VIM::KMT2A-rearranged sarcomas: A report of two new cases confirming an entity with distinct histologic features.

The recently described KMT2A-rearranged sarcomas are rare emerging entities where the KMT2A gene fuses with YAP1 and, less commonly, VIM, resulting in two distinct morphologies. Unlike the sclerosing epithelioid fibrosarcoma-like features that characterize tumors with KMT2A::YAP1 fusions, VIM::KMT2A-rearranged sarcomas are more uniformly cellular and lack the extensively sclerotic background seen in the former. Most tumors behave aggressively with metastases on presentation. Here, we describe the clinicopathologic and molecular findings in two additional cases of VIM::KMT2A rearranged sarcomas that arose in the deep soft tissues of adult males. Both tumors were composed of hypercellular fascicles of uniform spindle cells with pale eosinophilic cytoplasm and ovoid nuclei. The stroma had scant delicate collagen with occasional thin-walled ectatic blood vessels and perivascular hyalinization. Immunohistochemical studies showed an unspecific staining pattern with diffuse positivity for CD99 and BCL2 and variable staining for S100 protein. RNA-sequencing detected the presence of VIM::KMT2A gene fusion involving VIM exon 4 and KMT2A exon 2 in both cases. Sarcomas with VIM::KMT2A gene fusions seem to have sufficient morphologic features to warrant distinction from KMT2A-rearranged sarcomas with YAP1 partner. Without the benefit of molecular testing, these tumors pose a diagnostic challenge due to their lack of specific immunohistochemical profile and great morphologic overlap with other monomorphic spindle cell neoplasms.

Outcome After Surgical Treatment of Dermatofibrosarcoma Protuberans (DFSP): Does it Require Extensive Follow-up and What is an Adequate Resection Margin?

INTRODUCTION: Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous tumour of indeterminate malignant potential. The mainstay treatment for DFSP is surgical resection. Given the reported high local recurrence rate, the ideal resection margin for DFSP is unclear. The purpose of this study was to ascertain the local recurrence and metastatic rate of DFSP and DFSP with fibrosarcomatous degeneration (FS-DFSP), with specific attention to margin status in an attempt to address the issue of margin adequacy. METHODS: Patients treated for DFSP at a single sarcoma centre were identified from a prospective database. DFSP and FS-DFSP patients with and without prior surgery were included. Patients were followed after surgery to monitor complications, local recurrence and metastasis. RESULTS: The study included 200 patients: 166 patients with DFSP and 34 patients with FS-DFSP. In the DFSP group, nine patients (5.4%) had positive margins, one case (0.6%) developed local recurrence (LR) and no patients developed distant metastases. In the FS-DFSP group, seven patients (20.6%) had positive margins, six patients (17.6%) developed local recurrence (LR) and eight patients (23.5%) developed distant metastases, of which three (37.5%) were in the lungs, one (12.5%) in bone and four (50%) in other soft tissue sites. DISCUSSION AND CONCLUSION: Local recurrence and metastases are extremely rare in patients with DFSP. Achieving a negative as opposed to a wide surgical margin may be sufficient to avoid local recurrence of most DFSP. We suggest that no ongoing surveillance for local or systemic relapse is required for DFSP patients after negative margin resection. For FS-DFSP, we recommend the same surveillance schedule, based on tumour grade, as other soft tissue sarcoma.

ZFP64::NCOA3 gene fusion defines a novel subset of spindle cell rhabdomyosarcoma.

Spindle cell rhabdomyosarcoma represents a rare neoplasm characterized by monomorphic spindle cells with a fascicular architecture and variable skeletal muscle differentiation. Following incidental identification of a ZFP64::NCOA3 gene fusion in an unclassified spindle cell sarcoma resembling adult-type fibrosarcoma, we performed a retrospective archival review and identified four additional cases with a similar histology and identical gene fusion. All tumors arose in adult males (28-71 years). The neoplasms were found in the deep soft tissues, two were gluteal, and one each arose in the thigh, abdominal wall, and chest wall. Morphologically, the tumors were characterized by spindle cells with a distinctive herringbone pattern and variable collagenous to myxoid stroma. The nuclei were relatively monomorphic with variable mitotic activity. Three tumors had immunoreactivity for MyoD1, and four contained variable expression of desmin and smooth muscle actin. All cases tested for myogenin, CD34, S100, pankeratin, and epithelial membrane antigen were negative. Targeted RNA sequencing revealed a ZFP64::NCOA3 fusion product in all five tumors. Three patients developed distant metastases, and two ultimately succumbed to their disease within 2 years of initial diagnosis. This study suggests ZFP64::NCOA3 fusions define a novel subtype of rhabdomyosarcoma with a spindle cell morphology and aggressive clinical behavior. The potential for morphologic and immunohistochemical overlap with several other sarcoma types underscores the value of molecular testing as a diagnostic adjunct to ensure accurate classification and management of these neoplasms.

