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

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.</p

Cost-Effectiveness of PET/CT Surveillance Schedules to Detect Distant Recurrence of Resected Stage III Melanoma

Objective: To estimate the cost-effectiveness of three surveillance imaging strategies using whole-body positron emission tomography (PET) with computed tomography (CT) (PET/CT) in a follow-up program for adults with resected stage III melanoma. Methods: An analytic decision model was constructed to estimate the costs and benefits of PET/CT surveillance imaging performed 3-monthly, 6-monthly, or 12-monthly compared with no surveillance imaging. Results: At 5 years, 3-monthly PET/CT surveillance imaging incurred a total cost of AUD 88,387 per patient, versus AUD 77,998 for 6-monthly, AUD 52,560 for 12-monthly imaging, and AUD 51,149 for no surveillance imaging. When compared with no surveillance imaging, 12-monthly PET/CT imaging was associated with a 4% increase in correctly diagnosed and treated distant disease; a 0.5% increase with 6-monthly imaging and 1% increase with 3-monthly imaging. The incremental cost-effectiveness ratio (ICER) of 12-monthly PET/CT surveillance imaging was AUD 34,362 for each additional distant recurrence correctly diagnosed and treated, compared with no surveillance imaging. For the outcome of cost per diagnostic error avoided, the no surveillance imaging strategy was the least costly and most effective. Conclusion: With the ICER for this strategy less than AUD 50,000 per unit of health benefit, the 12-monthly surveillance imaging strategy is considered good value for money

Cost-effectiveness analysis of PET/CT surveillance imaging to detect systemic recurrence in resected stage III melanoma: study protocol

Introduction In the new era of effective systemic therapies for advanced melanoma, early detection of lower volume recurrent disease using surveillance imaging can improve survival. However, intensive imaging follow-up strategies are likely to increase costs to health systems and may pose risks to patients. The objective of this study is to estimate from the Australian health system perspective the cost-effectiveness of four follow-up strategies in resected stage III melanoma over a 5-year period following surgical treatment with curative intent. Methods and analysis A decision-analytic model will be built to estimate the costs and benefits of (1) 12 monthly, (2) 6 monthly, (3) 3–4 monthly positron emission tomography/CT imaging for 5 years, compared with (4) no imaging follow-up. The model will be populated with probabilities of disease recurrence, test performance measures using data from >1000 consecutive resected stage III melanoma patients from Melanoma Institute Australia diagnosed between 2000 and 2017. Healthcare resource use, including surveillance imaging, doctor’s visits, subsequent tests and procedures to investigate suspicious findings, will be quantified from detailed patient records and valued using Australian reference pricing. Economic outcomes include cost per new distant melanoma recurrence detected and cost per diagnostic error avoided, for no imaging compared with the other strategies. Deterministic sensitivity analyses will examine the robustness of model results. Ethics and dissemination This study was approved by the Sydney Local Health District, Sydney Local Health District Ethics Review Committee (RPAH Zone), AU/1/830638 and the Australian Institute of Health and Welfare (EO2019-1-454). The results of this study will be published in peer-reviewed medical and health economics journals and will inform melanoma management guidelines

The Hybrid SPECT/CT as an Additional Lymphatic Mapping Tool in Patients with Breast Cancer

Background Conventional lymphoscintigraphy does not always define the exact anatomic location of a sentinel node. The lymphatic drainage pattern may be unusual or may not be shown at all. The recently introduced hybrid SPECT/CT imaging could help overcome these difficulties. SPECT is a tomographic version of conventional lymphoscintigraphy and the images have better contrast and resolution. When fused with the anatomical details provided by CT into one image, a meaningful surgical ‘‘roadmap’’ can be created. So far, there is little literature on the use of hybrid SPECT/CT in lymphatic mapping in patients with breast cancer. The purpose of this review was to report on these publications, including our own experience, focusing on patient selection, SPECT/CT settings, anatomic localization, and the detection of additional sentinel nodes. Methods The majority of investigators did not formulate indications for additional SPECT/CT after conventional imaging but scanned all patients eligible for sentinel node biopsy. The SPECT/CT settings used in the studies of this review were mostly similar, but the methods used for conventional imaging were more variable. Results All studies demonstrated an improved anatomical localization by performing additional SPECT/CT; sentinel nodes outside the axilla or nodes close to the injection sit

