Sarcoma[JOURNAL]
Sun
200 papers
Targeting the FAK-Src Complex in Desmoplastic Small Round Cell Tumors, Ewing Sarcoma, and Rhabdomyosarcoma.
van Erp AEM, Hillebrandt-Roeffen MHS, van Bree NFHN … +6 more , Plüm TA, Flucke UE, Desar IME, Fleuren EDG, van der Graaf WTA, Versleijen-Jonkers YMH
Sarcoma · 2022 · PMID 35655525 · Full text
Desmoplastic small round cell tumors (DSRCTs), Ewing sarcoma (ES), and alveolar and embryonal rhabdomyosarcoma (ARMS and ERMS) are malignant sarcomas typically occurring at young age, with a poor prognosis in the metasta...
Desmoplastic small round cell tumors (DSRCTs), Ewing sarcoma (ES), and alveolar and embryonal rhabdomyosarcoma (ARMS and ERMS) are malignant sarcomas typically occurring at young age, with a poor prognosis in the metastatic setting. New treatment options are necessary. Src family kinase inhibitor dasatinib single-agent treatment has been investigated in a phase 2 study in patients with advanced sarcomas including ES and RMS but failed as a single agent in these subtypes. Since previous studies demonstrated high FAK and Src activities in RMS and ES tissue and cell lines, and dasatinib treatment was shown to upregulate activated FAK, we hypothesized that FAK-Src combination treatment could potentially be an interesting treatment option for these tumor types. We examined the effects of targeting the FAK-Src complex by addressing (p)FAK and (p)Src expressions in tumor sections of DSRCT ( = 13), ES ( = 68), ARMS ( = 21), and ERMS ( = 39) and by determining the antitumor effects of single and combined treatment with FAK inhibitor defactinib and multikinase (Abl/SFK) inhibitor dasatinib on cell lines of each subtype. effects were assessed in DSRCT and ERMS models. Concurrent pFAK and pSrc expressions (H-score >50) were observed in DSRCT (67%), ES (6%), ARMS (35%), and ERMS (19%) samples. Defactinib treatment decreased pFAK expression and reduced cell viability in all subtypes. Dasatinib treatment decreased pSrc expression and cell viability in each subtype. Combination treatment led to a complete reduction in pFAK and pSrc in each cell line and showed enhanced cell viability reduction, drug synergy, DNA damage induction, and a trend toward higher apoptosis induction in DSRCT, ERMS, and ARMS but not in ES cells. These promising results unfortunately do not translate into promising results as we did not observe a significant effect on tumor volume , and the combination did not show superior effects compared to dasatinib single-agent treatment.
Free Vascularized Fibula Salvage of Failed CPH in Pediatric Sarcoma Patients.
Pires G, Moss WD, Luo J … +4 more , Zhang R, Jones KB, Kwok AC, Agarwal JP
Sarcoma · 2022 · PMID 35586727 · Full text
BACKGROUND: Due to extended life expectancy and recent improvements in surgical techniques, limb salvage has replaced amputation as the gold standard and is now performed in 90-95% of upper extremity malignancies. Howeve...
BACKGROUND: Due to extended life expectancy and recent improvements in surgical techniques, limb salvage has replaced amputation as the gold standard and is now performed in 90-95% of upper extremity malignancies. However, many of these salvage procedures are associated with significant postsurgical complications. In particular, the clavicula pro humero (CPH) procedure is associated with high rates of nonunion. We present our experience with upper extremity salvage using the free vascularized fibular flap (VFF) after failure or nonunion of the original CPH procedure in the pediatric population. METHODS: Five patients under the age of 18 diagnosed with upper extremity sarcoma who underwent tumor resection with immediate CPH reconstruction complicated with nonunion, and subsequent revision with free VFF were included. Data on patient demographics, oncologic characteristics, surgical procedures, intraoperative details, postoperative complications, and time to graft union were recorded. RESULTS: Five patients (average age = 8.4 years; range = 5-10 years at surgery date) underwent secondary limb salvage procedure with free VFF reconstruction following failed CPH reconstruction for proximal humeral osteosarcoma ( = 4) or Ewing sarcoma ( = 1). The mean follow-up was 3.7 years. Complications occurred in five patients (100%), with three patients requiring reoperation (60%). Four patients achieved graft union (average union time = 3.7 months) and successful limb reconstruction. Four patients were alive with no local recurrence of the disease. One patient did not achieve union and was lost to follow-up. CONCLUSION: Primary bone tumors in the pediatric population require wide surgical resection, and reconstruction often has high complication rates that can warrant further procedures. A free VFF is a viable option for upper extremity salvage after previously failed reconstructions because it provides vascularized tissue to a scarred tissue bed and allows for the replacement or augmentation of large bony defects.
Bone Metastases in Patients with Leiomyosarcoma: A Retrospective Analysis of Survival and Surgical Management.
LiBrizzi CL, Vankara A, Meyer CF … +2 more , Levin AS, Morris CD
Sarcoma · 2022 · PMID 35570847 · Full text
BACKGROUND: Leiomyosarcomas (LMS) are malignancies with smooth muscle differentiation. Metastasis to the bone is not uncommon. The literature on the clinical course and management of such metastases is limited. Our study...
