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The worldwide medical community is striving to pursue the most appropriate clinical choices in the worst event of pandemic of the modern times [1], with over 1 million patients affected by COVID‐19 (i.e., swab positive patients with or without symptoms) reported so far [1]. In this context, the aim of the ideal management of cancer patients is to achieve the best possible balance between the two different issues to be considered, which include the risk of cancer progression and the risk of infectious disease.

Introduction: Prostate cancer (PCa) is one of the most common adult malignancies worldwide, and a major leading cause of cancer-related death in men in Western societies. In the last years, the prognosis of advanced PCa patients has been impressively improved thanks to the development of different therapeutic agents, including taxanes (docetaxel and cabazitaxel), second-generation anti-hormonal agents (abiraterone and enzalutamide), and the radiopharmaceutical Radium-223. However, great efforts are still needed to properly select the most appropriate treatment for each single patient.Areas covered: Several prognostic or predictive biomarkers have been studied, none of which has an established validated role in daily clinical practice. This paper analyzed the major biomarkers (including PSA, androgen receptor (AR) splice variants, βIII-tubulin, ALP, circulating tumor cells, and DNA repair genes) with a potential prognostic and/or predictive role in advanced PCa patients.Expert commentary: Surrogate biomarkers - measurable, reproducible, closely associated with tumor behavior and linked to relevant clinical outcomes - are urgently needed to improve PCa patient management.

Kidney transplantation leads to an increased risk of cancer. Melanoma is one of the most frequent neoplasms in kidney transplant recipients. Transplanted patients were excluded from trials with checkpoint inhibitors in melanoma. The authors performed a systematic review regarding the use of anti-PD1 and anti-CTLA4 agents in renal transplanted patients with melanoma. Thirty-four cases were included (24 progressive disease, eight partial responses and one stable disease) but no complete response were reported. Fourteen graft rejections were observed, especially with anti-PD1 agent. The median time from the start of immune-checkpoint inhibitor and rejection was 21 days. Response rate was similar between patients with rejection and patients without rejection. The benefit of immune-checkpoint inhibitors versus the risk of allograft rejection should be carefully weighted for each patient. A multidisciplinary approach should be considered to discuss the most appropriate treatment for every case, given the aggressiveness of melanoma in these subsets of patients.

Background Germ cell tumors represent, among solid cancers, a potentially curable disease even if up to 20% to 30% of patients (pts) relapse after first-line treatment especially considering intermediate and poor prognosis groups. In this scenario, patients are candidates for high-dose chemotherapy and autologous stem-cells transplantation as second-line treatment even though stem-cells mobilization potential can be affected by several cycles and regimens of chemotherapy. To date, plerixafor is authorized in poor mobilizer adult pts diagnosed with lymphoma or multiple myeloma and in pediatric solid tumors or lymphoma. Therefore, the use of plerixafor in adult pts with relapsing/refractory GCT is still off label. Materials and methods In our study, we describe mobilization and collection of peripheral blood stem cells for 10 pts with germ cell tumors. Six patients underwent plerixafor administration since classified as poor mobilizers based on WBC count (>5.000/μL) and CD34+ cell count ( Results On the first day of apheresis, plerixafor administration in poor mobilizers made possible a remarkable boost of CD34+ cells in such a way to overlap that of good mobilizers' (32/μL vs 35/μL, respectively, P > .05). Conclusion Therefore, in our experience, plerixafor made a good fraction of poor mobilizer patients eligible for mobilization and collection and able to undergo the predicted autologous stem-cells transplantation; thus, the lack of access to the use of plerixafor in this setting of patients risks jeopardizing an effective treatment, especially in case of poor prognosis.

Background. Immunotherapy represents a common therapeutic option for metastatic uveal melanoma, despite the low activity. Although overall survival is often dismal, long survivors can be observed. In this study, the prognostic role of the soluble isoforms of immunomodulatory receptors and cytokines/chemokines was evaluated as well as their ability to identify patients who can benefit more from anti-PD-1 therapy. Methods. Sera from 22 metastatic uveal melanoma patients were assayed to evaluate the levels of cytokines/chemokines and soluble immune checkpoint molecules by multiplex immunoassay analysis. The changes of these molecules during anti-PD-1 therapy were assessed. The correlation between soluble isoforms of immunomodulatory receptors/cytokines/chemokines and survival was analysed. A comparison between circulating immune profile of metastatic uveal melanoma and cutaneous melanoma during anti-PD-1 therapy was also performed. Results. The levels of sCD137, sCD28, sPD-1, sPD-L2 sLAG3, sCD80 and sTim3 were significantly enhanced during anti-PD-1 treatment. Similarly, the levels of IP-10, CCL2 and IDO activity were significantly increased during anti-PD-1 therapy. HVEM, IL-8 and IDO activity were higher in patients with survival 30 months. Serum GITR, sCD27, sPD-1, sCD80, IFNγ and IDO activity were significantly higher in uveal melanoma patients than in cutaneous melanoma patients during anti-PD-1 therapy. Conclusions. The molecules detected in uveal melanoma during anti-PD-1 treatment reflect the poor activation of immune system and may justify the limited response to immune checkpoint inhibitors. Nevertheless, some patients with metastatic uveal melanoma had a long survival. These patients could be identified through a score based on circulating immune molecules such as HVEM, IDO and IL-8. The comparison of immune profile during anti-PD-1 therapy between uveal melanoma and cutaneous melanoma reflects the different efficacy of immune checkpoint inhibitors in these diseases.

De-novo metastatic castration sensitive prostate cancer (mCSPC) is a subgroup of prostate cancer associated with poor prognosis. Recently, the treatment of mCSPC has been enriched by new life-prolonging options, including the combination of docetaxel or abiraterone acetate with androgen deprivation therapy (ADT). Of note, the advantage of chemohormonal therapy was more relevant in the subgroup of high-volume disease compared to low-volume, while the survival prolongation of abiraterone was observed only in high-risk patients. Choosing the most appropriate therapy is one of the most debated issues. This review describes the latest news on de-novo mCSPC to better outline patients' management. At the ESMO 2018 Congress two novel studies focused on this setting have been presented, trying to define the role of radiotherapy to the primary tumour and the efficacy of abiraterone acetate in the subset of low-risk patients. We have analysed these results in light of the evidence already available.

