Intraoperative Tumor Assessment Using Real-Time Molecular Imaging in Head and Neck Cancer Patients

Keulen, Stan van; Nishio, Naoki; Fakurnejad, Shayan; Berg, Nynke S. van den; Lu, Guolan; Birkeland, Andrew C.; Martin, Brock A.; Forouzanfar, Tymour; Colevas, A. Dimitrios; Rosenthal, Eben L.

doi:10.1016/j.jamcollsurg.2019.09.007

Cited by 33 publications

(30 citation statements)

References 24 publications

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“…We found a similar contrast in the autoradiographic analyses. Recent clinical studies describe TBRs between two and five after intravenous injection of fluorescently or dual-labeled tumor-targeting antibodies [24][25][26][27]. Methodological differences in analyses or tumor type might explain the difference in TBR between literature and our findings.…”

Section: Discussionsupporting

confidence: 39%

Ex Vivo Assessment of Tumor-Targeting Fluorescent Tracers for Image-Guided Surgery

Elekonawo

Gooyer

Bos

et al. 2020

Cancers

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Image-guided surgery can aid in achieving complete tumor resection. The development and assessment of tumor-targeted imaging probes for near-infrared fluorescence image-guided surgery relies mainly on preclinical models, but the translation to clinical use remains challenging. In the current study, we introduce and evaluate the application of a dual-labelled tumor-targeting antibody for ex vivo incubation of freshly resected human tumor specimens and assessed the tumor-to-adjacent tissue ratio of the detectable signals. Immediately after surgical resection, peritoneal tumors of colorectal origin were placed in cold medium. Subsequently, tumors were incubated with 111In-DOTA-hMN-14-IRDye800CW, an anti-carcinoembryonic antigen (CEA) antibody with a fluorescent and radioactive label. Tumors were then washed, fixed, and analyzed for the presence and location of tumor cells, CEA expression, fluorescence, and radioactivity. Twenty-six of 29 tumor samples obtained from 10 patients contained malignant cells. Overall, fluorescence intensity was higher in tumor areas compared to adjacent non-tumor tissue parts (p < 0.001). The average fluorescence tumor-to-background ratio was 11.8 ± 9.1:1. A similar ratio was found in the autoradiographic analyses. Incubation with a non-specific control antibody confirmed that tumor targeting of our tracer was CEA-specific. Our results demonstrate the feasibility of this tracer for multimodal image-guided surgery. Furthermore, this ex vivo incubation method may help to bridge the gap between preclinical research and clinical application of new agents for radioactive, near infrared fluorescence or multimodal imaging studies.

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Section: Discussionsupporting

confidence: 39%

Ex Vivo Assessment of Tumor-Targeting Fluorescent Tracers for Image-Guided Surgery

Elekonawo

Gooyer

Bos

et al. 2020

Cancers

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“…The detection of resection margins is mainly based on visualization, palpation, and surgeon's experience. Several groups started investigating intraoperative NIR imaging with ICG to distinguish between normal and malignant tissue tumors in head and neck cancer and demonstrated a good imaging contrast [4,24,25]. There is always concern that previous radical irradiation would damage the capillary and microvasculature network, provoking necrosis at the tumor site, tissue remodeling, and as such changes in optical tissue properties, hindering access of molecules to the tumor and making difficult clinical perception of tumor limits [26].…”

Section: Discussionmentioning

confidence: 99%

ICG-induced NIR fluorescence mapping in patients with head & neck tumors after the previous radiotherapy

