Melanoma: Ross MI

Coit DG, Andtbacka R, Bichakjian CK, Dilawari RA, Dimaio D, Guild V, Halpern AC, Hodi FS, Kashani-Sabet M, Lange JR, Lind A, Martin L, Martini MC, Pruitt SK, Ross MI, Sener SF, Swetter SM, Tanabe KK, Thompson JA, Trisal V, Urist MM, Weber J, Wong MK, Anonymous00048. · No affiliation provided · J Natl Compr Canc Netw. · Pubmed #19401060 No free full text.

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Houghton AN, Coit DG, Daud A, Dilawari RA, Dimaio D, Gollob JA, Haas NB, Halpern A, Johnson TM, Kashani-Sabet M, Kraybill WG, Lange JR, Martini M, Ross MI, Samlowski WE, Sener SF, Tanabe KK, Thompson JA, Trisal V, Urist MM, Walker MJ, Anonymous00370. · No affiliation provided · J Natl Compr Canc Netw. · Pubmed #16884669 No free full text.

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Balch CM, Ross MI. · No affiliation provided · Ann Surg Oncol. · Pubmed #10458675 No free full text.

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Balch CM, Ross MI. · No affiliation provided · J Am Coll Surg. · Pubmed #10437843 No free full text.

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Balch CM, Ross MI. · No affiliation provided · Ann Surg Oncol. · Pubmed #10340880 No free full text.

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Beasley GM, Ross MI, Tyler DS. · Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA. · Int J Hyperthermia. · Pubmed #18393007 No free full text.

Abstract: Hyperthermic isolated limb perfusion (HILP) with melphalan and more recently isolated limb infusion (ILI) with melphalan +/- dactinomycin are common treatment modalities for both in-transit melanoma of the extremity and advanced extremity sarcoma. In order to further optimize treatment, future research should focus on selection of appropriate patients, verification of a technique that produces consistent results while maintaining acceptable toxicity, and development of novel strategies and agents. Development of these novel agents and strategies has potential to not only improve the efficacy of regional chemotherapy but may also help guide future strategies for systemic treatment.

Ross MI. · MD Anderson Cancer Center, Houston, TX 77030, USA. · Int J Hyperthermia. · Pubmed #18392999 No free full text.

Abstract: In-transit disease is a unique form of regional lymphatic spread of melanoma that is considered an infrequent event although certain high-risk subgroups have been identified with higher incidence rates. Although this disease entity is associated with a high risk for distant relapse, regionally focused treatment of disease is important due to the high morbidity associated with in-transit disease. Isolated limb perfusion has been a utilized method of regional treatment since the 1950's. The technical aspects, indications, historical results, and toxicity of limb perfusion are reviewed. Finally, perfusion based treatment of in-transit melanoma is an excellent model for studying novel agents and regimens in both the pre-clinical and patient care setting.

Ross MI. · Department of Surgical Oncology, University of Texas M. D. Anderson Cancer Center, 1400 Holcombe Boulevard, Unit #444, Houston, TX 77030, USA. · Surg Oncol Clin N Am. · Pubmed #16632219 No free full text.

Abstract: Accurate melanoma staging is critical in establishing management strategies and estimating disease relapse. Combined with assessment of comorbidities and understanding treatment toxicities, risk assessment is central to offering appropriate surgical or systemic therapies. The American Joint Commission on Cancer (AJCC) melanoma staging system provides survival estimates within anatomically defined disease categories. Newer prognostic factors and methods of prognostic analyses can augment predictions for the presence of micro-metastatic disease and further define the risk for relapse. This article highlights relevant changes, evidence supporting future incorporation of more recently defined prognostic variables, novel approaches used as adjuncts to the current staging system, and future directions of the AJCC staging committee.

