Feasibility of radioguided occult lesion localization of clip-marked lymph nodes for tailored axillary treatment in breast cancer patients treated with neoadjuvant systemic therapy.

BACKGROUND: Selective removal of initially tumor-positive axillary lymph nodes in breast cancer patients who underwent neoadjuvant systemic treatment (NST) improves the accuracy of nodal staging and provides the opportunity for more tailored axillary treatment. This study evaluated whether radioguided occult lesion localization (ROLL) of clip-marked lymph nodes is feasible in clinical practice. METHODS: Prior to NST, a clip marker was placed inside a proven tumor-positive lymph node in all breast cancer patients (cTis-4N1-3 M0). After NST, technetium-99m-labeled macroaggregated albumin was injected in the clip-marked lymph nodes. The next day, these ROLL-marked nodes were selectively removed at surgery to evaluate the pathological response of the axilla. RESULTS: Thirty-seven patients (38 axillae) underwent clip insertion. After NST, the clip was visible by ultrasound in 36 procedures (95%). In the other two patients, the ROLL-node injection was performed in a sonographically suspicious unclipped node (1), and near the clip under computed tomography guidance (1). Initial surgery successfully identified the ROLL-marked node with clip in 33 procedures (87%). Removed specimens in the other five procedures contained only the sonographically suspicious tumor-positive unclipped node (1), a node with signs of complete response but no clip (2), a clip without node (1), and tissue without node nor clip, and a second successful ROLL-node procedure was performed (1). Overall, 10 ROLL-marked nodes had no residual disease. CONCLUSIONS: This study demonstrates that the ROLL procedure to identify clip-marked lymph nodes is feasible. This facilitates selective removal at surgery and may tailor axillary treatment in patients treated with NST.

Predictive risk factors for sentinel lymph node nonvisualization on planar lymphoscintigraphy using an intratumoral injection in patients with primary breast cancer.

OBJECTIVES: Lymphoscintigraphy is considered a useful tool to optimize sentinel lymph node (SLN) identification. Nonvisualization of the SLN is associated with a lower SLN identification rate. The aim of this study was to identify preoperative factors associated with SLN nonvisualization on lymphoscintigraphy. PATIENTS AND METHODS: A total of 2050 consecutive SLN procedures were evaluated from clinically node-negative breast cancer patients. Planar lymphoscintigraphy was performed at 3 h after an intratumoral injection of technetium-99m-nanocolloid. This technique was used for extra-axillary SLN identification. Patient, tumor, and treatment characteristics were analyzed for association with SLN nonvisualization. Factors with a P-value less than 0.1 in univariate analysis were included in a multivariate logistic regression model. RESULTS: The SLN visualization rate was 86.7%. In multivariate logistic regression, age of at least 70 years [odds ratio (OR): 3.24; 95% confidence interval (CI): 2.14-4.91)], BMI of at least 30 (OR: 1.93; 95% CI: 1.39-2.69), T3/T4-tumors (OR: 2.70; 95% CI: 1.37-5.32), medially/centrally located tumors (OR: 1.52; 95% CI: 1.17-1.99), previous mantle field radiation (OR: 4.04; 95% CI: 1.74-9.35), nonpalpable tumors (OR: 1.88; 95% CI: 1.36-2.60), and presence of iodine seeds (OR: 1.35; 95% CI: 1.02-1.78) were associated significantly with nonvisualization on lymphoscintigraphy. Nonvisualization was the strongest independent predictor of unsuccessful intraoperative SLN identification (P<0.001). Overall, the SLN identification rate was 97.7% because of the use of additional imaging and blue dye. CONCLUSION: This study reports new tumor and treatment-related risk factors for nonvisualization on lymphoscintigraphy by using an intratumoral injection in primary breast cancer. We recommend a periareolar subcutaneous injection to improve SLN visualization in patients with limited prognostic and therapeutic relevance of internal mammary chain SLN identification.

Sentinel lymph node nonvisualization after intratumoral radioisotope tracer injection in breast cancer is not associated with a higher nodal metastasis rate or worse outcomes.

