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Approximately 40% of malignant melanomas are diagnosed in patients older than 65 years. Elderly patients with melanoma present clinicopathological features related to a more aggressive biology, and they are often diagnosed with advanced stage of disease. Interestingly, in older patients the immune system can be altered with changes both in the innate system and in the adaptive immune system with the acquisition of a pro-inflammatory and immune suppressive phenotype. Immunotherapy with immune checkpoint inhibitors has reshaped the treatment strategies and prognosis of patients with melanoma, and particularly, older age should not be considered a contraindication for immunotherapy. However, data regarding efficacy and safety of immunotherapy in elderly population are still limited because frail older patients are generally excluded from clinical trials. Recently, real-world data have shed light on similar efficacy and safety of immunotherapy in older population compared with younger counterpart. The aim of the present review was to summarize the available knowledge on the underlying immune system in older patients with a diagnosis of melanoma and the immunotherapeutic approaches in this population.

Prognostic characterization in the initial assessment of patients with advanced cancer disease is an essential step to plan the most appropriate therapeutic program. Since clinical prediction of survival (CPS) may be of limited value, some authors have tried to integrate specific prognostic factors into prognostic multidimensional scores. We carried out a prospective cohort study in two palliative care units to compare the accuracy of the Palliative Prognostic (PaP) Score, the Objective Prognostic Score (OPS), and the Palliative Prognostic Index (PPI). In addition, we compared the accuracy of the CPS independently estimated by different healthcare professionals and we tested the role of laboratory results, together with clinical and social factors in predicting survival. Clinical and laboratory data of 334 advanced cancer patients were prospectively collected from the time of in-hospital admission. PaP Score was the most accurate index of survival prediction, followed by PPI; CPS estimates' accuracy was similar among physicians and nurse. All healthcare professionals tended to underestimate the real survival. Integrating CPS with multidimensional indexes may further improve the patient's management. The degree of autonomy and the number of metastatic sites were independent prognostic factors for 30-days mortality and overall survival in multivariate analysis.

Background: Over the last few years, the introduction of newer systemic therapies (e.g. CDKi) significantly changed the treatment paradigm of patients (pts) with MBC. The purpose of this work is to evaluate the impact of CDKi introduction in clinical practice in terms of medical oncology workload. Methods: We examined a consecutive series of 492 pts who received therapy for MBC in Academic Hospital of Udine during two historical cohorts A (2016-2017) and B (2018-2019), respectively before and after the first CDKi approval in Italy. Data about 2020 were not collected due to confounding effect of SARS-CoV-2 pandemic. Pts with no luminal MBC or enrolled in clinical trial were excluded. We performed descriptive analyses to examine any differences in terms of number and type of outpatient visits to the oncology department (i.e. planned visits, unplanned presentations and i.v. treatment sessions) between the two cohorts. Results: We analyzed a total number of 2,645 oncology activities deriving from 42 pts (cohort A) and 57 pts (cohort B) who started first line treatment for luminal MBC. Median age was 66 and 70 years respectively. In the first group, pts receiving chemotherapy were 23.8% and those treated with CDKi were 7,14%. In the second group, chemotherapy was administered in 22.8% of pts and CDKi in 49.12%. In cohort A, number of planned visits, unplanned presentations and i.v. treatment sessions were respectively 643, 82 and 418. In cohort B, number of planned visits, unplanned presentations and treatment sessions were 892, 114 and 496. During the period of observation (two years), for each pts mean number of planned visits were 15,30 (cohort A) vs 15,64 (cohort B), mean number of unplanned presentations were 1,95 (cohort A) vs 2 (cohort B), treatment i.v. sessions were 9,9 (cohort A) vs 8,7 (cohort B). Conclusions: With the limits of a retrospective analysis, no differences were found between two cohorts of pts. Notably, there was a slight decrease of i.v. treatment sessions after CDKi introduction. Other analysis are ongoing to evaluate the workload in terms of instrumental and blood chemistry tests. This data further support the handy use of this drugs into clinical practice. Legal entity responsible for the study: Azienda Sanitaria Universitaria Friuli Centrale (ASUFC) Funding: Has not received any funding. Disclosure: M. Mansutti: Financial Interests, Institutional, Advisory Board: AstraZeneca;Financial Interests, Institutional, Advisory Board, invited speaker: Novartis;Financial Interests, Institutional, Advisory Board, invited speaker: Eli Lilly;Financial Interests, Institutional, Advisory Board, invited speaker: Pfizer;Financial Interests, Institutional, Advisory Board: MSD Italia;Financial Interests, Institutional, Advisory Board, invited speaker: EISAI;Financial Interests, Institutional, Advisory Board: Pierre Fabre;Financial Interests, Institutional, Advisory Board: Roche;Financial Interests, Institutional, Advisory Board: Celgene. All other authors have declared no conflicts of interest.

