1413P - ATRX-associated alternative lengthening of telomere (ALT) may be correlated with chemotherapy response in leiomyosarcoma (LMS)

Date 10 October 2016
Event ESMO 2016 Congress
Session Poster display
Topics Soft Tissue Sarcomas
Presenter Po-Hsiang Huang
Citation Annals of Oncology (2016) 27 (6): 483-492. 10.1093/annonc/mdw388
Authors P. Huang1, R. Hong1, Y. Jeng2, J. Liau2, W.T. Chen3
  • 1Department Of Oncology, National Taiwan University Hospital, 100 - Taipei/TW
  • 2Department Of Pathology, National Taiwan University Hospital, Taipei/TW
  • 3Department Of Oncology, National Taiwan University Hospital, Taipei/TW

Abstract

Background

Response to systemic chemotherapy in LMS varies and no predictive biomarker exists. ALT, a common mechanism to maintain telomere in sarcoma, is associated with altered DNA repair mechanism. Loss of a chromatin modifier α-thalassemia/mental retardation syndrome X-linked (ATRX) has been implicated as one of the factors leading to ALT. We aimed to determine the relationship between ALT, ATRX and chemotherapy response in patients with advanced LMS.

Methods

Histology-proven advanced LMS patients (pts) treated with systemic chemotherapy in National Taiwan University Hospital from January 1995 to December 2014 were selected. Patient demographic data and clinical outcomes including tumor response, progression-free survival and overall survival were recorded. We used formalin-fixed paraffin-embed tumor samples for ALT and ATRX status assessment by telomere-specific fluorescence in situ hybridization and immunohistochemistry, respectively.

Results

30 pts with advanced LMS treated with systemic chemotherapy were identified. Table 1 summarizes the clinicopathological information. 21 pts received anthracycline-based first line chemotherapy. 20 pts (67%) were ALT-positive (ALT+). 10 pts (33%) were ATRX-negative (ATRX-), among which all but 1 were also ALT+. ALT positivity was not correlated with chemotherapy response (odds ratio = 1.25, p = 0.7844). In the 9 ALT + /ATRX- patients, a lower odds, albeit non-significant, of response to chemotherapy was noted compared to non ALT + /ATRX- patients (11.3% vs 42.9%, odds ratio = 0.17, 95% CI = 0.01-1.58, p = 0.11). PFS was significantly shorter in ALT + / ATRX- patients (median 2.0 mos vs 7.7 mos, p 

Conclusions

ALT+ with ATRX- may predict poorer response to chemotherapy in advanced LMS.

Clinical trial identification

Legal entity responsible for the study

Po-Hsiang Huang

Funding

Department of Oncology, National Taiwan University Hospital

Disclosure

All authors have declared no conflicts of interest.