Amputation in patients with extremity soft tissue sarcoma: the experience of an East Asian referral center.

BACKGROUND: This study aimed to investigate the characteristics and clinical outcomes in a series of patients with extremity soft tissue sarcoma (STS) who underwent amputation at a large East Asian referral center. PATIENTS AND METHODS: Of the 652 patients who underwent surgery for extremity STS, data of 37 consecutive patients who underwent amputation were reviewed retrospectively. The median follow-up period was 96.0 months (range, 15-216). The patients were classified in to three cohorts. The primary localized (PL) group included patients who underwent amputation as a primary surgical procedure with curative intent. The recurrent localized (RL) group included patients who underwent amputation as a revision procedure after failure of previous limb sparing surgeries. The metastatic group included patients who underwent amputation as a palliative procedure. RESULTS: There were 22 cases of amputation in 596 STS patients and the amputation rate was 3.6% (22/596). Further, 1.8% (9/490) of patients with primary localized STS underwent amputation. Patients with localized STS who underwent amputation had a 5-year disease-specific survival (DSS) rate of 89.9% (95% Confidence Interval (CI), 87.1-92.7%), a local-recurrence-free survival (LRFS) of 84.1% (95% CI, 80.5-87.6%), and a metastasis-free survival (MFS) of 84.6%. (95% CI, 81.1-88.0%) Compared with previous studies, our results showed higher DSS and MFS rates with similar LRFS. CONCLUSIONS: The amputation rate of extremity STS in our institute in East Asia was similar but slightly lower than that reported in Western studies. The oncologic outcome of amputation reported in this study was higher than that indicated in Western studies and oncologic outcome of amputation was not statistically different from those of limb salvage surgery. However, considering the small cohort in single institute study, there is a possibility of selection bias and future multi-center study is necessary. From our results, amputation is still a feasible option for appropriately selected patients unsuitable for limb-conserving surgery.

Comparison of survival prediction models for bone metastases of the extremities following surgery.

Aims: This study aimed to compare the performance of survival prediction models for bone metastases of the extremities (BM-E) with pathological fractures in an Asian cohort, and investigate patient characteristics associated with survival. Methods: This retrospective cohort study included 469 patients, who underwent surgery for BM-E between January 2009 and March 2022 at a tertiary hospital in South Korea. Postoperative survival was calculated using the PATHFx3.0, SPRING13, OPTIModel, SORG, and IOR models. Model performance was assessed with area under the curve (AUC), calibration curve, Brier score, and decision curve analysis. Cox regression analyses were performed to evaluate the factors contributing to survival. Results: The SORG model demonstrated the highest discriminatory accuracy with AUC (0.80 (95% confidence interval (CI) 0.76 to 0.85)) at 12 months. In calibration analysis, the PATHfx3.0 and OPTIModel models underestimated survival, while the SPRING13 and IOR models overestimated survival. The SORG model exhibited excellent calibration with intercepts of 0.10 (95% CI -0.13 to 0.33) at 12 months. The SORG model also had lower Brier scores than the null score at three and 12 months, indicating good overall performance. Decision curve analysis showed that all five survival prediction models provided greater net benefit than the default strategy of operating on either all or no patients. Rapid growth cancer and low serum albumin levels were associated with three-, six-, and 12-month survival. Conclusion: State-of-art survival prediction models for BM-E (PATHFx3.0, SPRING13, OPTIModel, SORG, and IOR models) are useful clinical tools for orthopaedic surgeons in the decision-making process for the treatment in Asian patients, with SORG models offering the best predictive performance. Rapid growth cancer and serum albumin level are independent, statistically significant factors contributing to survival following surgery of BM-E. Further refinement of survival prediction models will bring about informed and patient-specific treatment of BM-E.

Case Series of Soft Tissue Sarcoma Patients with Brain Metastasis with Implications from Genomic and Transcriptomic Analysis.

