International Center-Level Variation in Utilization of Completion Lymph Node Dissection and Adjuvant Systemic Therapy for Sentinel Lymph Node-Positive Melanoma at Major Referral Centers.

OBJECTIVE: The aim of this study was to determine overall trends and center-level variation in utilization of completion lymph node dissection (CLND) and adjuvant systemic therapy for sentinel lymph node (SLN)-positive melanoma. SUMMARY BACKGROUND DATA: Based on recent clinical trials, management options for SLN-positive melanoma now include effective adjuvant systemic therapy and nodal observation instead of CLND. It is unknown how these findings have shaped practice or how these contemporaneous developments have influenced their respective utilization. METHODS: We performed an international cohort study at 21 melanoma referral centers in Australia, Europe, and the United States that treated adults with SLN-positive melanoma and negative distant staging from July 2017 to June 2019. We used generalized linear and multinomial logistic regression models with random intercepts for each center to assess center-level variation in CLND and adjuvant systemic treatment, adjusting for patient and disease-specific characteristics. RESULTS: Among 1109 patients, performance of CLND decreased from 28% to 8% and adjuvant systemic therapy use increased from 29 to 60%. For both CLND and adjuvant systemic treatment, the most influential factors were nodal tumor size, stage, and location of treating center. There was notable variation among treating centers in management of stage IIIA patients and use of CLND with adjuvant systemic therapy versus nodal observation alone for similar risk patients. CONCLUSIONS: There has been an overall decline in CLND and simultaneous adoption of adjuvant systemic therapy for patients with SLN-positive melanoma though wide variation in practice remains. Accounting for differences in patient mix, location of care contributed significantly to the observed variation.

A Clinical Decision Tool to Calculate Pretest Probability of Sentinel Lymph Node Metastasis in Primary Cutaneous Melanoma.

BACKGROUND: Although sentinel lymph node biopsy (SLNB) status is a strong prognostic indicator for cutaneous melanoma, unnecessary SLNBs have substantial cost and morbidity burden. OBJECTIVE: This study was designed to develop, validate, and present a personalized, clinical, decision-making tool using nationally representative data with clinically actionable probability thresholds (Expected Lymphatic Metastasis Outcome [ELMO]). METHODS: Data from the Surveillance, Epidemiology, and End Results (SEER) Registry from 2000 to 2017 and the National Cancer Database (NCDB) from 2004 to 2015 were used to develop and internally validate a logistic ridge regression predictive model for SLNB positivity. External validation was done with 1568 patients at a large tertiary referral center. RESULTS: The development cohort included 134,809 patients, and the internal validation cohort included 38,518 patients. ELMO (AUC 0.85) resulted in a 29.54% SLNB reduction rate and greater sensitivity in predicting SLNB status for T1b, T2a, and T2b tumors than previous models. In external validation, ELMO had an accuracy of 0.7586 and AUC of 0.7218. Limitations of this study are potential miscoding, unaccounted confounders, and effect modification. CONCLUSIONS: ELMO ( https://melanoma-sentinel.herokuapp.com/ ) has been developed and validated (internally and externally) by using the largest publicly available dataset of melanoma patients and was found to have high accuracy compared with other published models and gene expression tests. Individualized risk estimates for SLNB positivity are critical in facilitating thorough decision-making for healthcare providers and patients with melanoma.

Sentinel lymph node biopsy in patients with T1a cutaneous malignant melanoma: A multicenter cohort study.

