Sentinel lymph node biopsy (SLNB) is recommended for patients with >pT1b cutaneous melanoma, and should be considered and discussed with patients diagnosed with pT1b cutaneous melanoma for the... Show moreSentinel lymph node biopsy (SLNB) is recommended for patients with >pT1b cutaneous melanoma, and should be considered and discussed with patients diagnosed with pT1b cutaneous melanoma for the purpose of staging, prognostication and determining eligibility for adjuvant therapy. Previously, the clinicopathologic and gene expression profile (CP-GEP, Merlin Assay (R)) model was developed to identify patients who can forgo SLNB because of a low risk for sentinel node metastasis. The aim of this study was to evaluate the clinical use and implementation of the CP-GEP model in a prospective multicenter study in the Netherlands. Both test performance and feasibility for clinical implementation were assessed in 260 patients with T1-T4 melanoma. The CPGEP model demonstrated an overall negative predictive value of 96.7% and positive predictive value of 23.7%, with a potential SLNB reduction rate of 42.2% in patients with T1-T3 melanoma. With a median time of 16 days from initiation to return of test results, there was sufficient time left before the SLNB was performed. Based on these outcomes, the model may support clinical decision-making to identify patients who can forgo SLNB in clinical practice. Show less
Rietbergen, D.D.D.; Arias-Bouda, L.M.P.; Hage, J.A. van der; Olmos, R.A.V. 2021
Introduction and objectives: To evaluate the migration of Tc-99m-tilmanocept from the injection site (IS) as well as the uptake in sentinel nodes (SNs) and non-SNs for lymphatic mapping in patients... Show moreIntroduction and objectives: To evaluate the migration of Tc-99m-tilmanocept from the injection site (IS) as well as the uptake in sentinel nodes (SNs) and non-SNs for lymphatic mapping in patients with breast cancer and melanoma, scheduled for SN biopsy after interstitial tracer administration.Materials and methods: For 29 primary tumours in 28 patients (mean age: 62y, range: 45-81y) scheduled for SN biopsy planar images were acquired 10 and 120 min after administration of 74 MBq Tc-99m-tilmanocept, in order to evaluate lymphatic drainage as well as uptake ratios between injection site (IS), SN and non-SN. SPECT/CT was performed immediately after delayed planar images to enable anatomical lymph node localization.Results: SNs were visualized in all patients (100%) with drainage to 34 basins. Uptake in non-SNs was perceived in 16 basins (47%). Number of SNs was concordant between early and delayed images in all basins excepting five (86%). In 24 patients tracer migrated to one lymph node basin (LNB), in three to 2 and in one to 4. When IS was included (n = 29) on image, IS/SN ratio could be measured per LNB. The IS/SN ratio at 2 h compared to 15 min decreased with an average of 66% (range: 15-96%). SN/non-SN 2 h ratio in LNBs with visible non-SNs averaged 6.6 (range: 2.3-15.6). In 9 patients with two SNs SN1/SN2 ratio averaged 1.9 on delayed images. At histopathology, SNs were found to be tumour positive in 7 basins (20%).Conclusion: Tc-99m-tilmanocept appears to meet the requirements for improved SN imaging in breast cancer and melanoma on the basis of early and persistent SN visualization frequently accompanied by no or markedly less non-SN uptake.This is associated to rapid migration from the injection site together with increasing SN uptake and retention as expressed by decreasing IS/SN and persistently high SN/non-SN ratios. Further head-to-head comparison of Tc-99m-tilmanocept with standard SN radiotracers in larger series of patients is necessary. (C) 2020 Sociedad Espanola de Medicina Nuclear e Imagen Molecular. Published by Elsevier Espana, S.L.U. All rights reserved. Show less
Background: Sentinel node (SN) biopsy in penile cancer (PeCa) is typically performed using Tc-99m-nanocolloid and blue dye. Recent reports suggested that the hybrid (radioactive and fluorescent)... Show moreBackground: Sentinel node (SN) biopsy in penile cancer (PeCa) is typically performed using Tc-99m-nanocolloid and blue dye. Recent reports suggested that the hybrid (radioactive and fluorescent) tracer indocyanine green (ICG)-99mTc-nanocolloid may improve intraoperative optical SN identification.Objective: The current study aimed to confirm the reliability of ICG-Tc-99m-nanocolloid and to assess whether blue dye is still of added value.Design, setting, and participants: A total of 400 >= T1G2N0 PeCa patients were staged with SN biopsy at a single European