Melanoma: Coit DG

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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Coit DG. · No affiliation provided · Ann Surg Oncol. · Pubmed #15965729 No free full text.

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Coit DG. · No affiliation provided · Ann Surg Oncol. · Pubmed #11314931 No free full text.

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Ariyan CE, Coit DG. · Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. · Semin Diagn Pathol. · Pubmed #18697711 No free full text.

Abstract: Sentinel lymph node (SLN) biopsy has evolved over the years to become one of the most useful tools in the treatment of melanoma. Large, multi-institutional studies have confirmed that in experienced hands it is an accurate, reliable technique to identify tumor in the draining lymph nodes. The complications of the procedure are low, and it is generally well tolerated. The presence of melanoma in the sentinel lymph node is the most important predictive factor in patients with intermediate thickness melanomas. In patients with thin melanomas (<1 mm), the incidence of a positive SLN is low. The choice to perform a SLN biopsy in these patients must be weighed with risk factors such as Clark level, ulceration, sex and mitotic rate. In patients with thick melanomas (>4 mm), most studies have supported the prognostic value of SLN status. Patients with desmoplastic melanomas have a high risk of local recurrence, but low risk of SLN metastasis if the pathology demonstrates a pure desmoplastic form. Younger patients have a higher incidence of positive lymph nodes, yet an overall more favorable prognosis compared to older patients. Patients should understand that this procedure remains primarily a staging tool, as large prospective randomized trials have not demonstrated an overall survival benefit.

Katz SC, Bowne WB, Wolchok JD, Busam KJ, Jaques DP, Coit DG. · Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. · Am J Surg. · Pubmed #17368297 No free full text.

Abstract: BACKGROUND: Melanoma has the potential to spread to virtually any organ, including the gallbladder. The role of intervention in this rare entity must be based on a thorough appreciation of the underlying disease biology. METHODS: We present a review of all patients treated for gallbladder melanoma at Memorial Sloan-Kettering Cancer Center (MSKCC) between 1991 and 2003. RESULTS: The study group consisted of 13 patients with melanoma metastatic to the gallbladder. The median survival was 12 months following the diagnosis, and only 1 patient survived more than 42 months. Factors associated with improved outcome included symptomatic metastases and metastatic disease confined to the gallbladder (P < .05). Cholecystectomy led to the resolution of right upper quadrant pain in all patients for the duration of their survival. CONCLUSIONS: In patients with melanoma metastatic to the gallbladder, overall survival is determined more by the biology of the disease than treatment. In the presence of symptoms, cholecystectomy is often effective palliation in carefully selected patients.

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.

Wong SL, Coit DG. · Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. · Curr Opin Oncol. · Pubmed #15075909 No free full text.

Abstract: PURPOSE OF REVIEW: The purpose of this brief review is to highlight recent advances in the surgical treatment of metastatic melanoma; to review factors important in the decision-making process of selecting the most appropriate patients for resection; and to discuss the current literature in the context of site of recurrence. RECENT FINDINGS: While there are relatively few new findings on the surgical treatment of metastatic melanoma, recent reports do support prior observations in the field. The recently revised staging system for melanoma groups metastatic disease according to prognostic features. There is currently a great deal of interest in the use of 18-fluorodeoxyglucose positron emission tomography (FDG-PET) to more accurately evaluate metastatic disease. The use stereotactic radiosurgery for brain metastases has expanded recently and adds to local treatment options. When procedures are performed with palliative intent, treatment goals must be clearly defined and communicated among the patient, family and surgeon. Improved understanding of the goals of palliative surgery may be facilitated by the concept of a palliative triangle, which helps define the decision making process among the patient, family members, and surgeon. SUMMARY: Metastatic melanoma is usually associated with a dismal prognosis. When a procedure is performed with palliative intent, appropriately selected patients usually experience reliable relief of symptoms and improved quality of life. Improved survival after a complete resection with curative intent is often predicted by good performance status, longer disease-free interval, limited extent of metastatic disease, and less aggressive tumor biology.

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.

Allen PJ, Coit DG. · Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. · Ann Surg Oncol. · Pubmed #12374659 No free full text.

