Melanoma: Glass EC

Alazraki N, Glass EC, Castronovo F, Olmos RA, Podoloff D, Anonymous00207. · Division of Nuclear Medicine, Emory University School of Medicine, Veterans Affairs Medical Center, Atlanta, Georgia 30033, USA. · J Nucl Med. · Pubmed #12368382 links to  free full text

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Glass EC. · V.A. Greater Los Angeles Healthcare System, Los Angeles, California, USA. · Cancer Treat Res. · Pubmed #17953410 No free full text.

This publication has no abstract.

Cochran AJ, Essner R, Rose DM, Glass EC. · Department of Pathology and Laboratory Medicine, Jonsson Comprehensive Cancer Center, UCLA School of Medicine, Los Angeles, CA 90095-1732, USA. · Langenbecks Arch Surg. · Pubmed #10958508 No free full text.

Abstract: The management of clinically negative regional lymph nodes in early-stage melanoma has been controversial for many years. While some advocate wide excision of the primary with elective node dissection (ELND), others recommend excision of the primary alone and therapeutic node dissection (TLND) for recurrences in the nodal basin. ELND is based on the concept that metastases occur by passage of the tumor from the primary to the regional nodes and distant sites, in which case early dissection of regional nodes will disrupt metastatic progression and prevent the spread of disease. Advocates of the "wait and watch" approach suggest that regional node metastases are markers for disease progression and that distant disease can occur without node metastases. Four randomized prospective studies comparing ELND and TLND have not demonstrated overall survival advantage for ELND, but suggest that patients with early regional metastases may benefit from ELND. As an alternative, Morton et al., from UCLA and the John Wayne Cancer Institute, devised intraoperative lymphatic mapping and sentinel lymphadenectomy (LM/SL). These minimally invasive operative procedures allow identification of the first and key (sentinel) lymph node (SN). The technique accurately maps the lymphatics by lymphoscintigraphy, and vital blue dye leads the surgeon to the SN. The pathologist then concentrates on seeking metastases in the nodes most likely to contain metastases. Patients with tumor-positive SN undergo completion lymph node dissection (CLND), while those without SN metastases avoid the complications and costs associated with this procedure. Morton et al., in a report on their initial experience of LM/SL, performed CLND in all cases regardless of SN tumor status and demonstrated the precise staging capacity of the procedure. Since this initial report, numerous studies have validated the accuracy and low morbidity of the procedure. Each center must master a learning phase. The procedure is dependent on the close cooperation of nuclear medicine physicians, surgeons, and pathologists. While LM/SL is now almost standard practice in the US, the results of clinical trials are awaited to determine whether LM/SL can replace ELND and TLND in the management of early-stage melanoma.

Morton DL, Cochran AJ, Thompson JF, Elashoff R, Essner R, Glass EC, Mozzillo N, Nieweg OE, Roses DF, Hoekstra HJ, Karakousis CP, Reintgen DS, Coventry BJ, Wang HJ, Anonymous00289. · John Wayne Cancer Institute, Santa Monica, CA 90404, USA. · Ann Surg. · Pubmed #16135917 links to  free full text

