Sarcoma[JOURNAL]
Sun
200 papers
Ifosfamide, Carboplatin, and Etoposide (ICE) in Combination with Regional Hyperthermia as Salvage Therapy in Patients with Locally Advanced Nonmetastatic and Metastatic Soft-Tissue Sarcoma.
Bücklein V, Limmroth C, Kampmann E … +9 more , Schuebbe G, Issels R, Roeder F, Angele M, Dürr HR, Knösel T, Abdel-Rahman S, Di Gioia D, Lindner LH
Sarcoma · 2020 · PMID 32189990 · Full text
Patients with localized relapse of soft-tissue sarcoma (STS) after anthracycline-based chemotherapy have a dismal prognosis, particularly when surgery is not possible. To facilitate resection and improve long-term tumor...
Patients with localized relapse of soft-tissue sarcoma (STS) after anthracycline-based chemotherapy have a dismal prognosis, particularly when surgery is not possible. To facilitate resection and improve long-term tumor control, we applied an intensified perioperative treatment consisting of ICE (ifosfamide 6 g/m, carboplatin 400 mg/m, and etoposide 600 mg/m) in combination with regional hyperthermia (RHT) to maximize local control. Here, we retrospectively evaluate the safety and efficacy of this strategy. Patients aged ≥18 years with locally advanced high-risk STS, either with or without metastasis, treated with ICE + RHT after the failure of first-line anthracycline-based chemotherapy were included in this analysis. Radiographic response, toxicity, progression-free survival (PFS), and overall survival (OS) were assessed. Between 1996 and 2018, 213 sarcoma patients received ICE at our centre. Of these, 110 patients met the selection criteria (progressive disease, suitable high-grade STS histology, anthracycline pretreatment, RHT treatment) for this analysis. Fifty-four patients had locally advanced disease without metastases (LA-STS), and 56 patients had additional metastatic disease (M-STS). Disease control was achieved in 59% of LA-STS patients and in 47% of M-STS patients. For LA-STS, 21% of the patients achieved radiographic response, facilitating resection in 4 patients (7%), compared with 11% of the M-STS patients, facilitating resection in 5 patients (9%). PFS was significantly longer in LA-STS than in M-STS (10 vs. 4 months, < 0.0001). Median OS was 26 months in LA-STS and 12 months in M-STS. Disease control was the only independent prognostic factor for improved OS in multivariate analysis. Toxicity was high with neutropenic fever occurring in 25% of the patients and three therapy-related deaths (3%). ICE + RHT demonstrated activity in high-risk STS and facilitated resection in selected patients after anthracycline failure. Disease control was associated with improved OS. Based on the observed toxicities, the dose should be reduced to 75%.
Oncological Treatment Considerations Differ across Surgical Subspecialties Treating Malignant Peripheral Nerve Sheath Tumors: An International Survey.
Martin E, Slooff WM, van Houdt WJ … +3 more , van Dalen T, Verhoef C, Coert JH
Sarcoma · 2020 · PMID 32189989 · Full text
BACKGROUND: Malignant peripheral nerve sheath tumors (MPNSTs) are rare and aggressive soft tissue sarcomas (STS) that, because of their origin, are operated by several surgical subspecialties. This may cause differences...
