Sentinel-Lymph-Node Multicenter Trials.

Well executed multicenter clinical trials often provide significant evidence and support for, or against, foundational aspects of clinical procedures perceived to improve clinical management of a medical condition. In this review, discussed are reports of multicenter clinical trials designed to investigate sentinel lymph node biopsy procedures in seven types of cancer: breast, melanoma, head and neck, gastric, colon, uterine, and vulvar-with focus on the most recent reports of the hypotheses, objectives, parameters, data, results, implications, and impacts of the included trials. Such trials generally enroll more subjects, in shorter time periods, than do single-center studies. Such studies generally also have greater diversities among investigator practitioners and investigative environments than do single-center studies. The greater number of subjects provides more power to statistical analyses performed in such studies. The more rapid accrual usually results in data being more consistently acquired. The diversities of practitioners and environments may produce results that are more conservative than might be obtained from more "focused" studies; however, diversities in a study often identify implicitly results that are more robust-that is results applicable by more practitioners and applicable in more environments.

Sentinel Lymph Node Biopsy Procedures.

Accurate staging of many cancers with no clinical evidence of lymph node involvement is often a critical component of the management of such cancers and is generally and historically accomplished by accurate pathological assessment of multiple nodes. Unfortunately, such assessment usually involves excision of the multiple nodes and can result in significant morbidities. Over the past half century, and particularly over the last quarter century, investigators have defined and refined the "sentinel lymph node(s)" concept and have developed and investigated sentinel lymph node biopsy (SLNB) procedures. Such procedures are designed to stage cancers primarily via assessment of the sentinel nodes of the cancers and to do so with limited risk of morbidities. For some cancers (e.g., breast, melanoma, head and neck, penile), there are SLNB procedures that are used routinely. For other cancers, there are SLNB procedures being investigated that will yet prove successful and practical or successful but not practical or neither practical nor successful. In this review, SLNB procedures for breast, melanoma (adult and pediatric), head-and-neck, gastrointestinal (gastric, esophageal, colon), genitourinary (penile, prostate), and gynecological (uterine, cervical, vulvar, ovarian) cancers are discussed, including results of significant clinical trials performed using such in the management of these various cancers.

Harmonic subtraction for evaluating right ventricle ejection fraction from planar equilibrium radionuclide angiography.

We report an initial investigation of a subtraction-based method to estimate right ventricle ejection fraction (RVEF) from ECG-gated planar equilibrium radionuclide angiography (ERNA) data. Twenty-six consecutive patients referred for scintigraphic evaluation of cardiac function prior to chemotherapy had ECG-gated first-pass (FP) imaging and ERNA imaging performed following the same radiotracer injection. RVEF was computed from FP images (RVEFFP) and separately from ERNA images (RVEFERNA). Standard methods for computing ejection fractions were used to obtain RVEFFP values. RVEFERNA values were obtained using harmonic subtraction of the left ventricular contribution from a biventricular region of interest contoured on the equilibrium images acquired in the shallow right anterior oblique projection. Clinically acquired chest CT data were used to derive information regarding the relative position of the left and right ventricle and about the presence of pulmonary artery enlargement. Computation of RVEFERNA was successful for each of the 26 patients. Computation of RVEFFP failed for four patients. For the 22 patients for which RVEF was computed using both methods, the average RVEFFP was 49% and the average RVEFERNA was 51%, with coefficients of variation of 11 and 7.5%, respectively. Low RVEFERNA values were associated with pulmonary artery dilation. Estimation of RVEFERNA, using a harmonic subtraction-based method of computation is clinically feasible and accurate in the patient population studied. The results support further investigation in patients with frank heart failure.

Lymphoscintigraphy and sentinel nodes.

It has been validated that sentinel lymph node biopsy (SLNB) shows whether a patient's breast cancer or melanoma has spread to regional lymph nodes. As a result, management of patients with these cancers has been revolutionized. SLNB has replaced axillary lymph node dissection (ALND) as the staging modality of choice for early breast cancer and has replaced complete lymph node dissection as the staging modality of choice for melanoma in patients whose SLNBs indicate no metastases. Recently concluded multicenter, randomized trials for breast cancer with 5- to 10-y outcome data have shown no significant differences in disease-free survival rates or overall survival rates between SLNB and ALND groups but have shown significantly lower morbidity with SLNB than with ALND. The lowest false-negative rates (5.5%-6.7%) were seen in studies that used preoperative lymphoscintigraphy and dual mapping during surgery. To assess the survival impact of SLNB in melanoma, the Multicenter Selective Lymphadenectomy Trial I was performed. Melanoma-specific survival rates were not different between subjects randomized to SLNB with lymphadenectomy for nodal metastasis on biopsy and subjects randomized to observation with lymphadenectomy for nodal relapse. However, the 10-y disease-free survival rates were better for the SLNB group than for the observation group, specifically among patients with intermediate-thickness melanomas or thick melanomas.

