Contribución de la medicina nuclear en la cirugía de precisión en el cáncer de mama / Nuclear medicine contribution to precision surgery in breast cancer

La medicina nuclear ha contribuido significativamente en la cirugía de precisión en el cáncer de mama en las últimas décadas. La cirugía radioguiada (CRG) ha permitido la biopsia del ganglio centinela (GC) en la evaluación de la infiltración ganglionar regional modificando el manejo de pacientes con cáncer de mama precoz. Para la axila, el procedimiento de la biopsia del GC ha significado un decremento de complicaciones y una mejor calidad de vida en comparación con la disección de los ganglios linfáticos axilares. Originalmente, la biopsia del GC se indicó principalmente en tumores cT1-2, sin evidencia de metástasis en los ganglios linfáticos axilares. Sin embargo, en los últimos años la biopsia del GC también se está ofreciendo a pacientes con tumores grandes o multifocales, carcinoma ductal in situ, recidiva del cáncer de mama ipsilateral y a pacientes que reciben tratamiento sistémico neoadyuvante (TSN) para cirugía conservadora de mama. Paralelamente a esta evolución, varias asociaciones científicas están tratando de homogeneizar cuestiones como la elección del radiotrazador, el lugar de inyección de la mama, la estandarización de las imágenes preoperatorias y el momento de la biopsia del GC en relación con el TSN, así como el manejo de las metástasis no axilares del GC (p. ej., cadena mamaria interna). Además, la CRG se usa actualmente para lograr la extirpación de tumores de mama primarios mediante inyección intralesional de radiocoloides o mediante implantación de semillas de yodo radiactivo que también se emplean para marcar los ganglios linfáticos axilares metastásicos. Este último procedimiento contribuye a manejar la axila con ganglios positivos en combinación con la PET/TC con [18F]FDG en un esfuerzo por adaptar el tratamiento sistémico y locorregional (AU)

Nuclear medicine has significantly contributed to precision surgery in breast cancer in the past decades. Radioguided surgery (RGS) has enabled sentinel node (SN) biopsy in assessing regional nodal involvement modifying the management of patients with early breast cancer. For the axilla the SN procedure has resulted in fewer complications and better quality of life when compared with axillary lymph node dissection. Originally, SN biopsy principally concerned cT1-2 tumors without evidence of axillary lymph node metastases. However, in last years SN biopsy is also being offered to patients with large or multifocal tumors, ductal carcinoma in situ, ipsilateral breast cancer relapse, and to patients receiving neoadjuvant systemic treatment (NST) for breast sparing surgery. Parallel to this evolution various scientific associations are trying to homogenise issues such as radiotracer choice, breast injection site, preoperative imaging standardisation and SN biopsy timing in relation to NST as well as management of non-axillary SN metastasis (e.g. internal mammary chain). Additionally, RGS is currently used to accomplish primary breast tumour excision either by intralesional radiocolloid injection or by radioactive iodine seed implantation which is also employed to target metastatic axillary lymph nodes. This latter procedure contributes to manage the node-positive axilla in combination with 18F-FDG PET/CT in an effort to tailor systemic and loco regional treatment (AU)

Aportación de la medicina nuclear intervencionista a la cirugía de precisión molecularmente dirigida / nterventional nuclear medicine's contribution to molecularly targeted precision surgery

El abordaje quirúrgico de las distintas enfermedades, no solo oncológicas, ha evolucionado. Como ha sido acuñado de forma muy gráfica por el grupo de Veronesi, estamos pasando de los «tratamientos máximos tolerables a los mínimos eficaces» y este recorrido no puede ser llevado a cabo de otra forma que mediante un planteamiento de trabajo multidisciplinar y multimodalidad. Obligatoriamente multidisciplinar porque es necesaria la colaboración entre cirujanos, oncólogos, radiólogos, médicos nucleares, patólogos y todo aquel relacionado con el seguimiento de los pacientes, y obligatoriamente multimodalidad porque nos debemos encaminar hacia una cirugía de precisión a la medida de cada paciente en la que, por parte de la Medicina Nuclear, tiene mucho que decir la imagen híbrida (SPECT/TC y PET/TC), los trazadores bimodales, el empleo de nuevos aliados como la ecografía o nuestra propia adaptación a la cirugía robótica. Todo un amplio abanico de posibilidades construido a partir de un sólido cimiento como es la gammagrafía preoperatoria, que posibilita la identificación de los tejidos diana y cuyo conocimiento previo a la intervención permite plantear el abordaje quirúrgico necesario para cada paciente (AU)