BACKGROUND: Sentinel lymph node biopsy is not routinely recommended for T1a cutaneous melanoma due to the overall low risk of positivity. Prognostic factors for positive sentinel lymph node (SLN+) in this population are poorly characterized. OBJECTIVE: To determine factors associated with SLN+ in patients with T1a melanoma. METHODS: Patients with pathologic T1a (<0.80 mm, nonulcerated) cutaneous melanoma from 5 high-volume melanoma centers from 2001 to 2020 who underwent wide local excision with sentinel lymph node biopsy were included in the study. Patient and tumor characteristics associated with SLN+ were analyzed by univariate and multivariable logistic regression analyses. Age was dichotomized into ≤42 (25% quartile cutoff) and >42 years. RESULTS: Of the 965 patients identified, the overall SLN+ was 4.4% (N = 43). Factors associated with SLN+ were age ≤42 years (7.5% vs 3.7%; odds ratio [OR], 2.14; P = .03), head/neck primary tumor location (9.2% vs 4%; OR, 2.75; P = .04), lymphovascular invasion (21.4% vs 4.2%; OR, 5.64; P = .01), and ≥2 mitoses/mm2 (8.2% vs 3.4%; OR, 2.31; P = .03). Patients <42 years with ≥2 mitoses/mm2 (N = 38) had a SLN+ rate of 18.4%. LIMITATIONS: Retrospective study. CONCLUSION: SLN+ is low in patients with T1a melanomas, but younger age, lymphovascular invasion, mitogenicity, and head/neck primary site appear to confer a higher risk of SLN+.

Is the presence of tumor-infiltrating lymphocytes predictive of outcomes in patients with melanoma?

BACKGROUND: The significance of tumor-infiltrating lymphocytes (TILs) in melanoma is debated. This article presents a multicenter, retrospective study assessing the predictive and prognostic value of TILs. METHODS: The Sentinel Lymph Node Working Group database was queried from 1993 to 2018 for cases with known TIL data. TILs were categorized as absent or present, which included nonbrisk (NB), brisk (B), and present but unspecified TIL levels. Clinicopathologic factors were correlated with TILs, sentinel lymph node (SLN) status, and melanoma-specific survival (MSS). RESULTS: Overall, 3203 patients were included. The median thickness was 1.5 mm, and 469 cases had SLN metastases. TILs were present in 2458 cases (76.7%), with NB, B, and unspecified TILs seen in 1691 (68.8%), 691 (28.1%), and 76 (3.1%), respectively. Multivariable analysis showed that the presence of TILs significantly predicted a negative SLN biopsy (P < .05). The median follow-up was 25.2 months. MSS was significantly better for cases with TILs than cases without TILs (P < .001). According to multivariable analysis, age, gender, thickness, mitotic rate, ulceration, lymphovascular invasion, and SLN status were significantly prognostic of MSS (all P values < .05). Although TILs were not prognostic of MSS, when multiple imputation was used and the SLN status was excluded, the presence of TILs was significantly prognostic of improved MSS (hazard ratio, 0.78; 95% confidence interval, 0.64-0.95; P = .0154). CONCLUSIONS: TILs are a favorable marker because their presence significantly predicts a negative SLN, and the absence of TILs may be a prognostic marker of worse survival in patients with a positive SLN but not a negative SLN. TILs may also serve as a prognostic marker of survival when the SLN status is not considered.

Is There a Relationship Between TILs and Regression in Melanoma?

BACKGROUND: The relationship between tumor-infiltrating lymphocytes (TILs) and regression in melanoma is unknown. This report describes a large multicenter study assessing the association between TILs and regression. METHODS: The Sentinel Lymph Node Working Group database was queried from 1993 to 2018 for cases with TILs and regression data. Clinicopathologic factors were correlated with regression and TIL status, sentinel lymph node (SLN) status, and overall survival (OS). RESULTS: The study enrolled 2450 patients. In 1811 cases, TILs (73.9%) were present, with regression present in 328 of these 1811 (18.1%) cases and in 49 (7.7%) of 639 cases without TILs. The presence of TILs was significantly associated with regression (p < 0.0001) as well as a negative SLN (p < 0.05). However, when TILs were stratified by regression status, only absence or presence of both TILs and regression were significantly associated with SLN metastases (p = 0.038). Although the presence of TILs was associated with OS (p < 0.05), regression status by itself was not (p = 0.2058 and 0.252, respectively). Furthermore, when TILs were stratified by regression status, only the presence of TILs with or without regression was significantly associated with improved OS (p = 0.0081 and 0.0137, respectively) versus the absence of both TILs and regression, with regression status not significantly affecting OS for patients with or without TILs (p = 0.2314 and 0.65, respectively). CONCLUSIONS: Regression is highly correlated with TILs, but only TILs are significantly associated with SLN metastasis and OS in melanoma patients, whereas regression is not. The impact of regression on outcomes ultimately appears dependent upon the absence or presence of TILs.

