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ABSTRACT Gastrointestinal stromal tumors are rare malignancies characterized by c-kit and PDGFR-α mutations targeted by imatinib. Pleural effusion is a very rare side effect of imatinib treatment. A 65-year-old female with metastatic gastrointestinal stromal tumor developed electrolyte imbalance, severe peripheral edema and progressively worsening dyspnea 2 months after starting imatinib. Having excluded cardiovascular and pulmonary disorders, imatinib was discontinued and prednisone 25 mg orally daily was begun. The patient's condition improved substantially over the next 48 h with a progressive decrease in dyspnea and a reduction in pleural effusion and peripheral edema. All side effects had resolved within 1 month. In view of the partial response obtained, the patient re-started imatinib after a 1-week interruption. Prednisone was maintained and there was no further toxicity.

Alberto Bongiovanni,1 Nada Riva,1 Sebastiano Calpona,1 Marianna Ricci,1 Erica Gunelli,1 Chiara Liverani,1 Federico La Manna,1 Alessandro De Vita,1 Manuela Monti,1 Stefano Severi,2 Federica Pieri,3 Elena Amadori,1 Riccardo Galassi,1 Davide Cavaliere,4 Alberto Zaccaroni,5 Andreas Tartaglia,6 Veronica Lunedei,7 Andrea Gardini,8 Laura Mercatali,1 Dino Amadori,1 Toni Ibrahim11Osteoncology and Rare Tumors Center, 2Nuclear Medicine Unit, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, 3Pathology Unit, 4Unit of Oncological Surgery and Advanced Therapies, 5Endocrine Surgery Unit, 6Endocrinology Unit, 7Gastroenterology and Digestive Endoscopy Unit, 8Department of General Surgery, Morgagni-Pierantoni Hospital, Forlì, ItalyBackground: We present a retrospective analysis of metronomic capecitabine in metastatic gastroenteropancreatic neuroendrocrine tumors (GEP-NETs). A review of the literature is also presented.Methods: From January 2007 to December 2013, ten patients with metastatic GEP-NETs (four pancreatic and six ileal) who progressed after treatment with somatostatin analogs and other cytotoxic agents received oral capecitabine 1,500 mg/day continuously. The median patient age was 68 (range 29–82) years. The median treatment duration was 8 months.Results: Five (50%) patients achieved a partial radiographic response, four (40%) showed stable disease, and one (10%) progressed. Median overall survival was 56 months. Three of the four pancreatic patients achieved a partial radiographic response that lasted for a median of 15.5 months; overall survival and progression-free survival in this subgroup was 58 and 6 months, respectively.Conclusion: Data in the literature show that capecitabine has only occasionally been used as a single agent, with increased toxicity. Only one study using single-agent capecitabine reported a progression-free survival of 9.9 months and overall survival of 36.5 months, without an objective response or major toxicity. In our experience, metronomic capecitabine was well tolerated, although minor side effects may have been underestimated due to the retrospective nature of our study. This regimen also seems to be feasible in elderly people. Although high response rates and prolonged response duration indicate the potential efficacy of this treatment, our results should be interpreted cautiously because of the small number of patients involved. Capecitabine was most effective in the pancreatic subgroup, which would seem to be more sensitive to chemotherapy.Keywords: capecitabine, gastroenteropancreatic neuroendocrine tumors, metronomic chemotherapy

Alberto Bongiovanni,1 Nada Riva,1 Marianna Ricci,1 Chiara Liverani,1 Federico La Manna,1 Alessandro De Vita,1 Flavia Foca,2 Laura Mercatali,1 Stefano Severi,3 Dino Amadori,4 Toni Ibrahim1 1Osteoncology and Rare Tumors Center, 2Unit of Biostatistics and Clinical Trials, 3Nuclear Medicine Unit, 4Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, FC, Italy Background and aim: To investigate the efficacy of platinum-based chemotherapy in patients with metastatic gastroenteropancreatic neuroendocrine carcinoma (mGEP-NEC) and define predictive and prognostic factors. Methods: Twenty mGEP-NEC patients were treated with cisplatin or carboplatin/etoposide between April 2010 and October 2014. Both large-cell and small-cell histologies were included. Cisplatin 25 mg/m2 was administered on days 1–3 followed by etoposide 100 mg/m2 on days 1–3 every 21 days. Carboplatin 300 mg/m2 was administered on day 1 followed by etoposide 100 mg/m2 on days 1–3. Results: Of the 19 evaluable patients, 13 obtained a partial response, four showed stable disease, and two progressed. Median overall survival (mOS) was 13.5 months and median progression-free survival (mPFS) was 10.9 months. Gallium-68 positron emission tomography/computerizsed tomography-positive patients had a higher, albeit not significantly, OS than those with negative results (75% vs 34.3% at 18 months; P=0.06). mPFS was 19.3 and 6.3 months (P55%, respectively. mOS was 8.1 months in the latter group but was not reached in the Ki67 ≤55% group (P-value =0.039). Patients with a lower body mass index (BMI) had a better prognosis in terms of both OS and PFS. Patients with BMI≥25 had a mOS of 11.7 months (P=0.0293) and a mPFS of 6.2 months (P=0.0057). Conclusion: Platinum-based chemotherapy showed good efficacy in mGEP-NEC patients. Those with Ki67 ≤55%, positive Gallium-68 positron emission tomography/computerized tomography and BMI

