Timing of Adjuvant Immunotherapy in Stage III Melanoma, Does it Matter?

BACKGROUND: The optimal time to initiate adjuvant immune checkpoint inhibitors (ICI) following resection remains undefined. Herein, we investigated the impact of time to adjuvant ICI on survival in patients with stage III melanoma. METHODS: Patients with resected stage III melanoma receiving adjuvant immune therapy were identified within a multi-institutional retrospective cohort. Patients were stratified by time to adjuvant ICI: within 6 weeks, 6-12 weeks, and greater than 12 weeks from surgery. Recurrence-free survival (RFS) was compared among time strata with Kaplan-Meier and Cox proportional hazards methods in the multi-institutional cohort. RESULTS: Altogether, 626 patients were identified within the multi-institutional cohort: 39% of patients initiated adjuvant ICI within 6 weeks, 42.2% within 6-12 weeks, and 18.8% greater than 12 weeks from surgery. In a multivariate Cox model, adjusting for histology, nodal tumor burden, and pathologic stage, we found that increased time to adjuvant ICI was associated with improved RFS. Patients who initiated adjuvant ICI within 6 weeks of surgery had worse RFS. These findings were preserved in a conditional landmark analysis and separate subgroups of patients with (1) new melanoma diagnoses, (2) occult stage III disease, and (3) those receiving anti-PD-1 monotherapy. CONCLUSIONS: Outcomes for patients with stage III melanoma are not compromised when adjuvant ICI is initiated beyond 6 weeks from resection. Additional work is needed to better understand the underlying mechanisms and implications of timing of adjuvant ICI on long-term outcomes.

Sentinel lymph node biopsy status improves adjuvant therapy decision-making in patients with clinical stage IIB/C melanoma: A population-based analysis.

BACKGROUND: Given the results of the recent KEYNOTE-716 trial, the performance of sentinel lymph node (SLN) biopsy for patients with clinical stage IIB/C melanoma has been questioned. OBJECTIVE: Determine the utility of SLN status in guiding the recommendations for adjuvant therapy. METHODS: Patients with clinical stage IIB/C cutaneous melanoma who underwent wide local excision and SLN biopsy between 2004 and 2011 were identified from the Surveillance, Epidemiology, and End Results database. Two prognostic models, with and without SLN status, were developed predicting risk of melanoma-specific death (MSD). The primary outcome was net benefit at treatment thresholds of 20% to 40% risk of 5-year MSD. RESULTS: For the 4391 patients included, the 5-year MSD rate was 46%. The model estimating 5-year MSD risk that included SLN status provided greater net benefit at treatment thresholds from 30% to 78% compared to the model without SLN status. The added net benefit for the SLN biopsy-containing model persisted in subgroup analysis of patients in different age groups and with various T stages. LIMITATIONS: Retrospective study. CONCLUSIONS: A prognostic model with SLN status estimating patient risk for 5-year MSD provides superior net benefit compared to a model with primary tumor staging factors alone for threshold mortality rates ≥30%.

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+.

National Practice Patterns in the Management of the Regional Lymph Node Basin After Positive Sentinel Lymph Node Biopsy for Cutaneous Melanoma.

BACKGROUND: Immediate completion lymph node dissection (CLND) for patients with sentinel lymph node (SLN) metastasis from cutaneous melanoma has been replaced largely by ultrasound nodal surveillance since the publication of two landmark trials in 2016 and 2017. National practice patterns of CLND remain poorly characterized. METHODS: Patients with a diagnosis of cutaneous melanoma in 2016 and 2018 without clinical nodal disease who underwent sentinel lymph node biopsy (SLNB) were identified from the National Cancer Database (NCDB). Characteristics associated with CLND were analyzed by uni- and multivariate logistic regression. Overall survival (OS) was estimated using Kaplan-Meier and Cox proportional hazards regression analyses. RESULTS: Of the 3517 patients included in the study, 1405 had disease diagnosed in 2016. The patients with cutaneous melanoma diagnosed in 2016 had a median age of 60 years and a tumor thickness of 2.3 mm compared to 62 years and 2.4 mm, respectively, for the patients with cutaneous melanoma diagnosed in 2018. According to the NCDB, 40 % (n = 559) of the patients underwent CLND in 2016 compared with 6 % (n = 132) in 2018. The factors associated with receipt of CLND in 2018 included younger age (odds ratio [OR], 0.97; 95 % confidence interval [CI], 0.95-0.99; p = 0.001), rural residence (OR, 3.96; 95 % CI, 1.50-10.49; p = 0.006), head/neck tumor location (OR, 1.88; 95 % CI, 1.10-3.23; p = 0.021), and more than one positive SLN (OR, 1.80; 95 % CI, 1.17-2.76; p = 0.007). The 5-year OS did not differ between the patients who received SLNB only and those who underwent CLND (hazard ratio [HR], 0.93; p = 0.54). CONCLUSION: The rates of CLND have decreased nationally. However, patients with head/neck primary tumors who live in rural locations are more likely to undergo CLND, highlighting populations for which treatment may be non-uniform with national practice patterns.

