A randomized, non-comparative phase 2 study of neoadjuvant immune-checkpoint blockade in retroperitoneal dedifferentiated liposarcoma and extremity/truncal undifferentiated pleomorphic sarcoma.

Based on the demonstrated clinical activity of immune-checkpoint blockade (ICB) in advanced dedifferentiated liposarcoma (DDLPS) and undifferentiated pleomorphic sarcoma (UPS), we conducted a randomized, non-comparative phase 2 trial ( NCT03307616 ) of neoadjuvant nivolumab or nivolumab/ipilimumab in patients with resectable retroperitoneal DDLPS (n = 17) and extremity/truncal UPS (+ concurrent nivolumab/radiation therapy; n = 10). The primary end point of pathologic response (percent hyalinization) was a median of 8.8% in DDLPS and 89% in UPS. Secondary end points were the changes in immune infiltrate, radiographic response, 12- and 24-month relapse-free survival and overall survival. Lower densities of regulatory T cells before treatment were associated with a major pathologic response (hyalinization > 30%). Tumor infiltration by B cells was increased following neoadjuvant treatment and was associated with overall survival in DDLPS. B cell infiltration was associated with higher densities of regulatory T cells before treatment, which was lost upon ICB treatment. Our data demonstrate that neoadjuvant ICB is associated with complex immune changes within the tumor microenvironment in DDLPS and UPS and that neoadjuvant ICB with concurrent radiotherapy has significant efficacy in UPS.

High Community-Level Social Vulnerability is Associated with Worse Recurrence-Free Survival (RFS) After Resection of Extremity and Truncal Soft Tissue Sarcoma.

BACKGROUND: Although social vulnerability has been associated with worse postoperative and oncologic outcomes in other cancer types, these effects have not been characterized in patients with soft tissue sarcoma. This study evaluated the association of social vulnerability and oncologic outcomes. METHODS: The authors conducted a single-institution cohort study of adult patients with primary and locally recurrent extremity or truncal soft tissue sarcoma undergoing resection between January 2016 and December 2021. The social vulnerability index (SVI) was measured on a low (SVI 1-39%, least vulnerable) to high (60-100%, most vulnerable) SVI scale. The association of SVI with overall survival (OS) and recurrence-free survival (RFS) was evaluated by Kaplan-Meier analysis and Cox proportional hazard regression. RESULTS: The study identified 577 patients. The median SVI was 44 (interquartile range [IQR], 19-67), with 195 patients categorized as high SVI and 265 patients as low SVI. The median age, tumor size, histologic subtype, grade, comorbidities, stage, follow-up time, and perioperative chemotherapy and radiation utilization were similar between the high and low SVI cohorts. The patients with high SVI had worse OS (p = 0.07) and RFS (p = 0.016) than the patients with low SVI. High SVI was independently associated with shorter RFS in the multivariate analysis (hazard ratio, 1.64; 95% confidence interval, 1.06-2.54) but not with OS (HR, 1.47; 95% CI 0.84-2.56). CONCLUSION: High community-level social vulnerability appears to be independently associated with worse RFS for patients undergoing resection of extremity and truncal soft tissue sarcoma. The effect of patient and community-level social risk factors should be considered in the treatment of patients with extremity sarcoma.

Serum Tumor Markers and Outcomes in Patients With Appendiceal Adenocarcinoma.

