Development of machine learning model algorithm for prediction of 5-year soft tissue myxoid liposarcoma survival.

BACKGROUND: Predicting survival in myxoid liposarcoma (MLS) patients is very challenging given its propensity to metastasize and the controversial role of adjuvant therapy. The purpose of this study was to develop a machine-learning algorithm for the prediction of survival at five years for patients with MLS and externally validate it using our institutional cohort. METHODS: Two databases, the surveillance, epidemiology, and end results program (SEER) database and an institutional database, were used in this study. Five machine learning models were created based on the SEER database and performance was rated using the TRIPOD criteria. The model that performed best on the SEER data was again tested on our institutional database. RESULTS: The net-elastic penalized logistic regression model was the best according to our performance indicators. This model had an area under the curve (AUC) of 0.85 when compared to the SEER testing data and an AUC of 0.76 when tested against institutional database. An application to use this calculator is available at https://sorg-apps.shinyapps.io/myxoid_liposarcoma/. CONCLUSION: MLS is a soft-tissue sarcoma with adjunct treatment options that are, in part, decided by prognostic survival. We developed the first machine-learning predictive algorithm specifically for MLS using the SEER registry that retained performance during external validation with institutional data.

Clinical outcomes of patients with advanced synovial sarcoma or myxoid/round cell liposarcoma treated at major cancer centers in the United States.

BACKGROUND: Outcomes data regarding advanced synovial sarcoma (SS) and myxoid/round cell liposarcoma (MRCL) are limited, consisting primarily of retrospective series and post hoc analyses of clinical trials. METHODS: In this multi-center retrospective study, data were abstracted from the medical records of 350 patients from nine sarcoma centers throughout the United States and combined into a registry. Patients with advanced/unresectable or metastatic SS (n = 249) or MRCL (n = 101) who received first-line systemic anticancer therapy and had records of tumor imaging were included. Overall survival (OS), time to next treatment, time to distant metastasis, and progression-free survival (PFS) were evaluated using the Kaplan-Meier method and Cox regression. RESULTS: At start of first-line systemic anticancer therapy, 92.4% of patients with SS and 91.1% of patients with MRCL had metastatic lesions. However, 74.7% of patients with SS and 72.3% of patients with MRCL had ≥2 lines of systemic therapy. Median OS and median PFS from first-line therapy for SS was 24.7 months (95% CI, 20.9-29.4) and 7.5 months, respectively (95% CI, 6.4-8.4). Median OS and median PFS from start of first-line therapy for MRCL was 29.9 months (95% CI, 27-44.6) and 8.9 months (95% CI 4.5-12.0). CONCLUSIONS: To the best of our knowledge, this is the largest retrospective study of patients with SS and MRCL. It provides an analysis of real-world clinical outcomes among patients treated at major sarcoma cancer centers and could inform treatment decisions and design of clinical trials. In general, the survival outcomes for this selected population appear more favorable than in published literature.

Prognostic relevance of SMC family gene expression in human sarcoma.

OBJECTIVE: To explore the prognostic value of the expression of genes encoding structural maintenance of chromosomes (SMCs) in human sarcoma. RESULTS: We found that the levels of SMC1A, SMC2, SMC3, SMC4, SMC5 and SMC6 mRNA were all higher in most tumors compared to normal tissues, and especially in sarcoma. According to the Cancer Cell Line Encyclopedia (CCLE), SMC1A, SMC2, SMC3, SMC4, SMC5 and SMC6 are also highly expressed in sarcoma cell lines. Results of Gene Expression Profiling Interactive Analysis (GEPIA) indicated that high expression of SMC1A was significantly related to poor overall survival (OS) (p<0.05) and disease-free survival (DFS) in sarcoma (p<0.05). Additionally, strong expression of SMC2 was significantly related to poor OS in sarcoma (p<0.05). In contrast, SMC3, SMC4, SMC5, and SMC6 expression had no significant impact on OS or DFS in sarcoma. CONCLUSIONS: Expression of SMC family members is significantly different in sarcoma relative to normal tissues, and SMC1A and SMC2 may be useful as prognostic biomarkers. METHODS: We performed a detailed comparison of cancer and normal tissues regarding the expression levels of mRNA for SMC family members in various cancers including sarcoma through ONCOMINE and GEPIA (Gene Expression Profile Interactive Analysis) databases.