Abstract: When deciding whether or not to perform a resection for metastatic melanoma, one should follow general principles that apply to the patient with melanoma as well as to the patient with metastases from other types of primary tumors. When the resection is palliative, the success of surgical treatment will be governed by the presence of identifiable symptoms, the morbidity of the procedure, the course of the disease, and the ability to communicate treatment goals among surgeon, patient, and family. When the resection is performed with curative intent, long-term survival depends on the ability of the surgeon to select patients with a pattern of recurrence suggestive of a less aggressive tumor biology. Regardless of the extent of the operative procedure, resection of metastases in patients whose disease recurs early after the treatment of the primary tumor, in those who present with multiple lesions, and in those who present with disease that cannot be completely resected will only rarely be associated with subsequent long-term survival.

Spanknebel K, Temple L, Hiotis S, Yeh A, Coit DG. · Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. · Surg Oncol Clin N Am. · Pubmed #11928800 No free full text.

Abstract: Efforts to improve the survival of patients with metastatic melanoma have led to 67 prospective randomized clinical trials investigating the use of agents comprising three main areas of therapy: systemic chemotherapy-based regimens, immunotherapy, and vaccine therapy

Allen PJ, Coit DG. · Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA. · Curr Opin Oncol. · Pubmed #11880715 No free full text.

Abstract: When deciding to perform a resection for metastatic melanoma one should first decide whether the intent of the procedure is curative or palliative. When the resection is palliative, the success of surgical treatment will depend on the presence of identifiable symptoms, the morbidity of the procedure, the course of the disease, and the ability to communicate the treatment goals among surgeon, patient, and family. When the resection is curative, survival will depend on the ability of the surgeon to select patients with a pattern of recurrence suggestive of less aggressive tumor biology. Factors generally found predictive of improved survival, and therefore reflective of tumor biology, include longer disease-free interval, fewer numbers of metastases, and the ability to obtain a complete resection. Resection of metastases in patients who recur within one-year, who present with multiple lesions, and who present with disease that cannot be completely resected, will not result in long-term survival.

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.

Ghossein RA, Bhattacharya S, Coit DG. · Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. · Recent Results Cancer Res. · Pubmed #11092034 No free full text.

Abstract: The detection of circulating tumor cells (CTC) and bone marrow micrometastases (BMM) by reverse transcriptase polymerase chain reaction (RT-PCR) may help predict recurrence and survival in malignant melanoma (MM). Since the appearance of the original article by Smith et al. in 1991 (Lancet 338:1227), several groups have attempted the detection of CTC and BMM in MM using RT-PCR for melanocytic specific markers, mainly tyrosinase mRNA. Most studies show that tyrosinase is not present in the PB and BM of control individuals without MM. The PCR positivity rates in MM are extremely variable, ranging from 0% to 100%. There was a correlation between RT-PCR and stage in some but not all of the studies. These disparate findings could in part be explained by differences in RNA extraction and blood separation techniques, to unrecognized contamination leading to false positive results, or differences in patient selection. Despite these discrepancies, we and others have shown that RT-PCR for tyrosinase mRNA in PB is able to predict overall survival (OS) and disease-free survival (DFS) in a statistically significant manner. In AJCC stage II-IV patients rendered surgically free of disease, we found that blood tyrosinase positivity was an independent predictor of OS and DFS. We also found that BM tyrosinase positivity is an independent predictor of DFS in the same group of patients. RT-PCR may help identify subgroups of patients at high risk for early relapse for more aggressive adjuvant therapy. Large prospective studies and interlaboratory quality assurance initiatives are necessary to confirm the accuracy and prognostic value of these RT-PCR assays.

Olson JA, Jaques DP, Coit DG, Hwu WJ. · Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York, USA. · Clin Plast Surg. · Pubmed #10941559 No free full text.

Abstract: Strategies based on evidence are required to accurately stage and effectively follow patients with melanoma. The goal of staging is to define the extent of disease at the time of presentation to direct and assign prognosis. Patient surveillance is performed to assess treatment results and detect recurrences amenable to further treatment. Staging and surveillance require careful use of resources to be cost effective. This article addresses preoperative staging and post-treatment surveillance of patients with melanoma and outlines a method of follow-up based on available data.