Surgical Outcomes of Primary Dermatofibrosarcoma Protuberans: A Retrospective, Multicenter Study.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is a locally aggressive tumor with a low rate of metastatic disease. Previous series have shown a superiority of Mohs micrographic surgery (MMS) compared with wide local excision (WLE). Likewise, there is paucity of data examining the long-term follow-up of patients. OBJECTIVE: The purpose of the current study was to examine the outcome of surgical treatment of primary DFSP of the trunk and extremities. METHODS: We reviewed 236 patients (115 females, 121 males, mean age 41 ± 15 years) undergoing MMS (n = 81, 34%) or WLE (n = 155, 66%) to treat a primary DFSP. Mean tumor size and follow-up was 4 ± 2 cm and 7 years, respectively. Final margins were negative in 230 (97%) patients. RESULTS: There was no difference (p > 0.05) in patient age, sex, tumor size, negative margin excision, or history of a previous inadvertent excision between patients who underwent WLE and those undergoing MMS. There were two cases of local recurrence and two cases of metastasis, with no difference in the 5-year local recurrence-free survival (98% vs. 99%, p = 0.69) or metastatic-free survival (98% vs. 100%, p= 0.27) between WLE and MMS. CONCLUSION: There was no difference in oncologic outcome comparing MMS with WLE for DFSP outside the head and neck. The goal of treatment for DFSP is to achieve a negative margin, regardless of surgical treatment modalities. A 'less is more' approach to follow-up can likely be taken for patients with completely resected DFSP in easy-to-examine anatomical areas. In these patients, no formal follow-up should be required.

The Toronto Sarcoma Flap Score: A Validated Wound Complication Classification System for Extremity Soft Tissue Sarcoma Flap Reconstruction.

BACKGROUND: Flap reconstruction plays an important role in limb preservation after wide resection of extremity soft tissue sarcoma (ESTS), but can be associated with high rates of postoperative wound complications. Currently, no standardized system exists for the classification of these complications. This study aimed to develop a standardized classification system for wound complications after ESTS flap reconstruction. METHODS: Outcomes of ESTS flap reconstructions were analyzed in a retrospective cohort of 300 patients. All wound- and flap-related complications were identified and categorized. Based on these data, a scoring system was developed and validated with a prospective cohort of 100 patients who underwent ESTS flap reconstruction. RESULTS: A 10-point scoring system was developed based on the level of intervention required to treat each complication observed in the retrospective cohort. Raters applied the scoring system to the prospective patient cohort. Validation studies demonstrated excellent inter-rater and intra-rater reliability (weighted Cohen's kappa range, 0.82 [95% CI, 0.5-1.0] to 0.99 [95% CI, 0.98-1.0] and 0.95 [95% CI, 0.84-1.0] to 0.97 [95% CI, 0.92-1.0], respectively). The majority of the raters reported the score to be simple, objective, and reproducible (respective mean scores, 4.76 ± 0.43, 4.53 ± 0.62, and 4.56 ± 0.56 on 5-point Likert scales). CONCLUSION: The Toronto Sarcoma Flap Score (TSFS) is a simple and objective classification system with excellent inter- and intra-rater reliability. Universal adoption of the TSFS could standardize outcome reporting in future studies and aid in the establishment of clinical benchmarks to improve the quality of care in sarcoma reconstruction.

Staging and Surveillance of Myxoid Liposarcoma: Follow-up Assessment and the Metastatic Pattern of 169 Patients Suggests Inadequacy of Current Practice Standards.

