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.

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.

Clinical Impact of External Beam Radiotherapy for Surgically Resected Primary Retroperitoneal Liposarcoma.

INTRODUCTION: EORTC-62092 (STRASS) was a phase 3, randomized study that compared surgery alone versus surgery plus neoadjuvant radiotherapy (RT) for retroperitoneal sarcomas. RT was not associated with improved abdominal recurrence-free survival, the primary outcome measure, although on subanalysis, there may have been benefit for well-differentiated (WD) liposarcoma. This study investigated the real-world use and outcomes of RT (neoadjuvant and adjuvant) for the management of retroperitoneal liposarcoma. METHODS: We queried the National Cancer Database (NCDB) (2004-2017) for patients with nonmetastatic, primary retroperitoneal liposarcoma treated with resection with or without RT (n = 3911). Patients were stratified by treatment type and histology [WD (n = 2252), dedifferentiated (DD) (n = 1659)]. Propensity score (PS) matching was used before comparison of treatment groups. Overall survival (OS) was the primary outcome measure. RESULTS: Median follow-up time was 4.1 years, and median OS was 10.7 years. There was no association between RT and OS for either WDLPS or DDLPS cohorts. We performed a subgroup analysis of neoadjuvant RT only, similar to STRASS. For WDLPS after PS matching (n = 208), neoadjuvant RT was not associated with OS (hazard ratio [HR] 1.01, p = 0.0523) but was associated with longer postoperative hospital stay (p = 0.012). For DDLPS after PS matching (n = 290), neoadjuvant RT was not associated with OS (HR 1.02, p = 0.889). For both WD-LPS and DD-LPS, utilization of neoadjuvant RT was associated with treatment at high-volume (≥ 10 cases/year) and academic/network facilities. CONCLUSIONS: For primary retroperitoneal liposarcoma treated with surgical resection, radiotherapy was not associated with an overall survival benefit in this propensity-matched, adjusted analysis of the NCDB.

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.

Hypofractionated, 3-week, preoperative radiotherapy for patients with soft tissue sarcomas (HYPORT-STS): a single-centre, open-label, single-arm, phase 2 trial.

BACKGROUND: The standard preoperative radiotherapy regimen of 50 Gy delivered in 25 fractions for 5 weeks for soft tissue sarcomas results in excellent local control, with major wound complications occurring in approximately 35% of patients. We aimed to investigate the safety of a moderately hypofractionated, shorter regimen of radiotherapy, which could be more convenient for patients. METHODS: This single-centre, open-label, single-arm, phase 2 trial (HYPORT-STS) was done at a single tertiary cancer care centre (MD Anderson Cancer Center, Houston, TX, USA). We administered preoperative radiotherapy to a dose of 42·75 Gy in 15 fractions of 2·85 Gy/day for 3 weeks (five fractions per week) to adults (aged ≥18 years) with non-metastatic soft tissue sarcomas of the extremities or superficial trunk and an Eastern Cooperative Oncology Group performance status of 0-3. The primary endpoint was a major wound complication occurring within 120 days of surgery. Major wound complications were defined as those requiring a secondary operation, or operations, under general or regional anaesthesia for wound treatment; readmission to the hospital for wound care; invasive procedures for wound care; deep wound packing to an area of wound measuring at least 2 cm in length; prolonged dressing changes; repeat surgery for revision of a split thickness skin graft; or wet dressings for longer than 4 weeks. We analysed our primary outcome and safety in all patients who enrolled. We monitored safety using a Bayesian, one-arm, time-to-event stopping rule simulator comparing the rate of major wound complications at 120 days post-surgery among study participants with the historical rate of 35%. This trial is registered with ClinicalTrials.gov, NCT03819985, recruitment is complete, and follow-up continues. FINDINGS: Between Dec 18, 2018, and Jan 6, 2021, we assessed 157 patients for eligibility, of whom 120 were enrolled and received hypofractionated preoperative radiotherapy. At no time did the stopping rule computation indicate that the trial should be stopped early for lack of safety. Median postoperative follow-up was 24 months (IQR 17-30). Of 120 patients, 37 (31%, 95% CI 24-40) developed a major wound complication at a median time of 37 days (IQR 25-59) after surgery. No patient had acute radiation toxicity (during radiotherapy or within 4 weeks of the radiotherapy end date) of grade 3 or worse (Common Terminology Criteria for Adverse Events [CTCAE] version 4.0) or an on-treatment serious adverse event. Four (3%) of 115 patients had late radiation toxicity (≥6 months post-surgery) of at least grade 3 (CTCAE or Radiation Therapy Oncology Group/European Organisation for Research and Treatment of Cancer Late Radiation Morbidity Scoring Scheme): femur fractures (n=2), lymphoedema (n=1), and skin ulceration (n=1). There were no treatment-related deaths. INTERPRETATION: Moderately hypofractionated preoperative radiotherapy delivered to patients with soft tissue sarcomas was safe and could therefore be a more convenient alternative to conventionally fractionated radiotherapy. Patients can be counselled about these results and potentially offered this regimen, particularly if it facilitates care at a sarcoma specialty centre. Results on long-term oncological, late toxicity, and functional outcomes are awaited. FUNDING: The National Cancer Institute.