Regression in melanoma is significantly associated with a lower regional recurrence rate and better recurrence-free survival.

BACKGROUND AND OBJECTIVES: The prognostic significance of regression in predicting melanoma recurrences is unknown. We present a large multicenter study correlating regression with recurrence. METHODS: The Sentinel Lymph Node Working Group database was queried from 1993 to 2018 for cases with regression data. Clinicopathologic factors were correlated with overall and first-site of recurrence and with recurrence-free survival (RFS). RESULTS: There were 4790 patients and the median follow-up was 39.6 months. Regression and recurrences were seen in 1081 (22.6%) and 773 (16.1%) cases, respectively. First-site locoregional and distant recurrences were seen in 412 (8.6%) and 352 (7.3%) patients, respectively. Regression was seen in 15.8% and 24.7% of all cases with and without recurrences (p < 0.0001), respectively, while regression was seen in 14.3% and 17.9% of first-site locoregional and distant recurrent cases, respectively, compared with 23.3% and 22.9% of patients with regression and without first-site locoregional and distant recurrences, respectively (p = 0.29). On multivariable analysis, after controlling for age, gender, thickness, ulceration, lymphovascular invasion, and sentinel lymph node status, regression significantly predicted improved RFS (p = 0.004) and fewer first-site regional recurrences (p = 0.017). CONCLUSION: Our data suggest that regression is a favorable prognostic marker in melanoma and predicts significantly better RFS and decreased first-site regional recurrences.

Clinical Utility of Dermoscopy and 31-Gene Expression Profiling by Dermatology Providers in Melanoma Management Care.

OBJECTIVE: A 31-gene expression profile (31-GEP) test that predicts metastatic risk in patients with cutaneous malignant melanoma (CMM) has previously been validated and is available for clinical use. The test dichotomizes patients into lower risk and higher risk groups based on differences that correspond to unique genetic expression patterns. Although the impact of such a test on dermatology providers' clinical decision-making has been studied, little is known about whether there exists an association between certain clinical features, such as dermoscopy, and 31-GEP results. METHODS: In this retrospective analysis of 31-GEP test results ordered by dermatologists, we evaluated the frequency of dermoscopic features, using a modified dermoscopy three-point checklist, in 17 cases (n=17) and compared these findings to other key clinicopathologic features including tumor thickness, ulceration, and mitotic rate to 31-GEP results. Additionally, we evaluated the dermatologist's perspective and incorporation of GEP testing as part of patient discussion on melanoma management. RESULTS: 31-GEP stratified patients into 4 groups; groups 1A and 1B are considered low risk of metastasis or recurrence, while 2A and 2B are considered high risk. Of the 17 cases, we had fifteen group 1A (88.23%), one 1B (5.88%), and one 2B (5.88%) result. Overall frequency of dermoscopic features is as follows; 100% of lesions presented with asymmetry, 47% with round structures, and 70.6% with blue-white color. The average time providers spent explaining and ordering the test was 15 minutes, with a range of 10 to 20 minutes. CONCLUSIONS: This study represents our experience and understanding of the dermatologist’s role ordering 31-GEP in the care pathway of melanoma patients and we recommend that dermatology providers consider ordering the test for newly diagnosed CMM patients. J Drugs Dermatol. 2022;21(12): doi:10.36849/JDD.6889.

Active surveillance of patients who have sentinel node positive melanoma: An international, multi-institution evaluation of adoption and early outcomes after the Multicenter Selective Lymphadenectomy Trial II (MSLT-2).