BACKGROUND: Unlike other sarcoma subtypes, myxoid liposarcoma (MLS) has a propensity for extra-pulmonary metastases. Computed tomography (CT) scan of the chest, abdomen, and pelvis has become an accepted practice for surveillance. However, recent literature suggests that this may be inadequate. This study aimed to assess the ability of current imaging methods to detect metastases adequately in this population. METHODS: The study identified 169 patients with MLS diagnosed between 2000 and 2016. The timing and location of metastases, the reasons leading to the MLS diagnosis, and the imaging methods were recorded. The locations of metastases were classified into the following categories: pulmonary, soft tissue, bone, retroperitoneal, intraperitoneal, solid organ, and lymph node. RESULTS: An initial diagnosis of metastasis was made at presentation with staging CT scan for 3 (10 %) of 31 patients, with a follow-up surveillance CT scan for 15 (48 %) of the patients or with subsequent imaging obtained in response to patient-reported symptoms for 13 (42 %) of the patients. The proportions of patients who had metastases in each location were as follows: soft tissue (84 %), pulmonary (68 %), intraabdominal (48 %), solid organ (48 %), bone (45 %), lymph node (32 %), and retroperitoneal (29 %). Although 14 patients had bone metastases, only 1 patient had a sclerotic/blastic presentation visualized on CT scan, and the diagnosis for the remaining 13 patients was determined by magnetic resonance imaging (MRI). CONCLUSION: Due to metastatic disease identified outside surveillance imaging for 58 % of the patients, the diversity of locations, and the significant failure of CT and bone scan to identify bone metastases, this study questioned the adequacy of CT scan for surveillance of MLS. Consideration should be given to the use of whole-body MRI for detection of metastasis in MLS.

Curability of patients with lymph node metastases from extremity soft-tissue sarcoma.

BACKGROUND: Lymph node metastases (LNM) rarely occur in adult extremity soft-tissue sarcoma (STS), affecting approximately 5% of patients. To the authors' knowledge, few studies to date have evaluated the prognosis and survival of patients with LNM. METHODS: A retrospective review was performed of a single-center, prospectively collected STS database. Demographic, treatment, and oncologic data for patients with STS of the extremity with LNM were obtained from clinical and radiographic records. RESULTS: Of 2689 patients with extremity STS, a total of 120 patients (4.5%) were diagnosed with LNM. LNM occurred most frequently among patients diagnosed with clear cell sarcoma (27.6%), epithelioid sarcoma (21.9%), rhabdomyosarcoma (17.3%), angiosarcoma (14.0%), and extraskeletal myxoid chondrosarcoma (9.3%). A total of 98 patients (81.7%) underwent LNM surgical resection. Patients with isolated LNM had a greater 5-year overall survival (57.3%) compared with patients with American Joint Committee on Cancer (AJCC) eighth edition stage IV STS with only systemic metastases (14.6%) or both LNM and systemic disease (0%; P < .0001). Patients with isolated LNM had an overall survival rate (52.9%) similar to that of patients with localized AJCC stage III tumors (ie, large, high-grade tumors) (49.3%) (P = .8). Patients with late, isolated, metachronous LNM had a 5-year overall survival rate (61.2%) that was similar to that of patients with isolated synchronous LNM at the time of presentation (53.6%) (P = .4). CONCLUSIONS: Many different types of STS develop LNM. Patients with extremity STS with isolated LNM should not be considered as having stage IV disease as they are according to the current AJCC eighth edition classification because they have significantly better survival than those with systemic metastases. Patients with isolated, late, metachronous LNM have a survival similar to that of patients with isolated synchronous LNM at the time of presentation. LAY SUMMARY: The results of the current study demonstrated that patients diagnosed with isolated lymph node metastases have a prognosis similar to that of patients diagnosed with localized American Joint Committee on Cancer stage III soft-tissue sarcomas, which also equates to a significantly better overall survival compared with patients with systemic metastases. Therefore, the authors recommend modifications to the most recent eighth edition of the American Joint Committee on Cancer staging system to clearly distinguish patients with isolated lymph node metastases to acknowledge their better prognosis compared with those with systemic metastases.

Extrameningeal solitary fibrous tumors-surgery alone or surgery plus perioperative radiotherapy: A retrospective study from the global solitary fibrous tumor initiative in collaboration with the Sarcoma Patients EuroNet.

