Monitoring neoadjuvant therapy responses in rectal cancer using multimodal nonlinear optical microscopy.

Lian-Huang Li,Wei-Zhong Jiang,Guo-Xian Guan,Jian-Xin Chen,Xing-Fu Wang,Shuang-Mu Zhuo,Zhi-Fen Chen,Li-Wei Jiang,Xing Liu

doi:10.18632/oncotarget.22366

Abstract

Most patients with rectal cancer have a better prognosis after receiving neoadjuvant therapy because of its remarkable curative effect. However, no device delivers real-time histopathologic information on treatment response to help clinicians tailor individual therapeutic strategies. We assessed the potential of multimodal nonlinear optical microscopy to monitor therapeutic responses, including tumoral and stromal responses. We found that two-photon excited fluorescence imaging can, without labeling, identify colloid response, inflammatory cell infiltration, vascular proliferation, and tumor regression. It can also directly detect rare residual tumor cells, which may be helpful for distinguishing tumor shrinkage from tumor fragmentation. In addition, second harmonic generation imaging shows the ability to monitor three types of fibrotic responses: mature, intermediate, and immature. We also determined nonlinear spectra, collagen density, and collagen orientation indexes to quantitatively analyze the histopathologic changes induced by neoadjuvant therapy in rectal cancer. Our work demonstrates that nonlinear optical microscopy has the potential to become a label-free, real-time, in vivo medical imaging technique and provides the groundwork for further exploration into the application of nonlinear optical microscopy in a clinical setting.

Highlights

Neoadjuvant radiochemotherapy has become a standard of care for patients with locally advanced rectal cancer
Tumor regression is important because the chance of obtaining a negative circumferential resection margin (CRM) is increased after extensive tumor regression; tumor response can take the form of either tumor shrinkage or tumor fragmentation [25]
It is presented that multimodal nonlinear optical microscopy can be used to monitor therapy response to neoadjuvant treatment

Summary

Introduction

Neoadjuvant radiochemotherapy has become a standard of care for patients with locally advanced rectal cancer. This preoperative treatment is associated with improved local control, reduced postoperative local recurrence, and higher sphincter preservation rate in rectal cancer patients and can improve postoperative survival and prognosis [1,2,3]. Tumor response to neoadjuvant therapy should be used to determine operation timing because, after neoadjuvant therapy, a tumor needs to progress from necrosis to apoptosis to complete fibrosis, but these pathologic changes cannot be assessed accurately in preoperative evaluation. Real-time monitoring of disease response to therapy requires standardization www.impactjournals.com/oncotarget to design risk-adapted preoperative and postoperative treatments and optimize patient outcomes. Assessment of neoadjuvant therapy response is currently suboptimal [7]

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Conclusion