Importance: Serum tumor markers carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and cancer antigen 125 (CA125) have been useful in the management of gastrointestinal and gynecological cancers; however, there is limited information regarding their utility in patients with appendiceal adenocarcinoma. Objective: To assess the association of serum tumor markers (CEA, CA19-9, and CA125) with clinical outcomes and pathologic and molecular features in patients with appendiceal adenocarcinoma. Design, Setting, and Participants: This is a retrospective cohort study at a single tertiary care comprehensive cancer center. The median (IQR) follow-up time was 52 (21-101) months. Software was used to query the MD Anderson internal patient database to identify patients with a diagnosis of appendiceal adenocarcinoma and at least 1 tumor marker measured at MD Anderson between March 2016 and May 2023. Data were analyzed from January to December 2023. Main Outcomes and Measures: Association of serum tumor markers with survival in patients with appendiceal adenocarcinoma. Cox proportional hazards regression analyses were also performed to assess associations between clinical factors (serum tumor marker levels, demographics, and patient and disease characteristics) and patient outcomes (overall survival). Results: A total of 1338 patients with appendiceal adenocarcinoma were included, with a median (range) age at diagnosis of 56.5 (22.3-89.6) years. The majority of the patients had metastatic disease (1080 patients [80.7%]). CEA was elevated in 742 of the patients tested (56%), while CA19-9 and CA125 were elevated in 381 patients (34%) and 312 patients (27%), respectively. Individually, elevation of CEA, CA19-9, or CA125 were associated with worse 5-year survival; elevated vs normal was 81% vs 95% for CEA (hazard ratio [HR], 4.0; 95% CI, 2.9-5.6), 84% vs 92% for CA19-9 (HR, 2.2; 95% CI, 1.4-3.4), and 69% vs 93% for CA125 (HR, 4.6; 95% CI, 2.7-7.8) (P < .001 for all). Quantitative evaluation of tumor markers was associated with outcomes. Patients with highly elevated (top 10th percentile) CEA, CA19-9, or CA125 had markedly worse survival, with 5-year survival rates of 59% for CEA (HR, 9.8; 95% CI, 5.3-18.0), 64% for CA19-9 (HR, 6.0; 95% CI, 3.0-11.7), and 57% for CA125 (HR, 7.6; 95% CI, 3.5-16.5) (P < .001 for all). Although metastatic tumors had higher levels of all tumor markers, when restricting survival analysis to 1080 patients with metastatic disease, elevated CEA, CA19-9, or CA125 were all still associated worse survival (HR for CEA, 3.4; 95% CI, 2.5-4.8; P < .001; HR for CA19-9, 1.8; 95% CI, 1.2-2.7; P = .002; and HR for CA125, 3.9; 95% CI, 2.4-6.4; P < .001). Interestingly, tumor grade was not associated with CEA or CA19-9 level, while CA-125 was slightly higher in high-grade tumors relative to low-grade tumors (mean value, 18.3 vs 15.0; difference, 3.3; 95% CI, 0.9-3.7; P < .001). Multivariable analysis identified an incremental increase in the risk of death with an increase in the number of elevated tumor markers, with an 11-fold increased risk of death in patients with all 3 tumor markers elevated relative to those with none elevated. Somatic mutations in KRAS and GNAS were associated with significantly higher levels of CEA and CA19-9. Conclusions and Relevance: In this retrospective study of serum tumor markers in patients with appendiceal adenocarcinoma, CEA, CA19-9, and CA125 were associated with overall survival in appendiceal adenocarcinoma. Given their value, all 3 biomarkers should be included in the initial workup of patients with a diagnosis of appendiceal adenocarcinoma.

SABR for Sarcoma Lung Metastases: Indications for Treatment and Guidance for Patient Selection.

PURPOSE: The lungs are the most common site of metastasis for patients with soft tissue sarcoma. SABR is commonly employed to treat lung metastases among select patients with sarcoma with limited disease burden. We sought to evaluate outcomes and patterns of failure among patients with sarcoma treated with SABR for their lung metastases. METHODS AND MATERIALS: We performed a retrospective review of patients treated at a tertiary cancer center between 2006 and 2020. Patient disease status at the time of SABR was categorized as either oligorecurrent or oligoprogressive. The Kaplan-Meier method was used to estimate disease outcomes. Uni- and multivariable analyses were conducted using the Cox proportional hazards model. RESULTS: We identified 70 patients with soft tissue sarcoma treated with SABR to 98 metastatic lung lesions. Local recurrence-free survival after SABR treatment was 83% at 2 years. On univariable analysis, receipt of comprehensive SABR to all sites of pulmonary metastatic disease at the time of treatment was associated with improved progression-free survival (PFS; hazard ratio [HR], 0.51 [0.29-0.88]; P = .02). On multivariable analysis, only having systemic disease controlled at the time of SABR predicted improved PFS (median PFS, 14 vs 4 months; HR, 0.37 [0.20-0.69]; P = .002) and overall survival (median overall survival, 51 vs 14 months; HR, 0.17 [0.08-0.35]; P < .0001). CONCLUSIONS: SABR provides durable long-term local control for sarcoma lung metastases. The most important predictor for improved outcomes was systemic disease control. Careful consideration of these factors should help guide decisions in a multidisciplinary setting to appropriately select the optimal candidates for SABR.

Repeat Cytoreduction and Hyperthermic Intraperitoneal Chemotherapy for Recurrent Mucinous Appendiceal Adenocarcinoma: A Viable Treatment Strategy with Demonstrable Benefit.