Cortese

Kerrien

Yakavets

et al. 2020

Photodiagnosis and Photodynamic Therapy

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Background:The distinction between tumor and healthy tissues is complicated in the areas previously subjected to radiation therapy (RT). This is related to the fact that tissues can undergo delayed and irreversible deterioration such as inflammation, vascular alteration and fibrosis. The trials related to the fluorescence -guided surgery (FSG) in Head and Neck Squamous Cell Carcinoma (HNSCC) patients, previously subjected to RT, have not yet been reported. The present study addresses for the first time the possibilities of tumor near-infrared (NIR) imaging using Indocynaine Green (ICG) in irradiated areas.Methods: Four patients with histologically confirmed HNSCC were included in this study. All included patients were previously treated with RT with at least 50 Gy. RT-radiation fields from original treatment fully encompassed the second tumor or recurrence. ICG was injected via cephalic vein 45 min before the images were captured using a NIR camera system Artemis. The images were also captured before ICG injection serving as background signal. The fluorescence intensity measurements were carried out using specially designed software.Results: ICG fluorescence clearly demonstrated a significant difference in fluorescence intensity between healthy and tumor tissues in 2 of 4 patients. Histology post-resection analysis confirmed a complete tumor resection with safe surgical margins. No difference between tumor and surrounding healthy tissue was detected in patients with an epidermoid carcinoma developed from sclerohypertrophic lichen. Conclusions:In our pilot study, we clearly established the feasibility of using NIR FGS with ICG to delineate tumor and healthy tissues in irradiated areas in infiltrating lichenfree tumors.

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“…While PFD associated with PICs can be exploited to identify tumor margins during surgical resection and possibly detection of occult metastases, subsequent PIT of the resected tumor bed may assist in the treatment of residual microscopic tumor [201,202], as discussed below. Currently, there are ongoing studies using targeted PFD for real-time molecular imaging in head and neck cancer resection surgeries [203].…”

Section: Optical Imaging For Diagnostics and Therapy Guidance In Pdt mentioning

confidence: 99%

“…The other area of PDT that is upcoming is the use of the property of most PSs not only to elicit photochemistry but also to have finite quantum yields of fluorescence. This has led to the development and FDA approval of image-guided surgery [203,294,500,501] with a PDT agent and opens up the option, in principle, of treatment following surgery in the same procedure [201]. PDP enhanced immuno-oncology is a future focus in the field.…”

Section: Perspectivementioning

confidence: 99%

Photodynamic therapy, priming and optical imaging: Potential co-conspirators in treatment design and optimization — a Thomas Dougherty Award for Excellence in PDT paper

Silva

Saad

Thomsen

et al. 2020

J. Porphyrins Phthalocyanines

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Photodynamic therapy is a photochemistry-based approach, approved for the treatment of several malignant and non-malignant pathologies. It relies on the use of a non-toxic, light activatable chemical, photosensitizer, which preferentially accumulates in tissues/cells and, upon irradiation with the appropriate wavelength of light, confers cytotoxicity by generation of reactive molecular species. The preferential accumulation however is not universal and, depending on the anatomical site, the ratio of tumor to normal tissue may be reversed in favor of normal tissue. Under such circumstances, control of the volume of light illumination provides a second handle of selectivity. Singlet oxygen is the putative favorite reactive molecular species although other entities such as nitric oxide have been credibly implicated. Typically, most photosensitizers in current clinical use have a finite quantum yield of fluorescence which is exploited for surgery guidance and can also be incorporated for monitoring and treatment design. In addition, the photodynamic process alters the cellular, stromal, and/or vascular microenvironment transiently in a process termed photodynamic priming, making it more receptive to subsequent additional therapies including chemo- and immunotherapy. Thus, photodynamic priming may be considered as an enabling technology for the more commonly used frontline treatments. Recently, there has been an increase in the exploitation of the theranostic potential of photodynamic therapy in different preclinical and clinical settings with the use of new photosensitizer formulations and combinatorial therapeutic options. The emergence of nanomedicine has further added to the repertoire of photodynamic therapy’s potential and the convergence and co-evolution of these two exciting tools is expected to push the barriers of smart therapies, where such optical approaches might have a special niche. This review provides a perspective on current status of photodynamic therapy in anti-cancer and anti-microbial therapies and it suggests how evolving technologies combined with photochemically-initiated molecular processes may be exploited to become co-conspirators in optimization of treatment outcomes. We also project, at least for the short term, the direction that this modality may be taking in the near future.

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Intraoperative Tumor Assessment Using Real-Time Molecular Imaging in Head and Neck Cancer Patients

Cited by 33 publications

References 24 publications

Ex Vivo Assessment of Tumor-Targeting Fluorescent Tracers for Image-Guided Surgery

Ex Vivo Assessment of Tumor-Targeting Fluorescent Tracers for Image-Guided Surgery

ICG-induced NIR fluorescence mapping in patients with head & neck tumors after the previous radiotherapy

Photodynamic therapy, priming and optical imaging: Potential co-conspirators in treatment design and optimization — a Thomas Dougherty Award for Excellence in PDT paper

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