Unraveling the clinicopathological and molecular changes induced by neoadjuvant chemotherapy and endocrine therapy in hormone receptor-positive/HER2-low and HER2-0 breast cancer.

BACKGROUND: The characterization and comparison of gene expression and intrinsic subtype (IS) changes induced by neoadjuvant chemotherapy (NACT) and endocrine therapy in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 (HER2)-low versus HR+/HER2-0 breast cancer (BC) has not been conducted so far. Most evidence on the association of HER2 status with pathologic responses and prognosis in HR+/HER2-negative BC is controversial and restricted to NACT-treated disease. Similarly, a temporal heterogeneity in HER2 status has been described only with NACT. METHODS: We retrospectively recruited a consecutive cohort of 186 patients with stage I-IIIB HR+/HER2-negative BC treated with neoadjuvant therapy (NAT). Available diagnostic biopsies and surgical samples were characterized for main pathological features, PAM50 IS and ROR-P score, and gene expression. Associations with pathologic complete response, residual cancer burden-0/I, event-free survival (EFS) and overall survival (OS) based on HER2 status were assessed. Pre/post pathologic/molecular changes were analyzed in matched samples. RESULTS: The HER2-low (62.9%) and HER2-0 (37.1%) cohorts did not differ significantly in main baseline features, treatments administered, breast-conserving surgery, pathologic complete response and residual cancer burden-0/I rates, EFS, and OS. NAT induced, regardless of HER2 status, a significant reduction of estrogen receptor/progesterone receptor and Ki67 levels, a down-regulation of PAM50 proliferation- and luminal-related genes/signatures, an up-regulation of selected immune genes, and a shift towards less aggressive IS and lower ROR-P. Moreover, 25% of HER2-0 changed to HER2-low and 34% HER2-low became HER2-0. HER2 shifts were significant after NACT (P < 0.001), not neoadjuvant endocrine therapy (P = 0.063), with consistent ERBB2 mRNA level dynamics. HER2 changes were not associated with EFS/OS. CONCLUSIONS: HER2-low and HER2-0 status change after NAT in ∼30% of cases, mostly after NACT. Targeted adjuvant strategies should be investigated accordingly. Molecular downstaging with current chemo/endocrine agents and immunotherapy should not rely on HER2 immunohistochemical levels in HR+/HER2-negative BC. Instead, HER2-low-targeted approaches should be explored to pursue more effective and/or less toxic dimensional downstaging.

Multidisciplinary radio-guided surgery team: Alternative to change the current paradigm.

INTRODUCTION: Given the constant increase in the healthcare demand for examinations related to radio-guided surgery (RGS), our hospital adopted new professional profiles in the RGS team, in order to partially reduce the time spent by nuclear medicine physicians on this task. AIM: To analyze the process of incorporating the profiles of Diagnostic Imaging Technician (DIT) and Sentinel Node Referent Nurse (SNRN), evaluating their deployment in the procedures linked to the technique. MATERIAL AND METHODS: Analysis of RGS activity during the period 2018-2022, focusing on pre-surgical and surgical procedures related to breast cancer (BC) and malignant melanoma (MM), as they are those pathologies on which the transfer of care competencies was concentrated. Chronological evolution of the competencies assumed by the different profiles during their integration into the RGS team. RESULTS: RGS's healthcare activity during the analyzed period experienced an increase of 109%. BC and MM were the pathologies that accounted for by far the greatest demand for care. The transfer of competencies in these two pathologies occurred in a progressive and staggered manner, with 74% (460/622) of the administration phase being carried out by the SNRN and 64% (333/519) of the surgeries by the DIT in 2022. CONCLUSIONS: The creation of a multidisciplinary RGS team that includes different professional profiles (nuclear medicine physician [MN], ERGC and TSID) is an effective strategy to respond to the increase in the complexity and number of all procedures related to RGS.

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.

Sentinel node referent nurse: Description, validation and application in clinical practice.

INTRODUCTION: In 2019 the opportunity to add a nurse within the radioguided surgery (RGS) team was generated. The referent nurse model was adapted to, the sentinel node (SN) preoperative approaches. OBJECTIVES: To describe the process performed to define the sentinel node referent nurse (SNRN) profile, to validate its practical application and to establish its clinical implementation. MATERIAL AND METHODS: Methodology of analysis and continuous improvement in the management of processes (cycle PDCA): definition and planning of the SNRN functions in the breast cancer protocol, performance of a pilot test with 20 patients and analysis of the data in order to validate the circuit and establish its final clinical implementation. RESULTS: New procedure flows-charts were elaborated, adding the figure of the SNRN, its function and nursing interventions during the process. In the pilot test a 58.3% reduction in subjective anxiety, a 75% decrease of the overall anxiety level, a 100% knowledge of the test and an acceptable patient perception of pain's level during the radiotracer administration were obtained. Regarding technical quality, 8/10 items assessed reached the level previously established by the RGS team. CONCLUSIONS: The increasing complexity of the SN biopsy technique has created the opportunity to implement nursing care in the presurgical SN localization process. The profile of the SNRN is ideal for carrying it out and has led to improvements in the nursing diagnoses and assessed items.