Ross MI. · Department of Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. · Clin Cancer Res. · Pubmed #16609051 links to  free full text

Abstract: Accurate risk assessment is central to the process of making rational surgical and systemic treatment recommendations for melanoma patients and in establishing appropriate clinical trial stratification criteria. The current American Joint Commission on Cancer melanoma staging system incorporated relevant prognostic variables to provide a framework for the estimation of risk for recurrence; however, significant prognostic heterogeneity exists within the stage groupings. In the stage I/II group, survival rates range from 40% to 95% as defined by the combination of tumor thickness and ulceration. The use of novel prognostic factors, such as mitotic rate, sentinel node biopsy, and prognostic modeling using a variety of factors, can minimize this prognostic heterogeneity and provide a more accurate and individualized prognostic profile. Recent modifications in the stage III criteria include the number of positive nodes, whether the nodal disease is microscopic or clinically apparent, and the presence of an ulcerated primary. Through these factors, survival estimates can be provided, but like the stage I/II group, wide ranges in prognosis exist. The complexion of the stage III population is in evolution as a result of increasing numbers of patients being diagnosed as having microscopic sentinel node disease. Contemporary efforts are focused on defining the prognosis and natural history of this group. Through prognostic modeling using the number of nodes involved, ulceration status, and a measure of disease burden--disease in the sentinel node--relatively homogeneous subgroups can be identified. Long-term follow-up of patients staged with PCR molecular techniques on sentinel nodes shows conflicting value in assessing prognosis and therefore cannot be routinely used outside a clinical trial. The combination of genomic profiling using microarray analyses and the development of targeted therapy holds the future promise of individualizing prognosis and therapy.

Balch CM, Soong SJ, Atkins MB, Buzaid AC, Cascinelli N, Coit DG, Fleming ID, Gershenwald JE, Houghton A, Kirkwood JM, McMasters KM, Mihm MF, Morton DL, Reintgen DS, Ross MI, Sober A, Thompson JA, Thompson JF. · American Society of Clinical Oncology, Alexandria, VA, USA. · CA Cancer J Clin. · Pubmed #15195788 links to  free full text

Abstract: A completely revised staging system for cutaneous melanoma was implemented in 2003. The changes were validated with a prognostic factors analysis involving 17,600 melanoma patients from prospective databases. This major collaborative study of predicting melanoma outcome was conducted specifically for this project, and the results were used to finalize the criteria for this evidence-based staging system. In fact, this was the largest prognostic factors analysis of prospectively followed melanoma patients ever conducted. Important results that shaped the staging criteria involved both the tumor-node-metastasis (TNM) criteria and stage grouping for all four stages of melanoma. Major changes in the staging include: (1) melanoma thickness and ulceration are the dominant predictors of survival in patients with localized melanoma (Stages I and II); deeper level of invasion (ie, IV and V) was independently associated with reduced survival only in patients with thin or T1 melanomas. (2) The number of metastatic lymph nodes and the tumor burden were the most dominant predictors of survival in patients with Stage III melanoma; patients with metastatic nodes detected by palpation had a shorter survival compared with patients whose nodal metastases were first detected by sentinel node excision of clinically occult or "microscopic" metastases. (3) The site of distant metastases (nonvisceral versus lung versus all other visceral metastatic sites) and the presence of elevated serum lactate dehydrogenase (LDH) were the dominant predictors of outcome in patients with Stage IV or distant metastases. (4) An upstaging was implemented for all patients with Stage I, II, and III disease when a primary melanoma is ulcerated by histopathological criteria. (5) Satellite metastases around a primary melanoma and in-transit metastases were merged into a single staging entity that is grouped into Stage III disease. (6) A new convention was implemented for defining clinical and pathological staging so as to take into account the new staging information gained from lymphatic mapping and sentinel node biopsy.

Pawlik TM, Ross MI, Gershenwald JE. · Department of Surgical Oncology, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA. · Ann Surg Oncol. · Pubmed #15070595 No free full text.

