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Objectives: The aim of this study was to investigate efficacy and safety of eribulin in heavily pretreated patients with advanced breast cancer (BC) in a real-life setting. Methods: This retrospective monocentric study included patients with HER-2-negative metastatic BC, pretreated with anthracyclines and taxanes, who were referred to the Oncology Department of Spedali Civili of Brescia from May 2012 to April 2017. Patients received the same dose of eribulin as that used in the EMBRACE trial: 1.4 mg/m2 on days 1 and 8 every 21 days. Results: In a total of 53 patients, 32% obtained a partial response, 11% a stable disease, and 43% a clinical benefit (CB). After a median follow-up of 36 months, median progression-free survival (PFS) was 4.7 months and median overall survival (OS) 13.53 months. Median PFS was significantly longer in patients who reported a CB compared to those with no CB, while survival outcomes (PFS and OS) were better in patients who received > 6 cycles of eribulin. Eribulin showed a good tolerability profile with acceptable toxicities, similar to those reported in EMBRACE. Conclusions: Our experience in a real-world setting confirms the activity, efficacy, and good tolerability profile of eribulin in heavily pretreated BC patients.

Objectives To describe the prevalence, severity, and self-reported characteristics of taste alterations (TAs) induced by chemotherapy and to investigate TAs across chemotherapy regimens. Sample & setting 243 adult patients from five outpatient practices in Northern Italy. Methods & variables Correlation, univariate, and multivariate linear regression analyses. Variables include TAs, symptoms reported by patients, and the effect of TAs on quality of life. Results A majority of the study sample reported TAs. Difficulty in tasting saltiness was most common, followed by difficulty in tasting umami and sweetness. The severity and characteristics of TAs changed across chemotherapy regimens. TAs correlated with quality of life and were significantly associated with patient's age and a 21-day chemotherapy schedule. Implications for nursing TAs are a frequent side effect of chemotherapy, with varying characteristics that have a negative effect on quality of life. Healthcare professionals should routinely assess for TAs and provide patients with specific management strategies depending on the nature of TAs.

Introduction: Circulating Tumor Cells (CTCs) levels are dynamic indicators of prognosis and response to therapy in metastatic breast cancer (MBC) patients (pts). CTCs levels have been reported to be higher in pts with bone than visceral metastases, respectively. However, little is known about CTCs levels in pts with BM involvement. We analysed CTC patterns in patients with either visceral, bone or BM to test the hypothesis that BM involvement would facilitate tumor cells to enter the systemic circulation as CTCs. Patients and methods: Sites and extension of metastatic disease were identified with conventional imaging. Bone metastases were diagnosed with either bone scintigraphy or CT-PET and the BM involvement was documented histologically by BM biopsy and metabolically by CT-PET. A training set of 10 pts was evaluated by both BM biopsy and CT-PET to verify the diagnostic performance of CT-PET in identifying BM metastases (M+). We found a 100% concordance between BM biopsy and CT-PET and we therefore used CT-PET for further analyses. The CellSearch System (Veridex LLC, Raritan, NJ, USA) was used for the isolation and enumeration of CTCs in peripheral blood. The Student's t-test and the two-way ANOVA test were used to compare means of CTCs among patients with different metastatic patterns. Results: The CTCs mean and median scores of 129 MBC pts were analysed. Final analysis focused on 101 pts with bone M+. Thirty-three pts had bone M+ alone and 68 pts had bone and visceral M+ (including lymphnodes, brain, liver and lung/pleura). Number of metastatic sites was 1, 2, 3, 4, 5 in 30%, 37%, 25%, 6% and 2% of pts, respectively. BM involvement was documented in 27 (27%) of pts in the whole series and in 12 (33%) of pts with bone M+ alone. Mean CTCs score in the whole series was 392 (0-9993) and the median number of CTCs was 20. In the whole series, BM involvement was associated with higher mean CTCs scores (1350 vs 42, p .014). In pts with bone M+ alone, mean CTCs score was 696 (0-7000) and pts with BM involvement had higher mean CTCs scores (1846 vs 39, p 0.37). Among the different metastatic patterns, the association of bone with BM involvement and liver M+ was correlated with the highest CTCs numbers. We could not perform comparisons in the 68 pts with both bone and visceral localizations because of the variety of metastatic patterns. However, the two-way ANOVA showed a significant influence of BM involvement on mean CTCs scores in pts with different metastatic patterns (p >.001). Conclusions: This work confirms that pts with bone metastases have higher numbers of CTCs than pts with visceral metastases. Extensive bone disease with BM involvement is characterized by an increase in CTCs numbers compared to bone disease without BM involvement. Bone marrow metastases are metabolically more active by CT-PET and can be accurately detected by metabolic imaging without need of BM biopsy. Further studies are ongoing. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-07-19.

e12504Background: Aromatase-inhibitors (AIs) decrease the bone mineral density (BMD) and increase the risk of clinical fractures but the mechanism underlying the increased fracture risk (FR) is not...