Pathologic Factors Associated with Low Risk of Lymph Node Metastasis in Nonmucinous Adenocarcinoma of the Appendix.

BACKGROUND: Right hemicolectomy (RHC) for nodal staging is recommended for nonmucinous adenocarcinoma of the appendix (NMACA), but it is unclear whether a subgroup of patients at low risk for lymph node (LN) metastasis exists who may be managed with a less extensive resection. PATIENTS AND METHODS: Patients with NMACA without distant metastases who underwent margin negative resection via either RHC or appendectomy/partial colectomy (A/PC) were evaluated from the National Cancer Database (2004-2016). Patients at low risk for LN metastasis were identified. Multivariable survival analysis was performed, and 5-year overall survival (OS) was estimated. RESULTS: Of the 2487 patients included, 652 [26.2%; 95% confidence interval (CI) 24.5-28.0%] had LN metastases. T4 T stage [odds ratio (OR) 4.2, p = 0.032], poorly/undifferentiated histology (OR 2.2, p = 0.004), and lymphovascular invasion (LVI) (OR 4.4, p < 0.001) were associated with LN positivity. One hundred and thirteen patients (4.5%) had tumors at low risk for LN metastasis (T1 T stage, well/moderately differentiated tumors without LVI), and the rate of LN metastasis for this group was 1.8% (95% CI 0.5-6.2%). Conversely, the LN metastasis rate among the 2374 non-low-risk patients was 27.4% (95% CI 25.6-29.2%). Performance of A/PC instead of RHC was associated with a survival disadvantage among all patients (hazards ratio 1.5, p = 0.049), but among the low-risk cohort, 5-year OS did not differ based on resection type (88.3% A/PC versus 92.7% RHC, p = 0.305). CONCLUSIONS: Although relatively uncommon, early, pathologically favorable NMACA is associated with a very low risk of LN metastasis. These select patients may be managed with a less extensive resection without compromising oncologic outcomes.

Lymph Node Evaluation after Neoadjuvant Chemotherapy for Patients with Gastric Cancer.

BACKGROUND: Adequate lymphadenectomy with at least 16 nodes retrieved at the time of gastrectomy is a quality measure recommended to ensure adequate staging. The minimum nodal retrieval recommended after receipt of neoadjuvant chemotherapy (NACT) is less defined. METHODS: Patients with clinical stages 1 to 3 gastric adenocarcinoma who received NACT and surgical resection were identified from the 2004-2015 National Cancer Database. The optimal nodal harvest number was calculated with Cox spline regression modeling. Cohorts with a nodal harvest higher or lower than this number were 1:1 propensity score-matched. Overall survival (OS) was analyzed using Kaplan-Meier survival estimates. RESULTS: Among 4337 patients receiving NACT, the optimal minimal nodal harvest at gastrectomy was 23 nodes. Compared with the patients who had fewer than 23 nodes retrieved, the patients with at least 23 nodes examined (n = 1073, 24.7%) were more likely to be female (26.1% vs 22%; p = 0.006) and non-white (29.3% vs 18.5%; p < 0.0001), to have a Charlson-Deyo score of 0 (71.5% vs 66.8%; p = 0.005), and to have undergone resection at an academic facility (67.9% vs 51.5%; p < 0.0001). The patients with at least 23 nodes examined had higher proportions of high-grade tumor (62% vs 57.4%; p = 0.030), pT3 or pT4 tumor (56.3% vs 48.7%; p < 0.0001), body tumor (21.3% vs 12.5%; p < 0.0001), or antrum/pylorus tumor (15.3% vs 11.4%; p < 0.0001). The patients with at least 23 nodes were more likely to have lymph node metastases identified (61% vs 51%; p < 0.0001). After matching, the patients with at least 23 nodes (n = 990) demonstrated an improved 5-year OS (57.9% vs 49%; p = 0.001). CONCLUSIONS: The extent of lymphadenectomy during gastrectomy for gastric adenocarcinoma should not be reduced after NACT because adequate lymph node retrieval remains important for prognostication.

