Bagaria, Sanjay P.

PURPOSEMore than 80% of patients who undergo sentinel lymph node (SLN) biopsy have no nodal metastasis. Here, we describe a model that combines clinicopathologic and molecular variables to identify patients with thin- and intermediate-thickness melanomas who may forgo the SLN biopsy procedure because of their low risk of nodal metastasis.PATIENTS AND METHODSGenes with functional roles in melanoma metastasis were discovered by analysis of next-generation sequencing data and case-control studies. We then used polymerase chain reaction to quantify gene expression in diagnostic biopsy tissue across a prospectively designed archival cohort of 754 consecutive thin- and intermediate-thickness primary cutaneous melanomas. Outcome of interest was SLN biopsy metastasis within 90 days of melanoma diagnosis. A penalized maximum likelihood estimation algorithm was used to train logistic regression models in a repeated cross-validation scheme to predict the presence of SLN metastasis from molecular, clinical, and histologic variables.RESULTSExpression of genes with roles in epithelial-to-mesenchymal transition (glia-derived nexin, growth differentiation factor 15, integrin-β3, interleukin 8, lysyl oxidase homolog 4, transforming growth factor-β receptor type 1, and tissue-type plasminogen activator) and melanosome function (melanoma antigen recognized by T cells 1) were associated with SLN metastasis. The predictive ability of a model that only considered clinicopathologic or gene expression variables was outperformed by a model that included molecular variables in combination with the clinicopathologic predictors Breslow thickness and patient age (area under the receiver operating characteristic curve, 0.82; 95% CI, 0.78 to 0.86; SLN biopsy reduction rate, 42%; negative predictive value, 96%).CONCLUSIONA combined model that included clinicopathologic and gene expression variables improved the identification of patients with melanoma who may forgo the SLN biopsy procedure because of their low risk of nodal metastasis.

Abstract Background Acral melanoma is the most common subtype of melanoma in Chinese patients and one of the least common in Caucasian patients. It has been unclear if outcomes differ between Chinese and Caucasian patients diagnosed with Acral Melanoma. This study investigated patient characteristics and survival differences between Chinese and Caucasian Acral Melanoma patients. Methods Two large institutional melanoma databases from Fudan University Shanghai Cancer Center (FUSCC) and Mayo Clinic enterprise, were retrospectively reviewed from 2009 to 2015. Clinicopathologic and survival data were collected and analyzed between the two groups. The primary outcome was disease-specific survival (DSS) and was calculated using the Kaplan Meier (KM) method. Results The Chinese group presented with more advanced disease compared with Caucasians: thicker Breslow depth (median 3.0 mm vs. 1.2 mm, p=0.003), more ulcerated disease (66.1% vs 29%; p<0.001), and advanced stages (stage II/III 84.3% vs. 37.1%; p<0.001). No significant difference was identified in terms of age at diagnosis, location, histologic subtypes, or node positive rate. The 5-year DSS rate was 68.4% and 73% (p=0.56) for Chinese and Caucasians, respectively. Male gender, Breslow thickness, ulceration, and positive sentinel lymph nodes predicted worse DSS on multivariate Cox regression analysis. Conclusions There appears to be no difference in stage-stratified survival between Chinese and Caucasians, supporting the implementation of clinical trials of AM that could include both Chinese and Caucasian patients.

Abstract Background Schwannomas are rare tumours that pose a significant management challenge in the abdomen, retroperitoneum and pelvis. No data are available to inform management strategy. Methods A collaborative international cohort study, across specialist sarcoma units, was conducted to include adults presenting between 2000 and 2017 with histopathologically confirmed schwannomas within the abdomen, retroperitoneum or pelvis. Results Of 485 patients across 12 centres, 38 (7·8 per cent) were discharged without follow-up, 199 (41·0 per cent) underwent early resection and 248 (51·1 per cent) had radiological monitoring. Of these 248 patients, 96 (38·7 per cent) eventually had surgery, giving an overall resection rate of 60·8 per cent (295 of 485). At baseline, median tumour volume was 90·1 (i.q.r. 26·5–262·0) cm3. The estimated growth rate was 10·5 (95 per cent c.i. 9·4 to 11·6) per cent per year, and was consistent in the short term (within 2 years of diagnosis) and long term (beyond 2 years) (ρ = 0·405, P = 0·021). A decision to operate was more common in symptomatic patients (P &lt; 0·001) and for rapidly growing tumours (growth rate more than 20 per cent per year) (P = 0·025). R0/R1 resection was achieved in 91·6 per cent of patients (263 of 287). Kaplan–Meier long-term recurrence rates after R0/R1 resection were 2·3 and 6·7 per cent at 3 and 5 years respectively. Conclusion Specific recommendations include: indications for early surgery, prediction of growth from radiological monitoring, promotion of selective submacroscopic resection and cessation of postoperative imaging surveillance.