Experimental models of undifferentiated pleomorphic sarcoma and malignant peripheral nerve sheath tumor.

Undifferentiated pleomorphic sarcoma (UPS) and malignant peripheral nerve sheath tumor (MPNST) are aggressive soft tissue sarcomas that do not respond well to current treatment modalities. The limited availability of UPS and MPNST cell lines makes it challenging to identify potential therapeutic targets in a laboratory setting. Understanding the urgent need for improved treatments for these tumors and the limited cellular models available, we generated additional cell lines to study these rare cancers. Patient-derived tumors were used to establish 4 new UPS models, including one radiation-associated UPS-UPS271.1, UPS511, UPS0103, and RIS620, one unclassified spindle cell sarcoma-USC060.1, and 3 new models of MPNST-MPNST007, MPNST3813E, and MPNST4970. This study examined the utility of the new cell lines as sarcoma models by assessing their tumorigenic potential and mutation status for known sarcoma-related genes. All the cell lines formed colonies and migrated in vitro. The in vivo tumorigenic potential of the cell lines and corresponding xenografts was determined by subcutaneous injection or xenograft re-passaging into immunocompromised mice. USC060.1 and UPS511 cells formed tumors in mice upon subcutaneous injection. UPS0103 and RIS620 tumor implants formed tumors in vivo, as did MPNST007 and MPNST3813E tumor implants. Targeted sequencing analysis of a panel of genes frequently mutated in sarcomas identified TP53, RB1, and ATRX mutations in a subset of the cell lines. These new cellular models provide the scientific community with powerful tools for detailed studies of tumorigenesis and for investigating novel therapies for UPS and MPNST.

Real-world use of palbociclib monotherapy in retroperitoneal liposarcomas at a large volume sarcoma center.

Palbociclib has been evaluated in early phase trials for well-differentiated liposarcoma (WDLPS) and dedifferentiated liposarcoma (DDLPS) patients, with reported median progression-free survival (PFS) of 18 weeks. Here, we report on real-world use and surgical outcomes associated with palbociclib treatment. We retrospectively reviewed 61 consecutive patients with retroperitoneal WDLPS (n = 14) or DDLPS (n = 47) treated with palbociclib monotherapy between 1 March 2016 and 28 February 2021 at The University of Texas MD Anderson Cancer Center. At palbociclib initiation, median age was 64 (interquartile range [IQR] 56-72). In WDLPS and DDLPS cohorts, the median number of prior systemic treatments was 0 (IQR 0-0) and 2 (IQR 0-4), respectively. Median number of prior surgeries was 2 (WDLPS IQR 1-2.75) and 2 (DDLPS IQR 1-3). Median PFS was 9.2 (WDLPS IQR 3.9-21.9) and 2.6 months (DDLPS IQR 2.0-6.1), with median time on treatment of 7.4 months (WDLPS IQR 3.5-14.2) and 2.7 months (DDLPS IQR 2.0-5.7). Twelve patients ultimately underwent surgical resection. Resections were macroscopically complete (R0/R1) in half (n = 6/12), among whom only one patient experienced relapse after resection (median follow-up 7.5 months). All patients who underwent macroscopically incomplete resections progressed after surgery with median time to progression of 3.3 months (IQR 2.3-4.4). Surgery after palbociclib treatment was not associated with improved overall survival. Efficacy of palbociclib monotherapy for patients with advanced WDLPS and DDLPS is disappointing. While palbociclib may have been used to delay surgery, there was no clear benefit from treatment and few patients achieved prolonged tumor control.