BACKGROUND: Leiomyosarcomas (LMS) are malignancies with smooth muscle differentiation. Metastasis to the bone is not uncommon. The literature on the clinical course and management of such metastases is limited. Our study describes the clinical course of LMS to the bone, including survival rates, prognostic factors, and surgical management. METHODS: We retrospectively reviewed 396 LMS patients presenting at an academic center between 1995 and 2020. We included LMS patients diagnosed with bone metastases and excluded patients with primary LMS of bone. We evaluated survival time with the Kaplan-Meier survival method and used Cox's proportional hazards regression analysis to determine factors associated with survival. RESULTS: Forty-five patients with LMS (11%) had bone metastases. The most common LMS subtypes with bone metastases were uterine ( = 18, 40%) and retroperitoneal ( = 15, 33%). Bone metastasis was not an independent predictor of mortality by Cox regression analysis (HR 1.0, 95% CI: 0.67-1.5). Patients more frequently metastasized to the axial ( = 29, 64%) than to the appendicular ( = 5, 11%) skeleton. Bone was the first site of metastasis in 13 patients (29%). Patients presented with bone metastases at a median of 32.7 months (IQR: 5.2, 62.6) after initial LMS diagnosis. Twelve patients (27%) sustained a pathologic fracture. Twenty (44%) required surgical management, with 30 surgeries total. Three (15%) had a failure of reconstructive constructs. The median overall survival time was 69.7 months (IQR: 43.2, 124.5). There were no associations between the LMS subtype and survival. Pathologic fracture was an independent predictor of mortality by Cox regression analysis (HR 5.4, 95% CI: 1.8-16). CONCLUSION: The majority of patients with metastatic LMS to bone survive greater than 5 years and frequently require surgical intervention. Extended survival in this patient population should inform fixation and implant choice. No anatomic subtype was associated with risk for bone metastases. Pathologic fracture was associated with worse survival.
Plexin-B2 and Semaphorins Do Not Drive Rhabdomyosarcoma Proliferation or Migration.
Karki A, Purohit R, Nosack S … +4 more , Bharathy N, Michalek JE, Chen S, Keller C
Sarcoma · 2022 · PMID 35570846 · Full text
Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma for which subsets of patients have longstanding unmet clinical needs. For example, children with alveolar rhabdomyosarcoma and metastases at diagnos...
Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma for which subsets of patients have longstanding unmet clinical needs. For example, children with alveolar rhabdomyosarcoma and metastases at diagnosis will experience only 8% disease-free 5-year survival for nonlocalized unresectable recurrent disease. Hence, development of novel therapeutic strategies is urgently needed to improve outcomes. The Plexin-Semaphorin pathway is largely unexplored for sarcoma research. However, emerging interest in the Plexin-Semaphorin signaling axis in pediatric sarcomas has led to phase I cooperative group dose-finding clinical trials, now completed (NCT03320330). In this study, we specifically investigated the protein expression of transmembrane receptor Plexin-B2 and its cognate SEMA4C ligands in clinical RMS tumors and cell models. By RNA interferences, we assessed the role of Plexin-B2 in cell growth and cell migration ability in selected alveolar and embryonal RMS cell model systems. Our results affirmed expression of Plexin-B2 across human samples, while also dissecting expression of the different protein subunits of Plexin-B2 along with the assessment of preferred Semaphorin ligands of Plexin-B2. Plexin-B2 knockdown had positive or negative effects on cell growth, which varied by cell model system. Migration assayed after Plexin-B2 knockdown revealed selective cell line specific migration inhibition, which was independent of Plexin-B2 expression level. Overall, these findings are suggestive of context-specific and possibly patient-specific (stochastic) role of Plexin-B2 and SEMA4 ligands in RMS.
Time and Accuracy to Establish the Diagnosis of Soft Tissue Tumors: A Comparative Analysis from the Swiss Sarcoma Network.
Wellauer H, Studer G, Bode-Lesniewska B … +1 more , Fuchs B
Sarcoma · 2022 · PMID 35535046 · Full text
Soft tissue tumors are rare tumors, and their histological examination remains a challenge. The establishment of the correct initial histopathologic diagnosis is critical. However, due to the rarity of soft tissue and bo...
Soft tissue tumors are rare tumors, and their histological examination remains a challenge. The establishment of the correct initial histopathologic diagnosis is critical. However, due to the rarity of soft tissue and bone tumors and the inherent difficulty of their classification and diagnostics, discrepancies may occur in up to one third of cases. For these reasons, several studies recommend the involvement of experienced pathologists frequently performing sarcoma diagnostics. Until now, there is only scarce information about how long it takes to establish a correct sarcoma diagnosis. We thus analyzed all consecutive patients presented to the Swiss Sarcoma Network Tumor Board (SSN-MDT/SB) with a primary diagnosis of a soft tissue tumor over a 2-year period (01/2019 to 12/2020) based on a tumor biopsy. We then compared the final histopathological diagnosis of two comparable institutions with similar case load, but different workflows: (i) institution A, with an initial diagnosis performed by a local pathologist, and reviewed by a reference pathologist, and (ii) institution B, with the final diagnosis performed directly by a reference pathologist. In addition, we analyzed the time from biopsy to establishment of the diagnosis. A total of 347 cases were analyzed, 196 from institution A, and 149 from institution B. In 77.6% of the cases, the diagnosis from the local pathologist was concordant with the expert review. Minor discrepancies were found in 10.2% of the cases without any consecutive changes in treatment strategy. In the remaining 12.2% of the cases, there were major discrepancies which influenced the treatment strategy directly. Establishing the final report took significantly longer in institution A (4.7 working days) than in institution B (3.3 working days; < 0.01). Our results confirm the importance of a pathological second review by a reference pathologist. We recommend direct analysis by experts, as diagnoses can be made more accurately and quickly. Within the SSN, establishing the sarcoma diagnosis is overall accurate and quick but still can be improved.