PURPOSE: Brain metastasis rarely occurs in soft tissue sarcoma (STS). Here, we present five cases of STS with brain metastases with genetic profiles. MATERIALS AND METHODS: We included five patients from Seoul National University Hospital who were diagnosed with STS with metastasis to the brain. Tissue from the brain metastasis along with that from the primary site or other metastases were used for DNA and RNA sequencing to identify genetic profiles. Gene expression profiles were compared with sarcoma samples from The Cancer Genome Atlas. RESULTS: The overall survival after diagnosis of brain metastasis ranged from 2.2 to 34.3 months. Comparison of mutational profiles between brain metastases and matched primary or other metastatic samples showed similar profiles. In two patients, copy number variation profiles between brain metastasis and other tumors showed several differences including MYCL, JUN, MYC, and DDR2 amplification. Gene ontology analysis showed that the group of genes significantly highly expressed in the brain metastasis samples was enriched in the G-protein coupled receptor activity, structural constituent of chromatin, protein heterodimerization activity, and binding of DNA, RNA, and protein. Gene set enrichment analysis showed enrichment in the pathway of neuroactive ligand-receptor interaction and systemic lupus erythematosus. CONCLUSION: The five patients had variable ranges of clinical courses and outcomes. Genomic and transcriptomic analysis of STS with brain metastasis implicates possible involvement of complex expression modification and epigenetic changes rather than the addition of single driver gene alteration.

Does the Clinical Presentation of Secondary Osteosarcoma in Patients Who Survive Retinoblastoma Differ From That of Conventional Osteosarcoma and How Do We Detect Them?

BACKGROUND: Osteosarcoma is the most common secondary malignancy among survivors of retinoblastoma. Most previous reports on secondary malignancy of retinoblastoma included all types of secondary malignancies without a focus on osteosarcoma, owing to its rarity. In addition, there are few studies suggesting tools for regular surveillance for early detection. QUESTIONS/PURPOSES: (1) What are the radiologic and clinical characteristics of secondary osteosarcoma after retinoblastoma? (2) What is the clinical survivorship? (3) Is a radionuclide bone scan a reasonable imaging modality for early detection in patients with retinoblastoma? METHODS: Between February 2000 and December 2019, we treated 540 patients for retinoblastoma. Twelve patients (six male, six female) subsequently developed an osteosarcoma in the extremities; two of these patients had two sites of osteosarcoma (10 femurs, four tibiae) . A Technetium-99m bone scan image was examined annually in all patients for regular surveillance after the treatment of retinoblastoma as per our hospital's policy. All patients were treated with the same strategy as that used for primary conventional osteosarcoma, namely neoadjuvant chemotherapy, wide excision, and adjuvant chemotherapy. The median follow-up period was 12 years (range 8 to 21 years). The median age at the time of diagnosis of osteosarcoma was 9 years (range 5 to 15 years), and the median interval from retinoblastoma diagnosis to osteosarcoma diagnosis was 8 years (range 5 to 15 years). Radiologic characteristics were assessed with plain radiographs and MRI, while clinical characteristics were assessed through a retrospective review of medical records. For clinical survivorship, we evaluated overall survival, local recurrence-free survival, and metastasis-free survival. We reviewed the results of bone scans and clinical symptoms at the time of diagnosis for osteosarcoma after retinoblastoma. RESULTS: In nine of 14 patients, the tumor had a diaphyseal center, and five of the tumors were located at the metaphysis. The femur was the most common site (n = 10), followed by the tibia (n = 4). The median tumor size was 9 cm (range 5 to 13 cm). There was no local recurrence after surgical resection of the osteosarcoma, and the 5-year overall survival rate after the diagnosis of osteosarcoma was 86% (95% CI 68% to 100%). In all 14 tumors, the Technetium bone scan showed increased uptake in the lesions. Ten of 14 tumors were examined in clinic because of patient complaints of pain in the affected limb. Four patients showed no clinical symptoms detected by abnormal uptake on bone scan. CONCLUSION: For unclear reasons, secondary osteosarcomas in patients who were alive after the treatment of retinoblastoma had a slight predilection for the diaphysis of the long bone compared with patients with spontaneous osteosarcoma in other reports. The clinical survivorship of osteosarcoma as a secondary malignancy after retinoblastoma may not be inferior to that of conventional osteosarcoma. Close follow-up with at least yearly clinical assessment and bone scans or other imaging modalities appears to be helpful in detecting secondary osteosarcoma after the treatment of patients with retinoblastoma. Larger multi-institutional studies will be needed to substantiate these observations.Level of Evidenc e Level IV, therapeutic study.

Whole-Genome Sequencing Reveals Mutational Signatures Related to Radiation-Induced Sarcomas and DNA-Damage-Repair Pathways.

