UvA-DARE (Digital Academic Repository)

Transcription

1 UvADARE (Digital Academic Repository) In search of the sentinel node : validation and sophistication of lymphatic mapping and sentinel node biopsy in breast cancer and melanoma van der Ploeg, I.M.C. Link to publication Citation for published version (APA): van der Ploeg, I. M. C. (2009). In search of the sentinel node : validation and sophistication of lymphatic mapping and sentinel node biopsy in breast cancer and melanoma Amsterdam: Nederlands Kanker Instituut Antoni Van Leeuwenhoekziekenhuis General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulations If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. UvADARE is a service provided by the library of the University of Amsterdam ( Download date: 10 Jul 2018

2 CHAPTER 12 The additional value of SPECT/CT in lymphatic mapping in breast cancer and melanoma Van der Ploeg IMC, Nieweg OE, Valdés Olmos RA, Rutgers EJTh, Kroon BBR, Hoefnagel CA J Nucl Med, 2007; 48: SPECTCT 143

3 Abstract Introduction: The recent introduction of SPECT/CT integrates physiological data of SPECT with anatomical data of CT into one image. The purpose of this pilot study was to explore the additional value of SPECT/CT in breast cancer and melanoma patients with inconclusive conventional images. Methods: Thirtyone patients had conventional lymphoscintigrams with unexpected lymphatic drainage, six lymphoscintigrams were difficult to interpret, and three patients had no visualization on conventional imaging. SPECT/CT was performed immediately after delayed conventional imaging. Results: SPECT/CT showed six additional sentinel nodes in four patients, of which two were tumourpositive and led to upstaging and tailored management in 5% of patients. SPECT/CT depicted sentinel nodes in three patients with nonvisualization on delayed conventional imaging. Conclusion: SPECT/CT was of additional value in finding the exact anatomic location of sentinel nodes in patients with inconclusive conventional images. SPECT/CT also detects additional sentinel nodes and sentinel nodes in patients with nonvisualization. 144 SPECTCT

4 Introduction Conventional lymphoscintigraphy visualizes the sentinel node(s) in the great majority of patients with breast cancer or melanoma. In some patients the precise location of a sentinel node may be difficult to determine due to an unexpected lymphatic drainage pattern. 1 Singlephoton emission computed tomography (SPECT) might overcome some of these limitations due to better contrast and resolution. Despite these improvements, SPECT images lack the anatomical detail that is necessary to create a meaningful surgical roadmap. Several investigators have fused SPECT images with separately acquired CT images to address this issue. 1,2 The fusion of independently performed SPECT and CT has proved to be complicated due to the need for special computer software with external and internal landmarks. Different patient positioning and movement of internal organs may also cause errors in the alignment of the two studies. Recently, a hybrid imaging method has been introduced consisting of both a SPECT camera and a CT scanner in one device. The patient s position does not need to be changed and fusion of the two images into one is easier. 1,2 Furthermore, the correction for attenuation and scatter led to improved sentinel node visualization on SPECT. A number of authors have reported successful introduction of the SPECT/CT technique in lymphatic mapping in several clinical situations. 312 The purpose of this study was to explore the additional value of SPECT/CT in breast cancer and melanoma patients with inconclusive conventional images. Indications 1. Unusual lymphatic drainage patterns 2. Lymphatic patterns that are difficult to interpret Including cases of Extraaxillary drainage in breast cancer patients Drainage to more than one lymph node basin Drainage not to the nearest lymph node basin Sentinel lymph node that close to the injection site Deeply located sentinel nodes 3. Nonvisualization No lymphatic drainage at late conventional images, not even after massage of tumour injection site Table 1. Indications on conventional lymphoscintigraphy for additional SPECT/CT. Patients and methods At the Netherlands Cancer Institute, lymphoscintigraphy is an integral element of lymphatic mapping. Forty patients underwent subsequent SPECT/CT after delayed conventional imaging. The group consisted of thirtyone women with breast cancer, and seven men and two women with melanoma. Five melanomas were located Chapter 12 SPECT/CT 145

