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Cancers
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Research on Fluorescence-Guided Surgery in Cancer Treatment
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Research on Fluorescence-Guided Surgery in Cancer Treatment

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: 30 November 2025 | Viewed by 7492

Special Issue Editor

Dr. Julius Höhne

E-Mail Website
Guest Editor
Department of Neurosurgery, Paracelsus Medical University, Nuremberg, Germany
Interests: glioma; brain tumors; fluorescence-guided surgery; confocal endomicroscopy; cranioplasty; traumatic brain injury

Special Issue Information

Dear Colleagues,

Fluorescence-guided surgery (FGS) is a novel technique that uses fluorescent agents to enhance the visualization of tumor margins and residual tumor cells during surgery. FGS has been shown to improve the extent of resection and the accuracy of biopsy in various types of cancers, such as gliomas, metastases, lymphomas, meningiomas, and others. However, FGS also faces some challenges, such as the limited availability of approved fluorescent agents, the variability of tumor fluorescence, the interference of background fluorescence, and the need for specialized equipment and training. This Special Issue aims to provide an overview of the current state of the art and the future perspectives of FGS in cancer treatment. If you are a neurosurgeon, neurologist, or other healthcare professional with expertise in these areas and are interested in sharing your research and insights with our audience, we encourage you to consider submitting an article for this Special Issue. Our goal is to provide a forum for the exchange of ideas and knowledge and to promote the advancement of neurosurgery. We welcome original research articles and review articles that contribute to our understanding of these exciting developments. Please contact us for more information and to submit your article.

Dr. Julius Höhne
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • fluorescence-guided surgery
  • fluorescent agents
  • tumor fluorescence
  • tumor margin detection
  • residual tumor assessment
  • glioma surgery
  • fluorescein sodium
  • 5-aminolevulinic acid
  • confocal endomicroscopy
  • Raman spectroscopy

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Published Papers (4 papers)