BACKGROUND AND OBJECTIVES: Preoperative lymphoscintigraphy does not always visualize a sentinel lymph node (SLN). The study aim was to investigate whether persistent nonvisualization after additional single-photon emission computed tomography (SPECT)/CT or a second radiotracer injection in breast cancer patients is associated with nodal metastases or worse outcome due to potential understaging and consequently undertreatment. METHODS: Altogether 2042 consecutive SLN procedures were evaluated. All patients were clinically node-negative, underwent axillary ultrasound and fine-needle aspiration cytology (US/FNAC) of suspicious nodes. Lymphoscintigraphy was performed at 3 to 4 hours after intratumoral injection of 99mTc-nanocolloid. SPECT/CT or a reinjection was performed when initial lymphoscintigraphy showed nonvisualization. RESULTS: Persistent nonvisualization was seen in 170 of 2042 procedures (8.3%). The nodal metastasis rate was 16.0% vs 18.0% for procedures with nonvisualization vs SLN visualization, respectively (P = 0.593). The regional recurrence rate of tumor-negative SLN biopsy procedures was equal between the visualization (0.7%, 11 of 1535) vs nonvisualization (0.7%, 1 of 144) group. Median follow-up was 48 months. Distant-metastasis free interval and overall survival was not significantly different between both groups ( P = 0.164 and 0.208, respectively). CONCLUSIONS: Persistent nonvisualization after lymphoscintigraphy plus SPECT/CT or radiotracer reinjection is not associated with a higher nodal metastasis rate or worse long term outcome when preoperative US/FNAC is performed.

Hybrid Surgical Guidance: Does Hardware Integration of γ- and Fluorescence Imaging Modalities Make Sense?

The clinically applied hybrid tracer indocyanine green-99mTc-nanocolloid enables combined radio- and fluorescence image guidance during sentinel node (SN) biopsy procedures. To provide optimal surgical guidance, this tracer requires the presence of both γ- and fluorescence modalities in the operating room. We reasoned that the combination or integration of these modalities could further evolve the hybrid surgical guidance concept. To study this potential, we clinically applied 2 setups that included the combination of γ-detection modalities and an open surgery fluorescence camera. Methods: To attach the fluorescence camera (VITOM) to either a γ-ray detection probe (GP; VITOM-GP) or a portable γ-camera (GC; Vitom GC), clip-on brackets were designed and printed in 3-dimensional sterilizable RC31. Both combined modalities were evaluated in, respectively, 5 and 6 patients with penile cancer during an SN biopsy procedure using indocyanine green-99mTc-nanocolloid. Intraoperatively, radio- and fluorescence-guided SN detection rates were scored at working distances of 0, 10, 20, and 30 cm for both combinations. Results: Using the VITOM-GP combination, we evaluated 9 SNs. γ-tracing rates were shown to be 100%, 88.9%, 55.6%, and 55.6% at a respective working distance of 0, 10, 20, and 30 cm. Detection rates for the fluorescence imaging-based detection were found to be 100%, 77.8%, and 77.8%, at respective working distances of 10, 20, and 30 cm. When the VITOM-GC setup was used, all 10 intraoperatively evaluated SNs could be visualized with the γ-camera independent of the working distance. Fluorescence detection rates were 90%, 80%, and 80% at 10-, 20-, and 30-cm working distances. The integrated detection modalities were shown to work synergistically; overall the, GC was most valuable for rough localization (10- to 30-cm range) of the SNs, the GP for providing convenient real-time acoustic feedback, whereas fluorescence guidance allowed detailed real-time SN visualization. Conclusion: Our findings suggest that full integration of a fluorescence camera with γ-detector (GP or GC) can be of value when a hybrid, radioactive and fluorescent tracer is used.

A New Portable Hybrid Camera for Fused Optical and Scintigraphic Imaging: First Clinical Experiences.

PURPOSE: Although portable gamma cameras (PGCs) have been helpful to depict sentinel nodes (SNs), sometimes nuclear physicians or surgeons have difficulties to interpret PGC images because of the lack of anatomical information. The aim of the present study was to develop and clinically test the prototype of a new portable hybrid camera (PHC), which adds optical to γ-imaging. METHODS: In 2 hospitals, the existing PGC (Sentinella S102; Oncovision) was upgraded with an optical module (BB2-08S2C-25; Point Grey Research) to build a PHC. Preoperative PHC overview images (positioned at 15 cm distance) and close-up image (position at <5 cm distance) were obtained from 25 patients (12 melanoma, 2 oral cavity, and 11 breast cancer) after conventional lymphoscintigraphy. Errors in the optical image coregistration were evaluated with a 5-mm accuracy for each patient. RESULTS: Conventional lymphoscintigraphy and the close-up PHC images depicted 55 SNs in total. In the PHC overview images, the optical module offered fused optical and γ-imaging indicating the image field of view and anatomical SN locations. Average optical image coregistration errors were 1.0 cm (range, 0-2.0 cm). CONCLUSIONS: Fused optical and γ-imaging with the prototype PHC is technically feasible and helpful for the image interpretation. The optical image visualizes the γ-image field of view, enabling SN localization in an anatomical context in a preoperative setting; however, for the operating room, the use of its optical component needs to be additionally adjusted.