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Balch CM, Buzaid AC, Soong SJ, Atkins MB, Cascinelli N, Coit DG, Fleming ID, Gershenwald JE, Houghton A, Kirkwood JM, McMasters KM, Mihm MF, Morton DL, Reintgen DS, Ross MI, Sober A, Thompson JA, Thompson JF. · Johns Hopkins Medical Institutions, Baltimore, MD, USA. · Semin Surg Oncol. · Pubmed #12923915 No free full text.

Abstract: The American Joint Committee on Cancer (AJCC) implemented major revisions of the melanoma TNM and stage grouping criteria in the recently published 6th edition of the Staging Manual. The new staging system better reflects independent prognostic factors that are used in clinical trials and in reporting the outcomes of various melanoma treatment modalities. Major revisions include: 1) melanoma thickness and ulceration but not level of invasion to be used in the T classification, 2) the number of metastatic lymph nodes rather than their gross dimensions and the delineation of microscopic vs. macroscopic nodal metastases to be used in the N classification, 3) the site of distant metastases and the presence of elevated serum lactic dehydrogenase (LDH) to be used in the M classification, 4) an upstaging of all patients with Stage I, II, and III disease when a primary melanoma is ulcerated, 5) a merging of satellite metastases around a primary melanoma and in transit metastases into a single staging entity that is grouped into Stage III disease, and 6) a new convention for defining clinical and pathological staging so as to take into account the new staging information gained from intraoperative lymphatic mapping and sentinel node biopsy.

Sondak VK, Ross MI, Schuchter LM. · University of Michigan, 3306 Comprehensive Cancer and Geriatrics Center, 1500 East Medical Center Drive, Ann Arbor, MI 48109-0932, USA. · Curr Treat Options Oncol. · Pubmed #12057118 No free full text.

Abstract: Metastatic melanoma beyond the regional nodes (American Joint Committee on Cancer stage IV) is a highly lethal disease. Few affected individuals survive beyond 5 years despite aggressive treatment. Clearly, effective adjuvant therapies to prevent the development of stage IV disease in at-risk patients are worthwhile and acceptable to patients, even if they are associated with significant toxicities. Improvements in our understanding of the prognosis and staging of melanoma have allowed us to better categorize patients based on their risk of developing metastatic disease, permitting the development of logical strategies using adjuvant therapies with toxicity profiles that are appropriate based on the level of risk for recurrence. Adherence to the standards of care for the surgical management of melanoma patients with high-risk primary disease or regional disease will help optimize the benefit that can be derived from adjuvant therapy. Clinical trials remain critically important as we seek to improve the outcome for melanoma patients, but for high-risk melanoma patients outside the context of clinical trials, adjuvant therapy with high-dose interferon-alfa2b should be considered a standard treatment option.

Balch CM, Buzaid AC, Soong SJ, Atkins MB, Cascinelli N, Coit DG, Fleming ID, Gershenwald JE, Houghton A, Kirkwood JM, McMasters KM, Mihm MF, Morton DL, Reintgen DS, Ross MI, Sober A, Thompson JA, Thompson JF. · Johns Hopkins Medical Institutions, Baltimore, MD, USA. · J Clin Oncol. · Pubmed #11504745 No free full text.

Abstract: PURPOSE: To revise the staging system for cutaneous melanoma under the auspices of the American Joint Committee on Cancer (AJCC). MATERIALS AND METHODS: The prognostic factors analysis described in the companion publication (this issue), as well as evidence from the published literature, was used to assemble the tumor-node-metastasis criteria and stage grouping for the melanoma staging system. RESULTS: Major changes include (1) melanoma thickness and ulceration but not level of invasion to be used in the T category (except for T1 melanomas); (2) the number of metastatic lymph nodes rather than their gross dimensions and the delineation of clinically occult (ie, microscopic) versus clinically apparent (ie, macroscopic) nodal metastases to be used in the N category; (3) the site of distant metastases and the presence of elevated serum lactic dehydrogenase to be used in the M category; (4) an upstaging of all patients with stage I, II, and III disease when a primary melanoma is ulcerated; (5) a merging of satellite metastases around a primary melanoma and in-transit metastases into a single staging entity that is grouped into stage III disease; and (6) a new convention for defining clinical and pathologic staging so as to take into account the staging information gained from intraoperative lymphatic mapping and sentinel node biopsy. CONCLUSION: This revision will become official with publication of the sixth edition of the AJCC Cancer Staging Manual in the year 2002.