Abstract: OBJECTIVE: The objective of this study was to evaluate, in an international multicenter phase III trial, the accuracy, use, and morbidity of intraoperative lymphatic mapping and sentinel node biopsy (LM/SNB) for staging the regional nodal basin of patients with early-stage melanoma. SUMMARY BACKGROUND DATA: Since our introduction of LM/SNB in 1990, this technique has been widely adopted and has become part of the American Joint Committee on Cancer (AJCC) staging system. Eleven years ago, the authors began the international Multicenter Selective Lymphadenectomy Trial (MSLT-I) to compare 2 treatment approaches: wide excision (WE) plus LM/SNB with immediate complete lymphadenectomy (CLND) for sentinel node (SN) metastases, and WE plus postoperative observation with CLND delayed until the subsequent development of clinically evident nodal metastases. METHODS: After each center achieved 85% accuracy of SN identification during a 30-case learning phase, patients with primary cutaneous melanoma (> or =1 mm with Clark level > or =III, or any thickness with Clark level > or =IV) were randomly assigned in a 4:6 ratio to WE plus observation (WEO) with delayed CLND for nodal recurrence, or to WE plus LM/SNB with immediate CLND for SN metastasis. The accuracy of LM/SNB was determined by comparing the rates of SN identification and the incidence of SN metastases in the LM/SNB group versus the subsequent development of nodal metastases in the regional nodal basin of those patients with tumor-negative SNs. Early morbidity of LM/SNB was evaluated by comparing complication rates between the 2 treatment groups. Trial accrual was completed on March 31, 2002, after enrollment of 2001 patients. RESULTS: Initial SN identification rate was 95.3% overall: 99.3% for the groin, 95.3% for the axilla, and 84.5% for the neck basins. The rate of false-negative LM/SNB during the trial phase, as measured by nodal recurrence in a tumor-negative dissected SN basin, decreased with increasing case volume at each center: 10.3% for the first 25 cases versus 5.2% after 25 cases. There were no operative mortalities. The low (10.1%) complication rate after LM/SNB increased to 37.2% with the addition of CLND; CLND also increased the severity of complications. CONCLUSIONS: LM/SNB is a safe, low-morbidity procedure for staging the regional nodal basin in early melanoma. Even after a 30-case learning phase and 25 additional LM/SNB cases, the accuracy of LM/SNB continues to increase with a center's experience. LM/SNB should become standard care for staging the regional lymph nodes of patients with primary cutaneous melanoma.

Essner R, Hsueh EC, Haigh PI, Glass EC, Huynh Y, Daghighian F. · Roy E. Coats Research Laboratories of the John Wayne Cancer Institute, Santa Monica, California 90404, USA. · J Surg Res. · Pubmed #11181005 No free full text.

Abstract: BACKGROUND: Whole-body positron emission tomography (PET) has been shown to be a highly sensitive method for detecting malignancy not imaged by conventional modalities. We have adapted a hand-held gamma-ray-sensitive probe to detect the radiation emission from the [(18)F]fluorodeoxyglucose (FDG) used in PET imaging. This pilot study was devised to examine the feasibility of using a hand-held probe to intraoperatively differentiate normal from tumor-bearing tissue. MATERIALS AND METHODS: A commercially available gamma probe was adapted to detect the radioactivity released from FDG and examined to determine the in vitro sensitivity for localization of a FDG point source. Eight consecutive patients underwent resection of metastatic colon cancer or melanoma; each received a preoperative injection of 7--10 mCi of FDG. The gamma probe was used to determine radioactive counts per second from tumor and normal tissue, and ratios of tumor to adjacent normal background were calculated. RESULTS: In vitro studies with a FDG point source demonstrated the probe could identify the source with a 50% reduction in maximum counts 1.7 +/- 0.1 cm from the source (full-width half-maximum measurement). Based on the results of their preoperative PET scans 17 tumors were identified from the 8 patients. Of the 17 tumors assessed the in vivo tumor-to-background ratios varied from 1.16:1 to 4.67:1 for the melanoma patients (13 tumors) and from 1.19:1 to 7.92:1 for colon cancer patients (4 tumors). Thirteen tumors were resected; four (2 patients) were unresectable. CONCLUSIONS: This study demonstrates the use of a hand-held gamma-ray-sensitive probe to intraoperatively differentiate the radioactivity released from FDG from tumor-bearing and adjacent normal tissue. While further studies are necessary for us to optimize the use of this probe, the intraoperative detection of FDG-avid malignancies may ultimately improve our ability to completely resect patients with metastatic disease.