The surgical approach to different pathologies, not only oncological, has evolved. As Veronesi's group has coined very graphically, we are moving from “maximum tolerable treatments to minimum effective treatments” and this journey cannot be carried out in any other way than through a multidisciplinary and multimodality approach. Multidisciplinary, because collaboration between surgeons, oncologists, radiologists, nuclear physicians, pathologists, and all those involved in patient follow-up is necessary, and multimodality, because we must move towards precision surgery tailored to each patient in which, on the part of Nuclear Medicine, hybrid imaging (SPECT/CT and PET/CT), bimodal tracers, the use of new allies such as ultrasound or our own adaptation to robotic surgery have a great deal to say A wide range of possibilities is built on the solid foundation of preoperative scintigraphy, which makes it possible to identify the target tissues and whose knowledge prior to surgery allows the necessary surgical approach to be considered for each patient (AU)

Interventional nuclear medicine's contribution to molecularly targeted precision surgery.

The surgical approach to different pathologies, not only oncological, has evolved. As Veronesi's group has coined very graphically, we are moving from "maximum tolerable treatments to minimum effective treatments" and this journey cannot be carried out in any other way than through a multidisciplinary and multimodality approach. Multidisciplinary, because collaboration between surgeons, oncologists, radiologists, nuclear physicians, pathologists, and all those involved in patient follow-up is necessary, and multimodality, because we must move towards precision surgery tailored to each patient in which, on the part of Nuclear Medicine, hybrid imaging (SPECT/CT and PET/CT), bimodal tracers, the use of new allies such as ultrasound or our own adaptation to robotic surgery have a great deal to say. A wide range of possibilities is built on the solid foundation of preoperative scintigraphy, which makes it possible to identify the target tissues and whose knowledge prior to surgery allows the necessary surgical approach to be considered for each patient.

Does 99mTc-tilmanocept, as next generation radiotracer, meet with the requirements for improved sentinel node imaging?

INTRODUCTION AND OBJECTIVES: To evaluate the migration of 99mTc-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 120min after administration of 74MBq 99mTc-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 2h compared to 15min decreased with an average of 66% (range: 15-96%). SN/non-SN 2h 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: 99mTc-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 99mTc-tilmanocept with standard SN radiotracers in larger series of patients is necessary.

Anatomical localization of radiocolloid tracer deposition affects outcome of sentinel node procedures in prostate cancer.