Radiation-induced sarcoma (RIS) is a rare but serious late complication arising from radiotherapy. Despite unfavorable clinical outcomes, the genomic footprints of ionizing radiation in RIS development remain largely unknown. Hence, this study aimed to characterize RIS genomes and the genomic alterations in them. We analyzed whole-genome sequencing in 11 RIS genomes matched with normal genomes to identify somatic alterations potentially associated with RIS development. Furthermore, the abundance of mutations, mutation signatures, and structural variants in RIS were compared with those in radiation-naïve spontaneous sarcomas. The mutation abundance in RIS genomes, including one hypermutated genome, was variable. Cancer-related genes might show different types of genomic alterations. For instance, NF1, NF2, NOTCH1, NOTCH2, PIK3CA, RB1, and TP53 showed singleton somatic mutations; MYC, CDKN2A, RB1, and NF1 showed recurrent copy number alterations; and NF2, ARID1B, and RAD51B showed recurrent structural variations. The genomic footprints of nonhomologous end joining are prevalent at indels of RIS genomes compared with those in spontaneous sarcoma genomes, representing the genomic hallmark of RIS genomes. In addition, frequent chromothripsis was identified along with predisposing germline variants in the DNA-damage-repair pathways in RIS genomes. The characterization of RIS genomes on a whole-genome sequencing scale highlighted that the nonhomologous end joining pathway was associated with tumorigenesis, and it might pave the way for the development of advanced diagnostic and therapeutic strategies for RIS.

EMMPRIN expression is associated with metastatic progression in osteosarcoma.

BACKGROUND: Extracellular matrix metalloproteinase inducer (EMMPRIN), a cell-surface glycoprotein, is overexpressed in several cancer types. EMMPRIN induces a metastatic phenotype by triggering the production of matrix metalloproteinase proteins (MMPs) such as MMP1 and MMP2, and vascular endothelial growth factor (VEGF) in cancer cells and the surrounding stromal cells. The purpose of this study was to investigate the expression and role of EMMPRIN in osteosarcoma. METHODS: The level of EMMPRIN expression was evaluated using reverse transcriptase polymerase chain reaction (RT-PCR) in 6 tumor-derived osteosarcoma cell lines and compared with that in normal osteoblasts. To study the prognostic significance of EMMPRIN expression, immunohistochemistry was carried out in prechemotherapy biopsies of 54 patients. siRNA knockdown of EMMPRIN in SaOS-2 cells was conducted to explore the role of EMMPRIN. To study the role of EMMPRIN in tumor-stromal interaction in MMP production and invasion, co-culture of SaOS-2 cells with osteoblasts and fibroblasts was performed. Osteosarcoma 143B cells were injected into the tail vein of BALB/c mice and lung metastasis was analyzed. RESULTS: EMMRIN mRNA expression was significantly higher in 5 of 6 (83%) tumor-derived cells than in MG63 cells. 90% of specimens (50/54) stained positive for EMMPRIN by immunohistochemistry, and higher expression of EMMPRIN was associated with shorter metastasis-free survival (p = 0.023). Co-culture of SaOS-2 with osteoblasts resulted in increased production of pro-MMP2 and VEGF expression, which was inhibited by EMMPRIN-targeting siRNA. siRNA knockdown of EMMPRIN resulted in decreased invasion. EMMPRIN shRNA-transfected 143B cells showed decreased lung metastasis in vivo. CONCLUSIONS: Our data suggest that EMMPRIN acts as a mediator of osteosarcoma metastasis by regulating MMP and VEGF production in cancer cells as well as stromal cells. EMMPRIN could serve as a therapeutic target in osteosarcoma.

Impact of surgical margin on survival in extremity soft tissue sarcoma: A systematic review and meta-analysis.

BACKGROUND: The impact of surgical margin status on the survival of patients with extremity soft tissue sarcoma (STS) remains to be clearly defined. The evidence regarding the impact of surgical margins on survival is limited by retrospective single-institution cohort studies. We conducted a systematic review and meta-analysis to examine the impact of surgical margin status on patient survival in extremity STS. METHODS: A literature search in the PubMed, EMBASE, and Cochrane Controlled Trials Register electronic databases, and a manual search of reference lists of original studies was performed. The following text words and/or Medical Subject Heading terms were searched: (neoplasm) or/and (sarcoma) and/or (connective tissue) and/or (soft tissue) and/or (extremity) and/or (extremity) and/or (surgical margin). RESULTS: Six selected studies that reported a total of 2917 cases of extremity STS were published between 1994 and 2013. All the eligible studies were observational cohort studies, and the sample size ranged from 95 to 1261 patients. A meta-analysis of 6 studies showed that a positive surgical margin predicted poor 5-year OS in a random-effects model (summary hazard ratio, 1.56; 95% confidence interval, 1.12-2.17). Moderate heterogeneity was observed among the studies (P < .075; heterogeneity, 45.6%). CONCLUSIONS: This meta-analysis supports the hypothesis that adequate surgical margins are associated with improved survival in extremity STS.