Prognostic Significance of Bone Metastasis in Soft Tissue Sarcoma Patients Receiving Palliative Systemic Therapy: An Explorative, Retrospective Pooled Analysis of the EORTC-Soft Tissue and Bone Sarcoma Group (STBSG) Database.
Kantidakis G, Litière S, Gelderblom H … +9 more , Fiocco M, Judson I, van der Graaf WTA, Italiano A, Marréaud S, Sleijfer S, Mechtersheimer G, Messiou C, Kasper B
Sarcoma · 2022 · PMID 35401025 · Full text
BACKGROUND: Soft-tissue sarcomas (STS) constitute a rare group of heterogeneous mesenchymal tumours containing more than 100 histologic subtypes. Here, we investigate whether, and if so, to what extent, skeletal metastas...
BACKGROUND: Soft-tissue sarcomas (STS) constitute a rare group of heterogeneous mesenchymal tumours containing more than 100 histologic subtypes. Here, we investigate whether, and if so, to what extent, skeletal metastases affect the outcome of patients with advanced or metastatic disease. MATERIALS AND METHODS: Selected patients participated in five clinical trials of EORTC-STBSG. Individuals were included if they started treatment with an active drug and had advanced/metastatic STS. The endpoints of interest were overall survival (OS) and progression-free survival (PFS). Univariate and multivariate pooled analyses (after correcting for 12 covariates) were employed with Kaplan-Meier and Cox regression to model the impact of bone metastasis at presentation per treatment line stratified by study. For the subset of patients with bone metastasis, the impact of another metastatic organ site was explored with multivariate Cox regression models. RESULTS: 565 out of 1034 (54.6%) patients received first-line systemic treatment for locally advanced or metastatic disease. Bone metastases were present in 140 patients (77 first-line, 63 second-line or higher). The unadjusted difference in OS/PFS with or without bone metastasis was statistically significant only for first-line patients. For OS, the adjusted hazard ratios for bone metastasis presence were 1.33 (95%-CI: 0.99-1.78) and 1.11 (95%-CI: 0.81-1.52) for first-line/second-line or higher treated patients, respectively. Likewise, the adjusted hazard ratios for PFS were 1.31 (95%-CI: 1.00-1.73) and 1.07 (95%-CI: 0.80-1.43). Effects were not statistically significant, despite a trend in first-line patients for both endpoints. Subgroup analyses indicated bone and lymph node metastasis as the most detrimental combination for OS and bone and lung metastasis for PFS. CONCLUSIONS: Adult STS patients receiving palliative systemic therapy with bone metastasis carried an overall worse prognosis than STS patients without bone metastases. Skeletal metastasis was detrimental for both OS and PFS, independent of the treatment line. Findings may have implications for the management of these patients.
A Multidisciplinary Team Approach Is Highly Effective in the Management of Nondiagnostic Bone Tumour Biopsies: A 10-Year Retrospective Review at a Specialist Sarcoma Unit.
Osman K, Hussain S, Downes F … +3 more , Sumathi V, Botchu R, Evans S
Sarcoma · 2022 · PMID 35386233 · Full text
Nondiagnostic (ND) biopsies are frequently encountered during the investigation of bone tumours and can lead to treatment delay. We performed a retrospective review of all ND bone tumour biopsies discussed at our regiona...
Nondiagnostic (ND) biopsies are frequently encountered during the investigation of bone tumours and can lead to treatment delay. We performed a retrospective review of all ND bone tumour biopsies discussed at our regional MDT meeting between 2004 and 2014 with the aim of establishing the incidence of ND biopsies, identifying any factors that could predict the requirement for repeat biopsies, and evaluating the effectiveness of multidisciplinary team (MDT) decisions. We identified 98 ND out of 4949 biopsies. Diagnostic yield (DY) was 98%, 76%, and 40% for the first, second, and third successive biopsy, respectively. With an MDT approach utilising radiological and clinical information, the diagnostic success rate achieved was 99%, 85%, and 80% for the first, second, and third biopsies, respectively. Although a repeat biopsy was only performed in 34% of cases, there were no patients originally diagnosed with a benign lesion that re-presented with the same lesion subsequently being malignant throughout the study period. Malignant primary bone tumours ( < 0.01) and malignant secondary tumours (=0.02) were more likely to undergo repeat biopsy compared to benign and infective lesions. Upper limb (=0.04) and lower limb (=0.03) were more likely than pelvic and spinal tumours to undergo a repeat biopsy. Tumours of haematological origin frequently required multiple biopsies. Our study demonstrated that a specialist MDT approach leads to high diagnostic rates and is a safe and effective method of preventing unnecessary, repeat biopsies where the initial biopsy is ND.
Comparison of 3D Conformal Proton Therapy, Intensity-Modulated Proton Therapy, and Intensity-Modulated Photon Therapy for Retroperitoneal Sarcoma.
Chung C, Trofimov A, Adams J … +6 more , Kung J, Kirsch DG, Yoon S, Doppke K, Bortfeld T, Delaney TF
Sarcoma · 2022 · PMID 35345672 · Full text
BACKGROUND: External beam radiation therapy (RT) for retroperitoneal sarcoma often requires treatment of large target volumes close to critical normal tissues. Radiation may be limited by adjacent organs at risk (OAR). I...