PURPOSE: Diagnostic imaging modalities have moderate sensitivity for the identification of lymph node (LN) metastases in prostate cancer (PCa) patients. Mapping the lymphatic drainage from the prostate can help to identify the LNs directly draining from the tumour (sentinel nodes (SNs)); the LNs stated to have the highest chance of containing metastatic cancer cells. Although the lymphatic drainage may differ between segments within the prostate, the location of the primary tumour is not routinely taken into account during peripheral zone-aimed tracer administration. This study evaluates whether linking the SN procedure to the primary cancer deposits increases the identification accuracy of lymphatic metastases. METHODS: Sixty-seven PCa patients, scheduled for robot-assisted laparoscopic prostatectomy (RALP) and extended lymph node dissection (ePLND) with subsequent SN biopsy, were included in this retrospective study. After injection of the hybrid tracer ICG-99mTc-nanocolloid in the prostate, SN mapping was performed based on lymphoscintigraphy and SPECT/CT. SNs were resected using a combination of radio- and fluorescence guidance. Pathology was used to determine the primary tumour location and metastatic spread. Fluorescence imaging of paraffin-embedded prostate tissue was used to determine the location of the tracer deposits in the prostate. This deposition was related to the primary tumour location, the lymphatic drainage pattern of the injected tracer, and the metastatic spread. RESULTS: In total 265 radioactive LNs (211 SNs and 54 higher-echelon nodes in 64 patients; 4.3 LNs per patient; IQR: 2-6) were identified. In three patients (4%) preoperative imaging did not allow identification of SNs. Tumour-positive SN visualization within the pelvis was shown to be influenced by intraprostatic location of tracer administration. This could be concluded from (1) a clear correlation between lymphatic drainage to the right or left side of the body and tracer deposition on the right or left side of the prostate, (2) visualization of a higher number of LNs after dorsal tracer deposition compared with ventral tracer deposition, (3) different drainage patterns observed for tracer deposition into the base or apex of the prostate, and (4) the indication that intratumoural tracer deposition increases the chance of visualizing nodal metastases compared with extratumoural tracer deposition. CONCLUSIONS: The correlation between the location of the tracer deposits, the location of the primary tumour, and the visualization of the (tumour-positive) SNs indicated that placement of tracer deposits is of influence on the visualized lymphatic drainage pattern. This suggests that tracer injection near or into the primary tumour site is beneficial for the identification of metastatic spread.

Actualización en cirugía radioguiada: del consenso internacional en ganglio centinela de cabeza y cuello a los avances en tumores ginecológicos y localización de lesiones no palpables / Update on radioguided surgery: from international consensus on sentinel node in head and neck cancer to the advances on gynaecological tumors and localization of non-palpable lesions

La presente revisión tiene como objetivo brindar una visión actualizada en diferentes campos de la cirugía radioguiada. En lo que se refiere a la biopsia del ganglio centinela en el carcinoma escamoso oral, se exponen los resultados del debate interactivo llevado a cabo en el reciente Congreso de nuestra especialidad sobre los aspectos más relevantes del Consenso de Londres. En los tumores ginecológicos, cáncer de endometrio y cérvix, se detallan las particularidades del drenaje, las indicaciones establecidas según las guías actuales y se presentan nuevos escenarios para el médico nuclear, como pueden ser la cirugía robótica y los trazadores híbridos. Por otra parte, la notable expansión de las indicaciones de la cirugía radioguiada de lesiones no palpables, ampliamente utilizada en patología mamaria, hace conveniente la puesta al día en dos procedimientos que han demostrado resultados satisfactorios, como son el nódulo pulmonar solitario y el osteoma osteoide

The aim of this review is to provide an updated perspective on different fields of radioguided surgery. With reference to the sentinel lymph node biopsy in oral squamous cell carcinoma, we present the results of the interactive debate held at the recent Congress of our specialty about the more relevant aspects of the London Consensus. Drainage peculiarities and indications according to the current guidelines on gynaecological tumours, endometrial and cervical cancer, are detailed and new scenarios for nuclear medicine physicians are presented; robotic surgery and hybrid tracers, for instance. Moreover, the notable growth in radioguided surgery indications for non-palpable lesions, widely used in mammary pathology, make it advisable to update two procedures which have shown satisfying results, such as the solitary pulmonary nodule and the osteoid osteoma

Freehand-SPECT with 99mTc-HDP as tool to guide percutaneous biopsy of skeletal lesions detected on bone scintigraphy. / Freehand-SPECT con 99mTc-HDP como herramienta para guiar la biopsia percutánea de lesiones esqueléticas detectadas en la gammagrafía ósea.