Reeves ME, Coit DG. · Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York, USA. · Surg Clin North Am. · Pubmed #10836008 No free full text.

Abstract: Advances in the understanding of the biology and treatment of melanoma have moved the care of melanoma patients into an increasingly multidisciplinary environment. Surgeons must understand these advances because they will often be responsible for directing the overall care of these patients. Most patients with melanomas more than 1 mm in diameter and no evidence of metastatic disease should be offered SLNB to more accurately stage them and direct decisions about participation in postoperative adjuvant therapy trials. Until the results of the MSLT are known, the effect of SLNB and ELND on outcome remains unknown. SLNs should be analyzed with serial sectioning and immunohistochemistry to avoid missing micro-metastatic disease. Based on the results of the ECOG-1684 trial, the FDA approved IFN-alpha 2b for the adjuvant treatment of melanoma patients with thick primary tumors (> 4 mm) or resected nodal disease. IFN-alpha 2b treatment is expensive and potentially toxic. The data from ECOG-1684 do not support the use of IFN-alpha 2b in patients with node-negative disease. In light of the ECOG-1690 trial results, the role of high-dose IFN-alpha 2b in the management of patients with resected nodal disease is considerably less clear. Any recommendations for treatment with high-dose IFN-alpha 2b should be made only after weighing the costs, side effects, and potential benefits for individual patients. Numerous, less toxic, promising, adjuvant immunotherapeutic strategies have been developed and are being tested in multicenter, prospective, randomized trials. These strategies include GMK, PMCV, and Melacine. If the results of any of these trials show a survival advantage compared with placebo or equivalent survival compared with IFN-alpha 2b, these immunotherapeutic agents will become the adjuvant treatment of choice for patients with resected high-risk melanoma. RT-PCR detection of tyrosinase in SLNs can identify patients with submicroscopic nodal disease who may be at increased risk for recurrence or death from melanoma. An ongoing, prospective, randomized trial will determine whether patients with histologically negative but RT-PCR-positive SLNs will benefit from lymphadenectomy or adjuvant IFN-alpha 2b therapy. RT-PCR can also identify minimal residual disease in peripheral blood and bone marrow from patients with high-risk melanoma, but RT-PCR analysis of peripheral blood and bone marrow is still experimental, and procedural details need to be standardized and prospectively validated in large patient groups before its use can be considered the standard of care.

Wong SL, Kattan MW, McMasters KM, Coit DG. · Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA. · Ann Surg Oncol. · Pubmed #15827679 No free full text.

Abstract: BACKGROUND: The threshold and indications for sentinel lymph node (SLN) biopsy in patients with melanoma remain somewhat arbitrary. Many variables associated with SLN positivity have previously been identified, including a significant association between the American Joint Committee on Cancer (AJCC) staging system and SLN status. We developed a user-friendly nomogram that takes several characteristics into account simultaneously to more accurately predict the presence of SLN metastasis for an individual patient. METHODS: A total of 979 patients who underwent successful SLN biopsy for cutaneous melanoma at a single institution between February 1991 and November 2003 were included in the analysis. Predictors were used to develop a nomogram, based on logistic regression analysis, to predict the probability of SLN positivity. A large multi-institutional trial with 3108 patients was used to validate the predictive accuracy of the nomogram compared with the AJCC staging system. RESULTS: The nomogram was developed and found to be accurate and discriminating. The concordance index of the nomogram, a measure of predictive ability, was .694 when evaluated with the validation dataset. In contrast, the concordance index of the AJCC staging system was lower (.663; P < .001). CONCLUSIONS: Using commonly available clinicopathologic information, we developed a nomogram to accurately predict the probability of a positive SLN in patients with melanoma. This tool takes several characteristics into account simultaneously. This model should enable improved patient counseling and treatment selection.

Kammula US, Ghossein R, Bhattacharya S, Coit DG. · Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. · J Clin Oncol. · Pubmed #15459222 No free full text.