centre. SNs were preoperatively identified with lymphoscintigraphy and single-photon emission computed tomography. Intraoperatively, SNs were detected via gamma tracing, blue staining, and fluorescence imaging.Outcome measurements and statistical analysis: All patients (n = 400, 740 groins) received ICG-Tc-99m-nanocolloid. Intraoperative SN identification rates were retrospectively evaluated. In those patients who received ICG-Tc-99m-nanocolloid and blue dye (n = 266, 492 groins), SN visualisation rates were compared using the McNemar test.Results and limitations: In total, 740 groins were assessed. No tracer-related (allergic) reactions were reported. All preoperatively defined SNs (n = 1163) were localised intraoperatively. Of all excised SNs, 98% were detectable with gamma probe and 96% were visible with fluorescence imaging. In the analysis of the patients who received ICG-Tc-99m-nanocolloid and blue dye, fluorescence imaging yielded a 39% higher SN detection rate than blue dye (95% confidence interval 36-43%, p < 0.001). Of the SNs that were tumour positive, 100% were intraoperatively visualised by fluorescence imaging, whereas merely 84% of the positive nodes stained blue.Conclusions: This study confirms that ICG-Tc-99m-nanocolloid is a reliable SN tracer for PeCa that significantly improves optical SN detection over blue dye.Patient summary: Hybrid indocyanine green (ICG)-Tc-99m-nanocolloid is a safe and reliable sentinel node (SN) tracer, as established in this large series of 400 penile cancer patients (740 groins). It enables accurate pre- and intraoperative SN identification and significantly improves SN detection rate compared with blue dye, without staining the surgical field or the need for an additional injection. (c) 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved. Show less
Veij Mestdagh, P.D. de; Schreuder, W.H.; Vogel, W.V.; Donswijk, M.L.; Werkhoven, E. van; Wal, J.E. van der; ... ; Al-Mamgani, A. 2019
Background The majority of patients with head and neck squamous cell carcinoma (HNSCC) receive bilateral elective nodal irradiation (ENI), in order to reduce the risk of regional failure. Bilateral... Show moreBackground The majority of patients with head and neck squamous cell carcinoma (HNSCC) receive bilateral elective nodal irradiation (ENI), in order to reduce the risk of regional failure. Bilateral ENI, as compared to unilateral ENI, is associated with higher incidence of acute and late radiation-induced toxicity with subsequent deterioration of quality of life. Increasing evidence that the incidence of contralateral regional failure (cRF) in lateralized HNSCC is very low (< 10%) suggests that it can be justified to treat selected patients unilaterally. This trial aims to minimize the proportion of patients that undergo bilateral ENI, by using lymph drainage mapping by SPECT/CT to select patients with a minimal risk of contralateral nodal failure for unilateral elective nodal irradiation. Methods In this one-armed, single-center prospective trial, patients with primary T1-4 N0-2b HNSCC of the oral cavity, oropharynx, larynx (except T1 glottic) or hypopharynx, not extending beyond the midline and planned for primary (chemo) radiotherapy, are eligible. After Tc-99m-nanocolloid tracer injection in and around the tumor, lymphatic drainage is visualized using SPECT/CT. In case of contralateral lymph drainage, a contralateral sentinel node procedure is performed on the same day. Patients without contralateral lymph drainage, and patients with contralateral drainage but without pathologic involvement of any removed contralateral sentinel nodes, receive unilateral ENI. Only when tumor cells are found in a contralateral sentinel node the patient will be treated with bilateral ENI. The primary endpoint is cumulative incidence of cRF at 1 and 2 years after treatment. Secondary endpoints are radiation-related toxicity and quality of life. The removed lymph nodes will be studied to determine the prevalence of occult metastatic disease in contralateral sentinel nodes. Discussion This single-center prospective trial aims to reduce the incidence and duration of radiation-related toxicities and improve quality of life of HNSCC patients, by using lymph drainage mapping by SPECT/CT to select patients with a minimal risk of contralateral nodal failure for unilateral elective nodal irradiation. Show less
