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8536 Background: t-AML is a syndrome occurring after exposure to chemo or radiotherapy. Since for similar treatments only some patients ends developing a secondary leukemia, it has been proposed a genetic predisposition associated to this syndrome. Methods: To analyse single nucleotide polymorphisms (SNPs) on genes that could be involved on risk of developing t-AML by means of RFLP and SNP genome screening using high density microarrays .Two groups of individuals were genotyped: Group A, composed by patients that develop t-AML after chemotherapy for breast cancer (BC) and Group B (control), formed by chemotherapy treated BC patients that after a period of more than 10 years have not developed t-AML. We have studied 12 polymorphisms on genes from drug detoxification pathways (NOQ1, GSTP1), DNA repair (XPC[3 ], XRCC1[2 ], NBS1, ERCC5 and XRCC3) and DNA synthesis (MTHFR[2 ]), in which the nucleotide change implies a change in the protein sequence (nA=16, nB=18) . Alternatively, for each patient, more than 10.000 SNPs were genotyped by means of of high density microarrays (Affymetrix) (nA=12, nB=18). The alele frequencies for each SNP between two groups were compared. Results: In RFLP study, we observe two SNPs on MTHFR gene displaying remarkably different allele frequencies between BC patients (Table). In microarray study, we found 12 SNPs with differences of allele frequency higher that 45% between A and B groups, located 6 on chromosome 8. Conclusions: The results suggest that the MHFTR gene is a candidate for being studied by its possible relation with the genetic predisposition to develop t-AML after BC treatment although its functional implication with the disease must still be elucidated. Moreover, data from SNP arrays suggest that the genome regions marked by those 12 SNPs, specially those on chromosome 8, are candidate for being studied by its possible relation with the genetic predisposition to develop t-AML after BC treatment. Financed by FIS G03/008. [Table: see text] No significant financial relationships to disclose.

TPS4155 Background: GC represents a worldwide problem; radical surgery remaining the gold standard of curative treatment. In the West, even with peri-operative chemotherapy, 5-year survival rate is approximately 40%. GC is a heterogeneous disease, well characterized by different molecular classifications, all having in common the role of the immune system and a T-cell inflamed phenotype across all subtypes. The anti-PD-L1 Av antibody has demonstrated efficacy in GC with response rates of around 10% in the refractory setting. The addition of other immune checkpoint inhibitors to chemotherapy have demonstrated efficacy in the metastatic setting. The combination of Av to perioperative chemotherapy may increase pathological responses by a synergistic effect, and then improving the survival (OS). Methods: The MONEO is an open-label, non-randomized, multicentric, phase II study that explores the combination of Av plus peri-operative FLOT (docetaxel, oxaliplatin, fluorouracil/leucovorin) in resectable GC pts. EudraCT 2019-000782-21; ClinicalTrials NCT03979131. Main inclusion criteria require pts with histologically proven GC, stage Ib (T1N1 only) - IIIC (7th AJCC Ed), available paraffin block from diagnosis and surgery, evaluable disease (RECIST 1.1) amenable to radical surgery. Significant comorbidities and active autoimmune diseases are excluded. Treatment consists of surgery with 4 peri-operatory cycles of FLOT + Av, followed by Av up to one year. The primary objective is the pathological complete response (pCR) rate, compared to historical data. Secondary objectives include OS, disease-free survival, R0 resection rate, tolerability and biomarker analysis. Key point is the comprehensive biomarker analysis from tissue and blood samples (pathological immune response, TCR clonality, immune contexture characterization, immunodynamic monitoring). Statistics for an estimated 33% pCR (historical 16%), 82% power, 0.1 one-side type I error. 37 pts will be recruited from 10 Spanish centers. The sponsor is Vall d'Hebron Institute of Oncology (VHIO), principal investigators Dr. Melero and Dr. Alsina. In compliance with the Helsinki Declaration. At a data cut-off day of 5th of February 2021, 38 patients have been enrolled, 27 of them have had the surgery. Although the difficulties during the COVID19 pandemia, only two patients had been withdrawn from the study. Clinical trial information: NCT03979131.

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