Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster Display session 1

6117 - VEGFR2 and ITGA polymorphisms as novel pan-sarcoma biomarkers for sensitivity prediction as well as toxicity prevention anti-angiogenesis therapy in pediatric and young adult

Date

28 Sep 2019

Session

Poster Display session 1

Presenters

Qiyuan Bao

Citation

Annals of Oncology (2019) 30 (suppl_5): v683-v709. 10.1093/annonc/mdz283

Authors

Q. Bao, Y. shen, W. zhang

Author affiliations

  • Orthopaedic Oncology, Ruijin Hospital, 200032 - shanghai/CN
More

Resources

Abstract 6117

Background

The impact of germline mutations of the angiogenesis pathways on the therapeutic response has been extensively studied for the carcinoma population. However, such information is almost unknown for pediatric and young adult sarcoma, for which the field has seen the rapid growth the use of the anti-angiogenic therapy.

Methods

In this study, we retrospectively analyzed 79 tissue sarcoma patients less than 45 yrs old receiving anti-angiogenic therapy (apatinib). In 67 (84%) of these patients, twenty previously reported single nuclear polymorphism (SNPs) in the angiogenesis pathway were genotyped to screen for potential toxicity and predictive biomarkers.

Results

The mean 6 mo PFS rate was 64%, with the duration of response varying from no response to more than 26 months. Multivariate analysis indicated that hand-foot reactions, hair depigmentation and spontaneously pneumothorax (SP) remain independent toxicity biomarkers for greater PFS. Interestingly, we observed a strong correlation of ITGA2 rs1126643 polymorphism vs surgical wound complications (C/C 4% vs C/T 24% vs T/T 33% , p = 0.008) as well as SP (C/C 13.8% vs C/T 36.4% vs T/T 66%), suggesting that integrin mechanisms might underle both toxicities. Moreover, VEGFR2 rs2071559 polymorphism remains the only sensitivity biomarker for mPFS (mutation vs WT, 12 mo vs 5 mo), regardless of the sarcoma subtypes. Suprisingly, such mutations were associated with the incidence of hair depigmentation (R = 0.398, p = 0.026), further supporting that hair discoloration is a mechanism-based toxicity biomarker. Moreover, significantly higher frequencies such mutations (0.53 for ITGA polymorphism, 0.59 for VEGFR2 polymorphism) were seen in our cohort than the general Han Chinese (1000G project database) suggesting a theoretical impact on the sarcomagenesis.

Conclusions

Our study is the first one examining the angiogenesis germline polymorphism for the younger population in bone and soft tissue cancer. VEGFR2 (rs2071559) as well as ITGA (rs1126643) might serve as pan-sarcoma biomarkers for VEGFR2-targeted therapy and warrant further validation for its biological and clinical implications.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Ruijin Hospital, Orthopaedic Oncology Group.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.