Natural history of undifferentiated pleomorphic sarcoma: Experience from the US Sarcoma Collaborative.

BACKGROUND: Undifferentiated pleomorphic sarcoma (UPS) is a relatively rare but aggressive neoplasm. We sought to utilize a multi-institutional US cohort of sarcoma patients to examine predictors of survival and recurrence patterns after resection of UPS. METHODS: From 2000 to 2016, patients with primary UPS undergoing curative-intent surgical resection at seven academic institutions were retrospectively reviewed. Epidemiologic and clinicopathologic factors were reviewed by site of origin. Overall survival (OS), recurrence-free survival (RFS), time-to-locoregional (TTLR), time-to-distant recurrence (TTDR), and patterns of recurrence were analyzed. RESULTS: Of the 534 UPS patients identified, 53% were female, with a median age of 60 and median tumor size of 8.5 cm. The median OS, RFS, TTLR, and TTDR for the entire cohort were 109, 49, 86, and 46 months, respectively. There were no differences in these survival outcomes between extremity and truncal UPS. Compared with truncal, extremity UPS were more commonly amenable to R0 resection (87% vs. 75%, p = 0.017) and less commonly associated with lymph node metastasis (1% vs. 6%, p = 0.031). R0 resection and radiation treatment, but not site of origin (extremity vs. trunk) were independent predictors of OS and RFS. TTLR recurrence was shorter for UPS resected with a positive margin and for tumors not treated with radiation. CONCLUSION: For patients with resected extremity and truncal UPS, tumor size >5 cm and positive resection margin are associated with worse survival OS and RFS, irrespectively the site of origin. R0 surgical resection and radiation treatment may help improve these survival outcomes.

Extremity Soft Tissue Sarcoma: A Multi-Institutional Validation of Prognostic Nomograms.

BACKGROUND: Prognostic nomograms for patients with resected extremity soft tissue sarcoma (STS) include the Sarculator and Memorial Sloan Kettering (MSKCC) nomograms. We sought to validate these two nomograms within a large, modern, multi-institutional cohort of resected primary extremity STS patients. METHODS: Resected primary extremity STS patients from 2000 to 2017 were identified across nine high-volume U.S. institutions. Predicted 5- and 10-year overall survival (OS) and distant metastases cumulative incidence (DMCI), and 4-, 8-, and 12-year disease-specific survival (DSS) were calculated with Sarculator and MSKCC nomograms, respectively. Predicted survival probabilities stratified in quintiles were compared in calibration plots to observed survival assessed by Kaplan-Meier estimates. Cumulative incidence was estimated for DMCI. Harrell's concordance index (C-index) assessed discriminative ability of nomograms. RESULTS: A total of 1326 patients underwent resection of primary extremity STS. Common histologies included: undifferentiated pleomorphic sarcoma (35%), fibrosarcoma (13%), and leiomyosarcoma (9%). Median tumor size was 8.0 cm (IQR 4.5-13.0). Tumor grade distribution was: Grade 1 (13%), Grade 2 (9%), Grade 3 (78%). Median OS was 172 months, with estimated 5- and 10-year OS of 70% and 58%. C-indices for 5- and 10-year OS (Sarculator) were 0.72 (95% CI 0.70-0.75) and 0.73 (95% CI 0.70-0.75), and 0.72 (95% CI 0.69-0.75) for 5- and 10-year DMCI. C-indices for 4-, 8-, and 12-year DSS (MSKCC) were 0.71 (95% CI 0.68-0.75). Calibration plots showed good prognostication across all outcomes. CONCLUSIONS: Sarculator and MSKCC nomograms demonstrated good prognostic ability for survival and recurrence outcomes in a modern, multi-institutional validation cohort of resected primary extremity STS patients. External validation of these nomograms supports their ongoing incorporation into clinical practice.

Extraskeletal myxoid chondrosarcoma: Clinicopathological features and outcomes from the United States sarcoma collaborative database.

BACKGROUNDS AND OBJECTIVES: This investigation described clinicopathological features and outcomes of extraskeletal myxoid chondrosarcoma (EMC) patients. METHODS: EMC patients were identified from the United States Sarcoma Collaborative database between 2000 and 2016. Overall survival (OS) and recurrence-free survival (RFS) were calculated, and prognostic factors were analyzed. RESULTS: Sixty individuals with a mean age of 55 years were included, and 65.0% (n = 39) were male. 73.3% (n = 44) had a primary tumor. A total of 41.6% (n = 25) developed tumor relapse following resection. The locoregional recurrence rate was 30.0% (n = 18/60), and mean follow-up was 42.7 months. The 5-year OS was 71.0%, while the 5-year RFS was 41.4%. On multivariate analysis for all EMC, chemotherapy (hazard ratio [HR], 6.054; 95% confidence interval [CI], 1.33-27.7; p = 0.020) and radiation (HR, 5.07, 95% CI, 1.3-20.1; p = 0.021) were independently predictive of a worse RFS. Among patients with primary EMC only, the 5-year OS was 85.3%, with a 30.0% (n = 12) locoregional recurrence rate, though no significant prognostic factors were identified. CONCLUSIONS: Long-term survival with EMC is probable, however there exists a high incidence of locoregional recurrence. While chemotherapy and radiation were associated with a worse RFS, these findings were likely confounded by recurrent disease as significance was lost in the primary EMC-only subset.