Background No standard treatment has been defined for metastatic uveal melanoma (mUM). Although clinical trials testing Nivolumab/Pembrolizumab for cutaneous melanoma did not include mUM, anti PD-1 agents are commonly used for this disease. Patients and methods In this prospective observational cohort single arm study, we investigated efficacy and safety of Pembrolizumab as first-line therapy for mUM. The efficacy was evaluated in terms of progression-free survival (PFS), response rate and overall survival (OS). Toxicity was also assessed. Results Seventeen patients were enrolled. A median of 8 cycles were administered (range 2–28). Two patients achieved partial response (11.7%), 6 a disease stabilization (35.3%), whereas 9 (53%) had a progression. No complete response was observed. PFS of the overall population was 3.8 months. PFS was 9.7 months for patients with an interval higher than 5 years from diagnosis of primary tumor to metastatic disease and 2.6 months for patients with an interval lower than 5 years [p = 0.039, HR 0.2865 (95% CI 0.0869–0.9443)]. Median OS was not reached. The two responding patients were still on treatment with Pembrolizumab at the time of data analysis. Survival was 12.8 months for patients with clinical benefit, while OS for progressive patients was 3.1 months. PD-L1 expression and genomic abnormalities predictive of relapse after diagnosis of primary tumor were not associated with PFS. Toxicity was mild, without grade 3–4 side effects. Conclusions The efficacy of Pembrolizumab does not seem particularly different when compared to other agents for mUM, but responding patients had a remarkable disease control.

Numerous studies showed that bladder urothelial carcinoma and upper urothelial tract carcinoma (UTUC) display clinical and genomic similarities. In order to analyze that the same panel of biomarkers used in the diagnosis of bladder urothelial carcinoma could be suitable for early detection of UTUC, we performed a retrospective study in which we analyzed Bladder EpiCheck scores in the urinary samples obtained by selective ureteral catheterization in a high-grade UTUC cohort, correlating the results with urinary cytology and diagnostic urethral biopsies. The present study represents a retrospective analysis of 82 patients with clinically localized high-grade UTUC (60 renal pelvis UTUC, 22 ureter UTUC) who had undergone a radical nephroureterectomy (RNU) at our Urology department from June 2018 to November 2020. Before any surgical procedure, one sample of urine, obtained by selective ureteral catheterization, was collected for each patient for cytological examination, and the remaining material was stored for the Bladder EpiCheck test. Our results showed that the sensitivity of the methylation test for high-grade UTUC was about 97.4%, significantly higher than the sensitivity of urinary cytology either considering the HGUC cytological diagnosis or including in the positive cases the SHGUC cytological diagnosis (97.4% versus 59% or 70.5%). The methylation analysis of urinary samples may represent a valid tool in the diagnostic process of patients with suspected UTUC. In cases with a difficult clinical decision after upper urinary tract biopsy and cytology, the methylation test could assist in the clinical management of UTUC patients.

Determining the most appropriate management strategy for patients with large tumor masses is a very challenging issue. Unconventional radiotherapy modalities, such as spatially fractionated radiation therapy (SFRT), are associated with dramatic responses. Recent studies have suggested that systemic immune activation may be triggered by SFRT delivery to primary tumor lesion. This report describes the case of a patient treated with a novel form of immune-sparing partially ablative irradiation (ISPART) for a bulky peritoneal metastasis from renal cell cancer, refractory to anti-PD-1 therapy (nivolumab) as third-line therapy after sequential therapy with sunitinib and cabozantinib. The observed response suggests that there may be a synergistic effect between ISPART and immunotherapy. This case report supports the inclusion of ISPART in patients presenting with bulky lesions treated with checkpoint inhibitors .Lay abstract Managing large tumor masses is a very challenging issue. In recent years, radiotherapy methods have been linked with good responses, which may be due to the activation of immune mechanisms. We describe the case of a patient with a large tumor mass from renal cell cancer. The patient had already been treated with anti-PD-1 therapy, after treatment with sunitinib and cabozantinib, along with radiotherapy. The results suggest that radiotherapy together with immunotherapy is very effective in enhancing immune response.

Background: Immune checkpoint inhibitor (ICI)–mediated psoriasis poses significant diagnostic and therapeutic challenges. Objective: To report data on ICI-mediated psoriasis, emerging from the largest cohort to date, to our knowledge, and to propose a step-by-step management algorithm. Methods: The medical records of all patients with ICI-mediated psoriasis were retrospectively reviewed across 9 institutions. Results: We included a cohort of 115 individuals. Grade 1, 2, and 3 disease severity was reported in 60 of 105 (57.1%, 10 missing data), 34 of 105 (32.4%), and 11 of 105 (10.5%), respectively. The ratio between exacerbation and de novo cases was 1:4.3. The most common systemic therapy was acitretin (23 patients, 20.1%), followed by systemic steroids (8 patients, 7%), apremilast (7 patients, 6.1%), methotrexate (5 patients, 4.3%) and biologics (4 patients, 3.6%). Overall, 29 of 112 patients (25.9%) interrupted and 20 of 111 (18%) permanently discontinued ICIs because of psoriasis. Body surface area of greater than 10% at baseline had a 3.6 increased risk for ICI treatment modification (odds ratio, 3.64; 95% confidence interval, 1.27-10.45; P =.03) and a 6.4 increased risk for permanent discontinuation (odds ratio, 6.41; 95% confidence interval, 2.40-17.11; P

In this paper we aimed to address the role of pulmonary metastasectomy (PM) in patients affected by Lung Metastases (LM) from Renal Cell Carcinoma (RCC) and to analyse prognostic factors affecting overall survival (OS), disease-free interval (DFI) between primary RCC and first LM, and disease-free survival (DFS) after PM and before lung recurrence. Medical records of 210 patients who underwent PM from RCC in 4 Italian Thoracic Centres, from January 2000 to September 2019, were collected and analysed. All patients underwent RCC resection before lung surgery. The main RCC histology was clear cells (188, 89.5%). The 5- and 10-year OS from the first lung operation were 60% and 34%, respectively. LM synchronous with RCC (p = 0.01) and (Karnofsky Performance Status Scale) KPSS &lt, 80% (p &lt, 0.001) negatively influenced OS. Five- and 10-year DFI were 54% and 28%, respectively. The main factors negatively influencing DFI were: male gender (p = 0.039), KPSS &lt, 80% (p = 0.009) and lactate dehydrogenase &gt, 1.5 times 140 U/L (p = 0.001). Five- and 10-year disease-free survival were 54% and 28%, respectively, multiple LM (p = 0.036), KPSS &lt, 80% (p = 0.001) and histology of RCC other than clear cells negatively influenced disease-free survival. Conclusions: patients with KPSS &gt, 80%, single metachronous LM with a long DFI from RCC diagnosis, and clear cell histology, benefit from pulmonary metastasectomy.