Prognostic Significance of Primary Tumor-Infiltrating Lymphocytes in a Contemporary Melanoma Cohort.

BACKGROUND: The prognostic impact of tumor-infiltrating lymphocytes (TILs) on outcomes and treatment efficacy for patients with melanoma in the contemporary era remains poorly characterized. METHODS: Consecutive patients who underwent wide excision and sentinel lymph node biopsy for cutaneous melanoma 1 mm thick or thicker at a single institution were identified (2006-2019). The patients were stratified based on primary tumor TIL status as brisk (bTILs), non-brisk (nbTILs), or absent (aTILs). Associations between patient factors and outcomes were analyzed using multivariable analysis. RESULTS: Of the 1017 patients evaluated, 846 (83.2 %) had primary TILs [nbTILs (n = 759, 89.7 %) and bTILs (n = 87, 10.3 %)]. In the multivariable analysis, the patients with any type of TILs had higher rates of regression [odds ratio (OR), 1.86; p = 0.016], lower rates of acral lentiginous histology (OR, 0.22; p < 0.001), and lower rates of SLN positivity (OR, 0.64; p = 0.042) than those without TILs. The multivariable analysis found no association between disease-specific survival and bTILs [hazard ratio (HR), 1.04; p = 0.927] or nbTILs (HR, 0.89; p = 0.683). An association was found between bTILs and recurrence-free survival (RFS) advantage [bTILs (HR 0.46; p = 0.047), nbTILs (HR 0.71; p = 0.088)], with 5-year RFS rates of 84 % for bTILs, 71.8 % for nbTILs, and 68.4 % for aTILs (p = 0.044). For the 114 immune checkpoint blockade (ICB)-naïve patients who experienced a recurrence treated with ICB therapy, no association was observed between progression-free survival and bTILs (HR, 0.64; p = 0.482) or nbTILs (HR, 0.58; p = 0.176). CONCLUSIONS: The prognostic significance of primary TILs in the contemporary melanoma era appears complex. Further studies characterizing the phenotype of TILs and their association with regional metastasis and responsiveness to ICB therapy are warranted.

An Internally Validated Prognostic Risk-Score Model for Disease-Specific Survival in Clinical Stage I and II Merkel Cell Carcinoma.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare cutaneous malignancy for which factors predictive of disease-specific survival (DSS) are poorly defined. METHODS: Patients from six centers (2005-2020) with clinical stage I-II MCC who underwent sentinel lymph node (SLN) biopsy were included. Factors associated with DSS were identified using competing-risks regression analysis. Risk-score modeling was established using competing-risks regression on a training dataset and internally validated by point assignment to variables. RESULTS: Of 604 patients, 474 (78.5%) and 128 (21.2%) patients had clinical stage I and II disease, respectively, and 189 (31.3%) had SLN metastases. The 5-year DSS rate was 81.8% with a median follow-up of 31 months. Prognostic factors associated with worse DSS included increasing age (hazard ratio [HR] 1.03, p = 0.046), male sex (HR 3.21, p = 0.021), immune compromise (HR 2.46, p = 0.013), presence of microsatellites (HR 2.65, p = 0.041), and regional nodal involvement (1 node: HR 2.48, p = 0.039; ≥2 nodes: HR 2.95, p = 0.026). An internally validated, risk-score model incorporating all of these factors was developed with good performance (AUC 0.738). Patients with ≤ 4.00 and > 4.00 points had 5-year DSS rates of 89.4% and 67.2%, respectively. Five-year DSS for pathologic stage I/II patients with > 4.00 points (n = 49) was 79.8% and for pathologic stage III patients with ≤ 4.00 points (n = 62) was 90.3%. CONCLUSIONS: A risk-score model, including patient and tumor factors, based on DSS improves prognostic assessment of patients with clinically localized MCC. This may inform surveillance strategies and patient selection for adjuvant therapy trials.