McMasters KM, Reintgen DS, Ross MI, Gershenwald JE, Edwards MJ, Sober A, Fenske N, Glass F, Balch CM, Coit DG. · Department of Surgery, University of Louisville, James Graham Brown Cancer Center, KY 40202, USA. · J Clin Oncol. · Pubmed #11387357 No free full text.

Abstract: Although sentinel lymph node (SLN) biopsy for melanoma has been adopted throughout the United States and abroad as a standard method of determining the pathologic status of the regional lymph nodes, some controversy still exists regarding the validity and utility of this procedure. SLN biopsy is a minimally invasive procedure, performed on an outpatient basis at the time of wide local excision of the melanoma, with little morbidity. Numerous studies have documented the accuracy of this procedure for identifying nodal metastases. There are four major reasons to perform SLN biopsy. First, SLN biopsy improves the accuracy of staging and provides valuable prognostic information for patients and physicians to guide subsequent treatment decisions. Second, SLN biopsy facilitates early therapeutic lymph node dissection for those patients with nodal metastases. Third, SLN biopsy identifies patients who are candidates for adjuvant therapy with interferon alfa-2b. Fourth, SLN biopsy identifies homogeneous patient populations for entry onto clinical trials of novel adjuvant therapy agents. Overall, the benefit of accurate nodal staging obtained by SLN biopsy far outweighs the risks and has important implications for patient management.

Gershenwald JE, Buzaid AC, Ross MI. · Department of Surgical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA. · Clin Lab Med. · Pubmed #11221515 No free full text.

Abstract: Although a standardized and uniformly accepted cancer staging system is an essential and fundamental requirement to enable meaningful comparisons across patient populations, the sometimes capricious biologic behavior of melanoma makes developing such a staging system particularly difficult. Since the earliest well-documented attempts at classifying patients with cutaneous melanoma were described more than 50 years ago, the identification of increasingly powerful prognostic factors has led to sequential modifications of the cutaneous melanoma staging system. The current AJCC staging system is based on relatively well-established prognostic factors; however, several recent reports have identified additional prognostic factors not included in the current system, and other studies support the re-evaluation of some of the currently employed staging criteria. Some of the more controversial areas include the relevance of level of invasion versus tumor thickness, optimal cutoffs for tumor thickness, importance of ulceration, the grouping of satellites with in-transit metastases, the inclusion of microsatellites and local recurrences as a separate staging criterion, the replacement of size of nodal mass with number of positive nodes, the importance of nodal metastases in more than one nodal basin, and the prognostic significance of distant metastases. Future modifications of the staging system are anticipated to better incorporate these observations. Stage-specific staging recommendations for the patient with melanoma provide the clinician with a framework to most efficiently assess extent of disease in an era of cost-conscious clinical practice. In the asymptomatic patient with primary melanoma (stage I or II), we recommend a chest roentgenogram and evaluation of alkaline phosphatase and LDH levels; extensive radiologic evaluations are not indicated, because the rate of detection in this population is extremely low. Additional staging information should also be obtained by the technique of lymphatic mapping and sentinel lymphadenectomy. For patients with local-regional disease (stage III, satellites, and local recurrence), a selective approach to imaging studies is warranted. For this patient population, we recommend complete blood count, liver function tests including alkaline phosphatase and LDH, a chest roentgenogram, and a CT scan of the abdomen. Although the yield of these tests, particularly CT of the abdomen, in detecting distant metastases in asymptomatic patients is low, they may identify false-positive abnormalities and provide an important baseline for future studies in this high-risk population. For patients with disease below the waist or in the head and neck region, we recommend CT of the pelvis and CT of the neck, respectively. Additional studies should be done only if clinically indicated. Finally, patients with known systemic disease (stage IV) should be more comprehensively evaluated, because the likelihood of detecting asymptomatic metastases is higher. Accordingly, in addition to the work-up outlined previously for stage III patients, we also perform a CT scan of the chest and MR imaging of the brain; other studies (e.g., bone scan, gastrointestinal series) are performed on the basis of symptoms.