Actual long-term survival after resection of stage III soft tissue sarcoma.

BACKGROUND: Actuarial survival based on the Kaplan-Meier method can overestimate actual long-term survival, especially among those with factors of poor prognosis. Patients with American Joint Committee on Cancer stage III soft tissue sarcoma (STS) represent a subset with a high risk of STS-specific mortality. Therefore, we aimed to characterize the clinicopathological characteristics associated with actual long-term survival in patients with stage III STS. METHODS: We retrospectively reviewed 116 patients who underwent surgical resection for stage III STS with curative intent between March 2000 and December 2013. Long-term survivors (n = 61), defined as those who survived beyond 5 years, were compared with short-term survivors (n = 36), who died of STS within 5 years. RESULTS: Multivariate logistic regression analyses showed that a tumor size < 10 cm [odds ratio (OR) 3.95, p = 0.047], histological grade of 2 (OR 8.12, p = 0.004), and American Society of Anesthesiologists (ASA) score of 1 (OR 11.25, p = 0.001) were independently associated with actual 5-year survival. However, 66% of the long-term survivors exhibited factors of poor prognosis: 36% had a tumor size > 10 cm and 48% had a histological grade of 3. Leiomyosarcoma (3 of 10) was negatively associated with actual long-term survival. CONCLUSIONS: Actual 5-year survival after resection of stage III STS was associated with tumor size, histological grade, and ASA score. However, majority of the actual 5-year survivors exhibit factors of poor prognosis, suggesting that aggressive treatment should be offered for a chance of long-term survival in these patients.

Delta-like Factor 1 as a Possible Therapeutic Target for Sarcomas.

BACKGROUD: Cancer stem cells (CSCs) are cells characterized by their self-renewal and tumorigenic potential. The purpose of this study was to discover the role of the delta-like factor 1 (DLK1) in sarcoma. METHODS: mRNA expression of DLK1 from 13 sarcoma cell lines was examined. Isolated CSCs from the tumors were examined using fluorescence-activated cell sorting (FACS) with CD133, the CSC marker, or sphere-forming assay. The relationship between DLK1 and CSCs in sarcoma was examined using cell proliferation and cell invasion assays after they were treated with DLK1 short interfering RNA (siRNA). RESULTS: A high expression of DLK1 mRNA was observed in all sarcoma cell lines. However, CSCs were isolated from over expressed sarcomas of the DLK1 gene, and they have shown to be expressed lower than the wild type. The anti-cancer effects of DLK1 siRNA inhibited cell proliferation and invasion in U2OS, A204, and sw872. In addition, treatment with DLK1 siRNA inhibited cell invasion in sw872 CSCs. DLK1 gene induces tumorigenesis in various sarcoma cells and regulates the invasiveness of liposarcoma. These results suggest that DLK1 could serve as a possible therapeutic target for sarcoma. CONCLUSIONS: Our study showed that the DLK1 gene induces tumorigenesis in various sarcomas and is associated with invasive mechanism in sarcoma. These results suggest DLK1 could serve as a possible therapeutic target in a variety of sarcomas.

Transepiphyseal resection for osteosarcoma in patients with open physes using MRI assessment.