BackgroundUntil now, no robust data supported the efficacy, safety and recommendation for influenza vaccination in patients with cancer receiving immune checkpoint inhibitors (ICIs).MethodsThe prospective multicenter observational INfluenza Vaccine Indication During therapy with Immune checkpoint inhibitors (INVIDIa-2) study investigated the clinical effectiveness of influenza vaccination in patients with advanced cancer receiving ICIs, enrolled in 82 Italian centers from October 2019 to January 2020. The primary endpoint was the time-adjusted incidence of influenza-like illness (ILI) until April 30, 2020. Secondary endpoints regarded ILI severity and vaccine safety.ResultsThe study enrolled 1279 patients; 1188 patients were evaluable for the primary endpoint analysis. Of them, 48.9% (581) received influenza vaccination. The overall ILI incidence was 8.2% (98 patients). Vaccinated patients were significantly more frequently elderly (pvs 29.8%, p=0.027). ILI lethality was, respectively, 0% in vaccinated and 4.3% in unvaccinated patients. Vaccine-related adverse events were rare and mild (1.5%, grades 1–2).ConclusionThe INVIDIa-2 study results support a positive recommendation for influenza vaccination in patients with advanced cancer receiving immunotherapy.

Biopsy proven Gleason score is essential to decide treatment modalities for prostate cancer, either surgical (radical prostatectomy) or non-surgical (active surveillance, watchful waiting, radiation therapy and hormone therapy). Several studies indicated that biopsy proven Gleason score may underestimate Gleason score at radical prostatectomy, hence we aimed to calculate the minimum length of biopsy cores needed to have Gleason score agreement. We evaluated 115 prostate cancer patients who underwent multiparametric magnetic resonance/transperineal ultrasonography fusion biopsy and subsequently, radical prostatectomy. Biopsy proven Gleason score was consistent with Gleason score at subsequent radical prostatectomy in 82.6% of patients, while in 17.4% of patients, Gleason score was higher at radical prostatectomy. Gleason score agreement showed a strong direct association with a ratio &gt, 0.05 between the total volume of biopsies performed in tumor area and the volume of the corresponding tumor at radical prostatectomy. A significant association was also found with a ratio &ge, 0.0034 between the tumor volume in the biopsy and the volume of the corresponding tumor at radical prostatectomy and with a ratio &ge, 0.086 between the tumor volume in the biopsy and the total volume of biopsies performed in the tumor area. These results could be exploited to calculate the minimum length of biopsy cores needed to have a correct Gleason score estimation and therefore be used in fusion targeted biopsies with volume adjustments.

With the introduction of immune checkpoint inhibitors (ICIs) and next-generation vascular endothelial growth factor receptor&ndash, tyrosine kinase inhibitors (VEGFR&ndash, TKIs), the survival of patients with advanced renal cell carcinoma (RCC) has improved remarkably. However, not all patients have benefited from treatments, and to date, there are still no validated biomarkers that can be included in the therapeutic algorithm. Thus, the identification of predictive biomarkers is necessary to increase the number of responsive patients and to understand the underlying immunity. The clinical outcome of RCC patients is, in fact, associated with immune response. In this exploratory pilot study, we assessed the immune effect of TKI therapy in order to evaluate the immune status of metastatic renal cell carcinoma (mRCC) patients so that we could define a combination of immunological biomarkers relevant to improving patient outcomes. We profiled the circulating levels in 20 mRCC patients of exhausted/activated/regulatory T cell subsets through flow cytometry and of 14 immune checkpoint-related proteins and 20 inflammation cytokines/chemokines using multiplex Luminex assay, both at baseline and during TKI therapy. We identified the CD3+CD8+CD137+ and CD3+CD137+PD1+ T cell populations, as well as seven soluble immune molecules (i.e., IFN&gamma, sPDL2, sHVEM, sPD1, sGITR, sPDL1, and sCTLA4) associated with the clinical responses of mRCC patients, either modulated by TKI therapy or not. These results suggest an immunological profile of mRCC patients, which will help to improve clinical decision-making for RCC patients in terms of the best combination of strategies, as well as the optimal timing and therapeutic sequence.

Aim: INVIDIa was a retrospective, multicenter study, exploring the clinical efficacy of influenza vaccine in 300 cancer patients undergoing immunotherapy. Overall survival (OS) was immature at the initial report. Methods: We reported the final OS analysis from the original study population and within subgroups. Results: Both at the univariate and multivariate analysis, the occurrence of influenza syndrome (IS) was significantly related to better OS in the overall population (OR: 0.53 [95% CI: 0.32–0.88]; p = 0.01). In the lung cancer subgroup, receiving flu vaccine and/or developing IS was related to better OS (p = 0.04). Within elderly patients, the flu vaccine was the main variable for the relative OS advantage (p = 0.05). Conclusion: Receiving the flu vaccine and/or developing IS was related to better OS within the INVIDIa population.

Diarrhoea is one of the most burdensome and common adverse events of chemotherapeutics, and has no standardised therapy to date. Increasing evidence suggests that the gut microbiome can influence the development of chemotherapy-induced diarrhoea. Here we report findings from a randomised clinical trial of faecal microbiota transplantation (FMT) to treat diarrhoea induced by tyrosine kinase inhibitors (TKI) in patients with metastatic renal cell carcinoma (ClinicalTrials.gov number: NCT04040712). The primary outcome is the resolution of diarrhoea four weeks after the end of treatments. Twenty patients are randomised to receive FMT from healthy donors or placebo FMT (vehicle only). Donor FMT is more effective than placebo FMT in treating TKI-induced diarrhoea, and a successful engraftment is observed in subjects receiving donor faeces. No serious adverse events are observed in both treatment arms. The trial meets pre-specified endpoints. Our findings suggest that the therapeutic manipulation of gut microbiota may become a promising treatment option to manage TKI-dependent diarrhoea., Tyrosine kinase inhibitors (TKIs) have improved the clinical outcomes of patients with metastatic renal cell carcinoma (mRCC), however TKI-related diarrhoea is a common and serious adverse effect. Here the authors show in a randomized clinical trial that faecal microbiota transplantation from healthy donors can improve TKI-induced diarrhoea in patients with mRCC.