Surgical Outcomes and Prognostic Factors of Myxoid Liposarcoma in Extremities: A Retrospective Study.

OBJECTIVES: To evaluate treatments and prognostic factors for the myxoid liposarcoma in extremities. METHODS: We retrospectively reviewed 34 patients histologically diagnosed with myxoid liposarcoma arising in the extremities, treated in our hospital from 2010 to 2017. We recorded tumor locations, max diameter, operations, complications, radiation, chemotherapy, survival, recrudescence, and metastases. Overall survival, treatments, and prognostic factors were subsequently analyzed. RESULTS: The mean age of 34 patients with myxoid liposarcoma in extremities was 49.1 years, and the mean follow-up period was 65.1 months. The median survival time was 190 months. Five of 14 patients accepted recrudescence resection and two patients of 20 patients who underwent primary tumor resection or unplanned operation died of tumor progression. Although no statistical difference was found (X 2 = 3.331, P = 0.068), the lower mortality was confirmed in the patients who accepted primary tumor resection or unplanned operation. Eleven patients with a tumor diameter of 8.6 ± 4.7 cm accepted wide resection, while 23 patients with 17.2 ± 8.8 cm tumors accepted marginal resection. Statistical difference was found between the size of tumors with relatively wide resection and those with relatively marginal resection (F = 9.130, P = 0.005). No recurrence or metastasis occurred in patients who accepted wide resection, while 14 patients presented with local recurrence and 8 patients developed distant metastases among the 23 patients with marginal resection. Seven patients died of metastases, while one patient lived with metastases. No significant difference in survival was found between different surgical methods (X 2 = 0.9460, P = 0.3307). The average diameter of eight patients with distant metastases was 21.7 cm, which was considerable larger than the 12.1 cm of patients without metastasis. This difference was proven significant upon the statistical analysis (F = 9.412, P = 0.004). CONCLUSIONS: Wide resection achieved good local control but was not unambiguously superior in long-term survival. Myxoid liposarcoma tumors with larger diameters were more difficult to be submitted to wide resection and were more likely to present with distant metastasis.

Prognostic factors of patients with extremity myxoid liposarcomas after surgery.

BACKGROUND: Extremity myxoid liposarcoma (MLS) is a rare soft tissue sarcoma in adults. We performed this study to define distinctive clinical features of extremity MLS by assessing prognostic factors. METHODS: Between 1973 and 2015, 1756 patients with extremity MLS who underwent surgical resection were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database of the US National Cancer Institute. Both overall survival (OS) and cancer-specific survival (CSS) were assessed using the Kaplan-Meier method (to obtain OS and CSS curves) and a Cox proportional hazards regression model. RESULTS: Of the 1756 patients with extremity MLS, the mean and median patient age at diagnosis were 47 and 45 years, respectively. More than half (n = 1027, 58.5%) of the patients were male. In terms of location, 10.5% tumors were located in the upper limbs and 89.5% in lower limbs. All patients received local surgery, and about half of the patients (57.2%) received radiation treatment. The 5- and 10-year OS rates of the entire cohort were 86.4% and 75.9%, respectively. The 5- and 10-year CSS rates were 90.5% and 85.2%, respectively. On multivariate analysis, older age, male gender, high tumor grade, and tumor size > 10 cm were found to be independent risk factors of both decreased OS and CSS. Year of diagnosis ≥ year 2000 was significantly associated with an increased CSS. In addition, radiation treatment failed to become an independent risk factor for either OS or CSS. CONCLUSION: We identified age, gender, tumor grade, year of diagnosis, and tumor size as independent prognostic factors for OS and CSS in patients with extremity MLS.

Myxoid Liposarcoma: Prognostic Factors and Metastatic Pattern in a Series of 148 Patients Treated at a Single Institution.

