Preoperative Sentinel Lymph Node Mapping Research Articles

Comparative aspects of targeted sentinel lymph node mapping in veterinary and human medicine: opportunities for future research.

There is a significant overlap in the genetic, metabolic and epigenetic alterations between human and companion animal cancers, including those of the oral cavity, breast, bladder, skin, lungs and pancreas. In many cancer types, the identification and removal of affected lymph nodes are essential for accurate cancer management, including treatment and prognosis. Historically, lymphadenectomy and subsequent radical resection based on regional anatomy, palpation and lymph node aspirates were considered sufficient; however, modern approaches with sentinel lymph node mapping (SLN) mapping have increased the accuracy of surgical decision-making. Preoperative and intraoperative SLN mapping techniques in veterinary patients parallel those used in human medicine. While many of these techniques are highly successful, the main challenges with current methodologies are their sensitivity and specificity for the presence of cancer, which can be overcome via precision medicine and targeted SLN mapping agents. Given the large population of dogs and cats with cancer, the crossover of knowledge between species can help to deepen our understanding of many of these cancers and can be useful in evaluating new drugs and/or therapies. In this review, we discuss SLN mapping techniques in veterinary medicine and the concept of precision medicine as it relates to targeted SLN mapping imaging agents. The large number of companion animals affected by cancer is an underutilized resource to bridge the translational gap and we aim to provide a reference for the use of dogs and cats as a comparative model for human SLN mapping.

A SPECT/NIR Fluorescence Dual-Modality Imaging Agent Composed of Drugs and Hospital Available Isotope for Preoperative Sentinel Lymph Node Mapping and Intraoperative Biopsy.

Sentinel lymph node (SLN) mapping-guided biopsy is crucial for cancer staging and treatment. Optical/nuclide dual-modality imaging agents for mapping SLN are ideal for preoperative planning and intraoperative biopsy, which are enabled by penetration-depth unlimited nuclide imaging and dynamic real-time optical imaging, respectively. However, commonly reported dual-modality imaging agents are composed of novel but safety-unproven materials, making their quick clinical translation challenging. Herein, we report a novel nanoparticle composed of facile hospital-available drugs and isotope for single-photon emission computed tomography (SPECT)/near-infrared (NIR) fluorescence imaging to detect SLNs. Indocyanine green-human serum albumin (ICG-HSA) nanoparticles (NPs) were synthesized by ICG-induced HSA self-assembly and further 99mTc-labeling via a one-step, facile hospital-available method. After injecting 99mTc-ICG-HSA into the rats' forepaw pads, the rats' draining axillary lymph nodes were visualized by preoperative mapping with SPECT/CT and intraoperative biopsy with NIR fluorescence. The axillary lymph nodes of rats were identified by pathology and fluorescent staining after execution. Additionally, its toxicity testing and comparison with 99mTc-sulfur colloid imaging were also explored. The study reported a self-assembled 99mTc-ICG-HSA with a high radiochemical yield (85.6 ± 3.8%). Compared with conventional 99mTc-sulfur colloid, 99mTc-ICG-HSA NPs showed faster SLN identification, higher renal clearance, and lower hepatic retention. Furthermore, NIRF imaging allowed for the accurate visualization of the SLN and guided SLN biopsy intraoperatively. Notably, the 99mTc-ICG-HSA NPs were composed of hospital-available drugs and isotope, which are safe for acute toxicity evaluation by a certified institute. The proposed 99mTc-ICG-HSA NPs are safe and capable of noninvasive SLN identification and biopsy guidance with multi-modal imaging strategies and could be a promising tool for clinically assisted SLN biopsy.

