Adjuvant radiotherapy after salvage surgery for melanoma recurrence in a node field following a previous lymph node dissection.

BACKGROUND AND OBJECTIVES: Adjuvant radiotherapy (RT) can be given to melanoma patients following salvage surgery for node field recurrence after a previous regional node dissection, but the value of this treatment strategy is poorly documented. This study evaluated long-term node field control and survival of patients treated in this way in an era before effective adjuvant systemic therapy became available. METHODS: Data for 76 patients treated between 1990 and 2011 were extracted from an institutional database. Baseline patient characteristics, treatment details and oncological outcomes were analysed. RESULTS: Adjuvant RT with conventional fractionation (median dose 48 Gy in 20 fractions) was given to 43 patients (57%) and hypofractionated RT (median dose 33 Gy in 6 fractions) to 33 patients (43%). The 5-year node field control rate was 70%, 5-year recurrence-free survival 17%, 5-year melanoma-specific survival 26% and 5-year overall survival 25%. CONCLUSIONS: Salvage surgery with adjuvant RT achieved node field control in 70% of melanoma patients with node field recurrence following a prior node dissection. However, disease progression at distant sites was common and survival outcomes were poor. Prospective data will be required to assess outcomes for contemporary combinations of surgery, adjuvant RT and systemic therapy.

Sentinel Node Biopsy for Melanoma Patients with a Local Recurrence or In-Transit Metastasis.

BACKGROUND: Sentinel node (SN) biopsy (SNB) is not routinely performed for melanoma patients with local recurrence (LR) or in-transit metastasis (ITM). This study aimed to describe the technique, findings, and prognostic value of this procedure, and the outcome for such patients at our institution. METHODS: Prospectively collected data were obtained from the Melanoma Institute Australia database. Patients who had SNB for LR or ITM between 1992 and 2015 were included in the study. Patient and primary tumor characteristics, lymphoscintigrams, SNB results, and follow-up data were analyzed. RESULTS: Overall, 7999 patients underwent SNB, 128 (1.6%) of whom met the selection criteria. The SNB procedure was performed for 85 of 1516 patients with LR (6%), 17 of 1671 patients with ITM from a known primary tumor (1%), and 26 of 170 patients who presented with ITM from an unknown primary site (15%). The SN identification rate was 100%. Metastatic melanoma was identified in an SN from 16 of the 128 patients (13%). Follow-up data were available for 114 patients. The false-negative rate was 27%. The SN-positive patients had significantly worse overall survival than the SN-negative patients, with respective 5-year survival rates of 54% and 81% (P = 0.01). CONCLUSION: The SNB procedure was performed infrequently for LR or ITM. The SNs were positive for 13% of the patients with LR or ITM. Positive SNs were associated with worse overall survival. Despite the false-negative rate of 27%, the procedure yielded information that was relevant for staging and prognosis. The SNB procedure should be considered for patients with LR or ITM.

The prognostic value of tumor mitotic rate in children and adolescents with cutaneous melanoma: A retrospective cohort study.

BACKGROUND: Mitotic rate is a strong predictor of outcome in adult patients with primary cutaneous melanoma, but for children and adolescent patients this is unknown. OBJECTIVE: We sought to assess the prognostic value of primary tumor mitotic rate in children and adolescents with primary melanoma. METHODS: This was a cohort study of 156 patients who were <20 years of age and who had clinically localized cutaneous melanoma. Patients <12 years of age were classified as children and those 12 to 19 years of age as adolescents. Clinicopathologic and outcome data were collected. Recurrence-free and melanoma-specific survival were calculated. Univariable and multivariable analyses were performed using Cox proportional hazard models. RESULTS: Thirteen of 156 patients (8%) were children. The mitotic rate was ≥1/mm2 in 104 patients (67%) and correlated with increasing Breslow thickness. A positive sentinel node was found in 23 of 61 patients (38%) in whom a sentinel lymph node biopsy specimen was obtained. The median follow-up was 61 months. Five-year melanoma-specific and recurrence-free survival rates were 91% and 84%, respectively. Mitotic rate was a stronger predictor of outcome than tumor thickness and was the only factor independently associated with recurrence-free survival. LIMITATIONS: This research was conducted at a single institution and the sample size was small. CONCLUSION: Mitotic rate is an independent predictor of recurrence-free survival in children and adolescents with clinically localized melanoma.

Detailed pathological examination of completion node dissection specimens and outcome in melanoma patients with minimal (<0.1 mm) sentinel lymph node metastases.