BACKGROUND: Malignant peripheral nerve sheath tumors (MPNSTs) are rare and aggressive soft tissue sarcomas (STS) that, because of their origin, are operated by several surgical subspecialties. This may cause differences in oncologic treatment recommendations based on presentation. This study investigated these differences both within and between subspecialties. METHODS: A survey was distributed among several (inter)national surgical societies. Differences within and between subspecialties were analyzed by -tests. RESULTS: In total, 30 surgical oncologists, 30 neurosurgeons, 85 plastic surgeons, and 29 "others" filled out the survey. Annual caseload, tumor sites operated, and fellowship training differed significantly between subspecialties. While most surgeons agreed upon preoperative use of MRI, the use of radiological staging and FDG-PET use differed between subspecialties. Surgical oncologists agreed upon core needle biopsies as an ideal type of biopsy while other subspecialties differed in opinion. On average, 53% of surgeons always consider preservation of function preoperatively, but 42% would never perform less extensive resections for function preservation. Respondents agreed that radiotherapy should be considered in tumor sizes >10 cm, microscopic, and macroscopic positive margins. A preferred sequence of radiotherapy administration differed between subspecialties. There was no consensus on indications and sequence of administration of chemotherapy in localized disease. CONCLUSION: Surgical oncologists generally agree on preoperative diagnostics; other subspecialties do not. Considering the preservation of function differed among all subspecialties. Surgeons do agree on some indications for radiotherapy, yet the use of chemotherapy in localized MPNSTs lacks consensus. A preferred sequence of multimodal therapy differs between and within surgical subspecialties, but surgical oncologists prefer neoadjuvant radiotherapy.
Analysis of the Chemotherapy-Free Interval following Image-Guided Ablation in Sarcoma Patients.
Sutton C, Zhang Y, Kim D … +7 more , Yarmohammadi H, Ziv E, Boas FE, Sofocleous CT, Tap WD, D'Angelo SP, Erinjeri JP
Sarcoma · 2020 · PMID 32148436 · Full text
One way to enhance quality of life for patients with metastatic sarcoma is to maximize time off chemotherapy-a chemotherapy-free interval. While image-guided ablation of sarcoma metastases may reduce the need for chemoth...
One way to enhance quality of life for patients with metastatic sarcoma is to maximize time off chemotherapy-a chemotherapy-free interval. While image-guided ablation of sarcoma metastases may reduce the need for chemotherapy, it remains unknown how long ablation could extend the chemotherapy-free interval. The purpose of our study was to determine the chemotherapy-free interval in comparison to overall survival and progression-free survival in sarcoma patients who undergo ablation procedures. An IRB-approved, single institution, HIPAA compliant database was queried for sarcoma patients who underwent image-guided ablation procedures between 2007 and 2018. Patient demographics, histologic subtype, and other clinical characteristics were recorded. Kaplan-Meier analysis was performed to compute median overall survival, median progression-free survival (local and distant), and the median chemotherapy-free interval (systemic and cytotoxic) after ablation. Univariate and multivariate analyses were performed using the log-rank test and Cox proportional-hazards model, respectively. A total of 100 sarcoma patients were included in the analysis. The most common histologic subtype was leiomyosarcoma (38%). Median overall survival after ablation of sarcoma metastases was 52.4 months (95% CI: 46.9-64.0 months). The median systemic chemotherapy-free interval following ablation of sarcoma metastases was 14.7 months (95% CI: 8.6-34.3 months). The median cytotoxic chemotherapy-free interval following ablation of sarcoma metastases was 81.3 months (95% CI: 34.3-median not reached). In conclusion, ablation of sarcoma metastases can provide an extended systemic chemotherapy-free interval of greater than 1 year. Ablation of sarcoma metastases may improve patient quality of life by extending the chemotherapy-free interval.
Thirty-Day Outcomes following Pediatric Bone and Soft Tissue Sarcoma Surgery: A NSQIP Pediatrics Analysis.
Gallaway KE, Ahn J, Callan AK
Sarcoma · 2020 · PMID 32148435 · Full text
BACKGROUND: Pediatric bone and soft tissue sarcomas are rare; therefore, national registries are essential tools for orthopedic oncology research. Past studies provide excellent data on long-term prognosis and survival t...