Talimogene Laherparepvec (T-VEC) for the Treatment of Advanced Locoregional Melanoma After Failure of Immunotherapy: An International Multi-Institutional Experience.

BACKGROUND: Talimogene laherparepvec (T-VEC) is an oncolytic virus approved for the treatment of unresectable, recurrent melanoma. The role of T-VEC after progression on systemic immunotherapy (IO) remains undefined. The goal of this study was to characterize the efficacy of T-VEC after failure of IO in patients with unresectable metastatic melanoma. METHODS: An international, multi-institutional review of AJCC version 8 stage IIIB-IV melanoma patients treated with T-VEC after failure of IO was performed at six centers from October 2015-December 2020. Primary outcome was in-field response; secondary outcomes included analyses of in-field and overall progression-free survival (PFS) and in-field and overall disease-free survival (DFS) after a complete response. Subset analysis of T-VEC initiation sequentially after or concurrently with IO was performed. RESULTS: Of 112 patients, median age at T-VEC initiation was 69 years (range 21-93); 65 (58%) were male. Before T-VEC, 57% patients received one IO regimen, 42% received two or more, with most patients (n = 74, 66%) receiving T-VEC sequential to IO. Most were stage 3C (n = 51, 46%) at T-VEC initiation, 29 (26%) received injections to nodal disease. Over median follow-up of 14 months, in-field response at final T-VEC injection was 37% complete (CR), 14% partial (PR). T-VEC initiation sequentially or concurrently did not significantly affect in-field response (p = 0.26). Median in-field PFS was 15 months (95% confidence interval 4.6-NE). Median overall DFS after CR was 32 months (95% confidence interval 17-NE). CONCLUSIONS: T-VEC after failure of IO is effective in unresectable, metastatic stage IIIB-IV melanoma. T-VEC initiation sequentially or concurrently did not significantly affect in-field response.

Postsplenectomy morbidity and mortality in patients with immune thrombocytopenic purpura: A national cohort study.

BACKGROUND: We sought to identify factors associated with 30-day morbidity, and their impact on 30-day mortality, among patients undergoing splenectomy for immune thrombocytopenic purpura (ITP). METHODS: Using the ACS-NSQIP database, patients undergoing splenectomy for ITP were identified (2005-2019), and those with and without postoperative complications within 30 days of surgery were compared. RESULTS: Of 2483 patients evaluated, 280 (11.3%) developed 30-day morbidity: infection (n= 145 [5.8%]), venous thromboembolism (n = 71 [2.9%]), acute renal failure (n = 7 [0.3%]), respiratory failure (n = 40 [1.6%]), cardiac arrest/myocardial infarction (n = 16 [0.6%]), cerebrovascular accident (n = 4 [0.2%]), or postoperative blood transfusion (n = 62 [2.5%]). Risk-factors for 30-day morbidity included age ≥50 years (odds ratio [OR] 1.50, p = 0.020), body mass index ≥30 kg/m2 (OR 1.45, p = 0.023), functional dependence (OR 2.90, p = 0.009), preoperative albumin <3.5 g/dL (OR 2.10, p < 0.001), preoperative platelets <30 000/µL (OR 1.54, p = 0.020), open surgical approach (OR 2.32, p < 0.001), and inpatient status before surgery (OR 1.85, p = 0.040). Among patients at low-risk for 30-day morbidity (no risk-factors present), the 30-day morbidity rate was 5.0% versus 41.5% for ≥5 risk-factors (p < 0.001). Thirty-day mortality was 1.2%. CONCLUSIONS: Thirty-day morbidity and mortality are low with splenectomy for ITP. Select patients have particularly low perioperative risk and may benefit from early splenectomy if initial medical therapy fails.