AIMS: For paediatric and adolescent patients with growth potential, preservation of the physiological joint by transepiphyseal resection (TER) of the femur confers definite advantages over arthroplasty procedures. We hypothesized that the extent of the tumour and changes in its extent after neoadjuvant chemotherapy are essential factors in the selection of this procedure, and can be assessed with MRI. The oncological and functional outcomes of the procedure were reviewed to confirm its safety and efficacy. METHODS: We retrospectively reviewed 16 patients (seven male and nine female, mean age 12.2 years (7 to 16)) with osteosarcoma of the knee who had been treated by TER. We evaluated the MRI scans before and after neoadjuvant chemotherapy for all patients to assess the extent of the disease and the response to treatment. RESULTS: The mean follow-up period was 64.3 months (25 to 148) after surgery and no patients were lost to follow-up. On MRI evaluation, 13 tumours were near but not in contact with the physes and three tumours were partially in contact with the physes before neoadjuvant chemotherapy. Bone oedema in the epiphysis was observed in eight patients. After neoadjuvant chemotherapy, bone oedema in the epiphysis disappeared in all patients. In total, 11 tumours were not in contact and five tumours were in partial contact with the physes. The postoperative pathological margin was negative in all patients. At the last follow-up, 12 patients were continuously disease-free and three had no evidence of disease. One patient died due to the disease. Functionally, the patients with retained allograft or recycled autograft had a mean knee range of flexion of 126° (90° to 150°). The mean Musculoskeletal Tumor Society functional score was 27.6 (23 to 30). CONCLUSION: TER is an effective limb-salvage technique for treating malignant metaphyseal bone tumours in paediatric and young osteosarcoma patients with open physes when a good response to chemotherapy and no progression of the tumour to the epiphysis have been confirmed by MRI. Cite this article: Bone Joint J 2020;102-B(6):772-778.

Postoperative delirium in patients undergoing surgery for bone metastases.

Postoperative delirium (PD), characterized by acute onset of global impairment in consciousness and cognition, is a common complication following major surgeries and is often associated with adverse outcomes. Because of the multiple comorbidities of the patient along with extensive nature of the surgery, patients undergoing surgery for bone metastases may be prone to developing PD. However, no study exists regarding PD in patients who undergo surgery for bone metastases.Two hundred seventy six patients with mean age of 64 years (range, 16-94) who underwent surgery for bone metastases were reviewed. The diagnosis of PD was made by the psychiatrist, according to fourth edition of the Diagnostic and Statistical Manual of Mental Disorders. Possible perioperative clinic-pathologic factors that may be associated with the development of PD were investigated.Among the 276 patients, 9% (n = 25) developed PD. On multivariate logistic regression analysis, history of psychiatric disorders (odds ratio [OR] = 9.63; 95% confidence interval [CI] 1.78-21.74, P = .004), high preoperative serum C-reactive protein (CRP) level (OR = 1.17; 95% CI 1.06-1.29, P = .001), low preoperative serum albumin level (OR = 0.13; 95% CI 0.03-0.48, P = 0.002), and high dose of opioid analgesics received in the immediate postoperative period (OR = 1.05; 95% CI 1.01-1.07, P = .001) were independently associated with the development of PD. Patients with PD had lower survival (log rank, P = .001) than patients without PD.Incidence of PD is considerable in patients undergoing surgery for bone metastases. History of psychiatric disorders, preoperative serum albumin and CRP levels, and the dose of postoperative opioid analgesics are associated with the development of PD.

Factors Associated with Disease Stabilization of Desmoid-Type Fibromatosis.

BACKGROUND: Spontaneous disease stabilization of desmoid-type fibromatosis (DF) has been demonstrated in many reports, and the watchful waiting approach without any frontline treatment is becoming popular as an initial management strategy. In this study, we aimed to assess the disease stabilization rate and identify predictive factors for disease stabilization of DF in patients with conservative treatment. METHODS: We reviewed 76 patients with sporadic extra-abdominal DF who were managed with frontline conservative treatment in our institute. The minimum follow-up was 12 months. Stabilization was defined as radiological evidence of no change or continuous decrease in size of the tumor for six months or more. The primary endpoint was stabilization of DF. Possible patient-, disease-, and treatment-related factors predictive of disease stabilization were analyzed with multivariate analysis. RESULTS: At final follow-up, 54 of the 76 tumors (71%) were stable, and mean time to stabilization was 30.4 months (range, 7 to 112 months). On Kaplan-Meier survival analysis, the spontaneous stabilization rate was 25.4% at one year, 52.7% at two years, and 70.9% at three years. The mean time to spontaneous stabilization was longer in patients with ≤ 40 years of age (p = 0.022) or recurrence (p = 0.041). On multivariate analysis with the Cox proportional hazard method, recurrence (hazard ratio [HR], 1.79; p = 0.041) and younger age (HR, 2.04; p = 0.022) were identified as independent prognostic factors for longer time to disease stabilization. CONCLUSIONS: Frontline conservative treatment seems to be the optimal treatment for most patients with DF. Younger patients or those with recurrence may require longer time to spontaneous disease stabilization.