BACKGROUND: External beam radiation therapy (RT) for retroperitoneal sarcoma often requires treatment of large target volumes close to critical normal tissues. Radiation may be limited by adjacent organs at risk (OAR). Intensity-modulated radiation therapy has been shown to improve target coverage and reduce doses to OAR. OBJECTIVES: To compare target coverage and dose to OAR with 3D conformal proton therapy (3D CPT), intensity-modulated proton therapy (IMPT), and intensity-modulated photon therapy (IMXT). METHODS: We performed a comparative study of treatment plans with 3D CPT, IMPT, and IMXT for ten patients with retroperitoneal sarcomas. RT was delivered to 50.4 Gy to the clinical target volume (CTV), the structures considered at risk for microscopic disease. RESULTS: CTVs ranged from 74 to 357 cc (mean 188 cc). Dose conformity was improved with IMPT, while 3D CPT provided better dose homogeneity. Mean dose to the liver, small bowel, and stomach was reduced with IMPT compared with 3D CPT or IMXT. CONCLUSIONS: IMPT, 3D CPT, and IMXT provide excellent target coverage for retroperitoneal sarcomas. OAR dose is lower with IMPT and 3D CPT, and IMPT achieves the closest conformity. These techniques offer the opportunity for further dose escalation to areas with positive margins.
Gene Expression and Cellular Copper Levels between Low and Highly Metastatic Osteosarcoma Provide a Case for Novel Repurposing with Disulfiram and Copper.
Mandell JB, Douglas N, Ukani V … +9 more , Beumer JH, Guo J, Payne J, Newman R, Mancinelli L, Intini G, Anderson CJ, Watters R, Weiss K
Sarcoma · 2022 · PMID 35125923 · Full text
Aldehyde dehydrogenase 1A1 (ALDH) is a cancer stem cell marker highly expressed in metastatic cells. Disulfiram (Dis) is an FDA-approved antialcoholism drug that inhibits ALDH and has been studied as a candidate for drug...
Aldehyde dehydrogenase 1A1 (ALDH) is a cancer stem cell marker highly expressed in metastatic cells. Disulfiram (Dis) is an FDA-approved antialcoholism drug that inhibits ALDH and has been studied as a candidate for drug repurposing in multiple neoplasia. Dis cytotoxicity in cancer cells has been shown to be copper-dependent, in part due to Dis's ability to function as a bivalent metal ion chelator of copper (Cu). The objectives of this research were to test expression levels and Cu concentrations in sarcoma patient tumors and human osteosarcoma (OS) cell lines with differing metastatic phenotypes. We also sought to evaluate Dis + Cu combination therapy in human OS cells. Intracellular Cu was inversely proportional to the metastatic phenotype in human OS cell lines (SaOS2 > LM2 > LM7). Nonmetastatic human sarcoma tumors demonstrated increased Cu concentrations compared with metastatic tumors. qPCR demonstrated that expression was significantly increased in highly metastatic LM2 and LM7 human OS cell lines compared with low metastatic SaOS2. Tumor cells from sarcoma patients with metastatic disease displayed significantly increased expression compared with tumor cells from patients without metastatic disease. Serum Cu concentration in canine OS versus normal canine patients demonstrated similar trends. Dis demonstrated selective cytotoxicity compared with human multipotential stromal cells (MSCs): Dis-treated OS cells demonstrated increased apoptosis, whereas MSCs did not. CuCl combined with Dis and low-dose doxorubicin resulted in a superior cytotoxic effect in both SaOS2 and LM7 cell lines. In summary, gene expression and Cu levels are altered between low and highly metastatic human OS cells, canine samples, and patient tumors. Our findings support the feasibility of a repurposed drug strategy for Dis and Cu in combination with low-dose anthracycline to specifically target metastatic OS cells.
Effect of Resident and Fellow Involvement on Outcomes of Sarcoma Surgery: A NSQIP Database Cross-Sectional Study.
Jang ES, Artin MG, Boddapati V … +5 more , Chan CM, Spiguel AR, Gibbs CP, Scarborough MT, Tyler WK
Sarcoma · 2021 · PMID 34961809 · Full text
BACKGROUND: The complexity of sarcoma surgery often justifies surgical assistants of higher levels of academic training: senior residents, fellows, or co-surgeons. The association between the level of training of assista...
BACKGROUND: The complexity of sarcoma surgery often justifies surgical assistants of higher levels of academic training: senior residents, fellows, or co-surgeons. The association between the level of training of assistants and outcomes of these procedures has yet to be studied. METHODS: The Current Procedural Terminology (CPT) codes comprising the "core" procedures for musculoskeletal oncology fellowships were gathered. After CPTs primarily capturing nononcologic procedures were excluded, the National Surgical Quality Improvement Program (NSQIP) database was used to find procedures with these CPTs. The severity of complications was assessed using the Severity Weighting of Postoperative Adverse Events in Orthopedic Surgery (SWORD) score. Resident/fellow presence was analyzed both as a binary variable and stratified by level of training. RESULTS: In 159 cases meeting inclusion criteria, higher-level assistants were associated with increased rate of any complication (=0.006) and greater need for transfusion (=0.001) but also tended to be used in cases of longer duration (=0.001) and with higher total work relative value units (wRVUs) (=0.001). Multivariate analysis showed that while higher-wRVU procedures persisted as an independent predictor of increased complications (OR 1.028 per RVU unit, =0.002), neither the presence nor level of training of assistants had an independent effect on complication rates. Other independent predictors of 30-day complications were treatment comorbidity (OR 3.433, =0.010) and lower extremity location of the tumor (OR 4.393, =0.006). Severity of complications did not differ between any of the groups on either univariate or multivariate analysis. CONCLUSIONS: Trainees of higher levels of academic training tend to be present for longer, higher-complexity musculoskeletal oncology cases, but the overall severity of complications from these do not significantly differ from lower-risk cases without trainees. Orthopedic oncologists may reassure patients that the presence of trainees and co-surgeons is not only safe but it may also help reduce the severity of complications in more complex procedures.