5 on the trunk and four in the head and neck region. The mean age was 55 years. The indications for performing additional SPECT/CT images were conventional lymphoscintigrams with an unusual lymphatic drainage pattern, conventional images that were difficult to interpret or conventional lymphoscintigrams with nonvisualization (table 1). The first indication was present in two melanoma patients and 29 breast cancer patients. The second was present in six melanoma patients. The last indication concerned one melanoma patient and two breast cancer patients. A dosage of 80 MBq Technetium99nanocolloid (Nanocoll, GE Healthcare, Eindhoven, the Netherlands) for melanoma and a dosage of 120MBq Technetium 99nanocolloid for breast cancer patients was injected immediately before lymphoscintigraphy. In patients with breast cancer, the tracer was injected into the tumour. The conventional images were performed ten minutes, two hours and four hours after radiotracer injection. In patients with melanoma, the radiopharmaceutical was injected intracutaneously in four equal depots around the primary tumour or biopsy site. Static images were performed at fifteen minutes and two hours and were preceded by a dynamic study of ten minutes. A dualhead gamma camera equipped with lowenergy highresolution collimators (Vertex, Philips, Eindhoven, the Netherlands) was used. Both anterior and lateral images were routinely made, additional images were obtained if needed. The lateral images in breast cancer patients were made in the prone position with the hanging breast technique. A Cobalt57 flood source was placed behind the patient to outline the body contour. The location of a sentinel node was marked on the skin with indelible ink. SPECT/CT images were made immediately after the delayed conventional images. The SPECT/CT system (Symbia T, Siemens, Erlangen, Germany) consisted of a dualhead variableangle gamma camera equipped with lowenergy highresolution collimators and a multislice spiral CT optimized for rapid rotation. SPECT acquisition (matrix 128x128, 60 frames à 25sec/frame) was performed using sixdegreeangle steps in a twentysecond time frame. For CT (130 KV, 17 mas, B60s kernel), five millimetre slices were obtained. After reconstruction, SPECT images were corrected for attenuation and scatter. Both SPECT and CT axial five millimetre slices were generated using an Esoft 2000 application package (Siemens, Erlangen, Germany). These were transferred to picture archiving and communication systems (PACS) after generation of Dicom files. Fusion of images was performed using an Osirix Dicom viewer (version 2.7) in a Unixbased operating system (MAC OS X, Power G5, Apple Inc., Cupertino, CA, U.S.A.). Two nuclear medicine physicians evaluated the images. The SPECT/CT images were also analyzed using 2D orthogonal reslicing in axial, sagittal and coronal orientation. Maximum intensity projections (MIP) 3D display was generated to localize sentinel nodes in relation to anatomic structures. The number and location of the sentinel node(s) were determined and described after the conventional lymphoscintigraphic images as well as after the SPECT/CT images. The next day, 1 ml of patent blue dye (Laboratoire Guerbet, AulnaySousBois, France) was injected at the tumour site, immediately before the operation. The dye and 146 SPECT/CT Chapter 12

6 a gammaray detection probe (Neoprobe, Johnson & Johnson Medical, Hamburg, Germany) were used to identify the sentinel node(s). A sentinel node was defined as a lymph node upon which the primary tumour drains directly. All harvested sentinel nodes were examined by the pathologist using stepsectioning, and both haematoxylineosin and immunohistochemistry staining. Location SNs on SPECT/CT Axilla N SNs per location (49%) N SNs only on SPECT/CT Breast cancer patients 2* Additional value SPECT/CT More precise location, but not always decisive for Internal mammary chain (35%) 1 Precise intercostal localization all SNs, decisive for Supraclavicular region (4%) Infraclavicular region (8%) Interpectoral region (4%) TOTAL 75 (100%) 3 Axilla 9 (33%) Melanoma patients 2 More precise location, but not always decisive for Supraclavicular region 6 (22%) Scapular region 4 (15%) 1* Neck region 4 (15%) Occipital region 1 (4%) Auricular region 3 (11%) TOTAL 27 (100%) 3 Table 2. Sentinel lymph node characteristics. SN(s)= sentinel node(s), * one axillary and one scapular sentinel node, only visible on SPECT/CT, were tumourpositive Chapter 12 SPECT/CT 147

