-line is ado-trastuzumab-emtansine (T-DM1). The registration trial of pertuzumab, however, did not include early-relapsing patients, defined as patients experiencing tumor relapse ≤12 months from the end of (neo)adjuvant anti-HER2 therapy. Conversely, the pivotal trial of T-DM1 included some patients relapsing ≤6 months after the end of (neo)adjuvant trastuzumab. Thus, a proportion of early-relapsing patients are currently eligible to receive T-DM1 as first-line treatment. Nevertheless, no direct comparison exists between the two regimens in this clinical setting. Patients and methods We retrospectively compared T-DM1 versus P + T + taxane as first-line treatment in two cohorts of early-relapsing patients in an Italian ‘real-world’ setting, involving 14 public health care institutions. The primary endpoint was progression-free survival. Secondary endpoints included patients' characterization, overall survival and post-progression survival. Univariate and multivariate analyses were carried out. All tests were two-sided and a P ≤ 0.05 was considered statistically significant. Results Among 1252 screened patients, 75 met the inclusion criteria. Forty-four (58.7%) received P + T + taxane and 31 (41.3%) received T-DM1. The two cohorts showed similar characteristics of aggressiveness and no significant differences in treatment history. T-DM1, compared with P + T + taxane was associated with worse progression-free survival (adjusted hazard ratio: 2.26, 95% confidence interval: 1.13-4.52, P = 0.021) and overall survival (adjusted hazard ratio: 3.95, 95% confidence interval: 1.38-11.32, P = 0.010), irrespective of previous (neo)adjuvant treatment, age, hormone receptors status, time-to-relapse (≤6 months or within 6-12 months) and presence of visceral/brain metastases. No differences were observed in post-progression survival (P = 0.095). Conclusions Our study suggests superiority for P + T + taxane over T-DM1 as up-front treatment of early-relapsing HER2+ metastatic breast cancer, which merits further assessment in larger and prospective trials., Highlights • This is the first study comparing pertuzumab + trastuzumab + taxane (P + T + taxane) with T-DM1 in early-relapsing HER2+ MBC. • The majority of early-relapsing HER2+ MBC have high-grade, node-positive, large primary tumors. • First-line T-DM1 compared with P + T + taxane is associated with worse progression-free survival. • First-line T-DM1 compared with P + T + taxane is associated with worse overall survival. • Post-progression survival does not differ between the two treatments cohorts.

We conduct a bicentric cohort study to assess the existence of a possible association between drug-induced photosensitivity and Breslow thickness among melanoma patients. Our study suggests that women who have multiple chronic photosensitizing drugs intake are more likely to develop thicker cutaneous melanoma. Larger cohort studies are needed to confirm this finding

Background: BRAF (v-raf murine sarcoma viral oncogene homolog B1) and MEK (mitogen activated protein kinase) inhibitors, as well as immunotherapy against cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and the programmed cell death 1 (PD-1) receptor and its ligand (PD-L1), have shown good results in improving the disease-free survival of patients with metastatic melanoma (MM). The aim of this review is to summarize the main oral adverse events (oAEs) occurring in patients undergoing target or immunotherapy. We proposed two separate sections: oAEs during the treatment with (1) target therapies with BRAF and MEK inhibitors and tyrosine kinase inhibitors (gingival hyperplasia, pigmentation disorders, squamo-proliferative lesions) and (2) immunotherapies with CTLA-4 or PD1 inhibitors (lichenoid reactions, immuno-bullous reactions, xerostomia and other reactions). Adverse events frequently include oAEs, although these are often misdiagnosed and under-reported. Indeed, the oral cavity is not routinely evaluated during clinical practice. The symptomatology related to oAEs is significant since it may represent the first manifestation of a severe systemic reaction, possibly leading to difficulties in nutrition with a consequent impact on patients’ quality of life. A careful examination of the oral cavity is recommended during the evaluation of oncologic patients in order to promptly detect the onset of new manifestations.