OBJECTIVES: The authors reported a retrospective study on myxoid liposarcomas (MLs), evaluating factors that may influence overall survival (OS), local recurrence-free survival (LRFS), metastasis-free survival (MFS), and analyzing the metastatic pattern. METHODS: 148 MLs were analyzed. The sites of metastases were investigated. RESULTS: Margins (p = 0.002), grading (p = 0,0479), and metastasis (p < 0,0001) were significant risk factors affecting overall survival (OS). Type of presentation (p = 0.0243), grading (p = 0,0055), margin (p = 0.0001), and local recurrence (0.0437) were risk factors on metastasis-free survival (MFS). Authors did not observe statistically significant risk factors for local recurrence-free survival (LRFS) and reported 55% extrapulmonary metastases and 45% pulmonary metastases. CONCLUSION: Margins, grading, presentation, local recurrence, and metastasis were prognostic factors. Extrapulmonary metastases were more frequent in myxoid liposarcoma.

Quantification of fat content in lipid-rich myxoid liposarcomas with MRI: a single-center experience with survival analysis.

OBJECTIVE: To determine the fat content of myxoid liposarcomas (MLS) on MRI and to identify any association between lipid content and survival. MATERIALS AND METHODS: The fat percentage of MLS diagnosed between January 2006 and December 2016 at a single institution was assessed by two radiologists on preoperative MR images. A Cox proportional hazard model was used to determine any association between tumor fat percentage and survival time. Tumor fat percentage was the single predictor in the model. A significance level of 0.05 was used. The Kaplan-Meier estimator was also used to provide a nonparametric estimate of the survivor function within the entire sample and within two patient subgroups consists of lipid-rich and lipid-poor tumors. Lipid-rich tumors were defined as any tumors showing more than 20% of fat on MRI. A 20% cutoff was determined arbitrarily. RESULTS: Of the 43 cases identified through retrospective review, 8 tumors demonstrated ≥10% fat on MRI, and 4 tumors demonstrated ≥20% fat (highest fat percentage, 38%). There was no significant survival difference between patients with high tumor fat, which was defined as ≥20% fat, compared with those with little to no tumor fat. CONCLUSION: Myxoid liposarcomas may demonstrate a higher fat content on MRI than has previously been reported in the literature. Increased tumor fat percentage in lipid-rich tumors was not found to be associated with increased risk of death. Radiologists must be aware of the existence of MLS lesions with higher fat content.

The role of histology, grading, location of tumour and ploidy in evaluation of outcome in patients with liposarcoma.

Department of Tumour Pathology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Kraków, Poland The review of literature indicates that several clinico-morphological factors such as location of the primary tumour as well as its size, histologic subtype, and grade or even selected molecular changes may significantly affect survival of liposarcoma (LPS) patients. Data concerning prognostic importance of DNA ploidy status in LPS cells are extremely limited and results of flow cytometry (FCM) studies have never been compiled with the current classification of malignant adipocytic tumours. Based on evaluation of material from 54 liposarcomas which was available for both histological and FCM analysis, we distinguished four prognostic groups of patients. The best prognosis was noticed for diploid and grade G1 well-differentiated or myxoid liposarcomas localised on extremities. None of the patients with lipoma-like WDLPS and myxoid liposarcoma grade 1 metastasised, while metastases were observed among patients with dedifferentiated LPS (70% of 5-year MFS) and cellular myxoid or round cell liposarcoma (20% of 5-year MFS, only). The metastasis-free survival curves for the above mentioned groups of patients differed significantly (p = 0.00001).

Clinical relevance of peroxisome proliferator-activated receptor-gamma expression in myxoid liposarcoma.

BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPARγ) is a ligand-activated transcription factor that belongs to the nuclear hormone receptor superfamily. PPARγ is essential in adipocyte differentiation from precursor cells. Its antitumorigenic effects are reported in certain malignancies; however, its effects in liposarcoma are unclear. METHODS: We analyzed PPARγ expression using immunohistochemistry (IHC) in 46 patients with myxoid liposarcoma [MLS; median age, 47 years (range, 14-90 years) and mean follow-up period, 91 months (range, 13-358 months)]. PPARγ mRNA expression levels were measured by quantitative reverse transcription polymerase chain reaction. Further, we evaluated the correlation of PPARγ expression with clinical outcomes. RESULTS: We found that the metastasis-free survival rate was significantly higher in lower PPARγ expressers [34 patients with labeling index (LI) <50 %] than in higher expressers (12 patients with LI ≥50 %; p = 0.01). Cox multivariate analysis revealed that a higher PPARγ level was an independent predictor of metastasis (relative risk = 6.945, p = 0.026). Furthermore, using 28 fresh MLS specimens, we confirmed an increased PPARγ mRNA expression level in the higher LI group (p = 0.001). CONCLUSIONS: In this study, higher PPARγ expression in MLS was a risk factor associated with distant metastasis; therefore, it would be a novel prognostic marker for MLS. Further analyses will help to understand the correlation between PPARγ expression and tumor malignancy in liposarcoma.