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Research

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16 pages, 2511 KB  
Article
Brightly Visualizing Pancreatic Cancer Margins in Orthotopic Mouse Models with an Anti-CA19-9 Antibody Conjugated to a Near-Infrared Fluorophore
by Kristin E. Cox, Javier Bravo, Sunidhi Jaiswal, Siamak Amirfakhri, Thinzar M. Lwin, Abhijit Aithal, Sumbal Talib, Lily J. Jih, Aylin Din Parast Saleh, Keita Kobayashi, Kavita Mallya, Maneesh Jain, Robert M. Hoffman, Aaron M. Mohs, Surinder K. Batra and Michael Bouvet
Cancers 2025, 17(16), 2617; https://doi.org/10.3390/cancers17162617 - 10 Aug 2025
Viewed by 983
Abstract
Background/Purpose: The only potentially curative procedure for pancreatic cancer is R0 resection, which is difficult to achieve due to poorly defined tumor margins. In the present study, we used an anti-CA19-9 antibody conjugated to a near-infrared fluorophore in orthotopic mouse models to target [...] Read more.
Background/Purpose: The only potentially curative procedure for pancreatic cancer is R0 resection, which is difficult to achieve due to poorly defined tumor margins. In the present study, we used an anti-CA19-9 antibody conjugated to a near-infrared fluorophore in orthotopic mouse models to target and visualize pancreatic cancer. Methods: Orthotopic models of the human pancreatic cancer cell lines SW1990 and BxPC3 were established by implanting tumor fragments into the pancreas of athymic nude mice. Anti-CA19-9 and control IgG were conjugated with IRDye800CW. Mice received 50 µg of CA19-9–IRDye800CW or IgG-IRDye800CW via tail-vein injection and were imaged after 72 h. MIA PaCa-2, a CA19-9-negative cell line, was used in subcutaneous models to assess targeting specificity. Results: Using the LI-COR Pearl imaging system in the SW1990 model, the tumor-to-pancreas ratio (TPR) was 4.51 (±0.74), and the tumor to the liver ratio (TLR) was 3.05 (±0.60) with CA19-9-IRDye800CW, while the TPR was 1.67 (±0.16) and the TLR was 0.95 (±0.05) for the non-specific control IgG–IRDye800CW. Using a clinically available fluorescence laparoscope, CA19-9-1RDye800CW demonstrated a TPR of 2.34 (±0.44) and a TLR of 2.23 (±0.49), compared to 1.11 (±0.13) and 0.69 (±0.07), respectively, for IgG-IRDye800CW in the SW1990 orthotopic model. In the BxPC3 models, the TPR was 3.82 (±0.55) and the TLR was 4.13 (±0.77) for CA19-9-IRDye800CW compared to 2.40 (±0.31) and 1.49 (±0.23), respectively, for IgG-IRDye800CW. Conclusions: CA19-9-IRDye800CW provided specific in vivo targeting of two human pancreatic cancer cell lines in orthotopic nude mouse models with superior TPRs and TLRs compared to IgG-IRDye800CW. This tumor-specific fluorescent CA19-9 antibody is a promising clinical tool for improved visualization of pancreatic cancer. Full article
(This article belongs to the Special Issue Research on Fluorescence-Guided Surgery in Cancer Treatment)
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16 pages, 2086 KB  
Article
Comparative Analysis of Clinical Outcomes in High-Grade Glioma Patients: 5-ALA Fluorescence-Guided Surgery vs. Conventional White-Light Resection
by Nurzhan Ryskeldiyev, Aidos Moldabekov, Dinara Berdibayeva, Aiman Maidan, Torebek Tursynbekov, Dimash Davletov, Muratbek Tleubergenov, Assel Kabykenova, Diana Kerimbayeva, Aidos Doskaliyev and Serik Akshulakov
Cancers 2025, 17(12), 1897; https://doi.org/10.3390/cancers17121897 - 6 Jun 2025
Viewed by 2225
Abstract
Background High-grade gliomas (HGGs) are aggressive brain tumors with poor prognoses. Maximizing the extent of resection (EOR) is a critical surgical goal. Fluorescence-guided surgery using 5-aminolevulinic acid (5-ALA) has been proposed to enhance tumor visualization and resection. MethodsWe retrospectively analyzed 141 patients with [...] Read more.
Background High-grade gliomas (HGGs) are aggressive brain tumors with poor prognoses. Maximizing the extent of resection (EOR) is a critical surgical goal. Fluorescence-guided surgery using 5-aminolevulinic acid (5-ALA) has been proposed to enhance tumor visualization and resection. MethodsWe retrospectively analyzed 141 patients with histologically confirmed HGGs who underwent either 5-ALA-guided (n = 71) or conventional white-light (n = 70) resection between 2018 and 2023. Propensity score matching and multivariate Cox regression models were used to assess the impact of 5-ALA on surgical outcomes and survival. Results: Gross total resection (GTR) was significantly more common in the 5-ALA group than the conventional white-light group (28.17% vs. 12.86%, p = 0.0245). Kaplan–Meier analysis showed no statistically significant difference in overall survival between groups after matching (log-rank p = 0.6371). However, patients with GTR had significantly improved survival compared to those with subtotal resection (log-rank p = 0.0423). Multivariate Cox regression identified radiotherapy (HR = 0.291, 95% CI: 0.166–0.513, p < 0.001), higher Karnofsky Performance Status (HR = 0.962, 95% CI: 0.942–0.982, p = 0.0003), and GTR (HR = 0.476, 95% CI: 0.272–0.834, p = 0.0091) as independent predictors of improved survival. 5-ALA usage was not an independent predictor (HR = 0.885, 95% CI: 0.554–1.413, p = 0.612). Radiotherapy and chemotherapy were more frequently administered in the conventional white-light group (p = 0.0404 and p = 0.0085, respectively). Conclusions 5-ALA fluorescence-guided surgery significantly increases the rate of gross total resection in high-grade glioma patients but does not independently confer a survival advantage. Survival outcomes are primarily influenced by the extent of resection, adjuvant therapy, and functional status. Integration of 5-ALA within a comprehensive oncological framework may enhance its clinical utility. Full article
(This article belongs to the Special Issue Research on Fluorescence-Guided Surgery in Cancer Treatment)
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Review

