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Background: Platinum-based doublets are the standard chemotherapy for lung cancer. The identification of markers associated with drug-toxicity may improve the success of the treatment. Single nucleotide polymorphisms (SNPs) mapping into the genes involved in platinum transport or detoxification may explain occurrence of toxicities. In this study, we evaluated the role of 3 SNPs in predicting the onset of adverse events for lung cancer patients receiving cisplatin or carboplatin in adjuvant, neo-adjuvant and metastatic settings. Methods: Eighty-two patients affected by non-small-cell and small-cell lung cancer treated with cisplatin-or carboplatin-based chemotherapy (stage II-IV) were enrolled. Before genetic analysis, patients signed a written informed consent. DNA was extracted from peripheral blood samples and genotypes were determined by Real-Time PCR. We selected and analyzed 3 SNPs: ABCB1 c.3435C>T/rs1045642, ABCC2 -24C>T/rs717620 and GSTP1 c.313A>G/rs1695. Patient characteristics and genotypes were correlated with haematological, gastrointestinal and renal toxicity as recorded by Common Terminology Criteria for Adverse Event (CTCAE) v4.03. No neurological toxicity was observed in our patients. Results: Variant alleles were present in 53% of patients for ABCB1 c.3435C>T, 18.3% for ABCC2 -24C>T, and 34.8% for GSTP1 c.313A>G. Heterozygous CT at ABCB1 c.3435 were associated to a lower risk of haematological toxicity compared to homozygous CC (OR=0.20; 95% CI 0.05, 0.69; p=0.01). Similar results were observed by genetic dominant model (CT+TT vs CC) and haematological toxicity (OR=0.26; 95% CI 0.09, 0.79; p=0.02).No other significant associations were found between toxicity and SNPs. Multivariate analysis confirmed an independent value for the ABCB1 c.3435 C>T polymorphism. Conclusions:The present study reveals that ABCB1 c.3435C> T polymorphism influences platinum toxicity. The T allele seems to exert a protective effect on the development of toxicities. Further studies, such as epigenetic regulation ones, are needed to validate and shed more light on this association.

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10053 Background: Rare cancers (RC) are a challenge in terms of quality of care, access to health resources and clinical research. The Italian Rare Cancer Network (RTR: “Rete Tumori Rari”) is a clinical collaborative effort to improve quality of care in adult rare solid cancers in Italy. RTR enables institutions to share clinical cases and to rationalize access to distant reference centers minimizing patient migration. It indirectly promotes collaborative clinical research by encouraging accrual into clinical trials and supporting observational studies. Methods: RTR includes 150 oncology institutions across Italy. Clinical cases are shared asynchronously over a secure Web resource. Data, images and transactions are stored in an online clinical record. Patients are shared: 1. "logically”, when they are dealt with following common clinical practice guidelines; 2. "virtually”, when they are discussed over the network between two or more centers; 3: "physically", when they are referred to an excellence center for a specific treatment modality. Pathology review is arranged through transferal of paraffin-embedded specimens and upload of consultations. While it was chosen not to implement telepathology facilities, a teleradiology resource is now available. Results: From 2003 to 2011, more than 5,000 rare cancers cases (mostly sarcomas) have been uploaded. More than 1,300 teleconsultations have been delivered, while more than 1,000 patients moved across the network during their experience of disease. 700 cases were reviewed pathologically: amongst 365 cases originally diagnosed as soft tissues sarcomas up to 2010, treatment-relevant discordances were recorded in more than one third. An observational prospective study on gastrointestinal stromal tumors was done, enrolling 800 patients. An original paper documenting the activity of a drug in a highly specific sarcoma subgroup was published. Conclusions: Clinical asynchronous online collaboration on RC is feasible through a Web-based secure environment and proved the most practical way of clinical distant sharing. Pathologic review was a crucial network service, with a special added value in RC. Retrospective and prospective observational studies, and unplanned observations in very rare cases, were an interesting by-product.

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