PURPOSE: To assess the feasibility of using freehand Single Photon Emission Computed Tomography (freehandSPECT) for the identification of technetium-99m-hydroxydiphosphonate (99mTc-HDP) positive bone lesions and to evaluate the possibility of using these imaging data-sets for augmented- and virtual-reality based navigation approaches. MATERIAL AND METHODS: In 20 consecutive patients referred for scintigraphy with 99mTc-HDP, 21 three-dimensional freehandSPECT-images were generated using a handheld gamma camera. Concordance of the two different data sets was ranked. Furthermore, feasibility of segmenting the hotspot of tracer accumulation for navigation purposes was assessed. RESULTS: In 86% of the cases freehandSPECT images showed good concordance with the corresponding part of the scintigraphic images. In lesions with a signal to background ratio (SBR) >1.36, freehandSPECT provided an automatically segmented reference point for navigation purposes. In 14% of the cases (average SBR 1.82, range 1.0-3.4) freehandSPECT images showed intermediate concordance due to difficult anatomical area or negative bone scintigraphy and could not be used as navigation targets. CONCLUSION: In this pilot study, in 86% of the cases freehandSPECT demonstrated good concordance with traditional scintigraphy. A lesion with a SBR of 1.36 or more was suitable for navigation. These high-quality freehandSPECT images supported the future exploration navigation strategies, e.g. guided needle biopsies.

Update on radioguided surgery: from international consensus on sentinel node in head and neck cancer to the advances on gynaecological tumors and localization of non-palpable lesions. / Actualización en cirugía radioguiada: del consenso internacional en ganglio centinela de cabeza y cuello a los avances en tumores ginecológicos y localización de lesiones no palpables.

The aim of this review is to provide an updated perspective on different fields of radioguided surgery. With reference to the sentinel lymph node biopsy in oral squamous cell carcinoma, we present the results of the interactive debate held at the recent Congress of our specialty about the more relevant aspects of the London Consensus. Drainage peculiarities and indications according to the current guidelines on gynaecological tumours, endometrial and cervical cancer, are detailed and new scenarios for nuclear medicine physicians are presented; robotic surgery and hybrid tracers, for instance. Moreover, the notable growth in radioguided surgery indications for non-palpable lesions, widely used in mammary pathology, make it advisable to update two procedures which have shown satisfying results, such as the solitary pulmonary nodule and the osteoid osteoma.

Next generation of radiotracers for sentinel lymph node biopsy: What is still necessary to establish new imaging paradigms? / Nueva generación de radiotrazadores para la biopsia del ganglio centinela: ¿qué es necesario para establecer nuevos paradigmas de imagen?

Sentinel lymph node (SLN) biopsy is now the standard of care for regional staging in several solid tumors. The interstitial administration of a radiotracer around the primary tumor provide the possibility to sequentially obtain images with a gamma camera and visualize lymphatic mapping and the SLN. There is, however, a large geographical variability in those radiotracers and nanocolloids ranging from 15-100nm which are most widely employed in Europe, while filtered and unfiltered 99mTc-sulfur colloid (range 20-1000nm) is usually used in the USA with different drawbacks in its use. The new radiotracer 99mTc-Tilmanocept, designed specifically for the identification of SLNs and recently becoming commercially available in USA and Europe, appears to have the potency to overcome the shortcomings described for the conventional radiotracers used until now for SLN biopsy and at the same time to transform current imaging paradigms. After delineating the challenges for the next generation of radiotracers, this paper discusses the properties of 99mTc-Tilmanocept, its validation process for SLN biopsy and its emerging clinical applications in various malignancies.

The best of both worlds: a hybrid approach for optimal pre- and intraoperative identification of sentinel lymph nodes.