Exploring an alternative pre-operative sentinel lymph node mapping method using a Magnetic tracer and MRI for melanoma patients – SCARLETT study protocol

Exploring an alternative pre-operative sentinel lymph node mapping method using a Magnetic tracer and MRI for melanoma patients – SCARLETT study protocol

Exploring an alternative pre-operative sentinel lymph node mapping method using a Magnetic tracer and MRI for potential use in melanoma patients

Background: Sentinel lymph node (SLN) biopsy is considered an important prognostic procedure in staging malignant melanomas. Since the location of the SLN can vary, pre-operative SLN-mapping is essential. However, the current gold standard for pre-operative SLN-mapping with dual tracing technique, using the radioisotope Technetium combined with Patent Blue, is associated with several drawbacks (e.g. radiation exposure, allergic reactions, and logistic challenges).

Sentinel lymph node biopsy with a handheld cordless magnetic probe following preoperative MR lymphography using superparamagnetic iron oxide for clinically N0 early oral cancer: A feasibility study

PurposeRadioisotope (RI) tracers are generally used for preoperative mapping of sentinel lymph node (SLN) and intraoperative detection with a portable γ probe. However, the use of RI has several limitations. Therefore, a method without RI is required for the widespread application of SLN biopsy. The purpose of this study was to evaluate the feasibility of SLN biopsy with a handheld cordless magnetic probe following magnetic resonance lymphography (MRL) using superparamagnetic iron oxide (SPIO) and for clinically N0 early oral cancer. Materials and methodsMRL using SPIO and SLNB with the handheld cordless magnetic probe were performed for 27 patients with clinically N0 early oral cancer. ResultsIn all 27 patients (100%), SLNs were detected by MRL, and the total and mean number of SLNs were 73 and 2.7, respectively. All SLNs identified by MRL were detectable using the magnetic probe in all patients. ConclusionsSLNB with handheld cordless magnetic probe following preoperative SLN mapping by MRL using SPIO is feasible, without RI use, for neck management in cases of clinically N0 early oral cancer.

Advantages of Sentinel Lymph Node Mapping by Single Photon Emission Computed Tomography/Computed Tomography in Early-Stage Malignant Head-and-Neck Skin Tumors.

Background:The aim of this study was to determine the advantages of preoperative sentinel lymph node mapping (SLNM) by single photon emission computed tomography/computed tomography (SPECT / CT) in patients with early-stage cutaneous head-and-neck malignancies.Materials and Methods:We conduct a 7-year and 6 months retrospective, cross-sectional study. Patients with early-stage malignant head-and-neck skin tumors and cutaneous adnexa who underwent SLNM by SPECT/CT from March 2012 and December 2019, were included in the study.Results:We retrospectively analyzed 28 patients: Melanoma was the most frequent tumor (64.2%), followed by squamous cell carcinoma (25%). The anterior cheek was the most common functional subsite (25%). Twenty-seven patients (96.4%) had a successful SLN detection with SPECT/CT. Neck lymph node dissection was performed in 23 patients (82.1%). According to the pathological specimen, lymph nodes were found in all of them; hence, the efficacy of the SPECT/CT for SLNM was 100%. At 7-year follow-up, systemic recurrence was found in one patient (3.6%), another had locoregional recurrence (3.6%), and the mortality rate was 3.6%.Conclusions:In early-stage malignant head-and-neck skin tumors, there is a high concordance between SLN found by SPECT/CT and the histopathological results. Preoperative SPECT/CT accurately detects the SLN, assesses unexpected lymph nodes and their drainage pathways, and facilitates their location by reliably showing the relationships between sentinel nodes and important anatomic structures. This allows to perform a clear preoperative evaluation, an accurate staging for all patients and to avoid excessive dissections that could result in cosmetic and functional deformities.

