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.

Increased homeostatic cytokines and stability of HIV-infected memory CD4 T-cells identify individuals with suboptimal CD4 T-cell recovery on-ART.

Clinical outcomes are inferior for individuals with HIV having suboptimal CD4 T-cell recovery during antiretroviral therapy (ART). We investigated if the levels of infection and the response to homeostatic cytokines of CD4 T-cell subsets contributed to divergent CD4 T-cell recovery and HIV reservoir during ART by studying virologically-suppressed immunologic responders (IR, achieving a CD4 cell count >500 cells/µL on or before two years after ART initiation), and virologically-suppressed suboptimal responders (ISR, did not achieve a CD4 cell count >500 cells/µL in the first two years after ART initiation). Compared to IR, ISR demonstrated higher levels of HIV-DNA in naïve, central (CM), transitional (TM), and effector (EM) memory CD4 T-cells in blood, both pre- and on-ART, and specifically in CM CD4 T-cells in LN on-ART. Furthermore, ISR had higher pre-ART plasma levels of IL-7 and IL-15, cytokines regulating T-cell homeostasis. Notably, pre-ART PD-1 and TIGIT expression levels were higher in blood CM and TM CD4 T-cells for ISR; this was associated with a significantly lower fold-changes in HIV-DNA levels between pre- and on-ART time points exclusively on CM and TM T-cell subsets, but not naïve or EM T-cells. Finally, the frequency of CM CD4 T-cells expressing PD-1 or TIGIT pre-ART as well as plasma levels of IL-7 and IL-15 predicted HIV-DNA content on-ART. Our results establish the association between infection, T-cell homeostasis, and expression of PD-1 and TIGIT in long-lived CD4 T-cell subsets prior to ART with CD4 T-cell recovery and HIV persistence on-ART.

Oncologic Outcomes of Multi-Institutional Minimally Invasive Inguinal Lymph Node Dissection for Melanoma Compared with Open Inguinal Dissection in the Second Multicenter Selective Lymphadenectomy Trial (MSLT-II).

BACKGROUND: Minimally invasive inguinal lymphadenectomy (MILND) is safe and feasible, but limited data exist regarding oncologic outcomes. METHODS: This study performed a multi-institutional retrospective cohort analysis of consecutive MILND performed for melanoma between January 2009 and June 2016. The open ILND (OILND) comparative cohort comprised patients enrolled in the second Multicenter Selective Lymphadenectomy Trial (MSLT-II) between December 2004 and March 2014.The pre-defined primary end point was the same-basin regional nodal recurrence, calculated using properties of binomial distribution. Time to events was calculated using the Kaplan-Meier method. The secondary end points were overall survival, progression-free survival, melanoma-specific survival (MSS), and distant metastasis-free survival (DMFS). RESULTS: For all the patients undergoing MILND, the same-basin regional recurrence rate was 4.4 % (10/228; 95 % confidence interval [CI], 2.1-7.9 %): 8.2 % (4/49) for clinical nodal disease and 3.4 % (6/179) for patients with a positive sentinel lymph node (SLN) as the indication. For the 288 patients enrolled in MSLT-II who underwent OILND for a positive SLN, 17 (5.9 %) had regional node recurrence as their first event. After controlling for ulceration, positive LN count and positive non-SLNs at the time of lymphadenectomy, no difference in OS, PFS, MSS or DMFS was observed for patients with a positive SLN who underwent MILND versus OILND. CONCLUSION: This large multi-institutional experience supports the oncologic safety of MILND for melanoma. The outcomes in this large multi-institutional experience of MILND compared favorably with those for an OILND population during similar periods, supporting the oncologic safety of MILND for melanoma.

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.

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.

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.

Minimally invasive inguinal lymphadenectomy.

The focus of this article is not purely on the technical aspects of a novel procedure, but also the considerations a team might pursue in adopting, modifying, or developing a new procedure of any type. Performing a minimally invasive inguinal lymphadenectomy is challenging even to individuals experience in laparoscopic techniques and with open lymphadenectomy. This article summarizes the approach to adopting any new technique and specifically addresses the learning curve for minimally invasive lymphadenectomy. In addition, specific technical aspects of the procedure are enumerated.

Development of a surgical oncology training curriculum for accreditation.

In 2011, the American Board of Surgery announced a new specialty board certification for Complex General Surgical Oncology. The development of a 2-year fellowship training curriculum was based on the core values of multidisciplinary care, surgical management of oncologic disease, education in basic research and clinical trial design, community outreach, patient counseling, and leadership in oncology. This article highlights the elements necessary for developing a fellowship training program in the context of these core values.

The Prognostic Value of Lymphovascular Invasion in Truncal and Extremity Soft Tissue Sarcomas: An Analysis from the National Cancer Database.