Sentinel Lymph Node Biopsy and Formal Lymphadenectomy for Soft Tissue Sarcoma: A Single Center Experience of 86 Consecutive Cases.

BACKGROUND: Lymph node metastases (LNMs) are rare in patients with soft tissue sarcoma (STS), and there is limited evidence to guide clinical management. We describe our experience with sentinel lymph node biopsy (SLNB) and lymphadenectomy in STS patients. METHODS: A single-center, retrospective review was performed for patients with STS treated with SLNB and/or lymphadenectomy from 1994 to 2018. Clinicopathologic characteristics, multimodality treatment, regional/distant recurrence-free survival (RFS), and overall survival (OS) were examined. RESULTS: Eighty-six patients underwent SLNB (n = 34) and/or lymphadenectomy (n = 60) for STS. The most frequent histologic subtypes were epithelioid, clear cell, and undifferentiated pleomorphic sarcoma. Eight of 34 (23.5%) patients had a positive SLNB with 5-year OS of 71.4% compared with 71.9% for those with a negative SLNB. Eight of the 26 SLN-negative patients (30.8%) eventually developed nodal recurrence (n = 2) and/or (n = 6) distant metastasis with an estimated 5-year OS of 50%. Of patients undergoing lymphadenectomy, estimated 5-year OS was 44.6% and median RFS was 12 months. Eight (13.3%) had distant disease at time of lymphadenectomy, 20 (33.3%) developed distant recurrence after lymphadenectomy, and 6 (10%) developed regional-only recurrence. Patients with regional-only recurrence after lymphadenectomy had an estimated 5-year OS of 66.7% compared with 29.1% for those who recurred distantly. CONCLUSIONS: Patients with positive SLNB had similar survival to those with negative SLNB. Lymphadenectomy for isolated nodal disease is associated with poor RFS but reasonable 5-year OS when recurrence is regional-only. In STS, regional disease appears clinically distinct from distant metastatic disease and has better outcomes.

Sarculator is a Good Model to Predict Survival in Resected Extremity and Trunk Sarcomas in US Patients.

BACKGROUND: Sarculator is an online validated nomogram that predicts overall survival of patients with resected, primary extremity sarcomas. However, its ability to accurately predict outcomes in US patients with sarcoma is unknown. PATIENTS AND METHODS: Patients from the National Cancer Data Base (NCDB) (2006-2016) with resected stage I-III primary extremity or trunk sarcoma were included. Predicted overall survival (pOS) was calculated using the Sarculator algorithm, which includes patient age, tumor size (cm), grade (1-3), and histology, and compared with actual overall survival (aOS). Harrell's C-index was calculated to determine the discriminatory ability of Sarculator (0.7 = good, 0.8 = strong, 1.0 = perfect model), and calibration plots were created. RESULTS: In total, 9738 patients were included. Five-year pOS was 73.7% compared with aOS of 68.9%. The C-index for the entire cohort was 0.726. By stage, the C-index was 0.730 for stage I, 0.708 for stage II, and 0.679 for stage III. By histology, C-indices were highest for leiomyosarcoma (0.745), myxofibrosarcoma (0.722), and other histologies (0.721). By sociodemographic variables, Sarculator performed better for patients < 50 years (C-index 0.722), of other/unknown race (C-index 0.781), with private insurance (C-index 0.715), treated at a center other than a community cancer programs (C-index > 0.7), and with no comorbidities (C-index 0.716). Outcomes by zip code educational attainment and income were not markedly different (all C-indices > 0.7). CONCLUSIONS: Sarculator is overall a good predictor of aOS and useful tool for clinicians to aid in survival prognostication. However, clinicians should be aware of populations for whom Sarculator's predictions may be less accurate. Future work could focus on enhancing the Sarculator algorithm specifically for US patients by including demographic variables.

Evaluating the Impact of Surveillance Follow-Up Intervals in Patients Following Resection of Primary Well-Differentiated Liposarcoma of the Retroperitoneum.