Nuclear medicine imaging and therapy: gender biases in disease.

Gender-based medicine is medical research and care conducted with conscious consideration of the sex and gender differences of subjects and patients. This issue of Seminars is focused on diseases for which nuclear medicine is part of routine management and for which the diseases have sex- or gender-based differences that affect incidence or pathophysiology and that thus have differences that can potentially affect the results of the relevant nuclear medicine studies. In this first article, we discuss neurologic diseases, certain gastrointestinal conditions, and thyroid conditions. The discussion is in the context of those sex- or gender-based aspects of these diseases that should be considered in the performance, interpretation, and reporting of the relevant nuclear medicine studies. Cardiovascular diseases, gynecologic diseases, bone conditions such as osteoporosis, pediatric occurrences of some diseases, human immunodeficiency virus-related conditions, and the radiation dose considerations of nuclear medicine studies are discussed in the other articles in this issue.

The EANM and SNMMI practice guideline for lymphoscintigraphy and sentinel node localization in breast cancer.

PURPOSE: The accurate harvesting of a sentinel node in breast cancer includes a sequence of procedures with components from different medical specialities, including nuclear medicine, radiology, surgical oncology and pathology. The aim of this document is to provide general information about sentinel lymph node detection in breast cancer patients. METHODS: The Society of Nuclear Medicine and Molecular Imaging (SNMMI) and the European Association of Nuclear Medicine (EANM) have written and approved these guidelines to promote the use of nuclear medicine procedures with high quality. The final result has been discussed by distinguished experts from the EANM Oncology Committee, the SNMMI and the European Society of Surgical Oncology (ESSO). CONCLUSION: The present guidelines for nuclear medicine practitioners offer assistance in optimizing the diagnostic information from the SLN procedure. These guidelines describe protocols currently used routinely, but do not include all existing procedures. They should therefore not be taken as exclusive of other nuclear medicine modalities that can be used to obtain comparable results. It is important to remember that the resources and facilities available for patient care may vary.

Status of sentinel lymph node for breast cancer.

Long-awaited results from randomized clinical trials designed to test the validity of sentinel lymph node biopsy (SLNB) as replacement of axillary lymph node dissection (ALND) in management of early breast cancer have recently been published. All the trials conclude SLNB has survival rates comparable to those of ALND (up to 10 years in one study) and conclude SLNB has less morbidity than ALND. All the trials support replacing ALND with SLNB for staging in early breast cancer; all support SLNB as the standard of care for such cancer. The SLNB protocols used in the trials varied, and no consensus that would suggest a standard protocol exists. The results of the trials and of other peer-reviewed research do, however, suggest a framework for including some specific methodologies in accepted practice. This article highlights the overall survival and disease-free survival data as reported from the clinical trials. This article also reviews the status of SLN procedures and the following: male breast cancer, the roles of various imaging modalities (single-photon emission computed tomography/computed tomography, positron emission tomography/computed tomography, and ultrasound), ductal carcinoma in situ, extra-axillary SLNs, SLNB after neoadjuvant chemotherapy, radiation exposure to patients and medical personnel, and a new radiotracer that is the first to label SLNs not by particle trapping but by specific macrophage receptor binding. The proper Current Procedural Terminology (CPT) code for lymphoscintigraphy and SLN localization prior to surgery is 78195.

MR∕PET quantification tools: registration, segmentation, classification, and MR-based attenuation correction.

PURPOSE: Combined MR∕PET is a relatively new, hybrid imaging modality. A human MR∕PET prototype system consisting of a Siemens 3T Trio MR and brain PET insert was installed and tested at our institution. Its present design does not offer measured attenuation correction (AC) using traditional transmission imaging. This study is the development of quantification tools including MR-based AC for quantification in combined MR∕PET for brain imaging. METHODS: The developed quantification tools include image registration, segmentation, classification, and MR-based AC. These components were integrated into a single scheme for processing MR∕PET data. The segmentation method is multiscale and based on the Radon transform of brain MR images. It was developed to segment the skull on T1-weighted MR images. A modified fuzzy C-means classification scheme was developed to classify brain tissue into gray matter, white matter, and cerebrospinal fluid. Classified tissue is assigned an attenuation coefficient so that AC factors can be generated. PET emission data are then reconstructed using a three-dimensional ordered sets expectation maximization method with the MR-based AC map. Ten subjects had separate MR and PET scans. The PET with [(11)C]PIB was acquired using a high-resolution research tomography (HRRT) PET. MR-based AC was compared with transmission (TX)-based AC on the HRRT. Seventeen volumes of interest were drawn manually on each subject image to compare the PET activities between the MR-based and TX-based AC methods. RESULTS: For skull segmentation, the overlap ratio between our segmented results and the ground truth is 85.2 ± 2.6%. Attenuation correction results from the ten subjects show that the difference between the MR and TX-based methods was <6.5%. CONCLUSIONS: MR-based AC compared favorably with conventional transmission-based AC. Quantitative tools including registration, segmentation, classification, and MR-based AC have been developed for use in combined MR∕PET.