BACKGROUND: Pediatric bone and soft tissue sarcomas are rare; therefore, national registries are essential tools for orthopedic oncology research. Past studies provide excellent data on long-term prognosis and survival trends but fail to examine treatment-specific morbidity. The aim of this study is to use a national registry to describe patient demographics, comorbidities, and adverse events in the first thirty days following surgical management of pediatric bone and soft tissue sarcomas. METHODS: A retrospective review of patients in the American College of Surgeons National Surgical Quality Improvement Program-Pediatrics database (NSQIP-P) was performed. The cohort was partitioned by tumor origin (bone versus soft tissue) and tumor location (axial versus appendicular). RESULTS: One-hundred ninety-two patients were identified. Bone sarcomas were more common (71.9%) and predominately appendicular (62.3%), while soft tissue sarcomas were predominately axial (77.8%). The overall complication rate was 8.9%. The most frequent etiologies were wound dehiscence (3.6%) and infectious complications such as surgical site infections (2.6%), pneumonia (1.6%), urinary tract infections (1.6%), and colitis (1.0%). Twenty-four percent of patients experienced bleeding requiring transfusion. The unplanned readmission rate was 12.5% (3.6% related to principle procedure), and the unplanned reoperation rate was 4.7% (4.2% related to principle procedure). The mortality rate was 1.0%. Neoadjuvant chemotherapy was associated with higher rates of wound dehiscence and infectious complications. There were no differences in adverse events with respect to tumor origin or location. CONCLUSION: Approximately 1 in 11 pediatric patients will experience a complication in the first thirty days following surgery. However, perioperative mortality remains low. This study represents the first comprehensive review of pediatric bone and soft tissue sarcoma surgery in the NSQIP-P database. As the case volume of NSQIP-P continues to grow, NSQIP-P has the potential to become a powerful tool for pediatric orthopedic oncology research.
Targeting Refractory Sarcomas and Malignant Peripheral Nerve Sheath Tumors in a Phase I/II Study of Sirolimus in Combination with Ganetespib (SARC023).
Kim A, Lu Y, Okuno SH … +13 more , Reinke D, Maertens O, Perentesis J, Basu M, Wolters PL, De Raedt T, Chawla S, Chugh R, Van Tine BA, O'Sullivan G, Chen A, Cichowski K, Widemann BC
Sarcoma · 2020 · PMID 32089640 · Full text
PURPOSE: Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft tissue sarcomas. Combining Hsp90 inhibitors to enhance endoplasmic reticulum stress with mTOR inhibition results in dramatic MPNST shrinkage...
PURPOSE: Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft tissue sarcomas. Combining Hsp90 inhibitors to enhance endoplasmic reticulum stress with mTOR inhibition results in dramatic MPNST shrinkage in a genetically engineered MPNST mouse model. Ganetespib is an injectable potent small molecule inhibitor of Hsp90. Sirolimus is an oral mTOR inhibitor. We sought to determine the safety, tolerability, and recommended dose of ganetespib and sirolimus in patients with refractory sarcomas and assess clinical benefits in patients with unresectable/refractory MPNSTs. . In this multi-institutional, open-label, phase 1/2 study of ganetespib and sirolimus, patients ≥16 years with histologically confirmed refractory sarcoma (phase 1) or MPNST (phase 2) were eligible. A conventional 3 + 3 dose escalation design was used for phase 1. Pharmacokinetic and pharmacodynamic measures were evaluated. Primary objectives of phase 2 were to determine the clinical benefit rate (CBR) of this combination in MPNSTs. Patient-reported outcomes assessed pain. RESULTS: Twenty patients were enrolled (10 per phase). Toxicities were manageable; most frequent non-DLTs were diarrhea, elevated liver transaminases, and fatigue. The recommended dose of ganetespib was 200 mg/m intravenously on days 1, 8, and 15 with sirolimus 4 mg orally once daily with day 1 loading dose of 12 mg. In phase 1, one patient with leiomyosarcoma achieved a sustained partial response. In phase 2, no responses were observed. The median number of cycles treated was 2 (1-4). Patients did not meet the criteria for clinical benefit as defined per protocol. Pain ratings decreased or were stable. CONCLUSION: Despite promising preclinical rationale and tolerability of the combination therapy, no responses were observed, and the study did not meet parameters for further evaluation in MPNSTs. This trial was registered with (NCT02008877).
