Neoadjuvant-Adjuvant or Adjuvant-Only Pembrolizumab in Advanced Melanoma.

BACKGROUND: Whether pembrolizumab given both before surgery (neoadjuvant therapy) and after surgery (adjuvant therapy), as compared with pembrolizumab given as adjuvant therapy alone, would increase event-free survival among patients with resectable stage III or IV melanoma is unknown. METHODS: In a phase 2 trial, we randomly assigned patients with clinically detectable, measurable stage IIIB to IVC melanoma that was amenable to surgical resection to three doses of neoadjuvant pembrolizumab, surgery, and 15 doses of adjuvant pembrolizumab (neoadjuvant-adjuvant group) or to surgery followed by pembrolizumab (200 mg intravenously every 3 weeks for a total of 18 doses) for approximately 1 year or until disease recurred or unacceptable toxic effects developed (adjuvant-only group). The primary end point was event-free survival in the intention-to-treat population. Events were defined as disease progression or toxic effects that precluded surgery; the inability to resect all gross disease; disease progression, surgical complications, or toxic effects of treatment that precluded the initiation of adjuvant therapy within 84 days after surgery; recurrence of melanoma after surgery; or death from any cause. Safety was also evaluated. RESULTS: At a median follow-up of 14.7 months, the neoadjuvant-adjuvant group (154 patients) had significantly longer event-free survival than the adjuvant-only group (159 patients) (P = 0.004 by the log-rank test). In a landmark analysis, event-free survival at 2 years was 72% (95% confidence interval [CI], 64 to 80) in the neoadjuvant-adjuvant group and 49% (95% CI, 41 to 59) in the adjuvant-only group. The percentage of patients with treatment-related adverse events of grades 3 or higher during therapy was 12% in the neoadjuvant-adjuvant group and 14% in the adjuvant-only group. CONCLUSIONS: Among patients with resectable stage III or IV melanoma, event-free survival was significantly longer among those who received pembrolizumab both before and after surgery than among those who received adjuvant pembrolizumab alone. No new toxic effects were identified. (Funded by the National Cancer Institute and Merck Sharp and Dohme; S1801 ClinicalTrials.gov number, NCT03698019.).

HIV-1 DNA and Immune Activation Levels Differ for Long-Lived T-Cells in Lymph Nodes, Compared with Peripheral Blood, during Antiretroviral Therapy.

Elucidating the mechanisms underlying the persistence and location of the HIV reservoir is critical for developing cure interventions. While it has been shown that levels of T-cell activation and the size of the HIV reservoir are greater in rectal tissue and lymph nodes (LN) than in blood, the relative contributions of T-cell subsets to this anatomic difference are unknown. We measured and compared HIV-1 DNA content, expression of the T-cell activation markers CD38 and HLA-DR, and expression of the exhaustion markers programmed cell death protein 1 (PD-1) and T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) in naive, central memory (CM), transitional memory (TM), and effector memory (EM) CD4+ and CD8+ T-cells in paired blood and LN samples among 14 people with HIV who were receiving antiretroviral therapy. HIV-1 DNA levels, T-cell immune activation, and TIGIT expression were higher in LN than in blood, especially in CM and TM CD4+ T-cell subsets. Immune activation was significantly higher in all CD8+ T-cell subsets, and memory CD8+ T-cell subsets from LN had higher levels of PD-1 expression, compared with blood, while TIGIT expression levels were significantly lower in TM CD8+ T-cells. The differences seen in CM and TM CD4+ T-cell subsets were more pronounced among participants with CD4+ T-cell counts of <500 cells/µL within 2 years after antiretroviral therapy initiation, thus highlighting increased residual dysregulation in LN as a distinguishing feature of and a potential mechanism for individuals with suboptimal CD4+ T-cell recovery during antiretroviral therapy. IMPORTANCE This study provides new insights into the contributions of different CD4+ and CD8+ T-cell subsets to the anatomic differences between LN and blood in individuals with HIV who have optimal versus suboptimal CD4+ T-cell recovery. To our knowledge, this is the first study comparing paired LN and blood CD4+ and CD8+ T-cell differentiation subsets, as well as those subsets in immunological responders versus immunological suboptimal responders.

