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.
Resources from the same session
5107 - Tolerability of PCV in Low Grade Glioma: a Real World Experience
Presenter: Razia Aslam
Session: Poster Display session 1
Resources:
Abstract
6171 - Molecular EGFR/PD-L1 profile of glioblastoma: Hints for therapeutic strategies
Presenter: Wojciech Szopa
Session: Poster Display session 1
Resources:
Abstract
4418 - Role of Intraoperative MRI (iMRI) in neurosurgery, potential imaging tool for maximizing gross total resection (GTR) rate of CNS tumours.
Presenter: Shweta Wadhwa
Session: Poster Display session 1
Resources:
Abstract
4791 - Tumor related impairments of neurocognitive functions in patients with brain metastases
Presenter: Lei Wen
Session: Poster Display session 1
Resources:
Abstract
5372 - Is radiation therapy influencing Alzheimer’s in Brain and Head and Neck Cancers?
Presenter: Anas Saad
Session: Poster Display session 1
Resources:
Abstract
2329 - Mature Treatment Results of 120 Cases of Acoustic Neuroma Treated with Cyberknife at a single institution.
Presenter: Shawn Malone
Session: Poster Display session 1
Resources:
Abstract
3207 - A phase II/III trial of high-dose, intermittent sunitinib in patients with recurrent glioblastoma: the STELLAR study
Presenter: Cyrillo Brahm
Session: Poster Display session 1
Resources:
Abstract
3589 - CNS penetration and Preliminary Efficacy of Sacutizumab Govitecan in Breast Brain Metastasis and Glioblastoma: A Surgical Study
Presenter: Andrew Brenner
Session: Poster Display session 1
Resources:
Abstract
1969 - Wedge resection with omission of lymph node dissection as an optional treatment strategy in octogenarians or older with early stage non-small cell lung cancers
Presenter: Takahiro Mimae
Session: Poster Display session 1
Resources:
Abstract
5116 - Characterization of lung tumorspheres reveals cancer stem-like cells potential targets and prognostic markers in non-small cell lung cancer
Presenter: Alejandro Herreros Pomares
Session: Poster Display session 1
Resources:
Abstract