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19 pages, 1779 KB  
Review
Current and Emerging Fluorescence-Guided Techniques in Glioma to Enhance Resection
by Trang T. T. Nguyen, Hayk Mnatsakanyan, Eunhee Yi and Christian E. Badr
Cancers 2025, 17(16), 2702; https://doi.org/10.3390/cancers17162702 - 19 Aug 2025
Viewed by 984
Abstract
Maximal safe surgical resection remains a critical component of glioblastoma (GBM) management, improving both survival and quality of life. However, complete tumor removal is hindered by the infiltrative nature of GBM and its proximity to eloquent brain regions. Fluorescence-guided surgery (FGS) has emerged [...] Read more.
Maximal safe surgical resection remains a critical component of glioblastoma (GBM) management, improving both survival and quality of life. However, complete tumor removal is hindered by the infiltrative nature of GBM and its proximity to eloquent brain regions. Fluorescence-guided surgery (FGS) has emerged as a valuable tool to enhance intraoperative tumor visualization and optimize resection outcomes. Currently used fluorophores such as 5-aminolevulinic acid (5-ALA), fluorescein sodium (FS), and indocyanine green (ICG) have distinct advantages but are limited by suboptimal specificity, shallow tissue penetration, and technical constraints. 5-ALA and SF often yield unreliable signals in low-grade tumors or infiltrative regions and also pose challenges such as phototoxicity and poor depth resolution. In contrast, near-infrared (NIR) fluorescence imaging represents a promising next-generation approach, providing superior tissue penetration, reduced autofluorescence, and real-time delineation of tumor margins. This review explores the mechanisms, clinical applications, and limitations of currently approved FGS agents and highlights future directions in image-guided neurosurgery. Full article
(This article belongs to the Special Issue Research on Fluorescence-Guided Surgery in Cancer Treatment)
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Other

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15 pages, 1695 KB  
Systematic Review
Utility and Safety of 5-ALA Guided Surgery in Pediatric Brain Tumors: A Systematic Review
by Cheng Wang, Ying Yu, Yafei Wang, Jiahua Yu and Chenran Zhang
Cancers 2024, 16(21), 3677; https://doi.org/10.3390/cancers16213677 - 30 Oct 2024
Cited by 3 | Viewed by 2581
Abstract
Background: 5-Aminolevulinic acid-guided surgery for adult gliomas has been approved by the European Medicines Agency and the US Food and Drug Administration, becoming a reliable tool for improving gross total resection rates and patient outcomes. This has led several medical centers to explore [...] Read more.
Background: 5-Aminolevulinic acid-guided surgery for adult gliomas has been approved by the European Medicines Agency and the US Food and Drug Administration, becoming a reliable tool for improving gross total resection rates and patient outcomes. This has led several medical centers to explore the off-label use of 5-ALA in the resection of pediatric brain tumors, assessing its efficacy and safety across various tumor types. However, given the differences between children and adults, the appropriateness of 5-ALA use in pediatric populations has not yet been fully established. Methods: We collected eligible publications from Embase, Scopus, PubMed, and Proquest, ultimately selecting 27 studies. Data extraction and retrospective analysis of 249 surgical cases were conducted to determine the current efficacy and safety of 5-ALA in pediatric brain tumors. The fluorescence rate and utility stratified by several clinical features, including WHO grade, tumor classification, and tumor location, were analyzed. Results: Most studies suggest that 5-ALA can enhance tumor identification in high-grade tumors, including glioblastomas and anaplastic astrocytomas. Changes in survival or recurrence rates associated with 5-ALA-guided resection have not been reported. None of the cases reported significant postoperative complications related to the use of 5-ALA. Conclusions: 5-ALA can aid in the resection of high-grade gliomas in pediatric patients. The efficacy of 5-ALA in low-grade gliomas and other tumors may require enhancement with additional tools or modified administration protocols. The safety of 5-ALA has reached a preliminary consensus, although further randomized controlled trials and data on survival and molecular characteristics are needed. Full article
(This article belongs to the Special Issue Research on Fluorescence-Guided Surgery in Cancer Treatment)
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