The impact of hospital volume on racial disparities in resected rectal cancer.

BACKGROUND: Although high volume centers (HVC) equate to improved outcomes in rectal cancer, the impact of surgical volume related to race is less defined. METHODS: Patients who underwent surgical resection for stage I-III rectal adenocarcinoma were divided into cohorts based on race and hospital surgical volume. Outcomes were analyzed following 1:1 propensity-score matching using logistic, Poisson, and Cox regression analyses with marginal effects. RESULTS: Fifty-four thousand one hundred and eighty-four (91.5%) non-Black and 5043 (8.5%) Black patients underwent resection of rectal cancer. Following 1:1 matching of non-Black (N = 5026) and Black patients, 5-year overall survival (OS) of Black patients was worse (72% vs. 74.4%, average marginal effects [AME] 0.66, p = 0.04) than non-Black patients. When compared to non-Black patients managed at HVCs, Black patients had worse OS (70.1% vs. 74.7%, AME 1.55, p = 0.03), but this difference was not significant when comparing OS between non-Black and Black patients managed at HVCs (72.3% vs. 74.7%, AME 0.62, p = 0.06). Length of stay was longer among Black and HVC patients across all cohorts. There was no difference across cohorts in 90-day mortality. CONCLUSIONS: Although racial disparities exist in rectal cancer, this disparity appears to be ameliorated when patients are managed at HVCs.

Impact of the affordable care act's medicaid expansion on presentation stage and perioperative outcomes of colorectal cancer.

BACKGROUND AND OBJECTIVES: Medicaid expansion has improved healthcare coverage and preventive health service use. To what extent this has resulted in earlier stage colorectal cancer diagnoses and impacted perioperative outcomes is unclear. METHODS: This was a retrospective difference-in-difference study using the National Cancer Database on adults (40-64) with Medicaid or no insurance, diagnosed with colorectal adenocarcinomas before (2010-2013) and after (2015-2018) expansion. The primary outcome was early-stage (American Joint Committee on Cancer Stage 0-1) diagnosis. The secondary outcomes were rate of local excision, emergency surgery, postoperative length of stay, rates of minimally invasive surgery, postoperative mortality, and overall survival (OS). RESULTS: Medicaid expansion was associated with an increase in early-stage diagnoses for patients with colorectal cancers (odds ratio [OR]: 1.28, 95% confidence interval [CI]: 1.15-1.43), an increase in local excision (OR: 1.39, 95% CI: 1.13-1.69), and a decreased rate of emergent surgery (OR: 0.85, 95% CI: 0.75-0.97) and 90-day mortality (OR: 0.75, 95% CI: 0.59-0.97). Additionally, patients in expansion states postexpansion had an improved 5-year OS (hazard ratio: 0.88, 95% CI: 0.83-0.94). CONCLUSIONS: Insurance coverage expansion may be particularly important for optimizing stage of diagnosis, subsequent survival, and perioperative outcomes for socioeconomically vulnerable patients.

Association of type II diabetes mellitus with characteristics and outcomes for patients undergoing sentinel lymph node biopsy for cutaneous melanoma.

BACKGROUND AND OBJECTIVES: Type II diabetes mellitus (T2DM) can lead to an immunosuppressed state, but whether T2DM is associated with worse outcomes for patients with melanoma has not been well studied. METHODS: Consecutive patients diagnosed with clinical stage I-II cutaneous melanoma who underwent sentinel lymph node biopsy at a single institution (2007-2016) were identified. Melanoma characteristics and recurrence/survival outcomes were compared between patients with and without T2DM at the time of melanoma diagnosis. RESULTS: Of 1128 patients evaluated, 111 (9.8%) had T2DM (n = 94 [84.7%] non-insulin dependent [NID-T2DM]; n = 17 [15.3%] insulin dependent [ID-T2DM]). T2DM patients were more likely to be older (odds ratio [OR] 1.04, p < 0.001), male (OR 2.15, p = 0.003), have tumors >1.0 mm (OR 1.88, p = 0.023), and have microsatellitosis (OR 2.29, p = 0.030). Five-year cumulative incidence of melanoma recurrence was significantly higher for patients with ID-T2DM (46.7% ID-T2DM vs. 25.7% NID-T2DM vs. 17.1% no T2DM, p < 0.001), and on multivariable analysis, ID-T2DM was independently associated with melanoma recurrence (hazard ratio 2.57, p = 0.015). No difference in 5-year disease-specific survival was observed between groups. CONCLUSIONS: ID-T2DM appears to be associated with more advanced melanoma and increased risk for melanoma recurrence. Further study as to whether this reflects differences in tumor biology or host factors is warranted.