The availability of accurate, reliable and up-to-date information concerning the state of marine resources is essential to create a decision support system for sustainable fishing to protect ecosystems. Within the Interreg Italy-Croatia SUSHI DROP Project (SUstainable fiSHeries wIth DROnes data Processing) a prototype of an Unmanned Underwater Vehicle (UUV) was developed as a detection system capable of surveying the benthic zone in deep waters of the Adriatic Sea. Traditional survey methods based on the capture of living organisms, for example through the use of trawl nets, are invasive, extremely expensive and at the same time prohibited in protected marine areas. The need to develop accurate and non-invasive methods to map and study marine ecosystems is highlighted in the EU Strategy for the Adriatic-Ionian Region (EUSAIR) action plan. To meet these objectives, a UUV system equipped with various scientific instruments has been implemented and in this work we present the first surveys carried out.

Background: Since December 2019, the global population has been experiencing an unprecedented challenge due to Corona virus disease (COVID-19). A pandemic was declared by the World Health Organization on March 11th 2020, with an escalation of new cases worldwide. Dermatology units experienced a reorganization of regular activity, also providing clinical diagnosis and medical assistance to COVID-19-positive patients who developed cutaneous manifestations. Objective: To evaluate the impact of the COVID-19 pandemic on Italian dermatologic clinical practice. Materials & Methods: This was a prospective online survey, consisting of a questionnaire with 35 multiple-choice questions uploaded on the website of the Italian Society of Dermatology and Venereology — SIDeMaST. Results: A total of 136 dermatologists, 78 women (57%) and 58 men (43%), participated in the survey. The mean age was 58 ± 14 years. In total, 60% of participants reported an impact of the pandemic on their practice, in most cases consisting of a remarkable reduction in routine clinical activity (58%). Concern regarding possible infection was evaluated with a score ranging from 0 (no concern) to 5 (extremely concerned): the fear of becoming infected was high (≥3 in 40%), as was the fear of infecting families, colleagues or patients (≥3 points in 45%). Conclusion: The COVID-19 pandemic is having a strong impact on dermatology practice in Italy. The identification of critical points may help scientific societies to improve the clinical scenario and create specific strategies to overcome the emergency.

BACKGROUND: The incidence of cutaneous melanoma (cm) has increased in the last decades. germline mutations in the high-penetrance melanoma susceptibility gene CDKN2A (Cyclin-dependent kinase inhibitor 2a) are associated with a younger age at diagnosis and an increased risk to develop pancreatic cancer. METHODS: We retrospectively analyzed the data of patients with prior diagnosis of cm referring to our service from January 2005 to may 2017. the aim was to investigate the rate of multiple cms (mPm), assessing their clinical/pathological features. moreover, the genetic tests of patients who had undergone CDKN2A/CDKN2B, CDK4 and MITF screening were evaluated. RESULTS: One hundred fifteen patients (9.26%) were diagnosed with MPMs: 70 males (60.87%) and 45 women (39.13%). 75 patients (43 males and 32 females) underwent genetic screening for germline mutations. The screening revealed that 4/75 patients (5.33%) were carriers of the non-synonymous missense variation c.442g>a (p.ala148thr) in CDKN2A exon 2 in heterozygosis, 3 of whom had at least one in-situ melanoma. In 1 patient (1.33%) we detected the variation c.249C>A, p.His83Gln in CDKN2A exon 2 in heterozygosis and in 1 patient (1.33%) the mutation c.952g>a (p.glu318lys) in MITF gene was found. CONCLUSIONS: This study confirms the need for a full body skin examination and a prolonged surveillance in patients affected by cM, as MPMs were detected in up to 10% of total cases in our series and synchronous lesions in 1/5. Moreover, it reflects the great variability of cM high-susceptibility genes mutational status within the Italian territory. Patients carrying c.952g>a (p.glu318lys) MITF mutation have a higher risk to develop a nodular cm.