INTRODUCTION: Many patients with mucinous appendiceal adenocarcinoma experience peritoneal recurrence despite complete cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). Prior work has demonstrated that repeat CRS/HIPEC can prolong survival in select patients. We sought to validate these findings using outcomes from a high-volume center. PATIENTS AND METHODS: Patients with mucinous appendiceal adenocarcinoma who underwent CRS/HIPEC at MD Anderson Cancer Center between 2004 and 2021 were stratified by whether they underwent CRS/HIPEC for recurrent disease or as part of initial treatment. Only patients who underwent complete CRS/HIPEC were included. Initial and recurrent groups were compared. RESULTS: Of 437 CRS/HIPECs performed for mucinous appendiceal adenocarcinoma, 50 (11.4%) were for recurrent disease. Patients who underwent CRS/HIPEC for recurrent disease were more often treated with an oxaliplatin or cisplatin perfusion (35%/44% recurrent vs. 4%/1% initial, p < 0.001), had a longer operative time (median 629 min recurrent vs. 511 min initial, p = 0.002), and had a lower median length of stay (10 days repeat vs. 13 days initial, p < 0.001). Thirty-day complication and 90-day mortality rates did not differ between groups. Both cohorts enjoyed comparable recurrence free survival (p = 0.82). Compared with patients with recurrence treated with systemic chemotherapy alone, this select cohort of patients undergoing repeat CRS/HIPEC enjoyed better overall survival (p < 0.001). CONCLUSIONS: In appropriately selected patients with recurrent appendiceal mucinous adenocarcinoma, CRS/HIPEC can provide survival benefit equivalent to primary CRS/HIPEC and that may be superior to that conferred by systemic therapy alone in select patients. These patients should receive care at a high-volume center in the context of a multidisciplinary team.

The Clinical Significance of CEA, CA19-9, and CA125 in Management of Appendiceal Adenocarcinoma.

Importance: Serum tumor markers CEA, CA19-9, & CA125 have been useful in the management of gastrointestinal and gynecological cancers, however there is limited information regarding their utility in patients with appendiceal adenocarcinoma. Objective: Assessing the association of serum tumor markers (CEA, CA19-9, and CA125) with clinical outcomes, pathologic, and molecular features in patients with appendiceal adenocarcinoma. Design: This is a retrospective study with results reported in 2023. The median follow-up time was 43 months. Setting: Single tertiary care comprehensive cancer center. Participants: Under an approved Institutional Review Board protocol, the Palantir Foundry software system was used to query the MD Anderson internal patient database to identify patients with a diagnosis of appendiceal adenocarcinoma and at least one tumor marker measured at MD Anderson between 2016 and 2023. Results: A total of 1,338 patients with appendiceal adenocarcinoma were included, with a median age of 56.5 years. The majority of the patients had metastatic disease (80.7%). CEA was elevated in more than half of the patients tested (56%), while CA19-9 and CA125 were elevated in 34% and 27%, respectively. Individually, elevation of CEA, CA19-9, or CA125 were associated with worse 5-year survival; 82% vs 95%, 84% vs 92%, and 69% vs 93% elevated vs normal for CEA, CA19-9, and CA125 respectively (all p<0.0001). Quantitative evaluation of tumor markers increased prognostic ability. Patients with highly elevated (top 10th percentile) CEA, CA19-9 or CA125 had markedly worse survival with 5-year survival rates of 59%, 64%, and 57%, respectively (HR vs. normal : 9.8, 6.0, 7.6, all p<0.0001). Although metastatic tumors had higher levels of all tumor markers, when restricting survival analysis to 1080 patients with metastatic disease elevated CEA, CA19-9 or CA125 were all still associated worse survival (HR vs. normal : 3.4, 1.8, 3.9, p<0.0001 for CEA and CA125, p=0.0019 for CA19-9). Interestingly tumor grade was not associated with CEA or CA19-9 level, while CA-125 was slightly higher in high relative to low-grade tumors (18.3 vs. 15.0, p=0.0009). Multivariable analysis identified an incremental increase in the risk of death with an increase in the number of elevated tumor markers, with a 11-fold increased risk of death in patients with all three tumor markers elevated relative to those with none elevated. Mutation in KRAS and GNAS were associated with significantly higher levels of CEA and CA19-9. Conclusions: These findings demonstrate the utility of measuring CEA, CA19-9, and CA125 in the management of appendiceal adenocarcinoma. Given their prognostic value, all three biomarkers should be included in the initial workup of patients diagnosed with appendiceal adenocarcinoma.