7 Results The exact anatomic location of the sentinel node that prompted the SPECT/CT was better visualized with this technique compared to conventional lymphoscintigraphic imaging in all patients (table 2, figures 14). This was found valuable by the operating surgeons and specified in almost all cases. In the majority of breast cancer patients, SPECT/CT specified the location of internal mammary chain nodes, for example the exact intercostal space or a position underneath a rib (figure 1). An example of the additional value of SPECT/CT in a melanoma patient is shown in figure 2. Conventional images suggested a sentinel node on either side of the neck and suggest these to be dorsally. SPECT/CT revealed that each node was in fact located in the supraclavicular region, which changed. Figure 1. Conventional lymphoscintigraphy of a woman with right breast cancer (A) depicts one internal mammary chain sentinel node (ascending arrow) with a secondechelon node (descending arrow). Axial fused SPECTCT (B) and 3D SPECT/CT Maximum Intensity Projection of the thorax (C) enable tracing of the sentinel node (arrow), displayed using colourwash, underneath the rib at the second intercostal space close to the right border of the sternum. In another woman with left breast cancer, axial SPECT/CT fused image (D) visualizes an interpectoral sentinel node (arrow). 148 SPECT/CT Chapter 12

8 Figure 2. A man with a melanoma medially from the left scapula. Conventional anterior imaging and a lateral lymphoscintigram from the left (A+B) visualize a sentinel node on either side of the neck (ascending arrows) and suggest these to be dorsally. A third sentinel node is depicted cranial from the primary tumour site (descending arrows). SPECT/CT (C) shows the first two nodes (ascending arrows) to be in fact located in the supraclavicular region on each side. This finding prompted the surgeon to place the patient on the operating table in the supine position rather than the prone position. The exact anatomical location of the third sentinel node (arrow) is shown on the right SPECT/CT image (D). Conventional imaging visualized 96 sentinel nodes in 37 of the 40 patients (mean 2.6, range 15). SPECT/CT showed these same nodes plus six additional nodes (mean 2.6, range 06) in four patients (10%), two with melanoma and two with breast cancer. Three of these patients (8%) did not have lymphatic drainage on conventional lymphoscintigrams, not even after massaging of the injection site with delayed imaging and an additional dose of the radiopharmaceutical. Five of the six extravisualized sentinel nodes were found intraoperatively. Two of the five harvested sentinel nodes only visualized by SPECT/CT were the only tumourpositive nodes excised in two patients (5%), which led to different disease stage and a change in management. Chapter 12 SPECT/CT 149

9 Figure 3. A woman with right breast cancer. Conventional lymphoscintigraphy (A+C) shows no evident (axillary) drainage on both the anterior or lateral images. Axial SPECT/CT fused image (B) shows one axillary sentinel node (arrow). Note that on 3D fused SPECT/CT Maximum Intensity Projection of the thorax (D) also one internal mammary sentinel dose (ascending arrow) is displayed just below the fourth rib. Figure 4. A man with a melanoma at the left scapular region. Anterior (A) conventional imaging depicts sentinel nodes at the left supraclavicular (descending arrow) and axillary (descending arrow) regions. Lateral conventional imaging (B) also shows a sentinel node (descending arrow) located in the left scapular area. On axial SPECT/CT fused images (C) not only the left scapular sentinel node (descending arrow) is visualized but also another sentinel node (lower horizontal arrow) and second echelon node (upper horizontal arrow) at the right scapular region. The right scapular sentinel node was not visualized on conventional images. 150 SPECT/CT Chapter 12