Morton DL, Thompson JF, Essner R, Elashoff R, Stern SL, Nieweg OE, Roses DF, Karakousis CP, Mozzillo N, Reintgen D, Wang HJ, Glass EC, Cochran AJ. · John Wayne Cancer Institute, Santa Monica, CA 90404, USA. · Ann Surg. · Pubmed #10522715 links to  free full text

Abstract: OBJECTIVE: To evaluate the multicenter application of intraoperative lymphatic mapping, sentinel lymphadenectomy, and selective complete lymph node dissection (LM/SL/SCLND) for the management of early-stage melanoma. SUMMARY BACKGROUND DATA: The multidisciplinary technique of LM/SL/SCLND has been widely adopted, but not validated in a multicenter trial. The authors began the international Multicenter Selective Lymphadenectomy Trial (MSLT) 5 years ago to evaluate the survival of patients with early-stage primary melanoma after wide excision alone versus wide excision plus LM/SL/SCLND. This study examined the accuracy of LM/SL/SCLND in the MSLT, using the experience of the organizing center (John Wayne Cancer Institute [JWCI]) as a standard for comparison. METHODS: Before entering patients into the randomization phase, each center in the MSLT was required to finish a 30-case learning phase with complete nuclear medicine, pathology, and surgical review. Selection of MSLT patients in the LM/SL/SCLND treatment arm was based on complete pathologic and surgical data. The comparison group of JWCI patients was selected using these criteria: primary cutaneous melanoma having a thickness > or =1 mm with a Clark level > or =III, or a thickness <1 mm with a Clark level > or =IV (MSLT criterion); LM/SL performed between June 1, 1985, and December 30, 1998; and patient not entered in the MSLT. The accuracy of LM/SL/SCLND was determined by comparing the rates of sentinel node (SN) identification and the incidence of SN metastases in the MSLT and JWCI groups. RESULTS: There were 551 patients in the MSLT group and 584 patients in the JWCI group. In both groups, LM performed with blue dye plus a radiocolloid was more successful (99.1 %) than LM performed with blue dye alone (95.2%) (p = 0.014). After a center had completed the 30-case learning phase, the success of SN identification in the MSLT group was independent of the center's case volume or experience in the MSLT. CONCLUSIONS: Lymphatic mapping and sentinel lymphadenectomy can be successfully learned and applied in a standardized fashion with high accuracy by centers worldwide. Successful SN identification rates of 97% can be achieved, and the incidence of nodal metastases approaches that of the organizing center. A multidisciplinary approach (surgery, nuclear medicine, and pathology) and a learning phase of > or =30 consecutive cases per center are sufficient for mastery of LM/SL in cutaneous melanoma. Lymphatic mapping performed using blue dye plus radiocolloid is superior to LM using blue dye alone.

Conway WC, Faries MB, Nicholl MB, Terando AM, Glass EC, Sim M, Morton DL. · Department of Surgical Oncology, John Wayne Cancer Institute at Saint John's Health Center, Santa Monica, CA, USA. · Ann Surg Oncol. · Pubmed #19277787 No free full text.

Abstract: BACKGROUND: Age-related outcomes have become increasingly common in evaluating patients with melanoma. For instance, as age increases, sentinel node (SN) nonidentification increases and SN positivity decreases. Furthermore, advanced age is a risk factor for in-transit disease. We hypothesized that increasing age is accompanied by alterations in lymphatic function, possibly explaining these findings. METHODS: Our center's melanoma database was queried to identify patients who underwent successful sentinel node biopsy after lymphoscintigraphy. Records of those treated between 2000 and 2005 were reviewed for age, sex, drainage basin, intraoperative radioactivity, and SN pathology. RESULTS: The 858 patients had a mean age of 55 years; 59% were men. Mean radioactivity in the hottest SN was 5232 counts per second; 179 patients (21%) had SN metastases. SN count rates were significantly and inversely related to age (P < .001 by Pearson correlation, analysis of variance, and chi(2) test). Mean counts per second were 6105, 5883, and 2720 for axillary, inguinal, and cervical basins, respectively (P < .01), and count rates in these basins were consistently lower with increasing age (neck and axilla, P < .001; groin, P = .060; Pearson correlation). Multivariate analysis confirmed an independent inverse association between age and count rates (P < .001), overall and within each primary tumor site. CONCLUSIONS: Lymphatic function, as assessed by radiocolloid transit to and uptake within the SN, declines with age. Altered lymphatic function in older patients may modify metastatic patterns; knowledge of this may help clarify findings of reduced nodal positivity and increased in-transit disease in this population.

