New Sarculator Prognostic Nomograms for Patients With Primary Retroperitoneal Sarcoma: Case Volume Does Matter.

OBJECTIVE: To update the current Sarculator retroperitoneal sarcoma (RPS) prognostic nomograms considering the improvement in patient prognosis and the case volume effect. BACKGROUND: Survival of patients with primary RPS has been increasing over time, and the volume-outcome relationship has been well recognized. Nevertheless, the specific impact on prognostic nomograms is unknown. METHODS: All consecutive adult patients with primary localized RPS treated at 8 European and North American sarcoma reference centers between 2010 and 2017 were included. Patients were divided into 2 groups: high-volume centers (HVC, ≥13 cases/year) and low-volume centers (LVC, <13 cases/year). Primary end points were overall survival (OS) and disease-free survival (DFS). Multivariable analyses for OS and DFS were performed. The nomograms were updated by recalibration. Nomograms performance was assessed in terms of discrimination (Harrell C index) and calibration (calibration plot). RESULTS: The HVC and LVC groups comprised 857 and 244 patients, respectively. The median annual primary RPS case volume (interquartile range) was 24.0 in HVC (15.0-41.3) and 9.0 in LVC (1.8-10.3). Five-year OS was 71.4% (95% CI: 68.3%-74.7%) in the HVC cohort and 63.3% (56.8%-70.5%) in the LVC cohort ( P =0.012). Case volume was associated with both OS (LVC vs. HVC hazard ratio 1.40, 95% CI: 1.08-1.82, P =0.011) and DFS (hazard ratio 1.93, 95% CI: 1.57-2.37, P <0.001) at multivariable analyses. When applied to the study cohorts, the Sarculator nomograms showed good discrimination (Harrell C index between 0.68 and 0.73). The recalibrated nomograms showed good calibration in the HVC group, whereas the original nomograms showed good calibration in the LVC group. CONCLUSIONS: New nomograms for patients with primary RPS treated with surgery at high-volume versus low-volume sarcoma reference centers are available in the Sarculator app.

Distribution and Rate of Myxoid Liposarcoma Spine Metastases: Impact on Surveillance Imaging.

BACKGROUND: Myxoid liposarcoma (LPS) has a unique tendency to spread to extrapulmonary sites, including osseous sites such as the spine, and adjacent sites such as the paraspinous tissue. No clear consensus exists to guide the approach to imaging in these patients. OBJECTIVE: The aim of this study was to investigate the rate and distribution of spine metastases in patients with myxoid LPS and detection modality. METHODS: Records of all patients with myxoid LPS evaluated at our sarcoma center were retrospectively reviewed. Disease patterns and imaging modality utilization were analyzed. RESULTS: Between 2000 and 2020, 164 patients with myxoid LPS were identified. The majority (n = 148, 90%) presented with localized disease, with half (n = 82, 50%) of all patients developing metastases or recurrence during their disease course. With a median follow-up of 69.2 months, spine/paraspinous metastases developed in 38 patients (23%), of whom 35 (92%) already had synchronous, non-spine metastases. Spine disease was only visible on magnetic resonance imaging (MRI), as opposed to other imaging modalities, for over one-quarter of patients with spine metastases (n = 10). For patients with metastatic disease, spine metastases were associated with worse median overall survival (2.1 vs. 8.7 years, p < 0.001). CONCLUSION: Spine metastases occurred in nearly one-quarter of patients with myxoid LPS and represented an advanced disease state, as they primarily presented in the setting of synchronous, non-spine metastases, and were associated with worse overall survival. Routine surveillance with spine MRI in patients with localized disease likely provides no benefit but may be considered in those with known metastatic disease.

Management of Recurrent Retroperitoneal Sarcoma.

Recurrence after resection of retroperitoneal sarcoma is common and varies by histological subtype. Pattern of recurrence is similarly affected by histology (e.g., well-differentiated liposarcoma is more likely to recur locoregionally, whereas leiomyosarcoma is more likely to develop distant metastases). Radiotherapy may provide effective locoregional control in limited circumstances and the data on the impact of chemotherapy are scant. Surgery for locally recurrent disease is associated with the greatest survival benefit; however, data are retrospective and from a highly selected subgroup of patients. Limited retrospective data have also suggested a survival association with the resection of limited distant metastases. Given the complexity of these patients, multidisciplinary evaluation at a high-volume sarcoma center is critical.