OBJECTIVE: The aim of this study was to determine the association between lymphovascular invasion (LVI) and overall survival (OS) in truncal/extremity soft tissue sarcomas (STS). METHODS: The National Cancer Database (NCDB) was queried for all patients, ages 18-85 years, who underwent resection of primary, truncal/extremity STS between 2010 and 2012, and had LVI data. The primary endpoint was OS. RESULTS: Among 6169 patients identified, the most common histology groups were (1) liposarcoma (LPS, 24%), (2) undifferentiated pleiomorphic sarcoma (UPS, 19%), and (3) leiomyosarcoma (LMS, 15%); 449 patients (7%) were LVI-positive. There were no differences in demographics or comorbidities between the LVI groups. Compared with LVI-negative patients, LVI-positive patients were more likely to have larger (> 5 cm: 80% vs. 66%), deep (80% vs. 68%), and high-grade tumors (82% vs. 57%). They were also more likely to have positive margins (27% vs. 17%), nodal (16% vs. 2%) and metastatic disease (21% vs. 4%), and receive chemotherapy (37% vs. 18%; all p < 0.001). LVI was associated with worse median OS (39 months vs. MNR; p < 0.001), which persisted on stratum-specific analyses for all tumor grades, size categories, and stages I-III, but not stage IV. On multivariable Cox regression, LVI was associated with worse OS (hazard ratio [HR] 1.84, 95% confidence interval [CI] 1.39-2.44), while accounting for other significant prognostic factors. Among non-metastatic, curative-intent resections (n = 5696), LVI was still associated with worse OS (HR 1.79, 95% CI 1.28-2.49). CONCLUSIONS: LVI appears to be an important adverse pathologic factor in truncal and extremity STS. Even when taking into account other established prognostic factors, LVI was predictive of worse OS. Knowledge of LVI status may help to better risk-stratify patients and guide management strategies, and should be considered in future prognostic classification schemes and nomograms.

Survey of Surgical Oncology Fellowship Graduates 2005-2016: Insight into Initial Practice.

BACKGROUND: Despite burgeoning interest in Complex General Surgical Oncology (CGSO) fellowship training, little is reported about postgraduate employment. The goal of this study was to characterize CGSO graduates' first employment and to identify factors that influenced this decision. METHODS: The National Cancer Institute (NCI) and Society of Surgical Oncology developed and distributed an electronic survey to CGSO fellows who graduated from 2005 to 2016. RESULTS: The survey response rate was 47% (237/509). Fifty-seven percent of respondents were first employed as faculty surgeons at a university-based/affiliated hospital, with 15% returning to their residency institution. The distribution of respondents' current employment across the United States mirrored the locations of their hometowns. Eighty-five percent of respondents care for patients across at least three disease types, most commonly hepatopancreatobiliary (81%), esophagus/gastric (75%), and sarcoma (74%). Twenty-seven percent of respondents spend the majority of their time in one area of surgical oncology; melanoma, breast, and head/neck were the most common. Two-thirds of respondents (67%) reported that they performed either clinical or basic science research as part of their current position. Multiple factors influenced the decision of first faculty position. CONCLUSIONS: Most CGSO graduates are employed at academic medical centers across the country in proximity to NCI-designated centers, treat a variety of disease types, and spend a percentage of their time dedicated to clinical research.

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.

Management of intussusception in patients with melanoma.

BACKGROUND: Increased cross-sectional imaging for surveillance of metastatic melanoma has led to more diagnoses of asymptomatic intussusception. METHODS: We performed a multi-institutional retrospective review of patient records with a history of metastatic melanoma and a diagnosis of intussusception. Patients were divided into three groups: 1) asymptomatic patients without current evidence of melanoma (no evidence of disease [NED]); 2) asymptomatic intussusception and known active metastatic melanoma; 3) symptomatic intussusception and known active metastatic melanoma; the number of patients requiring surgery and intraoperative findings were recorded. RESULTS: We reviewed 73 patients diagnosed with intussusception from 2004 to 2017. Among asymptomatic patients with NED (n = 16), 14 spontaneously resolved and 2 underwent pre-emptive surgery without abnormal intraoperative findings. Of asymptomatic patients with active metastatic disease (n = 32), 25 were initially observed and 7 underwent pre-emptive surgery and 9 of the 25 initially observed patients required surgery for development of symptoms. In this group, all 16 patients undergoing surgery (50% of the group) had intraoperative findings of intussusception and/or metastatic intestinal melanoma.. All symptomatic patients with metastatic melanoma (n = 25) underwent surgery; all had intraoperative findings of intussusception and/or metastatic melanoma except 1 (Meckel's diverticulum). CONCLUSION: Asymptomatic patients with NED do not require surgery and intussusception will likely resolve spontaneously. Asymptomatic patients with known metastatic melanoma may be initially observed, but a low threshold for surgery should be maintained. Symptomatic patients with known metastases should undergo surgery.

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.

Sentinel Lymph Node Biopsy and Management of Regional Lymph Nodes in Melanoma: American Society of Clinical Oncology and Society of Surgical Oncology Clinical Practice Guideline Update.