10 Discussion Conventional lymphoscintigraphy is necessary in tracing the direct lymphatic pathway from a primary tumour site to the sentinel lymph node. The combination of dynamic and static conventional images at several time intervals after radiotracer injection makes this possible. Conventional lymphoscintigraphic imaging identifies sentinel nodes in more than 98% of melanoma patients and in more than 95% of breast cancer patients. 13,14 The concept of a single device performing both functional and anatomical imaging eventually led to the development of hybrid SPECT/CT imaging systems. 15,16 Keidar et al. described the technical aspects of SPECT/CT in Although conventional lymphoscintigraphy shows the lymphatic pathway and the sentinel node in most cases, subsequent SPECT/CT better specifies the anatomical location of the node. The current study shows the additional value of SPECT/CT in determining the exact anatomic location of sentinel nodes in patients with breast cancer or melanoma. SPECT/CT remarkably specified the location of internal mammary chain and other nonaxillary sentinel nodes in breast cancer patients. These nodes are typically small and often accumulate little radioactivity. It may be impossible to locate such a node with a gammaray detection probe through the intact skin, making the location of the incision somewhat of a gamble. We feel that these nodes are important as their tumourstatus prompts us to modify the subsequent management in 29% of patients with an internal mammarychain sentinel node and in 18% of patients with sentinel nodes in other unusual locations. 17,18 In melanoma patients, SPECT/CT is especially helpful in localizing sentinel nodes draining from primary tumours high on the trunk and in the head and neck area. In four patients in our study (10%), six additional sentinel nodes were detected by SPECT/CT, of which two were tumourpositive. The results of our pilot study are similar to what was found by other investigators. A review of the literature revealed the use of SPECT/CT in 732 patients with melanoma, breast cancer, head and neck malignancies and urological cancers. 312,19 The traced articles mention rates of sentinel nodes only found on SPECT/CT and not detected with conventional imaging ranging from 10% 30%. 3,69 In one of these studies however, sentinel nodes were detected by conventional lymphoscintigraphic imaging but missed on SPECT/CT in 1% of the included patients. 9 Some articles mention sentinel nodes missed by both conventional lymphoscintigraphy and SPECT/ CT ranging from 3% to 31% of the patients. 3,9,10 Two reports describe percentages of metastatic sentinel nodes detected by SPECT/CT only. In melanoma this was the case in 3% of all studied patients, while in a report focusing on bladder cancer this percentage was 83%. 3,11 Other investigators describe the incidence of patients with initially missed metastatic nodes detected only by SPECT/CT ranging between 0% 5%. 6,8,9 One study focused on overweight breast cancer patients and reported that SPECT/CT detected significantly more sentinel nodes than conventional imaging (91% Chapter 12 SPECT/CT 151

11 vs. 78%) in this patient group. 19 Several studies demonstrated improved anatomical localization of sentinel nodes by SPECT/CT in 98%100% of the examined patients. 3,11,12 A study performed in 157 breast cancer patients specified the additional sites of lymphatic drainage only detected by SPECT/CT in the following regions: axilla (n=23), internal mammary chain (n=5), within the breast (n=2) and in the interpectoral fossa (n=3). 9 Using a hybrid SPECT/ CT, an intraoperative detection rate of sentinel nodes has been reported as high as 100%. 5,11 One study showed the detection rate with only the blue dye method to be 85%, while this was 100% when both conventional and SPECT/CT images were obtained. 5 The majority of investigators who used SPECT/CT as an additional imaging tool in lymphatic mapping did not formulate their indications. We limited the use of SPECT/CT to difficult and unusual cases, because we believe conventional lymphoscintigraphy is an excellent preoperative mapping technique for most patients. Based on our experience in the first twenty patients, we added nonvisualization as a new indication, because SPECT/CT visualized drainage in patients whose conventional images did not reveal a sentinel node. Besides that, we feel that the added costs and extra time related to SPECT/CT is more justified when used on indication. SPECT/CT was useful in finding the exact anatomical location of sentinel nodes and in detecting additional sites of drainage. This facilitates surgical exploration and eventually leads to a more accurate staging. In the future, SPECT/CT may also obviate preoperative skin marking and could perhaps replace delayed lateral conventional imaging. Whether SPECT/CT should be used in all patients or only for specific indications needs to be studied further. Acknowledgements The authors thank Christel Feenstra and colleagues of the Department of Nuclear Medicine for their technical support in the image acquisition and reconstruction of SPECT/CT studies. MarieJeanne VrankcenPeeters and Hester Oldenburg operated most of the breast cancer patients mentioned in this pilot study and helped collecting the required data. 152 SPECT/CT Chapter 12