Robotic versus thoraco-laparoscopic minimally invasive Ivor Lewis esophagectomy, a matched-pair single-center cohort analysis.

Minimally invasive esophagectomy (MIE) is becoming more widespread with a documented improvement in postoperative morbidity based on level I evidence. However, there is a lack of consensus regarding the optimal MIE approach, conventional thoracoscopy/laparoscopy vs robotics as well as the ideal anastomotic technique. All patients who underwent MIE via an Ivor Lewis approach with a side-to-side stapled anastomosis were included. The thoracoscopy-laparoscopy (TL) group was compared to the robotic group with respect to perioperative outcomes using the entire cohorts and after 1:1 propensity score matching. Comparisons were made using the Mann-Whitney U and Fisher's exact tests. Between July 2013 and November 2020, 72 TL and 67 robotic Ivor Lewis MIE were performed. After comparing the two unadjusted cohorts and 51 propensity matched pairs, there was a decrease in Clavien-Dindo Grade 2 or above complications in the robotic vs TL group (59.7% vs 41.8% [P = 0.042], (62.7% vs 39.2% [P = 0.029]), respectively. In both analyses, there was a reduction in hospital length of stay (median of 8 vs 7 days, P < 0.001) and a trend toward less anastomotic leaks in the robotic group (Unadjusted: 12.5 vs 3% [P = 0.057], Propensity-matched analysis: 13.7% vs 3.9% [P = 0.16]), respectively. A clinically significant decrease in overall morbidity, cardiac complications and hospital length of stay was observed in the robotic Ivor Lewis cohort when compared with the TL group at a high volume MIE program. Side-to-side stapled thoracic anastomoses utilizing a robotic platform provides the best outcomes in this single institution experience.

Impact of resection margin on outcomes in high-grade soft tissue sarcomas of the extremity-A USSC analysis.

BACKGROUND: The optimal margin of resection for high-grade extremity sarcomas and its impact on survival has long been questioned in the setting of adjuvant radiotherapy. The objective of this study was to investigate the impact of resection status on recurrence and survival. METHODS: All patients with primary, nonmetastatic, high-grade extremity sarcomas that underwent surgical resection from January 2000 to April 2016 in the U.S. Sarcoma Collaborative (USSC) were retrospectively reviewed. Recurrence patterns, recurrence-free survival (RFS), and overall survival (OS) were examined in multivariate analyses (MVA). RESULTS: A cohort of 959 patients was identified with a median follow-up of 34.7 months from diagnosis. R0 resection was achieved in 86.7% (831) while R1 resection in 13.3% (128). Locoregional recurrence for R0 and R1 groups occurred in 9.1% (76) versus 14.8% (19; p = .05) while distant recurrence occurred in 24.7% (205) versus 26.6% (34; p = .65), respectively. Median RFS was 171.2 versus 48.5 (p = .01) while median OS was 149.8 versus 71.5 months (p = .02) for the R0 versus R1 group, respectively. On MVA, female gender (hazard ratio [HR] = 0.69, p = .007) and adjuvant radiotherapy (0.7, p = .04) were associated with improved OS, whereas older age (HR = 1.03, p < .001) and tumor size (HR = 1.01, p < .001) were associated with worse OS. R0 resection status was associated with improved locoregional RFS (HR = 0.56, p = .03) but not with distant RFS (HR = 0.84, p = .4) or OS (HR = 0.7, p = .052). CONCLUSIONS: In high-grade extremity sarcomas, tumor size and gender are predictive of OS while R0 resection status is associated with improved locoregional recurrence rate without a significant impact on distant RFS or OS.

A novel preoperative risk score to guide patient selection for resection of soft tissue sarcoma lung metastases: An analysis from the United States Sarcoma Collaborative.