Neoadjuvant radiation for cutaneous and soft tissue angiosarcoma.

BACKGROUND AND OBJECTIVES: Neoadjuvant radiation (NRT) is frequently utilized in soft tissue sarcomas to increase local control. Its utility in cutaneous and soft tissue angiosarcoma remains poorly defined. METHODS: This retrospective cohort study was performed using the National Cancer Database (2004-2016) evaluating patients with clinically localized, surgically resected angiosarcomas. Factors associated with receipt of NRT in the overall cohort and margin positivity in treatment naïve patients were identified by univariate and multivariable logistic regression analyses. Survival was assessed using Kaplan-Meier analysis. RESULTS: Of 597 patients, 27 (4.5%) received NRT. Increasing age (odds ratio [OR] 0.95, p = 0.025), tumor size more than or equal to 5 cm (OR 3.16, p = 0.02), and extremity tumor location (OR 3.99, p = 0.04) were associated with receipt of NRT. All patients who received NRT achieved an R0 resection (p = 0.03) compared with 17.9% of patients without NRT. Factors associated with risk of margin positivity included tumor size more than or equal to 5 cm (OR 1.85, p = 0.01), and head/neck location (OR 2.24, p = 0.006). NRT was not significantly associated with improved survival (p = 0.21). CONCLUSIONS: NRT improves rates of R0 resection but is infrequently utilized in cutaneous and soft tissue angiosarcoma. Increased usage of NRT, particularly for patients with lesions more than or equal to 5 cm, or head and neck location, may help achieve complete resections.

Sentinel lymph node biopsy in patients with clinical stage IIB/C cutaneous melanoma: A national cohort study.

BACKGROUND: Approval of adjuvant anti-programmed cell death protein 1 therapy for pathologic stage IIB/C cutaneous melanoma has led some to question the role of sentinel lymph node (SLN) biopsy in the clinical stage IIB/C disease. OBJECTIVE: To determine the prognostic significance of SLN staging on disease-specific survival (DSS) for clinical stage IIB/C primary cutaneous melanoma in the preimmunotherapy era. METHODS: A retrospective cohort study was performed evaluating patients who underwent excision of clinical stage IIB/C cutaneous melanoma using the Surveillance, Epidemiology, and End Results database (2004-2011). Patients who did and did not undergo SLN biopsy were compared using propensity matching, and among those who underwent SLN biopsy, matched patients were further stratified by SLN status (SLN positive [SLN+] or SLN negative [SLN-]). RESULTS: Of the 8562 patients evaluated, 6021 (70.3%) underwent SLN biopsy. SLN positivity was associated with significantly reduced 5-year DSS among matched patients who underwent SLN biopsy (47.1% SLN+ vs 75.5% SLN-; P < .001). Five-year DSS remained significantly different across matched T-stages: T3b (54.2% SLN+ vs 64.8% SLN-; P = .004), T4a (55.5% SLN+ vs 71.6% SLN-; P = .001), and T4b (38.6% SLN+ vs 60.9% SLN-; P < .001). LIMITATIONS: Retrospective study. CONCLUSION: For patients with clinical stage IIB/C cutaneous melanoma, SLN status provides essential prognostic information.

Optimizing Detection of Lymphatic Invasion in Primary Cutaneous Melanoma With the Use of D2-40 and a Paired Melanocytic Marker.