Aims and Background Advanced chemorefractory epithelial thymic tumors are still a challenge in clinical oncology. A therapeutic approach targeting a key molecular pathway could be the ideal solution in a neoplasm that can overexpress epidermal growth factor receptor (EGFR) in the epithelial component. Methods A patient with metastatic heavily pretreated thymic carcinoma was evaluated for EGFR expression in the primary tumor. Results Strong EGFR expression was revealed by immunohistochemistry. The patient received erlotinib therapy but had obtained no response after four months of treatment. Conclusion This preliminary experience suggests that erlotinib may not be a useful therapeutic choice in advanced pretreated thymic carcinomas.

Salivary gland carcinomas are rare cancers, comprising 1-5% of head and neck cancers. They represent a morphologically and clinically diverse group of tumors. The most commonly histopathologic types are mucoepidermoid cancer, adenoid cystic cancer and adenocarcinomas. Malignant salivary gland tumors generally present as painless, slow-growing tumors that are indistinguishable from benign tumors. Surgery is the principal treatment and is curative in early stage. Radiation therapy should be considered in most patients after surgical resection. Chemotherapy is reserved for palliative treatment of metastatic disease but results are disappointing. Recent studies have investigated the role of targeted therapies in a palliative setting. Multicentre cooperative group clinical trials are required to assess novel therapies to maximize patient resources in this uncommon tumor.

Expert consensus-based recommendations regarding key issues in the use of primary (or neoadjuvant) systemic treatment (PST) in patients with early breast cancer are a valuable resource for practising oncologists. PST remains a valuable therapeutic approach for the assessment of biological antitumor activity and clinical efficacy of new treatments in clinical trials. Neoadjuvant trials provide endpoints, such as pathological complete response (pCR) to treatment, that potentially translate into meaningful improvements in overall survival and disease-free survival. Neoadjuvant trials need fewer patients and are less expensive than adjuvant trial, and the endpoint of pCR is achieved in months, rather than years. For these reasons, the neoadjuvant setting is ideal for testing emerging targeted therapies in early breast cancer. Although pCR is an early clinical endpoint, its role as a surrogate for long-term outcomes is the key issue. New and better predictors of treatment efficacy are needed to improve treatment and outcomes. After PST, accurate management of post-treatment residual disease is mandatory. The surgery of the sentinel lymph-node could be an acceptable option to spare the axillary dissection in case of clinical negativity (N0) of the axilla at the diagnosis and/or after PST. No data exists yet to support the modulation of the extent of locoregional radiation therapy on the basis of the response attained after PST although trials are underway.

Purpose To assess the role of pathologic complete response (pCR) after neoadjuvant therapy as surrogate end point of disease-free survival (DFS) and overall survival (OS) in patients with breast cancer, we performed a trial-based meta-regression of randomized studies comparing different neoadjuvant systemic treatments. Methods The systematic literature search included electronic databases and proceedings of oncologic meetings. Endocrine therapy trials were excluded. Treatment effects on DFS and OS were expressed as hazard ratios (HRs), and treatment effects on pCR were expressed as odds ratios (ORs). A weighted regression analysis was performed on log-transformed treatment effect estimates to test the association between treatment effects on the surrogate outcome and treatment effects on the clinical outcome. Results Twenty-nine trials, 59 arms, and 30 comparisons, for a total of 14,641 patients, were included in the analysis. Using the complete set of data, the regression of either the log(HR) for DFS or the log(HR) for OS on the log(OR) for pCR demonstrated only weak associations (R2 = 0.08; 95% CI, 0 to 0.47; and R2 = 0.09; 95% CI, 0.01 to 0.41, respectively). Better associations were found in an exploratory analysis assessing a subset of trials comparing intensified/dose-dense chemotherapy versus standard-dose regimens (DFS: R2 = 0.79; 95% CI, 0.26 to 0.95; P = .003; and OS: R2 = 0.57; 95% CI, 0.19 to 0.93; P = .03). Conclusion This meta-regression analysis of 29 heterogeneous neoadjuvant trials does not support the use of pCR as a surrogate end point for DFS and OS in patients with breast cancer. However, pCR may potentially meet the criteria of surrogacy with specific systemic therapies.