BACKGROUND: Surgical resection for sarcoma lung metastases has been associated with improved overall survival (OS). METHODS: Patients who underwent curative-intent resection of sarcoma lung metastases (2000-2016) were identified from the US Sarcoma Collaborative. Patients with extrapulmonary metastatic disease or R2 resections of primary tumor or metastases were excluded. Primary endpoint was OS. RESULTS: Three hundred and fifty-two patients met inclusion criteria. Location of primary tumor was truncal/extremity in 85% (n = 270) and retroperitoneal in 15% (n = 49). Forty-nine percent (n = 171) of patients had solitary and 51% (n = 180) had multiple lung metastasis. Median OS was 49 months; 5-year OS 42%. Age ≥55 (HR 1.77), retroperitoneal primary (HR 1.67), R1 resection of primary (HR 1.72), and multiple (≥2) lung metastases (HR 1.77) were associated with decreased OS(all p < 0.05). Assigning one point for each factor, we developed a risk score from 0 to 4. Patients were then divided into two risk groups: low (0-1 factor) and high (2-4 factors). The low-risk group (n = 159) had significantly better 5-year OS compared to the high-risk group (n = 108) (51% vs. 16%, p < 0.001). CONCLUSION: We identified four characteristics that in aggregate portend a worse OS and created a novel prognostic risk score for patients with sarcoma lung metastases. Given that patients in the high-risk group have a projected OS of <20% at 5 years, this risk score, after external validation, will be an important tool to aid in preoperative counseling and consideration for multimodal therapy.

A multi-institutional validation study of prognostic nomograms for retroperitoneal sarcoma.

BACKGROUND AND OBJECTIVES: Prognostic nomograms for patients undergoing resection of retroperitoneal sarcoma (RPS) include the Sarculator and Memorial Sloan Kettering (MSK) sarcoma nomograms. We sought to validate the Sarculator and MSK nomograms within a large, modern multi-institutional cohort of patients with primary RPS undergoing resection. METHODS: Patients who underwent resection of primary RPS between 2000 and 2017 across nine high-volume US institutions were identified. Predicted 7-year disease-free (DFS) and overall survival (OS) and 4-, 8-, and 12-year disease-specific survival (DSS) were calculated from the Sarculator and MSK nomograms, respectively. Nomogram-predicted survival probabilities were stratified in quintiles and compared in calibration plots to observed survival outcomes assessed by Kaplan-Meier estimates. Discriminative ability of nomograms was quantified by Harrell's concordance index (C-index). RESULTS: Five hundred and two patients underwent resection of primary RPS. Histologies included leiomyosarcoma (30%), dedifferentiated liposarcoma (23%), and well-differentiated liposarcoma (15%). Median tumor size was 14.0 cm (interquartile range [IQR], 8.5-21.0 cm). Tumor grade distribution was: Grade 1 (27%), Grade 2 (17%), and Grade 3 (56%). Median DFS was 31.5 months; 7-year DFS was 29%. Median OS was 93.8 months; 7-year OS was 51%. C-indices for 7-year DFS, and OS by the Sarculator nomogram were 0.65 (95% confidence interval [CI]: 0.62-0.69) and 0.69 (95%CI: 0.65-0.73); plots demonstrated good calibration for predicting 7-year outcomes. The C-index for 4-, 8-, and 12-year DSS by the MSK nomogram was 0.71 (95%CI: 0.67-0.75); plots demonstrated similarly good calibration ability. CONCLUSIONS: In a diverse, modern validation cohort of patients with resected primary RPS, both Sarculator and MSK nomograms demonstrated good prognostic ability, supporting their ongoing adoption into clinical practice.

Intraoperative Botulinum Toxin Chemodenervation and Analgesia in Abdominal Wall Reconstruction.

Purpose. To analyze the impact of botulinum toxin chemodenervation on postoperative opiate consumption through a novel intraoperative injection protocol. Methods. A retrospective review of the implementation of a novel intraoperative botulinum toxin injection into both rectus and oblique musculature. Patients undergoing open retrorectus release, with and without intraoperative chemodenervation with Botox, were retrospectively collected between 2015 and 2019. Demographics, comorbidities, and opioid use in morphine milligram equivalents (MMEs) were retrospectively captured. Basic descriptive statistics and linear regression analysis were performed. Results. 19 patients in the Botox and 22 in the no Botox group were analyzed. Basic demographics were similar with female preponderance in the Botox group, 58% vs 27%, P = .05. Median hernia length was 15 cm for both groups (P = .57), median hernia width was 8 vs 9 cm (P = .39), epidural catheter used in 0 vs 4 (P = .11), transverse abdominal plane blocks in 3 vs 4 (P = 1), median MME usage was 191 vs 230 (P = .37) in the inpatient setting, 225 vs 300 (P = .17) in the outpatient setting, and 405 vs 568 (P = .07) in total for Botox vs no Botox groups. Stepwise linear regression analysis identified Botox as the only predictor for MME usage, P = .048. Conclusions. Chemodenervation was the only factor associated with reduced opioid usage compared to a standard group using multimodality analgesia. The role of muscular pain in laparotomy is likely underappreciated and understudied. Intraoperative selective muscular chemodenervation may play a significant role in recovery from abdominal surgery and requires further study.

