Determinants of outcome in melanoma patients with cerebral metastases.

PURPOSE: To analyze prognostic factors, effects of treatment, and survival for patients with cerebral metastases from melanoma. PATIENTS AND METHODS: All melanoma patients with cerebral metastases treated at the Sydney Melanoma Unit between 1952 and 2000 were identified. From 1985 to 2000, patients were diagnosed and treated using consistent modern techniques and this cohort was analyzed in detail. Multivariate analysis of prognostic factors for survival was performed. RESULTS: A total of 1137 patients with cerebral metastases were identified; 686 were treated between 1985 and 2000. For these 686 patients, the median time from primary diagnosis to cerebral metastasis was 3.1 years (range, 0 to 41 years). A total of 646 patients (94%) have died as a result of melanoma. The median survival from the time of diagnosis of cerebral metastasis was 4.1 months (range, 0 to 17.2 years). Treatment was as follows: surgery and postoperative radiotherapy, 158 patients; surgery alone, 47 patients; radiotherapy alone, 236 patients; and supportive care alone, 210 patients. Median survival according to treatment received for these four groups was 8.9, 8.7, 3.4, and 2.1 months, respectively; the differences between surgery and nonsurgery groups were statistically significant. On multivariate analysis, significant factors associated with improved survival were surgical treatment (P <.0001), no concurrent extracerebral metastases (P <.0001), younger age (P =.0007), and longer disease-free interval (P =.036). Prognostic factors analysis confirmed the important influence of patient selection on treatment received. CONCLUSION: This large series documents the characteristics of patients who developed cerebral metastases from melanoma. Median survival was dependent on treatment, which in turn was dependent on patient selection.

Elective lymph node dissection in patients with primary melanoma of the trunk and limbs treated at the Sydney Melanoma unit from 1960 to 1991.

BACKGROUND: The value of elective lymph node dissection (ELND) in melanoma remains controversial. Published prospective and retrospective studies can be criticized, and results from two ongoing randomized trials are not yet available. A previous retrospective review from the Sydney Melanoma Unit (SMU) showed apparent survival benefit from ELND, especially in tumors of intermediate thickness. STUDY DESIGN: We undertook a retrospective analysis of all patients treated at the SMU since 1960 for melanoma of the trunk or limbs measuring 1.5 mm or more in thickness, without clinical lymph node metastases, whose definitive wide excision (WE) with or without ELND was performed at the SMU within 60 days of initial diagnosis. RESULTS: There were 1,278 patients who fulfilled these criteria. Of these, 845 (66 percent) were treated with ELND and the remaining 34 percent were treated with WE alone. The median follow-up period was 58 months. Patients with thicker tumors and younger age more commonly underwent ELND. Among patients with thinner tumors, males underwent ELND more commonly than females. A multivariate proportional hazard model of melanoma-specific survival stratified by tumor thickness was chosen to allow for the imbalances between the two groups. With or without allowance for covariates, no benefit from ELND was found in the whole group or any subset. In contrast to previous studies from the SMU, we deliberately excluded from the present study patients referred only after WE with or without ELND elsewhere, because these might have been a selectively biased poor prognostic group. CONCLUSIONS: This study does not indicate a benefit from ELND for melanomas of the trunk or limbs measuring over 1.5 mm in thickness.

Experience with 998 cutaneous melanomas of the head and neck over 30 years.

Between 1960 and 1990, a total of 998 patients were treated at the Sydney Melanoma Unit for cutaneous melanoma of the head and neck. There were 595 male and 403 female patients, with a median age of 53 years. The most common primary lesion site was the face (47%), followed by the neck (29%), scalp (14%), and ear (10%). Histologic types were as follows: superficial spreading 30%, nodular melanoma 28%, lentigo maligna melanoma 16%, and other 26%. All patients underwent surgical treatment. Primary closure of wounds was achieved in 52% of patients, and excision margins were 2 cm or less in 45%. A total of 152 patients had therapeutic neck dissections, and 234 had elective neck dissections. The overall local recurrence rate was 13%, and this was significantly influenced by increasing tumor thickness and Clark level. The recurrence rate in the neck after neck dissection was 24%, and the rate of parotid recurrences was 14%. Melanoma-specific survival was 77% at 5 years and 66% at 10 years for the entire group. By univariate analysis, survival varied significantly with age, tumor thickness, ulceration, anatomic sub-site, histologically positive nodes, and the presence of distant metastases. A diagnosis of lentigo maligna melanoma and elective lymph node dissection both appeared to improve survival. With multivariate analysis, all of these factors remained significant prognostic factors except elective node dissection, which lost its beneficial influence.