BACKGROUND: Solitary fibrous tumor (SFT) is a rare mesenchymal malignancy. Although surgery is potentially curative, the local relapse risk is high after marginal resections. Given the lack of prospective clinical trial data, the objective of the current study was to better define the role of perioperative radiotherapy (RT) in various SFT presentations by location. METHODS: This was retrospective study performed across 7 sarcoma centers. Clinical information was retrieved from all adult patients with extrameningeal, primary, localized SFT who were treated between 1990 and 2018 with surgery alone (S) compared with those who also received perioperative RT (S+RT). Differences in treatment characteristics between subgroups were tested using analysis of variance statistics and propensity score matching. Local control and overall survival rates were calculated from the start of treatment until progression or death from any cause. RESULTS: Of all 549 patients, 428 (78%) underwent S, and 121 (22%) underwent S+RT. The median follow-up was 52 months. After correction for mitotic count and surgical margins, S+RT was significantly associated with a lower risk of local progression (hazard ratio, 0.19: P = .029), an observation further confirmed by propensity score matching (P = .012); however, this association did not translate into an overall survival benefit. CONCLUSIONS: The results from this retrospective study investigating perioperative RT in patients with primary extrameningeal SFT suggest that combining RT with surgery in the management of this patient population is significantly associated with a reduced risk of local failures, especially in patients who have less favorable resection margins and in those who have tumors with a high mitotic count.

Designing a Rational Follow-Up Schedule for Patients with Extremity Soft Tissue Sarcoma.

PURPOSE: The risk of tumor recurrence after resection of soft tissue sarcoma (STS) necessitates surveillance in follow-up. The objective of this study was to determine the frequency/timing of metastasis and local recurrence following treatment for soft tissue sarcoma, and to use these data to justify an evidence-based follow-up schedule. METHODS: Utilizing a prospective database, a retrospective single center review was performed of all patients with minimum 2-year follow-up after resection of a localized extremity STS. Kaplan-Meier estimates were used to calculate the incidence of local recurrence and metastases on an annual basis for 10 years. RESULTS: We identified a total of 230 low-grade, 626 intermediate-grade and 940 high-grade extremity STS and a total of 721 events, 150 local recurrences and 571 metastases. Based on tumor size and grade, follow-up cohorts were developed that had similar metastatic risk. Using pre-determined thresholds for metastatic event, a follow-up schedule was established for each cohort. CONCLUSION: Based on our results we recommend that patients with small low-grade tumors undergo annual follow-up for 5 years following definitive local treatment. Patients with large low-grade tumors, small intermediate-grade and small high-grade tumors should have follow-up every 6 months for the first 2 years, then yearly to 10 years. Only patients with large intermediate- or high-grade tumors require follow-up every 3 months for the first 2 years, then every 6 months for years 3-5, followed by annually until 10 years.

Can the ACS-NSQIP surgical risk calculator predict postoperative complications in patients undergoing sacral tumor resection for chordoma?

BACKGROUND AND OBJECTIVES: The ACS-NSQIP surgical risk calculator is an online tool that estimates the risk of postoperative complications. Sacrectomies for chordoma are associated with a high rate of complications. This study was to determine if the ACS-NSQIP calculator can predict postoperative complications following sacrectomy. METHODS: Sixty-five (42 male, 23 female) patients who underwent sacrectomy were analyzed using the Current Procedural Terminology (CPT) codes: 49215 (excision of presacral/sacral tumor), 63001 (laminectomy of sacral vertebrae), 63728 (laminectomy for biopsy/excision of sacral neoplasm) and 63307 (sacral vertebral corpectomy for intraspinal lesion). The predicted rates of complications were compared to the observed rates. RESULTS: Complications were noted in 44 (68%) patients. Of the risk factors available to input to the ACS-NSQIP calculator, tobacco use (OR, 20.4; P < .001) was predictive of complications. The predicted risk of complications based off the CPT codes were: 49215 (16%); 63011 (6%); 63278 (11%) and 63307 (15%). Based on ROC curves, the use of the ACS-NSQIP score were poor predictors of complications (49215, AUC 0.65); (63011, AUC 0.66); (63307, AUC 0.67); (63278, AUC 0.64). CONCLUSION: The ACS-NSQIP calculator was a poor predictor of complications and was marginally better than a coin flip in its ability to predict complications following sacrectomy for chordoma.

Advancing patient age is associated with worse outcomes in low- and intermediate-grade primary chondrosarcoma of the pelvis.

BACKGROUND: Conventional primary pelvic chondrosarcoma often presents as a low- or intermediate-grade tumor in older patients. Although this is the most common variant of pelvic chondrosarcoma, studies examining treatment outcomes are lacking. The purpose of this study was to evaluate patients with these tumors to determine their outcomes of treatment. METHODS: Seventy-three patients (grade I [n = 19, 26%] and grade II [n = 54, 74%]) were reviewed including 55 (75%) males and 18 (25%) females, with a mean age of 51 (range, 17-81) years and follow-up of 9 ± 5 years. RESULTS: The 10-year disease-specific survival was 71%. Grade II disease (hazard ratio [HR], 6.74; P = .04) and age ≥50 years (HR, 3.97; P = .02) was associated with death due to disease. The 10-year local recurrence- and metastatic-free survival were 79% and 72%. Of the patients with a local recurrence (n = 11), 7 (64%) recurred at a higher histological grade. Patient age ≥50 years was associated with local recurrence (HR, 10.03; P = .02) and metastatic disease (HR, 4.20; P = .02). CONCLUSION: Advancing patient age was an independent risk factor for worse survival and disease recurrence. Tumors often recurred locally at a higher grade and as such wide local excision remains the treatment of choice for these tumors.