PURPOSE: To update the American Society of Clinical Oncology (ASCO)-Society of Surgical Oncology (SSO) guideline for sentinel lymph node (SLN) biopsy in melanoma. METHODS: An ASCO-SSO panel was formed, and a systematic review of the literature was conducted regarding SLN biopsy and completion lymph node dissection (CLND) after a positive sentinel node in patients with melanoma. RESULTS: Nine new observational studies, two systematic reviews and an updated randomized controlled trial (RCT) of SLN biopsy, as well as two randomized controlled trials of CLND after positive SLN biopsy, were included. RECOMMENDATIONS: Routine SLN biopsy is not recommended for patients with thin melanomas that are T1a (non-ulcerated lesions < 0.8 mm in Breslow thickness). SLN biopsy may be considered for thin melanomas that are T1b (0.8 to 1.0 mm Breslow thickness or <0.8 mm Breslow thickness with ulceration) after a thorough discussion with the patient of the potential benefits and risk of harms associated with the procedure. SLN biopsy is recommended for patients with intermediate-thickness melanomas (T2 or T3; Breslow thickness of >1.0 to 4.0 mm). SLN biopsy may be recommended for patients with thick melanomas (T4; > 4.0 mm in Breslow thickness), after a discussion of the potential benefits and risks of harm. In the case of a positive SLN biopsy, CLND or careful observation are options for patients with low-risk micrometastatic disease, with due consideration of clinicopathological factors. For higher risk patients, careful observation may be considered only after a thorough discussion with patients about the potential risks and benefits of foregoing CLND. Important qualifying statements outlining relevant clinicopathological factors, and details of the reference patient populations are included within the guideline.

Performance of a prognostic 31-gene expression profile in an independent cohort of 523 cutaneous melanoma patients.

BACKGROUND: The heterogeneous behavior of patients with melanoma makes prognostication challenging. To address this, a gene expression profile (GEP) test to predict metastatic risk was previously developed. This study evaluates the GEP's prognostic accuracy in an independent cohort of cutaneous melanoma patients. METHODS: This multi-center study analyzed primary melanoma tumors from 523 patients, using the GEP to classify patients as Class 1 (low risk) and Class 2 (high risk). Molecular classification was correlated to clinical outcome and assessed along with AJCC v7 staging criteria. Primary endpoints were recurrence-free (RFS) and distant metastasis-free (DMFS) survival. RESULTS: The 5-year RFS rates for Class 1 and Class 2 were 88% and 52%, respectively, and DMFS rates were 93% versus 60%, respectively (P < 0.001). The GEP was a significant predictor of RFS and DMFS in univariate analysis (hazard ratio [HR] = 5.4 and 6.6, respectively, P < 0.001 for each), along with Breslow thickness, ulceration, mitotic rate, and sentinel lymph node (SLN) status (P < 0.001 for each). GEP, tumor thickness and SLN status were significant predictors of RFS and DMFS in a multivariate model that also included ulceration and mitotic rate (RFS HR = 2.1, 1.2, and 2.5, respectively, P < 0.001 for each; and DMFS HR = 2.7, 1.3 and 3.0, respectively, P < 0.01 for each). CONCLUSIONS: The GEP test is an objective predictor of metastatic risk and provides additional independent prognostic information to traditional staging to help estimate an individual's risk for recurrence. The assay identified 70% of stage I and II patients who ultimately developed distant metastasis. Its role in consideration of patients for adjuvant therapy should be examined prospectively.

The Oncologic Impact of Postoperative Complications Following Resection of Truncal and Extremity Soft Tissue Sarcomas.

INTRODUCTION: Postoperative complications (POCs) negatively impact oncologic outcomes in some malignancies; however, little is known regarding their effect in soft tissue sarcoma (STS). The aim of this study was to determine the impact of POCs on survival after resection of truncal and extremity STS. METHODS: All patients who underwent resection for a primary truncal or extremity STS at a single academic institution from 2000 to 2015 were included and analyzed. Primary outcome was disease-specific survival (DSS). RESULTS: Among 546 STS patients, POCs occurred in 159 (29%) patients; 57% were major and 55% were surgical site infections. Patients with POCs were older (61 vs. 53 years), had more comorbidities (50 vs. 38%), longer operative time (127 vs. 93 min), higher-grade tumors (93 vs. 86%), and were more likely to receive preoperative radiation (42 vs. 33%; all p < 0.05). There was no difference in receipt of postoperative therapy between the POCs and no POCs groups (19 vs. 18%, p = 0.74). Median follow-up for survivors was 37 months, and the 5-year DSS for the entire cohort was 78%. Compared with patients without POCs, patients with POCs had a worse DSS (68% vs. 81%, p = 0.001). Predictors for decreased DSS on univariate analysis included POCs (hazard ratio [HR] 2.12, 95% confidence interval [CI] 1.37-3.28, p = 0.001), advanced age, neurovascular/bone resection, positive margin, high grade, and preoperative and postoperative therapy (all p < 0.05). POCs (HR 1.76, 95% CI 1.08-2.87, p = 0.02) remained an independent predictor for reduced DSS on multivariate analysis, along with age (HR 1.02, p = 0.046) and tumor grade (HR 7.62, p = 0.046). CONCLUSIONS: POCs following resection of truncal and extremity STS are associated with decreased DSS. Efforts to optimize modifiable risk factors and decrease the rate of POCs warrant further investigation.