Intravascular lymphomatosis (IVL) is a rare, malignant B- or T-cell lymphoma with remarkable affinity for the endothelial cells of small vessels, particularly within the skin and central nervous system. It is a disease that mimics several neurological disorders, particularly those of cerebrovascular ischemic origin. The prognosis is generally poor, with a rapidly fatal outcome. As a result the diagnosis is often made at post-mortem. We report a rare case of a 73-year-old patient with IVL complicated by intracerebral haemorrhage. In literature two cases of systemic IVL complicated by intracerebral haemorrhage have been reported, but they presented initially with a disseminated intravascular coagulation (DIC). This is the first case of brain IVL complicated by intracerebral haemorrhage not associated to DIC. Increasing awareness of this disease as a differential diagnosis to a common clinical presentation may lead to more opportunities to evaluate new diagnostic and treatment approaches.

Leptomeningeal dissemination of low-grade gliomas is an uncommon event. A 43-year old male presented with dizziness, gait ataxia, and diplopia. A nonenhancing lesion in the right cerebellar peduncle was identified, subtotally resected, and diagnosed as a grade II astrocytoma. After one year a nodular spread in the brain and leptomeninges was diagnosed, so the patient started chemotherapy with temozolomide and liposomal cytarabine. Complete remission was achieved after 12 months of treatment and the patient is still free from the disease after a follow-up of 24 months. We suggest that this combination may be a valuable treatment option.

We describe the case of a 39-year-old man with disseminated testicular seminoma that was refractory to salvage chemotherapy, and who had complete remission after imatinib administration. In September, 1999, the patient underwent a right orchifunicolectomy for a classical seminomatous tumour. A CT scan of the chest and abdomen showed retroperitoneal bulky disease (massive enlargement of right periaortic, paracaval, and interaortocaval lymph nodes of at least 4·3 cm in diameter). Baseline alpha-fetoprotein and human chorionic gonadotropin were within the normal ranges of 0·5–9·0 ng/ml and 0–2 mUI/ml, respectively, whereas lactate dehydrogenase concentration was increased at 722 UI/L (normal range 200–479 UI/L). The tumour was staged as pT1 N2. A classic chemotherapy regimen of cisplatin, etoposide, and bleomicin was given for three cycles, after which the patient’s concentrations of lactate de hydrogenase normalised and he had a complete response. The patient had standard follow-up according to the European Society for Medical Oncology recommendations. His fi rst relapse occurred in October, 2000, when retroperitoneal lymph-node involvement (right paracaval lymph nodes at least 5 cm in diameter that involved the right ureter and needed a pielostomy) and an increase in lactate dehydrogenase concentration to 1342 UI/L was noted. The patient underwent a classic second-line chemotherapy regimen with cisplatin, ifosfamide, and etoposide. A CT scan showed a reduction of the mean diameter of lymph nodes to 1 cm after two cycles, a complete response in all disease sites after four cycles, and normalisation of lactate de hydrogenase concentration to 293 UI/L after four cycles. At the end of chemotherapy, the patient received consolidation radiotherapy (2400 cGy in 12 fractions). A second relapse occurred 3 months later, with a CT scan showing lung metastases and supradiaphragmatic and infra diaphragmatic enlarged lymph-nodes. Tumour markers, including lactate dehydrogenase (326 UI/L), were normal. Between June, 2001, and November, 2001, after mobilisation and collection of peripheral-blood stem cells, the patient received two cycles of induction chemotherapy with gemcitabine and paclitaxel, followed by intensifi cation with high-dose chemotherapy (CARBOPEC—carboplatin, etoposide, and cyclophosphamide—with reinfusion of peripheral stem cells), and had a complete response in the thorax and a partial response in the abdomen with a residual mass of 1·5 cm disappearing 3 months later. In March, 2004, after 28 months of sustained complete remission, further restaging showed multiple bilateral metastases in the lung parenchyma (fi gures 1A and 1B). The CT scan did not show any infradiaphragmatic or supradiaphragmatic nodal metastases, unlike at the time of high-dose chemotherapy. Tumour markers were negative. A biopsy of the lung metastases was not done because CT images were indicative for secondary tumours. Because several investigators have reported KIT expression in a wide variety of human malignancies, and have shown that the kinase activity of KIT might be involved in the pathophysiology of some of these tumours—including germ-cell tumours and, more frequently, seminomas—we assessed KIT expression in the orchiectomy specimen by immunohistochemistry. Staining for KIT was strongly positive (fi gure 2). A standard avidin-biotin staining protocol was used with a polyclonal rabbit antibody for KIT (Dako A4502; Dako Corp, Carpinteria, CA, USA). The patient started receiving imatinib at the dose recommended for the treatment of gastrointestinal stromal tumours (400 mg/day). Treatment was well-tolerated, with Lancet Oncol 2007; 8: 1039–40