Treatment Variation and Long-Term Outcomes of Low-Grade Appendiceal Neoplasms.

BACKGROUND: Heterogenous nomenclature describing appendiceal neoplasms has added to uncertainty around their appropriate treatment. Although a recent consensus has established the term low-grade appendiceal neoplasm (LAMN), we hypothesize that significant variation remains in the treatment of LAMNs. METHODS: We retrospectively reviewed our prospectively maintained appendiceal registry, identifying patients with LAMNs from 2009 to 2019. We assessed variability in treatment, including whether patients underwent colectomy, spread of disease at presentation, and long-term outcomes. RESULTS: Of 136 patients with LAMNs, 88 (35%) presented with localized disease and 48 (35%) with disseminated peritoneal disease. Median follow-up was 2.9 years (IQR 1.9-4.4), and 120 (88%) patients underwent pre-referral surgery. Among 26 pre-referral colectomy patients, 23 (88%) were performed for perceived oncologic need/nodal evaluation; no nodal metastases were identified. In patients with resected LAMNs without radiographic evidence of disseminated disease, 41 (47%) underwent second look diagnostic laparoscopy (DL) to evaluate for occult metastases. No peritoneal metastases were identified. Patients with disseminated disease were treated with cytoreductive surgery/heated intraperitoneal chemotherapy (CRS/HIPEC). For patients undergoing CRS/HIPEC, 5-year recurrence-free survival was 94% (95% CI 81-98%). For patients with localized disease, 5-year RFS was 98% (95% CI 85-99%). CONCLUSIONS: Significant variation exists in treatment patterns for LAMNs, particularly prior to referral to a high-volume center. Patients frequently underwent colectomy without apparent oncologic benefit. In the current era of high-quality cross sectional imaging, routine use of DL has low yield and is not recommended. Recurrence in this population is rare, and low-intensity surveillance can be offered. Overall prognosis is excellent, even with peritoneal disease.

Neighborhood-Level Socioeconomic Disadvantage Predicts Outcomes in Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Malignancy.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) improves survival in select patients with peritoneal metastases (PM), but the impact of social determinants of health on CRS/HIPEC outcomes remains unclear. PATIENTS AND METHODS: A retrospective review was conducted of a multi-institutional database of patients with PM who underwent CRS/HIPEC in the USA between 2000 and 2017. The area deprivation index (ADI) was linked to the patient's residential address. Patients were categorized as living in low (1-49) or high (50-100) ADI residences, with increasing scores indicating higher socioeconomic disadvantage. The primary outcome was overall survival (OS). Secondary outcomes included perioperative complications, hospital/intensive care unit (ICU) length of stay (LOS), and disease-free survival (DFS). RESULTS: Among 1675 patients 1061 (63.3%) resided in low ADI areas and 614 (36.7%) high ADI areas. Appendiceal tumors (n = 1102, 65.8%) and colon cancer (n = 322, 19.2%) were the most common histologies. On multivariate analysis, high ADI was not associated with increased perioperative complications, hospital/ICU LOS, or DFS. High ADI was associated with worse OS (median not reached versus 49 months; 5 year OS 61.0% versus 28.2%, P < 0.0001). On multivariate Cox-regression analysis, high ADI (HR, 2.26; 95% CI 1.13-4.50; P < 0.001), cancer recurrence (HR, 2.26; 95% CI 1.61-3.20; P < 0.0001), increases in peritoneal carcinomatosis index (HR, 1.03; 95% CI 1.01-1.05; P < 0.001), and incomplete cytoreduction (HR, 4.48; 95% CI 3.01-6.53; P < 0.0001) were associated with worse OS. CONCLUSIONS: Even after controlling for cancer-specific variables, adverse outcomes persisted in association with neighborhood-level socioeconomic disadvantage. The individual and structural-level factors leading to these cancer disparities warrant further investigation to improve outcomes for all patients with peritoneal malignancies.

Efficacy of Systemic Chemotherapy in Patients With Low-grade Mucinous Appendiceal Adenocarcinoma: A Randomized Crossover Trial.