Abstract PS14-21: Refining loco-regional therapy for inflammatory breast cancer protocol in progress

Abstract Background: Inflammatory breast cancer (IBC) is the most aggressive locally advanced breast cancer subtype. It is associated with loco-regional recurrence rates of 12-25%, and neoadjuvant chemotherapy (NAC) followed by modified radical mastectomy and comprehensive chest wall and regional nodal radiotherapy remain the standard of care. As has been demonstrated in non-IBC, achievement of pathologic complete response (pCR) has been shown to be associated with improved loco-regional control, recurrence-free and overall survival. Advances in NAC for IBC have resulted in improved pCR rates in both the breast and the axilla, with overall axillary pCR rates of approximately 30%, reaching as high as 67% in patients with HER2-positive disease receiving HER2-directed therapy. Hypothesis: Sentinel lymph node biopsy (SLNB) may be feasible in IBC patients who experience a good clinical and pathologic response in the axilla to NAC. Primary Objective: To evaluate the sentinel lymph node (SLN) identification rate in stage III IBC patients who experience cN0 status at completion of NAC. Secondary Objective: To assess the incidence of lymphedema following standard local-regional therapy for IBC. Methods and Study procedures: In this feasibility study, 50 patients with cT4dN0-2M0 IBC will be enrolled in order to evaluate 40 patients whose axillary nodal status becomes cN0 upon completion of NAC. All patients will undergo a research breast biopsy and lymphoscintigram pre and post NAC to evaluate lymphatic drainage patterns and patency of breast and axillary lymphatics. Post NAC lymphoscintigraphy will be appropriately timed for pre-operative SLN mapping and all patients will undergo SLNB using dual tracers (Tc99 Sulfur colloid and blue dye) with immediate axillary lymph node dissection (ALND), at the time of mastectomy. The patient-reported Lymphedema Symptom Intensity and Distress Survey (LSIDS-A) will be collected at 6 timepoints. Patients will be followed for 2 years post-surgery for oncologic outcomes. Correlatives: We plan to evaluate genetic and phenotypic heterogeneity in IBC and to assess markers of angiogenesis and lymph-angiogenesis associated with IBC, as well as to explore immunologic aspects of the tumor microenvironment and their association with pCR. Statistics: The identification rate will be calculated as number of patients in whom SLNs were successfully identified over the number of patients with cN0 disease after NAC in whom SLN mapping was attempted. Using a Simon two-stage design (α=.10, β=.10), a SLN identification rate of ≥90% would result in considering this procedure feasible whereas an identification rate of ≤75% (null hypothesis) would lead to the conclusion that it is not feasible. In the first stage, if greater than 18 of 25 patients have SLNs identified, then a total of 40 patients will be enrolled. If fewer than 33 of 40 patients have SLN identified, then the null hypothesis is rejected. Citation Format: Faina Nakhlis, Meredith Regan, Heather Jacene, Beth Harrison, Jennifer Bellon, Jean Landry, Eren Yeh, Elizabeth Mittendorf, Beth Overmoyer, Tari King. Refining loco-regional therapy for inflammatory breast cancer protocol in progress [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS14-21.

Evaluation of camera-based freehand SPECT in preoperative sentinel lymph node mapping for melanoma patients

BackgroundAssessment of lymphatic status via sentinel lymph node (SLN) biopsy is an integral and crucial part of melanoma surgical oncology. The most common technique for sentinel node mapping is preoperative planar scintigraphy of an injected gamma-emitting lymphatic tracer followed by intraoperative node localization using a non-imaging gamma probe with auditory feedback. In recent years, intraoperative visualization of SLNs in 3D has become possible by coupling the probe to an external system capable of tracking its location and orientation as it is read out, thereby enabling computation of the 3D distribution of the tracer (freehand SPECT). In this project, the non-imaging probe of the fhSPECT system was replaced by a unique handheld gamma camera containing an array of sodium iodide crystals optically coupled to an array of silicon photomultipliers (SiPMs). A feasibility study was performed in which preoperative SLN mapping was performed using camera fhSPECT and the number of detected nodes was compared to that visualized by lymphoscintigraphy, probe fhSPECT, and to the number ultimately excised under non-imaging probe guidance.ResultsAmong five subjects, SLNs were detected in nine lymphatic basins, with one to five SLNs detected per basin. A basin-by-basin comparison showed that the number of SLNs detected using camera fhSPECT exceeded that using lymphoscintigraphy and probe fhSPECT in seven of nine basins and five of five basins, respectively. (Probe fhSPECT scans were not performed for four basins.) It exceeded the number excised under non-imaging probe guidance for seven of nine basins and equaled the number excised for the other two basins.ConclusionsFreehand SPECT using a prototype SiPM-based gamma camera demonstrates high sensitivity for detection of SLNs in a preoperative setting. Camera fhSPECT is a potential means for efficiently obtaining real-time 3D activity distribution maps in applications such as image-guided percutaneous biopsy, and surgical SLN biopsy or radioguided tumor excision.