BACKGROUND: Resection of recurrent retroperitoneal well-differentiated liposarcoma (RP-WDLPS) is unlikely to result in cure. Thus, most clinicians delay surgery after recurrence until symptom intolerance or increasing rate of disease progression. The aim of this study was to determine whether longer surveillance intervals in this population would impact outcomes or delay treatment in those who recur. METHODS: A retrospective review of patients with primary RP-WDLPS who underwent resection between April 1996 and April 2017 and surveillance at MDACC (n = 91) was performed. RESULTS: Median age at diagnosis of primary RP-WDLPS was 61 years; median tumor size was 30 cm. Complete resection was achieved in 85 (93.4%) patients. Among patients who underwent complete resection, recurrence occurred in 53 (60.2%) with median time to recurrence of 27.0 months. Thirty-six (69.6%) of these patients underwent resection of recurrent disease at a median 40.2 months from primary tumor resection. Surveillance imaging at 4-month (vs 3-month) intervals would not have impacted recurrence management in 84 (95.5%) patients; imaging at 6-month (vs 3-month) intervals would not have impacted management of recurrence in 80 (90.9%). CONCLUSIONS: Recurrence was common, often occurring beyond the early postoperative period following primary RP-WDLPS resection. More frequent surveillance imaging (q3-4 vs q6 months) in the first 2 years following primary RP-WDLPS resection may not significantly impact timing of surgery or systemic therapy for recurrence. If longer surveillance intervals were shown to be safe with equivalent outcomes in prospective studies, the resulting change in practice could lead to decreased anxiety and cost for patients and healthcare systems.

Enhancer reprogramming in PRC2-deficient malignant peripheral nerve sheath tumors induces a targetable de-differentiated state.

Malignant peripheral nerve sheath tumors (MPNSTs) are soft tissue sarcomas that frequently harbor genetic alterations in polycomb repressor complex 2 (PRC2) components-SUZ12 and EED. Here, we show that PRC2 loss confers a dedifferentiated early neural-crest phenotype which is exclusive to PRC2-mutant MPNSTs and not a feature of neurofibromas. Neural crest phenotype in PRC2 mutant MPNSTs was validated via cross-species comparative analysis using spontaneous and transgenic MPNST models. Systematic chromatin state profiling of the MPNST cells showed extensive epigenomic reprogramming or chromatin states associated with PRC2 loss and identified gains of active enhancer states/super-enhancers on early neural crest regulators in PRC2-mutant conditions around genomic loci that harbored repressed/poised states in PRC2-WT MPNST cells. Consistently, inverse correlation between H3K27me3 loss and H3K27Ac gain was noted in MPNSTs. Epigenetic editing experiments established functional roles for enhancer gains on DLX5-a key regulator of neural crest phenotype. Consistently, blockade of enhancer activity by bromodomain inhibitors specifically suppressed this neural crest phenotype and tumor burden in PRC2-mutant PDXs. Together, these findings reveal accumulation of dedifferentiated neural crest like state in PRC2-mutant MPNSTs that can be targeted by enhancer blockade.

Certain risk factors for patients with desmoid tumors warrant reconsideration of local therapy strategies.

BACKGROUND: The objective of this study was to evaluate treatment outcomes for patients with desmoid tumors (DTs) receiving local therapy with surgery alone, radiation therapy (RT) alone, or combined modality therapy (RT and surgery). METHODS: This was a cross-sectional cohort study of 412 patients with nonmesenteric DTs who received local therapy at the authors' institution between 1965 and 2018. RESULTS: The median follow-up time was 95 months (range, 1-509 months). Local recurrence occurred in 127 patients (31%) at a median time of 21 months (interquartile range, 12-38 months). The 5-year local control (LC) rate was 67%. Patient or tumor factors that were significantly associated with poorer 5-year LC in a multivariable analysis included an age ≤ 30 years (57% vs 75% for an age > 30 years; hazard ratio [HR], 1.73; P = .004), an extremity location (57% vs 71% for a nonextremity location; HR, 1.77; P = .004), and large tumors (59% for >10 cm [HR, 2.17; P = .004] and 65% for 5.1-10 cm [HR, 1.71; P = .02] vs 76% for ≤5 cm). Subset analyses of these high-risk patients revealed no local therapy strategy to be superior for young patients ≤ 30 years old (HR for surgery, 1.42; P = .33; HR for RT, 1.36; P = .38) or for large tumors > 10 cm (HR for surgery, 1.55; P = .46; HR for RT, 0.91; P = .91). However, for patients with extremity tumors, surgery alone was significantly associated with inferior LC (HR for surgery, 5.15; P < .001; HR for RT, 1.51; P = .38). CONCLUSIONS: Local therapy provides durable tumor control in the majority of patients with DTs. However, young patients, patients with an extremity location, and patients with large tumors are at increased risk of recurrence. When active treatment is indicated, systemic therapy should perhaps be considered as a first-line option in these high-risk subsets. Prospective multi-institutional studies evaluating this strategy are warranted.