Association between patient age and the risk of mortality following local recurrence of a sacral chordoma.

BACKGROUND: Local recurrence (LR) of sacral chordoma is a difficult problem and the mortality risk associated with LR remains poorly described. The purpose of this study was to evaluate the risk of mortality in patients with LR and determine if patient age is associated with mortality. METHODS: A total of 218 patients (144 male, 69 female; mean age 59 ± 15 years) with sacrococcygeal chordomas were reviewed. Cumulative incidence functions and competing risks for death due to disease and nondisease mortality were employed to analyze mortality trends following LR. RESULTS: The 10-year overall survival (OS) was 55%. Patients with LR had 44% 10-year OS, similar to patients without (59%; P = .38). The 10-year OS between those less than 55 compared with ≥55 years were similar (69% vs 48%; P = .52). The 10-year death due to disease was worse in patients with LR compared with those without (44% vs 84%; P < .001). In patients without LR, patients ≥55 years were 1.6-fold more likely to experience death due to other causes. CONCLUSIONS: Patients with an LR are more likely to die due to disease. Advanced patient age was associated with higher all-cause mortality following resection of sacral chordoma. LR of chordoma was associated with increased disease-specific mortality, regardless of age.

Midterm Success of a Custom, Non-Fluted, Diaphyseal, Press-Fit Stem Used With a Tumor Megaprosthesis System.

BACKGROUND: High rates of aseptic loosening with cemented prostheses have led to increased utilization of uncemented stems in the setting of megaprosthetic reconstruction. Theoretic concerns of rotational instability resulted in early stem designs with de-rotational mechanisms such as flutes or side plates. However, these designs have their own associated complications, and mechanical data suggest they are unnecessary. The purpose of this study is to evaluate outcomes and survivorship of an unfluted diaphyseal press-fit stem in the setting of megaprosthetic reconstruction. METHODS: Forty-five patients (46 stems), with a minimum 3-year follow-up, underwent reconstruction using 1 of 2 fully porous coated, unfluted, press-fit stems between 2005 and 2013: revision stem with adapter to the megaprosthesis (revision stem), or custom megaprosthesis stem (custom stem). Complications were described using the Henderson classification system, and subanalyses evaluated stem-related failures and survival. Radiographic evaluation of stem fixation was determined via evidence of bone bridging, spot welding, resorption, subsidence, and pedestal formation. Four patients had early stem removal for local recurrence or infection and were thus excluded from the radiographic analyses. RESULTS: Twenty-eight femoral (15 revision stem, 13 custom stem) and 14 tibial (6 revision stem, 8 custom stem) stems were reviewed. Average follow-up was 81 months (range, 42-140 months). Revision for implant-related complications occurred in 7 of 41 (17%), all in revision stems (3 adapter failures, 4 polyethylene wear). At final follow-up, all stems were retained without evidence of aseptic loosening, although 7 of 41 (17%) exhibited mild stress shielding. CONCLUSION: A non-fluted, press-fit stem used with a tumor prosthesis provided a stable bone-prosthesis interface at midterm follow-up.

Extended intralesional curettage preferred over resection-arthrodesis for giant cell tumour of the distal radius.

