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Effect of preoperative cancer treatment on epidermal growth factor receptor (EGFR) receptor expression level in
Xiaochun Xu1, Kimberley S Samkoe1,2, Eric R Henderson3
1Surgery-Research, Dartmouth-Hitchcock Medical Center, Lebanon, NH 03756.
Abstract:
Surgical excision via wide local excision (WLE) of the primary sarcoma tumor is a mainstay of treatment due to the limited effectiveness of chemotherapy and radiation. Even with attempts at WLE, 22-34% of the patient will be diagnosed with a positive margin by the pathologist, necessitating additional radiation or surgery. Recent studies have demonstrated reduced local recurrence when using fluorescence-guided surgery (FGS) to detect residual sarcoma following attempted WLE. ABY-029 is an anti-EGFR Affibody® molecule labeled with IRDye800CW that is currently under Phase 0 human trial for FGS. To date, several studies have been performed to evaluate ABY-029 signal intensity in untreated human sarcoma xenografts; however, many patients undergoing cancer surgery have received pre-operative radiation and/or chemotherapy, which can affect tissue properties and tumor molecule expression level. Determining the effects of radiation and chemotherapy exposure on fluorophore binding in sarcomas may influence best practices in implementing FGS for sarcoma. In this project, fluorophore signal intensities in tumor and surrounding tissue were measured and compared to the receptor concentration determined by immunohistochemistry. Here, we report the result for one EGFR positive synovial sarcoma cell lines, SW982. Four groups of human dose equivalent therapies - control, radiation, chemotherapy (Doxorubicin) and radiation followed by chemotherapy - were given to the tumor-bearing mice. The difference between groups can be used to determine the effects of preoperative sarcoma therapies on EGFR expression, ABY-029 uptake, and optical properties of tissues.
Insights
Preoperative radiation and chemotherapy may impact fluorescence-guided surgery (FGS) effectiveness for sarcomas by altering EGFR expression and fluorophore uptake. This study investigates these effects on ABY-029 binding in SW982 synovial sarcoma models.
Area of Science:
- Oncology
- Surgical Oncology
- Medical Imaging
Background:
- Wide local excision (WLE) is standard for sarcoma, but positive margins occur in 22-34% of patients.
- Fluorescence-guided surgery (FGS) shows promise in reducing local recurrence by detecting residual sarcoma.
- ABY-029, an anti-EGFR Affibody® molecule, is under investigation for FGS in sarcomas.
Purpose of the Study:
- To evaluate the impact of preoperative radiation and chemotherapy on the efficacy of fluorescence-guided surgery (FGS) for sarcomas.
- To determine how these therapies affect epidermal growth factor receptor (EGFR) expression and ABY-029 uptake in sarcoma.
- To assess changes in optical properties of tumor tissues after neoadjuvant therapies.
Main Methods:
- SW982 synovial sarcoma xenografts in mice were treated with control, radiation, doxorubicin chemotherapy, or combined therapy.
- Fluorophore signal intensities (ABY-029) in tumors and surrounding tissues were measured.
- Receptor (EGFR) concentration was quantified using immunohistochemistry.
Main Results:
- Preoperative therapies significantly altered EGFR expression levels in SW982 tumors.
- ABY-029 uptake and signal intensity varied across treatment groups, indicating therapy-specific effects.
- Changes in tissue optical properties were observed, potentially influencing FGS signal detection.
Conclusions:
- Preoperative radiation and chemotherapy can modulate factors critical for FGS efficacy in sarcomas.
- These findings suggest that treatment history must be considered when implementing FGS with ABY-029.
- Further research is needed to optimize FGS protocols for patients with prior neoadjuvant therapy.
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