Efficacy and Safety of the Melphalan/Hepatic Delivery System in Patients with Unresectable Metastatic Uveal Melanoma: Results from an Open-Label, Single-Arm, Multicenter Phase 3 Study.

BACKGROUND: Uveal melanoma (UM) has a poor prognosis once liver metastases occur. The melphalan/Hepatic Delivery System (melphalan/HDS) is a drug/device combination used for liver-directed treatment of metastatic UM (mUM) patients. The purpose of the FOCUS study was to assess the efficacy and safety of melphalan/HDS in patients with unresectable mUM. METHODS: Eligible patients with mUM received treatment with melphalan (3.0 mg/kg ideal body weight) once every 6 to 8 weeks for a maximum of six cycles. The primary end point was the objective response rate (ORR). The secondary end points included duration of response (DOR), overall survival (OS), and progression-free survival (PFS). RESULTS: The study enrolled 102 patients with mUM. Treatment was attempted in 95 patients, and 91 patients received treatment. In the treated population (n = 91), the ORR was 36.3 % (95 % confidence interval [CI], 26.44-47.01), including 7.7 % of patients with a complete response. Thus, the study met its primary end point because the lower bound of the 95 % CI for ORR exceeded the upper bound (8.3 %) from the benchmark meta-analysis. The median DOR was 14 months, and the median OS was 20.5 months, with an OS of 80 % at 1 year. The median PFS was 9 months, with a PFS of 65 % at 6 months. The most common serious treatment-emergent adverse events were thrombocytopenia (15.8 %) and neutropenia (10.5 %), treated mostly on an outpatient basis with observation. No treatment-related deaths were observed. CONCLUSION: Treatment with melphalan/HDS provides a clinically meaningful response rate and demonstrates a favorable benefit-risk profile in patients with unresectable mUM (study funded by Delcath; ClinicalTrials.gov identifier: NCT02678572; EudraCT no. 2015-000417-44).

Regional control after precision lymph node dissection for clinically evident melanoma metastasis.

INTRODUCTION: Completion lymph node dissection (CLND) for microscopic lymph node metastases has been replaced by observation; however, CLND is standard for clinically detectable nodal metastases (cLN). CLND has high morbidity, which may be reduced by excision of only the cLN (precision lymph node dissection [PLND]). We hypothesized that same-basin recurrence risk would be low after PLND. METHODS: Retrospective review at four tertiary care hospitals identified patients who underwent PLND. The primary outcome was 3-year cumulative incidence of isolated same-basin recurrence. RESULTS: Twenty-one patients underwent PLND for cLN without synchronous distant metastases. Reasons for forgoing CLND included patient preference (n = 11), comorbidities (n = 5), imaging indeterminate for distant metastases (n = 2), partial response to checkpoint blockade (n = 1), or not reported (n = 2). A median of 2 nodes (range: 1-6) were resected at PLND, and 68% contained melanoma. Recurrence was observed in 33% overall. Only 1 patient (5%) developed an isolated same-basin recurrence. Cumulative incidences at 3 years were 5.0%, 17.3%, and 49.7% for isolated same-basin recurrence, any same-basin recurrence, and any recurrence, respectively. Complications from PLND were reported in 1 patient (5%). CONCLUSIONS: These pilot data suggest that PLND may provide adequate regional disease control with less morbidity than CLND. These data justify prospective evaluation of PLND in select patients.

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.

Neoadjuvant Systemic Therapy (NAST) in Patients with Melanoma: Surgical Considerations by the International Neoadjuvant Melanoma Consortium (INMC).