Rare osteosarcoma cell subpopulation protein array and profiling using imaging mass cytometry and bioinformatics analysis.

BACKGROUND: Single rare cell characterization represents a new scientific front in personalized therapy. Imaging mass cytometry (IMC) may be able to address all these questions by combining the power of MS-CyTOF and microscopy. METHODS: We have investigated this IMC method using < 100 to up to 1000 cells from human sarcoma tumor cell lines by incorporating bioinformatics-based t-Distributed Stochastic Neighbor Embedding (t-SNE) analysis of highly multiplexed IMC imaging data. We tested this process on osteosarcoma cell lines TC71, OHS as well as osteosarcoma patient-derived xenograft (PDX) cell lines M31, M36, and M60. We also validated our analysis using sarcoma patient-derived CTCs. RESULTS: We successfully identified heterogeneity within individual tumor cell lines, the same PDX cells, and the CTCs from the same patient by detecting multiple protein targets and protein localization. Overall, these data reveal that our t-SNE-based approach can not only identify rare cells within the same cell line or cell population, but also discriminate amongst varied groups to detect similarities and differences. CONCLUSIONS: This method helps us make greater inroads towards generating patient-specific CTC fingerprinting that could provide an accurate tumor status from a minimally-invasive liquid biopsy.

The degree of sclerosis is associated with prognosis in well-differentiated liposarcoma of the retroperitoneum.

BACKGROUND AND OBJECTIVES: Well-differentiated liposarcomas (WDL) are often partly composed of sclerotic tissue, however, the amount varies widely between tumors, and its prognostic significance is unknown. We hypothesized that tumors with more sclerosis would behave more aggressively. METHODS: Primary retroperitoneal WDL from 29 patients resected at our institution with follow-up were histologically evaluated by soft tissue pathologists blinded to outcome. Tumors with ≥ 10% sclerosis were designated "sclerotic" while tumors with < 10% sclerosis were designated as "minimally sclerotic". Cellular and dedifferentiated tumors were excluded. Clinical parameters and radiologic assessments on computed tomography (CT) were recorded. RESULTS: Histological evaluation identified 13 minimally sclerotic WDL and 16 sclerotic WDL. Median follow-up was 9 years (range, 3-20). Median recurrence-free survival (RFS) and median overall survival (OS) were 6.16 and 13.9 years, respectively. Compared with patients with sclerotic WDL, those with minimally sclerotic WDL had superior RFS (HR = 0.17 [95% CI, 0.06-0.53], P = .002) and OS (log-rank test, P = .002). Sclerotic WDL exhibited higher Houndsfield Units than minimally sclerotic WDL (26 vs 1, P = .040). CONCLUSIONS: Minimally sclerotic WDL were associated with more favorable outcome compared with sclerotic tumors. Assessment of sclerosis in WDL is likely a useful prognostic marker.

Treatment at low-volume hospitals is associated with reduced short-term and long-term outcomes for patients with retroperitoneal sarcoma.

BACKGROUND: Retroperitoneal sarcomas (RPS) are rare tumors for which complete surgical resection remains the mainstay of treatment. The objective of the current study was to determine the impact of hospital case volume on outcomes in patients with RPS. METHODS: A total of 6950 patients with primary RPS who underwent surgical resection were identified from the National Cancer Data Base (1998-2011). Treating hospitals were classified by annual case volume; low-volume hospitals (LVHs) and high-volume hospitals (HVHs) were defined as those with ≤10 cases per year and >10 cases per year, respectively. Overall survival (OS) was compared using Kaplan-Meier curves. Cox proportional hazard models were created to compare risks. RESULTS: Of the 1131 reporting hospitals, the majority (1127 hospitals; 99.6%) were LVHs treating the majority of patients (6270 patients; 90.2%). Patients treated at LVHs were more likely to have lower grade and smaller tumors, receive radiotherapy, and undergo incomplete macroscopic (R2) resection. Patients treated at HVHs had lower 30-day readmission rates (1.8% vs 3.4%; P<.001), 30-day (1.9% vs 3.1%; P=.004) and 90-day (3.2% vs 5.7%; P=.007) mortality, longer median OS (76.2 months vs 64.2 months; P<.001), and higher 5-year OS rates (58% vs 52%; P<.001). After controlling for age, sex, insurance status, tumor size, tumor grade, surgical resection margin status, and radiotherapy administration, treatment at an HVH was found to be independently associated with a reduced risk of death (hazard ratio, 0.77; 95% confidence interval, 0.65-0.91 [P=.003]). CONCLUSIONS: Primary RPS are rare tumors, and to our knowledge few surgeons and institutions have significant experience and expertise in their multidisciplinary management and surgical resection. Although additional studies are needed, patient outcomes may be impacted by the case volume and expertise of the treating facility.