We analyzed data from 738 HER2‐positive metastatic breast cancer (mbc) patients treated with pertuzumab‐based regimens and/or T‐DM1 at 45 Italian centers. Outcomes were explored in relation to tumor subtype assessed by immunohistochemistry (IHC). The median progression‐free survival at first‐line (mPFS1) was 12 months. Pertuzumab as first‐line conferred longer mPFS1 compared to other first‐line treatments (16 vs. 9 months, p = 0.0001), regardless of IHC subtype. Median PFS in second‐line (mPFS2) was 7 months, with no difference by IHC subtype, but it was more favorable with T‐DM1 compared to other agents (7 vs. 6 months, p = 0.03). There was no PFS2 gain in patients with tumors expressing both hormonal receptors (HRs; p = 0.17), while a trend emerged for tumors with one HR (p = 0.05). Conversely, PFS2 gain was significant in HRs‐negative tumors (p = 0.04). Median overall survival (mOS) was 74 months, with no significant differences by IHC subtypes. Survival rates at 2 and 3 years in patients treated with T‐DM1 in second‐line after pertuzumab were significantly lower compared to pertuzumab‐naïve patients (p = 0.01). When analyzed by IHC subtype, the outcome was confirmed if both HRs or no HRs were expressed (p = 0.02 and p = 0.006, respectively). Our results confirm that HRs expression impacts the clinical behavior and novel treatment‐related outcomes of HER2‐positive tumors when treatment sequences are considered. Moreover, multivariate analysis showed that HRs expression had no effect on PFS and OS. Further studies are warranted to confirm our findings and clarify the interplay between HER2 and estrogen receptor pathways in HER2‐positive (mbc) patients., What's new? About half of breast cancers positive for human epidermal growth factor (HER2) also express hormone receptors but the impact of hormone receptor status on the success of HER2‐directed treatments is not fully explored. Here the authors retrospectively assessed tumor behavior and treatment outcomes in 738 women with HER2+ metastatic breast cancer treated with new generation anti‐HER2 agents. Distinct hormone receptor expression patterns significantly affected the progression free and overall survival, justifying further studies to define optimal treatment regimens and the interplay between hormone receptor and HER2 signaling.

Background:This prospective, multicentre, observational INVIDIa-2 study is investigating the clinical efficacy of influenza vaccination in advanced-cancer patients receiving immune-checkpoint inhibitors (ICIs), enrolled in 82 Italian centres, from October 2019 to January 2020. The primary endpoint was the incidence of influenza-like illness (ILI) until 30 April 2020. All the ILI episodes, laboratory tests, complications, hospitalizations and pneumonitis were recorded. Therefore, the study prospectively recorded all the COVID-19 ILI events.Patients and methods:Patients were included in this non-prespecified COVID-19 analysis, if alive on 31 January 2020, when the Italian government declared the national emergency. The prevalence of confirmed COVID-19 cases was detected as ILI episode with laboratory confirmation of SARS-CoV-2. Cases with clinical-radiological diagnosis of COVID-19 (COVID-like ILIs), were also reported.Results:Out of 1257 enrolled patients, 955 matched the inclusion criteria for this unplanned analysis. From 31 January to 30 April 2020, 66 patients had ILI: 9 of 955 cases were confirmed COVID-19 ILIs, with prevalence of 0.9% [95% confidence interval (CI): 0.3–2.4], a hospitalization rate of 100% and a mortality rate of 77.8%. Including 5 COVID-like ILIs, the overall COVID-19 prevalence was 1.5% (95% CI: 0.5–3.1), with 100% hospitalization and 64% mortality. The presence of elderly, males and comorbidities was significantly higher among patients vaccinated against influenza versus unvaccinated ( p = 0.009, p Conclusion:COVID-19 has a meaningful clinical impact on the cancer-patient population receiving ICIs, with high prevalence, hospitalization and an alarming mortality rate among symptomatic cases. Influenza vaccination does not protect from SARS-CoV-2 infection.

Pneumonitis is a rare but serious adverse event caused by cancer immunotherapy. The diagnosis between COVID-19-induced pneumonia and immunotherapy-induced pneumonitis may be challenging in the era of COVID-19 outbreak. Some clinical symptoms and radiological findings of pneumonitis can be attributed to the coronavirus infection as well as to an immune-related adverse event. Identifying the exact cause of a pneumonitis in patients on treatment with immunotherapy is crucial to promptly start the most appropriate treatment. The proper management of immune checkpoint inhibitors for the risk of pneumonia must take into account a series of parameters. Accurate attention should be payed to symptoms like cough, fever and dyspnea during immunotherapy.

Background We performed a multicenter retrospective observational study to investigate the impact of clinical-pathological features and therapeutic strategies on both the complications and survival of patients with bone metastases (BMs) from malignant melanoma. Patients and methods A total of 305 patients with melanoma and radiological evidence of BMs were retrospectively enrolled from 19 Italian centers. All patients received conventional treatments in accordance with each own treating physician's practice. Both univariate and multivariate models were used to explore the impact of melanoma features, including skeletal-related events (SREs), and different treatments on both overall survival (OS) and time-to-SREs. The chi-squared test evaluated the suitability of several parameters to predict the occurrence of SREs. Results Eighty-three percent of patients had metachronous BMs. The prevalent (90%) bone metastatic site was the spine, while 45% had involvement of the appendicular skeleton. Forty-seven percent experienced at least one SRE, including palliative radiotherapy (RT) in 37% of cases. No melanoma-associated factor was predictive of the development of SREs, although patients receiving early treatment with bone-targeted agents showed 62% lower risk and delayed time of SRE occurrence. Median OS from the diagnosis of bone metastasis was 10.7 months. The multivariate analysis revealed as independent prognostic factors the number of BMs, number of metastatic organs, baseline lactate dehydrogenase levels, and treatment with targeted therapy or immunotherapy. Subgroup analyses showed the best OS (median = 16.5 months) in the subset of patients receiving both immunotherapy and palliative RT. Conclusion Based on our results, patients undergoing immunotherapy and palliative RT showed an OS benefit suggestive of a possible additive effect. The apparent protective role of bone targeting agent use on SREs observed in our analysis should deserve prospective evaluation.