Trends in the Use of Adjuvant Chemotherapy for High-Grade Truncal and Extremity Soft Tissue Sarcomas.

BACKGROUND: In the randomized controlled trial (RCT) EORTC 62931, adjuvant chemotherapy failed to show improvement in relapse-free survival (RFS) or overall survival (OS) for patients with resected high-grade soft tissue sarcoma (STS). We evaluated whether the negative results of this 2012 RCT have influenced multidisciplinary treatment patterns for patients with high-grade STS undergoing resection at seven academic referral centers. METHODS: The U.S. Sarcoma Collaborative database was queried to identify patients who underwent curative-intent resection of primary high-grade truncal or extremity STS from 2000 to 2016. Patients with recurrent tumors, metastatic disease, and those receiving neoadjuvant chemotherapy were excluded. Patients were divided by treatment era into early (2000-2011, pre-European Organisation for Research and Treatment of Cancer [EORTC] trial) and late (2012-2016, post-EORTC trial) cohorts for analysis. Rates of adjuvant chemotherapy and clinicopathologic variables were compared between the two cohorts. Univariate and multivariate regression analyses were used to determine factors associated with OS and RFS. RESULTS: 949 patients who met inclusion criteria were identified, with 730 patients in the early cohort and 219 in the late cohort. Adjuvant chemotherapy rates were similar between the early and late cohorts (15.6% versus 14.6%; P = 0.73). Patients within the early and late cohorts demonstrated similar median OS (128 months versus median not reached, P = 0.84) and RFS (107 months versus median not reached, P = 0.94). Receipt of adjuvant chemotherapy was associated with larger tumor size (13.6 versus 8.9 cm, P < 0.001), younger age (53.3 versus 63.7 years, P < 0.001), and receipt of adjuvant radiation (P < 0.001). On multivariate regression analysis, risk factors associated with decreased OS were increasing American Society of Anesthesiologists class (P = 0.02), increasing tumor size (P < 0.001), and margin-positive resection (P = 0.01). Adjuvant chemotherapy was not associated with OS (P = 0.88). Risk factors associated with decreased RFS included increasing tumor size (P < 0.001) and margin-positive resection (P = 0.03); adjuvant chemotherapy was not associated with RFS (P = 0.23). CONCLUSIONS: Rates of adjuvant chemotherapy for resected high-grade truncal or extremity STS have not decreased over time within the U.S. Sarcoma Collaborative, despite RCT data suggesting a lack of efficacy. In this retrospective multi-institutional analysis, adjuvant chemotherapy was not associated with RFS or OS on multivariate analysis, consistent with the results from EORTC 62931. Rates of adjuvant chemotherapy for high-grade STS were low in both cohorts but may be influenced more by selection bias based on clinicopathologic variables such as tumor size, margin status, and patient age than by prospective, randomized data.

Analysis of textbook outcomes among patients undergoing resection of retroperitoneal sarcoma: A multi-institutional analysis of the US Sarcoma Collaborative.

BACKGROUND: The novel composite metric textbook outcome (TO) has increasingly been used as a quality indicator but has not been reported among patients undergoing surgical resection for retroperitoneal sarcoma (RPS) using multi-institutional collaborative data. METHODS: All patients who underwent resection for RPS between 2000 to 2016 from eight academic institutions were included. TO was defined as a patient with R0/R1 resection that discharged to home and was without transfusion, reoperation, grade ≥2 complications, hospital-stay >50th percentile, or 90-day readmission or mortality. Univariate and multivariable analyses were performed. RESULTS: Among 627 patients, 56.1% were female and the median age was 59 years. A minority of patients achieved a TO (34.9%). Factors associated with achieving a TO were tumor size <20 cm and low tumor grade, while ASA class ≥3, history of a prior cardiac event, resection of left colon/rectum, distal pancreatic resection, major venous resection and drain placement were associated with not achieving a TO (all P < .05). Achievement of a TO was associated with improved survival (median:12.7 vs 5.9 years, P < .01). CONCLUSIONS: Among patients undergoing resection for RPS, failure to achieve TO is common and associated with significantly worse survival. The use of TO may inform patient expectations and serve as a measure for patient-level hospital performance.