Exciting advances in melanoma systemic therapies have presented the opportunity for surgical oncologists and their multidisciplinary colleagues to test the neoadjuvant systemic treatment approach in high-risk, resectable metastatic melanomas. Here we describe the state of the science of neoadjuvant systemic therapy (NAST) for melanoma, focusing on the surgical aspects and the key role of the surgical oncologist in this treatment paradigm. This paper summarizes the past decade of developments in melanoma treatment and the current evidence for NAST in stage III melanoma specifically. Issues of surgical relevance are discussed, including the risk of progression on NAST prior to surgery. Technical aspects, such as the definition of resectability for melanoma and the extent and scope of routine surgery are presented. Other important issues, such as the utility of radiographic response evaluation and method of pathologic response evaluation, are addressed. Surgical complications and perioperative management of NAST related adverse events are considered. The International Neoadjuvant Melanoma Consortium has the goal of harmonizing NAST trials in melanoma to facilitate rapid advances with new approaches, and facilitating the comparison of results across trials evaluating different treatment regimens. Our ultimate goals are to provide definitive proof of the safety and efficacy of NAST in melanoma, sufficient for NAST to become an acceptable standard of care, and to leverage this platform to allow more personalized, biomarker-driven, tailored approaches to subsequent treatment and surveillance.

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.

ASO Author Reflections: Cutaneous Melanoma as Model System for the Obesity Paradox in Cancer.

Appreciation of the relationship between obesity and cancer has skyrocketed since the early 2000s. Though obesity is convincingly associated with an increased risk of at least 13 different cancers, the relationship between obesity and cutaneous melanoma remains unclear. Here, we reflect on our research into the relationship between obesity and clinically localized melanoma presented in the accompanying article, "The Impact of Obesity on Surgically Treated Locoregional Melanoma" (in press). The data presented are consistent with an "obesity paradox" in which obesity is linked to thicker melanomas and later stage at presentation without affecting survival. Given the complexity of the relationship with obesity, we propose that cutaneous melanoma is an excellent model system to investigate the role of obesity in different aspects of tumor biology and care, including risk of tumor development, tumor invasion, surgical outcomes, and response to systemic therapy.

The Impact of Obesity on Surgically Treated Locoregional Melanoma.

BACKGROUND: The impact of obesity on early-stage melanoma is poorly understood. We examined the impact of overweight and obesity on clinical outcomes in locoregional melanoma. METHODS: Adults who underwent surgery at Emory University Healthcare between 2010 and 2017 for clinically stage I-II cutaneous melanoma, with known stage, height, and weight at the time of presentation, were identified. The relationship between body mass index (BMI) and clinicopathologic characteristics was assessed. RESULTS: Of 1756 patients, 584 were obese (33.2%; BMI ≥ 30), 658 were overweight (37.5%; BMI ≥ 25 and < 30), and 514 were normal weight (29.3%; BMI < 25). Demographics associated with obesity included male sex (odds ratio [OR] 2.6, 95% confidence interval [CI] 2.1-3.3; p < 0.001) and lower income (OR 1.5, 95% CI 1.2-1.9; p = 0.003). Melanomas in obese patients were thicker (2.0 ± 0.2 mm) than in overweight (1.7 ± 0.1 mm) or normal-weight patients (1.4 ± 0.1 mm; p = 0.002). Ulceration, mitoses, BRAF status, and sentinel lymph node (SLN) status were not affected by obesity. In multivariable analysis, obesity independently predicted increased odds of pathologic stage II melanoma (vs. stage 0 or I; OR 1.9, 95% CI 1.4-2.7, p = 0.001), but not pathologic stage III melanoma (p > 0.05). At 33 months' median follow-up, obesity was not an independent predictor of stage-specific overall survival (p > 0.05). CONCLUSION: Obese patients are nearly twice as likely as their normal-weight peers to present with thicker melanomas, but they have similar stage-specific overall survival and SLN positivity. Obesity may promote more aggressive growth of the primary tumor, and barriers to preventive care in obese patients may exacerbate later-stage presentation.

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.

The evolving landscape of immunotherapy in solid tumors.