We carried out a retrospective observational study of 264 HER2-positive advanced breast cancer (ABC) patients to explore the efficacy of first-line treatment with pertuzumab/trastuzumab/taxane in real-world setting. Survival data were analyzed by Kaplan Meier curves and log rank test. Median follow-up, length of pertuzumab/trastuzumab/taxane treatment and of pertuzumab, trastuzumab maintenance were 21, 4 and 15 months, respectively. The response rate was 77.3%, and the clinical benefit rate 93.6%. Median progression-free survival (mPFS) was 21 months, and median overall survival (mOS) was not reached. When comparing patients by trastuzumab-pretreatment, similar PFS were observed, although a longer OS was reached in trastuzumab-naïve patients (p = 0.02). Brain metastases at baseline and their development in course of therapy were associated with significantly shorter PFS (p = 0.0006) and shorter OS, although at a not fully statistically relevant extent (p = 0.06). The addition of maintenance endocrine therapy (ET) to pertuzumab/trastuzumab maintenance was associated with longer PFS (p = 0.0001), although no significant differences were detected in OS (p = 0.31). Results were confirmed by propensity score analysis (p = 0.003 and p = 0.46, respectively). In multivariate models, longer PFS was related to lower Performance Status (PS) (p = 0.07), metastatic stage at diagnosis (p = 0.006) and single metastatic site (p

Introduction: Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominantly inherited endocrine tumor syndrome characterized by the development of cancer in various endocrine organs, particularly in the pituitary, parathyroid and pancreas. Moreover, in some cases, also non-endocrine tumors can be diagnosed, developing atypical phenotypes. Case report: We report herein the clinical history of a patient affected by MEN-1 syndrome who developed atypical features for this disease. The patient's clinical history started in August 2015 when he was referred, at the age of 23 years, to the Emergency Department of our Hospital for the occurrence of progressive asthenia, weakness, tremors and syncope. The biochemical test documented hyper-calcemia and severe hypoglycemia. The patient was referred to our Neuroendocrine Tumor and Pituitary Unit and he was diagnosed with pancreatic insulinoma, hypercalcemic hyperparathyroidism, and a prolactin secreting pituitary adenoma. The MEN-1 syndrome was suspected and genetic tests for mutation of menin resulted positive for the pathogenic variant c1548dupG. In January 2016, the patient was diagnosed with intratubular germ cell neoplasia, consisting of a mature teratoma and yolk sac tumor and he underwent a right orchiectomy. Conclusion: This is the first case report showing the clear association of MEN-1 syndrome with yolk sac tumors and teratomas, as in our case, the c1548dupG represents a pathogenic variant rather than a SNP. This case suggests the opportunity of an accurate evaluation of the testis particularly in young MEN-1 affected patients and that a prompt screening for neoplastic disease should involve all the endocrine glands.

9536 Background: Metastatic uveal melanoma (mUM) is a rare and aggressive disease. No standard therapy has been established. All the available treatments derive from trials in cutaneous melanoma. A minority of patients with mUM can benefit from immunotherapy. Immunological features of a group of patients with metastatic UM treated with Pembrolizumab were analyzed in order to explore the immune-response in this disease and the potential factors able to select the patients who can benefit from immunotherapy. Methods: Blood samples from 12 UM patients before (T0) and during treatment with Pembrolizumab (T1: after 1 cycle of Pembrolizumab; T2: after 3 cycle of Pembrolizumab) were collected. Peripheral blood mononucleated cells (PBMCs) were isolated and characterized for markers expression. Sera were analyzed for a panel of soluble (s) immune checkpoints and cytokines. The correlation between immunological parameters with PFS and OS was explored. Blood samples from 6 metastatic cutaneous melanoma (CM) patients with a confirmed response to anti PD-1 agents were also collected during the treatment and analyzed for PBMCs and sera. Results: Soluble CTLA4, sPD-L1, sCD137, sTIM3 were significantly higher in UM than in CM. CD137 was significantly higher in UM patients progressed with Pembrolizumab than in the 2 responsive patients (512 pg/ml vs < 12.9 pg/ml, respectively, p = 0.04) who are still alive and on treatment after a median follow-up of 24 months. Low sGITR, sCD137, sHVEM, and sTIM3 are associated with longer PFS. IL-8 was lower in CM than UM (2.5 pg/ml vs 40.7 pg/ml) and in the responsive versus progressed UM patients (3,7 pg/ml vs 118 pg/ml, p = 0,042). Low levels of IL-8 and IL-1-alpha are significantly associated with longer PFS (p = 0.011 and 0.010 respectively). In responsive patients CD137 expression on CD3+, CD4+ and CD8+ T cells was higher than in progressed patients, while sCD137 was absent. Conclusions: A group of s-immune checkpoints and cytokines correlate with Pembrolizumab effectiveness in mUM. High expression of CD137 on T cells associated with the absence of its soluble form in responders could suggest the correlation between the retention of this co-stimulatory molecule and efficacy of anti-PD1.

Introduction and purpose Choroidal metastases (CM) are the most common intraocular malignancies. With longer survival rates for cancer patients, CM will be increasingly encountered. We evaluated clinical and ultrasonographic (US) characteristics of CM in order to identify diagnostic biomarkers that correlate with the primary tumor site. Methods The medical records of all patients with CM evaluated at the Ocular Oncology Unit between February 2010 and March 2020 were analyzed. Results 82 eyes of 70 patients were included. The primary cancer site was lung in 26 patients (37%), breast in 23 (33%), kidney in 9 (13%), gastrointestinal in 5 (7%), thyroid in 5 (7%), parathyroids and prostate respectively in 2 (3%). Fifty-five patients (78%) had other systemic metastases at the time of ocular diagnosis. Ten (14%) patients had no history of primary cancer. Bilateral CM were found in 20 patients (29%); fifty-six eyes (68%) had a single CM. The epicenter of CM was predominantly macula (43 eyes, 52%). The mean thickness was 4,1 mm (range 1,8–12,3). US structure was inhomogeneous in 67 eyes (82%). Reflectivity was mainly medium (39%) and medium-low (39%). In particular, CM from lung cancer showed lower reflectivity than those from the breast (p = 0,02). CM deriving from lung cancer were typically dome-shaped, whereas CM originating from breast were characteristically plateau shaped (p = 0,02). Seventy-four (91%) eyes presented fluid on optical coherence tomography. Conclusion We significatively found that CM from lung cancer generally appear dome-shaped with medium-low internal reflectivity, whereas those from breast cancer typically present a plateau appearance and higher internal reflectivity. Though it is hard to identify the site of the primary tumor relying exclusively on clinical and US aspects, morphology and internal reflectivity can be considered as diagnostic biomarkers. Thus, the origin of the primary tumor can be suspected by integrating a constellation of findings.