miR-135b, a key regulator of malignancy, is linked to poor prognosis in human myxoid liposarcoma.

Myxoid/round cell (RC) liposarcomas (MLS) were originally classified into two distinct populations based on histological differences; a myxoid component and a RC component. It is notable that, depending on an increase of the RC component, the prognosis significantly differs. Hence, the RC component is associated with metastasis and poor prognosis. However, the molecular mechanisms that contribute to the malignancy of the RC component still remain largely unknown. Here, we report microRNA-135b (miR-135b), a key regulator of the malignancy, highly expressed in the RC component and promoting MLS cell invasion in vitro and metastasis in vivo through the direct suppression of thrombospondin 2 (THBS2). Decreased THBS2 expression by miR-135b increases the total amount of matrix metalloproteinase 2 (MMP2) and influences cellular density and an extracellular matrix structure, thereby resulting in morphological change in tumor. The expression levels of miR-135b and THBS2 significantly correlated with a poor prognosis in MLS patients. Overall, our study reveals that the miR-135b/THBS2/MMP2 axis is tightly related to MLS pathophysiology and has an important clinical implication. This work provides noteworthy evidence for overcoming metastasis and improving patient outcomes, and sheds light on miR-135b and THBS2 as novel molecular targets for diagnosis and therapy in MLS.

Efficacy of neoadjuvant hypofractionated radiotherapy in patients with locally advanced myxoid liposarcoma.

BACKGROUND: Myxoid liposarcoma (MLPS) has been reported to be more radiosensitive compared with other soft tissue sarcomas (STS). The use of preoperative hypofractionated radiotherapy 5 × 5 Gy for five consecutive days, and then immediate surgery in patients with locally advanced STS showed a good local control rate. The main objective of our work was to assess the efficacy of hypofractionated radiotherapy in preoperative setting in patients with locally advanced primary MLPS. METHODS: From February 1999 to March 2014, 32 patients with primary MLPS were treated with preoperative hypofractionated radiotherapy for 5 consecutive days followed by immediate surgery (median dose 5 × 5 Gy). Median size of the tumor 10.5 cm. In one patient the tumor was located on the upper extremity, the other (31 patients) had their tumors located on the lower extremity. RESULTS: In 90% patients histologically negative surgical margins (R0) were obtained. 34% patients had distant recurrence of the disease, local recurrence was found in 9.3% of the patients. 5-year local relapse-free survival rate was 90% and overall survival was 68%. In all analyzed surgical specimens the radiotherapy response features (hyalinization, fibrosis, paucicelularity, hemorrhages, dilatation of vessels) were detected. We have not found statistically significant differences in terms of OS and LRFS for RCC component, tumor grade, BCL2, TP53, postsurgery necrosis and tumor size. In postradiotherapy specimens significantly higher positivity of TP53 expression was detected as compared to primary biopsies. CONCLUSION: Combined therapy with hypofractionated radiotherapy followed by immediate surgery seems to be effective therapy in MLPS demonstrating good local control and pathological response to therapy.

Chondroitin sulfate synthase 1 expression is associated with malignant potential of soft tissue sarcomas with myxoid substance.