Sentinel Lymph Node Biopsy for Extremity and Truncal Soft Tissue Sarcomas: A Systematic Review of the Literature.

BACKGROUND: Regional lymph node metastasis (RLNM) occurs infrequently in patients with soft tissue sarcoma (STS), although certain STS subtypes have a higher propensity for RLNM. The identification of RLNM has significant implications for staging and prognosis; however, the precise impact of node-positive disease on patient survival remains a topic of controversy. Although the benefits of sentinel lymph node biopsy (SLNB) are well documented in patients with melanoma and breast cancer, whether this procedure offers a benefit in STS is controversial. METHODS: A systematic literature search was performed and articles reviewed to determine if SLNB in patients with extremity/truncal STS impacts disease-free or overall survival. RESULTS: Six studies were included. Rates of sentinel lymph node positivity were heterogeneous (range 4.3-50%). The impact of SLNB on patient outcomes remains unclear. The overall quality of available evidence was low, as assessed by the Grading of Recommendations, Assessment, Development, and Evaluation system. CONCLUSIONS: The literature addressing the impact of nodal basin evaluation on the staging and management of patients with extremity/truncal STS is confounded by heterogeneous patient cohorts and clinical practices. Multicenter prospective studies are warranted to determine the true incidence of RLNM and whether SLNB could benefit patients with clinically occult RLNM at diagnosis.

Retrospective Analysis of Retroperitoneal-Abdominal-Pelvic Ganglioneuromas: An International Study by the Transatlantic Australasian Retroperitoneal Sarcoma Working Group (TARPSWG).

OBJECTIVE: The Transatlantic Australasian Retroperitoneal Sarcoma Working Group conducted a retrospective study on the disease course and clinical management of ganglioneuromas. BACKGROUND: Ganglioneuromas are rare tumors derived from neural crest cells. Data on these tumors remain limited to case reports and single-institution case series. METHODS: Patients of all ages with pathologically confirmed primary retroperitoneal, intra-abdominal, and pelvic ganglioneuromas between January 1, 2000, and January 1, 2020, were included. We examined demographic, clinicopathologic, and radiologic characteristics, as well as clinical management. RESULTS: Overall, 328 patients from 29 institutions were included. The median age at diagnosis was 37 years with 59.1% of patients being female. Symptomatic presentation comprised 40.9% of cases, and tumors were often located in the extra-adrenal retroperitoneum (67.1%). At baseline, the median maximum tumor diameter was 7.2 cm. One hundred sixteen (35.4%) patients underwent active surveillance, whereas 212 (64.6%) patients underwent resection with 74.5% of operative cases achieving an R0/R1 resection. Serial tumor evaluations showed that malignant transformation to neuroblastoma was rare (0.9%, N=3). Tumors undergoing surveillance had a median follow-up of 1.9 years, with 92.2% of ganglioneuromas stable in size. With a median follow-up of 3.0 years for resected tumors, 84.4% of patients were disease free after resections, whereas recurrences were observed in 4 (1.9%) patients. CONCLUSIONS: Most ganglioneuromas have indolent disease courses and rarely transform to neuroblastoma. Thus, active surveillance may be appropriate for benign and asymptomatic tumors particularly when the risks of surgery outweigh the benefits. For symptomatic or growing tumors, resection may be curative.

Preoperative Radiotherapy in Patients With Primary Retroperitoneal Sarcoma: EORTC-62092 Trial (STRASS) Versus Off-trial (STREXIT) Results.