Morton DL, Thompson JF, Cochran AJ, Mozzillo N, Elashoff R, Essner R, Nieweg OE, Roses DF, Hoekstra HJ, Karakousis CP, Reintgen DS, Coventry BJ, Glass EC, Wang HJ, Anonymous00082. · Department of Surgical Oncology, John Wayne Cancer Institute at Saint John's Health Center, Santa Monica, CA 90404, USA. · N Engl J Med. · Pubmed #17005948 links to  free full text

Abstract: BACKGROUND: We evaluated the contribution of sentinel-node biopsy to outcomes in patients with newly diagnosed melanoma. METHODS: Patients with a primary cutaneous melanoma were randomly assigned to wide excision and postoperative observation of regional lymph nodes with lymphadenectomy if nodal relapse occurred, or to wide excision and sentinel-node biopsy with immediate lymphadenectomy if nodal micrometastases were detected on biopsy. RESULTS: Among 1269 patients with an intermediate-thickness primary melanoma, the mean (+/-SE) estimated 5-year disease-free survival rate for the population was 78.3+/-1.6% in the biopsy group and 73.1+/-2.1% in the observation group (hazard ratio for recurrence[corrected], 0.74; 95% confidence interval [CI], 0.59 to 0.93; P=0.009). Five-year melanoma-specific survival rates were similar in the two groups (87.1+/-1.3% and 86.6+/-1.6%, respectively). In the biopsy group, the presence of metastases in the sentinel node was the most important prognostic factor; the 5-year survival rate was 72.3+/-4.6% among patients with tumor-positive sentinel nodes and 90.2+/-1.3% among those with tumor-negative sentinel nodes (hazard ratio for death, 2.48; 95% CI, 1.54 to 3.98; P<0.001). The incidence of sentinel-node micrometastases was 16.0% (122 of 764 patients), and the rate of nodal relapse in the observation group was 15.6% (78 of 500 patients). The corresponding mean number of tumor-involved nodes was 1.4 in the biopsy group and 3.3 in the observation group (P<0.001), indicating disease progression during observation. Among patients with nodal metastases, the 5-year survival rate was higher among those who underwent immediate lymphadenectomy than among those in whom lymphadenectomy was delayed (72.3+/-4.6% vs. 52.4+/-5.9%; hazard ratio for death, 0.51; 95% CI, 0.32 to 0.81; P=0.004). CONCLUSIONS: The staging of intermediate-thickness (1.2 to 3.5 mm) primary melanomas according to the results of sentinel-node biopsy provides important prognostic information and identifies patients with nodal metastases whose survival can be prolonged by immediate lymphadenectomy. (ClinicalTrials.gov number, NCT00275496 [ClinicalTrials.gov].).

Shen P, Glass EC, DiFronzo LA, Giuliano AE. · Joyce Eisenberg Keefer Breast Cancer Center, John Wayne Cancer Institute at Saint John's Health Center, Santa Monica, California 90404, USA. · Ann Surg Oncol. · Pubmed #11314941 No free full text.