PurposeSentinel lymph node biopsy is an essential staging tool in patients with clinically localized oral cavity squamous cell carcinoma. The harvesting of a sentinel lymph node entails a sequence... Show morePurposeSentinel lymph node biopsy is an essential staging tool in patients with clinically localized oral cavity squamous cell carcinoma. The harvesting of a sentinel lymph node entails a sequence of procedures with participation of specialists in nuclear medicine, radiology, surgery, and pathology. The aim of this document is to provide guidelines for nuclear medicine physicians performing lymphoscintigraphy for sentinel lymph node detection in patients with early N0 oral cavity squamous cell carcinoma.MethodsThese practice guidelines were written and have been approved by the European Association of Nuclear Medicine (EANM) and the International Atomic Energy Agency (IAEA) to promote high-quality lymphoscintigraphy. The final result has been discussed by distinguished experts from the EANM Oncology Committee, and national nuclear medicine societies. The document has been endorsed by the Society of Nuclear Medicine and Molecular Imaging (SNMMI).These guidelines, together with another two focused on Surgery and Pathology (and published in specialised journals), are part of the synergistic efforts developed in preparation for the 2018 Sentinel Node Biopsy in Head and Neck Consensus Conference.ConclusionThe present practice guidelines will help nuclear medicine practitioners play their essential role in providing high-quality lymphatic mapping for the care of early N0 oral cavity squamous cell carcinoma patients. Show less
IntroductionGuidelines advocate the use of combined detection techniques to achieve optimal results for sentinel node (SN) biopsy. The fluorescent and radioactive (dual-) tracer ICG-Tc-99m... Show moreIntroductionGuidelines advocate the use of combined detection techniques to achieve optimal results for sentinel node (SN) biopsy. The fluorescent and radioactive (dual-) tracer ICG-Tc-99m-nanocolloid has been shown to facilitate SN biopsy in several indications. It was reported that an opto-nuclear probe permitted the detection of near-infrared fluorescence and gamma-rays. The aim of the current study was to evaluate this device in a large patient group and to test it in both open and laparoscopic surgery implications.MethodsThirty-three patients scheduled for SN biopsy with the dual-tracer were retrospectively analyzed. Pre-operative lymphoscintigraphy was performed in all patients; in 18 patients (55%), a SPECT/CT scan was also performed. Radioactive and fluorescent signatures in the SNs were assessed in vivo and ex vivo using the opto-nuclear probe.ResultsOne or more SNs were identified in all patients (identification rate 100%). Planar lymphoscintigraphic images revealed 95 hot spots that were considered as SNs. This number increased to 103 SNs when SPECT/CT was used. During surgery, 106 SNs were excised. In vivo, the fluorescence mode of the opto-nuclear probe was able to locate 79 SNs (74.5%). When the gamma-ray detection option of the same probe was used, this number increased to 99 SNs (93.3%). Ex vivo analysis revealed fluorescence in 93.3% of the excised nodes and radioactivity in 95.2%.ConclusionsThis study underlines the feasibility of using the dual-tracer/opto-nuclear probe combination for SN resections. The use of the opto-nuclear technology has been extended to laparoscopic surgery. This study also underlines the fluorescence tracing can complement traditional radio-tracing approaches. Show less
To investigate the feasibility of lymph drainage mapping (LDM) using SPECT/CT to help select head and neck cancer (HNSCC) patients for unilateral elective neck irradiation (ENI). Patients with... Show moreTo investigate the feasibility of lymph drainage mapping (LDM) using SPECT/CT to help select head and neck cancer (HNSCC) patients for unilateral elective neck irradiation (ENI). Patients with lateralized HNSCC treated with radiotherapy routinely undergo bilateral ENI, despite the incidence of contralateral regional failure being relatively low even after unilateral ENI. We hypothesized that patients with a lateralized tumor without visible lymph drainage to the contralateral neck have an extremely low risk of contralateral involved nodes. Excluding the contralateral neck from elective irradiation will reduce radiation-induced toxicity and improve quality-of-life.Fifty-five patients with lateralized cT1-3N0-2bM0 HNSCC not crossing the midline underwent LDM. Radiolabeled Tc-99m-nanocolloid was injected in 4-5 depots around and in the primary tumor. Lymph drainage patterns were visualized using planar scintigraphy and SPECT/CT after 4 h. We report on the incidence of contralateral drainage, the