Does Reconstruction with Reimplantation of Sterilized Tumor Bone Provide Survival Benefit in Diaphyseal Osteosarcoma?
Nayak P, Gulia A, Puri A
Sarcoma · 2020 · PMID 32051679 · Full text
Does reimplantation of sterilized tumor bone for reconstruction provide outcome benefits in intercalary osteosarcoma based on the potential immunogenic effect of reimplanted sterilized tumor tissue? Of 720 cases of surgi...
Does reimplantation of sterilized tumor bone for reconstruction provide outcome benefits in intercalary osteosarcoma based on the potential immunogenic effect of reimplanted sterilized tumor tissue? Of 720 cases of surgically treated high-grade osteosarcoma patients treated at our institute from 2006 to 2013, 61 had predominantly diaphyseal disease. All patients were nonmetastatic at presentation. Patient and tumor characteristics, treatment details, and local recurrence-free, metastasis-free, and overall survival were compared for 24 patients who had reconstruction with sterilized tumor bone reimplantation vs 37 who did not. Both the groups were well matched in terms of baseline characteristics. Means were compared with the -test, proportions with the chi-square test, and survival with the log-rank test. The Kaplan-Meier method was used to construct time to event curves. Cox proportional hazard regression modeling was employed for multivariate time to event analysis. Twenty-two had extracorporeal radiation and reimplantation (ECRT) with or without the vascularised fibula. Fifty-gray single dose was used in all cases. Two had pasteurization and reimplantation. Thirty seven had non-reimplantation reconstructions (including intercalary or osteoarticular endoprosthesis, pedicled bone grafts, rotation-plasty, and amputations). Five-year local recurrence-free survival was 85% for reimplantation and 97% for non-reimplantation groups (=0.17). Five-year metastasis-free survival was 63% and 54%, respectively (=0.44). Five-year overall survival was 70% and 58%, respectively (=0.39). The data from this study did not demonstrate significantly better local recurrence-free, distant relapse-free, or overall survival benefit in the tumor bone reimplantation group.
Radiomics and Machine Learning Differentiate Soft-Tissue Lipoma and Liposarcoma Better than Musculoskeletal Radiologists.
Malinauskaite I, Hofmeister J, Burgermeister S … +4 more , Neroladaki A, Hamard M, Montet X, Boudabbous S
Sarcoma · 2020 · PMID 31997918 · Full text
Distinguishing lipoma from liposarcoma is challenging on conventional MRI examination. In case of uncertain diagnosis following MRI, further invasive procedure (percutaneous biopsy or surgery) is often required to allow...
Distinguishing lipoma from liposarcoma is challenging on conventional MRI examination. In case of uncertain diagnosis following MRI, further invasive procedure (percutaneous biopsy or surgery) is often required to allow for diagnosis based on histopathological examination. Radiomics and machine learning allow for several types of pathologies encountered on radiological images to be automatically and reliably distinguished. The aim of the study was to assess the contribution of radiomics and machine learning in the differentiation between soft-tissue lipoma and liposarcoma on preoperative MRI and to assess the diagnostic accuracy of a machine-learning model compared to musculoskeletal radiologists. 86 radiomics features were retrospectively extracted from volume-of-interest on T1-weighted spin-echo 1.5 and 3.0 Tesla MRI of 38 soft-tissue tumors (24 lipomas and 14 liposarcomas, based on histopathological diagnosis). These radiomics features were then used to train a machine-learning classifier to distinguish lipoma and liposarcoma. The generalization performance of the machine-learning model was assessed using Monte-Carlo cross-validation and receiver operating characteristic curve analysis (ROC-AUC). Finally, the performance of the machine-learning model was compared to the accuracy of three specialized musculoskeletal radiologists using the McNemar test. Machine-learning classifier accurately distinguished lipoma and liposarcoma, with a ROC-AUC of 0.926. Notably, it performed better than the three specialized musculoskeletal radiologists reviewing the same patients, who achieved ROC-AUC of 0.685, 0.805, and 0.785. Despite being developed on few cases, the trained machine-learning classifier accurately distinguishes lipoma and liposarcoma on preoperative MRI, with better performance than specialized musculoskeletal radiologists.