Ambulation Recovery After Surgery for Metastases to the Femur.

BACKGROUND: Postoperative ambulation recovery after surgery for femur metastases has significant implications for not only the patient's quality of life but also administration of further cancer treatment. Thus, identification of preoperative predictors of ambulation recovery is necessary to set appropriate expectations and guide treatment. This study aimed to assess ambulation recovery rate and identify predictors of ambulation recovery in patients undergoing surgery for femur metastases. MATERIALS AND METHODS: A total of 244 patients who underwent surgery for femur metastases at our institution were reviewed. Patients were considered ambulatory if they were able to walk independently or walk with aids and nonambulatory if they were wheelchair bound or bedridden. The following potential clinicopathologic factors that might predict postoperative ambulation recovery were evaluated: premorbid general status, cancer burden, and local factors. RESULTS: A total of 165 patients (68%) regained ambulatory status postoperatively. A multivariate analysis revealed poor Eastern Cooperative Oncology Group (ECOG) performance status (odds ratio [OR], 5.327; p < .001) and nonambulatory premorbid ambulatory status (OR, 7.459; p < .001) as independent predictors of poor ambulation recovery after surgery for femur metastases. Postoperative ambulatory status was significantly associated with postoperative survival time (p < .001). CONCLUSION: Postoperative ambulation recovery rate in our cohort was 68%. Premorbid ambulatory status and ECOG performance status are predictors of ambulation recovery in patients undergoing surgery for femur metastases. IMPLICATIONS FOR PRACTICE: Postoperative ambulation recovery rate in this cohort was 68%. Premorbid ambulatory status and Eastern Cooperative Oncology Group performance status are predictors of ambulation recovery in patients undergoing surgery for femur metastases.

The role of chemotherapy and radiotherapy in localized extraskeletal osteosarcoma.

PURPOSE: The role of chemotherapy (CT) and radiotherapy (RT) for management of extraskeletal osteosarcoma (ESOS) remains controversial. We examined disease outcomes for ESOS patients and investigated the association between CT/RT with recurrence and survival. PATIENTS AND METHODS: Retrospective review at 25 international sarcoma centers identified patients ≥18 years old treated for ESOS from 1971 to 2016. Patient/tumour characteristics, treatment, local/systemic recurrence, and survival data were collected. Kaplan-Meier survival and Cox proportional-hazards regression and cumulative incidence competing risks analysis were performed. RESULTS: 370 patients with localized ESOS treated definitively with surgery presented with mainly deep tumours (n = 294, 80%). 122 patients underwent surgical resection alone, 96 (26%) also received CT, 70 (19%) RT and 82 (22%) both adjuvants. Five-year survival for patients with localized ESOS was 56% (95% CI 51%-62%). Almost half of patients (n = 173, 47%) developed recurrence: local 9% (35/370), distant 28% (102/370) or both 10% (36/370). Considering death as a competing event, there was no significant difference in cumulative incidence of local or systemic recurrence between patients who received CT, RT, both or neither (local p = 0.50, systemic p = 0.69). Multiple regression Cox analysis showed a significant association between RT and decreased local recurrence (HR 0.46 [95% CI 0.26-0.80], p = 0.01). CONCLUSION: Although the use of RT significantly decreased local recurrences, CT did not decrease the risk of systemic recurrence, and neither CT, nor RT nor both were associated with improved survival in patients with localized ESOS. Our results do not support the use of CT; however, adjuvant RT demonstrates benefit in patients with locally resectable ESOS.

Prognoses of superficial soft tissue sarcoma: The importance of fascia-tumor relationship on MRI.