The glycosyltransferases chondroitin sulfate synthase 1 (CHSY1) and exostoses-like 3 (EXTL3) specifically function in biosynthesis of the glycans chondroitin sulfate and heparan sulfate, respectively. Although these glycans play important roles in pathogenesis of various tumors, their significance in soft tissue sarcoma remains unknown. Here, we asked whether CHSY1 or EXTL3 expression correlates with malignant potential of soft tissue sarcomas with myxoid substance. To do so, we examined 40 samples representing specific types, including 12 cases of myxoid liposarcoma, 14 of myxofibrosarcoma, 12 of malignant peripheral nerve sheath tumor, and 2 of low-grade fibromyxoid sarcoma. We performed immunohistochemistry with anti-CHSY1 and anti-EXTL3 antibodies and compared enzyme expression levels with tumor histologic grade as assessed by the Fédération Nationale des Centres de Lutte Contre le Cancer classification and with patient 5-year survival rate. CHSY1 and EXTL3 were expressed in 72.5% and 32.5% of all tumors, respectively. Notably, CHSY1 was strongly expressed in myxofibrosarcoma and malignant peripheral nerve sheath tumor compared with other tumors and significantly associated with higher- rather than lower-grade tumors (P < .01). High expression of CHSY1 was also significantly associated with poorer patient outcomes (P = .031) and higher stages assessed by American Joint Committee on Cancer staging system (P = .004). By contrast, EXTL3 expression was not correlated with histologic grade or patient prognosis. We conclude that CHSY1 expression is closely associated with malignant potential of soft tissue sarcomas with myxoid substance.

Prognostic factors for the recurrence of myxoid liposarcoma: 20 cases with up to 8 years follow-up.

INTRODUCTION: Myxoid liposarcomas (MLS) are the second most common type of liposarcoma. Although some MRI findings are distinctively characteristics of MLS, the diagnosis can be tricky in tumors with a large portion of round cells (RC). Known predictors of an unfavorable outcome include age, tumor size, high RC content and positive resection margins. The goal of this retrospective study was to define prognostic factors for recurrence, with special emphasis on the percentage of RCs and medical care provided in a non-specialized center. PATIENTS AND METHODS: Twenty patients (11 women, 9 men) with a mean age of 44.3 years (18-73) were reviewed after a mean of 55.9 months. Six of these patients had been operated at a non-specialized center. The diagnostic MRI was read by a specialized radiologist and the resection procedures performed by two specialized surgeons. Tumors were labeled as either "pure myxoid liposarcoma" or "myxoid/round-cell liposarcoma". The local recurrence-free survival rate and mortality rate were calculated. RESULTS: Fifteen patients had undergone an MRI during the initial assessment. The typical MRI findings of MLS were present in four of them. The MRI suggested a non-specific lesion in the other 11 patients. After correlation with pathology findings, these tumors contained more than 5% round cells. The fourteen patients treated at our facility had undergone a biopsy, while none of the ones treated outside did. Five patients had R0 resection margins and 15 had R1 margins. Prognostic factors for recurrence consisted of age, tumor size >10 cm, R1 resection margins, FNCLCC grade 2+R1 margins, medical care at a non-specialized center, and >5% round cells. There were eight local recurrences and three metastases (15%). Two patients died (90% overall survival rate). DISCUSSION: The risk of local recurrence was 3.86 times greater in this study when the tumor contained more than 5% RCs, which is consistent with published data. The MLS diagnosis was made only four times based on the initial MRI because misleading nature of high RC tumors. R1 resection margins are a risk factor for local recurrence. However, cases with R1 margins have a recurrence rate that is similar to R0 cases when the surgery is performed at a specialized cancer center. Treatment of MLS in a non-specialized center is a key negative prognostic factor. The reported rate of metastasis varies. Atypical extrapulmonary localizations are common, and often multifocal. MRI has been shown to be superior at detecting secondary lesions and some have suggested that a full-body MRI should be performed. CONCLUSION: Prognostic factors for the recurrence of myxoid liposarcomas have been identified. MRI analysis is not definitive and must be supplemented by a biopsy.

Is multimodality therapy necessary for the management of pure myxoid liposarcomas? A multi-institutional series of pure myxoid liposarcomas of the extremities and torso.