Optimization of the Therapeutic Approach to Patients with Sarcoma: Delphi Consensus.
Álvarez Álvarez R, Cruz Jurado J, Del Muro Solans XG … +4 more , Giner JL, López Pousa A, Martín-Broto J, Valverde CM
Sarcoma · 2019 · PMID 31975783 · Full text
Soft tissue sarcomas (STS) constitute a heterogeneous group of rare solid tumors associated with significant morbidity and mortality. The evaluation and treatment of STS require a multidisciplinary team with extensive ex...
Soft tissue sarcomas (STS) constitute a heterogeneous group of rare solid tumors associated with significant morbidity and mortality. The evaluation and treatment of STS require a multidisciplinary team with extensive experience in the management of these types of tumors. National and international clinical practice guidelines for STS do not always provide answers to a great many situations that specialists have to contend with in their everyday practice. This consensus provides a series of specific recommendations based on available scientific evidence and the experience of a group of experts to assist in decision-making by all the specialists involved in the management of STS.
Prognostic Factors in Dedifferentiated Chondrosarcoma: A Retrospective Analysis of a Large Series Treated at a Single Institution.
Miao R, Choy E, Raskin KA … +8 more , Schwab JH, Nielsen GP, Deshpande V, Chebib I, DeLaney TF, Hornicek FJ, Cote GM, Chen YE
Sarcoma · 2019 · PMID 31915413 · Full text
BACKGROUND: Dedifferentiated chondrosarcomas (DDCSs) are highly malignant tumors with a dismal prognosis and present a significant challenge in clinical management. METHODS: In an IRB approved retrospective protocol, we...
BACKGROUND: Dedifferentiated chondrosarcomas (DDCSs) are highly malignant tumors with a dismal prognosis and present a significant challenge in clinical management. METHODS: In an IRB approved retrospective protocol, we identified 72 patients with DDCS treated at our institution between 1993 and 2017 and reviewed clinicopathological characteristics, treatment modalities, and outcomes to analyze prognostic factors. RESULTS: Femur (44.4%), pelvis (22.2%), and humerus (12.5%) were most commonly involved sites. Twenty-three patients (31.9%) presented with distant metastasis, and 3 (4.2%) of them also had regional lymph node involvement. The median overall survival (OS) was 13.9 months. On multivariate analysis, pathological fracture, larger tumor size, lymph node involvement, metastasis at diagnosis, extraosseous extension, and undifferentiated pleomorphic sarcoma component correlated with worse OS, whereas surgical resection and chemotherapy were associated with improved OS. For progression-free survival (PFS), pathological fracture and metastasis at diagnosis showed increased risk, while chemotherapy was associated with decreased risk. Among patients who received chemotherapy, doxorubicin and cisplatin were significantly associated with improved PFS but not OS. Among patients without metastasis at diagnosis, 17 (34.7%) developed local recurrence. Thirty-one (63.3%) developed distant metastases at a median interval of 18.1 months. On multivariate analysis, R1/R2 resection was related with local recurrence, while macroscopic dedifferentiated component was associated with distant metastasis. CONCLUSIONS: The prognosis of DDCS is poor. Complete resection remains a significant prognostic factor for local control. Chemotherapy with doxorubicin and cisplatin seems to have better PFS. More prognostic, multicenter trials are warranted to further explore the effectiveness of chemotherapy in selected DDCS patients.
Comparison of MRI and Histopathology with regard to Intramedullary Extent of Disease in Bone Sarcomas.