Background: The aim of this study was to identify potential variables influencing the clinical presentation of breakthrough cancer pain (BTP). Methods: Cancer patients with a diagnosis of BTP were enrolled. Demographic and clinical characteristics, as well as background pain and BTP characteristics were collected. Multivariate analyses were conducted to assess the correlation between BTP characteristics and the variables examined. Results: Data of 4016 patients were analysed. Average daily number of BTP episodes was 2.4, mean intensity was 7.5, and a mean duration was 43.3 min. A short onset BTP was observed in 68.9% of patients. In 30.5% of patients BTP was predictable. There were 86.0% of participants who reported a marked interference of BTP with their daily activities. Furthermore, 86.8% of patients were receiving opioids for the management of BTP. The average time to meaningful pain relief was 16.5 min and 70.9% of patients were satisfied with their BTP medications. Age, head and neck cancer, Karnofsky, background pain intensity, predictable and fast onset BTP were independently associated with the number of BTP episodes. BTP pain intensity was independently associated with background pain intensity, fast onset BTP, and Karnofsky. Neuropathic pain mechanism was independently associated with unpredictable BTP. Variables independently associated with a longer duration of BTP were age, place of visit, cancer diagnosis, disease-oriented therapy, background pain intensity and mechanism, and unpredictable BTP. Age, Karnofsky, background pain intensity, fast onset, and long duration of BTP were independently associated with interference with daily activity. Conclusions: BTP has a variable presentation depending on interdependent relationships among its different characteristics.

Background Cancer multidisciplinary team meetings (MDMs) are commonly acknowledged as a good clinical practice. One of the roles of MDMs is to identify the best diagnostic and therapeutic strategies for patients (pts) with new diagnosis of early breast cancer (EBC). In this setting, the purpose of the study was to define whether there was agreement between the planned program (i.e. MDMs-based decision) and that actually applied (i.e. actual therapeutic choice, ATC). In addition, the study explored factors associated with discordance. Methods We conducted a monocentric retrospective study of a consecutive series of 291 pts with new diagnosis of EBC, discussed at MDMs at the University Hospital of Udine (Italy), from January 2017 to June 2018. Results Median age was 62 years (range 27-88 years). Among invasive EBC patients, the most frequent phenotype was luminal-A (38%), followed by luminal-B (33%), HER2-positive (12%) and triple negative (5%). Thirty-four pts (12%) had diagnosis of in situ carcinoma (DCIS). Median time from MDMs discussion to first oncological examination was two weeks. Rate of discordance between MDMs-based decision and final choice, during face to face consultation with the oncologist, was 15.8% (46/291). Among cases with discordance, 19 pts (41.3%) had age > 70 years; 8 pts (17%) had a diagnosis of DCIS, 13 pts (28%) luminal-B carcinoma, 12 pts (26%) luminal-A, 9 pts (20%) HER2-positive and 4 pts (9%) triple negative EBC. The most frequent reason for changing the MDMs-based program was clinical decision by the oncologist at the first evaluation (87%). Follow-up was preferred to the chemotherapy proposed within the MDMs by 15% of pts, and to the endocrine therapy in 39% cases (among these, 44.5% had diagnosis of DCIS). In our study 16/46 pts (35%) had a therapeutic change from chemotherapy to endocrine therapy: among these pts, 7/16 had a luminal-B and 6/16 had a HER2-positive disease. Further analysis aiming at evaluating variables which could predict discordance between MDMs proposal and face to face oncological consultation are ongoing. Conclusions The results of our study could be useful for enhance the role of MTD and identify unmet needs in decision making process in EBC. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