McMasters KM, Sondak VK, Lotze MT, Ross MI. · Department of Surgery, University of Louisville, KY, USA. · Ann Surg Oncol. · Pubmed #10458685 No free full text.

Abstract: BACKGROUND: Recent advances in the staging and treatment of melanoma were reviewed. METHODS: A literature-based review was performed. RESULTS: The current American Joint Committee on Cancer (AJCC) Staging system for melanoma has several drawbacks. Proposed changes in the staging system to take into account simplified tumor thickness categories, tumor ulceration, and the number (rather than size) of nodal metastases will allow stage groups with more uniform prognosis. The widespread application of sentinel lymph node biopsy for nodal staging allows accurate nodal staging with minimal morbidity. Reverse transcriptase-polymerase chain reaction (RT-PCR) is a very sensitive molecular staging test that may prove useful for identifying early metastatic disease. There is finally an effective adjuvant therapy for melanoma--interferon alfa-2b. Other adjuvant therapies, including melanoma vaccines, may provide effective and less toxic alternatives. New immunotherapy and gene therapy strategies are under investigation. CONCLUSIONS: Ongoing and future adjuvant therapy trials will benefit from improved melanoma staging by accrual of homogeneous groups of patients. New approaches for adjuvant therapy await completion of clinical trials. Innovative new therapies offer hope for patients with advanced disease.

Kim KB, Eton O, Davis DW, Frazier ML, McConkey DJ, Diwan AH, Papadopoulos NE, Bedikian AY, Camacho LH, Ross MI, Cormier JN, Gershenwald JE, Lee JE, Mansfield PF, Billings LA, Ng CS, Charnsangavej C, Bar-Eli M, Johnson MM, Murgo AJ, Prieto VG. · Department of Melanoma Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. · Br J Cancer. · Pubmed #18728664 No free full text.

Abstract: Metastatic melanoma cells express a number of protein tyrosine kinases (PTKs) that are considered to be targets for imatinib. We conducted a phase II trial of imatinib in patients with metastatic melanoma expressing at least one of these PTKs. Twenty-one patients whose tumours expressed at least one PTK (c-kit, platelet-derived growth factor receptors, c-abl, or abl-related gene) were treated with 400 mg of imatinib twice daily. One patient with metastatic acral lentiginous melanoma, containing the highest c-kit expression among all patients, had dramatic improvement on positron emission tomographic scan at 6 weeks and had a partial response lasting 12.8 months. The responder had a substantial increase in tumour and endothelial cell apoptosis at 2 weeks of treatment. Imatinib was fairly well tolerated: no patient required treatment discontinuation because of toxicity. Fatigue and oedema were the only grade 3 or 4 toxicities that occurred in more than 10% of the patients. Imatinib at the studied dose had minimal clinical efficacy as a single-agent therapy for metastatic melanoma. However, based on the characteristics of the responding tumour in our study, clinical activity of imatinib, specifically in patients with melanoma with certain c-kit aberrations, should be examined.

McMasters KM, Noyes RD, Reintgen DS, Goydos JS, Beitsch PD, Davidson BS, Sussman JJ, Gershenwald JE, Ross MI, Anonymous00130. · The Department of Surgery, University of Louisville, James Graham Brown Cancer Center and Center for Advanced Surgical Technologies (CAST), Louisville, Kentucky 40202, USA. · J Surg Oncol. · Pubmed #15221928 No free full text.