BACKGROUND: For patients with sentinel lymph node (SLN)-positive cutaneous melanoma, the Second Multicenter Selective Lymphadenectomy trial demonstrated equivalent disease-specific survival (DSS) with active surveillance using nodal ultrasound versus completion lymph node dissection (CLND). Adoption and outcomes of active surveillance in clinical practice and in adjuvant therapy recipients are unknown. METHODS: In a retrospective cohort of SLN-positive adults treated at 21 institutions in Australia, Europe, and the United States from June 2017 to November 2019, the authors evaluated the impact of active surveillance and adjuvant therapy on all-site recurrence-free survival (RFS), isolated nodal RFS, distant metastasis-free survival (DMFS), and DSS using Kaplan-Meier curves and Cox proportional hazard models. RESULTS: Among 6347 SLN biopsies, 1154 (18%) were positive and had initial negative distant staging. In total, 965 patients (84%) received active surveillance, 189 (16%) underwent CLND. Four hundred thirty-nine patients received adjuvant therapy (surveillance, 38%; CLND, 39%), with the majority (83%) receiving anti-PD-1 immunotherapy. After a median follow-up of 11 months, 220 patients developed recurrent disease (surveillance, 19%; CLND, 22%), and 24 died of melanoma (surveillance, 2%; CLND, 4%). Sixty-eight patients had an isolated nodal recurrence (surveillance, 6%; CLND, 4%). In patients who received adjuvant treatment without undergoing prior CLND, all isolated nodal recurrences were resectable. On risk-adjusted multivariable analyses, CLND was associated with improved isolated nodal RFS (hazard ratio [HR], 0.36; 95% CI, 0.15-0.88), but not all-site RFS (HR, 0.68; 95% CI, 0.45-1.02). Adjuvant therapy improved all-site RFS (HR, 0.52; 95% CI, 0.47-0.57). DSS and DMFS did not differ by nodal management or adjuvant treatment. CONCLUSIONS: Active surveillance has been adopted for most SLN-positive patients. At initial assessment, real-world outcomes align with randomized trial findings, including in adjuvant therapy recipients. LAY SUMMARY: For patients with melanoma of the skin and microscopic spread to lymph nodes, monitoring with ultrasound is an alternative to surgically removing the remaining lymph nodes. The authors studied adoption and real-world outcomes of ultrasound monitoring in over 1000 patients treated at 21 centers worldwide, finding that most patients now have ultrasounds instead of surgery. Although slightly more patients have cancer return in the lymph nodes with this strategy, typically, it can be removed with delayed surgery. Compared with up-front surgery, ultrasound monitoring results in the same overall risk of melanoma coming back at any location or of dying from melanoma.

What is the Cost-Effective Treatment for Melanoma Patients with a Positive Sentinel Node?

BACKGROUND: Survival for positive sentinel lymph node (SLN) patients does not differ between completion lymph node dissection (CLND) and nodal observation (OBS). However, treating these patients with CLND and checkpoint inhibitors, such as pembrolizumab (PEM), improves outcomes. This study evaluated the cost-effectiveness of OBS, CLND, and CLND with PEM (CLND-PEM) treatments. METHODS: A Markov model was designed to simulate treatment for a theoretical cohort of 1000 positive SLN patients per therapy with a 5-year follow-up period. An intervention was cost-effective if its incremental cost-effectiveness ratio among therapies was below the willingness-to-pay threshold of $100,000 per quality-adjusted life year (QALY). RESULTS: Compared with CLND or CLND-PEM, OBS resulted in fewer lymphedema cases but in more disease recurrences. Compared with OBS, CLND had higher costs and lower QALYs. Although CLND-PEM had a lower number of recurrences and deaths than OBS or CLND, it had higher costs and lower QALYs than OBS, and thus was not cost-effective. However, with the effects of CLND from CLND-PEM removed, allowing evaluation of PEM effects alone (PEM alone), the resulting QALYs were the highest, but PEM alone still was not cost-effective compared with OBS ($1.2 million per QALY). By reducing the drug cost to less than $14,404 per patient, PEM alone would become cost-effective. CONCLUSIONS: Compared with CLND, CLND-PEM, and PEM alone, OBS was cost-effective for managing positive SLN patients. Although CLND-PEM and PEM alone result in fewer recurrences and deaths, these therapies were not cost-effective due to the quality-of-life decrement of CLND and the current high drug cost of PEM.