Neoadjuvant radiation improves margin-negative resection rates in extremity sarcoma but not survival.

BACKGROUND AND OBJECTIVES: Radiation improves limb salvage in extremity sarcomas. Timing of radiation therapy remains under investigation. We sought to evaluate the effects of neoadjuvant radiation (NAR) on surgery and survival of patients with extremity sarcomas. MATERIALS AND METHODS: A multi-institutional database was used to identify patients with extremity sarcomas undergoing surgical resection from 2000-2016. Patients were categorized by treatment strategy: surgery alone, adjuvant radiation (AR), or NAR. Survival, recurrence, limb salvage, and surgical margin status was analyzed. RESULTS: A total of 1483 patients were identified. Most patients receiving radiotherapy had high-grade tumors (82% NAR vs 81% AR vs 60% surgery; P < .001). The radiotherapy groups had more limb-sparing operations (98% AR vs 94% NAR vs 87% surgery; P < .001). NAR resulted in negative margin resections (90% NAR vs 79% surgery vs 75% AR; P < .0001). There were fewer local recurrences in the radiation groups (14% NAR vs 17% AR vs 27% surgery; P = .001). There was no difference in overall or recurrence-free survival between the three groups (OS, P = .132; RFS, P = .227). CONCLUSION: In this large study, radiotherapy improved limb salvage rates and decreased local recurrences. Receipt of NAR achieves more margin-negative resections however this did not improve local recurrence or survival rates over.

Is a Nomogram Able to Predict Postoperative Wound Complications in Localized Soft-tissue Sarcomas of the Extremity?

BACKGROUND: Postoperative wound complications are challenging in patients with localized extremity soft-tissue sarcomas. Various factors have been associated with wound complications, but there is no individualized predictive model to allow providers to counsel their patients and thus offer methods to mitigate the risk of complications and implement appropriate measures. QUESTIONS/PURPOSES: We used data from multiple centers to ask: (1) What risk factors are associated with postoperative wound complications in patients with localized soft-tissue sarcomas of the extremity? (2) Can we create a predictive nomogram that will assess the risk of wound complications in individual patients after resection for soft-tissue sarcoma? METHODS: From 2000 to 2016, 1669 patients undergoing limb-salvage resection for a localized primary or recurrent extremity soft-tissue sarcoma with at least 120 days of follow-up at eight participating United States Sarcoma Collaborative institutions were identified. Wound complications included superficial wounds with or without drainage, deep wounds with drainage because of dehiscence, and intentional opening of the wound within 120 days postoperatively. Sixteen variables were selected a priori by clinicians and statisticians as potential risk factors for wound complications. A univariate analysis was performed using Fisher's exact tests for categorical predictors, and Wilcoxon's rank-sum tests were used for continuous predictors. A multiple logistic regression analysis was used to train the prediction model that was used to create the nomogram. The prediction performance of the datasets was evaluated using a receiver operating curve, area under the curve, and calibration plot. RESULTS: After controlling for potential confounding factors such as comorbidities, functional status, albumin level, and chemotherapy use, we found that increasing age (odds ratio 1.02; 95% confidence interval, 1.00-1.03; p = 0.008), BMI (OR 1.05; 95% CI, 1.02-1.09; p = 0.004), lower-extremity location (OR 6; 95% CI, 2.87-12.69; p < 0.001), and neoadjuvant radiation (OR 2; 95% CI, 1.47-3.16; p < 0.001) were associated with postoperative wound complications (area under the curve 69.2% [range 62.8%-75.6%]). CONCLUSIONS: We found that age, BMI, tumor location, and timing of radiation are associated with the risk of wound complications. Based on these factors, a validated nomogram has been established that can provide an individualized prediction of wound complications in patients with a resected soft-tissue sarcoma of the extremity. This may allow for proactive management with nutrition and surgical techniques, and help determine the delivery of radiation in patients with a high risk of having these complications. LEVEL OF EVIDENCE: Level III, therapeutic study.

Hepatic arterial infusion chemotherapy for colorectal liver metastases revisited.