Introduction & objectives: Prostate cancer (PCa)-associated mortality results from metastasis to bone and resistance to androgen deprivation or cytotoxic therapy. Despite early detection of primary PCa, advanced castration resistant prostate cancer (CRPC) and bone metastases (BM) are detected in 10% of patients already at the time of initial diagnosis. The majority of recurrences might be due to cancer cells with stem cell-like properties (cancer stem cell-like, CSC-like). These could be therapy-resistant in a dormant state at the primary site or have metastasize prior to diagnosis of the primary tumor. CSC-like cells are the most tumorigenic and metastatic, however, current treatments target the differentiated tumor bulk cells. Understanding the mechanisms of PCa tumor initiation and metastasis by CSC-like cells is crucial for proper prognosis of high risk patient groups. Materials & methods: To model CSC-like cells we generated organoids from patient-derived tissues (here termed as “canceroids”) and established patient-derived xenografts (PDXs). Canceroids were derived from bulk tumor tissues; primary PCa, bone metastasis from PCa tissue (BM-PCa), established PDX models LAPC9 and BM18 and lymph node (LN) metastasis from PCa (LAPC4) PDX models. Cytotoxic compounds and androgen inhibitors are tested on the canceroids from different BM or LN tissues using viability assays (CellTiter Glo assay) and 3D imaging by confocal and light sheet microscopy. Results: We have generated several canceroid lines from human primary PCa and from established PDX models that maintain key features of the CSC-like cells, previously characterized on the tumor itself (AR, PSA, Cytokeratins). The luminal phenotype of BM18 is evidently maintained in the BM18 canceroids, based on positive cytokeratin (CK)18 and absent CK5 expression. LAPC4 organoids contain CK5 and CK18 cells, in line with the mixed basal and luminal phenotype. Imaging of PSA and cytokeratin distribution confirms the luminal phenotype of the canceroids. BM18 and LAPC9 canceroids are maintained both in presence and absence of dihydrotestosterone indicating that androgen independent growth properties of the tumor are conserved in the canceroids. Viability assays indicate that canceroids respond to chemotherapeutics (cabacitaxel, docetaxel) and partially to hormone inhibitors (abiraterone, enzalutamide). Conclusions: Identification of the oncogenic properties of metastatic CSC-like (sub)populations has both prognostic and therapeutic applications. Establishment of CSC-derived organoids is the first step towards routine derivation from metastasis or primary PCa tissues as a potential platform for personalized drug compound evaluation. Citation Format: Sofia Karkampouna, Federico la Manna, Eugenio Zoni, Lijkele Beimers, Peter Kloen, Antoinette Wetterwald, Joël Grosjean, Irena Klima, Marco Giovanni Cecchini, Martin Spahn, George Niklaus Thalmann, Marianna Kruithof- de Julio. Establishment, characterization and drug response of primary and metastatic prostate organoids [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3885. doi:10.1158/1538-7445.AM2017-3885

11128 Background: Bone Metastases (BM) are responsible of the high morbidity, low quality of life and poor prognosis of patients with BC. The evaluation of bone response to treatment is still contr...

e22248 Background: The debate on the association between Vit D deficiency and breast cancer risk is still open. Some studies indicate that ethnic differences play a role in the circulating levels of serum Vit D. Moreover, single nucleotide polymorphisms (SNPs) in the Vit D receptor (VDR) have been associated with various types of cancer.The study evaluates Vit D and Binding Protein (DBP) levels, VDR and DBP polymorphisms in Tanzanian and Italian healthy donors (HD) and breast cancer patients (BCP). Methods: The study provides 200 adult women: 100 Tanzanian and 100 Italians (for each population: 50 donors, 25 primary and 25 advanced breast cancer patients). At first, analysis on serum Vit D concentrations has been performed until now on 25 HD and 25 BCP from Italy. The analysis on the overall population is ongoing. All bio-molecular characterization are performed at IRST IRCCS in Italy. The association between Vit D serum concentration and osteoporosis risk factors was evaluated. Results: From Sept to Dec ...

Background Leiomyosarcoma (LMS) is an aggressive soft tissue sarcoma derived from smooth muscle cells typically of uterine, gastrointestinal or soft tissue origin. The prognosis for this tumor is poor, with survival rates among the lowest of all soft tissue sarcomas. Surgery is the best approach for localized disease. The principal role of chemotherapy is prevalently in the treatment of metastatic disease. Trabectedin, a promising new DNA-damaging agent with a mechanism of action that differs from that of traditional alkylating agents, has been approved in Europe for the treatment of patients with advanced soft tissue sarcoma after failure of anthracyclines and ifosfamide, Case presentation We report the case of a 53-year-old woman with metastatic well differentiated uterine leiomyosarcoma refractory to multiple treatments who underwent 22 cycles of trabectedin over 30 months, obtaining a partial response according to RECIST (Response Evaluation Criteria in Solid Tumors) criteria, with good tolerability, and maintaining the response for 10 months after trebectedin withdrawal. Conclusion This very prolonged response, which persisted after drug discontinuation, suggests that trabectedin exerts an oncostatic effect rather than the cytotoxic one produced by other chemotherapeutic agents. Our experience also raises the question of the best way to evaluate trabectedin efficacy.