Gulia A, Puri A, Subi TS … +3 more , Gupta SM, Juvekar SL, Rekhi B
Sarcoma · 2019 · PMID 31885489 · Full text
In today's era, limb salvage surgery is the procedure of choice and current standard of care in appropriately selected patients of bone sarcomas. For adequate oncologic clearance, preoperative evaluation of the extent of...
In today's era, limb salvage surgery is the procedure of choice and current standard of care in appropriately selected patients of bone sarcomas. For adequate oncologic clearance, preoperative evaluation of the extent of tumor is mandatory. The present study was done to compare measurements of bone sarcomas (osteosarcoma, Ewing's sarcoma, and chondrosarcoma) as determined by magnetic resonance imaging (MRI) with the histopathological extent seen on resected specimens. We prospectively evaluated 100 consecutive patients with a diagnosis of bone sarcoma who underwent limb salvage surgery between May 2014 and December 2014. The maximum longitudinal (cranio-caudal) dimension of tumor on the noncontrast T1-WI sequence of MRI (irrespective of whether it was pre/postchemotherapy) was compared with the gross dimensions of the tumor on histopathology. The arithmetic mean difference, Wilcoxon signed-rank test, and Spearman's correlation analysis were used to test the differences and correlation between groups. Mean tumor size on MRI based on the largest extent on MRI was 12.1 ± 4.85 cm (mean ± standard deviation), while it was 10.77 ± 4.6 cm (mean ± standard deviation) on histopathology. In 79 cases, MRI overestimated the extent of disease; the mean was 1.79 cm with a standard deviation of 1.56 cm. When the disease extent was underestimated on MRI (13 cases), the mean was 0.58 cm with a standard deviation of 0.43 cm. In 8 cases (osteosarcoma (7), Ewing's sarcoma (1)), MRI measurement was equal to histopathology. The Spearman correlation analysis showed a high correlation of tumor length on histopathology with the MRI for all patients ( = 0.948, < 0.0001). We thus conclude that MRI is accurate in delineating the extent of bone sarcomas. A margin of 2 cm from the maximum tumor extent is adequate to ensure appropriate surgical resection.
Efficacy and Safety of Nanosomal Docetaxel Lipid Suspension-Based Chemotherapy in Sarcoma: A Multicenter, Retrospective Study.
Narayanan P, Dattatreya PS, Prasanna R … +8 more , Subramanian S, Jain K, Somanath NS, Joshi N, Bunger D, Khan MA, Chaturvedi A, Ahmad I
Sarcoma · 2019 · PMID 31827370 · Full text
OBJECTIVE: To evaluate the efficacy and safety of nanosomal docetaxel lipid suspension (NDLS, DoceAqualip) based chemotherapy in patients with sarcoma. METHODS: In this retrospective, multicenter (6 centers), observation...