12 References 1. EvenSapir E. Sentinel node scintigraphic mapping using SPECT/CT. In: Israel O, Goldsmith S, eds. Hybrid SPECT/CT Imaging in Clinical practice. New York, The United States of America: Taylor and Fransic group;2006: Keidar Z, Israel O, Krausz Y. SPECT/CT in tumour imaging: technical aspects and clinical applications. Semin Nucl Med. 2003;33: Kretschmer L, Altenvoerde G, Meller J et al. Dynamic lymphoscintigraphy and image fusion of SPECT and pelvic CTscans allow mapping of aberrant pelvic sentinel lymph nodes in malignant melanoma. Eur J Cancer. 2003;39: Kim W, Menda Y, Willis J, Bartel T et al. Use of lymphoscintigraphy with SPECT/CT for sentinel node localization in a case of vaginal melanoma. Clin Nucl Med. 2006;31: Ishihara T, Kaguchi A, Matsushita S et al. Management of sentinel lymph nodes in malignant skin tumours using dynamic lymphoscintigraphy and the singlephotonemission computed tomography/computed tomography combined system. Int J Clin Oncol. 2006;11: Wagner A, Schicho K, Glaser C et al. SPECTCT for topographic mapping of sentinel lymph nodes prior to gamma probeguided biopsy in head and neck squamous cell carcinoma. J Craniomaxillofac Surg. 2004;32: EvenSapir E, Lerman H, Lievshitz G et al. Lymphoscintigraphy for sentinel node mapping using a hybrid SPECT/CT system. J Nucl Med. 2003;44: Khafif A, Schneebaum S, Fliss DM et al. Lymphoscintigraphy for sentinel node mapping using a hybrid single photon emission CT (SPECT)/CT system in oral cavity squamous cell carcinoma. Head Neck 2006;28: Lerman H, Metser U, Lievshitz G et al. Lymphoscintigraphic sentinel node identification in patients with breast cancer: the role of SPECTCT. Eur J Nucl Med Mol Imaging 2006;33: Kizu H, Takayama T, Fukuda M et al. Fusion of SPECT and multidetector CT images for accurate localization of pelvic senti nel lymph nodes in prostate cancer patients. J Nucl Med Technol. 2005;33: Sherif A, Garske U, de la Torre M et al. Hybrid SPECTCT: an additional technique for sentinel node detection of patients with invasive bladder cancer. Eur Urol. 2006; 50: Schillaci O, Danieli R, Manni C et al. Is SPECT/CT with a hybrid camera useful to improve scintigraphic imaging interpretation? Nucl Med Commun. 2004;25: Morton DL, Wen DR, Wong JH et al. Technical details of intraoperative lymphatic mapping for early stage melanoma. Arch Surg. 1992;127: Nieweg OE, Jansen L, Valdés Olmos RA et al. Lymphatic mapping and sentinel lymph node biopsy in breast cancer. Eur J Nucl Med. 1999;26: Hasegawa BH, Stebler B, Rutt BK et al. A prototype highpurity germanium detector system with fast photoncounting circuitry for medical imaging. Med Phys. 1991;18: Lang TF, Hasegawa BH Liew SH et al. Description of a prototype emissiontransmission computed tomography imaging system. J Nucl Med. 1992; 33: Estourgie SH, Tanis PJ, Nieweg OE et al. Should the hunt for internal mammary chain sentinel nodes begin? An evaluation of 150 breast cancer patients. Ann Surg Oncol. 2003;10: Van Rijk MC, Tanis PJ, Nieweg OE et al. Clinical implications of sentinel nodes outside the axilla and internal mammary chain in patients with breast cancer. J Surg Oncol. 2006;94: Lerman H, Lievshitz G, Zak O et al. Improved sentinel node identification by SPECT/CT in overweight patients with breast cancer. J Nucl Med. 2007;48:2016. Chapter 12 SPECT/CT 153