Background High BMI is associated with better survival in metastatic melanoma patients (MM pts), while sarcopenia is linked to poorer outcome in pts with stage III. The aim of this study was to examine the prognostic impact of body-mass index (BMI), baseline sarcopenia, loss of skeletal muscle mass (LSMM) on overall survival (OS) in MM pts who received immunotherapy (IT). Methods The retrospective series included 42 consecutive MM pts (Jan 2011-Dec 2018) treated with IT in a single referral center. Sarcopenia was defined according to Prado’s criteria. Skeletal muscle index (SMI) was calculated as cross-sectional-area of muscle (cm2), using CT-scan, at the L3 level divided by the square of the height (m2). Early LSMM, during IT, was defined as a decrease in SMI > =10% from baseline at first evaluation. BMI was calculated as weight (kg) divided by the square of height (m2) and categorized according to standard WHO definitions. Weight loss was analyzed as continuous variable. Results At baseline, 27 pts (64,3%) were male, 26 pts (61.9%) were =25. Out of 42 pts, 30 (71.4%) had a CT-scan at first evaluation, and 30% of them had an early LSMM. Median OS was 11.38 months. Both in univariate and multivariate analysis, ECOG PS > =1, and early LSMM > =10% were significantly associated with worse OS. Conversely, pts with weight loss had better OS (Table). Table . 1367P OS univariate analysis OS multivariate analysis Factors HR p 95% Confidence Interval HR p 95% Confidence Interval PS ECOG³1 3.02 0.01 (1.29-7.08) 3.99 0.043 (1.04-15.31) Weight loss 0.88 0.03 (0.78-0.98) 0.85 0.02 (0.74-0.97) Early LSMM > =10% 4.24 0.006 (1.50-11.97) 3.09 0.04 (1.04-9.22) Conclusions Early LSMM > =10% and ECOG PS > =1 may negatively influence the outcome of MM pts treated with IT. Further prospective studies are needed to confirm these data. Legal entity responsible for the study Maria Grazia Vitale. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

Background Patients (pts) with melanoma brain metastases (BM) have a historically poor prognosis, with a reported median overall survival (mOS) of 4-6 months. Aim of this study is to evaluate predictive factors of survival in pts with melanoma BM. Secondly, a multivariate model was used to define groups with distinct prognosis. Methods Consecutive pts with melanoma BM treated in two Italian cancer centers were included in this 10-year retrospective cohort study (2008-2018). Baseline clinicopathological factors, systemic and loco-regional treatments were registered. The Kaplan-Meier method and the Cox model were used to analyze the association of prognostic factors and OS. Results 150 pts with melanoma BM were enrolled in this study: 42% with a single BM, 51.3% with ≥ 3 extracranial metastatic sites and 38% with an ECOG performance status (PS) of 0. About 50.7% of pts had a BRAF mutation. Notably, 56% of pts were asymptomatic at BM diagnosis, and 40% presented high LDH levels at baseline. Overall, mOS after BM diagnosis was 5.78 months (95% CI 4.80-6.67), and median intracranial progression-free survival was 4.63 months (95% CI 3.81-5.12). According to treatment modality, stereotactic radiosurgery/neurosurgery plus systemic therapy showed the best outcome (mOS 12.32 months, 95% CI 7.92-25.30). A multivariate model was used to identify baseline prognostic factors independently associated with OS (Table). Conversely, sex and symptomatic BM did not significantly impact on OS. Predicted survival functions defined 3 distinct prognostic groups (P Table . 1363P Covariates HR 95% CI P Points BRAF wild type 1.95 1.22-3.12 1 BM > 1 2.20 1.35-3.59 1 LDH ≥ 2 x upper normal limit 1.83 1.07-3.11 0.026 1 ECOG PS > 0 2.68 1.62-4.43 0.0001 1 Extracranial metastatic sites ≥ 3 1.91 1.17-3.1 1 Age ≥ 65 1.86 1.15-3.02 0.012 1 Conclusions This score can be useful for stratifying prognosis in pts with melanoma BM. Prospective studies are needed to validate this score and to explore how it may guide treatment strategy. Legal entity responsible for the study Dipartimento di Oncologia, Azienda Sanitaria Universitaria Integrata di Udine. Funding Has not received any funding. Disclosure F. Puglisi: Honoraria (self), Advisory / Consultancy: Amgen; Advisory / Consultancy: Celgene; Advisory / Consultancy: Eisai; Advisory / Consultancy: Eli Lilly; Honoraria (self), Advisory / Consultancy: Ipsen; Honoraria (self), Research grant / Funding (self): Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy, Research grant / Funding (self): Roche; Honoraria (self): Pierre Fabre; Advisory / Consultancy: Merck Sharp & Dohme; Advisory / Consultancy: Takeda; Research grant / Funding (self): Astrazeneca. All other authors have declared no conflicts of interest.