BACKGROUND AND OBJECTIVES: The treatment of patients with pure (<5% round cell component) myxoid liposarcomas (pMLS) has not been well characterized. We hypothesized that multimodality therapy (oncological resection with radiation therapy) may not be necessary for pMLS. METHODS: Patients who underwent resection of localized pMLS at three institutions from 2000 to 2010 were identified and treatment variables were analyzed. RESULTS: Of 75 pts with pMLS, the median tumor size was 10 cm, the majority (95%) were deep tumors, and located in lower extremity. Radiation (XRT) was administered to 58 pts(77%). Comparing the no XRT to XRT patients, lower extremity location (77% vs. 79%, P=1.0), tumor size (13 vs. 11 cm, P=0.3), and positive margins (13% vs. 16%, P=1.0) were similar. The majority (82%) of patients not receiving XRT had deep tumors. After a median follow-up of 60 months, 2 pts (3%) developed local recurrence and 10 pts (13%) developed distant recurrence with a mean recurrence-free survival (RFS) and disease-specific survival (DSS) of 114 and 148 mos, respectively. In multivariate analyses, increasing age and tumor size were the only significant predictors of recurrence. XRT was not a significant predictor of RFS in multivariate analysis. CONCLUSIONS: pMLS is an STS subtype with favorable tumor biology and an extremely low-rate of local recurrence. Our results suggest that multimodality therapy may not be necessary for all pMLS.

Clinicopathologic prognostic factors of pure myxoid liposarcoma of the extremities and trunk wall.

BACKGROUND: Myxoid liposarcoma is generally considered a low grade tumor but the presence of areas of round cells exceeding 5% is reportedly associated with a worse prognosis. Whether "pure" tumors without round cells are low grade has not been confirmed. While radiotherapy has been used for patients' myxoid liposarcoma it is unclear whether it reduces local recurrences. QUESTIONS/PURPOSES: We therefore determined the survival, roles of radiotherapy for local control, and prognostic factors of pure myxoid liposarcoma of the extremities and trunk wall. METHODS: We retrospectively reviewed 53 patients histologically diagnosed with pure myxoid liposarcoma arising in extremities and the trunk wall. Nine patients of the 53 received radiotherapy for primary tumors. Clinical features and prognosis was determined, and various factors were analyzed as to their usefulness as prognostic factors (age, gender, location, size, depth, surgical margin, and adjuvant radiotherapy). The minimum followup was 12 months (mean, 60 months; range, 12-226 months). RESULTS: Seven (13%) and 6 (11%) patients developed a local recurrence and distant metastasis, respectively. The 5- and 10-year disease-specific and disease-free survival rates were 90% and 83% and 77% and 77%, respectively. Radiotherapy had no impact on either overall or disease free survival. Age (older than 60 years) independently predicted worse overall and disease-free survival. CONCLUSIONS: In pure myxoid liposarcoma located in the extremities and trunk wall, relatively few patients developed distant metastasis suggesting the tumor is generally low grade. Local control could be achieved with wide surgical margins without radiotherapy. Age was associated with lower survival but size and depth were not. Myxoid liposarcoma in older patients requires special consideration for treatment and followup.

Radiosensitivity translates into excellent local control in extremity myxoid liposarcoma: a comparison with other soft tissue sarcomas.

BACKGROUND: Myxoid liposarcoma has been reported to be more radiosensitive compared with other soft tissue sarcomas (STS). The authors report the results of multidisciplinary treatment of extremity myxoid liposarcoma compared with a contemporary cohort of other STS subtypes with an emphasis on the role of radiotherapy (RT) in improving local control. METHODS: Between 1989 and 2004, 691 patients were identified from a prospective STS database who underwent combined management for localized extremity STS and were followed for a minimum of 12 months or until death. All patients underwent surgery together with pre or postoperative RT, depending on their presenting characteristics and resection margins. Demographics and outcomes were compared between patients with myxoid liposarcoma and other STS subtypes (other-STS). RESULTS: Of 691 patients, 88 patients had myxoid liposarcoma and 603 had other STS subtypes (other-STS). Median age was 48 and 60 years for the myxoid liposarcoma and other-STS groups, respectively. Median follow-up was 86 and 61 months, respectively. For myxoid liposarcoma and other-STS groups, preoperative RT was used in 57% versus 61% of patients and postoperative RT in 43% versus 39%, respectively. The 5-year local recurrence-free survival was 97.7% for patients with myxoid liposarcoma compared with 89.6% for patients with other-STS tumors (P = .008). High-grade tumors were present in 7% and 59% of myxoid liposarcoma and other-STS patients, respectively (P = .0003). Two myxoid liposarcoma patients with local recurrence had positive resection margins, whereas only 33% of patients in the other-STS group who developed a local recurrence had positive resection margins. No patients with myxoid liposarcoma required amputation as primary management, whereas 8 (1.3%) required amputation as primary management in the other-STS group. Systemic disease control was superior in myxoid liposarcoma compared with other-STS patients, with 5-year overall and metastasis-free survival rates of 93.9% versus 76.4% (P = .0008) and 89.1% versus 66.0% (P = .0001) respectively. Of 12 myxoid liposarcoma patients with distant metastases, 7 appeared in nonpulmonary sites. In comparison, 205 (34%) patients with other-STS tumors developed systemic disease but 78% had pulmonary metastases. CONCLUSIONS: Multidisciplinary management of extremity STS achieves high rates of local control. Myxoid liposarcoma is associated with higher rates of local control compared with other STS subtypes, after combined surgery and radiation, suggesting a particular radiosensitivity that can be exploited to improve oncologic outcome in appropriate cases.