Free Functional Latissimus Dorsi Reconstruction of the Quadriceps and Hamstrings following Oncologic Resection of Soft Tissue Sarcomas of the Thigh.
Houdek MT, Wellings EP, Mallett KE … +3 more , Honig RL, Rose PS, Moran SL
Sarcoma · 2021 · PMID 34924809 · Full text
BACKGROUND: Limb-salvage surgery combined with radiotherapy has become the primary treatment for soft tissue sarcomas of the extremity. Free functional latissimus flaps (FFLF) are an option to restore function in the set...
BACKGROUND: Limb-salvage surgery combined with radiotherapy has become the primary treatment for soft tissue sarcomas of the extremity. Free functional latissimus flaps (FFLF) are an option to restore function in the setting of volumetric muscle loss. The purpose of the current study was to examine the use of FFLF in patients undergoing resection of thigh sarcoma. METHODS: Twelve patients with a sarcoma involving the hamstring ( = 6), quadriceps ( = 5), or combined ( = 1) defects which included multiple muscle groups were reviewed. This included 9 males and 3 females with a mean age and body mass index of 56 ± 12 years and 31.3 ± 5.7 kg/m. RESULTS: The mean defect volume and operative time was 3,689 ± 2,314 cm and 587 ± 73 minutes. Following reconstruction, the mean knee range of motion (ROM), MSTS93 score, and muscle strength was 89 ± 24°, 90 ± 15%, and 4 ± 1; with 75% of patients ambulating without gait aids. Seven (58%) patients sustained a complication, namely, delayed wound healing ( = 2). CONCLUSION: Although there was a high incidence of complications, FFLF can restore active knee ROM and function, with most patients ambulating without gait aids following reconstruction of large oncologic defects in the thigh.
Osteosarcoma of the Pelvis: Clinical Presentation and Overall Survival.
Brown JM, Matichak D, Rakoczy K … +1 more , Groundland J
Sarcoma · 2021 · PMID 34912177 · Full text
INTRODUCTION: Osteosarcoma is the most common sarcoma of bone. Pelvic osteosarcoma presents a significant therapeutic challenge due to potential late symptom onset, metastatic dissemination at diagnosis, and inherent dif...
INTRODUCTION: Osteosarcoma is the most common sarcoma of bone. Pelvic osteosarcoma presents a significant therapeutic challenge due to potential late symptom onset, metastatic dissemination at diagnosis, and inherent difficulties of wide surgical resection secondary to the complex and critical anatomy of the pelvis. The rates of survival are well reported for osteosarcoma of the appendicular skeleton, but specific details regarding presentation and survival are less known for osteosarcoma of the pelvis. METHODS: The Surveillance, Epidemiology, and End Results (SEER) program was queried for primary osteosarcoma of the bony pelvis from 2004 to 2015. Cases with Collaborative Staging variables (available after 2004) were analyzed by grade, histologic subtype, surgical intervention, tumor size, tumor extension, and presence of metastasis at diagnosis. The 2-, 5-, and 10-year survival rates were assessed with respect to these variables. The SEER database was then queried for age, tumor size, surgical intervention, metastasis at time of presentation, and survivorship data for patients with primary osteosarcoma of the upper extremity, lower extremity, vertebrae, thorax, and face/skull, and rates for all anatomic locations were then compared to patients with primary pelvic osteosarcoma. RESULTS: A total of 292 cases of pelvic osteosarcoma were identified from 2004 to 2015 within the database, representing 9.8% of cases among all surveyed primary sites. The most common histologic subtype was osteoblastic osteosarcoma (69.9%), followed by chondroblastic osteosarcoma (22.3%). The majority of cases were high-grade tumors (94.3%), of size >8 cm (72.0%), and with extension beyond the originating bone (74.0%). For the entire pelvic osteosarcoma group, the 2-, 5-, 10-year survival rates were 45.6%, 26.5%, and 21.4%, respectively, which were the poorest among surveyed anatomic sites. The 5-year overall survival was an abysmal 5.3% for patients with metastatic disease at diagnosis, and 37.0% for non-metastatic pelvic osteosarcoma treated with surgery and chemotherapy. When compared to other locations, pelvic osteosarcoma had higher rates of metastatic disease at presentation (33.5%), larger median tumor size (11.0 cm), and older median age at diagnosis (47.5 years). While over 85% of patients with tumors at the extremities received surgery, only 47.4% of pelvic osteosarcomas in this cohort received surgical resection-likely influenced by larger tumor size, sacral involvement, frequency of metastasis, older age, or delayed referral to a sarcoma center. CONCLUSION: This study clarifies presenting features and clinical outcomes of pelvic osteosarcomas, which often present with large, high-grade tumors with extracompartmental extension, high likelihood of metastatic disease at diagnosis, and a potential limited ability to be addressed surgically. The survival rates of primary osteosarcoma of the pelvis are poor and are lower than osteosarcomas from other anatomic locations. While acknowledging the influence of metastasis, tumor characteristics, and advanced age on the decision to undergo surgical excision of a pelvic osteosarcoma, the rates of surgical resection are low and highlight the importance of understanding appropriate conditions for oncologic resection of pelvic sarcomas.
Clinical Outcomes and Prognostic Factors for Patients with Malignant Peripheral Nerve Sheath Tumour.