Importance: Appendiceal adenocarcinoma is a rare tumor, and given the inherent difficulties in performing prospective trials in such a rare disease, there are currently minimal high-quality data to guide treatment decisions, highlighting the need for more preclinical and clinical investigation for this disease. Objective: To prospectively evaluate the effectiveness of fluoropyrimidine-based systemic chemotherapy in patients with inoperable low-grade mucinous appendiceal adenocarcinoma. Design, Setting, and Participants: This open-label randomized crossover trial recruited patients at a single tertiary care comprehensive cancer center from September 2013 to January 2021. The data collection cutoff was May 2022. Enrollment of up to 30 patients was planned. Eligible patients had histological evidence of a metastatic low-grade mucinous appendiceal adenocarcinoma, with radiographic imaging demonstrating the presence of mucinous peritoneal carcinomatosis and were not considered candidates for complete cytoreductive surgery. Key exclusion criteria were concurrent or recent investigational therapy, evidence of bowel obstruction, and use of total parenteral nutrition. Data were analyzed from November 2021 to May 2022. Interventions: Patients were randomized to either 6 months observation followed by 6 months of chemotherapy, or initial chemotherapy followed by observation. Main Outcomes and Measures: The primary end point was the percentage difference in tumor growth in treatment and observation groups. Key secondary end points included patient-reported outcomes in the chemotherapy and observation periods, objective response rate, rate of bowel complications, and differences in overall survival (OS). Results: A total of 24 patients were enrolled, with median (range) age of 63 (38 to 82) years, and equal proportion of men and women (eg, 12 men [50%]); all patients had ECOG performance status of 0 or 1. A total of 11 patients were randomized to receive chemotherapy first, and 13 patients were randomized to receive observation first. Most patients (15 patients [63%]) were treated with either fluorouracil or capecitabine as single agent; 3 patients (13%) received doublet chemotherapy (leucovorin calcium [folinic acid], fluorouracil, and oxaliplatin or folinic acid, fluorouracil, and irinotecan hydrochloride), and bevacizumab was added to cytotoxic chemotherapy for 5 patients (21%). Fifteen patients were available to evaluate the primary end point of difference in tumor growth during treatment and observation periods. Tumor growth while receiving chemotherapy increased 8.4% (95% CI, 1.5% to 15.3%) from baseline but was not significantly different than tumor growth during observation (4.0%; 95% CI, -0.1% to 8.0%; P = .26). Of 18 patients who received any chemotherapy, none had an objective response (14 patients [77.8%] had stable disease; 4 patients [22.2%] had progressive disease). Median (range) OS was 53.2 (8.1 to 95.5) months, and there was no significant difference in OS between the observation-first group (76.0 [8.6 to 95.5] months) and the treatment-first group (53.2 [8.1 to 64.1] months; hazard ratio, 0.64; 95% CI, 0.16-2.55; P = .48). Patient-reported quality-of-life metrics identified that during treatment, patients experienced significantly worse fatigue (mean [SD] score, 18.5 [18.6] vs 28.9 [21.3]; P = .02), peripheral neuropathy (mean [SD] score, 6.67 [12.28] vs 38.89 [34.88]; P = .01), and financial difficulty (mean [SD] score, 8.9 [15.2] vs 28.9 [33.0]; P = .001) compared with during observation. Conclusions and Relevance: In this prospective randomized crossover trial of systemic chemotherapy in patients with low-grade mucinous appendiceal adenocarcinoma, patients did not derive clinical benefit from fluorouracil-based chemotherapy, given there were no objective responses, no difference in OS when treatment was delayed 6 months, and no difference in the rate of tumor growth while receiving chemotherapy. Trial Registration: ClinicalTrials.gov Identifier: NCT01946854.

Prognostic significance of acellular mucin in patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) for appendiceal neoplasms.