BACKGROUND: Distal radius giant cell tumour (GCT) is known to be associated with distinct management difficulties, including high rates of local recurrence and lung metastases compared to other anatomic locations. Multiple treatment options exist, each with different outcomes and complications. QUESTIONS/PURPOSES: To compare oncological and functional outcomes and complications following treatment of patients with distal radius GCT by extended intralesional curettage (EIC) or resection-arthrodesis. METHODS: Patients operated on for distal radius GCT were identified from prospectively collected databases at four Canadian musculoskeletal oncology specialty centres. There were 57 patients with a mean age of 35.4 years (range 17-57). Thirteen tumours were Campanacci grade 2, and 40 were Grade 3 (4 unknown). Twenty patients presented with an associated pathologic fracture. There were 34 patients treated by EIC and 23 by en bloc resection and wrist arthrodesis. All resections were performed for grade 3 tumours. The mean follow-up was 86 months (range 1-280). RESULTS: There were a total of 11 (19%) local recurrences: 10 of 34 (29%) in the EIC group compared to only 1 of 23 (4%) in the resection-arthrodesis group (p = 0.028). For the 10 patients with local recurrence following initial treatment by EIC, 7 underwent repeat EIC, while 3 required resection-arthrodesis. The one local recurrence following initial resection was managed with repeat resection-arthrodesis. Six of the 11 local recurrences followed treatment of Campanacci grade 3 tumours, while 4 were in grade 2 lesions and in one case of recurrence the grade was unknown. There were no post-operative complications after EIC, whereas 7 patients (30%) had post-operative complications following resection-arthrodesis including 4 infections, one malunion, one non-union and one fracture (p = 0.001). The mean post-operative Musculoskeletal Tumor Society score was 33.5 in the curettage group compared to 27 in the resection group (p = 0.001). The mean Toronto Extremity Salvage Score was 98.3% following curettage compared to 91.5% after resection (p = 0.006). No patients experienced lung metastasis or death. CONCLUSIONS: EIC is an effective alternative to wide resection-arthrodesis following treatment of distal radius GCT, with the advantage of preserving the distal radius and wrist joint function, but with a higher risk of local recurrence. Most local recurrences following initial treatment by EIC could be managed with iterative curettage and joint preservation. Wide excision and arthrodesis were associated with a significantly lower risk of tumour recurrence but was technically challenging and associated with more frequent post-operative complications. EIC was associated with better functional scores. Resection should be reserved for the most severe grade 3 tumours and recurrent and complex cases not amenable to treatment with EIC and joint salvage. LEVEL OF EVIDENCE: III, retrospective comparative trial.

Comparison of published risk models for prediction of outcome in patients with extrameningeal solitary fibrous tumour.

AIMS: Solitary fibrous tumours (SFTs) are fibroblastic mesenchymal tumours with a 10-30% metastatic rate. Several risk models have been proposed for extrameningeal SFT, but they have not been evaluated in direct comparison with each other. The aim of this study is to compare the utility of published risk models in a multi-institutional SFT cohort. METHODS AND RESULTS: Clinicopathological data were evaluated for a cohort of extrameningeal SFTs, and used to stratify tumours by the use of five proposed risk models designed for soft tissue and/or pleural SFT [modified Demicco, Pasquali, Salas overall survival (OS), Salas metastasis, and Salas local recurrence (LR)]. Kaplan-Meier and Cox proportional hazards models were used to assess OS, time to first metastasis, time to first LR, and recurrence-free survival (RFS). The study included 303 patients (109 from a referral cancer treatment centre; previously described in the original Demicco model) and an independent cohort from two large hospitals (n = 194). The median patient age was 54 years, and the median clinical follow-up (available for 220 patients) was 37 months. The independent cohort had a 13% risk of metastasis at 5 years and a 16% risk of metastasis at 10 years. In this cohort, the modified Demicco, Salas OS, and Salas metastasis models predicted metastasis and RFS, whereas the Pasquali model had the best correlation with OS. CONCLUSIONS: Multivariate risk models that include mitotic rate and patient age can more accurately predict aggressive behaviour in SFTs, with the modified Demicco and Salas OS risk models showing the best correlation with metastasis and RFS.

Low dose radiotherapy is associated with local complications but not disease control in sacral chordoma.

BACKGROUND: We reviewed the disease control and complications of the treatment of sacrococcygeal chordoma from four tertiary cancer centers with emphasis on the effects of radiotherapy in surgically treated patients. METHODS: A total of 193 patients with primary sacrococcygeal chordoma from 1990 to 2015 were reviewed. There were 124 males, with a mean age of 59 ± 15 years and a mean follow-up of 7 ± 4 years. Eighty-nine patients received radiotherapy with a mean total dose of 61.8 ± 10.9 Gy. RESULTS: The 10-year disease-free and disease-specific survival was 58% and 72%, respectively. Radiation was not associated with local recurrence (hazard ratio [HR], 1.13; 95% confidence interval [CI], 0.59-2.17; P = 0.71), metastases (HR, 0.93; 95% CI, 0.45-1.91; P = 0.85) or disease-specific survival (HR, 0.96; 95% CI, 0.46-2.00; P = 0.91). Higher doses (≥70 Gy; HR, 0.52; 95% CI, 0.20-1.32; P = 0.17) may be associated with reduced local recurrence. Radiotherapy was associated with wound complications (HR, 2.76; 95% CI, 1.64-4.82;, P < 0.001) and sacral stress fractures (HR, 4.73; 95% CI, 1.88-14.38; P < 0.001). CONCLUSIONS: In this multicenter review, radiotherapy was not associated with tumor outcome but associated with complications. The routine use of radiotherapy with en-bloc resection of sacrococcygeal chordomas should be reconsidered in favor of a selective, individualized approach with a radiation dose of ≥70 Gy.