BACKGROUND: Superficial soft tissue sarcoma (S-STS) has been reported to have more favorable prognoses than deep-seated STS. However, for some patients, poor prognoses have been observed and there is a need for better prognostication. The deep peripheral fascia lies in the border of the S-STS and can be consistently detected using magnetic resonance imaging (MRI). The relationship of the subcutaneous tumor with the fascia on MRI scan was reported to be useful in classifying the tumor as benign or malignant; this in turn, may reflect the biological aggressiveness of STS. This study was performed to evaluate the oncologic outcomes and to identify the prognostic factors of S-STS by focusing on the relationship of S-STS with the underlying fascia on MRI. MATERIAL AND METHODS: We retrospectively reviewed data on 253 patients who underwent resection of localized S-STS. Potential factors that might influence the oncologic outcomes were identified. The fascia-tumor relationship on MRI was classified into three groups: no fascial contact group (n = 46), fascial contact group (n = 77), and fascial invasion group (n = 84). RESULTS: Overall, 39 patients (16.5%) died due to S-STS; the 5- and 10-year survival rates were 82.6 ±â€¯2.9% and 73.2 ±â€¯4.5%, respectively. Fascial invasion detected on MRI scans (OR = 2.190, p = 0.034) and advanced age (OR = 2.408, p = 0.034) were found to be independent factors for worse disease specific survival. The fascia-tumor relationship on MRI scan was not associated with local recurrence of S-STS. CONCLUSION: The fascia-tumor relationship on MRI scan reflects the biological aggressiveness of S-STS and can serve as a prognostic factor.

Changing odds of survival over time among patients undergoing surgical resection of extremity soft tissue sarcoma.

BACKGROUND: While survival after surgical treatment of extremity soft tissue sarcoma (STS) is traditionally reported as actuarial survival, conditional survival (CS) may be more clinically relevant as it accounts for time already survived. We compared actuarial survival and CS of STS patients. MATERIALS AND METHODS: We analyzed 567 patients who underwent surgery for localized extremity STS. Actuarial survival was estimated using the Kaplan-Meier method. Cox proportional hazards model was used to evaluate factors associated with disease-specific survival. Five-year CS (CS5) estimates at "χ" year(s) after surgery were calculated as CS5 = S(χ + 5)/S(χ). RESULTS: Whereas actuarial survival decreased over time, CS5 increased. The postsurgical 1-, 3-, and 5-year CS5 values were 84.5%, 90.0%, and 93.8%, respectively, whereas the 6-, 8-, and 10-year actuarial survival rates were 82.0%, 79.4%, and 78.5%, respectively. The calculated CS5 exceeded actuarial survival especially in patients with risk factors such as large tumor size and Federation Nationale des Centers de Lutte Contre le Cancer (FNCLCC) grades 2 and 3 tumors. Patients with tumor size ≥5 cm had an actuarial survival of 73.9% at 10 years compared to a CS5 of 95.4% in patients alive at 5 years. Likewise, patients with FNCLCC grade 3 tumors had an actuarial survival of 71.1% at 10 years compared to a CS5 of 96.0% in patients alive at 5 years. CONCLUSIONS: Survival estimation by determination of CS can be dynamic and accurate especially in high-risk patients. CS can be useful for survival prediction and clinical decision making in extremity STS patients.

Comparison of the diagnostic performances of core needle biopsy in myxoid versus non-myxoid tumors.

BACKGROUND: Despite the overall diagnostic utility of core needle biopsy (CNB) comparable to incisional biopsy, increased diagnostic errors have been suggested of CNB for myxoid soft tissue tumors. This study compared the diagnostic performance of CNB between myxoid and non-myxoid soft tissue tumors. METHODS: 369 patients who underwent ultrasound-guided CNB prior to resection for soft tissue tumors were classified into two groups according to resection pathology; myxoid group (n = 75) and non-myxoid group (n = 294). One-hundred and ninety-three patients were male and the median age of the patients was 40 years. Two-hundred and sixty-three tumors were malignant. RESULTS: CNB correctly diagnosed malignancy in 84% (58 of 69) for the myxoid group and 95% (184 of 194) for the non-myxoid group. For diagnosing histologic grade of soft tissue sarcoma, CNB correctly identified high grade in 78% (18 of 23) for the myxoid group and 74% (94 of 128) for the non-myxoid group. Correct diagnosis rate of histological type was significantly lower in the myxoid group (63% [47 of 75] in the myxoid group and 83% [242 of 294] in the non-myxoid group, p = 0.013). CONCLUSION: Our study suggests that CNB is useful for myxoid soft tissue tumors of the extremity, with regard to diagnosing malignancy and histologic grade. However, CNB was less useful for identifying histologic subtype in myxoid tumors than in non-myxoid tumors.

Interleukin-7 Contributes to the Invasiveness of Prostate Cancer Cells by Promoting Epithelial-Mesenchymal Transition.