Abstract: The Sunbelt Melanoma Trial is an ongoing multicenter prospective randomized trial that involves 79 centers and over 3600 patients from across the United States and Canada. This is one of the first large randomized studies to incorporate molecular staging using reverse transcriptase polymerase chain reaction (RT-PCR). While the results related to the primary endpoints of the study are not yet available, several analyses have shed light on many aspects of sentinel lymph node (SLN) biopsy and melanoma prognostic factors. In particular, we have developed a practical definition of sentinel nodes based on the degree of radioactivity. We have established the low rate of postoperative complications associated with SLN biopsy as compared to complete lymph node dissection. We have identified factors that predict the presence of SLN metastases. In contrast, we have been unable to identify factors that indicate a low risk of non-sentinel node metastases in patients with a positive sentinel node, suggesting that completion lymphadenectomy is appropriate for such patients. We have further established the value of identifying interval or in-transit sentinel nodes, which can be the only site of nodal metastasis. We have evaluated the particular challenges associated with SLN biopsy of head and neck melanomas, have evaluated the patterns of early recurrence, and have identified an interesting correlation between increasing patient age and a number of prognostic factors. Future analyses will evaluate the benefit of early therapeutic lymphadenectomy and early institution of adjuvant interferon alfa-2b therapy, as well as the validity of molecular staging.

Chao C, Martin RC, Ross MI, Reintgen DS, Edwards MJ, Noyes RD, Hagendoorn LJ, Stromberg AJ, McMasters KM. · Department of Surgery, Division of Surgical Oncology, James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky 40202, USA. · Ann Surg Oncol. · Pubmed #14993020 No free full text.

Abstract: BACKGROUND: Age of patients with melanoma varies directly with mortality and inversely with the presence of sentinel lymph node (SLN) metastasis. To gain further insight into this apparent paradox, we analyzed the relationship between age and other major prognostic factors. METHODS: The Sunbelt Melanoma Trial is a prospective, randomized study with 79 institutions involving SLN biopsy for melanoma. Eligible patients were 18 to 70 years old with melanoma of > or = 1.0-mm Breslow thickness and clinically N0 regional lymph nodes. SLNs were evaluated by serial histological sections and immunohistochemistry for S-100 protein. RESULTS: A total of 3076 patients were enrolled in the study, with a median follow-up of 19 months. Five age groups were examined: 18 to 30, 31 to 40, 41 to 50, 51 to 60, and 61 to 70 years. Trends between age and several key prognostic factors was identified: as age group increased, so did Breslow thickness (analysis of variance; P <.001), the incidence of ulceration and regression, and the proportion of male patients (each variable: chi2, P <.001). The incidence of SLN metastasis, however, declined with increasing age (chi2; P <.001). CONCLUSIONS: As age increases, so does Breslow thickness, the incidence of ulceration and regression, and the proportion of male patients-all poor prognostic factors. However, the frequency of SLN metastasis declines with increasing age. It is not known whether this represents a decreased sensitivity (higher false-negative rate) of the SLN procedure in older patients or a different biological behavior (hematogenous spread) of melanomas in older patients.

Wrightson WR, Wong SL, Edwards MJ, Chao C, Reintgen DS, Ross MI, Noyes RD, Viar V, Cerrito PB, McMasters KM, Anonymous00483. · Division of Surgical Oncology, Department of Surgery, University of Louisville, James Graham Brown Cancer Center, Kentucky, USA. · Ann Surg Oncol. · Pubmed #12839853 No free full text.