Singular Value Decomposition of Pinhole SPECT Systems.

A single photon emission computed tomography (SPECT) imaging system can be modeled by a linear operator H that maps from object space to detector pixels in image space. The singular vectors and singular-value spectra of H provide useful tools for assessing system performance. The number of voxels used to discretize object space and the number of collection angles and pixels used to measure image space make the matrix dimensions H large. As a result, H must be stored sparsely which renders several conventional singular value decomposition (SVD) methods impractical. We used an iterative power methods SVD algorithm (Lanczos) designed to operate on very large sparsely stored matrices to calculate the singular vectors and singular-value spectra for two small animal pinhole SPECT imaging systems: FastSPECT II and M(3)R. The FastSPECT II system consisted of two rings of eight scintillation cameras each. The resulting dimensions of H were 68921 voxels by 97344 detector pixels. The M(3)R system is a four camera system that was reconfigured to measure image space using a single scintillation camera. The resulting dimensions of H were 50864 voxels by 6241 detector pixels. In this paper we present results of the SVD of each system and discuss calculation of the measurement and null space for each system.

Tc-99m pyrophosphate imaging of poloxamer-treated electroporated skeletal muscle in an in vivo rat model.

OBJECTIVE: This study investigates whether (99m)Tc pyrophosphate (PYP) imaging provides a quantitative non-invasive assessment of the extent of electroporation injury, and of the effect of poloxamer in vivo on electroporated skeletal muscle. METHODS: High-voltage electrical shock was used to produce electroporation injury in an anesthetized rat's hind limb. In each experiment, the injured limb was treated intravenously by either poloxamer-188, dextran, or saline, and subsequently imaged with (99m)Tc PYP. The radiotracer's temporal behavior among the experimental groups was compared using curve fitting of time-activity curves from the dynamic image data. RESULTS: The washout kinetics of (99m)Tc PYP changed in proportion to the electric current magnitude that produced electroporation. Also, (99m)Tc PYP washout from electroporated muscle differed between poloxamer-188 treatment and saline treatment. Finally, 10-kDa dextran treatment of electroporated muscle altered (99m)Tc PYP washout less than poloxamer-188 treatment. CONCLUSIONS: Behavior of (99m)Tc PYP in electroporated muscle appears to be an indicator of the amount of electroporation injury. Compared to saline, intravenous polaxamer-188 treatment reduced the amount of (99m)Tc PYP uptake. Coupled to results showing poloxamer-188 seals ruptured cellular membranes, lessens the extent of electroporation injury and improves cell viability, (99m)Tc PYP imaging appears to be a useful in vivo monitoring tool for the extent of electroporation injury.

Update on detection of sentinel lymph nodes in patients with breast cancer.

Sentinel lymph node biopsy is now the practice of choice for the management of many patients with breast cancer. This was not true in the early 1990s, when the first such procedures were performed and protocols for such were refined often. This was also not true in the first years of the 21st century, when a decade of collective experience and information acquired from numerous clinical investigations dictated additional subtle and not-so-subtle refinements of the procedures. However, it is true today; reports of the latest round of clinical investigations indicate that there are several breast cancer sentinel node procedures that result in successful identification of potential sentinel nodes in nearly all patients who are eligible for such procedures. A significant component of many of these successful sentinel node procedures is a detection and localization protocol that involves radiotracer methodologies, including radiopharmaceutical administration, preoperative nuclear medicine imaging, and intraoperative gamma counting. The present state and roles of nuclear medicine protocols used in breast cancer sentinel lymph node biopsy procedures is reviewed with emphasis on discussion of recent results, unresolved issues, and future considerations. Included are brief reviews of present radiotracer and blue-dye techniques for node localization, including remarks about injection strategies, counting probe technology, and radiation safety. Included also are discussions of on-going investigations of the implications of the presence of micrometastases; of the management value of detection, localization, and excision of extra-axillary nodes such as internal mammary nodes; and of the broad range of recurrence rates presently being reported. Remarks on the present and possible near- and long-term roles for nuclear medicine in the staging of breast cancer patients including comments on positron emission tomography and intraoperative imaging conclude the article.