Abstract: PURPOSE: Reverse transcriptase-polymerase chain reaction (RT-PCR) may provide an extremely sensitive method for detection of occult nodal disease. We evaluated the role of a single-marker RT-PCR assay for tyrosinase mRNA in the detection of melanoma sentinel lymph node (SLN) metastases and correlated the results with long-term clinical outcome. PATIENTS AND METHODS: One hundred twelve patients who underwent SLN biopsy for melanoma were prospectively analyzed. SLNs were bivalved, with half of each specimen evaluated by histologic methods and the other half evaluated by nested RT-PCR for tyrosinase. RESULTS: Fifteen patients (13%) had histologically positive SLNs, all of whom were also positive by RT-PCR (HISTO+/PCR+). Thirty-nine patients (35%) had SLNs that were negative by both histology and RT-PCR (HISTO-/PCR-). Fifty-eight patients (52%) were histologically negative but upstaged with a positive RT-PCR result (HISTO-/PCR+). Initially, at a median follow-up of 42 months, recurrence rates among the three cohorts were statistically different (HISTO+/PCR+, 53%; HISTO-/PCR+, 14%; and HISTO-/PCR-, 0%). However, at a longer median follow-up (67 months), recurrence rates for the HISTO-/PCR+ (24%) and HISTO-/PCR- (15%) groups were no longer statistically different (P =.25). The median time to relapse between the HISTO-/PCR+ and HISTO-/PCR- groups differed by 10 months (31 v 41 months, respectively). CONCLUSION: With extended follow-up of patients with histologically negative SLNs, detection of submicroscopic disease by tyrosinase RT-PCR does not define a subgroup that is at higher recurrence risk when compared with patients with RT-PCR-negative SLNs. Future studies evaluating molecular staging will require approximately 5 years of median follow-up to accurately define outcome for patients with occult melanoma metastases.

Schmidt CR, Panageas KS, Coit DG, Patel A, Brady MS. · Department of Surgery, Gastric and Mixed Tumor Service, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. · Ann Surg Oncol. · Pubmed #19194758 No free full text.

Abstract: BACKGROUND: The pathologic status of the sentinel lymph node (SLN) is a powerful prognostic factor for patients with intermediate thickness melanoma. We hypothesize that a high number of SLNs identified may be associated with poor outcome. METHODS: We evaluated the impact of number of SLNs removed in patients undergoing SLN mapping for cutaneous melanoma at our institution between 1996 and 2006. We excluded patients with multiple primary or synchronous primary lesions (n = 144) to eliminate any chance of erroneous association between a SLN and the wrong primary melanoma. We also excluded patients with in-transit disease (n = 37) and one patient in whom no SLN was identified, leaving 970 patients. We evaluated factors associated with the number of SLNs removed by multivariate Poisson regression and determined whether an increased number of SLNs was associated with poorer overall (OS) or recurrence-free survival (RFS). RESULTS: Clinical factors independently associated with increased number of SLNs were younger age and head and neck primary site. Pathologic factors associated with an increased number of SLNs were lymphovascular invasion and increased Breslow thickness. There was no association between number of SLNs removed and OS or RFS in all patients or in patients with negative SLNs (n = 803). CONCLUSIONS: The number of SLNs identified during staging of the regional nodal basin for primary melanoma is not an independent prognostic factor. Drainage to multiple SLNs is more common in the setting of an increased Breslow depth and lymphovascular invasion suggesting that tumors with these adverse features may enhance peritumoral lymphangiogenesis.

Moore Dalal K, Zhou Q, Panageas KS, Brady MS, Jaques DP, Coit DG. · Department of Surgery, David Grant United States Air Force Medical Center, Travis AFB, CA, USA. · Ann Surg Oncol. · Pubmed #18512102 No free full text.