Abstract: BACKGROUND: Sentinel lymph node (SLN) biopsy has become widely accepted as a method of staging the regional lymph nodes for patients with melanoma. Although it is often stated that SLN biopsy is a minimally invasive procedure associated with few complications, a paucity of data exists to specifically determine the morbidity associated with this procedure. This analysis was performed to evaluate the morbidity associated with SLN biopsy compared with completion lymph node dissection (CLND). METHODS: Patients were enrolled in the Sunbelt Melanoma Trial, a prospective multi-institutional study of SLN biopsy for melanoma. Patients underwent SLN biopsy and were prospectively followed up for the development of complications associated with this technique. Patients who had evidence of nodal metastasis in the SLN underwent CLND. Complications associated with SLN biopsy alone were compared with those associated with SLN biopsy plus CLND. RESULTS: A total of 2120 patients were evaluated, with a median follow-up of 16 months. Overall, 96 (4.6%) of 2120 patients developed major or minor complications associated with SLN biopsy, whereas 103 (23.2%) of 444 patients experienced complications associated with SLN biopsy plus CLND. There were no deaths associated with either procedure. CONCLUSIONS: SLN biopsy alone is associated with significantly less morbidity compared with SLN biopsy plus CLND.

Chao C, Wong SL, Edwards MJ, Ross MI, Reintgen DS, Noyes RD, Stadelmann WK, Lentsch E, McMasters KM, Anonymous00171. · Division of Surgical Oncology, James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky 40202, USA. · Ann Surg Oncol. · Pubmed #12513955 No free full text.

Abstract: BACKGROUND: Sentinel lymph node (SLN) biopsy for head and neck (H&N) melanomas may be more technically challenging compared with other locations because of complex lymphatic drainage patterns. This analysis was performed to compare the results of SLN biopsy for H&N, truncal, and extremity melanomas. METHODS: The Sunbelt Melanoma Trial includes patients aged 18 to 70 with melanomas > or = 1.0 mm thick. Statistical comparison was performed by chi2 or analysis of variance test. RESULTS: A total of 2610 patients were evaluated with a median follow-up of 18 months. The mean number of SLN per nodal basin was 2.8, 2.7, and 2.1 for H&N, truncal, and extremity melanomas, respectively. Median Clark level, Breslow thickness, and percentage of ulceration were similar between the groups. Peri-parotid SLN was identified in 25% of cases; there were no facial nerve injuries. SLN biopsy for H&N melanoma had higher false-negative rates at 1.5% (vs. 0.5% for trunk or extremity) but less histologically positive SLN at 15% (vs. 23.4%, and 19.5%; P <.001) compared with truncal and extremity melanoma. Blue dye was visualized less frequently in SLN of H&N melanoma patients compared with those with trunk or extremity melanomas. CONCLUSIONS: Preoperative lymphoscintigraphy and meticulous intraoperative search for blue/radioactive nodes may improve results in H&N melanomas.

Chao C, Wong SL, Ross MI, Reintgen DS, Noyes RD, Cerrito PB, Edwards MJ, McMasters KM, Anonymous00017. · Department of Surgery, Division of Surgical Oncology, James Graham Brown Cancer Center, University of Louisville, 315 East Broadway, Suite 309, KY 40202, USA. · Am J Surg. · Pubmed #12488154 No free full text.

Abstract: BACKGROUND: Patterns of early recurrence after sentinel lymph node (SLN) biopsy for melanoma was determined from the Sunbelt Melanoma Trial, which includes patients with Breslow thickness > or =1.0 mm and nonpalpable regional lymph nodes. METHODS: SLN were evaluated by routine histology and S-100 protein stain. Overall, there were 1,183 patients with a median follow-up of 16 months. RESULTS: SLN were positive in 233 of 1,183 patients (20%). The recurrence rate was greater among patients with histologically positive SLN than those with negative SLN (15.5% versus 6.0%, respectively, P <0.05). Patients with positive SLN were more likely to have distant metastases (as opposed to locoregional recurrence) than those with negative SLN (67% versus 46%, respectively, P <0.05). By multivariate analysis, SLN status, Breslow thickness, Clark level, and ulceration were significant independent factors associated with early recurrence. Of patients with negative SLN, 14 of 950 (1.5%) experienced metastatic disease in lymph node basins which were staged as negative for tumor by SLN biopsy initially. CONCLUSIONS: Early regional lymph node recurrence was very uncommon after positive SLN biopsy and completion lymphadenectomy. Patients with positive SLN are more likely than those with negative SLN to develop both local/in-transit recurrence and distant metastases within a short follow-up period.