OBJECTIVE: The aim of the present study was to compare the effect of radiotherapy (RT) on abdominal recurrence-free survival (ARFS) in patients with primary retroperitoneal sarcoma treated in the EORTC-STBSG-62092 (STRASS) phase 3 randomized controlled trial (STRASS cohort) and off-trial (STREXIT cohort) and to pool STRASS and STREXIT data to test the hypothesis that RT improves ARFS in patients with liposarcoma. BACKGROUND: The STRASS trial did not show any difference in ARFS between patients treated with preoperative radiotherapy+surgery (RT+S) versus surgery alone (S). METHODS: All consecutive adult patients not enrolled in STRASS and underwent curative-intent surgery for a primary retroperitoneal sarcoma with or without preoperative RT between 2012 and 2017 (STRASS recruiting period) among ten STRASS-recruiting centres formed the STREXIT cohort. The effect of RT in STREXIT was explored with a propensity score (PS)-matching analysis. Primary endpoint was ARFS defined as macroscopically incomplete resection or abdominal recurrence or death of any cause, whichever occurred first. RESULTS: STRASS included 266 patients, STREXIT included 831 patients (727 after excluding patients who received preoperative chemotherapy, 202 after 1:1 PS-matching). The effect of RT on ARFS in STRASS and 1:1 PS-matched STREXIT cohorts, overall and in patients with liposarcoma, was similar. In the pooled cohort analysis, RT administration was associated with better ARFS in patients with liposarcoma [N=321, hazard ratio (HR), 0.61; 95% confidence interval (CI), 0.42-0.89]. In particular, patients with well-differentiated liposarcoma and G1-2 dedifferentiated liposarcoma (G1-2 DDLPS, n=266) treated with RT+S had better ARFS (HR, 0.63; 95% CI, 0.40-0.97) while patients with G3 DDLPS and leiomyosarcoma had not. At the current follow-up, there was no association between RT and overall survival or distant metastases-free survival. CONCLUSIONS: In this study, preoperative RT was associated with better ARFS in patients with primary well-differentiated liposarcoma and G1-2 DDLPS.

Association of Liver Resection and Visiting More Than One Commission on Cancer Hospital for Colorectal Cancer With Liver Metastasis.

INTRODUCTION: Despite the advances in treatment, there are low rates of liver metastasectomy for colorectal cancer with liver metastasis (CRLM) in the United States. The aim of this study was to investigate the association between likelihood of liver metastasectomy for CRLM and seeking care at >1 versus 1 Commission on Cancer (CoC) hospital. METHODS: We performed a retrospective analysis of the National Cancer Database (2011-2017) for patients with CRLM. Patients were grouped based on seeking care at 1 CoC hospital or >1 CoC hospital. An adjusted multivariable Poisson regression interaction analysis was used to evaluate likelihood of liver metastasectomy for CRLM according to race and whether care was sought at >1 CoC hospital. RESULTS: We identified 25,956 patients with CRLM without extra-hepatic disease. 23,088 (89.0%) patients visited 1 CoC hospital and 2868 (11.1%) visited >1 CoC hospital. Black patients were less likely to seek care at >1 CoC hospital (relative risk [RR] 0.68, confidence intervalCI 0.60-0.76, P < 0.001). Undergoing liver metastasectomy was associated with higher likelihood of seeking care at >1 CoC hospital (RR 1.27, CI 1.26-1.52, P < 0.001). Among patients who sought care at >1 CoC hospital, there was no significant difference between White and Black patients undergoing liver metastasectomy (RR 0.86, 95% CI 0.71-1.04, P = 0.11). CONCLUSIONS: Patients with CRLM who sought care at >1 CoC hospital were more likely to undergo a liver metastasectomy. Among White and Black patients who sought care at >1 CoC hospital, there was no difference in likelihood of undergoing a liver metastasectomy.

Management of Locally Recurrent Retroperitoneal Sarcoma in the Adult: An Updated Consensus Approach from the Transatlantic Australasian Retroperitoneal Sarcoma Working Group.