How Often Do Acetabular Erosions Occur After Bipolar Hip Endoprostheses in Patients With Malignant Tumors and Are Erosions Associated With Outcomes Scores?

BACKGROUND: Bipolar endoprosthetic replacement is an option for reconstruction of the proximal femur to restore a functional extremity and salvage the limb. However, because these patients are young, there is a theoretical risk for long-term degenerative changes of the acetabulum. Currently, there is a paucity of data concerning the proportion of patients who experience degenerative acetabulum changes after reconstruction and whether these changes are associated with Musculoskeletal Tumor Society (MSTS) scores. QUESTIONS/PURPOSES: (1) What proportion of patients develop acetabular cartilage degeneration after bipolar hemiarthroplasty for malignant tumor-related reconstructions? (2) What is the survivorship free from revision for acetabular wear, erosions, or progressive arthritis? (3) Is there an association between the presence of acetabular erosions and lower MSTS scores? METHODS: Between 2000 and 2015, 148 patients underwent endoprosthetic reconstruction of the proximal femur with a bipolar hemiarthroplasty for a malignant tumor and were potentially eligible for this retrospective study. Minimum followup was 1 year except for those who died or were revised earlier; of the 148, no patients were lost to followup before that time who were not known to have died; mean followup on the remainder was 79 months (range, 12-220 months), and the mean time to death after surgery for those who died was 28 months (range, 0-196 months). Over the course of the study, 93 (63%) patients died. The mean (± SD) patient age was 57 ± 17 years, and 55% (81 of 148) of the patients were men. We used magnification-corrected supine AP plain radiographs of the hip to evaluate degenerative acetabulum changes, and we used the 1993 MSTS score to assess function through chart review and a longitudinally maintained institutional database. We used a competing-risks survivorship estimator rather than Kaplan-Meier because of the high proportion of patients who had died during the surveillance period. RESULTS: Nineteen patients (13%) developed cartilage erosion > 2 mm in the acetabulum, with two also developing protrusio after proximal femoral replacement with a bipolar endoprosthesis. Three additional patients also developed signs of protrusio. The mean acetabular wear after bipolar replacement was 1.2 mm. Patients with longer followup (p = 0.001) were at higher risk for developing acetabular wear. Six patients underwent conversion to THA to treat hip pain. At 10 years the cumulative incidence for conversion to THA for acetabular wear is 5% (95% confidence interval [CI], 0%-11%), whereas the cumulative incidence of death was 70% (95% CI, 61%-79%). There was no difference in mean MSTS scores between patients who developed > 2 mm of acetabular erosion (65% ± 25%) and those who did not (67% ± 20%; p = 0.77). CONCLUSIONS: Wear was uncommon among patients with malignant hip tumors treated with bipolar endoprostheses, but the followup here was short, and some patients indeed developed wear and underwent wear-related revisions to THA. Patients expected to survive more than a few years should have periodic radiographic surveillance and should be followed for a longer period to get a better sense for whether the problem worsens with time, as we expect it may, among patients who survive for longer periods. LEVEL OF EVIDENCE: Level III, therapeutic study.

Identifying actionable variants using next generation sequencing in patients with a historical diagnosis of undifferentiated pleomorphic sarcoma.