BACKGROUND: Recent reports indicate improved survival in patients undergoing surgical treatment for colorectal liver metastases (CRLM) with hepatic arterial infusion (HAI) pump chemotherapy compared to surgery alone. METHODS: Patients who underwent resection and/or ablation of CRLM between 1996 and 2016 were included from a single-institution prospectively maintained database. Proportional hazards regression analysis was performed to determine predictors of overall survival (OS) and 3:1 propensity score analysis (PSA). RESULTS: Of 349 patients included, 36 had HAI pumps placed (HAI group) and 313 did not (no-HAI group). There was no difference in primary tumor grade (p = 0.24), ECOG status (p = 0.44), tumor number (p = 0.1), tumor size (p = 0.56), margin status (p = 0.76) between the two groups. Median overall survival was 44.7months vs 37.1months for the HAI versus no-HAI group (p = 0.01). Cox proportional hazards regression analysis demonstrated positive margin status (HR:2.47,p < 0.0001), HAI therapy (HR:0.56,p = 0.02), preoperative chemotherapy (HR:0.69,p = 0.02) and tumor diameter (HR:1.07,p = 0.005) as predictors of OS. In 3:1 PSA, 32 HAI subjects were matched with 87 non-HAI subjects balancing all covariates. Median OS was 42.4 months versus 35.6 months for the HAI versus no-HAI group (p = 0.03). CONCLUSION: Surgical treatment of CRLM combined with HAI chemotherapy is associated with improved OS compared to surgery alone. Further study of this treatment approach is indicated.

Assessing the Role of Neoadjuvant Chemotherapy in Primary High-Risk Truncal/Extremity Soft Tissue Sarcomas: An Analysis of the Multi-institutional U.S. Sarcoma Collaborative.

BACKGROUND: The role of neoadjuvant chemotherapy (NCT) for high-risk soft tissue sarcoma (STS) is questioned. This study aimed to define which patients may experience a survival advantage with NCT. METHODS: All the patients from the U.S. Sarcoma Collaborative database (2000-2016) who underwent curative-intent resection of high-grade, primary truncal/extremity STS size 5 cm or larger were included in this study. The primary end points were recurrence-free survival (RFS) and overall survival (OS). RESULTS: Of the 4153 patients, 770 were included in the study. The median tumor size was 10 cm, and 669 of the patients (87%) had extremity tumors. The most common histology was undifferentiated pleomorphic sarcoma (UPS), found in 42% of the patients. Of the 770 patients, 216 (28%) received NCT. The patients who received NCT had deeper, larger tumors (p < 0.001). Of the patients with tumors 5 cm or larger and 8 cm or larger, NCT was not associated with improved RFS or OS. However for the patients with tumors 10 cm or larger, NCT was associated with improved 5-year RFS (51% vs 40%; p = 0.053) and 5-year OS (58% vs 47%; p = 0.043). By location, the patients with extremity tumors 10 cm or larger but not truncal tumors had improved 5-yearr RFS (54% vs 42%; p = 0.042) and 5-year OS (61% vs 47%; p = 0.015) with NCT. According to histology, no subtype had improved RFS or OS with NCT, although the patients with UPS had a trend toward improved 5-year RFS (56% vs 42%; p = 0.092) and 5-year OS (66% vs 52%; p = 0.103) with NCT. CONCLUSION: For the patients with high-grade STS, NCT was associated with improved RFS and OS when tumors were 10 cm or larger and located in the extremity. However, no histiotype-specific advantage was identified. Future studies assessing the efficacy of NCT may consider focusing on these patients, with added focus on histology-specific strategies.

Outcomes of Elderly Patients Undergoing Curative Resection for Retroperitoneal Sarcomas: Analysis From the US Sarcoma Collaborative.

BACKGROUND: The postoperative outcomes of elderly patients undergoing resection of retroperitoneal sarcomas (RPS) have not been widely studied. METHODS: Patients undergoing surgical resection for primary or recurrent RPS between 2000 and 2015 at participating US Sarcoma Collaborative institutions were identified. Patient demographics, perioperative morbidity, mortality, length of stay, discharge to home, disease-specific survival, and disease-free survival were compared between elderly (≥70 y, n = 171) and nonelderly (<70 y, n = 494) patients. RESULTS: There was no difference in perioperative morbidity (total and major complications elderly versus nonelderly: 39% versus 35%; P = 0.401 and 18% versus 17%; P = 0.646, respectively) or mortality between elderly and nonelderly patients with each group experiencing a 1% 30-d mortality rate. Length of stay and 30-d readmission rates were similar (elderly versus nonelderly; 7 d interquartile range [IQR: 5-9] versus 6 d [IQR: 4-9], P = 0.528 and 11% versus 12%, P = 0.667). Elderly patients were more likely to be discharged to a skilled nursing or rehabilitation facility (elderly versus nonelderly; 19% versus 7%, P < 0.001). There was no difference in 3-y disease-free survival between the elderly and nonelderly patients (41% versus 43%, P = 0.65); however, elderly patients had a lower 3-y disease-specific survival (60% versus 76%, P < 0.001). In elderly patients, the presence of multiple comorbidities and high-grade tumors were most predictive of outcomes. CONCLUSIONS: Advanced age was not associated with an increased risk of perioperative morbidity and mortality following resection of RPS in this multi-institutional review. Although short-term oncologic outcomes were similar in both groups, the risk of death after sarcoma recurrence was higher in elderly patients and may be related to comorbidity burden and tumor histology.