OBJECTIVE: To evaluate the efficacy and safety of nanosomal docetaxel lipid suspension (NDLS, DoceAqualip) based chemotherapy in patients with sarcoma. METHODS: In this retrospective, multicenter (6 centers), observational study, we analyzed the medical charts of adult patients of either sex, who were treated with NDLS (75 mg/m in 3-weekly cycles) based chemotherapy for the treatment of sarcoma. The efficacy outcomes were overall response rate (ORR: complete response (CR) + partial response (PR)) and disease control rate (DCR: CR + PR + stable disease (SD)) in patients who received NDLS-based chemotherapy in neoadjuvant and metastatic settings. Overall survival (OS) and safety were evaluated for all settings. RESULTS: Of 11 patients (neoadjuvant: 1, adjuvant: 3, and metastatic: 7) in this study, majority had leiomyosarcoma (63.6%, 7/11) followed by extraskeletal myxoid chondrosarcoma (EMC), high grade pleomorphic sarcoma of mandible, malignant fibrous histiocytoma of right thigh, and osteosarcoma of femur (9.1% each, 1/11 each). NDLS plus gemcitabine combination was used in 10 patients (90.9%), and NDLS plus cyclophosphamide was used in one patient with EMC (9.1%). Efficacy evaluation was performed for 7 patients (neoadjuvant: 1/1; metastatic: 6/7). Complete response was reported in one patient (soft tissue sarcoma of mandible) treated in neoadjuvant setting. In metastatic setting, ORR was 50% and DCR was 66.7% (CR: 16.7% (1/6), PR: 33.3% (2/6), SD: 16.7% (1/6)). At a median follow-up of 6.5 months (range: 0.06-20.2 months), median OS was not reached in neoadjuvant and adjuvant settings, but it was 15.8 months in metastatic setting. At least 1 AE was reported in 7 (63.6%) patients. Neutropenia, thrombocytopenia, lymphopenia, and anemia were the hematological AEs, whereas nausea, vomiting, and diarrhea were the most common nonhematological AEs. NDLS treatment was well tolerated without any new safety concerns. CONCLUSION: Nanosomal docetaxel lipid suspension-based chemotherapy was efficacious and well tolerated in the treatment of sarcoma. Further prospective trials are needed to confirm the data.
Revisiting the Role of Radiation Therapy in Chondrosarcoma: A National Cancer Database Study.
Catanzano AA, Kerr DL, Lazarides AL … +7 more , Dial BL, Lane WO, Blazer DG, Larrier NA, Kirsch DG, Brigman BE, Eward WC
Sarcoma · 2019 · PMID 31736653 · Full text
BACKGROUND: Although chondrosarcomas (CS) are mostly considered radioresistant, advancements in radiotherapy have brought attention to its use in these patients. Using the largest registry of primary bone tumors, the Nat...
BACKGROUND: Although chondrosarcomas (CS) are mostly considered radioresistant, advancements in radiotherapy have brought attention to its use in these patients. Using the largest registry of primary bone tumors, the National Cancer Database (NCDB), we sought to better characterize the current use of radiotherapy in CS patients and identify any potential survival benefit with higher radiation doses and advanced radiation therapies. METHODS: We retrospectively analyzed CS patients in the NCDB from 2004 to 2015 who underwent radiotherapy. The Kaplan-Meier method with statistical comparisons was used to identify which individual variables related to dosage and delivery modality were associated with improved 5-year survival rates. Multivariate proportional hazards analyses were performed to determine independent predictors of survival. RESULTS: Of 5,427 patients with a histologic diagnosis of chondrosarcoma, 680 received a form of radiation therapy (13%). The multivariate proportional hazards analysis controlling for various patient, tumor, and treatment variables, including RT dose and modality, demonstrated that while overall radiation therapy (RT) was not associated with improved survival (HR 0.96, 95% CI 0.76-1.20), when examining just the patient cohort with positive surgical margins, RT trended towards improved survival (HR 0.81, 95% CI 0.58-1.13). When comparing advanced and conventional RT modalities, advanced RT was associated with significantly decreased mortality (HR 0.55, 95% CI 0.38-0.80). However, advanced modality and high-dose RT both trended only toward improved survival compared to patients who did not receive any RT (HR 0.74, 95% CI 0.52-1.06 and HR 0.93, 95% CI 0.71-1.21, respectively). CONCLUSIONS: Despite the suggested radioresistance of CS, modern radiotherapies may present a treatment option for certain patients. Our results support a role for high-dose, advanced radiation therapies in selected high-risk CS patients with tumors in surgically challenging locations or unplanned positive margins. While there is an associated survival rate benefit, further, prospective studies are needed for validation.
High Recurrence Rate of Myxofibrosarcoma: The Effect of Radiotherapy Is Not Clear.
Teurneau H, Engellau J, Ghanei I … +2 more , Vult von Steyern F, Styring E
Sarcoma · 2019 · PMID 31662702 · Full text
BACKGROUND: Myxofibrosarcoma (MFS) is one of the more common types of soft-tissue sarcoma (STS) in patients over 60 years of age. Local recurrence (LR) rates have been reported to be higher compared to other STS types. P...