ABSTRACT: Dual immunohistochemical (IHC) staining with D2-40 and S100 improves detection of lymphatic invasion (LI) in primary cutaneous melanoma. However, limited data exist evaluating this technique using other melanocytic markers, and thus, the optimal marker for detection of LI is unestablished. To address this knowledge gap, a case-control study was performed comparing melanoma specimens from 22 patients with known lymphatic spread (LS) with a control group of 11 patients without LS. Specimens underwent dual IHC staining with D2-40 and MART-1, SOX-10, and S100 to evaluate for LI. Receiver operating characteristic analysis was used to estimate each stain's accuracy for detection of LI. The LS group was more likely to be ≥65 years (P = 0.04), have a tumor thickness of ≥1 mm (P < 0.01), and have ulcerated tumors (P = 0.02). Detection of LI with D2-40/MART-1 significantly correlated with LS (P = 0.03), and the D2-40/MART-1 stain was most accurate for LI based on receiver operating characteristic curve analysis (area under the curve [AUC] 0.705) in comparison with D2-40/SOX-10 (AUC 0.575) and D2-40/S100 (AUC 0.633). These findings suggest that MART-1 may be the optimal melanocytic marker to combine with D2-40 for detection of LI in melanoma. Further studies are needed to determine the utility of routinely performing these stains for histopathologic analysis of melanoma.

Preoperative Biopsy in Patients with Retroperitoneal Sarcoma: Usage and Outcomes in a National Cohort.

INTRODUCTION: Preoperative biopsy (PBx) is often recommended for retroperitoneal sarcoma (RPS), but its utilization rate and impact on perioperative management and outcomes remains undefined. METHODS: Using the National Cancer Database, patients who underwent resection of non-metastatic RPS were identified (2006-2014). Patients who did and did not undergo PBx of the primary tumor were compared using propensity matching, and factors associated with survival were assessed by multivariable analysis. RESULTS: Of 2620 patients, 1110 (42.4%) underwent PBx. Factors significantly associated with performance of PBx included male sex [odds ratio (OR) 1.2, P = 0.035], tumor size ≤ 5 cm (OR 1.5, P = 0.012), tumor size > 5 to ≤ 10 cm (OR 1.3, P = 0.009), non-well-differentiated liposarcoma histology (OR 2.0, P ≤ 0.001), and treatment at a high-volume center (OR 1.3, P = 0.021). Receipt of PBx was significantly associated with administration of neoadjuvant radiation (OR 8.8, P < 0.001) or systemic therapy (OR 3.3, P < 0.001), radical surgical resection (OR 1.6, P < 0.001), and complete tumor resection (OR 1.5, P < 0.003). Neoadjuvant radiation [hazard ratio (HR) 0.7, P = 0.003] and complete tumor resection (HR 0.6, P < 0.001) were significantly associated with improved overall survival (OS). Performance of PBx was not associated with OS (HR 1.1, P = 0.070), and following propensity matching, 5-year OS did not differ between the two groups (56.5% PBx vs 58.4% no PBx, P = 0.247). CONCLUSIONS: A minority of patients with non-metastatic RPS undergo PBx. PBx does not negatively impact survival, but may indirectly improve outcomes in select patients by virtue of receipt of neoadjuvant therapy and attainment of complete tumor resection.

Predictors of False Negative Sentinel Lymph Node Biopsy in Clinically Localized Merkel Cell Carcinoma.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is routinely recommended for clinically localized Merkel cell carcinoma (MCC); however, predictors of false negative (FN) SLNB are undefined. METHODS: Patients from six centers undergoing wide excision and SLNB for stage I/II MCC (2005-2020) were identified and were classified as having either a true positive (TP), true negative (TN) or FN SLNB. Predictors of FN SLNB were identified and survival outcomes were estimated. RESULTS: Of 525 patients, 28 (5.4%), 329 (62.7%), and 168 (32%) were classified as FN, TN, and TP, respectively, giving an FN rate of 14.3% and negative predictive value of 92.2% for SLNB. Median follow-up for SLNB-negative patients was 27 months, and median time to nodal recurrence for FN patients was 7 months. Male sex (hazard ratio [HR] 3.15, p = 0.034) and lymphovascular invasion (LVI) (HR 2.22, p = 0.048) significantly correlated with FN, and increasing age trended toward significance (HR 1.04, p = 0.067). The 3-year regional nodal recurrence-free survival for males >75 years with LVI was 78.5% versus 97.4% for females ≤75 years without LVI (p = 0.009). Five-year disease-specific survival (90.9% TN vs. 51.3% FN, p < 0.001) and overall survival (69.9% TN vs. 48.1% FN, p = 0.035) were significantly worse for FN patients. CONCLUSION: Failure to detect regional nodal microscopic disease by SLNB is associated with worse survival in clinically localized MCC. Males, patients >75 years, and those with LVI may be at increased risk for FN SLNB. Consideration of increased nodal surveillance following negative SLNB in these high-risk patients may aid in early identification of regional nodal recurrences.

