Oncologic Procedures Amenable to Fluorescence-guided Surgery

Abstract

Objective: Although fluorescence imaging is being applied to a wide range of cancers, it remains unclear which disease populations will benefit greatest. Therefore, we review the potential of this technology to improve outcomes in surgical oncology with attention to the various surgical procedures while exploring trial endpoints that may be optimal for each tumor type.

Background: For many tumors, primary treatment is surgical resection with negative margins, which corresponds to improved survival and a reduction in subsequent adjuvant therapies. Despite unfavorable effect on patient outcomes, margin positivity rate has not changed significantly over the years. Thus, patients often experience high rates of re-excision, radical resections, and overtreatment. However, fluorescence-guided surgery (FGS) has brought forth new light by allowing detection of subclinical disease not readily visible with the naked eye.

Methods: We performed a systematic review of clinicatrials.gov using search terms "fluorescence," "image-guided surgery," and "near-infrared imaging" to identify trials utilizing FGS for those received on or before May 2016.

Inclusion criteria: fluorescence surgery for tumor debulking, wide local excision, whole-organ resection, and peritoneal metastases.

Exclusion criteria: fluorescence in situ hybridization, fluorescence imaging for lymph node mapping, nonmalignant lesions, nonsurgical purposes, or image guidance without fluorescence.

Results: Initial search produced 844 entries, which was narrowed down to 68 trials. Review of literature and clinical trials identified 3 primary resection methods for utilizing FGS: (1) debulking, (2) wide local excision, and (3) whole organ excision.

Conclusions: The use of FGS as a surgical guide enhancement has the potential to improve survival and quality of life outcomes for patients. And, as the number of clinical trials rise each year, it is apparent that FGS has great potential for a broad range of clinical applications.

FIGURE 1.

Number of new clinical trials and publications by year. Methods for number of clinical trials: clinicatrials.gov searched for keywords ‘‘fluorescence,’’ ‘‘image-guided surgery,’’ and ‘‘near-infrared imaging’’ in May 2016, which produced 844 entries that were narrowed down to 68 studies by inclusion/exclusion criteria. Methods for publications per year: Searched PubMed Advanced Search Builder on July 7, 2016 for Title/Abstract containing ‘‘fluorescence imaging surgery’’ OR ‘‘fluorescence imaging resection’’ OR ‘‘fluorescence-guided surgery’’ OR ‘‘fluorescence guided resection’’ to produce 1099 results in humans and animals. Results further narrowed by applicable year (ie, 2015: January 1, 2015–Decemer 31, 2015).

FIGURE 2.

Mixed media representation demonstrating images obtained from FGS clinical trials. Debulking: preoperative gadolinium-enhanced MRI (left) and intraoperative 5-ALA-induced tumor fluorescence in GBM (right). Circular lines show intraoperative tumor location. Wide local excision: autofluorescence improving tumor margin delineation versus white light. Whole-organ resection: intraoperative fluorescence images of the parathyroid gland with (A) bright-field of parathyroid and thyroid from patient undergoing thyroidectomy, (B) NIR fluorescence showing parathyroid in red, and (C) bright-field and fluorescence images superimposed to show parathyroid fluorescence.

FIGURE 3.

Illustrative schematic of brain tumor debulking demonstrating (A) GBM in situ, (B) more complete debulking with 5-ALA FGS, and (C) remaining residual disease missed with traditional surgical resection.

FIGURE 4.

Illustrative schematic of WLE demonstrating (A) skin lesion in situ, (B) traditional surgical resection with white light, and (C) improved margin negativity with use of cancer-specific tumor marker fluorescently binding to residual, subclinical disease.

FIGURE 5.

Illustrative schematic of whole-organ resection during thyroidectomy demonstrating improved parathyroid gland detection with use of fluorescence imaging.

FIGURE 6.

Mixed media schematic illustrating the emerging bridge in preoperative tumor imaging and real-time tumor-specific identification.