Liposarcomas in young patients: a study of 82 cases occurring in patients younger than 22 years of age.

Liposarcomas typically occur in middle aged to older adults. Altogether, approximately 50 bona fide liposarcomas have been reported in children and adolescents, most of which have represented myxoid liposarcomas, with a good prognosis. We undertook a retrospective study of 82 liposarcomas occurring in patients below 22 years of age. Clinicopathologic and follow-up information was obtained. Fluorescence in situ hybridization for FUS, EWSR1, CHOP (DDIT3), and MDM2 was performed in 30 cases. The tumors occurred in 28 males and 54 females (5 to 22 y of age) and involved many locations. Fifty-six cases were typical myxoid liposarcomas, including 2 with round cell areas. The tumors were grade 1 (56 cases) and grade 3 (2 cases). Thirty-seven of 38 patients with follow-up are alive without disease and 1 is alive with disease (median 59 mo follow-up duration, range: 8 to 108 mo). Six cases showed myxoid liposarcoma with spindled growth ("spindle cell myxoid liposarcoma"); these arose in 5 females and 1 male (median age 14 y) and involved the thigh in 40% of cases. All were grade 1. Follow-up (4 of 6 patients) showed local recurrences in 2 cases and metastases in 1 case. Twelve tumors consisted of conventional myxoid liposarcoma and pleomorphic liposarcoma ("pleomorphic myxoid liposarcoma"); these arose in 4 males and 8 females (10 to 22 y of age) and often involved the mediastinum. Tumor grades were 2 (4 cases) and 3 (8 cases). Follow-up (10 patients) showed 7 dead of disease, 1 alive with disease, and 2 disease free. Four atypical lipomatous tumors were seen including 2 with low-grade dedifferentiation. Two local recurrences were seen; all patients are disease free. Two conventional pleomorphic liposarcomas were seen; 1 patient with follow-up is disease free. FUS-CHOP and EWSR1-CHOP rearrangements were identified by fluorescence in situ hybridization in 15/23 and 2/23 conventional myxoid liposarcomas, respectively, and in no other tumors. Amplification for MDM2 was absent in all cases. We conclude that conventional myxoid liposarcoma is by far the most common subtype of liposarcoma in young patients, with an excellent prognosis. Two apparently novel subtypes of liposarcoma, termed pleomorphic myxoid liposarcoma and spindle cell myxoid liposarcoma comprise considerable percentages of liposarcomas in this age group and should be distinguished from conventional myxoid liposarcoma and conventional pleomorphic liposarcoma. Pleomorphic myxoid liposarcoma and spindle cell myxoid liposarcoma most likely represent high-grade and low-grade variants of myxoid liposarcoma, respectively. Additional study of such cases will be necessary for definitive classification.

Excellent local control rates and distinctive patterns of failure in myxoid liposarcoma treated with conservation surgery and radiotherapy.