Prediction of potential metastatic sites in cutaneous head and neck melanoma using lymphoscintigraphy.

BACKGROUND: The technique of lymphoscintigraphy may allow a more selective approach to the management of clinically negative neck nodes among patients with cutaneous head and neck melanoma. PATIENTS AND METHODS: A group of 97 patients with cutaneous head and neck melanoma had preoperative lymphoscintigraphy using intradermal injections of technetium 99m antimony trisulfide colloid to identify sentinel nodes. Fifty-one patients were eligible for clinical analysis after initial definitive treatment by wide excision only (n = 11), wide excision and elective dissection of the neck (n = 19) or axilla (n = 1), or wide excision and a sentinel node biopsy procedure (n = 20). RESULTS: Sentinel nodes were identified in 95 of 97 lymphoscintigrams, and 85% of patients had multiple sentinel nodes. In 21 patients (22%), sentinel nodes were identified outside the parotid region and the 5 main neck levels, mostly in postauricular nodes (n = 13). Lymphoscintigrams were discordant with clinical predictions in 33 patients (34%). Lymph nodes were positive in 4 elective dissections and 4 sentinel node biopsies. Among 16 patients evaluable after wide excision and a negative sentinel node biopsy, 4 patients subsequently developed metastatic nodes; however, confident identification of all nodes marked as sentinel nodes on lymphoscintigraphy was not achieved at the original biopsy procedure in 3 of these patients. CONCLUSIONS: Lymphoscintigraphy and sentinel node biopsy are more difficult to perform in the head and neck than in other parts of the body. The reliability of sentinel node biopsy based on lymphoscintigraphy may be improved by identifying and marking all nodes that are considered to receive direct lymphatic drainage from the primary melanoma, and by use of a gamma probe intraoperatively.

Radical, modified, and selective neck dissection for cutaneous malignant melanoma.

BACKGROUND: The roles of modified and selective neck dissections in treating patients with clinical metastatic melanoma and the place of adjuvant radiotherapy are unclear. In the elective setting, the efficacy of various selective dissections also requires clarification. METHODS: The prospectively documented experience of the senior author (COB) was analyzed. A total of 175 patients had 183 neck dissections and 92 parotidectomies in 6 years. There were 75 therapeutic and 108 elective operations. Modified or selective neck dissections were performed in 58% of patients with clinical neck metastases. Ali but two elective operations were modified or selective dissections. Postoperative radiotherapy was given to 27 dissected necks. Minimum follow-up was 12 months, and 86% of patients were followed up for 2 years or to neck recurrence. RESULTS: Nodes were histologically positive in 80 dissections. The cumulative rate of control of metastatic melanoma in the neck was 86% at 5 years. Neck recurrence developed in 14% of radical dissections, 0% of modified, and 23% of selective dissections performed for clinical disease. Neck recurrence occurred after 5% of elective dissections. Recurrence was 7% among irradiated necks compared to 23% in nonirradiated (p-value not significant). The 5-year survival rate was 50%, and this was significantly worsened by increasing node involvement. CONCLUSIONS: Modified radical neck dissection is highly effective in controlling metastatic melanoma in selected patients. Selective dissections are less effective and need further study. Adjuvant radiotherapy appears to decrease the risk of neck recurrence. In the elective setting, recurrence is uncommon following the selective neck dissections described.

Adjuvant radiotherapy following neck dissection and parotidectomy for metastatic malignant melanoma.

BACKGROUND: Regional recurrence remains a problem in the management of patients with metastatic malignant melanoma in the cervical lymph nodes and parotid. In this study, the influence of the number of positive nodes, extracapsular spread, and the use of adjuvant radiotherapy on regional control and survival were analyzed. METHODS: A non-randomized, prospectively documented series of 143 patients with histologically positive nodes in the neck or parotid was analyzed. There were 152 dissected necks or parotids: 45 of these received postoperative radiotherapy, 6 x 5.5 Gy fractions over 3 weeks; 107 were not irradiated. RESULTS: The regional recurrence rate was 6.5% in the irradiated group, compared with 18.7% in the non-irradiated group (p = .055). The irradiated group, however, had more extensive nodal involvement than the non-irradiated group: 65% had two or more positive nodes, and 48% had extracapsular spread, compared with 40% and 19%, respectively, in the non-irradiated group. Survival was significantly worse when there was extracapsular spread (p < .05) or multiple node involvement (p < .01). By multivariate analysis, the use of adjuvant radiotherapy was associated with a trend toward improved regional control (p = .065), but survival was not improved. CONCLUSIONS: Adjuvant radiotherapy was associated with improved control of metastatic malignant melanoma in the neck and parotid; however, statistical significance was not reached. A prospective trial should be supported to clarify this question.