Role of radiation therapy for retroperitoneal sarcomas: An eight-institution study from the US Sarcoma Collaborative.

BACKGROUND: The use of radiation therapy in the treatment of retroperitoneal sarcomas has increased in recent years. Its impact on survival and recurrence is unclear. METHODS: A retrospective propensity score matched (PSM) analysis of patients with primary retroperitoneal soft tissue sarcomas, who underwent resection from 2000 to 2016 at eight institutions of the US Sarcoma Collaborative, was performed. Patients with metastatic disease, desmoid tumors, and palliative resections were excluded. RESULTS: Total 425 patients were included, 56 in the neoadjuvant radiation group (neo-RT), 75 in the adjuvant radiation group (adj-RT), and 294 in the no radiotherapy group (no-RT). Median age was 59.5 years, 186 (43.8%) were male with a median follow up of 31.4 months. R0 and R1 resection was achieved in 253 (61.1%) and 143 (34.5%), respectively. Overall 1:1 match of 46 adj-RT and 59 neo-RT patients was performed using histology, sex, age, race, functional status, tumor size, grade, resection status, and chemotherapy. Unadjusted recurrence-free survival (RFS) was 35.9 months (no-RT) vs 33.5 months (neo-RT) and 27.2 months (adj-RT), P = .43 and P = .84, respectively. In the PSM, RFS was 17.6 months (no-RT) vs 33.9 months (neo-RT), P = .28 and 19 months (no-RT) vs 27.2 months (adj-RT), P = .1. CONCLUSIONS: Use of radiotherapy, both in adjuvent or neoadjuvent setting, was not associated with improved survival or reduced recurrence rate.

Recurrence patterns after resection of retroperitoneal sarcomas: An eight-institution study from the US Sarcoma Collaborative.

BACKGROUND AND OBJECTIVES: Resection of primary retroperitoneal sarcomas (RPS) has a high incidence of recurrence. This study aims to identify patterns of recurrence and its impact on overall survival. METHODS: Adult patients with primary retroperitoneal soft tissue sarcomas who underwent resection in 2000-2016 at eight institutions of the US Sarcoma Collaborative were evaluated. RESULTS: Four hundred and ninety-eight patients were analyzed, with 56.2% (280 of 498) having recurrences. There were 433 recurrences (1-8) in 280 patients with 126 (25.3%) being locoregional, 82 (16.5%) distant, and 72 (14.5%) both locoregional and distant. Multivariate analyses revealed the following: Patient age P = .0002), tumor grade (P = .02), local recurrence (P = .0003) and distant recurrence (P < .0001) were predictors of disease-specific survival. The 1-, 3-, and 5-year survival rate for patients who recurred vs not was 89.6% (standard error [SE] 1.9) vs 93.5% (1.8), 66.0% (3.2) vs 88.4% (2.6), and 51.8% (3.6) vs 83.9% (3.3), respectively, P < .0001. Median survival was 5.3 years for the recurrence vs 11.3+ years for the no recurrence group (P < .0001). Median survival from the time of recurrence was 2.5 years. CONCLUSIONS: Recurrence after resection of RPS occurs in more than half of patients independently of resection status or perioperative chemotherapy and is equally distributed between locoregional and distant sites. Recurrence is primarily related to tumor biology and is associated with a significant decrease in overall survival.

PCI is Not Predictive of Survival After Complete CRS/HIPEC in Peritoneal Dissemination from High-Grade Appendiceal Primaries.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is a treatment option in patients with carcinomatosis from high-grade appendiceal (HGA) primaries. It is unknown if there is a Peritoneal Carcinomatosis Index (PCI) upper limit above which a complete CRS/HIPEC does not assure long-term survival. METHODS: Retrospective analysis from three centers was performed. The PCI was used to grade volume of of disease. Survival in relation to PCI was studied on patients with complete cytoreduction. RESULTS: Overall, 521 HGA patients underwent CRS/HIPEC from 1993 to 2015, with complete CRS being achieved in 50% (260/622). Mean PCI was 14.8 (standard deviation 8.7, range 0-36). Median survival for the complete CRS cohort was 6.1 years, while 5- and 10-year survival was 51.7% (standard error [SE] 4.6) and 36.1% (SE 6.3), respectively. Arbitrary cut-off PCI limits with 5-point splits (p = 0.63) were not predictive of a detrimental effect on survival as long as a complete CRS was achieved. A linear effect of the PCI on survival (p = 0.62) was not observed, and single-point PCI cohort splits within a PCI range of < 5 to > 10 were not predictive of survival for complete CRS patients. The PCI correlated with the ability to achieve a complete CRS, with a mean PCI of 14.7 (8.7) for completeness of cytoreduction (CC)0, 22.3 (7.8) for CC1 and 26.1 (9.5) for CC2/3 resections (p = 0.0001, hazard ratio 1.12, 95% confidence interval 1.09), with an HR of 1.15 for each 1-unit increase in the PCI score. Only 21% of the cohort achieved a complete CRS with a PCI ≥ 21. CONCLUSIONS: The PCI correlates with the ability to achieve a complete CRS in carcinomatosis from HGA. PCI is not associated with survival as long as a complete CRS can be achieved.

