Real-time in vivo assessment of radiofrequency ablation of human colorectal liver metastases using diffuse reflectance spectroscopy
Introduction
Colorectal cancer (CRC) has the world's third most frequent cancer incidence and cancer related death.1, 2 Up to 50% of CRC patients will develop metastatic disease, primarily in the liver.3 Approximately 25% of these patients are eligible for resection of the liver metastases. For the rest, radiofrequency (RF) ablation has shown to be a valuable treatment option when feasible.4 With the appropriate experience, open RF ablation procedures during surgery can be performed with local recurrence rates comparable to resection in selected patients.5, 6 Nonetheless, during ablation, there remains a degree of uncertainty on the actual ablated tumour free margin and treatment effect, as current imaging techniques (US, CT, or MRI) cannot accurately determine the advancing ablation margin during the RF ablation procedure.7, 8 While open RF ablation procedures during surgery generally report local recurrence rates below 20%,9, 10 local recurrence rates of percutaneous RF ablation vary between 9% and 40% depending on the number of lesions, size, and location.11, 12, 13 Lesions smaller than 4 cm treated percutaneous by experienced hands can reach local recurrences rates comparable to open RFA procedures.14, 15
Optical techniques, such as diffuse reflectance (DR) spectroscopy at the tip of a fibre-optic needle (i.e. spectroscopy needle) may enable real-time tissue monitoring by measuring specific physiological information from the examined tissue. By illuminating the tissue with a selected spectral band of light and subsequently measuring the reflected light that has been altered by scattering and absorption by the tissue, one can obtain an “optical fingerprint” of the tissue. This may enable real-time monitoring of the progress of ablation as well as determining the extent of the ablated area at various critical points of interest (e.g. near large vessels) after the procedure has been completed. In this way DR spectroscopy can determine the adequacy of the ablation, thereby potentially improving procedure outcome and local recurrence rates.
Various teams have successfully focused on spectroscopic detection of thermal damage of animal liver tissue. An increase in reflectance intensity and a decrease in overall fluorescence intensity are correlated with the histological degree of thermal liver tissue damage.16, 17, 18, 19 An ideal marker for RF ablation should provide a reliable measure whether or not tissue has been adequately ablated. In a recently published preclinical study we have demonstrated that thermal coagulation of liver tissue can be quantified using specific spectral information.20 The identified spectral characteristics were used to evaluate ablation margins during and after ablation. The aim of the current study is to determine whether DR spectroscopy used during radiofrequency (RF) ablation of colorectal liver metastases could aid in detecting when tissue becomes adequately ablated.
Section snippets
Patients and methods
This observational study was conducted at the Netherlands Cancer Institute – Antoni van Leeuwenhoek hospital under approval of the institutional review board (Dutch trial register NTR2557). Patients with unresectable CRLM scheduled for open intraoperative RF ablation, whether or not in combination with hepatic resection of additional liver metastases, were eligible for inclusion. Liver metastases (<4 cm) that were not eligible for resection were considered for RF ablation. Written informed
Results
A total of eight patients (5 male and 3 female) were included; mean age was 68 years (range: 47–71 years), median number of liver lesions per patient was 3 (range: 1–7). All lesions were treated by RF ablation, except in three patients where it was combined with partial liver resection.
Four patients had been treated with neo-adjuvant systemic treatment; i.e. capecitabine and oxaliplatin ± Bevacizumab for a median of four cycles (range 2–4). For the lesions in which ablation was monitored by DR
Discussion
Despite the widespread use of RF ablation, a major drawback in the current management of liver tumours with RF ablation is the lack of an effective modality to accurately monitor real-time progress of the ablation zone. In the current study we described the first spectroscopy-based feedback system to monitor thermal damage in vivo during a series of clinical RF ablation procedures. In the first part of the study a series of liver tumour ablations were performed in eight patients and reflectance
Conflict of interest
The author who is affiliated with Philips Research (B.H.W.H.) has financial interest in the subject matter, materials, and equipment, in the sense that he is employee of Philips. The prototype system described in this article is currently a research prototype and is not for commercial use. All other authors declare to have no conflict of interest.
Acknowledgement
The authors would like to thank the members of the Philips Research department for their technical support.
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2023, Journal of Drug Delivery Science and TechnologyLocal tumour control after radiofrequency or microwave ablation for colorectal liver metastases in relation to histopathological growth patterns
2022, HPBCitation Excerpt :Absence of viable tumour cells on post-ablative biopsies can be used to assess complete ablation and have been described as a predictor for LTP after ablation of CRLM.49,50 Ki-67 determination, Fluorescent tissue imaging, software assisted evaluation of the ablation zone and intraoperative spectroscopy have also been described as novel tools to predict successful ablation.50–54 Unfortunately, these techniques were not applied in our retrospective cohort of patients.
Immunofluorescence Assay of Ablated Colorectal Liver Metastases: The Frozen Section of Image-Guided Tumor Ablation?
2022, Journal of Vascular and Interventional RadiologyCitation Excerpt :This methodology could improve oncologic outcomes of TA in the treatment of cancer and is probably a required step in the evolution of ablation as potential local cure with outcomes comparable to hepatectomy (24). Reflectance spectroscopy has been used during RF ablation of CLMs, resulting in >97% correlation with histopathologic assessment and postablation CT imaging; however, it could only distinguish ablated tissues from nonablated ones (10). The investigators highlighted the value of the real-time feedback during ablation as a very important step in the effort to improve tumor ablation outcomes.
Radiofrequency ablation for liver: Comparison between expert eye and hyperspectral imaging assessment
2022, Photodiagnosis and Photodynamic TherapyCitation Excerpt :In this study, we used RF ablation for liver tissue. RF ablation is reported to be a successful cure for liver malignancies with a return chance similar to that of resection for some patients [22]. RF-induced ablation is widely accepted since it is clinically safe along with being successfully detrimental for proteins [19].
Hyperspectral image-based analysis of thermal damage for ex-vivo bovine liver utilizing radiofrequency ablation
2021, Surgical OncologyCitation Excerpt :On the other hand, it is not the optimum strategy due to the lack of ability to observe the thermal consequence with the ordinary image-guided methods, Computed Tomography (CT) and ultrasound (US) as a result of the high exertion to differentiating the tumor boundaries, due to gas bubble fact and tissue-damaging which emerge through the thermal process [28–30]. Recently, several researchers designed and implemented imaging approaches to verify the appropriate liver cancer ablation utilizing non-invasive versus the ordinary excisional tissue removal, such as diffuse reflectance spectroscopy (DRS) is utilized to assess RFA of 8 samples of a liver tumor with high accuracy (97–99%) to discriminate between the predicted thermal damage and the histology report [31]. Moreover, in another study utilizing the computed tomography (CT) with MWA to investigate 3 ex-vivo porcine samples with a thermal procedure (100 W 4.5 min), the results demonstrate ablation region (4.1 ± 0.2 × 5.6 ± 0.2) [32].
Optical signatures of thermal damage on ex-vivo brain, lung and heart tissues using time-domain diffuse optical spectroscopy
2024, Biomedical Optics Express
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Both authors contributed equally.