INTRODUCTION: Appendiceal neoplasms have a propensity for peritoneal dissemination. The standard of care for select individuals is CRS/HIPEC. In the current 8th AJCC Staging system, a finding of only intraperitoneal acellular mucin (M1a) is classified as Stage IVa. There is concern that the current AJCC system may over-stage patients. METHODS: This was a single-institution retrospective review of 164 cases of mucinous appendiceal neoplasm. Patients undergoing CRS/HIPEC with M1a disease were compared to patients with peritoneal deposits containing tumor cells (well-differentiated adenocarcinoma; low-grade mucinous carcinoma peritonei-M1b,G1). Overall and recurrence-free survival were assessed. RESULTS: Median age was 51 years, 70% were female, and 75% White. Sixty-four patients had M1a disease and 100 M1b,G1 disease. M1a disease had a lower median PCI score (11 vs. 20, p = .0001) and a higher rate of complete CRS (62% vs. 50%, p = .021). Median follow-up was 7.6 years (IQR 5.6-10.5 years). For M1a disease, there were no recurrences and only one patient died during the study interval. In comparison, for M1b disease, 66/100 (66%) recurred with a 5-year RFS of 40.5% (HR 8.0, 95% CI 4.9-15.1, p < .0001), and 31/100 (31%) died with a 5-year OS of 84.8% (HR 4.5, 95% CI 2.2-9.2, p < .0001). CONCLUSIONS: Acellular mucin (M1a disease) after CRS/HIPEC for appendiceal neoplasm is associated with longer OS and RFS compared to M1b, G1 disease. Current AJCC staging does not accurately reflect the differing outcomes of these two patient populations. The presence of acellular mucin in the peritoneal cavity should not be perceived as a metastatic equivalent.

Practice Pattern Variability in the Management of Regional Lymph Node Metastasis in Extremity and Trunk Soft Tissue Sarcoma: A Survey of the Society of Surgical Oncology and Musculoskeletal Tumor Society Membership.

BACKGROUND: Regional lymph node metastasis in extremity and trunk soft tissue sarcoma (ETSTS) is rare with no standardized management. We sought to determine management patterns for regional lymph node metastasis in ETSTS. METHODS: A survey regarding the management of ETSTS lymph node metastasis was distributed to the membership of the Musculoskeletal Tumor Society (MSTS) and the Society of Surgical Oncology (SSO) in January 2022. The survey queried the type of training (surgical oncology, orthopedic oncology), details of their practice setting, and management decisions of hypothetical ETSTS scenarios that involved potential or confirmed lymph node metastasis. RESULTS: The survey was distributed to 349 MSTS members (open rate of 63%, completion rate 21%) and 3026 SSO members (open rate of 55%, completion rate 4.7%) and was completed by 214 respondents, of whom 73 (34.1%) and 141 (65.9%) were orthopedic oncology and surgical oncology fellowship-trained, respectively. The majority of respondents practiced in an academic setting (n = 171, 79.9%) and treat >10 extremity sarcoma cases annually (n = 138, 62.2%). In scenarios with confirmed nodal disease for clear cell and epithelioid sarcoma, surgical oncologists were inclined to perform lymphadenectomy, while orthopedic oncologists were inclined to offer targeted lymph node excision with adjuvant radiation (p < 0.001). There was heterogeneity of responses regarding the management of nodal disease regardless of training background. CONCLUSION: Self-reported management of nodal disease in ETSTS was variable among respondent groups with differences and similarities based on training background. These data highlight the variability of practice for nodal disease management and the need for consensus-based guidelines.

Re-excision After Unplanned Excision of Soft Tissue Sarcoma is Associated with High Morbidity and Limited Pathologic Identification of Residual Disease.

BACKGROUND: Patients with unplanned excision (UPE) of trunk and extremity soft tissue sarcoma (STS) present a significant management challenge for sarcoma specialists. Oncologic re-resection has been considered standard practice after UPE with positive or uncertain margins. A strategy of active surveillance or "watch and wait" has been suggested as a safe alternative to routine re-excision. In this context, the current study sought to evaluate short-term outcomes and morbidity after re-resection to better understand the risks and benefits of this treatment strategy. METHODS: A retrospective, single-institution study reviewed patients undergoing oncologic re-resection after UPE of an STS during a 5-year period (2015-2020), excluding those with evidence of gross residual disease. Short-term clinical outcomes were evaluated together with final pathologic findings. RESULTS: The review identified 67 patients undergoing re-resection after UPE of an STS. Of these 67 patients, 45 (67%) were treated with a combination of external beam radiation therapy (EBRT) and surgery. Plastic surgery was involved for reconstruction in 49 cases (73%). The rate of wound complications after re-resection was 45 % (n = 30), with 15 % (n = 10) of the patients experiencing a major wound complication. Radiation therapy and plastic surgery involvement were independently associated with wound complications. Notably, 45 patients (67%) had no evidence of residual disease in the re-resection specimen, whereas 13 patients (19 %) had microscopic disease, and 9 patients (13%) had indeterminate pathology. CONCLUSION: Given the morbidity of re-resection and limited identification of residual disease, treatment plans and discussions with patients should outline the expected pathologic findings and morbidity of surgery.