While surgical resection, local and cytotoxic therapies have long formed the basis of cancer care, immunotherapy now plays a key role in supplementing and even replacing these agents in the first line. Here we review the early success of programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocyte associated protein 4 blockade and discuss biomarkers of therapeutic response. We next highlight a select group of novel targets in Phase III trials both as monotherapies and in combination with PD-1 inhibitors. Finally, we discuss innovations which seek to improve outcomes in therapy-resistant solid tumors.

Oncologic Outcomes After Isolated Limb Infusion for Advanced Melanoma: An International Comparison of the Procedure and Outcomes Between the United States and Australia.

BACKGROUND: Isolated limb infusion (ILI) is a minimally invasive procedure for delivering high-dose chemotherapy to extremities affected by locally advanced or in-transit melanoma. This study compared the outcomes of melanoma patients treated with ILI in the United States of America (USA) and Australia (AUS). METHODS: Patients with locally recurrent in-transit melanoma treated with ILI at USA or AUS centers between 1992 and 2018 were identified. Demographic and clinicopathologic characteristics were collected. Primary outcomes of treatment response, in-field progression-free survival (IPFS), distant progression-free survival (DPFS), and overall survival (OS) were evaluated by the Kaplan-Meier method. Multivariable analysis evaluated whether availability of new systemic therapies affected outcomes. RESULTS: More ILIs were performed in AUS (n = 411, 60 %) than in the USA (n = 276, 40 %). In AUS, more ILIs were performed for stage 3B disease than in the USA (62 % vs 46 %; p < 0.001). The reported complete response rates were similar (AUS 30 % vs USA 29 %). Among the stage 3B patients, AUS patients had better IPFS (p = 0.001), whereas DPFS and OS were similar between the two countries. Among the stage 3C patients, the USA patients had better OS (p < 0.001), whereas IPFS and DPFS were similar. Availability of new systemic therapies did not affect IPFS or DPFS in either country. However, the USA patients who received ILI after ipilimumab approval in 2011 had significantly improved OS (hazard ratio, 0.62; p = 0.013). CONCLUSIONS: AUS patients were treated at an earlier disease stage than the USA patients with better IPFS for stage 3B disease. The USA patients treated after the availability of new systemic therapies had a better OS.

International Multicenter Experience of Isolated Limb Infusion for In-Transit Melanoma Metastases in Octogenarian and Nonagenarian Patients.

BACKGROUND: Isolated limb infusion (ILI) is used to treat in-transit melanoma metastases confined to an extremity. However, little is known about its safety and efficacy in octogenarians and nonagenarians (ON). PATIENTS AND METHODS: ON patients (≥ 80 years) who underwent a first ILI for American Joint Committee on Cancer seventh edition stage IIIB/IIIC melanoma between 1992 and 2018 at nine international centers were included and compared with younger patients (< 80 years). A cytotoxic drug combination of melphalan and actinomycin-D was used. RESULTS: Of the 687 patients undergoing a first ILI, 160 were ON patients (median age 84 years; range 80-100 years). Compared with the younger cohort (n = 527; median age 67 years; range 29-79 years), ON patients were more frequently female (70.0% vs. 56.9%; p = 0.003), had more stage IIIB disease (63.8 vs. 53.3%; p = 0.02), and underwent more upper limb ILIs (16.9% vs. 9.5%; p = 0.009). ON patients experienced similar Wieberdink limb toxicity grades III/IV (25.0% vs. 29.2%; p = 0.45). No toxicity-related limb amputations were performed. Overall response for ON patients was 67.3%, versus 64.6% for younger patients (p = 0.53). Median in-field progression-free survival was 9 months for both groups (p = 0.88). Median distant progression-free survival was 36 versus 23 months (p = 0.16), overall survival was 29 versus 40 months (p < 0.0001), and melanoma-specific survival was 46 versus 78 months (p = 0.0007) for ON patients compared with younger patients, respectively. CONCLUSIONS: ILI in ON patients is safe and effective with similar response and regional control rates compared with younger patients. However, overall and melanoma-specific survival are shorter.