Abstract: BACKGROUND: An understanding of the methods of detection of recurrent melanoma after sentinel lymph node biopsy (SLNB) is essential for the coordination of a rational plan of follow-up. METHODS: Clinical stage I/II melanoma patients who underwent SLNB from 1991 to 2004 were identified from a prospectively maintained single-institution database. Detection of recurrence by self (awareness of symptoms or abnormal physical findings) or physician (discovered on routine physical or scheduled test) and timing of clinic visit were recorded. Postoperative follow-up included physical exam every 3-4 months for the first year, every 3-6 months for the second year, and every 6-12 months thereafter. Serum lactate dehydrogenase (LDH) and chest X-ray (CXR) were obtained annually. Computed tomography (CT) and positron emission tomography (PET) were performed selectively. RESULTS: Of 1062 patients who underwent SLNB, 203 (19%) experienced 230 initial sites of recurrence; 198 patients were evaluable for follow-up. Median follow-up after first recurrence was 17 months. Symptoms and self-detected physical findings were present in 109 patients (55%); 85 patients (78%) were seen earlier than their scheduled visit. Self-detected physical findings identified in-transit (n = 26; 24%) and nodal (n = 25; 23%) disease. Physician detection occurred in 89 patients (45%), nearly half by a scheduled radiographic test (CXR, 16%; CT, 29%; PET, 1%). The method of detection significantly predicted post-recurrence survival (p < 0.05). CONCLUSION: More than half of melanoma recurrences are self-detected; these patients have the most favorable post-recurrence survival rates because of the type of recurrence detected. The mode of detection is a significant predictor of post-recurrence survival. This supports an aggressive program of patient education in self-examination after SLNB for melanoma.

Neuman HB, Patel A, Ishill N, Hanlon C, Brady MS, Halpern AC, Houghton A, Coit DG. · Gastric and Mixed Tumor Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, Room H1221, New York, NY, 10065, USA. · Ann Surg Oncol. · Pubmed #18465172 No free full text.

Abstract: BACKGROUND: Survival of patients with stage IV melanoma is poor. In the current American Joint Committee on Cancer (AJCC) staging system, site of distant disease and lactate dehydrogenase (LDH) are the only prognostic factors included for stage IV disease. We sought to validate the current AJCC staging system in a contemporary, prospectively collected cohort of patients and explore additional factors that may influence prognosis. METHODS: Our prospective database was searched to identify patients with stage IV melanoma; only patients seen at our institution before developing stage IV disease were included (n = 589). Demographic, clinical, and tumor characteristics were abstracted. Univariate and multivariate assessment of prognostic factors associated with survival were performed by Cox regression. RESULTS: Overall median survival was 9 months. Differential survival by AJCC substage was observed (P < .001). For each site of disease described within the AJCC staging system, an abnormal LDH level was associated with a poorer prognosis. By multivariate analysis, older age at diagnosis (as a continuous variable, hazard ratio [HR] 1.02, 95% confidence interval [95% CI]) 1.01-1.02), an abnormal LDH (HR 1.42, 95% CI 1.11-1.82), site of disease (lung HR 1.22, 95% CI .89-1.66; other viscera 1.61, 95% CI 1.18-2.21), more than one organ involvement (HR 1.27, 95% CI 1.01-1.60), and more than one metastasis (HR 2.27, 95% CI 1.65-3.14) were independently associated with poorer survival. Sex, antecedent stage, and disease-free interval were not statistically significant. CONCLUSION: In our patient cohort, the AJCC staging system was valid. The strongest predictor of survival-the number of metastases present at the diagnosis of stage IV disease-represents a variable to consider in future staging systems.

Neuman HB, Patel A, Hanlon C, Wolchok JD, Houghton AN, Coit DG. · Gastric and Mixed Tumor Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, Room H1221, New York, New York 10021, USA. · Ann Surg Oncol. · Pubmed #17680317 No free full text.