Sentinel Lymph Node Biopsy Is Prognostic in Thickest Melanoma Cases and Should Be Performed for Thick Melanomas.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is recommended for intermediate thickness melanoma, but for thick melanoma, guidelines are less definitive about the use of SLNB in this population. We present a study on thick melanoma evaluating for prognostic factors. PATIENTS AND METHODS: The Sentinel Lymph Node Working Group database was queried for thick (> 4 mm) melanoma cases that had a SLNB from 1993 to 2018. Clinicopathologic characteristics were correlated with SLN status and melanoma-specific survival (MSS). RESULTS: There were 1235 patients. Median follow-up was 28 months. Median thickness was 5.9 mm, with 956, 175, and 104 cases presenting thickness > 4-8, > 8-12, and > 12 mm, respectively. SLN metastases were seen in 439 of 1235 (35.5%) cases and in 33.9%, 40.6%, and 42.3% of melanomas > 4-8, > 8-12, and > 12 mm, respectively. In each thickness group, MSS was significantly worse for SLN-positive compared with SLN-negative cases (all P < 0.005). Multivariable analysis showed that SLN metastasis, male gender, increasing thickness, lymphovascular invasion, and microsatellitosis significantly predicted worse MSS for melanomas > 4-8 mm, with SLN metastasis showing the greatest risk (HR 2.17, 95% CI 1.64-2.87, P < 0.0001). For melanomas > 8 mm, only SLN metastasis significantly predicted MSS (> 8-12 mm: HR 3.93, 95% CI 2.00-7.73, P < 0.0001; > 12 mm: HR 3.58, 95% CI 1.56-8.22, p < 0.0027). CONCLUSIONS: Thick melanoma patients with SLN metastasis have significantly worse MSS compared with SLN-negative patients, even in the thickest cases, and SLN status is the most powerful and/or only predictor of MSS. Given these results, SLNB shows important prognostic value in this population and is indicated for clinically localized thick melanoma.

Acral Lentiginous Melanoma: A United States Multi-Center Substage Survival Analysis.

BACKGROUND: Acral lentiginous melanoma is associated with worse survival than other subtypes of melanoma. Understanding prognostic factors for survival and recurrence can help better inform follow-up care. OBJECTIVES: To analyze the clinicopathologic features, melanoma-specific survival, and recurrence-free survival by substage in a large, multi-institutional cohort of primary acral lentiginous melanoma patients. METHODS: Retrospective review of the United States Melanoma Consortium database, a multi-center prospectively collected database of acral lentiginous melanoma patients treated between January 2000 and December 2017. RESULTS: Of the 433 primary acral lentiginous melanoma patients identified (median [range] age: 66 [8-97] years; 53% female, 83% white), 66% presented with stage 0-2 disease and the median time of follow-up for the 392 patients included in the survival analysis was 32.5 months (range: 0-259). The 5-year melanoma-specific survivals by stage were 0 = 100%, I = 93.8%, II = 76.2%, III = 63.4%, IIIA = 80.8%, and IV = 0%. Thicker Breslow depth ((HR) = 1.13; 95% CI = 1.05-1.21; P < .001)) and positive nodal status ((HR) = 1.79; 95% CI = 1.00-3.22; P = .050)) were independent prognostic factors for melanoma-specific survival. Breslow depth ((HR = 1.13; 95% CI = 1.07-1.20; P < .001), and positive nodal status (HR = 2.12; 95% CI = 1.38-3.80; P = .001) were also prognostic factors for recurrence-free survival. CONCLUSION: In this cohort of patients, acral lentiginous melanoma was associated with poor outcomes even in early stage disease, consistent with prior reports. Stage IIB and IIC disease were associated with particularly low melanoma-specific and recurrence-free survival. This suggests that studies investigating adjuvant therapies in stage II patients may be especially valuable in acral lentiginous melanoma patients.