e12533 Background: Primary brainstem tumors (PBST) are the most common neoplasm of central nervous system (CNS) in children. In adults PBST is a rare disease, the incidence was reported to be 5% of...

e12537 Background: The prognosis of patients (pts) with recurrent HGG is poor with a median survival of 3 to 6 months. To date, no second line of treatment is recognized as standard. Enhanced angio...

Despite advances in surgical techniques, improvement in radiation treatments and chemotherapy, and the addition of new biological agents to the armamentarium, the median survival of patients with high-grade malignant glioma has changed little over recent decades. However, advances in the fundamental understanding of brain tumor biology suggest that targeting molecular pathways underlying carcinogenesis may provide alternative or additional approaches to glioma treatment. Viruses, particularly adenoviruses, have been critical in the application and development of these molecular approaches. Adenoviruses have been engineered to function as vectors for delivering therapeutic genes for gene therapy, and as direct cytotoxic agents for oncolytic viral therapy. The purpose of this review is to provide a prospective on the use of adenoviruses in high-grade malignant glioma therapy.

12534 Background: Temozolomide, a novel alkylating agent, has shown activity in the treatment of patients with high-grade gliomas. The current standard of care for newly diagnosed glioblastoma is surgical resection to the extent feasible, followed by adjuvant chemo- radiotherapy according to Stupp regimen. Methods: We reviewed our experience with a combination of radiotherapy (fractionated focal irradiation in daily fractions of 2 Gy given 5 days per week for 6 weeks, for a total of 60 Gy) plus continuous daily temozolomide (75 mg per square meter of body-surface area per day, 7 days per week from the first to the last day of radiotherapy), followed by six cycles of adjuvant temozolomide (150 to 200 mg per square meter for 5 days during each 28-day cycle). Results: 43 patients , median ECOG PS= 0, were treated with concomitant RT and Temozolomide at our institution since March 2004. Median age was 63 (range 33–73), with 62% over 60 years. All patients had histologically confirmed high grade gliomas: glioblastoma multiforme (32), grade III oligodendroglioma (3), grade III oligoastrocytoma (2), grade III astrocytoma (6). 2/43 patients underwent only a biopsy, the remaining underwent debulking surgery. At a median follow-up of 17 months, the median progression-free survival (PFS) was 6 mo and median overall survival (OS) was 12 mo. Median PFS and median OS were similar in elderly ( = 60 years). Treatment was well tolerated. Only one patient had grade IV haematological toxicity. One patient discontinued treatment due to hepatotoxicity. Conclusions: Our findings confirm the results of the EORTC trial(Stupp R et al., 2005) No significant financial relationships to disclose.

9575 Background: The use of adjuvant therapy should be based on appropriate prognostic factors. The aim of this study was to correlate the clinical, biological and pathological characteristics of women with breast cancer lesions of ≤1 cm. Methods: The 3033 patients with invasive operable breast cancer attending the Universitary and Civic Hospitals of Verona between January 1992 and June 2001 were divided into two groups: 664 women (21.9%) with lesions of ≤1cm (group A) and 2369 (78.1%) with lesions >1cm (group B). The patients with a diagnosis of ductal carcinoma in situ, lobular carcinoma in situ or breast sarcoma were excluded. The Chi-squared test and linear correlation were used to study the associations between lesion diameter and other variables. Results: Chi-squared test. Group A had fewer involved nodes (85.1% had no node involvement vs 55%, p