Imura Y, Outani H, Takenaka S … +7 more , Yasuda N, Nakai S, Nakai T, Wakamatsu T, Tamiya H, Hamada K, Kakunaga S
Sarcoma · 2021 · PMID 34867073 · Full text
INTRODUCTION: Few studies have described the characteristics and prognostic factors of patients with malignant peripheral nerve sheath tumour (MPNST). In this study, we retrospectively investigated the clinicopathologica...
INTRODUCTION: Few studies have described the characteristics and prognostic factors of patients with malignant peripheral nerve sheath tumour (MPNST). In this study, we retrospectively investigated the clinicopathological features, clinical outcomes, and prognostic factors of these patients. . We recruited patients with MPNST who were treated at our institutions from 1991 to 2020. We collected and statistically analysed information on patient-, tumour-, and treatment-related factors. The median follow-up period was 61 months (range, 1-335.8 months). RESULTS: A total of 60 patients (31 males, 29 females) with a median age of 55 years (range, 8-84 years) at initial diagnosis were included. The median tumour size was 7 cm (range, 1.6-30 cm) in the greatest dimension. The 5-year overall survival (OS) rate of all patients was 69.5%. Univariate analysis revealed that large-sized tumour, metastasis at diagnosis, and no surgery of the primary tumour were significantly associated with patients with worse OS. Multivariate analysis identified surgery of the primary tumour as an independent prognostic factor for improved OS. Among patients with localised disease at diagnosis who underwent surgery of the primary tumour at our institutions, the 5-year OS, local recurrence-free survival (LRFS), and metastasis-free survival (MFS) rates were 81.1%, 78.2%, and 70.3%, respectively. Univariate analysis revealed that positive surgical margin was significantly correlated with unfavourable OS and LRFS, and high grade was a poor prognostic indicator for MFS. CONCLUSION: Complete surgical resection with negative surgical margins is necessary for a successful MPNST treatment. Multidisciplinary management of MPNST with aggressive features is important for optimising patient outcomes.
Role of Intraoperative Pathology Consultation by Imprint and Scrape Cytology in Soft Tissue Tumors and Tumor-Like Lesions.
Gautam R, Mohan H, Handa U … +1 more , Bisht B
Sarcoma · 2021 · PMID 34744482 · Full text
Intraoperative pathologic consultation plays an essential role in therapeutic decision making, possibly avoiding under or overtreatment of the patient. Common indications for intraoperative consultation include obtaining...
Intraoperative pathologic consultation plays an essential role in therapeutic decision making, possibly avoiding under or overtreatment of the patient. Common indications for intraoperative consultation include obtaining a diagnosis in an unknown pathology, ruling out malignancy, confirming a provisional diagnosis, and assessing margin status. Fifty patients undergoing surgery for soft tissue tumors or tumor-like lesions were included in the present prospective study to evaluate the role of intraoperative pathologic consultation by imprint and scrape cytology. Careful and quick gross examination of the specimen was performed, followed by processing for imprint and scrape smears. The prepared smears were evaluated by three pathologists and the cytological diagnosis compared subsequently with final histopathological diagnosis. Intraoperative consultation was primarily requested to make or confirm preoperative diagnosis. In 44.0% cases, no previous tissue/cytological diagnosis was available. In 56.0% cases, previous pathological diagnosis was available, but the reports were inconclusive or were reported from outside our institute. The diagnostic yield of imprint smears was 24% (5 malignant, 6 benign, and 1 inconclusive), and scrape smears was 100% (10 malignant, 38 benign, and 2 inconclusive). Paraffin-embedded sections yielded diagnosis in 100% cases (11 malignant, 38 benign, and 1 nonneoplastic). Imprint smears alone were not of much help in intraoperative diagnosis. Scrape smears were found to be superior to imprint smears in terms of diagnostic yield and accuracy. Combined imprint and scrape smear cytology did not provide any advantage in intraoperative provisional tissue diagnosis in soft tissue tumors.
The Influence of Personalised Sarcoma Care (PERSARC) Prediction Modelling on Clinical Decision Making in a Multidisciplinary Setting.
Hagenmaier HSF, van Beeck AGK, Haas RL … +11 more , van Praag VM, van Bodegom-Vos L, van der Hage JA, Krol S, Speetjens FM, Cleven AHG, Navas A, Kroon HM, Moeri-Schimmel RG, Leyerzapf NAC, van de Sande MAJ
Sarcoma · 2021 · PMID 34720664 · Full text
BACKGROUND: With soft-tissue sarcoma of the extremity (ESTS) representing a heterogenous group of tumors, management decisions are often made in multidisciplinary team (MDT) meetings. To optimize outcome, nomograms are m...
BACKGROUND: With soft-tissue sarcoma of the extremity (ESTS) representing a heterogenous group of tumors, management decisions are often made in multidisciplinary team (MDT) meetings. To optimize outcome, nomograms are more commonly used to guide individualized treatment decision making. PURPOSE: To evaluate the influence of Personalised Sarcoma Care (PERSARC) on treatment decisions for patients with high-grade ESTS and the ability of the MDT to accurately predict overall survival (OS) and local recurrence (LR) rates. METHODS: Two consecutive meetings were organised. During the first meeting, 36 cases were presented to the MDT. OS and LR rates without the use of PERSARC were estimated by consensus and preferred treatment was recorded for each case. During the second meeting, OS/LR rates calculated with PERSARC were presented to the MDT. Differences between estimated OS/LR rates and PERSARC OS/LR rates were calculated. Variations in preferred treatment protocols were noted. RESULTS: The MDT underestimated OS when compared to PERSARC in 48.4% of cases. LR rates were overestimated in 41.9% of cases. With the use of PERSARC, the proposed treatment changed for 24 cases. CONCLUSION: PERSARC aids the MDT to optimize individualized predicted OS and LR rates, hereby guiding patient-centered care and shared decision making.
