Microfluidic Techniques to Assess Radiosensitivity of HNSCC

Abstract

Objective: The ability to predict tumor radioresistance would avoid unnecessary treatment with associated side effects and negate salvage surgery. Microfluidic techniques can be exploited to replicate the in vivo tumor microenvironment.This study demonstrates how such technology can determine the response of HNSCC to radiotherapy in an individualistic manner. Method: Technique optimized using rat liver maintained in microfluidic devices, perfused with media for <17 days. Radiotherapy treatment (10-20Gy): single and fractionated doses. Effluent analyzed for urea, albumin, and lactate dehydrogenase (LDH, cell death indicator) to assess response. Nine HNSCC biopsies (T1-T3) were analyzed for LDH release following radiotherapy (2-30Gy). Results: Initial cell death decreased reproducibly to minimal levels in all tissues between 12-24 hours. Tissue remained viable for up to 17 days. Rat liver: 0-2 hours after 20Gy radiotherapy (single dose), an LDH surge with concomitant decrease in urea and albumin was observed. The tissue partly disintegrated. 2 × 10Gy fractionated doses resulted in effects after the second fraction. The tissue remained intact. HNSCC biopsies: Tongue base (n = 3), larynx (n = 3), lymph node metastases (n = 2) 30Gy: Larynx responded. Tongue base (postradiotherapy recurrence) did not. 10Gy: Tongue base responded, not larynx or lymph nodes. No response in any tissues with <10Gy. Conclusion: A model to assess tissue response to radiotherapy was successfully established using rat liver. Preliminary results with HNSCC samples have shown that a response to radiotherapy can be elicited at different doses using this technique. Correlation with histology and clinical response will further validate this technique as a predictive tool.