Is Cytoreductive Surgery with Hyperthermic Intraperitoneal Chemotherapy Justified for Biphasic Variants of Peritoneal Mesothelioma? Outcomes from the Peritoneal Surface Oncology Group International Registry.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) has dramatically improved the survival of patients with epithelioid peritoneal mesothelioma. It is unknown if CRS/HIPEC is indicated for the more aggressive biphasic mesothelioma variant. METHODS: A retrospective analysis of the Peritoneal Surface Oncology Group International (PSOGI) registry including data from 33 centers was performed. Survival was reviewed based on mesothelioma type, completion of cytoreduction, and volume of disease. RESULTS: Overall, 484 of 1165 (41.5%) CRS/HIPEC procedures with complete CC0 and CC1 cytoreductions were analyzed; 450 (93%) procedures were performed for epithelioid mesotheliomas, while 34 (7%) were performed for biphasic mesotheliomas. For patients with CC0 resection, 5-year survival was 64.5 and 50.2% (median 7.8 and 6.8 years; p = 0.015) for epithelioid and biphasic mesotheliomas, respectively, while inclusion of CC1 resections in the analysis resulted in inferior 5-year survival of 62.9% and 41.6% (median 7.8 and 2.8 years; p = 0.0012), respectively. Incomplete CC2 resections for biphasic primaries resulted in a median survival of 4.3 months. Univariate analysis of the biphasic cohort indicated Peritoneal Cancer Index (PCI; p = 0.015), CC status of resection (p < 0.0001), and Ki67 (p = 0.04) as predictors of survival. Systemic chemotherapy before (p = 0.55) or after (p = 0.7) CRS/HIPEC did not influence survival. In multivariate analysis, only PCI (p = 0.03) and CC (p = 0.04) remained significant. CONCLUSIONS: Long-term survival is achievable in patients with low-volume biphasic mesothelioma after complete macroscopic cytoreduction. Biphasic peritoneal mesotheliomas should not be considered as an absolute contraindication for CRS/HIPEC if there is low-volume disease and if complete cytoreduction can be achieved.

Perioperative chemotherapy is not associated with improved survival in high-grade truncal sarcoma.

BACKGROUND: The treatment benefit of perioperative chemotherapy (CTX) for truncal soft tissue sarcoma (STS) is not well established. This study evaluates the association of CTX with survival for patients with resected primary high-grade truncal STS. MATERIALS AND METHODS: Adult patients with high-grade truncal STS who had curative-intent resection from 2000 to 2016 at seven U.S. institutions were evaluated retrospectively. Patients were stratified by receipt of CTX. Kaplan-Meier curves with log-rank tests were used to compare overall survival (OS) and recurrence-free survival. Logistic regression models were used to evaluate characteristics associated with OS. RESULTS: Of patients with primary high-grade truncal STS, 235 underwent curative-intent resections. The most common histology was undifferentiated pleomorphic sarcoma and mean tumor size was 7.8 cm. Thirty percent of the patients received CTX (n = 70). Among patients receiving CTX, 34% (n = 24) had neoadjuvant CTX, 44% (n = 31) adjuvant CTX, and 21% (n = 15) had neoadjuvant and adjuvant CTX. Patients receiving CTX were more likely to receive radiation (51% versus 34%, P = 0.01), have deep tumors (86% versus 73%, P = 0.037) and solid organ invasion (14% versus 3%, P = 0.001). On univariate analysis, patients who received CTX had worse OS (P < 0.01) and a trend toward worse recurrence-free survival (P = 0.08). Margin status was the only variable associated with improved OS on multivariate analysis (odds ratio 4.36, 95% confidence interval 1.56, 12.13, P < 0.01). CONCLUSIONS: In this multi-institutional retrospective analysis of resected high-grade truncal STS, receipt of perioperative CTX was not associated with improved OS, which may be related to selection bias. Microscopically negative margin status was the only independent factor associated with OS.