Evaluating Thresholds to Adopt Hypofractionated Preoperative Radiotherapy as Standard of Care in Sarcoma.
Valle LF, Bernthal N, Eilber FC … +3 more , Shabason JE, Bedi M, Kalbasi A
Sarcoma · 2021 · PMID 34720663 · Full text
INTRODUCTION: Data supporting hypofractionated preoperative radiation therapy (RT) for patients with extremity and trunk soft tissue sarcoma (STS) are currently limited to phase II single-institution studies. We sought t...
INTRODUCTION: Data supporting hypofractionated preoperative radiation therapy (RT) for patients with extremity and trunk soft tissue sarcoma (STS) are currently limited to phase II single-institution studies. We sought to understand the type and thresholds of clinical evidence required for experts to adopt hypofractionated RT as a standard-of-care option for patients with STS. METHODS: An electronic survey was distributed to multidisciplinary sarcoma experts. The survey queried whether data from a theoretical, multi-institutional, phase II study of 5-fraction preoperative RT could change practice. Using endpoints from RTOG 0630 as a reference, the survey also queried thresholds for acceptable local control, wound complication, and late toxicity for the study protocol to be accepted as a standard-of-care option. Responses were logged from 8/27/2020 to 9/8/2020 and summarized graphically. RESULTS: The survey response rate was 55.3% (47/85). Local control is the most important clinical outcome for sarcoma specialists when evaluating whether an RT regimen should be considered standard of care. 17% (8/47) of providers require randomized phase III evidence to consider hypofractionated preoperative RT as a standard-of-care option, whereas 10.6% (5/47) of providers already view this as a standard-of-care option. Of providers willing to change practice based on phase II data, most (78%, 29/37) would accept local control rates equivalent to or less than those in RTOG 0630, as long as the rate was higher than 85%. However, 51.3% (19/37) would require wound complication rates superior to those reported in RTOG 0630, and 46% (17/37) of respondents would accept late toxicity rates inferior to RTOG 0630. CONCLUSION: Consensus building is needed among clinicians regarding the type and threshold of evidence needed to evaluate hypofractionated RT as a standard-of-care option. A collaborative consortium-based approach may be the most pragmatic means for developing consensus protocols and pooling data to gradually introduce hypofractionated preoperative RT into routine practice.
The Utility of Chest Imaging for Surveillance of Atypical Lipomatous Tumors.
Lazarides AL, Ferlauto HR, Burke ZDC … +8 more , Griffin AM, Leckey BD, Bernthal NM, Wunder JS, Ferguson PC, Visgauss JD, Brigman BE, Eward WC
Sarcoma · 2021 · PMID 34671190 · Full text
BACKGROUND: Unlike other soft tissue sarcomas, atypical lipomatous tumors (ALTs) are thought to have a low propensity for metastasis. Despite this, a standard of care for pulmonary metastasis (PM) surveillance has not be...
BACKGROUND: Unlike other soft tissue sarcomas, atypical lipomatous tumors (ALTs) are thought to have a low propensity for metastasis. Despite this, a standard of care for pulmonary metastasis (PM) surveillance has not been established. This study aimed to evaluate the utility of chest imaging for PM surveillance following ALT excision. METHODS: This was a multi-institution, retrospective review of all patients with primary ALTs of the extremities or superficial torso who underwent excision between 2006 and 2018. Minimum follow-up was two years. Long-term survival was evaluated using the Kaplan-Meier method. RESULTS: 190 patients with ALT were included. Average age was 61.7 years and average follow-up was 58.6 months (24 to 180 months). MDM2 testing was positive in 88 patients (46.3%), and 102 (53.7%) did not receive MDM2 testing. 188 patients (98.9%) had marginal excision, and 127 (66.8%) had marginal or positive margins. Patients received an average of 0.9 CT scans and 1.3 chest radiographs over the surveillance period. 10-year metastasis-free survival was 100%, with no documented deaths from disease. CONCLUSIONS: This study suggests that chest imaging does not have a significant role in PM surveillance following ALT excision, but advanced local imaging and chest surveillance may be considered in cases of local recurrence or concern for dedifferentiation.
Survival and Analysis in a Cohort of Orthopedics Patients with Malignant Peripheral Nerve Sheath Tumors.
Knewitz DK, Anderson CJ, Presley WT … +3 more , Horodyski M, Scarborough MT, Wallace MR
Sarcoma · 2021 · PMID 34646065 · Full text
Neurofibromatosis type 1 (NF1) is an autosomal dominant tumor syndrome in which benign plexiform neurofibromas are at risk of transforming into malignant peripheral nerve sheath tumors (MPNSTs), a very rare soft-tissue s...