PURPOSE: To evaluate the local control rates and patterns of metastatic relapse in patients with localized myxoid liposarcoma treated with conservation surgery and radiotherapy (RT). PATIENTS AND METHODS: Between 1960 and 2003, 127 patients with non-metastatic myxoid liposarcoma were treated with conservation surgery and RT at our institution. The median patient age was 39 years (range, 14-79 years). Of the 127 patients, 46% underwent preoperative RT (median dose, 50 Gy) and 54% underwent postoperative RT (median dose, 60 Gy). Also, 28% received doxorubicin-based chemotherapy as a part of their treatment. RESULTS: The median follow-up was 9.1 years. The overall survival rate at 5 and 10 years was 87% and 79%, respectively. The corresponding disease-free survival rates were 81% and 73%. The local control rate at > or =5 years was 97%. The actuarial rate of distant metastases at 5 and 10 years was 15% and 24%, respectively. Of the 27 patients who developed distant metastases, 48% did so in the retroperitoneum, 22% in other extrapulmonary soft tissues, 22% in the lung, 15% in bone, and 4% in the liver. CONCLUSION: The results of our study have shown that RT and conservation surgery for localized myxoid liposarcoma provide excellent local control. Distant metastatic relapse tended to occur in the retroperitoneum and other nonpulmonary soft tissues. Therefore, staging and surveillance imaging should include the abdomen and pelvis, as well as the thorax, for patients with localized myxoid liposarcoma.

Myxoid/round cell and pleomorphic liposarcomas: prognostic factors and survival in a series of patients treated at a single institution.

BACKGROUND: The objective of this study was to investigate prognostic factors and clinical outcome of myxoid/round cell and pleomorphic liposarcoma. METHODS: Three hundred twenty-nine patients with localized myxoid/round cell or pleomorphic liposarcoma who underwent surgery at the Istituto Nazionale per lo Studio e la Cura dei Tumori (Milan, Italy) over 25 years were reviewed. The rates of local recurrence, distant metastases, and survival were studied. RESULTS: Two hundred fourteen patients presented with primary disease, and 115 patients had locally recurrent tumors. The disease-specific survival rate was 75% at 10 years, and the local recurrence and distant metastases incidence were 25% and 15%, respectively. Presentation with recurrent disease, tumor size (>10 cm), tumor grade (French Federation of Cancer Centers grade II or III vs grade I), and positive surgical margins were independent predictors of death. Tumor site and radiation therapy also played a role, mostly related to their effect on local outcome. Pathologic grade and histologic subtype influenced distant metastases. Extrapulmonary metastases were associated with poorer postmetastatic disease-specific survival. CONCLUSIONS: Myxoid/round cell liposarcomas shared similar prognostic factors with other soft tissue sarcomas and had a relatively good clinical outcome. The presence of >5% of round cell component singled out a group of patients at greater risk of metastases and death but with a broad spectrum of disease aggressiveness. Extrapulmonary metastases were a peculiar pattern of myxoid/round cell liposarcoma that require special consideration for treatment and prognosis.

Skeletal metastases in myxoid liposarcoma: an unusual pattern of distant spread.

BACKGROUND: Myxoid liposarcoma (MLS), the second most common subtype of liposarcoma, occurs predominantly in the extremities of young adults and has a disproportionately high tendency to metastasize to unusual soft tissue locations, before disseminated spread or pulmonary metastases. Anecdotal evidence, mainly supported by isolated case reports, suggests that a subset of these patients also develop bone metastasis, especially within the spine, which was previously under-appreciated. STUDY DESIGN: In this study we investigate the incidence of osseous metastases in a well annotated sarcoma database and correlate this endpoint with clinicopathologic and molecular findings. RESULTS: From a total of 230 patients with MLS diagnosis confirmed histologically, who were managed and followed prospectively at MSKCC, 40 (17%) developed skeletal metastases, comprising 56% of all metastatic events. A significant number of these bone metastases were identified early in the disease course, before the manifestation of disease in sites where sarcomas usually metastasize, such as lung. From the time of 1st metastasis, the 5 years median survival was 16%. The majority (78%) of MLS patients developing bone metastases had a histologic high grade primary tumor. The median overall survival for the high grade tumors was 55 months, as compared to 105 months for low grade cases. Eleven (84%) of 13 cases tested by RT-PCR demonstrated a type II TLS-CHOP fusion transcript. CONCLUSION: These findings suggest that MLS has a high incidence of osseous metastases, with predilection to spine, and often associated with the most common type of TLS-CHOP transcript. Screening should include images of the spine in high-risk MLS patients to exclude spinal metastases.