BACKGROUND: Surgery is the mainstay of treatment for retroperitoneal sarcoma (RPS), but local recurrence is common. Biologic behavior and recurrence patterns differ significantly among histologic types of RPS, with implications for management. The Transatlantic Australasian RPS Working Group (TARPSWG) published a consensus approach to primary RPS, and to complement this, one for recurrent RPS in 2016. Since then, additional studies have been published, and collaborative discussion is ongoing to address the clinical challenges of local recurrence in RPS. METHODS: An extensive literature search was performed, and the previous consensus statements for recurrent RPS were updated after review by TARPSWG members. The search included the most common RPS histologic types: liposarcoma, leiomyosarcoma, solitary fibrous tumor, undifferentiated pleomorphic sarcoma, and malignant peripheral nerve sheath tumor. RESULTS: Recurrent RPS management was evaluated from diagnosis to follow-up evaluation. For appropriately selected patients, resection is safe. Nomograms currently are available to help predict outcome after resection. These and other new findings have been combined with expert recommendations to provide 36 statements, each of which is attributed a level of evidence and grade of recommendation. In this updated document, more emphasis is placed on histologic type and clarification of the intent for surgical treatment, either curative or palliative. Overall, the fundamental tenet of optimal care for patients with recurrent RPS remains individualized treatment after multidisciplinary discussion by an experienced team with expertise in RPS. CONCLUSIONS: Updated consensus recommendations are provided to help guide decision-making for treatment of locally recurrent RPS and better selection of patients who would potentially benefit from surgery.

Use of Neoadjuvant Imatinib to Facilitate Minimally Invasive Resection of Gastric Gastrointestinal Stromal Tumors.

BACKGROUND: Neoadjuvant imatinib is used to downstage surgery for large and/or unfavorably located gastric gastrointestinal stromal tumors (GISTs), but data regarding minimally invasive surgery (MIS) after neoadjuvant imatinib are limited. PATIENTS AND METHODS: We analyzed patients undergoing resection of nonmetastatic primary gastric GISTs larger than or equal to 4.5 cm in diameter at our institution between 2009 and 2020, as no tumors below this size received neoadjuvant imatinib. RESULTS: We identified 71 patients, 43 of whom (61%) received neoadjuvant imatinib. Patients receiving neoadjuvant imatinib had larger tumors at diagnosis [median diameter 8.6 cm (range 4.5-25 cm) versus 5.9 cm (range 4.5-11 cm), p < 0.01]. After a median 7.2 months of imatinib, tumors shrank by a median 34% in diameter, such that there was no longer a significant size difference at time of surgery between groups (median 6.3 cm versus 5.9 cm, p = 0.69). Of 29 patients for whom neoadjuvant imatinib was used to facilitate MIS, 21 (72%) underwent successful MIS, which accounted for 49% of the entire neoadjuvant cohort. In a multivariable regression model, smaller tumor size at time of surgery was predictive of successful MIS, but tumor location was not. CONCLUSIONS: Neoadjuvant imatinib caused significant tumor shrinkage, and MIS was successful in 72% of cases for which neoadjuvant imatinib was intended to facilitate it. Smaller tumor size at time of surgery, but not tumor location, was associated with successful MIS, which may help inform patient selection for neoadjuvant imatinib.

Association between race, hospital volume of major liver surgery, and access to metastasectomy for colorectal liver metastasis.

BACKGROUND: Previous studies have demonstrated that non-White patients with colorectal liver metastasis (CRLM) were significantly less likely to undergo liver metastasectomy compared to White patients. The aim of this study is to evaluate differences in access to liver metastasectomy for CRLM according to race and hospital-year volume of liver surgery (HVLS). METHODS: The National Cancer Database (2011-2017) was used to identify patients with CRLM. Hospitals were stratified into quartiles according to HVLS. An adjusted Poisson regression model was used to evaluate the interaction between race and HVLS and access to liver metastasectomy. RESULTS: We identified 27,340 patients with CRLM. Non-White patients were less likely to undergo a liver metastasectomy compared to White patients (RR 0.87, 95% CI 0.82-0.91, p < 0.001). This racial disparity persisted at the highest quartile HVLS hospitals. CONCLUSIONS: Receiving cancer care at hospitals with the highest HVLS did not translate into equal access to liver metastasectomy for non-White patients with CRLM.

Socioeconomic Disparities in Pancreas Cancer Resection and Survival in the Veterans Health Administration.