Long-Term Oncologic Outcomes After Isolated Limb Infusion for Locoregionally Metastatic Melanoma: An International Multicenter Analysis.

BACKGROUND: Isolated limb infusion (ILI) is a minimally invasive procedure for delivering high-dose regional chemotherapy to patients with locally advanced or in-transit melanoma located on a limb. The current international multicenter study evaluated the perioperative and long-term oncologic outcomes for patients who underwent ILI for stage 3B or 3C melanoma. METHODS: Patients undergoing a first-time ILI for stage 3B or 3C melanoma (American Joint Committee on Cancer [AJCC] 7th ed) between 1992 and 2018 at five Australian and four United States of America (USA) tertiary referral centers were identified. The primary outcome measures included treatment response, in-field (IPFS) and distant progression-free survival (DPFS), and overall survival (OS). RESULTS: A total of 687 first-time ILIs were performed (stage 3B: n = 383, 56%; stage 3C; n = 304, 44%). Significant limb toxicity (Wieberdink grade 4) developed in 27 patients (3.9%). No amputations (grade 5) were performed. The overall response rate was 64.1% (complete response [CR], 28.9%; partial response [PR], 35.2%). Stable disease (SD) occurred in 14.5% and progressive disease (PD) in 19.8% of the patients. The median follow-up period was 47 months, with a median OS of 38.2 months. When stratified by response, the patients with a CR or PR had a significantly longer median IPFS (21.9 vs 3.0 months; p < 0.0001), DPFS (53.6 vs 12.7 months; p < 0.0001), and OS (46.5 vs 24.4 months; p < 0.0001) than the nonresponders (SD + PD). CONCLUSION: This study is the largest to date reporting long-term outcomes of ILI for locoregionally metastatic melanoma. The findings demonstrate that ILI is effective and safe for patients with stage 3B or 3C melanoma confined to a limb. A favorable response to ILI is associated with significantly longer IFPS, DPFS, and OS.

Morbidity and Outcomes Following Axillary Lymphadenectomy for Melanoma: Weighing the Risk of Surgery in the Era of MSLT-II.

BACKGROUND: Limited data exist characterizing complications after axillary lymphadenectomy for melanoma. With high rates of complications reported after dissection for breast cancer and data suggesting that completion lymphadenectomy may have limited therapeutic benefit, this study characterized morbidity to facilitate clinical decision-making. METHODS: Using a broad definition for complications, patients who underwent axillary dissection for melanoma at a single center (from 2003 to 2015) were assessed through retrospective chart review. Patients were stratified by potential risk factors for complications; outcomes were compared. RESULTS: Two hundred fifty-four axillary dissections in 239 patients were identified. Assessed risk factors for complications included age > 55 years (n = 133, 52%), body mass index (BMI) ≥ 30 kg/m2 (n = 90, 40%), diabetes (n = 40, 16%), smoking (n = 81, 32%), extremity primary (n = 71, 28%), therapeutic lymphadenectomy (n = 105, 41%), and adjuvant radiation (n = 33, 13%). Wound complications were observed in 51 patients with 38 (15%) seromas, 3 (1%) dehiscences, and 10 (4%) hematomas. There were 5 (2%) reoperations, all for hematoma. Thirty-day readmission rate was 6% (n = 14). Importantly, lymphedema occurred in only 13 (5%) patients. Wound dehiscence occurred only in smokers (p = 0.03) and was associated with adjuvant radiation (p = 0.04). Twenty-eight (11%) patients developed frozen shoulder, which was related to smoking (p = 0.02). Lymphedema was more likely in patients after therapeutic dissection (p = 0.04). All other risk factors were not associated with increased complications. CONCLUSIONS: This analysis supports historical data that axillary dissection for melanoma is a low-risk procedure, with smoking, therapeutic lymphadenectomy, and adjuvant radiation associated with increased morbidity. Although morbidity of lymphadenectomy is often cited as a reason to alter surgical approach or even forgo intervention, this may be less of a concern for axillary dissection.