Abstract: BACKGROUND AND OBJECTIVE: Dermal and intraparenchymal (IP) injections of radiocolloid have been used for lymphoscintigraphic identification of the sentinel node (SN) in breast cancer. Because of our institute's extensive experience with dermal and IP lymphoscintigraphy for melanoma and breast cancer, we compared patterns of lymphatic migration after both types of injections to identify any differences in drainage patterns or SN identification. METHODS: Lymphoscintigrams (n = 31) after dermal injections in 30 patients with primary cutaneous melanoma on the breast were compared with lymphoscintigrams after IP injections in 97 consecutive patients with breast cancer. In each case, 400 microCi of filtered 99mTc-sulfur colloid was injected in four quadrants around the tumor or in the biopsy cavity. All lymphoscintigrams were reviewed for patterns of migration and SN location. RESULTS: Five of 31 (16%) dermal injections demonstrated bilateral axillary migration (n = 3) or a suprasternal SN (n = 2), neither of which was found with IP injections. Conversely, 3 of 97 (3%) IP injections demonstrated direct supraclavicular (n = 2) or costal margin (n = 1) nodes (P = .006), neither of which was found with dermal injections. Low axillary SNs were noted after 26 (84%) dermal and 93 (96%) IP injections (P = .037). The incidence of extra-axillary SNs was 26% (8 of 31) in the dermal group but only 5% (5 of 97) in the IP group (P = .0027). CONCLUSION: There is a significant difference in lymphatic drainage and SN localization between dermal and IP lymphoscintigraphy. This finding has implications for injection techniques when lymphatic mapping of the SN is undertaken to stage a breast carcinoma.

Essner R, Bostick PJ, Glass EC, Foshag LJ, Haigh PI, Wang HJ, Morton DL. · Roy E. Coats Research Laboratories of the John Wayne Cancer Institute, Santa Monica, CA 90404, USA. · Surgery. · Pubmed #10660755 No free full text.

Abstract: BACKGROUND: Radiopharmaceutical agents appear to improve the accuracy of sentinel node (SN) identification in patients with early-stage melanoma, but the optimal radiopharmaceutical agent and its timing from injection to surgery remain controversial. We undertook this investigation to examine the utility of 3 methods of intraoperative lymphatic mapping with radiopharmaceutical-directed sentinel lymphadenectomy (LM/SL). We suspected that concurrent injection of radiopharmaceutical and blue-dye would lead to the greatest success of SN identification. METHODS: The study was composed of 247 consecutive patients who had American Joint Committee on Cancer stage I or II melanoma. Before LM/SL, all patients underwent cutaneous lymphoscintigraphy by 1 of 3 techniques: technetium 99m (Tc 99m) human serum albumin (HSA) injected at least 24 hours before LM/SL (124 patients), Tc 99m filtered sulfur colloid (SC) injected no more than 4 hours before LM/SL (same-day SC, 95 patients), or Tc 99m SC injected at least 18 hours before LM/SL (prior-day SC, 28 patients). At the time of LM/SL, isosulfan blue dye was injected alone (SC groups) or with a second dose of HSA (HSA group). A hand-held gamma probe was used to determine the radioactive (hot) counts of blue-stained and nonstained nodes, and the in vivo and ex vivo node-to-background count ratios of the nodes were compared. RESULTS: Preoperative LS identified 299 drainage basins; LM/SL identified at least 1 SN in 119 (98%) of 121 basins using same-day SC, 142 (97%) of 146 basins using HSA, and 32 (100%) of 32 basins using prior-day SC. There was no difference (P = .62) in the accuracy rate between the 3 techniques. The total number of SNs was 463. Same-day SC yielded higher intraoperative node-to-background count ratios than did either of the other techniques (P < .0001). Same-day SC also had the greatest relative change in radioactivity between the blue sentinel node and the post-excision basin (P < .0001), and the highest rate of SNs that were both blue and hot (in vivo or ex vivo ratio > or = 2, P = .05). CONCLUSIONS: LS and LM/SL performed on the same day with a single injection of filtered Tc 99m SC serves as the most useful method for probe-directed LM/SL. This technique demonstrated the highest in vivo and ex vivo count ratios, fall-off of radioactivity between the excised nodes and post-excision basin, and concordance between blue dye and hot nodes. It should be recommended as the method of choice for probe-directed LM/SL.