The Devil's in the Details: Discrepancy Between Biopsy Thickness and Final Pathology in Acral Melanoma.

PURPOSE: We hypothesized that initial biopsy may understage acral lentiginous melanoma (ALM) and lead to undertreatment or incomplete staging. Understanding this possibility can potentially aid surgical planning and improve primary tumor staging. METHODS: A retrospective review of primary ALMs treated from 2000 to 2017 in the US Melanoma Consortium database was performed. We reviewed pathology characteristics of initial biopsy, final excision specimens, surgical margins, and sentinel lymph node biopsy (SLNB). RESULTS: We identified 418 primary ALMs (321 plantar, 34 palmar, 63 subungual) with initial biopsy and final pathology results. Median final thickness was 1.8 mm (range 0.0-19.0). There was a discrepancy between initial biopsy and final pathology thickness in 180 (43%) patients with a median difference of 1.6 mm (range 0.1-16.4). Final T category was increased in 132 patients (32%), including 47% of initially in situ, 32% of T1, 39% of T2, and 28% of T3 lesions. T category was more likely to be increased in subungual (46%) and palmar (38%) melanomas than plantar (28%, p = 0.01). Among patients upstaged to T2 or higher, 71% had ≤ 1-cm margins taken. Among the 27 patients upstaged to T1b or higher, 8 (30%) did not have a SLNB performed, resulting in incomplete initial staging. CONCLUSIONS: In this large series of ALMs, final T category was frequently increased on final pathology. A high index of suspicion is necessary for lesions initially in situ or T1 and consideration should be given to performing additional punch biopsies, wider margin excisions, and/or SLNB.

Chemoprevention agents for melanoma: A path forward into phase 3 clinical trials.

Recent progress in the treatment of advanced melanoma has led to unprecedented improvements in overall survival and, as these new melanoma treatments have been developed and deployed in the clinic, much has been learned about the natural history of the disease. Now is the time to apply that knowledge toward the design and clinical evaluation of new chemoprevention agents. Melanoma chemoprevention has the potential to reduce dramatically both the morbidity and the high costs associated with treating patients who have metastatic disease. In this work, scientific and clinical melanoma experts from the national Melanoma Prevention Working Group, composed of National Cancer Trials Network investigators, discuss research aimed at discovering and developing (or repurposing) drugs and natural products for the prevention of melanoma and propose an updated pipeline for translating the most promising agents into the clinic. The mechanism of action, preclinical data, epidemiological evidence, and results from available clinical trials are discussed for each class of compounds. Selected keratinocyte carcinoma chemoprevention studies also are considered, and a rationale for their inclusion is presented. These data are summarized in a table that lists the type and level of evidence available for each class of agents. Also included in the discussion is an assessment of additional research necessary and the likelihood that a given compound may be a suitable candidate for a phase 3 clinical trial within the next 5 years.

Recurrence of Melanoma After a Negative Sentinel Node Biopsy: Predictors and Impact of Recurrence Site on Survival.

BACKGROUND: Factors that predict melanoma recurrence after a negative sentinel lymph node biopsy (SLNB) are not well-defined. We evaluated melanoma recurrence patterns, factors prognostic for recurrence, and the impact of recurrence on outcomes after a negative SLNB. METHODS: The Sentinel Lymph Node Working Group database was evaluated from 1996 to 2016 for negative SLNB melanoma patients. Clinicopathologic characteristics were correlated with recurrence, overall survival (OS), and melanoma-specific survival (MSS). RESULTS: Median follow-up was 32.1 months. Recurrences developed in 558 of 5351 negative SLN patients (10.4%). First-site of recurrence included a local or in-transit recurrence (LITR) in 221 cases (4.1%), nodal recurrence (NR) in 109 cases (2%), and distant recurrence (DR) in 220 cases (4.1%). On multivariable analysis, age, thickness, head/neck or lower extremity primary, and microsatellitosis significantly predicted for an LITR as first-site. Having an LITR as first-site significantly predicted for a subsequent NR and DR, and significantly predicted for worse OS and MSS. Furthermore, thickness and head/neck or lower extremity primary significantly predicted for an NR as first-site, while a prior LITR significantly predicted for a subsequent NR. Factors significantly predictive for a DR included thickness, head/neck or trunk primary, ulceration, and lymphovascular invasion. Patients with any type of locoregional recurrence were at higher risk for a DR. CONCLUSIONS: Recurrences occur in 10.4% of negative SLN patients, with LITR and DR being the most common types. Importantly, having an LITR significantly predicts for a subsequent NR and DR, and is prognostic for worse survival after a negative SLNB.