Bevacizumab in combination with taxanes in HER2-negative metastatic breast cancer (MBC) patients has shown improved progression-free survival (PFS), despite the lack of clear overall survival (OS) benefit. We performed a retrospective analysis to evaluate the impact of paclitaxel-bevacizumab and of maintenance therapy with bevacizumab (BM) and endocrine therapy (ET) in the real-world practice. We identified 314 HER2-negative MBC patients treated in 12 cancer centers. Overall, the median PFS and OS were 14 and 40 months, respectively. Among the 254 patients potentially eligible for BM, 183 received BM after paclitaxel discontinuation until progression/toxicity. PFS and OS were improved in patients who had received BM in comparison with those potentially eligible but who did not receive BM (P

Background/Aim: In genetically engineered murine models of pancreatic ductal adenocarcinomas (PDAC), high levels of Runx3 increase the metastatic potential of cancer cells. Ιn this study we evaluated the role of Runx3 in human pancreatic cancer. Materials and Methods: Runx3 was retrospectively assessed by immunohistochemistry in seventy-eight tumor samples of patients who underwent surgical resection for PDCA and were followed at least for 24 months. Results: Thirty-two cases resulted completely negative for Runx3; forty-six showed highly variable expression. We established an optimal cut-off value of Runx3 in predicting distant metastasis equal to 0.04. The odds ratio (ORs) for development of distant metastases at multivariate analysis for patients having Runx3 ≥0.04 was 4.26 (p=0.043) and 4.68 (p=0.032) after adjusting for residual tumor and treatment, respectively; OR for development of metastases in multiple sites was 4.28 (p=0.025) for Runx3 ≥0.04. Conclusion: Our results support the ability of Runx3 to contribute to the dissemination of human PDAC thus confirming the observations from murine models.

Aim: Considering the unmet need for the counseling of cancer patients treated with immune checkpoint inhibitors (CKI) about influenza vaccination, an explorative study was planned to assess flu vaccine efficacy in this population. Methods: INVIDIa was a retrospective, multicenter study, enrolling consecutive advanced cancer outpatients receiving CKI during the influenza season 2016–2017. Results: Of 300 patients, 79 received flu vaccine. The incidence of influenza syndrome was 24.1% among vaccinated, versus 11.8% of controls; odds ratio: 2.4; 95% CI: 1.23–4.59; p = 0.009. The clinical ineffectiveness of vaccine was more pronounced among elderly: 37.8% among vaccinated patients, versus 6.1% of unvaccinated, odds ratio: 9.28; 95% CI: 2.77–31.14; p

The evidence emerged from the TOURANDOT trial encourages evaluating the role of anthropometric determinants on treatment outcomes in HER2-negative metastatic breast cancer patients treated with bevacizumab-including regimens. We thus analyzed data from a subgroup of these patients from a larger cohort previously assessed for treatment outcomes. Patients were included in the present analysis if body mass index values had been recorded at baseline. Clinical benefit rates, progression free survival and overall survival were assessed for the overall study population and subgroups defined upon molecular subtype. One hundred ninety six patients were included (N:196). Body mass index showed no impact on clinical benefit rates in the overall study sample and in the luminal cancer subset (p = 0.12 and p = 0.79, respectively), but did so in the triple negative subgroup, with higher rates in patients with body mass index ≥25 (p = 0.03). In the overall study sample, body mass index did no impact progression free or overall survival (p = 0.33 and p = 0.67, respectively). Conversely, in triple negative patients, progression free survival was significantly longer with body mass index ≥25 (6 vs 14 months, p = 0.04). In this subset, overall survival was more favorable (25 vs 19 months, p = 0.02). The impact of the molecular subtype was confirmed in multivariate models including the length of progression free survival, and number of metastatic sites (p < 0.0001). Further studies are warranted to confirm our findings in more adequately sized, ad hoc, prospective studies.

The number of elderly patients diagnosed with rectal cancer (RC) is very high and, considering colon and rectal cancer (CRC), is one of the leading causes of cancer-related death in the elderly [1]. However, the number of older patients enrolled in clinical trials is underrepresented and in most cases elderly population undertreated. Although, with the introduction of new treatments and better diagnostic techniques and surgical procedures, a better outcome is achievable today also in elderly patients diagnosed with resectable or metastatic rectal cancer, overall survival rate remains low. This is probably due to less aggressive diagnostic evaluation; less intensive chemotherapy, including anticipatory drug dose reduction or empiric schedule alteration; less aggressive surgery; and, finally yet importantly, also social conditions and limited access to healthcare system of elderly population with cancer.

Background Neoadjuvant chemotherapy demonstrated a survival benefit versus cystectomy alone in muscle-invasive urothelial bladder cancer. Despite this advantage, preoperative chemotherapy is not widely employed. When patients are unfit for cisplatin-based regimen, they are often candidates for immediate surgery. In our study, patients with muscle-invasive bladder cancer were treated with neoadjuvant chemotherapy. The principal objective was the rate of complete pathological response (pCR). Secondary end-points were disease-free survival (DFS), overall survival (OS) and toxicity. Patients and methods Patients (n=72) with Eastern Cooperative Oncology Group (ECOG) performance status 0-1, clinical stage cT3-4, and/or N+ muscle-invasive bladder cancer were enrolled. The chemotherapy regimen was established according to the cisplatin feasibility. Thirty patients were treated with cisplatin/gemcitabine (Gem) and 42 with carboplatin/Gem. Results The rate of pCR was 29.2%, 36% with cisplatin-based treatment and 23.8% with carboplatin (p=0.3574). DFS and OS were longer in pCR patients, while no difference was reported between cisplatin/Gem and Carboplatin/Gem groups. Conclusion Our results confirm the prognostic value of pCR in neoadjuvant chemotherapy for muscle-invasive bladder cancer. When the patients are not fit for cisplatin, a carboplatin/Gem regimen represents a valid option because of comparable long-term outcome. When cisplatin is not feasible, the exclusion of a preoperative treatment is not justified.

Background/aim Few clinical trials are available for advanced biliary tract carcinoma (BTC). We conducted this randomized phase II clinical trial to explore efficacy and safety of 5-fluorouracil/leucovorin (5-FU/LV - de Gramont) or the same regimen plus oxaliplatin (Folfox 4) as first-line treatment of advanced BTC. Patients and methods Primary endpoint was overall survival (OS); secondary endpoints were progression-free survival (PFS), response and toxicity. Results A total of 48 patients were enrolled, 23 in de Gramont arm and 25 in the Folfox arm. Disease control rate was 56.5% for de Gramont vs. 72% for Folfox. RR was 21.7% for de Gramont arm and 28% for Folfox arm (p=0.12). PFS was in favor of Folfox (5.2 vs. 2.8 months; p=0.031). OS was 7.5 and 13.0 months for de Gramont and Folfox arm respectively (p=0.0010). Toxicity was generally mild in both arms. Conclusion Folfox 4 could be considered a valid option as first-line treatment of BTC due to its efficacy and tolerability.