BACKGROUND: Disparities based on socioeconomic factors such as race, ethnicity, marital status, and insurance status are associated with pancreatic cancer resection, but these disparities are usually not observed for survival after resection. It is unknown if there are disparities when patients undergo their treatment in a non-fee-for-service, equal-access healthcare system such as the Veterans Health Administration (VHA). METHODS: Patients having T1-T3 M0 pancreatic adenocarcinoma diagnosed between 2006 and 2017 were identified from the VHA Corporate Data Warehouse. Socioeconomic, demographic, and tumor variables associated with resection and survival were assessed. RESULTS: In total, 2580 patients with early-stage pancreatic cancer were identified. The resection rate was 36.5%. Surgical resection was independently associated with younger age [odds ratio (OR) 0.94, p < 0.001], White race (OR 1.35, p = 0.028), married status (OR 1.85, p = 0.001), and employment status (retired vs. unemployed, OR 1.41, p = 0.008). There were no independent associations with Hispanic ethnicity, geographic region, or Social Deprivation Index. Resection was associated with significantly improved survival (median 21 vs. 8 months, p = 0.001). Among resected patients, survival was independently associated with younger age (HR 1.019, p = 0.002), geographic region (South vs. Pacific West, HR 0.721, p = 0.005), and employment (employed vs. unemployed, HR 0.752, p = 0.029). Race, Hispanic ethnicity, marital status, and Social Deprivation Index were not independently associated with survival after resection. CONCLUSIONS: Race, marital status, and employment status are independently associated with resection of pancreatic cancer in the VHA, whereas geographic region and employment status are independently associated with survival after resection. Further studies are warranted to determine the basis for these inequities.

Associations of gender, race, and ethnicity with disparities in short-term adverse outcomes after pancreatic resection for cancer.

BACKGROUND: Several studies have identified disparities in pancreatic cancer treatment associated with gender, race, and ethnicity. There are limited data examining disparities in short-term adverse outcomes after pancreatic resection for cancer. The aim of this study is to evaluate associations of gender, race, and ethnicity with morbidity and mortality after pancreatic resection for malignancy. METHODS: The American College of Surgeons National Surgical Quality Improvement database was retrospectively reviewed. The χ2 test and Student's t-test were used for univariable analysis and hierarchical logistic regression for multivariable analysis. RESULTS: Morbidity and major morbidity after pancreaticoduodenectomy are associated with male gender, Asian race, and Hispanic ethnicity, whereas 30-day mortality is associated with the male gender. Morbidity and major morbidity after distal pancreatectomy are associated with the male gender. Morbidity after pancreaticoduodenectomy is independently associated with male gender, Asian race, and Hispanic ethnicity; major morbidity is independently associated with male gender and Asian race, and mortality is independently associated with Hispanic ethnicity. CONCLUSIONS: Gender, race, and ethnicity are independently associated with morbidity after pancreaticoduodenectomy for cancer; gender and race are independently associated with major morbidity; and ethnicity is independently associated with mortality. Further studies are warranted to determine the basis of these associations.

Longitudinal prognostication in retroperitoneal sarcoma survivors: Development and external validation of two dynamic nomograms.

PURPOSE: The aim of this study was to create and validate dynamic nomograms to predict overall survival (OS) and disease-free survival (DFS) at different time points during follow-up in patients who had undergone resection of primary retroperitoneal sarcoma (RPS). METHODS: Patients with primary RPS operated upon between 2002 and 2017 at four and six referral centres comprised the development and external validation cohorts, respectively. Landmark analysis and multivariable Cox models were used to develop dynamic nomograms. Variables were selected using two backward procedures based on the Akaike information criterion. The prediction window was fixed at 5 years. Nomogram performances were tested in terms of calibration and discrimination on the development and validation cohorts. RESULTS: Development and validation cohorts totalled 1357 and 487 patients (OS analysis), and 1309 and 452 patients (DFS analysis), respectively. The final OS model included age, landmark time (TLM), tumour grade, completeness of resection and occurrence of local/distant recurrence. The final DFS model included TLM, histologic subtype, tumour size, tumour grade, multifocality and the interaction terms between TLM and size, grade and multifocality. For OS, Harrell C indices were higher than 0.7 in both cohorts, indicating very good discriminative capability. For DFS, Harrell C indices were between 0.64 and 0.72 in the development cohort and 0.62 and 0.68 in the validation cohort. Calibration plots showed good agreement between predicted and observed outcomes. CONCLUSION: Validated nomograms are available to predict the 5-year OS and DFS probability at different time points throughout the first 5 years of follow-up in RPS survivors.