Microsatellitosis in Patients with Melanoma.

BACKGROUND: Microsatellitosis (mS) in melanoma has been considered a marker of unfavorable tumor biology, leading to the current American Joint Committee on Cancer staging of IIIB/C/D disease, despite few investigative studies of this entity limited by the small sample sizes and incomplete nodal microstaging. We sought to better characterize outcomes and prognostic factors in a multi-institutional cohort of patients with mS and nodal microstaging. METHODS: The Sentinel Lymph Node Working Group cohort included 414 mS patients who underwent sentinel lymph node (SLN) biopsy. Cox regression analysis was used to evaluate the prognostic significance of established clinicopathologic characteristics. Melanoma-specific survival (MSS) of patients with mS was compared with 3002 similarly staged patients from the Surveillance, Epidemiology, and End Results (SEER) Program registry. RESULTS: The median age of the mS cohort was 64.9 years; 39.6% were female. Median thickness was 3 mm, 40.6% of cases were ulcerated, and the SLN positivity rate was 46.7%. Increasing thickness, male sex, and SLN positivity were significantly associated with poorer MSS. Stage IIIB/C/D 5-year MSS rates were 86.3% (95% confidence interval [CI] 79.4-93.3%), 54.1% (95% CI 45.4-59.7%), and 44.2% (95% CI 25.4-63.0%), respectively. MSS survival for the stage IIIB mS cohort was significantly better than a similarly staged SEER cohort (5-year MSS of 70.1%, 95% CI 66.0-74.2%), while no significant difference was observed for the stage IIIC or D cohorts. CONCLUSIONS: SLN metastases are common and are a significant prognostic factor in patients with mS. Survival in stage IIIB patients with mS was considerably more favorable than their stage would otherwise suggest, which has important implications for decisions regarding adjuvant therapy for patients with mS.

Completion lymphadenectomy for a positive sentinel node biopsy in melanoma patients is not associated with a survival benefit.

BACKGROUND: Completion lymph node dissection (CLND) for sentinel lymph node (SLN) disease in melanoma patients is debated. We evaluated the impact of CLND on survival and assessed for predictors of nonsentinel node metastasis (positive CLND). METHODS: Positive SLN melanoma patients were retrospectively identified in the Sentinel Lymph Node Working Group database. Clinicopathological factors were correlated with CLND status, overall survival (OS), and melanoma-specific survival (MSS). RESULTS: There were 953 positive SLN patients of whom 831 (87%) had CLND. Positive CLND was seen in 141 (17%) cases and was associated with worse OS and MSS (both P < 0.001). CLND was not performed (No-CLND) in 122 of 953 positive SLN cases (13%), of whom 100 had follow-up and 18 (18%) developed a nodal recurrence (NR). No significant differences in OS and MSS were seen comparing CLND with No-CLND (P = 0.084, P = 0.161, respectively) and comparing positive CLND with No-CLND NR patients (P = 0.565, P = 0.998, respectively). Gender, primary site, ulceration, and number of positive SLNs were correlated with nonsentinel node metastasis. CONCLUSIONS: Performance of CLND provides prognostic information but is not associated with a survival benefit. Clinical variables can predict a positive CLND in patients who may be at high risk of recurrence.