Radioguided surgery in primary hyperparathyroidism: a review of the different available techniques. / Cirugía radioguiada en el hiperparatiroidismo primario: revisión de las diferentes técnicas disponibles.

Parathyroidectomy has evolved over the years from bilateral neck exploration to a single gland approach using minimally invasive surgery. The precise presurgical localization of the problem gland, using functional techniques, such as double-phase scintigraphy with [99mTc] Tc-MIBI including SPECT-CT and PET-CT with [18F]-Choline and morphological ones, such as ultrasound have played a crucial role in this paradigm's shift. Radioguided surgery techniques have also adapted and grown with new contributions known for their indication in other fields. Thus, we currently have a wide range of techniques that have been added to the minimally invasive radioguided parathyroidectomy with [99mTc] Tc-MIBI, which was the first on the stage and for which more experience exists. Among them, in this update, we will discuss parathyroidectomy using ultrasound-guided ROLL technique as well as with the use of 125I seeds and finally, hybrid techniques that use radiotracer and fluorescence.

Cost-effectiveness analysis of imaging strategy for an intensive follow-up of patients with American Joint Committee on Cancer stage IIB, IIC and III malignant melanoma.

BACKGROUND: Many follow-up guidelines for patients with high-risk melanoma include expensive imaging studies, serum biomarkers and regular visits to the dermatologist, with little attention to cost-effectiveness. OBJECTIVES: To establish the cost-effectiveness of chest-abdomen-pelvis computed tomography (CT) and brain magnetic resonance imaging (MRI) in a follow-up protocol for patients at high risk of relapse. METHODS: This was a prospective single-centre cohort study of 290 patients with clinicopathological American Joint Committee on Cancer (AJCC) stage IIB, IIC and III melanoma. Patients had a body CT scan and brain MRI every 6 months and were withdrawn from the study after completing a 5-year follow-up or when metastases were detected. A cost-effectiveness analysis for each follow-up radiological procedure was performed. RESULTS: Patients underwent 1805 body CT scans and 1683 brain MRIs. Seventy-six metastases (26·2%) were identified by CT or MRI. CT scan was cost-effective in the first 4 years (cost-effectiveness ratio €4710·70-€14 437·10/patient with metastasis); brain MRI was cost-effective during the first year (cost-effectiveness ratio €14 090·60/patient with metastasis). Limitations included lack of survival analysis and comparisons with willingness-to-pay thresholds. CONCLUSIONS: Six-monthly CT scan of the chest, abdomen and pelvis is a cost-effective technique for the early detection of metastases in the first 4 years of follow-up in patients with AJCC stage IIC and III melanoma, and in the first 3 years in patients with AJCC stage IIB melanoma. In addition, brain MRI has been shown to be cost-effective only in the first year of follow-up in patients with AJCC stage IIC and III melanoma.

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.

Multimodal approach in radioguided surgery in a case of multiple paraganglioma. / Abordaje multimodal en la cirugía radioguiada de un caso de paraganglioma múltiple.

The case involves a 34-year-old woman who underwent surgical removal of a retroperitoneal paraganglioma adjacent to the left kidney's lower pole, previously visualized by CT and MRI. The 123I-MIBG scan was positive for this lesion and, in addition, another uptake was observed located caudally at the level of L5 and of smaller size and less intensity. The second lesion was not considered for surgical removal, due to its lack of morphological definition. One week after surgical intervention, the patient presented difficult-to-control high blood pressure. A second 123I-MIBG scan was performed. The previously described second image was more intense in this study, and surgery was planned to remove it. A combination of techniques including freehand-SPECT and a portable hybrid gamma camera (with optical camera) were used pre-operatively to identify the location of the lesion. The combination of intra-operative laparoscopic gamma probe and portable hybrid gamma camera enabled the tumor to be located, excised, and its complete removal to be monitored. The histopathology analysis confirmed a second paraganglioma.

Review of the role of the sentinel node biopsy in neoadjuvant chemotherapy in women with breast cancer and negative or positive axillary node at diagnosis. / Actualización de la biopsia del ganglio centinela tras quimioterapia neoadyuvante en el cáncer de mama sin y con afectación ganglionar al diagnóstico.

The role of the selective sentinel node biopsy (SNB) is increasing in relevance in breast cancer women with indication of neoadjuvant chemotherapy (NAC). The Radiosurgery Working Group of the SEMNIM is aware of the necessity of establishing the need for SNB before or after NAC, and also how to manage patients with axillary node-negative or node-positive. There is sufficient data to assess that the SNB with radioisotope techniques are feasible and safe in all these scenarios. An adequate axilla evaluation prior to surgery and the possibility of marking prior to NAC the nodes infiltrated must be the two main pillars to guarantee the success of the SNB. It has been shown that to incorporate the SNB in breast cancer women with indication of NAC increases the rate of a conservative treatment of the axilla that will be a clear benefit for these patients.

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.

18F-FDG PET/CT and sentinel lymph node biopsy in the staging of patients with cervical and endometrial cancer. Role of dual-time-point imaging.