Detecting near-the-injection-site sentinel nodes in head and neck melanomas with a high-resolution portable gamma camera.

BACKGROUND: In head/neck melanomas, near-the-injection-site sentinel nodes (NIS-SNs) may be missed on planar lymphoscintigraphy and/or SPECT/CT. The aim of the present study is to establish the performance of a portable gamma camera (PGC) to detect NIS-SNs in a simulation phantom set-up, and subsequently in head/neck melanoma patients scheduled for a SN procedure. METHODS: Five plastic Eppendorf tubes filled with technetium-99m-albumin nanocolloid were used to simulate 4 radiotracer deposit sites, as traditionally injected in melanoma patients, and 1 NIS-SN. A PGC was used with 2 pinhole collimators (2.5 and 4.0 mm). Image acquisition time was 1 minute with the camera positioned at various distances (range 1.5-15.5 cm). Results were compared with conventional lymphoscintigraphy and SPECT/CT acquired with a dual-head gamma camera as well with a gamma probe. Additionally, the same PGC setting was used in a case series of 3 patients with head/neck melanomas. RESULTS: The simulated NIS-SN was differentiated from the injection site at a distance of 3 mm with the 2.5-mm pinhole and at 5 mm with the 4-mm pinhole when the PGC was positioned at 1.5 cm distance. Planar lymphoscintigraphy, SPECT/CT, and the gamma probe depicted the NIS-SN separated from the injection site at distances of 7, 10, and 22 mm, respectively. In all 3 patients, 6 NIS-SNs were depicted with the PGC. CONCLUSION: A high-resolution PGC, positioned close to the skin, is able to detect SNs at distances of at least 3 mm from the injection site. A further clinical evaluation of this device to establish its added value in reducing false-negative procedures and potential recurrences is necessary.

Feasibility of preoperative (125)I seed-guided tumoural tracer injection using freehand SPECT for sentinel lymph node mapping in non-palpable breast cancer.

BACKGROUND: This study was designed to explore the feasibility of replacing the conventional peri-/intratumoural ultrasound (US)-guided technetium-99m albumin nanocolloid ((99m)Tc-nanocolloid) administration by an injection of the same tracer guided by a freehand single-photon emission computed tomography (SPECT) device in patients with non-palpable breast cancer with an iodine-125 ((125)I) seed as tumour marker, who are scheduled for a sentinel lymph node biopsy (SLNB). This approach aimed to decrease the workload of the radiology department, avoiding a second US-guided procedure. METHODS: In ten patients, the implanted (125)I seed was primarily localised using freehand SPECT and subsequently verified by conventional US in order to inject the (99m)Tc-nanocolloid. The following 34 patients were injected using only freehand SPECT localisation. In these patients, additional SPECT/CT was acquired to measure the distance between the (99m)Tc-nanocolloid injection depot and the (125)I seed. In retrospect, a group of 21 patients with US-guided (99m)Tc-nanocolloid administrations was included as a control group. RESULTS: The depth difference measured by US and freehand SPECT in ten patients was 1.6 ± 1.6 mm. In the following 36 (125)I seeds (34 patients), the average difference between the (125)I seed and the centre of the (99m)Tc-nanocolloid injection depot was 10.9 ± 6.8 mm. In the retrospective study, the average distance between the (125)I seed and the centre of the (99m)Tc-nanocolloid injection depot as measured in SPECT/CT was 9.7 ± 6.5 mm and was not significantly different compared to the freehand SPECT-guided group (two-sample Student's t test, p = 0.52). CONCLUSION: We conclude that using freehand SPECT for (99m)Tc-nanocolloid administration in patients with non-palpable breast cancer with previously implanted (125)I seed is feasible. This technique may improve daily clinical logistics, reducing the workload of the radiology department.