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
4125 - DUBLIN-3, a Stage IIIb/IV NSCLC Phase (Ph)3 Trial Comparing the Plinabulin (P)/Docetaxel(D) Combination with D Alone
Presenter: Ramon Mohanlal
Session: Poster Display session 1
Resources:
Abstract
3345 - Escalation plans and DNACPR discussions in the unwell oncology patient
Presenter: Raghad Elghadi
Session: Poster Display session 1
Resources:
Abstract
4165 - The Relation between the Symptom Burden of Hospitalized Patients with Incurable Cancer and the Quality-of-Life of Their Family Caregivers
Presenter: Eman Tawfik
Session: Poster Display session 1
Resources:
Abstract
1784 - Clinical predictors for analgesic response to radiotherapy in patients with painful bone metastases
Presenter: Ragnhild Habberstad
Session: Poster Display session 1
Resources:
Abstract
5323 - 30-Day Mortality in Palliative Radiotherapy
Presenter: Shing Fung Lee
Session: Poster Display session 1
Resources:
Abstract
3942 - The relationship between Naldemedine administration and the maximum dose of oral opioids
Presenter: Shinya Kajiura
Session: Poster Display session 1
Resources:
Abstract
3698 - Exposure to low energy amplitude modulated radiofrequency electromagnetic fields (EMF) is associated with rapid improvement in quality of life (QoL) status in patients with advanced hepatocellular carcinoma (HCC), using various analyses of EORTC-C30.
Presenter: Elizabeth Santana
Session: Poster Display session 1
Resources:
Abstract
3885 - Olanzapine Combined with 5-HT3 RA Plus Dexamethasone for Prevention and Treatment of Chemotherapy-Induced Nausea and Vomiting in High and Moderate Emetogenic Chemotherapy: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Presenter: Jian-Guo Zhou
Session: Poster Display session 1
Resources:
Abstract
5700 - Early Palliative care in advanced cancer, is it really effective?
Presenter: Raquel Gómez Bravo
Session: Poster Display session 1
Resources:
Abstract
5924 - Deprescribing Potentially Inappropriate Medication in Cancer Patients
Presenter: Simon Reuter
Session: Poster Display session 1
Resources:
Abstract