// Giovanni Schinzari 1 , Ernesto Rossi 1 , Francesco Pierconti 2 , Giovanna Garufi 1 , Santa Monterisi 1 , Antonia Strippoli 1 , Ettore D’Argento 1 , Alessandra Cassano 1 and Carlo Barone 1 1 Department of Medical Oncology, Universita Cattolica del Sacro Cuore, Rome, Italy 2 Department of Pathology, Universita Cattolica del Sacro Cuore, Rome, Italy Correspondence to: Giovanni Schinzari, email: giovanni.schinzari@unicatt.it Keywords: vinflunine; transitional cell carcinoma of the urothelium; second line; toxicity Received: July 18, 2017 Accepted: December 03, 2017 Published: January 11, 2018 ABSTRACT Vinflunine is the only cytotoxic agent tested as a second line therapy in transitional cell carcinoma of the urothelium in a phase III trial. It is not largely employed in clinical practice because of the high incidence of grade 3–4 toxicity. We evaluated efficacy and safety of Vinflunine at the dose of 280 mg/m 2 every 3 weeks associated with primary prophylaxis with granulocyte growth factors and laxatives for patients progressed after platinum + Gemcitabine. Overall survival was 8.5 months, progression-free survival 4.33 months and response rate 25%, with disease control rate 57.2%. Grade III-IV neutropenia occurred in 10.7% of the patients, grade III-IV anemia and grade III thrombocytopenia in 10.7% and 7.2%, respectively. Among non haematological toxicity, grade I-II constipation was reported in 14.2% of the patients, without grade III-IV adverse events. No discontinuation for toxicity was observed. This study underlines that Vinfluinine at a dose of 280 mg/m 2 associated with primary prophylaxis for neutropenia and constipation is effective and with a favorable toxicity profile.

// Mariantonietta Di Salvatore 1 , Filippo Pietrantonio 2 , Armando Orlandi 1 , Marzia Del Re 3 , Rosa Berenato 2 , Ernesto Rossi 1 , Marta Caporale 2 , Donatella Guarino 4 , Antonia Martinetti 2 , Michele Basso 1 , Roberta Mennitto 2 , Concetta Santonocito 4 , Alessia Mennitto 2 , Giovanni Schinzari 1 , Ilaria Bossi 2 , Ettore Capoluongo 4 , Romano Danesi 3 , Filippo de Braud 2 , Carlo Barone 1 1 Unit of Clinical Oncology, Universita Cattolica del Sacro Cuore, 00168 Rome, Italy 2 Medical Oncology Department, Fondazione IRCCS Istituto Nazionale dei Tumori, 20133 Milan, Italy 3 Clinical Pharmacology and Pharmacogenetic Unit, Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy 4 Laboratory of Clinical Molecular Biology, Institute of Biochemistry and Clinical Biochemistry, Universita Cattolica del Sacro Cuore, 00168 Rome, Italy Correspondence to: Mariantonietta Di Salvatore, email: mariantonietta.disalvatore@gmail.com Keywords: single nucleotid polymorphisms, bevacizumab, IL-8, eNOS, colorectal cancer Received: May 23, 2016 Accepted: November 02, 2016 Published: January 25, 2017 ABSTRACT Background : Predictive biomarkers of efficacy and toxicity of bevacizumab have not yet been validated. This study assessed the influence of IL-8, eNOS and VEGF-A polymorphisms in RAS mutated metastatic colorectal cancer patients receiving bevacizumab-based chemotherapy. Methods: 120 patients treated with first-line combination FOLFOX6 plus bevacizumab were included. A historical cohort of 112 RAS mutated colorectal cancer patients treated with FOLFOX6 alone served as control group. The following SNPs were analyzed: IL-8 c.-251T>A; eNOS c.-786T>C and c.-894G>T; VEGF-A c.936C>T, c.958T>C, c.1154A>G and c.2578C>A. Correlation of SNPs, baseline IL-8 serum levels and bevacizumab-efficacy was done. Results : In the bevacizumab group, carriers of the IL-8 alleles c.-251TA+AA showed a shorter PFS (P=0.002) and OS (P=0.03) compared to TT alleles. Patients with pre-treatment IL-8 18,25 pg/ml). IL-8 c.-251TA+AA carriers had significantly higher IL-8 levels (P T was found associated with higher severe toxicity (P=0.0002) in patients carrying the c.-894TT genotype. Conclusions : Although our data need prospective validation, IL-8 and eNOS SNPs may be have a role as predictive biomarkers for bevacizumab efficacy and toxicity.

No standard therapy is established for metastatic uveal melanoma. Liver involvement in uveal melanoma may lead to organ impairment, which represents a common cause of death. Tumor shrinkage might improve survival by delaying hepatic failure. Since the combination of cisplatin, vinblastine, dacarbazine allowed a high response rate in metastatic cutaneous melanoma, we explored efficacy and safety of this regimen in unresectable liver metastases of uveal melanoma. In the present phase II study we administered intravenously cisplatin (80 mg/mq, day 1), dacarbazine (250 mg/mq/day, days 1-3), vinblastine (2 mg maximum, day 1) every 21 days as first line treatment for patients with unresectable metastases of uveal melanoma and BRAF wild type. Primary endpoint was objective response rate; overall survival (OS), progression-free survival and toxicity were secondary endpoints. Partial responses were observed in five (20%) patients, stable disease in 12 (48%) patients; disease control rate was 68%. Median OS of all the patients was 13 months, median progression free survival was 5.5 months. OS of responding patients was 21 months; OS of patients with disease control was 18 months, significantly longer than survival of progressing patients (7 months, P=0.0003). Five (20%) patients experienced grade 3-4 toxicity. Combination of cisplatin, vinblastine and dacarbazine was feasible and demonstrate both an interesting objective response rate and a survival benefit for patients achieving a disease control. This regimen could be considered for patients with good performance status and unresectable liver limited disease.

No standard treatment has been established for metastatic uveal melanoma (mUM). Immunotherapy is commonly used for this disease even though UM has not been included in phase III clinical trials with checkpoint inhibitors. Unfortunately, only a minority of patients obtain a clinical benefit with immunotherapy. The immunological features of mUM were reviewed in order to understand if immunotherapy could still play a role for this disease.