PURPOSE: Hybrid image-guided surgery technologies such as combined radio- and fluorescence-guidance are increasingly gaining interest, but their added value still needs to be proven. In order to evaluate if and how fluorescence-guidance can help realize improvements beyond the current state-of-the-art in sentinel node (SN) biopsy procedures, use of the hybrid tracer indocyanine green (ICG)-99mTc-nancolloid was evaluated in a large cohort of patients. PATIENTS AND METHODS: A prospective trial was conducted (n = 501 procedures) in a heterogeneous cohort of 495 patients with different malignancies (skin malignancies, oral cavity cancer, penile cancer, prostate cancer and vulva cancer). After injection of ICG-99mTc-nanocolloid, SNs were preoperatively identified based on lymphoscintigraphy and SPECT/CT. Intraoperatively, SNs were pursued via gamma tracing, visual identification (blue dye) and/or near-infrared fluorescence imaging during either open surgical procedures (head and neck, penile, vulvar cancer and melanoma) or robot assisted laparoscopic surgery (prostate cancer). As the patients acted as their own control, use of hybrid guidance could be compared to conventional radioguidance and the use of blue dye (n = 300). This was based on reported surgical complications, overall survival, LN recurrence free survival, and false negative rates (FNR). RESULTS: A total of 1,327 SN-related hotspots were identified on 501 preoperative SPECT/CT scans. Intraoperatively, a total number of 1,643 SNs were identified based on the combination of gamma-tracing (>98%) and fluorescence-guidance (>95%). In patients wherein blue dye was used (n = 300) fluorescence-based SN detection was superior over visual blue dye-based detection (22-78%). No adverse effects related to the use of the hybrid tracer or the fluorescence-guidance procedure were found and outcome values were not negatively influenced. CONCLUSION: With ICG-99mTc-nanocolloid, the SN biopsy procedure has become more accurate and independent of the use of blue dye. With that, the procedure has evolved to be universal for different malignancies and anatomical locations.

De la imagen intervencionista a la guía intraoperatoria: nuevas perspectivas combinando herramientas avanzadas y navegación con la cirugía radioguiada / From interventionist imaging to intraoperative guidance: new perspectives by combining advanced tools and navigation with radio-guided surgery

La integración de tecnologías de imagen médica en los enfoques diagnósticos y terapéuticos puede proporcionar una perspectiva preoperatoria tanto en los aspectos anatómicos (tomografía computarizada, resonancia magnética o ecografía) como funcional (tomografía computarizada de emisión de fotón único, tomografía por emisión de positrones, linfogammagrafía o imagen óptica). Además, algunas modalidades de imagen se utilizan también en un entorno intervencionista (tomografía computarizada, ecografía, imágenes gammagráficas o imágenes ópticas), donde proporcionan al cirujano información en tiempo real durante el procedimiento. En la actualidad son factibles diversas herramientas y enfoques metodológicos para la navegación guiada por imágenes en la cirugía del cáncer. Con el desarrollo de nuevos trazadores y dispositivos portátiles de imagen, estos avances reforzarán el papel de la imagen molecular intervencionista (AU)

The integration of medical imaging technologies into diagnostic and therapeutic approaches can provide a preoperative insight into both anatomical (e.g. using computed tomography, magnetic resonance imaging, or ultrasound), as well as functional aspects (e.g. using single photon emission computed tomography, positron emission tomography, lymphoscintigraphy, or optical imaging). Moreover, some imaging modalities are also used in an interventional setting (e.g. computed tomography, ultrasound, gamma or optical imaging) where they provide the surgeon with real-time information during the procedure. Various tools and approaches for image-guided navigation in cancer surgery are becoming feasible today. With the development of new tracers and portable imaging devices, these advances will reinforce the role of interventional molecular imaging (AU)

From interventionist imaging to intraoperative guidance: New perspectives by combining advanced tools and navigation with radio-guided surgery. / De la imagen intervencionista a la guía intraoperatoria: nuevas perspectivas combinando herramientas avanzadas y navegación con la cirugía radioguiada.

The integration of medical imaging technologies into diagnostic and therapeutic approaches can provide a preoperative insight into both anatomical (e.g. using computed tomography, magnetic resonance imaging, or ultrasound), as well as functional aspects (e.g. using single photon emission computed tomography, positron emission tomography, lymphoscintigraphy, or optical imaging). Moreover, some imaging modalities are also used in an interventional setting (e.g. computed tomography, ultrasound, gamma or optical imaging) where they provide the surgeon with real-time information during the procedure. Various tools and approaches for image-guided navigation in cancer surgery are becoming feasible today. With the development of new tracers and portable imaging devices, these advances will reinforce the role of interventional molecular imaging.