McMasters KM, Chao C, Wong SL, Wrightson WR, Ross MI, Reintgen DS, Noyes RD, Cerrito PB, Edwards MJ, Anonymous00215. · Division of Surgical Oncology, Department of Surgery, James Graham Brown Cancer Center, University of Louisvill, 529 S Jackson St, Louisville, KY 40202, USA. · Arch Surg. · Pubmed #11982466 links to  free full text

Abstract: HYPOTHESIS: For patients with melanoma, interval or in-transit sentinel lymph nodes (SLNs) have the same risk for nodal metastasis as SLN in traditional (ie, cervical, axillary, and inguinal) nodal basins. DESIGN: Prospective clinical trial. SETTING: Multicenter study. PATIENTS: Eligible patients were aged 18 to 70 years with melanomas of at least 1.0-mm Breslow thickness and nodes with clinically negative findings. INTERVENTION: Sentinel lymph node biopsy was guided by preoperative lymphoscintigraphy to identify all SLNs. MAIN OUTCOME MEASURES: We evaluated interval nodal sites, including epitrochlear, popliteal, and subcutaneous or intramuscular nodes outside of traditional basins, for the presence of metastases. RESULTS: The SLNs were identified in 2332 nodal basins from 2000 patients. In 62 patients (3.1%), interval SLNs were identified. We found SLN metastases in 442 (19.5%) of 2270 conventional nodal basins and 13 (21.0%) of 62 interval sites. In 11 (84.6%) of the 13 cases in which we found an interval node that was positive for metastatic disease, it was the only site of nodal metastasis. CONCLUSIONS: Although interval SLNs are identified infrequently, they contain metastatic disease at nearly the same frequency as SLNs in cervical, axillary, and inguinal nodal basins. Positive interval SLNs are likely to be the only site of nodal metastasis. Therefore, detailed preoperative lymphoscintigraphy and meticulous intraoperative search for interval nodes should be performed.

McMasters KM, Wong SL, Edwards MJ, Chao C, Ross MI, Noyes RD, Viar V, Cerrito PB, Reintgen DS. · Division of Surgical Oncology, Department of Surgery, University of Louisville, Louisville, Kentucky 40202, USA. · Ann Surg Oncol. · Pubmed #11888869 No free full text.

Abstract: BACKGROUND: Completion lymph node dissection (CLND) may not be necessary for some patients because nodal metastasis is rarely detected beyond the sentinel lymph nodes (SLNs). This analysis was performed to determine, among patients with positive SLNs, the rate of nodal metastasis found in nonsentinel nodes (NSNs). METHODS: This analysis includes patients with positive sentinel nodes, detected by hematoxylin and eosin (H&E) staining or immunohistochemistry (IHC), who then underwent CLND. RESULTS: This analysis included 274 patients with at least one positive SLN who underwent CLND of 282 involved regional nodal basins. Of the 282 SLN-positive nodal basins, 45 (16%) were found to have positive NSNs in the CLND specimen. Breslow thickness, Clark level, presence of ulceration, histological subtype, presence of vertical growth phase, evidence of regression, presence of lymphovascular invasion, number of positive SLNs, age, sex, and presence of multiple draining nodal basins were not predictive of positive nodes in the CLND specimen. Patients with SLN metastases detected only by IHC had an equal likelihood of having positive NSNs as those patients with positive SLNs on H&E examination. CONCLUSIONS: No patient population could be identified with minimal risk of non-SLN metastasis. When a positive SLN is identified on either H&E staining or IHC, CLND should be performed routinely.