Melanoma is an important public health problem, and its incidence is increasing worldwide. The disease status of regional lymph nodes is the most important prognostic factor in early-stage melanoma patients. Sentinel lymph node biopsy (SLNB) was introduced in the early 1990s as a less invasive procedure than complete lymph node dissection to allow histopathologic evaluation of the "sentinel lymph node" (SLN), which is the first node along the lymphatic pathway from a primary tumor. Sentinel lymph node biopsy has minimal complication risks compared with standard complete lymph node dissection. Currently, SLNB is the accepted method for staging patients with clinically node-negative cutaneous melanoma and provides the most powerful prognostic information by evaluating the nodal basin status. The current practice of SLNB consists of the injection of Tc-labeled radiopharmaceutical, preoperative lymphoscintigraphy with the possibility of using the SPECT/CT hybrid imaging, and intraoperative SLN localization using a handheld gamma probe with or without the use of blue dye. Recently, the SLN localization and detection have been enhanced with the use of new tracers and new intraoperative devices, which have demonstrated to be particularly useful in melanomas of the head and neck region and in area of complex anatomy. Despite these important advances in the technology and the increasing experience in SLN mapping, major research centers have reported a false-negative rate higher than 15%. This relatively high false-negative rate, greater than those reported in the initial validation studies, points out the importance for the nuclear medicine community to continuously improve their knowledge on the biological behavior of melanoma and to improve the technical aspects that may allow more precise staging. For the SLNB procedure to be accurate, it is of critical importance that all "true" SLNs are identified and removed for examination. The aim of this article is to provide general information about the SLNB procedure in clinical practice highlighting the importance of standardization and accuracy of SLN identification in the light of the most recent technical innovations.
Axillary lymph node status, a major prognostic factor in early-stage breast cancer, provides information important for individualized surgical treatment. Because imaging techniques have limited sensitivity to detect metastasis in axillary lymph nodes, the axilla must be explored surgically. The histology of all resected nodes at the time of axillary lymph node dissection (ALND) has traditionally been regarded as the most accurate method for assessing metastatic spread of disease to the locoregional lymph nodes. However, ALND may result in lymphedema, nerve injury, shoulder dysfunction, and other short-term and long-term complications limiting functionality and reducing quality of life. Sentinel lymph node biopsy (SLNB) is a less invasive method of assessing nodal involvement. The concept of SLNB is based on the notion that tumors drain in an orderly manner through the lymphatic system. Therefore, the SLN is the first to be affected by metastasis if the tumor has spread, and a tumor-free SLN makes it highly unlikely for other nodes to be affected. Sentinel lymph node biopsy has become the standard of care for primary treatment of early breast cancer and has replaced ALND to stage clinically node-negative patients, thus reducing ALND-associated morbidity. More than 20 years after its introduction, there are still aspects concerning SLNB and ALND that are currently debated. Moreover, SLNB remains an unstandardized procedure surrounded by many unresolved controversies concerning the technique itself. In this article, we review the main indications, contraindications, and controversies of SLNB in breast cancer in the light of the most recent publications.
Ra alpha therapy is an important therapeutic option for men with CRPC and symptomatic skeletal metastases.
