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.

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.

The role of single-photon emission computed tomography and SPECT/computed tomography in oncologic imaging.

Single-photon emission computed tomography (SPECT) and hybrid SPECT/computed tomography (SPECT/CT) cameras have emerged as a dominant technology providing invaluable tools in the diagnosis, staging, therapy planning, and treatment monitoring of multiple cancers over the past decade. In the same way that positron emission tomography (PET) benefited from the addition of CT, functional SPECT and anatomic CT data obtained as a single study have shown improvements in diagnostic imaging sensitivity and specificity by improving lesion conspicuity, reducing false positives, and clarifying indeterminate lesions. Furthermore, the anatomic imaging better localizes the functional data, which can be critical in surgical and therapy planning. As more disease-specific imaging agents become available, the role of SPECT/CT in the new paradigms of molecular imaging for personalized medicine will expand. Established and emerging uses of SPECT/CT in a wide variety of oncologic diseases, as well as radiation exposure issues, are reviewed.

Intraoperative gamma imaging of axillary sentinel lymph nodes in breast cancer patients.

Sentinel lymph node (SLN) biopsy is now standard practice in the management of many breast cancer patients. Localization protocols vary in complexity and rates of success. The least complex involve only intraoperative gamma counting of radiotracer uptake or intraoperative visualization of blue-dye uptake; the most complex involve preoperative gamma imaging, intraoperative counting and intraoperative dye visualization. Intraoperative gamma imaging may improve some protocols. This study was conducted to obtain preliminary experience and information regarding intraoperative imaging. Sixteen patients were enrolled: 8 in a protocol that included intraoperative counting and dye visualization (probe/dye), 8 in a protocol that involved intraoperative imaging, counting and dye visualization (camera/probe/dye). Preoperative imaging of all 16 patients was performed using a GE 500 gamma camera with a LEAP collimator (300 cpm/muCi). The results of this imaging were not, however, given to the surgeon until the surgeon had completed the procedures required for the study. A Care Wise C-Trak probe was used for intraoperative counting. A Gamma Medica Inc. GammaCAM/OR (12.5 x 12.5 cm FOV) with a LEHR collimator (135 cpm/muCi) was used for intraoperative imaging. Times from start of surgery to external detection of a radioactive focus and to completion of excision of SLNs were recorded. Foci were detected preoperatively via imaging in 16/16 patients. Intraoperative external detection using the probe was accomplished in less than 4 min (mean = 1.5 min) in 15/16 patients, and via intraoperative imaging in 6/8 patients. The average time for completion of excision of nodes was 19 min for probe/dye and 28 min for camera/probe/dye. In one probe/dye case, review of the preoperative images prompted the surgeon to resume axillary dissection and remove one additional SLN.

Difference in filtered-back projection and iterative reconstruction in a patient with increased splanchnic uptake.

We performed a dual isotope, gated adenosine stress myocardial perfusion study on a 44-year-old man. Using filtered-back projection, images showed an inferior wall defect. However, intense liver uptake during adenosine stress was suspected to inaccurately cause diminished inferior wall counts. The patient has end-stage renal disease, diabetes mellitus, and hypertension. The excessive hepatic uptake was noted on planar rotating images and is likely related (at least in part) to reduced renal uptake (not shown subsequently). Using iterative reconstruction, the inferior cardiac defect was markedly reduced. The patient subsequently underwent surgery without complication.

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.