Several studies have reported an increase in vascular structures in malignant melanoma. Neovascularization can be enhanced by several factors. Among them, thymidine phosphorylase (TP) and cyclooxygenase-2 (COX-2) have been reported to play a role. The expressions of TP and COX-2 were evaluated trough immunohistochemistry in a series of 78 primary cutaneous melanomas diagnosed between 2000 and 2004. The expressions of TP and COX-2 through mRNA and western blot analysis were also evaluated in several melanoma cell lines. TP expression and COX-2 expression were considered positive in 25 cases (32%) and 22 cases (28.2%), respectively. TP-positive melanomas showed a lower mitotic rate (P=0.008), smaller thickness (P=0.01), and absence of lymphovascular invasion (P=0.04). COX-2-positive melanomas showed a higher mitotic rate (P=0.01) and higher thickness (P=0.03). COX-2 expression was associated with reduced disease-free survival (P=0.01). COX-2-positive cases showed a trend toward reduced survival, whereas TP was not correlated with overall survival. COX-2 expression was detected in four of 11 melanoma cell lines both by mRNA and by western blot analysis. Our data show that TP expression is associated with more favorable prognostic factors (such as thin melanoma, low mitotic count, and absence of lymphovascular invasion), whereas COX-2 expression is associated with poor prognostic factors (thicker melanoma and high mitotic count).

e13079Background: Elevated ALP and LDH levels have been associated with worse prognosis in several malignancies; however, their role in MBC remains unclear. We aim to explore the prognostic impact ...

e24014Background: The role of serum tumor markers (TM), such as Ca15-3 and CEA, in early intercepting breast cancer (BC) recurrences is still debated. Due to lack of sensitivity and specificity, TM...

Chemotherapy-induced amenorrhea occurs in about 20-70% of premenopausal breast cancer patients. Chemotherapy-induced amenorrhea can affect choice of hormonal therapy, fertility, and quality of life of breast cancer survivors. We retrospectively analyzed the incidence of amenorrhea after adjuvant chemotherapy and the subsequent recovery of the menses in 145 breast cancer patients. Age, smoking, alcohol consumption, body mass index, chemotherapy regimen, previous hormonal therapies, and previous childbearing were analyzed as potential predictive factors of ovarian function recovery. Median age was 42 years at the beginning of adjuvant chemotherapy with 30.3% of patients below 40 years of age. The majority (87.6%) of patients received anthracycline-based chemotherapy, 35.2% of patients received a cyclophosphamide-methotrexate-5-fluorouracil regimen and 42.8% received a taxane. The incidence of chemotherapy-induced amenorrhea was 80, and 35.3% of these patients resumed menses after a median of 8 months. In multivariate analysis, younger age (

Background:Periostin is a secreted adhesion protein, normally expressed in mesenchime-derived cells. Aberrant expression of the periostin gene in epithelial tumours seems to play a role in angiogenesis and metastases.Aims:To investigate periostin expression in a consecutive series of breast carcinomas and correlate it with established biological and prognostic factors.Methods:A consecutive series of 206 breast carcinomas was investigated by immunohistochemistry with a specific antiperiostin antibody. Immunohistochemical expression of oestrogen and progesterone receptors, Ki-67 (MIB-1), HER-2/neu, VEGF-A, VEGFR-1 and VEGFR-2 was analysed. Periostin expression was also investigated in MCF-7 and MDA-468 cell lines by immunohistochemistry, western blot and quantitative RT-PCR. Localisation of periostin was investigated in MCF-7 cells by the green fluorescent protein (GFP) approach.Results:Periostin was highly expressed in carcinoma cells, but not in normal breast tissues. The pattern of expression was mainly cytoplasmic. However, in 12% of cases a nuclear reactivity was observed. Nuclear periostin significantly correlated with tumour size, and with expression of oestrogen receptor, progesterone receptor, VEGF-A, VEGFR-1 and VEGFR-2. A nuclear localisation of periostin was also observed in MCF-7 and MDA-468 cell lines. In MCF-7 cells the nuclear localisation of periostin was also shown by transfection of a vector expressing a GFP-periostin chimeric protein.Conclusions:Results indicate that the aberrant gene expression of periostin in breast cancer cells is associated with an abnormal nuclear localisation of the protein. The nuclear localisation of periostin in breast cancer may induce significant biological effects.

e20507 Background: An accurate prediction of survival of advanced cancer patients (pts) is mandatory to avoid inappropriate therapies and tailor appropriate treatments; nonetheless, the Clinical Pr...

e12532 Background: Few studies have described patterns of metastatic spread according to the major breast cancer biologic subtypes (BS). The aim of this study was to determine the association of BS...