location of draining areas, and the size of underlying nodes.Lymphatic drainage was successfully visualized in 54 patients (98%). In 11 patients (20%) with visible contralateral drainage, 14 draining areas (16 nodes; median volume 0.50 cc, diameter 8.0 mm) were identified. Neck levels with contralateral drainage were level II (88%), III (25%), and IV (13%). Contralateral drainage was significantly higher in T3 compared to T1-2 tumors (45 and 14%, respectively, P = 0.035).SPECT/CT-guided LDM is feasible and can be used to guide unilateral ENI in HNSCC patients in prospective studies. In addition, the anatomical confidence in visualization of contralateral drainage indicates a potential for ENI limited to draining levels alone. Show less
Surgery is considered the golden standard to treat the primary tumour and regional spread of many different cancer types. In addition to the pathological evaluation of surgical margins, the... Show moreSurgery is considered the golden standard to treat the primary tumour and regional spread of many different cancer types. In addition to the pathological evaluation of surgical margins, the evaluation of lymph nodes is needed to stage the metastatic dissemination of the disease [1,2]. Both these aspects are critical in accomplishing radical excision and are, as such, providing true prognosis. However, the quest for complete cure should be in balance with the desire for minimally invasive surgery [3–5]. Hereby it can be assumed that surgical side effects may negatively influence the patient’s quality of life. Advanced image guided surgery technologies can be used to improve the surgical resection and to minimize the invasive nature of the procedure [6]. In this thesis both these technologies are discussed. Hereby we focussed on the locoregional assessment of the lymphatic tumour spread via sentinel lymph node procedures [7–11]. In addition technologies that support nerve-sparing surgery have been pursued. To realize these ambitious goals, a combination of imaging modalities has been used, ranging from fluorescence to nuclear imaging and hybrid combinations of the same. Show less
Intraoperative imaging using near-infrared (NIR) fluorescence is a fast developing imaging modality as it provides real-time visual information during surgery (Chapter 1). The ability to detect... Show moreIntraoperative imaging using near-infrared (NIR) fluorescence is a fast developing imaging modality as it provides real-time visual information during surgery (Chapter 1). The ability to detect lymph nodes and tumours that need to be resected can assist the surgeon to improve surgery by reducing time of the procedure, reducing iatrogenic damage, and improve the number of radical resections. This thesis focuses on the introduction of NIR fluorescence imaging into the clinic. Part 1 of this thesis describes the optimization of NIR fluorescence imaging for sentinel lymph node (SLN) biopsy using the clinically available NIR tracer Indocyanine green (ICG) in various cancer types. Moreover, these studies show both the limitations as the clinical benefit of NIR fluorescence for SLN biopsy. Part 2 describes the use of NIR light for tumour detection. Tissue absorption and scattering in the NIR light spectrum was used for neoadjunvant treatment response monitoring in breast cancer patients. Moreover, NIR fluorescence imaging using NIR contrast agents was used for the intraoperative detection of otherwise difficult to localize liver metastases of colorectal cancer. Show less
The work described in this thesis shows how intraoperative lesion identification can be improved via the introduction of (hybrid) tracers and optimised (hybrid) imaging modalities capable... Show more The work described in this thesis shows how intraoperative lesion identification can be improved via the introduction of (hybrid) tracers and optimised (hybrid) imaging modalities capable of detecting this tracers. In part one, the reader is introduced to the concept of fluorescence image-guided surgery and the evolution thereof. Furthermore the hybrid approach for image-guided surgical guidance is presented. Part two describes the clinical evaluation of the hybrid approach using the hybrid tracer indocyanine green-technetium 99m-nanocolloid. To further refine the hybrid approach for surgical guidance, part three of this thesis describes the development and evaluation of different types of (hybrid) imaging modalities. Show less
KleinJan, G.H.; Bunschoten, A.; Berg, N.S. van den; Olmos, R.A.V.; Klop, W.M.C.; Horenblas, S.; ... ; Leeuwen, F.W.B. van 2016