615 Background: Diarrhea is a common adverse event of tyrosine kinase inhibitors (TKI). No standard treatment for TKI-induced diarrhea has been established, although probiotics are commonly used. In several patients TKI dose reduction is necessary. Data showing the interplay between microbiota and TKI-induced diarrhea are reported. The therapeutic modulation of gut microbiota could be useful to ameliorate TKI-related diarrhea. Our study aims to explore the efficacy and safety of fecal microbiota transplantation (FMT), compared with current clinical practice approach, for the treatment of TKI-associated diarrhea in patients with metastatic renal cell carcinoma. Methods: Patients on treatment with Pazopanib/Sunitinib as first line therapy for metastatic renal cell carcinoma and TKI-associated diarrhea (³ 4 stools per day over baseline) were randomize to receive FMT from healthy donor by colonoscopy (fresh faeces) or probiotics (L. casei DG). The primary endpoint was the resolution of TKI-related diarrhea. Baseline fecal samples were collected from all patients and donors. All patients were followed up 7, 15, 30 and 60 days after the treatment for diarrhea. Results: 21 subjects, 10 in FMT arm and 11 in control arm, have been enrolled. At 7 day-follow-up, TKI-related diarrhea disappeared in 10 patients of the FMT group and in 6 patients of the control group (100% vs 54.5%, p = 0.02). At 15-day and 30-day, 9 patients in the FMT group and 0 patients in the control group experienced resolution of diarrhea (90% vs 0%, p = 0.0001). At 60-days 8/10 patients in FMT arm did not have diarrhea. Dose reduction was necessary in 4 patients of the control group. No serious adverse events associated with any of the two treatment protocols were observed. Metagenomic analyses on collected stool samples are ongoing. Conclusions: This open-label randomised controlled trial showed the effectiveness and safety of FMT compared with probiotics in curing TKI-related diarrhea in patients with metastatic renal cell carcinoma, avoiding the necessity of dose reduction. Considering the increasing evidence, the modulation of microbiota trough FMT could also affect the efficacy of immunotherapy for metastatic renal cell carcinoma.

Background: The role of bevacizumab in metastatic breast cancer is controversial. Identification of predictive biomarkers could help to select patients who really benefit from it. We evaluated the association of angiogenesis-related gene polymorphisms with the treatment outcome of bevacizumab in metastatic breast cancer patients. Patients and methods: eNOS-786T/C and -894G/T, IL-8-251T/A genomic polymorphisms were assessed in 31 metastatic breast cancer patients treated with bevacizumab plus chemotherapy in the first-line setting. Testing for association between each polymorphism and treatment outcome was performed. Results: Patients with IL-8 251 AA genotype showed a significantly lower progression-free survival in each combination comparison: "TT" vs "AA" (13 vs 8 months; p = 0.008); TT vs TA vs AA (13 vs 11 vs 8 months; p = 0.02); TT vs TA +AA (13 vs 11 months; p = 0.01); TT + TA vs AA (12 vs 8 months; p = 0.01) and a lower overall survival when compared with TT +TA genotype (26 vs 51 months, p = 0.04). Patients carrying eNOS 894 TT genotype showed a statistically significant lower progression-free survival than patients with GG genotype (11.5 vs 26.5 months; p = 0.04) with no differences in the overall survival. No association with response rate was found with any of the polymorphisms analyzed. Conclusion: These findings suggest that IL-8 251T/A and eNOS-894 G/T polymorphisms might have a role in predicting treatment outcome of bevacizumab in metastatic breast cancer. Our results are hypothesis generating and need to be confirmed in larger clinical trials.

e12504 Background: Pertuzumab (P) , Trastuzumab (T) and Docetaxel (D) is standard first-line treatment in patients (pts) with HER2 + metastatic breast cancer (MBC). This multicenter retrospetive observational study was performed to evaluate the activity of P and T in combination with D or Paclitaxel (Tx) in real world HER2 + MBC pts. Methods: We identified HER2 + MBC pts treated with P, T and D or Ptx optionally followed by P, T and endocrine therapy (ET) maintenance in hormone positive (HR+) BC, in 17 Italian cancer centres between 09/2012 and 08/2016. Overall Survival (OS) and Progression Free Survival (PFS) were calculated by the Kaplan-Meier product-limit method. Log-rank test was used to assess differences between subgroups. Results: 191 pts were included in our analysis. Pts characteristics: median age 54 years (range 29-80); PS 0 in 127 (67%) pts and PS 1 in 54 (28%); 107 (56%) had visceral metastases (mts), 23 (12%) only bone mts and 28 (15%) brain mts, 130 (68%) were ER/PgR +. 76 pts (40%) were metastatic at diagnosis; 148 (78) were treated with D while 43 (22%) with Tx. The ORR was 78% (CI 95% 72-84), RC 18% and RP 60%, only 10 (5%) had PD. To date, of the 54 pts treated with ET maintenance, 26% had a further improvement of response (7 pts had RC). At median follow-up of 17 months (mo) (range 6- 52), median PFS was 20 mo (95% CI 14-26) and median OS at 2 years was 80%. No differences in PFS were found for age (p = 0.92), PS (p = 0.18), receptor status (p = 0.57), visceral mts (p = 0.54) and chemotherapy (cht) type (p = 0.47), whereas number of mts site (1 vs > 1) affected PFS (28 vs 16 mo, p = 0.002). Moreover median PFS in naïve pts and in pts pretreated with only cht was 28 mo (95% CI, 20-36) and 27 mo (95% CI, 16-38) respectively, whereas in pts pretreated with T it was 12 mo (95% CI 16-38 p 0.002). In HR+ pts ET maintenance together with P and T had an impact on PFS (28 vs 15 mo, p = 0.01). Conclusions: Our analysis confirms, in real world HER2 MBC pts, the efficacy of P, T and a taxane combination in first line treatment; in this population PFS was shorter in pts pretreated with T. ET maintenance in association with P and T in HR+ pts improved PFS. Data collection is ongoing and update results will be presented.

11033 Background: Basing on preliminary observations of OPUS and PRIME studies, our group retrospectively suggested that KRAS mutational status could affect response to oxaliplatin. We further conf...

e17577 Background: Cancer patients (pts) present often with acute syndromes requiring an urgent management. This scenario has dramatically changed during the last years due to the higher prevalence...

e22015 Background: No biomarkers have yet been identified able to predict the efficacy of bevacizumab. We evaluated the influence of some angiogenesis-related gene polymorphisms on efficacy and tox...

e11613 Background: The prognostic value of pCR on survival seems to be different in various breast cancer subtypes and is still a matter of debate. We investigated the association between intrinsic...

e14556 Background: Surgical removal of liver metastases can provide a chance of cure for selected patients (pts) with metastatic colorectal cancer (CRC). Less data are currently available on CRC lu...