1044 Background: Obesity represents a well-known risk factor for the development of breast cancer and an adverse prognostic factor in early disease. Overweight is associated with reduced efficacy of aromatase inhibitors in adjuvant setting. Few data have been reported about the potential relationship of overweight and outcome in advanced breast cancer (ABC). Methods: We retrospectively evaluated body mass index (BMI) in a consecutive series of 400 ABC patients treated at our institution. BMI was calculated at baseline of diagnosis of ABC. We evaluated association of BMI and other prognostic and predictive markers with Progression Free Survival (PFS) and Overall Survival (OS). We evaluated PFS at first and subsequent lines of chemotherapy (CT) and endocrine therapy (ET). Overweight patients were defined as having BMI > 25. Results: Overweight patients were 52%. Median age of the population was 58 years. Median OS was 33.7 months. Overall, 76% of patients presented with ER+ and 17.7% with HER2+ ABC.Overweight was associated with increased age at diagnosis, menopausal status and luminal B or triple negative immunophenotype. At multivariate analysis, BMI > 25 was associated with better PFS at first-line ET (HR= 0.68, 95% CI 0.46-0.99). BMI was not associated with OS. Conclusions: BMI at baseline does not seem to be an adverse prognostic factor for ABC patients. Overweight may be associated with better PFS in endocrine responsive ABC treated with ET, especially in first-line setting. The role of BMI in ABC deserves to be further investigated.

e19014 Background: Cyclooxygenase-2 (COX-2) protein expression has been described in melanoma and it seems to be associated with tumor progression and angiogenesis. Thymidine phosphorylase (TP) is ...

e19623 Background: Analysis of relative importance of side effects of anticancer therapy is extremely useful in the process of clinical decision making. Previous studies have surveyed what patients...

1068 Background: Capecitabine (C) is an orally bioavailable prodrug that is converted to 5-fluorouracil in several enzymatic steps, the last of which is mediated by thymidine phosphorylase (TP). TP is expressed at high levels in over 50% of breast cancer (BC) specimens and elevated levels of TP have been hypothesized to predict therapeutic effect of C. Our study aimed at evaluating the potential relationship between immunohistochemical TP expression and benefit from C in terms of time to progression (TTP) in patients (pts) with metastatic BC. Methods: We retrospectively reviewed biopsies of 61 pts with BC treated with at least 3 cycles of C as single agent for metastatic disease, performing immunohistochemistry for TP and other biological markers. All patients received C 1,000 mg/m2 bid days 1 to 14 every 21 days. TTP was defined as the time between the beginning of therapy with C and disease progression or last follow-up. The following variables were analyzed as potential determinants of benefit from C: ...

21090 Background: Mesenchyme-specific genes are highly expressed by various types of human cancers. Recent lines of evidence suggest that periostin, a myoepithelial/basal gene, may play a role in the biology of breast cancer. Periostin is involved in metastatic process by taking part in mechanisms of adhesion and migration of epithelial cells. Furthermore, periostin seems to have a role in tumor angiogenesis through the up-regulation of vascular endothelial growth factor receptors in endothelial cells. We aimed at investigating the immunohistochemical expression of periostin in breast cancer and its correlation with established biological and prognostic factors. Methods: We performed immunohistochemical analysis of periostin in a consecutive series of 206 tumor samples from 200 patients with early breast carcinoma. To this aim, we used a specific antiperiostin antibody (Biovendor Laboratory Medicine, Inc., Palackeho 56, 612 00 Brno, Czech Republic). The intensity of immunoreactivity was scored as 0, 1, 2 or 3 denoting negative, weak, moderate and strong staining, respectively. Therefore, for statistical analysis, the periostin expression level for each case was putatively defined as positive if the predominant intensity was =1. We also analyzed immunohistochemical expression of Ki-67 (MIB-1), HER-2/neu, VEGF, VEGFR-1 and VEGFR- 2. Results: Periostin was found to be highly expressed by carcinoma cells, whereas it was absent in normal breast tissues. The pattern of expression was mainly cytoplasmic, although in some cases (11%) a nuclear reactivity was observed. A cytoplasmic expression was found in 108 out of 189 (57%) evaluable cases. Interestingly, a significant correlation was found between periostin expression and VEGF and VEGFR-1 (Spearman's rank test rho =0.37, p No significant financial relationships to disclose.