Precise mechanisms underlying interleukin-7 (IL-7)-mediated tumor invasion remain unclear. Thus, we investigated the role of IL-7 in tumor invasiveness using metastatic prostate cancer PC-3 cell line derivatives, and assessed the potential of IL-7 as a clinical target using a Janus kinase (JAK) inhibitor and an IL-7-blocking antibody. We found that IL-7 stimulated wound-healing migration and invasion of PC-3 cells, increased phosphorylation of signal transducer and activator of transcription 5, Akt, and extracellular signal-regulated kinase. On the other hand, a JAK inhibitor and an IL-7-blocking antibody decreased the invasiveness of PC-3 cells. IL-7 increased tumor sphere formation and expression of epithelial-mesenchymal transition (EMT) markers. Importantly, lentiviral delivery of IL-7Rα to PC-3 cells significantly increased bone metastasis in an experimental murine metastasis model compared to controls. The gene expression profile of human prostate cancer cells from The Cancer Genome Atlas revealed that EMT pathways are strongly associated with prostate cancers that highly express both IL-7 and IL-7Rα. Collectively, these data suggest that IL-7 and/or IL-7Rα are promising targets of inhibiting tumor metastasis.

Survival outcomes after adjuvant radiotherapy for aggressive fibromatosis depend on time frame and nuclear ß-catenin.

PURPOSE: To identify prognostic factors influencing progression-free survival (PFS) of aggressive fibromatosis (AF) after postoperative radiotherapy (PORT) and assess correlations between immunohistochemistry (IHC) features of ß-catenin/smooth muscle actin (SMA) and PFS. MATERIALS AND METHODS: Records of 37 patients with AF treated by PORT from 1984 to 2015 were retrospectively reviewed. Fifteen patients underwent wide excision for AF and 22 patients received debulking operation. The median total dose of PORT was 59.4 Gy. IHC staining results of ß-catenin and SMA were available for 11 and 12 patients, respectively. RESULTS: The median follow-up duration was 105.9 months. Five-year PFS rate was 70.9%. Tumor size or margin status was not related to PFS in univariate analysis (p = 0.197 and p = 0.716, respectively). Multivariate analysis showed that increased interval from surgery to PORT (>5.7 weeks) was a marginal risk factor for PFS (p = 0.054). Administration of PORT at the initial diagnosis resulted in significantly improved PFS compared to deferring PORT after recurrence (p = 0.045). Patient with both risk factors of deferring PORT after recurrence and interval from surgery to PORT >5.7 weeks had significantly lower 5-year PFS than patients without risk factor (34.1% vs. 100.0%; p = 0.012). Nuclear ß-catenin intensity tended to inversely correlate with 5-year PFS, although it did not reach statistical significance (62.5% at low vs. 100.0% at high; p = 0.260). SMA intensity was not related to PFS (p = 0.700). CONCLUSION: PORT should be performed immediately after surgery irrespective of margin status or tumor size especially in recurrent case. Nuclear ß-catenin staining intensity of IHC might correlate with local recurrence.

MRI surveillance for local recurrence in extremity soft tissue sarcoma.

INTRODUCTION: The role of MRI in surveillance for local recurrence (LR) remains uncertain in extremity soft tissue sarcoma (STS). The aims of this study were 1) to examine the usefulness of MRI in detecting LR, 2) to identify the characteristics of LR detected by MRI, and 3) to examine whether MRI surveillance is associated with oncologic outcome. MATERIALS AND METHODS: 477 patients who had regular surveillance for LR after surgery for extremity STS were reviewed. Surveillance was performed by routine MRI in 325 patients or other imaging modalities in 152 patients. RESULTS: The rate of MRI-detected LR, defined as clinically undetectable LR identified on MRI, was 10.5% in the MRI surveillance cohort. The detection rates of MRI-detected LR were significantly higher in the patients with high risk of LR. MRI-detected LRs were more commonly located in the thigh or buttock (p = 0.005), were smaller (p = 0.001) and had LRs without mass formation (p = 0.007) than non-MRI-detected LRs. On Kaplan-Meier analysis, patients with MRI-detected LR tended to have better post-LR survival (p = 0.104). CONCLUSION: Routine MRI surveillance can detect a significant number of clinically undetectable LRs in extremity STS especially for LRs in the thigh or buttock, small LRs or LRs without mass formation.