Sentinel Lymph Node Biopsy Using Preoperative Computed Tomographic Lymphography and Intraoperative Indocyanine Green Fluorescence Imaging in Patients With Localized Tongue Cancer

The indocyanine green method alone is unsuitable for sentinel lymph node biopsy in patients with oral cancer because of poor transcutaneous identification of the fluorescent signal through the platysma and sternocleidomastoid muscles. To assess the utility of a novel sentinel lymph node biopsy technique using preoperative computed tomographic (CT) lymphography followed by the intraoperative indocyanine green fluorescence method. In this prospective study performed at Akita University Hospital, Akita, Japan, participants comprised 18 patients with previously untreated cN0 tongue cancer (squamous cell carcinoma) were enrolled from November 2012 to November 2016. Median observer period was 38 (range, 14-62) months. Analysis was completed between January 10 and March 10, 2018. For preoperative sentinel lymph node mapping, CT lymphography was performed the day before sentinel lymph node biopsy. For sentinel lymph node biopsy, a minimum skin incision was made according to the predetermined location of sentinel lymph nodes. Sentinel lymph nodes were excised under indocyanine green fluorescence guidance. Identification rate of preoperative sentinel lymph node mapping by CT lymphography and the number of sentinel lymph node successfully identified by the intraoperative indocyanine green fluorescence method. Among 18 patients (8 men, 10 women; median age, 65.5 [range, 40-83] years), sentinel lymph nodes could be mapped by preoperative CT lymphography in 16 patients (89%). At least 1 sentinel lymph node was successfully identified and excised in each of these 16 patients using intraoperative indocyanine green fluorescence. Among the 16 patients in whom sentinel lymph nodes were excised, metastases to sentinel lymph nodes were found in 5 patients (31%). The novel sentinel lymph node biopsy technique of preoperative CT lymphography mapping with intraoperative indocyanine green fluorescence has a high potential for identifying sentinel lymph nodes in patients with cN0 tongue cancer. Because the intraoperative indocyanine green method alone cannot identify sentinel lymph nodes in the neck region, this combined method has clinical potential as a sentinel lymph node biopsy technique that does not require radioisotopes.

Apport de la TEMP/TDM pour la détection du ganglion sentinelle dans les cancers du col utérin et de l’endomètre

The sentinel lymph node procedure is still under evaluation for the management of cervical and endometrial carcinomas. The aim of our study was to determine the diagnostic accuracy of single-photon emission computed tomography/computed tomography (SPECT/CT) for preoperative sentinel lymph node mapping in uterine cancers. Sixty-eight patients with cervical (n=42) or endometrial carcinoma (n=26) underwent preoperative lymphoscintigraphy for sentinel node mapping. Sentinel node detection rate with conventional planar imaging was similar to that of SPECT/CT (87.1 versus 91.8 %) in the whole cohort. However, SPECT/CT detected a higher number of sentinel nodes in more than one third of patients, affected by either cervical or endometrial carcinoma. The rate of non or insufficiently contributive procedures (lack of uptake or unilateral uptake) in endometrial carcinomas was 47 % with conventional planar imaging, and 30 % with SPECT/CT. Sensitivity of both procedures for the detection of metastatic nodes was 81.8 %, compared to 100 % for the intraoperative combined detection (gamma probe sonde and blue dye). The impact of SPECT/CT for the sentinel lymph node detection in cervical and endometrial carcinomas needs further evaluation. Nevertheless, SPECT/CT may provide additional information when conventional planar imaging detects only unilateral uptake, may improve identification of atypical localizations, and facilitate surgical approach.