Background: External ear melanoma (EEM) is a rare condition with controversies in the literature. We analyzed patients with EEM in the United States compared to other head and neck melanomas (OHNMs). Methods: The National Cancer Database (NCDB) was used to select patients with head and neck melanoma from January 1, 2004 to December 31, 2015. Mann–Whitney and χ 2 tests were used to estimate statistical significance, and multivariate logistic regression to identify independent associations adjusted for confounders. Results: A total of 137,233 patients met the study criteria. Among them, 16,991 (12.4%) had EEM and 120,242 (87.6%) had OHNM. For patients with EEM, the mean (standard deviation) age was 66.26 (15.798) years. Most of the patients with EEM were men (85.5%), insured by Medicare (52.4%), and treated in Academic/Research Programs (47.7%) or Comprehensive Community Cancer Programs (32.3%). Most of the EEM tumors had invasive behavior (68.0%) were Stages 0 (30.3%) or I (40.3%), and were without ulceration (76.9%). Mean time to receive any treatment was 14.1 days for EEM compared with 14.6 days for OHNM (P < 0.001). We noticed a greater proportion of EEM in men (14.8%; adjusted odds ratio [aOR] 2.72 [2.605–2.852]; P < 0.001) compared to women (6.22%; reference). EEM was an independent factor for tumor Stage I (14.47%; aOR 1.61 [1.101–1.224], P < 0.001) and invasive behavior (13.86%; aOR 1.268 [1.15–1.389]; P < 0.001) compared to OHNM. Conclusion: EEM was associated with higher odds of invasive behavior compared to OHNM. Furthermore, men were found to have a higher likelihood to develop EEM compared to women.

Background: Eyelid melanoma (EM) is a rare condition that accounts for <1% of all cutaneous melanomas. In this analysis, patients diagnosed with EM in the United States were compared to those with other melanomas in the head and neck. Methods: The National Cancer Database was used to select patients with head and neck melanoma from 2004 to 2015. Results: A total of 137,233 patients met the criteria of the study. Among them, 2694 were diagnosed with EM (2%) and 134,539 in other head and neck locations (98%). Regarding the patients with EM, the mean age was 68.56 years (standard deviation 14.04). A greater number of them were treated in Academic/Research Programs (53.6%), insured by Medicare (55.7%), tumor in situ (52.2%), stage 0 (49%), and without ulceration (75.9%). The mean time to treatment commencement was 18.96 days for EM compared to 14.4 days for other melanoma in the head and neck regions (P < 0.001). There was a greater proportion of EM in female patients (odds ratio [OR] 2.371 [2.191–2.566], P < 0.001), compared to male; age greater than 80 years (OR 1.622 [1.360–1.934], P < 0.001) compared to 0 to 49 years. Moreover, EM was an independent predictor for treatment in Academic/Research Programs (OR 1.258 [1.160–1.365], P < 0.001) and diagnosis at autopsy (OR 1.414 [1.083–1.847], P = 0.011) compared to other melanoma in the head and neck region. Conclusion: These novel findings have the potential to guide clinical decision making in head and neck melanoma management.