Performance of long-term CT and PET/CT surveillance for detection of distant recurrence in patients with resected stage IIIA-D melanoma

Background Follow-up for patients with resected stage IIIA–D melanoma may include computed tomography (CT) or positron emission tomography (PET)/CT imaging to identify distant metastases. The aim of this study was to evaluate the test performance over follow-up time, of structured 6- and 12-monthly follow-up imaging schedules in these patients. Methods We conducted a retrospective analysis of consecutive resected stage IIIA–D melanoma patients from Melanoma Institute Australia (2000–2017). Patients were followed until a confirmed diagnosis of distant metastasis, end of follow-up schedule, or death. Test accuracy was evaluated by cross-classifying the results of the test against a composite reference standard of histopathology, cytology, radiologic imaging, and/or clinical follow-up, and then quantified longitudinally using logistic regression models with random effects. Results In total, 1373 imaging tests were performed among 332 patients. Distant metastases were detected in 110 (33%) patients during a median follow-up of 61 months (interquartile range 38–86), and first detected by imaging in 86 (78%) patients. 152 (68%) patients had at least one false-positive result. Sensitivity of the schedule over 5 years was 79% [95% confidence interval (CI) 70–86%] and specificity was 88% (95% CI 86–90%). There was no evidence of a significant difference in test performance over follow-up time or by American Joint Committee on Cancer (AJCC) substage. The positive predictive value ranged between 33 and 48% over follow-up time, reflecting a ratio of 1:2 false-positives per true-positive finding. Conclusions Regular 6- or 12-monthly surveillance imaging using CT or PET/CT has reasonable and consistent sensitivity and specificity over 5-year follow-up for resected stage IIIA–D melanoma patients. These data are useful when discussing the risks and benefits of long-term follow-up

History of sentinel node and validation of the technique

Sentinel node biopsy is a minimally invasive technique to select patients with occult lymph node metastases who may benefit from further regional or systemic therapy. The sentinel node is the first lymph node reached by metastasising cells from a primary tumour. Attempts to remove this node with a procedure based on standard anatomical patterns did not become popular. The development of the dynamic technique of intraoperative lymphatic mapping in the 1990s resulted in general acceptance of the sentinel node concept. This hypothesis of sequential tumour dissemination seems to be valid according to numerous studies of sentinel node biopsy with confirmatory regional lymph node dissection. This report describes the history and the validation of the technique, with particular reference to breast cancer

Feasibility of Sentinel Node Biopsy in Head and Neck Melanoma Using a Hybrid Radioactive and Fluorescent Tracer

This study was designed to examine the feasibility of combining lymphoscintigraphy and intraoperative sentinel node identification in patients with head and neck melanoma by using a hybrid protein colloid that is both radioactive and fluorescent. Eleven patients scheduled for sentinel node biopsy in the head and neck region were studied. Approximately 5 h before surgery, the hybrid nanocolloid labeled with indocyanine green (ICG) and technetium-99m ((99m)Tc) was injected intradermally in four deposits around the scar of the primary melanoma excision. Subsequent lymphoscintigraphy and single photon emission computed tomography with computed tomography (SPECT/CT) were performed to identify the sentinel nodes preoperatively. In the operating room, patent blue dye was injected in 7 of the 11 patients. Intraoperatively, sentinel nodes were acoustically localized with a gamma ray detection probe and visualized by using patent blue dye and/or fluorescence-based tracing with a dedicated near-infrared light camera. A portable gamma camera was used before and after sentinel node excision to confirm excision of all sentinel nodes. A total of 27 sentinel nodes were preoperatively identified on the lymphoscintigraphy and SPECT/CT images. All sentinel nodes could be localized intraoperatively. In the seven patients in whom blue dye was used, 43% of the sentinel nodes stained blue, whereas all were fluorescent. The portable gamma camera identified additional sentinel nodes in two patients. Ex vivo, all radioactive lymph nodes were fluorescent and vice versa, indicating the stability of the hybrid tracer. ICG-(99m)Tc-nanocolloid allows for preoperative sentinel node visualization and concomitant intraoperative radio- and fluorescence guidance to the same sentinel nodes in head and neck melanoma patient