Adjuvant Radiation Therapy for Clinical Stage III Melanoma in the Modern Therapeutic Era.

BACKGROUND: Adjuvant radiation therapy (RT) can decrease lymph node basin (LNB) recurrences in patients with clinically evident melanoma lymph node (LN) metastases following lymphadenectomy, but its role in the era of modern systemic therapies (ST), immune checkpoint or BRAF/MEK inhibitors, is unclear. PATIENTS AND METHODS: Patients at four institutions who underwent lymphadenectomy (1/1/2010-12/31/2019) for clinically evident melanoma LN metastases and received neoadjuvant and/or adjuvant ST with RT, or ST alone, but met indications for RT, were identified. Comparisons were made between ST alone and ST/RT groups. The primary outcome was 3-year cumulative incidence (CI) of LNB recurrence. Secondary outcomes included 3-year incidences of in-transit/distant recurrence and survival estimates. RESULTS: Of 98 patients, 76 received ST alone and 22 received ST/RT. Median follow-up time for patients alive at last follow-up was 44.6 months. The ST/RT group had fewer inguinal node metastases (ST 36.8% versus ST/RT 9.1%; P = 0.04), and more extranodal extension (ST 50% versus ST/RT 77.3%; P = 0.02) and positive lymphadenectomy margins (ST 2.6% versus ST/RT 13.6%; P = 0.04). The 3-year CI of LNB recurrences was lower for the ST/RT group compared with the ST group (13.9% versus 25.2%), but this reduction was not statistically significant (P = 0.36). Groups did not differ significantly in in-transit/distant recurrences (P = 0.24), disease-free survival (P = 0.14), or melanoma-specific survival (P = 0.20). CONCLUSIONS: In the era of modern ST, RT may still have value in reducing LNB recurrences in melanoma with clinical LN metastases. Further research should focus on whether select patient populations derive benefit from combination therapy, and optimizing indications for RT following neoadjuvant ST.

Association of the Affordable Care Act's Medicaid expansion with the diagnosis and treatment of clinically localized melanoma: A National Cancer Database study.

BACKGROUND: The Affordable Care Act's Medicaid expansion is associated with earlier diagnosis and improved care among lower socioeconomic status populations with cancer, but its impact on melanoma is undefined. OBJECTIVE: To determine the association of Medicaid expansion with stage of diagnosis and use of sentinel lymph node biopsy in nonelderly adult patients with newly diagnosed clinically localized melanoma. METHODS: Quasi-experimental, difference-in-differences retrospective cohort analysis using data from the National Cancer Database from 2010 to 2017. Patients from expansion versus nonexpansion states and diagnosed before (2010-2013) versus after (2014-2017) expansion were identified. RESULTS: Of 83,322 patients, 46.6% were female, and the median age was 55 years (interquartile range, 49-60). After risk adjustment, Medicaid expansion was associated with a decrease in the diagnosis of T1b stage or higher melanoma (odds ratio [OR], 0.93; 95% confidence interval [CI], 0.88-0.98; P = .011) and decrease in uninsured status (OR, 0.61; 95% CI, 0.52-0.72; P < .001) but was not associated with a difference in sentinel lymph node biopsy performance when indicated (OR, 1.06; 95% CI, 0.95-1.20; P = .29). LIMITATIONS: Retrospective study using a national database. CONCLUSION: In this study of patients with clinically localized melanoma, Medicaid expansion was associated with a decrease in the diagnosis of later T-stage tumors.