241PImpact of genomic alterations and HPV genotypes on clinical outcomes of Japanese patients with locally advanced cervical cancer. (24th November 2019)

• Record Type: Journal Article
• Authors: Kuno, I; Takayanagi, D; Yoshida, H; Hirose, S; Murakami, N; Uno, M; Ishikawa, M; Matsuda, M; Asami, Y; Shimada, Y; Okuma, K; Kohno, T; Itami, J; Shiraishi, K; Kato, T
• Is Part Of: Annals of oncology. Volume 30(2019)Supplement 9
• Publication Date: 2019-11-24
• Subjects: Oncology -- Periodicals; 616.992
• DOI: 10.1093/annonc/mdz426.017
• Languages: English
• ISSNs: 0923-7534

Abstract

Abstract: Background: The aims of this study were to investigate the genetic alternations of locally advanced cervical cancer and to elucidate the associations among clinico-pathological factors, genomic alterations and clinical outcomes of the patients receiving concurrent chemo-radiotherapy (CCRT). We performed the targeted sequencing for somatic mutations across the hotspot regions of 50 cancer-related genes using biopsy specimens. Methods: Seventy-six patients diagnosed as FIGO Stage III to IVA cervical cancer underwent radiation therapy or CCRT at National Cancer Center Hospital between January 2008 and December 2017. All the patients received external beam radiation therapy and brachytherapy. The most of chemotherapy regimen was cisplatin. Genomic DNAs extracted from formalin-fixed and paraffin-embedded tumor tissues were subjected to the analysis using an Ion AmpliSeq TM Cancer Hotspot Panel v2. Six patients were disqualified from this study because of low quality DNA. Oncogenic or pathogenic variants registered in the OncoKB and the ClinVar databases were defined as mutations. In the present study, gene aberrations with evidence levels 1A-3A were judged as actionable mutation for molecular targeted drugs. HPV infection was detected by in-situ hybridization and genotypes were determined by Sanger sequencing. Results: Seventy patients were enrolled in this study. Sixty-five patients (93%) had squamous cell carcinoma. Pathogenic mutations were detected in 47 cases (67%); frequencies of gene alterations in PIK3CA (51%), FBXW7 (10%), PTEN (7.1%) and TP53 (5.7%). The clinical factor associated with poor survival was the tumor diameter. Cox regression analysis showed the tumor diameter larger than 70mm were associated with shorter progression-free survival (PFS) (Hazard ratio = 2.96, P = 0.0048) in multivariate analysis. Patients infected without HPV16/18 had poor PFS than those with HPV 16/18 (Log-rank P = 0.025). TP53 mutants were correlated with poor PFS (Log-rank P = 0.044). Thirty-seven patients (53%) have actionable genomic alternations. Conclusions: Larger tumor diameter, non HPV16/18 and TP53 mutants correlated with worse outcomes to CCRT in the Japanese patients with locally advanced cervical cancer. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.