OBJECTIVE: Definitive staging for cervical (CC) and endometrial cancer (EC) takes place once surgery is performed. The aim of this study was to evaluate the role of PET/CT in detecting lymphatic metastasis in patients with CC and EC using dual-time-point imaging (DPI), taking the histopathological results of sentinel lymph node (SLN) and lymphadenectomy as the reference. MATERIAL AND METHODS: A prospective study was conducted on 17 patients with early CC, and 13 patients with high-risk EC. The patients had a pre-operative PET/CT, MRI, SLN detection, and lymphadenectomy, when indicated. PET/CT findings were compared with histopathological results. RESULTS: In the pathology study, 4 patients with CC and 4 patients with EC had lymphatic metastasis. PET/CT showed hypermetabolic nodes in 1 patient with CC, and 5 with EC. Four of these had metastasis, one detected in the SLN biopsy. Four patients who had negative PET/CT had micrometastasis in the SLN biopsy, 1 patient with additional lymph nodes involvement. The overall patient-based sensitivity, specificity, positive and negative predictive values, and accuracy of PET/CT to detect lymphatic metastasis was 20.0%, 100.0%, 100.0%, 87.9%, and 88.2%, respectively, in CC, and 57.1%, 88.9%, 66.7%, 84.2% and 80.0%, respectively, in EC. DPI showed higher retention index in malignant than in inflammatory nodes, although no statistically significant differences were found. CONCLUSIONS: PET/CT has low sensitivity in lymph node staging of CC and EC, owing to the lack of detection of micrometastasis. Thus, PET/CT cannot replace SLN biopsy. Although no statistically significant differences were found, DPI may help to differentiate between inflammatory and malignant nodes.

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.

Usefulness of (18)F-FDG PET/CT in recurrent basal cell carcinoma: Report of a case.

We analyze the case of a patient with left periorbital infiltrating basal cell carcinoma treated with surgical excision in October 2010. Surgery included orbital exenteration and reconstruction using skin graft and radiotherapy. In May 2013 a MR imaging showed a mass in the left orbital fossa, suggesting a recurrence in the graft. A basal cell carcinoma recurrence with perineural invasion was confirmed in the biopsy. On (18)F-FDG PET/CT performed, a hypermetabolic activity was observed in the left periorbital area with extension to surrounding sinus and bones. The use of (18)F-FDG PET/CT in patients with advanced basal cell carcinoma has not been fully explored due to the rarity of this entity. This case demonstrates the usefulness of this technique to determine the extent of non-melanocytic recurrent skin tumors, and its value in the staging and treatment control, supporting the incorporation of (18)F-FDG PET/CT in the management of advanced basal cell carcinoma.

Sentinel node approach in prostate cancer.

In general terms, one of the main objectives of sentinel lymph node (SLN) biopsy is to identify the 20-25% of patients with occult regional metastatic involvement. This technique reduces the associated morbidity from lymphadenectomy, as well as increasing the identification rate of occult lymphatic metastases by offering the pathologist those lymph nodes with the highest probability of containing metastatic cells. Pre-surgical lymphoscintigraphy is considered a "road map" to guide the surgeon towards the sentinel nodes and to ascertain unpredictable lymphatic drainages. In prostate cancer this aspect is essential due to the multidirectional character of the lymphatic drainage in the pelvis. In this context the inclusion of SPECT/CT should be mandatory in order to improve the SLN detection rate, to clarify the location when SLNs are difficult to interpret on planar images, to achieve a better definition of them in locations close to injection site, and to provide anatomical landmarks to be recognized during operation to locate SLNs. Conventional and laparoscopic hand-held gamma probes allow the SLN technique to be applied in any kind of surgery. The introduction and combination of new tracers and devices refines this technique, and the use of intraoperative images. These aspects become of vital importance due to the recent incorporation of robot-assisted procedures for SLN biopsy. In spite of these advances various aspects of SLN biopsy in prostate cancer patients still need to be discussed, and therefore their clinical application is not widely used.

[Sentinel node in melanoma and breast cancer. Current considerations]. / Ganglio centinela en melanoma y cáncer de mama. Consideraciones actuales.

The main objectives of sentinel node (SN) biopsy is to avoid unnecessary lymphadenectomies and to identify the 20-25% of patients with occult regional metastatic involvement. This technique reduces the associated morbidity from lymphadenectomy and increases the occult lymphatic metastases identification rate by offering the pathologist the or those lymph nodes with the highest probability of containing metastatic cells. Pre-surgical lymphoscintigraphy is considered a "road map" to guide the surgeon towards the sentinel nodes and to localize unpredictable lymphatic drainage patterns. The SPECT/CT advantages include a better SN detection rate than planar images, the ability to detect SNs in difficult to interpret studies, better SN depiction, especially in sites closer to the injection site and better anatomic localization. These advantages may result in a change in the patient's clinical management both in melanoma and breast cancer. The correct SN evaluation by pathology implies a tumoral load stratification and further prognostic implication. The use of intraoperative imaging devices allows the surgeon a better surgical approach and precise SN localization. Several studies reports the added value of such devices for more sentinel nodes excision and a complete monitoring of the whole procedure. New techniques, by using fluorescent or hybrid tracers, are currently being developed.