The role of nuclear medicine physicians in the multidisciplinary team for the management of patients with prostate cancer has been restricted because of a lack of available tools. The only drugs approved to relieve pain related to bone metastases were β-emitting radiopharmaceuticals. These drugs did not prove to prolong survival when used as single agent and resulted associated with important adverse events. This situation has changed with the introduction of radium 223 because of evidence of improved survival in patients, the good safety profile and the opportunity to avoid clonal selection of tumor cells. Cooperation among physicians involved in cancer management will lead to improvements in the treatment of bone metastases due to prostate cancer and is thought to extend to other tumor types. KeywordsThe management of most prostate cancer cases involves committed specialists such as urologists, medical oncologists, radiotherapists, and nuclear medicine physicians. Evidence shows that in men with high-risk prostate cancer, only a patient-focused program based on a multidisciplinary approach can result in improved survival [1]. The role of nuclear medicine physicians in this multidisciplinary team so far has been restricted to providing pain relief. In castration-resistant prostate cancer (CRPC) patients with bone metastases (mCRPC), radiopharmaceuticals turned out to be useful only for noncurative purposes, exclusively aiming at improving symptomatic pain control. In addition, the available drugs have induced considerable serious adverse events, mostly hematologic, and thus have prevented subsequent therapeutic approaches [2]. Therefore, radionuclide-based therapy for symptomatic bone metastases has remained underused and limited to the late phases of the disease [3].The lack of safe therapeutic approaches to extend survival in CRPC patients has been a challenge for nuclear medicine physicians accustomed to successfully treating other tumor types, such as thyroid tumors with radioiodine therapy, or treating hematologic malignancies with ibritumomab tiuxetan. The recent introduction of the radiopharmaceutical radium Ra 223 (Ra 223) dichloride represents a breakthrough because, for the first time, an impact of a radiopharmaceutical on survival of patients with bone metastases due to prostate cancer was demonstrated in a large Phase III trial [4]. This drug, in fact, received the category 1 recommendation as first-line and second-line option by National Comprehensive Cancer Network (NCCN) guideline similarly to chemotherapy [5], and thus the nuclear medicine physician assumed a key position in the current multidisciplinary team for the treatment of mCRPC. The team should evaluate which patients are suitable for Ra 223 dichloride without limiting access to patients in the terminal stages of the disease and should integrate the nuclear medicine physician into the team with the medical oncologist and surgeon. Future Oncol. (Epub ahead of print)
Evidence of cortical beta-amyloid (Aβ) load, assessed by Aβ positron emission tomography (Aβ-PET), is an established in vivo biomarker of Alzheimer’s disease (AD)-related pathophysiology. Qualitative assessment of Aβ-PET provides binary information; meanwhile semiquantitative approaches require a parcellation of PET image either manually or by placement of atlas-based volumes of interest. We supposed that a whole-brain approach with voxel-by-voxel standardized uptake value ratio (SUVr) parametric images may better elucidate the spatial trajectories of Aβ burden along the continuum of AD. Methods: We recruited 32 subjects with a diagnosis of probable AD dementia (ADD, n = 20) and mild cognitive impairment due to AD (MCI-AD, n = 12) according to the NIA-AA 2011 criteria. We also enrolled a control group of 6 cognitively healthy individuals (HCs) with preserved cognitive functions and negative Aβ-PET scan. The PET images were spatially normalized using the AV45 PET template in the MNI brain space. Subsequently, parametric SUVr images were calculated using the whole cerebellum as a reference region. A voxel-wise analysis of covariance was used to compare (between groups) the Αβ distribution pattern considering age as a nuisance covariate. Results: Both ADD and MCI-AD subjects showed a widespread increase in radiotracer uptake when compared with HC participants (p < 0.001, uncorrected). After applying a multiple comparison correction (p < 0.05, corrected), a relative large cluster of increased [18F]-florbetapir uptake was observed in the precuneus in the ADD and MCI-AD groups compared to HCs. Voxel-wise regression analysis showed a significant positive linear association between the voxel-wise SUVr values and the disease duration. Conclusions: The voxel-wise semiquantitative analysis shows that the precuneus is a region with higher vulnerability to Aβ depositions when compared to other cortical regions in both MCI-AD and ADD subjects. We think that the precuneus is a promising PET-based outcome measure for clinical trials of drugs targeting brain Aβ. We found a positive association between the overall Aβ-PET SUVr and the disease duration suggesting that the region-specific slow saturation of Aβ deposition continuously takes place as the disease progresses.