Neurofibromatosis type 1 (NF1) is an autosomal dominant tumor syndrome in which benign plexiform neurofibromas are at risk of transforming into malignant peripheral nerve sheath tumors (MPNSTs), a very rare soft-tissue sarcoma. The prognosis of patients with MPNSTs is poor, with most studies reporting <50% survival at five years. However, studies evaluating MPNSTs are limited and report heterogeneous results. Because no MPNST-specific evidence-based treatment guideline exists, individual institutional experiences are very informative to the field. The main objective of this study was to investigate and report MPNST prognostic clinical and genetic biomarkers from our institution's Orthopedics service experience treating 20 cases from 1992 to 2017. Most patients were treated with resection and adjuvant radiation. Extended follow-up, averaging 11.4 years (ranging 1.1 to 25.1), revealed excellent five-year survival rates: 70% for overall and 60% for metastatic disease. An S100 B immunonegative tumor phenotype was associated with a significantly worse outcome than MPNSTs with positive S100 B stain. In addition, gene mutation analysis was performed on 27 families with NF1 in which at least one affected family member developed MPNSTs. Of the 27 germline mutations, five were large deletions spanning (or nearly spanning) the gene (18.5%), substantially more than such deletions in NF1 in general, consistent with increased risk of MPNSTs in such cases.
Localized Angiosarcoma, Not One Disease: A Retrospective Single-Center Study on Prognosis Depending on the Primary Site and Etiology.
Schott I, Liffers ST, Farzaliyev F … +12 more , Falkenhorst J, Steinau HU, Treckmann JW, Podleska LE, Pöttgen C, Schildhaus HU, Ahrens M, Dirksen U, Murat FZ, Siveke JT, Bauer S, Hamacher R
Sarcoma · 2021 · PMID 34545273 · Full text
BACKGROUND: Angiosarcomas are rare and heterogeneous tumors with poor prognosis. The clinical subtypes are classified depending on the primary site and etiology. METHODS: We conducted a retrospective, monocentric study o...
BACKGROUND: Angiosarcomas are rare and heterogeneous tumors with poor prognosis. The clinical subtypes are classified depending on the primary site and etiology. METHODS: We conducted a retrospective, monocentric study of 136 patients with localized AS between May 1985 and November 2018. Overall survival (OS), local recurrence-free survival (LRFS), and metastasis-free survival (MFS) were estimated using the Kaplan-Meier method. To identify prognostic factors, univariate and multivariate analyses were performed based on Cox regressions. RESULTS: The median age was 67 years (19-72.8 years). Primary sites were cutaneous (27.2%), breast (38.2%), and deep soft tissue (34.6%). The majority was primary angiosarcomas (55.9%) followed by postradiation (40.4%) and chronic lymphedema angiosarcomas (2.9%). Prognosis significantly differed depending on the primary site and etiology. Shortest median OS and MFS were observed in deep soft tissue angiosarcomas, whereas cutaneous angiosarcomas, angiosarcomas of the breast, and radiation-associated angiosarcomas displayed worse median LRFS. Univariate analyses showed better OS for tumor size <10 cm ( = 0.009), negative surgical margins ( = 0.021), and negative lymph node status ( = 0.007). LRFS and MFS were longer for tumor size <10 cm ( = 0.012 and = 0.013). In multivariate analyses, age <70 years was the only independent positive prognostic factor for OS in all subgroups. For LRFS, secondary AS of the breast was a negative prognostic factor (HR: 2.35; = 0.035). CONCLUSIONS: Different behaviors and prognoses depending on the primary site and etiology should be considered for the treatment of this heterogeneous disease. In cutaneous angiosarcomas of the head/neck and postradiation angiosarcomas of the breast, local recurrence seems to have a crucial impact on OS. Therefore, improved local therapies and local tumor staging may have to be implemented. However, in deep soft tissue angiosarcomas, distant recurrence seems to have a major influence on prognosis, which indicates a benefit of additional perioperative chemotherapy.
Rhabdomyosarcoma in Adults: A Retrospective Analysis of Case Records Diagnosed between 1979 and 2018 in Western Denmark.
Mäkinen VN, Safwat A, Aggerholm-Pedersen N
Sarcoma · 2021 · PMID 34504392 · Full text
INTRODUCTION: Adult rhabdomyosarcoma is a rare tumour that has an inferior survival compared to the paediatric patient population. The reason for this consistently worse outcome remains mostly unknown. It has been sugges...
INTRODUCTION: Adult rhabdomyosarcoma is a rare tumour that has an inferior survival compared to the paediatric patient population. The reason for this consistently worse outcome remains mostly unknown. It has been suggested that this disparity may be related to biological and/or treatment-related factors, which in the literature has been shown to be distributed differently among paediatric and adult patients. The aim of this study was to clarify treatment outcome and clinicopathological factors for adult patients with rhabdomyosarcoma that were treated in Aarhus, Denmark, since 1979. METHODS: By searching the Aarhus Sarcoma Registers, data for all rhabdomyosarcoma patients, aged 18 years or more, between 1979 and 2018, were retrieved and analysed. RESULTS: Data from 50 patients were collected. No patients were lost to follow-up. For the entire cohort, 5- and 10-year overall survival rates were 30% and 18%, respectively. The median age was 46.5 years, and the median overall survival was 2.3 years. Tumour histology was embryonal 18%, alveolar 22%, pleomorphic 44%, and not otherwise specified 16%. The tumour site was unfavourable in more than 80% of the patients. Significant factors associated with inferior overall survival were histology and disease stage, although histological subtype was not significant in the multivariate model. Five-year overall survival was 40% for localised disease versus 15% for metastatic disease. CONCLUSION: Rhabdomyosarcoma in adults has a poorer prognosis than paediatric rhabdomyosarcoma and other high-grade sarcomas in adults. Adult rhabdomyosarcoma should continue to be treated aggressively, but new and tailored treatment strategies are needed to improve the long-term outcome. Previous predictors of poor survival in paediatric patients were valid in adults except for age, site (favourable versus unfavourable), and tumour size.
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