Salvage Surgery for Recurrent Retroperitoneal Well-Differentiated Liposarcoma: Early Reoperation may not Provide Benefit.

PURPOSE: Current evidence regarding salvage resection for recurrent retroperitoneal (RP) sarcomas generally lacks detailed histology-specific analyses, but the aggressiveness of these tumors varies widely by histology. We investigated associations between timing and extent of salvage surgery and survival outcomes in patients with recurrent RP well-differentiated liposarcoma (WDLPS). METHODS: The University of Texas MD Anderson Cancer Center Surgical Oncology sarcoma database was reviewed to identify patients with RP WDLPS who underwent surgical resection for first recurrent disease (salvage surgery) in 1995-2015. Medical records were retrospectively reviewed to identify factors associated with overall survival and disease-free survival. RESULTS: We identified 52 patients who underwent salvage surgery for RP WDLPS for first local recurrence; 28 (54%) underwent salvage surgery within 6 months after recurrence. Concomitant organ resections were performed in 32 (62%) patients, 4 (13%) of whom had pathologic invasion of resected organs. After R0/R1 resections (n = 45), 38 (84%) experienced a second local recurrence. Multivariable analyses revealed that organ invasion at the primary surgery [hazard ratio (HR) 13.08; p = 0.005] and disease-free interval < 1 year (HR 3.64; p = 0.044) were associated with shorter overall survival. Recurrence-to-salvage interval < 6 months was associated with shorter disease-free survival (HR 2.18; p = 0.025). Concomitant organ resection was associated with a longer hospital stay: ≥ 14 days (odds ratio 21.58; p = 0.007). CONCLUSIONS: Early salvage surgery may not always be the best approach for recurrent RP WDLPS patients. Because organ invasion is rare among recurrent RP WDLPS patients and concomitant organ resection is associated with a longer hospital stay, preservation of uninvolved organs should be considered.

Comparative Performance of the 7th and 8th Editions of the American Joint Committee on Cancer Staging Systems for Soft Tissue Sarcoma of the Trunk and Extremities.

BACKGROUND: The 8th edition American Joint Committee on Cancer (AJCC) staging for soft tissue sarcomas of the trunk/extremities divides T stage into four categories and upstages nodal disease to stage IV. We used the National Cancer Database (NCDB) to evaluate the prognostic power of the new system. METHODS: A total of 26,144 patients were identified from the NCDB from 2004 to 2013. Overall survival (OS) was compared using Kaplan-Meier and Cox proportional hazard models. RESULTS: Including T3 (10 cm > × >15 cm) and T4 (> 15 cm) categories resulted in an increased number of patients classified as stage III (5120 as IIIA [19.6%] and 4280 as IIIB [16.4%], vs. 7882 [30.1%] previously), and there was a small increase in the number of patients classified as stage IV (2776 [10.6%], vs. 2565 [9.8%] previously). In the 7th edition, the hazard ratio (HR) for death increases with stage, with large incremental increases between stages II-III and III-IV. In the 8th edition, the HR for death demonstrates smaller incremental increases between each stage. Five-year OS for 7th edition T1 and T2 patients was 78.8 and 58.8% (p < 0.01), respectively, versus 62.6, 53.5, and 56.1% for T2, T3, and T4 patients, respectively, in the 8th edition (p < 0.01). Patients with isolated nodal disease (n = 211) had a better 5-year OS than those with distant metastases (33.1% vs. 12.4%, p < 0.001). CONCLUSIONS: The AJCC 8th edition uses T stage to more accurately stratify OS in patients with large, high-grade tumors (T3/4) compared with those patients with T2 tumors, which facilitates risk assessment. The distinction between T3 and T4 may not be clinically significant. Patients with metastatic nodal disease have a survival outcome intermediate to those with stages III and IV disease.