Identification of patients at risk of metastasis using a prognostic 31-gene expression profile in subpopulations of melanoma patients with favorable outcomes by standard criteria.

BACKGROUND: A substantial number of patients who relapse and die from cutaneous melanoma (CM) are categorized as being at low risk by traditional staging factors. The 31-gene expression profile (31-GEP) test independently stratifies metastatic risk of patients with CM as low (Class 1, with 1A indicating lowest risk) or high (Class 2,with 2B indicating highest risk). OBJECTIVE: To assess risk prediction by the 31-GEP test within 3 low-risk (according to the American Joint Committee on Cancer) populations of patients with CM: those who are sentinel lymph node (SLN) negative, those with stage I to IIA tumors, and those with thin (≤1 mm [T1]) tumors. METHODS: A total of 3 previous validation studies provided a nonoverlapping cohort of 690 patients with 31-GEP results, staging information, and survival outcomes. Kaplan-Meier and Cox regression analysis were performed. RESULTS: The results included the identification of 70% of SLN-negative patients who experienced metastasis as Class 2, the discovery of reduced recurrence-free survival for patients with thin tumors and Class 2B biology compared with that of those with Class 1A biology (P < .0001); and determination of the 31-GEP test as an independent predictor of risk compared with traditional staging factors in patients with stage I to IIA tumors. LIMITATIONS: Diagnoses spanned multiple versions of pathologic staging criteria. CONCLUSIONS: The 31-GEP test identifies high-risk patients who are likely to experience recurrence or die of melanoma within low-risk groups of subpopulations of patients with CM who have SLN-negative disease, stage I to IIA tumors, and thin tumors.

Guidance of sentinel lymph node biopsy decisions in patients with T1-T2 melanoma using gene expression profiling.

AIM: Can gene expression profiling be used to identify patients with T1-T2 melanoma at low risk for sentinel lymph node (SLN) positivity? PATIENTS & METHODS: Bioinformatics modeling determined a population in which a 31-gene expression profile test predicted <5% SLN positivity. Multicenter, prospectively-tested (n = 1421) and retrospective (n = 690) cohorts were used for validation and outcomes, respectively. RESULTS: Patients 55-64 years and ≥65 years with a class 1A (low-risk) profile had SLN positivity rates of 4.9% and 1.6%. Class 2B (high-risk) patients had SLN positivity rates of 30.8% and 11.9%. Melanoma-specific survival was 99.3% for patients ≥55 years with class 1A, T1-T2 tumors and 55.0% for class 2B, SLN-positive, T1-T2 tumors. CONCLUSION: The 31-gene expression profile test identifies patients who could potentially avoid SLN biopsy.

Thirty Years of the Journal of Cancer Education: a Review.

Since its foundation in 1986, the Journal of Cancer Education (JCE) has served as an important outlet for myriad aspects of cancer education and currently serves as the official journal of the American and European Associations for Cancer Education. During its history, the JCE has been under the auspices of five publishers, with its first full year under the current publisher, Springer, in 2010. Print and distribution metrics from 2010 to present were obtained from Springer. These were compared to historical data including the first 10 years of the JCE, published by Dr. Bakemeier in 1995. Since its beginning, the JCE has consisted of four issues per year. The original contract for 256 pages per year has increased to an average of 858 pages from 2010 to 2014. In 2015, the JCE received a total of 344 submissions, up from 339 in 2014, and 262 the year before. This is a stark contrast to the roughly 44 submission received in 1994. Over this same period, the overall rejection rate has increased from 30% in 2010 to 45% in 2015. The number of online deals has increased from 347 in 2014 to 361 in 2015 and has been accompanied by a steady increase in the number of full-text article downloads: 19,000 in 2010 to 58,923 in 2015. Accordingly, the JCE has seen a pronounced and steady increase in impact factor, rising from 0.52 in 2009 to 1.368 in 2015. Since moving to Springer, the JCE has seen unprecedented growth, receiving increasing submissions yearly, an increasing number of subscription deals and online full-text downloads, and a corresponding increase in impact factor.