Preoperative sentinel lymph node mapping of the prostate using PET/CT fusion imaging and Ga-68-labeled tilmanocept in an animal model

Sentinel lymph node (SLN) identification with preoperative image guidance may improve pathological staging of prostate cancer by identifying nodes outside the standard template of dissection. Four anesthetized male dogs received an intra-prostatic injection of Ga-68-labeled tilmanocept. Every 20 min the pelvic lymph nodes were imaged using PET/CT fusion imaging. At 90 min post-injection a prostatectomy and extended lymphadenectomy were completed; ex vivo radioactivity was recorded for each node using a handheld gamma detector, and confirmed by calculation of percent-of-injected dose (%ID) via assay of Ga-68 radioactivity. SLNs were defined as containing >10 % of the maximum %ID. Preoperative PET/CT fusion imaging identified a mean of 4.25 lymph nodes per animal (range 3-7); the mean number of SLN per animal was 4.00 (range 2-6).Of the excised SLNs, 29 % were located in the standard external iliac and obturator distribution. The SLN %ID ranged from 0.07 to 2.40 % (mean 0.744 % ± 0.641 %); SLN ex vivo count rate ranged from 88 to 2,175 cpm (mean 896 ± 715 cpm); and the SLN standardize uptake values (SUVs) ranged from 13 to 237 (mean 79 ± 67).There was a high concordance of PET-CT imaging to SLN activity, with sensitivity of 93 %. In this feasibility study, pelvic SLNs attained SUVs within 60 min. PET/CT effectively identified SLNs with good anatomic specificity, and radioactivity by hand-held detection and scintillation counts demonstrated high concordance with preoperative imaging. Gallium-68-labaled tilmanocept was highly specific for sentinel nodes. Image-guided tumor resection and lymphadenectomy may become a promising future application in urologic oncology and warrants further investigation.

CT-SPECT and pre-operative sentinel lymph node mapping in breast cancer

Introduction: Pre-operative lymphoscintigraphy (LS) is widely used for mapping prior to sentinel lymph node biopsy (SLNB) in breast cancer. Combined CT/ single-photon emission computed CT (CT-SPECT), has been reported as superior, by improving visualisation and anatomical localisation. Previous studies have investigated use of CT-SPECT in selected groups, or after failed LS. In June 2010 pre-operative CT-SPECT replaced LS in our institution. This study assesses routine, unselected use of CT-SPECT prior to SLNB, and compares it to LS.

Sentinel lymph node detection in patients with vulvar carcinoma; Feasibility of intra-operative mapping with technetium-99m-labeled nanocolloid

Aims Sentinel lymph node (SLN) mapping appears to be feasible in patients with primary vulvar cancer. Previous protocols describe the injection of the technetium-99m-nanocolloid at least 3 h before surgery which involves two invasive procedures for the patient. In this study, we assessed the feasibility, safety, and accuracy of an intra-operative rather than preoperative SLN mapping in patients with primary vulvar cancer. Methods Patients with histologically confirmed squamous cell vulvar cancer and clinically FIGO stage Ib disease underwent intra-operative SLN mapping by intradermal injection of the nanocolloid around the tumor. SLN were identified and removed before a complete inguinofemoral lymphnode dissection was performed. Surgical and pathologic data on all patients were prospectively entered into a database. Results An SLN procedure was performed in 16 patients; 3 patients received unilateral lymphadenectomy, and 13 women underwent surgery on both groins. In all groins but 4 at least one SLN was clearly identified (detection rate 25/29, 86%). A median number of 2 SLN and 4 non-SLN per groin were removed. 3 of 16 patients (19%) had metastatic disease in the lymph nodes. There was no false negative SLN result. Conclusion Intra-operative SLN detection seems feasible in patients with early stage vulvar cancer. More patients need to be enrolled in this ongoing study before this more convenient technique can be considered safe.