Combined PET-CT and axillary lymph node marking with radioactive iodine seeds (MARI procedure) for tailored axillary treatment in node-positive breast cancer after neoadjuvant therapy.

BACKGROUND: The treatment of axillary lymph node metastases after neoadjuvant systemic therapy (NST) remains debatable and axillary lymph node dissection (ALND) is still the standard of care. Marking axillary lymph nodes with radioactive iodine seeds (MARI procedure) is accurate in restaging the axilla after NST (false-negative rate 7 per cent). Here, the potential of tailored axillary treatment, determined by combining the results of PET-CT before NST with those of the MARI procedure after NST, was analysed. METHODS: A cohort of axillary node-positive patients was used to construct a hypothetical treatment algorithm based on a combination of PET-CT and the MARI procedure. In the algorithm, the number of fluorodeoxyglucose (FDG)-avid axillary lymph nodes (1-3 versus 4 or more) before NST and the tumour status of the MARI node (positive versus negative) after NST were used to tailor axillary treatment. All patients in the cohort underwent ALND, allowing estimation of potential overtreatment and undertreatment. RESULTS: A total of 93 patients were included in the study. Between one and three FDG-avid axillary lymph nodes were observed in 59 patients, and four or more in 34 patients. The MARI node was tumour-negative in 32 patients and showed residual disease in 61. Treatment according to the constructed algorithm would have resulted in 74 per cent of patients avoiding an ALND, with potential undertreatment in three patients (3 per cent) and overtreatment in 16 (17 per cent). CONCLUSION: Tailored axillary treatment after NST in node-positive patients, by combining PET-CT before NST and the MARI procedure after NST, has the potential for ALND to be avoided in 74 per cent of patients.

A novel semi-robotized device for high-precision 18F-FDG-guided breast cancer biopsy.

PURPOSE: To assess the 3D geometric sampling accuracy of a new PET-guided system for breast cancer biopsy (BCB) from areas within the tumour with high 18F-FDG uptake. MATERIALS AND METHODS: In the context of the European Union project MammoCare, a prototype semi-robotic stereotactic prototype BCB-device was incorporated into a dedicated high resolution PET-detector for breast imaging. The system consists of 2 stacked rings, each containing 12 plane detectors, forming a dodecagon with a 186mm aperture for 3D reconstruction (1mm3 voxel). A vacuum-assisted biopsy needle attached to a robot-controlled arm was used. To test the accuracy of needle placement, the needle tip was labelled with 18F-FDG and positioned at 78 target coordinates distributed over a 35mm×24mm×28mm volume within the PET-detector field-of-view. At each position images were acquired from which the needle positioning accuracy was calculated. Additionally, phantom-based biopsy proofs, as well as MammoCare images of 5 breast cancer patients, were evaluated for the 3D automated locating of 18F-FDG uptake areas within the tumour. RESULTS: Needle positioning tests revealed an average accuracy of 0.5mm (range 0-1mm), 0.6mm (range 0-2mm), and 0.4mm (range 0-2mm) for the x/y/z-axes, respectively. Furthermore, the MammoCare system was able to visualize and locate small (<10mm) regions with high 18F-FDG uptake within the tumour suitable for PET-guided biopsy after being located by the 3D automated application. CONCLUSIONS: Accuracy testing demonstrated high-precision of this semi-automatic 3D PET-guided system for breast cancer core needle biopsy. Its clinical feasibility evaluation in breast cancer patients scheduled for neo-adjuvant chemotherapy will follow.

PET/CT with 18F-FDG predicts short-term outcome in stage II/III breast cancer patients upstaged to N2/3 nodal disease.