BACKGROUND: Nonsentinel lymph nodes (NSLNs) are rarely involved in patients with minimal volume melanoma metastases in sentinel lymph nodes (SLNs). Therefore, it has been suggested that completion lymph node dissection (CLND) is not required. However, the lack of routine immunohistochemical staining and multiple sectioning may have led to failure to identify additional positive nodes. The present study sought to more reliably determine the tumor status of NSLNs in patients with minimally involved SLNs and their clinical outcome. METHODS: A total of 21 tumor-negative CLND specimens from 20 patients with SLN metastases of <0.1 mm in diameter treated between 1991 and 2013 were examined with a more detailed pathologic protocol (five new sections stained with/for H&E, S-100, HMB45, Melan-A, and H&E). Clinical follow-up data were also obtained. RESULTS: Of the 343 examined NSLNs, 1 was found to harbor a 0.18-mm subcapsular sinus metastasis. No metastases were identified in the other NSLNs. Median follow-up was 48 months (range 17-130 months). Six patients (30 %) developed a recurrence. At the end of follow-up, 15 patients (75 %) were alive without sign of melanoma recurrence and 5 patients (25 %) had died of melanoma. Estimated 5-year melanoma-specific survival was 64 %. The patient with the additional positive NSLN remains without recurrence after 130 months follow-up. CONCLUSIONS: Although the risk of additional nodal involvement is low, detailed pathologic examination may identify NSLN metastases not identified using routine protocols. Therefore, nodal clearance appears to be the safest option for these patients, pending the results of prospective trials.

Staging 18F-FDG PET/CT influences the treatment plan in melanoma patients with satellite or in-transit metastases.

Whole-body positron emission tomography/computed tomography (PET/CT) and brain magnetic resonance imaging (MRI) are commonly used to stage patients with palpable lymph node metastases from melanoma, but their role in patients with satellite and/or in-transit metastasis (S&ITM) is unclear. The aim of this study was to establish the diagnostic value of PET/CT and brain MRI in these patients, and to assess their influence on subsequent management decisions. In this prospective study, 25 melanoma patients with a first presentation of S&ITM who had no clinical evidence of palpable nodal or distant metastasis underwent whole-body F-FDG PET/CT and brain MRI after a tentative pre-scan treatment plan had been made. Sensitivity and specificity of imaging were determined by pathological confirmation, clinical outcome and repeat PET/CT and MRI at 6 months. PET/CT led to a modification of the initial treatment plan in four patients (16%). All four were upstaged (AJCC stage eighth edition). PET/CT was false-positive in one patient, who had a Schwannoma in his trapezius muscle. A thyroid carcinoma was an incidental finding in another patient. The sensitivity of PET/CT was 58% and specificity 83%. In 6 months following the baseline PET/CT, further sites of in-transit or systemic disease were identified in 10 patients (40%). Brain MRI did not alter the treatment plan or change the disease stage in any patient. Whole-body PET/CT improved staging in melanoma patients with S&ITM and changed the originally-contemplated treatment plan in 16%. MRI of the brain appeared not to be useful.

Futility of imaging to stage melanoma patients with a positive sentinel lymph node.

The use of staging imaging in melanoma patients with a positive sentinel lymph node (SLN) has been reported to be of limited value. Improved accuracy resulting from the development of time-of-flight positron emission tomography (PET) and ongoing image quality improvement of computed tomography (CT) may challenge this statement. Our retrospective study assessed the clinical value of routine staging CT and PET/CT imaging in a recent cohort of asymptomatic SLN-positive patients. Between January 2011 and April 2014, 143 patients with a positive SLN were routinely staged using CT of various parts of the body or whole-body PET/CT. Scores were assigned for level of certainty for regional or distant metastases and incidental second primary malignancies. Diagnostic test performance was assessed, as well as the number and nature of ensuing additional diagnostic actions. CT was performed in 102 of 143 (71%) patients and PET/CT in 41 (29%) patients. The use of PET/CT increased over the study period. Metastases were found in two of the 143 patients (true-positive yield 1.4%). Sensitivity, specificity and positive predictive value were 11, 73 and 4% for CT and 17, 57 and 6%, respectively, for PET/CT. None of the 143 patients had a change in AJCC stage. Two other primary malignancies were found. Twenty-one (15%) patients were subjected to 37 additional investigations, referrals or procedures. Routine staging imaging with CT or PET/CT in SLN-positive patients is not useful. The yield is low and the results are often false positive, leading to unnecessary additional tests, most of which are costly and some potentially morbid.