There are limited data regarding the molecular characterization of undifferentiated pleomorphic sarcomas (UPS; formerly malignant fibrous histiocytoma). This study aimed to investigate the utility of next generation sequencing (NGS) in UPS to identify subsets of patients who harbour actionable mutations. Patients diagnosed with UPS underwent pathological re-evaluation by a pathologist specializing in sarcoma. Tumor DNA was isolated from archived fresh frozen tissue samples and genotyped using NGS with the Illumina MiSeq TruSeq Amplicon Cancer Panel (48 genes, 212 amplicons). In total, 95 patients initially classified with UPS were identified. Following pathology re-review the histological subtypes were reclassified to include: Myxofibrosarcoma (MFS, N = 44); UPS(N = 18); and Others (N = 27; including undifferentiated spindle cell sarcoma (N = 15) and dedifferentiated liposarcoma (N = 6)). Seven cases were excluded from further analysis for other reasons. Baseline demographics of the finalized cohort (N = 88) showed a median age of 66 years (32-95), primarily with stage I-III disease (92%) and high-grade (86%) lesions. Somatic mutations were identified in 31 cases (35%)(Total mutations = 36: solitary mutation(n = 27); two mutations( =n = 3); three mutations(n = 1)). The most commonly identified mutations were in TP53 (n = 24), ATM (n = 3) and PIK3CA (n = 2). Three of 43 patients with MFS and one of 18 patients with UPS had clinically relevant mutations, mainly related to biomarkers of prediction of response; however few had targetable driver mutations. Somatic mutation status did not influence disease free or overall survival. Based on the small number of clinically relevant mutations, these data do not support the routine use of targeted NGS panels outside of research protocols in UPS.

Influence of unplanned excisions on the outcomes of patients with stage III extremity soft-tissue sarcoma.

BACKGROUND: Soft-tissue sarcomas (STSs) are a heterogeneous group of malignant tumors that can be difficult to treat. This is particularly true after incomplete or unplanned excisions and especially for patients with American Joint Committee on Cancer stage III tumors, who are at high risk for relapse. Numerous studies have shown that an inadequate sarcoma excision is associated with a worse prognosis. However, other reports have suggested an improved prognosis for patients with an initial unplanned excision and subsequent re-excision in comparison with patients who undergo planned primary surgery. The purpose of this study was to determine the impact of an unplanned excision on treatment and subsequent oncologic and functional outcomes for patients with stage III extremity STS. METHODS: From the prospectively collected database at a tertiary-referral sarcoma center, all patients with stage III STS of the extremities treated between 1989 and 2010 were identified. Patient records were reviewed to identify patient demographics, tumor details, treatments, complications, and functional and oncologic outcomes. RESULTS: Five hundred patients with stage III STSs of the extremities were identified, and 94 of these patients (18.8%) were referred after inadequate excisions had been performed elsewhere. All 94 patients with unplanned excisions underwent re-excision in an attempt to achieve clear margins, and 83% of these patients had residual tumor in the re-excision specimen. In the re-excision group, the rates of plastic reconstruction (eg, skin grafts and rotational or free flaps) and amputation were significantly higher in comparison with the rates for patients who underwent a primary planned resection (P = .023 and P = .03, respectively). The rates of local recurrence, metastasis-free survival, and overall survival were not significantly different between the 2 groups, nor were the functional outcomes. CONCLUSIONS: Unplanned excision of stage III STS leads to an unfavorable clinical course and necessitates more extensive surgery. As a result of aggressive re-excision and multidisciplinary treatment, a negative effect on oncologic outcomes cannot be confirmed.

Oncologic Outcome and Quality of Life After Hindquarter Amputation for Sarcoma: Is it Worth it?

BACKGROUND AND OBJECTIVE: Hindquarter amputations for bone or soft tissue sarcoma cause a high degree of disability. The goal of this study was to analyze oncologic outcome and quality of life after resection in order to better select patients who are more likely to benefit from this operation. METHODS: Patients treated with a hindquarter amputation between 1989 and 2015 for a bone or soft tissue sarcoma were selected from our database. Clinical and histopathological features were analyzed for their prognostic value using Kaplan-Meier and Cox proportional hazard analysis. In addition, performance status, ambulatory status, and pain were assessed from the hospital charts for patients surviving longer than 1 year after surgery. RESULTS: Overall, 78 patients underwent a hindquarter amputation for sarcoma. The median hospital stay was 24 days and 49% of patients had wound complications. In-hospital mortality was 6%. Overall survival for patients with metastases at presentation was significantly worse than patients with localized disease only (p = 0.001, 5-year survival 41 vs. 0%). For patients treated for localized disease, the combination of age >65 years and tumor size ≥15 cm was significantly correlated with worse metastasis-free survival (p = 0.003) and overall survival (p = 0.01). In particular, patients younger than 65 years of age who survived more than 1 year had an acceptable performance status, with reasonable pain levels and mobility. CONCLUSION: Younger patients are more likely to benefit from hindquarter ampuations in terms of survival and functionality; however, for older patients with large tumors, a hindquarter amputation might not be beneficial.