INTRODUCTION: 18F-FDG PET/CT has high positive predictive value for the detection of avid lymph node metastases in breast cancer patients. We analysed the effect of upstaging lymph nodes by PET/CT on short-term outcome in stage II/III breast cancer patients. PATIENTS AND METHODS: A total of 278 stage II/III primary breast cancer patients (mean age 48.9 years, range 19-75 years) were re-staged with 18F-FDG PET/CT before start of pre-operative systemic treatment (PST). Patients were divided in three groups based on risk for local recurrence: a low - (T2N0), intermediate - (T0-2N1 and T3N0) and a high-risk group (T0-3N2-3, T3N1 and T4). Within these groups we looked at local recurrence-free survival (LRFS), recurrence-free survival (RFS) and overall survival (OS) within the first 3 years of follow-up. RESULTS: With a median follow-up (FU) of 50 months the RFS, LRFS and OS were 87%, 88% and 92% respectively for the whole group. PET/CT upstaged 43 patients from the low- and intermediate risk group to the high-risk group, based on detection of ≥4 avid axillary nodes or occult N2/3-disease. Patients upstaged with PET/CT had more events for all three analyses compared to the original risk groups, which resulted in a significantly worse RFS (69.8%; p = 0.03) a nearly significantly worse LRFS (p = 0.052) and no effect in OS (p = 0.433). DISCUSSION: Additional PET/CT staging allows breast cancer patients to be treated according to the true stage, still stage II/III breast cancer patients upstaged to N2/3 by PET/CT have worse short-term outcome, despite adjustment of treatment, than patients staged high-risk with conventional imaging.

Radioguided surgery and the GOSTT concept: From pre-operative image and intraoperative navigation to image-assisted excision.

Radio-guided surgery has been developed for application in those disease scheduled for surgical management, particularly in areas of complex anatomy. This is based on the use of pre-operative scintigraphic planar, tomographic and fused SPECT/CT images, and the possibility of 3D reconstruction for the subsequent intraoperative locating of active lesions using handheld devices (detection probes, gamma cameras, etc.). New tracers and technologies have also been incorporated into these surgical procedures. The combination of visual and acoustic signals during the intraoperative procedure has become possible with new portable imaging modalities. In daily practice, the images offered by these techniques and devices combine perioperative nuclear medicine imaging with the superior resolution of additional optical guidance in the operating room. In many ways they provide real-time images, allowing accurate guidance during surgery, a reduction in the time required for tissue location and an anatomical environment for surgical recognition. All these approaches have been included in the concept known as (radio) Guided intraOperative Scintigraphic Tumour Targeting (GOSTT). This article offers a general view of different nuclear medicine and allied technologies used for several GOSTT procedures, and illustrates the crossing of technological frontiers in radio-guided surgery.

Methodological aspects of 99mTc-sestamibi guided biopsy in breast cancer.

PURPOSE: This review aims to discuss the methodological aspects of dedicated molecular breast imaging (MBI) using 99mTc-sestamibi as radiotracer to guide biopsy of occult or unclear breast lesions on mammography (MG) and ultrasound (US) that are suspicious on MBI (BI-RADS criteria 4 and 5), including its advantages, limitations and future clinical applications. METHODS: Literature search was performed using the PubMed/MEDLINE database and "99mTc-sestamibi", "biopsy" and "breast cancer" as keywords. The search was restricted to English language. RESULTS: There are few studies on 99mTc-sestamibi guided biopsy methods; to our knowledge, no full studies have yet been reported on clinical validation of this new biopsy procedure. This review describes technical aspects of 99mTc-sestamibi guided biopsy and discusses the advantages and limitations of this procedure in comparison with MG, US and MRI-guided biopsy. CONCLUSIONS: MBI-guided biopsy appears to be a complementary modality and is principally indicated in the case of occult or unclear breast lesions on MG/US, that are suspicious on MBI. The future indication is in targeted biopsies in patients with large heterogeneous tumours. Further studies are needed to define the accuracy of this biopsy procedure.