Abstract: BACKGROUND: We reviewed a contemporary, single-institution experience to evaluate the natural history of stage-IV melanoma metastatic to the lung and identify factors predictive of survival. METHODS: A search of our prospective database was performed to identify patients with stage-IV melanoma and pulmonary metastases as the initial disease site; only patients seen at our institution prior to developing stage-IV disease and in whom treatment response was available were included. Patients' demographic, clinical, and treatment variables were recorded. Cox regression was used to identify factors independently predictive of survival. RESULTS: The study cohort was comprised of 122 patients. Median survival was 14 months (5-year survival of 8%). Clinical factors at time of diagnosis of stage IV independently predictive of survival were a solitary pulmonary metastasis (HR 2.7, CI 1.6-4.4, P<0.0005) and absence of extra-pulmonary disease (HR 1.9, CI 1.2-3.1, P = 0.01). Among treatment factors, only metastasectomy was independently predictive of survival (HR 0.42, CI 0.21-0.87, P = 0.02). Of the patients, 26 (21%) underwent metastasectomy, with a median survival of 40 months compared with 13 months in patients not selected for surgical treatment. Of these 26, 23 (88%) experienced recurrence at a median of 5 months after the procedure. No survival difference was seen between responders and non-responders to systemic therapy (P = 0.55). CONCLUSIONS: In stage-IV melanoma with pulmonary metastases, a solitary metastasis and absence of extra-pulmonary disease are predictive of survival. While these factors are often present in patients selected for pulmonary metastasectomy, this independently predicts survival. However, response to systemic therapy does not correlate with a survival difference.

Gold JS, Jaques DP, Busam KJ, Brady MS, Coit DG. · Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. · Ann Surg Oncol. · Pubmed #17453294 No free full text.

Abstract: BACKGROUND: It is common to obtain radiological studies around the time of a positive sentinel lymph node biopsy (SLNB) to exclude patients with distant metastases from completion lymph node dissection. The yield of such a work-up is unknown. METHODS: Patients were identified from a prospectively maintained database. Medical records were reviewed. RESULTS: Over an 8-year period, 181 patients had a positive SLNB. At least one study (computed tomography or magnetic resonance imaging of the brain; chest x-ray; computed tomography of the thorax, abdomen, or pelvis; positron-emission tomography scan; or bone scan) was obtained around the time of SLNB in 178 patients (98%). Studies were obtained after SLNB in 107 patients (59%). Studies ordered after SLNB resulted in indeterminate findings in 51 patients (48% of those studied). Among patients tested after SLNB, four were found to have metastatic disease (positive rate 3.7%). All of these patients had both a thick melanoma and macrometastasis within the SLN. The number of patients with indeterminate findings would be decreased and the yield of the work-up increased by 4 fold, by restricting the work-up to those with thick melanoma and macrometastasis. CONCLUSIONS: Radiological studies obtained after a positive SLN produce indeterminate findings in about half of the patients and identify distant disease in 3.7%. Restricting work-up to patients with thick melanoma and macrometastasis on SLNB would spare patients from indeterminate findings and increase the yield of the evaluation.

Dalal KM, Patel A, Brady MS, Jaques DP, Coit DG. · Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York, 10021, USA. · Ann Surg Oncol. · Pubmed #17406951 No free full text.

Abstract: BACKGROUND: Sentinel lymph node biopsy (SLNB) has become well accepted in management of patients with primary cutaneous melanoma. An understanding of the pattern of recurrence after SLNB is helpful in coordinating a rational plan of follow-up in these patients. We sought to determine the site and timing of initial recurrence and post-recurrence survival after SLNB. METHODS: Stage I/II melanoma patients who underwent SLNB during 1991-2004 were identified from a prospective single-institution database. Site and date of first recurrence after SLNB were recorded. Patterns of recurrence after SLNB and post-recurrence survival were analyzed. RESULTS: One thousand and forty-six patients underwent SLNB. The sentinel lymph node (SLN) was positive in 164 patients (16%). Median follow-up was 36 months for survivors. Median and 3-year relapse-free survival for SLN-positive patients were 41 months and 56%, and for SLN-negative patients were not reached and 87%, respectively (P < .0001). Of the SLN-positive patients, 47% experienced recurrence, compared with 14% SLN-negative patients. The pattern of recurrence stratified by SLN status was similar between the two groups (P = NS). After recurrence, the site of recurrence was the only significant prognostic factor influencing survival (P < .0001). CONCLUSIONS: Although SLN-positive patients experience recurrence far earlier and more frequently than SLN-negative patients, the pattern of recurrence is similar. After recurrence, its site is the primary determinant of survival.