Management of cutaneous melanoma has changed after introduction in the clinical routine of sentinel lymph node biopsy (SLNB) for nodal staging. By defining the nodal basin status, SLNB provides a powerful prognostic information. Nevertheless, some debate still surrounds the accuracy of this procedure in terms of false-negative rate. Several large-scale studies have reported a relatively high false-negative rate (5.6%-21%), correctly defined as the proportion of false-negative results with respect to the total number of "actual" positive lymph nodes. In this review, we identified all the technical aspects that the nuclear medicine physician, the surgeon, and the pathologist should take into account to improve accuracy of the procedure and minimize the false-negative rate. In particular, SPECT/CT imaging detects more SLNs than those found by planar lymphoscintigraphy. Furthermore, the nuclear medicine community should reach a consensus on the radioactive counting rate threshold to better guide the surgeon in identifying the lymph nodes with the highest likelihood of housing metastases ("true biologic SLNs"). Analysis of the harvested SLNs by conventional techniques is also a further potential source for error. More accurate SLN analysis (eg, molecular analysis by reverse transcriptase-polymerase chain reaction) and more extensive SLN sampling identify more positive nodes, thus reducing the false-negative rate.The clinical factors identifying patients at higher-risk local recurrence after a negative SLNB include older age at diagnosis, deeper lesions, histological ulceration, and head-neck anatomic location of the primary lesion.The clinical impact of a false-negative SLNB on the prognosis of melanoma patients remains controversial, because the majority of studies have failed to demonstrate overall statistically significant disadvantage in melanoma-specific survival for false-negative SLNB patients compared with true-positive SLNB patients.When new more effective drugs will be available in the adjuvant setting for stage III melanoma patients, the implication of an accurate staging procedure for the sentinel lymph nodes will be crucial for both patients and clinicians. Standardization and accuracy of SLN identification, removal, and analysis are required.
Prior administration of Sm-EDTMP does not cause additional toxicities for subsequent treatment with docetaxel and does not reduce the antitumor efficacy of the latter. This work justifies further investigations on the possible synergistic effects of combined strategies with the two agents.
Between 60 and 84 % of patients with solid cancers develop bone metastases, the main complication that severely impairs quality of life and performance status and constitutes one of the major challenges of oncological practice. Among other palliative treatments, therapy with bone-seeking radiopharmaceuticals is part of the armamentarium available in the clinical setting to treat bone pain caused by skeletal metastases. Although several radionuclides have been proposed to this purpose, the most widely used radiopharmaceuticals are the b -emitters 89 Srchloride and 153 Sm-ethylenediamine-tetra-methylene phosphonate ( 153 Sm-EDTMP), while the more recently approved a ?? emitter 223 Ra-chloride plays an increasing role in this scenario.Based on clinical experience acquired for over two decades, 153 Sm-EDTMP has an excellent profile in terms of both efficacy and toxicity, as confirmed by a recent systematic review and meta-analysis of literature on therapy with 89 Sr-chloride and 153 Sm-EDTMP published between 2001 and 2011 [1]. Compared with an overall efficacy for bone palliation of 70 % (either partial or complete) when used as single agents and 74 % when combined with other therapies, the overall toxicity as single agents was 11 %, mostly reversible mild-to-moderate side-effects. Furthermore, interest is growing also on the potential antitumor efficacy of these agents, especially if combined with chemotherapy agents.The market cost of 153 Sm-EDTMP is a drawback limiting a more widespread use of this radiopharmaceutical in low-income countries, thus reviving interest in earlier studies that had explored the potential of 177 Lu as a therapeutic radionuclide to be coupled with EDTMP (US Patent 4898724, 1990. Organic amine phosphonic acid complexes for the treatment of calcific tumors. Wilson DA, Volkert WA, Troutner DE, Goeckeler WF). Lutetium-177 has favorable characteristics such as the low energy b -emission, which should reduce toxicity, and a 6.73 day half-life, which is advantageous for the distribution logistics to distant areas. Moreover, the most important feature which makes the production of 177 Lu especially attractive is the very high thermal neutron capture cross-section of the target 176 Lu, through the reaction 176 Lu(n,c) 177 Lu, the highest (r = 2,060 barns) among all (n,c)-produced radionuclides currently used for therapy. Such large cross-section of the reaction ensures that 177 Lu can be produced with adequately high specific activity for radionuclide therapy applications even when using moderate flux reactors, as those that can be employed for medical use even in several low-income countries. It also ensures that there will be no constraints in the large-scale production of 177 Lu and hence the increasing global demand for this radionuclide in the coming years can be met comfortably. In this regard, enriched 176 Lu (with isotopic abundance above 80 %) is relatively inexpensive (200 euros/mg) and available through multiple sources; furthermore, in the long run the cost of 177 Lu should decrease...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.