Abstract Purpose: The role of surgery for first relapse locally recurrent retroperitoneal sarcoma (RPS-LR1) is uncertain. We report outcomes of the largest RPS-LR1 series and propose a new prognostic nomogram. Experimental Design: Patients with consecutive RPS-LR1 without distant metastases who underwent resection at 22 centers (2002–2011) were included. Endpoints were disease-free and overall survival (DFS, OS) and crude-cumulative-incidence (CCI) of local/distant recurrence from second surgery. Nomograms predicting DFS and OS from second surgery were developed and validated (calibration plots); discrimination was assessed (Harrell C index). Results: Of 684 patients identified, full prognostic variable data were available for 602. Initial surgery for primary RPS was performed at our institutions in 188 patients (31%) and elsewhere in 414 (69%). At a median follow-up of 119 months [Interquartile range (IQR), 80–169] from initial surgery and 75 months (IQR 50–105) from second surgery, 6-year DFS and OS were 19.2% [95% confidence interval (CI), 16.0–23.0%] and 54.1% (95% CI, 49.8–58.8%), respectively. Recurrence patterns and survival probability were histology-specific, with liposarcoma subtypes having the highest 6-year CCI of second local recurrence (LR, 60.2%–70.9%) and leiomyosarcoma (LMS) having higher 6-year CCI of distant metastasis (DM, 36.3%). Nomograms included age at second surgery, multifocality, grade, completeness of second surgery, histology, chemotherapy/radiotherapy at first surgery, and number of organs resected at first surgery. OS and DFS nomograms showed good calibration and discriminative ability (C index 0.70 and 0.67, respectively). Conclusions: We developed nomograms to predict DFS and OS for patients undergoing RPS-LR1 resection. Nomograms provide individualized, disease-relevant estimations of survival for RPS-LR1 patients and assist in clinical decisions.

Background. We sought to study the association between RPS case volume and outcomes. Although a relationship has been demonstrated between case volume and patient outcomes in some cancers, such a relationship has not been established for retroperitoneal sarcomas (RPSs). Study Design. The National Cancer Database (NCDB) was queried for patients undergoing treatment for primary RPS diagnosed between 2004 and 2013. Mean annual patient volume for RPS resection was calculated for all hospitals and divided into low volume (<5 cases/year), medium volume (5–10 cases/year), and high volume (>10 cases/year). Risk-adjusted regression analyses were performed to identify predictors of 30-day surgical mortality, R0 margin status, and overall survival (OS). Results. Our study population consisted of 5,407 patients with a median age of 61 years, of whom 47% were male and 3,803 (70%) underwent surgical resection. Absolute 30-day surgical mortality and R0 margin rate following surgery for low-, medium-, and high-volume institutions were 2.4%, 1.3%, and 0.5% (p=0.027) and 68%, 65%, and 82%, (p<0.001), respectively. Five-year overall survival rates for low, medium, and high-volume institutions were 56%, 57%, and 66%, respectively (p<0.001). Patients treated at low-volume institutions had a significantly higher risk of 30-day mortality (adjusted OR = 4.66, 95% CI 2.26–9.63) and long-term mortality (adjusted HR = 1.56, 95% CI 1.16–2.11) compared to high-volume institutions. Conclusion. We demonstrate the existence of a hospital sarcoma service line volume-oncologic outcome relationship for RPS at the national level and provide benchmark data for cancer care delivery systems and policy makers.

Introduction. Optimization of outcomes of extra-abdominal STS is not clearly understood. We sought to determine whether hospital surgical volume and adherence to NCCN guidelines, or both, are associated with outcomes in the treatment of extra-abdominal soft tissue sarcoma (STS).Methods. The National Cancer Database (NCDB) was queried for patients undergoing surgery for extra-abdominal STS diagnosed from 2003 to 2007. Mean annual hospital volume for STS surgery was divided into volume terciles (1T ≤3, 2T 4–10, and 3T ≥11 cases/year). Adherence to NCCN guidelines was determined. Primary outcome was overall survival.Results. Our study population consisted of 13,684 patients with a median age of 56 years. 3T hospitals were more likely to adhere to NCCN guidelines for stage III patients (63% versus 47%;p≤0.001) than 1T hospitals. On multivariable analysis, adherence to NCCN guidelines was associated with improved survival (HR = 0.79, CI 0.73–0.87;p<0.001), but hospital volume was not (3T versus 1T: HR = 0.92, CI 0.82–1.02;p=0.12). Five-year overall survival was comparable for compliant groups at 1T, 2T, and 3T hospitals (72%, 72.4%, and 72.6%, resp.). 3T hospitals were not associated with a lower risk of 30-day mortality (OR 0.70, 95% CI 0.44–1.11) compared to 1T hospitals but did have a higher R0 resection rate (OR 1.43, 95% CI 1.32–1.54).Conclusions. Adherence to NCCN guidelines, irrespective of hospital volume, is associated with improved overall survival for patients with extra-abdominal STS. High-volume hospitals more often adhere to guidelines, but low-volume hospitals that follow national guidelines may achieve comparable outcomes.