ESTRO 2021 Abstract Book

S299

ESTRO 2021

TRG 1-2 was obtained in twenty-seven patients (67.5%) and they were considered responder patients (RP) whereas the remaining 13 (32.5%) were no-responder (NRP), reporting a TRG of 3 to 5. The LC-MS/MS lipid profiling showed that among the analytes, lysophosphatidylcholines (LPC) were identified as variable important for the projection (VIP > 1) and significantly different expressed between NRPs and RPs at T0 (p value < 0.05). Some aminoacids (citrulline, alanine and ornithine) and acyl-carnitines (C18:2OH and C26) also resulted as major discriminant variables. Focusing the attention to 3 out of 4 lysophosphatidylcholines (C20:0- LPC, C22:0-LPC, C24:0-LPC), altered in our analysis, they reported a good sensitivity and specificity in discriminating from RP group with lower serum levels before CRT in NRP. Furthermore, the same lipidomic study revealed that, interestingly, C22- and C24-ceramides followed their respective LPC trend, due to lower expression before CRT in NRP. Finally, we analysed different ceramides at T14, T25 and T45: only in RP sphinganine-1-phosphate and sphingosine-1-phosphate increased during treatment (Table 1). These metabolites are described as important in cell migration, survival and differentiation.

Conclusion The analysed aminoacids, acyl-carnitines and ceramides resulted able to predict tumor response with lower levels in NRP before starting CRT (T0). In addition, ceramides levels were increased during CRT (T14) in RP. The potential role of these analytes could permit a treatment personalization in LARC patients. The study is still ongoing in order to validate a larger number of analytes in a larger population. OC-0403 MiR-200 family members as predictive biomarkers for radioresistance in cervical cancer A. Nilsen 1 , T. Hillestad 2 , V. Eide Skingen 3 , E. Aarnes 3 , C. Sæten Fjeldbo 1 , T. Hompland 3 , T. Sandø Evensen 2 , G. Balle Kristensen 4 , B. Grallert 3 , H. Lyng 3 1 Oslo University Hospital, Institute for cancer research, Radiation biology, OSLO, Norway; 2 Oslo University Hospital, Institute for cancer research, Core facilities, Oslo, Norway; 3 Oslo University Hospital, Institute for cancer research, Radiation biology, Oslo, Norway; 4 Oslo University Hospital, Institute for cancer research, Gynecologic oncology, Oslo, Norway Purpose or Objective Chemoradiotherapy is the standard treatment for locally advanced cervical cancer . Cancer recurrence in the central pelvic occurs in about one-fourth of relapsed patients, suggesting that the tumors are highly radioresistant. Predictive biomarkers of central recurrence are needed to select patients to trials evaluating radiosensitizing drugs . MicroRNAs (miRNAs) play major roles in gene regulation by post-transcriptional silencing of target genes, and have large potential as biomarkers due to high stability in tissues and biofluids. In the present work, we aimed to investigate whether altered expression of miRNAs may serve as biomarkers of chemoradiotherapy resistance in cervical cancer Materials and Methods The miRNA transcriptome was measured in tumor biopsies from patients with locally advanced cervical cancer by small RNA sequencing. MiRNAs with prognostic impact were identified by survival analysis in an explorative cohort of 90 patients, using two independent cohorts (n=110, n=79) for validation. Site-specific recurrence data of the explorative cohort and validation cohort 1 (n=200) were used to investigate associations between miRNA expression and central recurrence. Gene expression profiles of the 200 patients were determined by Illumina bead arrays. For selected miRNAs, potential target genes were collected from the miRGate database. The target genes that showed an inverse correlation with miRNA expression were further subjected to gene enrichment analysis. The radiation response was assessed by in vitro clonogenicity and by xenograft tumor growth delay in an established cervical cancer model overexpressing miR-200a, miR-200b and miR-429. Results Low expression of the miR-200 family members miR200a, miR-200b and miR-429 on chromosome 1q was associated with higher risk of cancer recurrence in the explorative cohort, using progression free survival as endpoint. This finding was validated in both independent cohorts, based on a miR-200 score generated from the expression level of these miRNAs. In the combined cohort of 200 patients, the miR-200 score was significantly correlated with central recurrence, but not with distant or lateral pelvic recurrence, suggesting radioresistance in tumors with low expression of the miR-200 family members. The score also appeared as a significant factor in multivariate analysis with clinical variables. More than two hundred miR-200 target genes