BACKGROUND: Myxofibrosarcoma (MFS) is one of the more common types of soft-tissue sarcoma (STS) in patients over 60 years of age. Local recurrence (LR) rates have been reported to be higher compared to other STS types. PATIENTS AND METHODS: Using a population-based series from the southern Sweden health care region, 56 consecutive patients with MFS and localized disease at diagnosis were analyzed with respect to LR and distant metastases after surgery ± adjuvant treatment. RESULTS: The overall local recurrence ( = 15) and metastasis ( = 13) rates were 27% and 21%, respectively; 6 patients had both. Surgical margin was the only statistically significant prognostic factor for LR. Patients operated with a marginal margin had an HR of 4.5 (CI 1.3-15.1, =0.02) and those operated with an intralesional margin 9.4 (CI 2.0-43.5, =0.004) compared to those operated with a wide surgical margin. There was no difference in the LR rate depending on radiotherapy or not, although the latter group had smaller and more superficial tumors. 23 patients received radiotherapy, 9 of whom developed LR, all within the irradiated field. A tumor size >5 cm and intralesional surgical margin were shown to be risk factors for distant metastases. CONCLUSIONS: The rate of LR for patients with myxofibrosarcoma was high. The impact of RT on local tumor control was unclear. The surgical margin was important for both local and distant tumor control. Large tumor size was a risk factor for distant metastasis.
Changes in Soft-Tissue Sarcoma Treatment Patterns over Time: A Population-Based Study in a Country with Universal and Centralized Healthcare.
Bozzo A, Seow H, Pond G … +1 more , Ghert M
Sarcoma · 2019 · PMID 31636505 · Full text
BACKGROUND: The clinical care of soft-tissue sarcoma (STS) patients is largely multidisciplinary involving clinicians from surgical disciplines, medical oncology, and radiation oncology. It is not clear if treatment patt...
BACKGROUND: The clinical care of soft-tissue sarcoma (STS) patients is largely multidisciplinary involving clinicians from surgical disciplines, medical oncology, and radiation oncology. It is not clear if treatment patterns for STS have changed over time. We present population-level data on changes in treatment patterns of patients diagnosed with STS of all stages in Ontario, Canada. METHODS: We performed a population-based cohort study using linked administrative databases in Ontario, Canada, of patients with STS between 2006 and 2015. Patients with the AJCC stage at the time of diagnosis were included. Patients were categorized into one of the seven treatment arms: single modality treatment (surgery, chemotherapy, or radiation therapy), bimodality therapy, or all three treatment modalities. Survival of STS patients of different stages is displayed with the Kaplan-Meier method. RESULTS: A total of 4696 patients were diagnosed with biopsy-proven sarcoma during the study period including 1915 patients with stage information available. Treatment patterns for patients with Stage 1 and 2 disease were similar enough to allow for grouping. The use of radiation therapy in Stage 1 and 2 patients increased by 15% over the study period. None of the 7 treatment regimens for Stage 3 patients changed appreciably during the study period. We observed that the use of chemotherapy for Stage 4 STS patients increased 36% during the study period. Overall patient survival was, as expected, highest in Stage 1 patients and lowest in Stage 4 patients. CONCLUSION: This is the first population-level study reporting of 7 different STS treatment regimens in a country with universal and centralized healthcare. Radiation therapy for local disease control and chemotherapy for Stage 4 patients have recently become more utilized. Survival from STS is highly dependent on stage at presentation. Other population-based studies from other countries are needed to establish the current international treatment patterns.
Safety and Efficacy of Hepatic Artery Embolization in Treating Solitary Fibrous Tumor Metastatic to the Liver.
Velayati S, Erinjeri JP, Brody LA … +10 more , Ziv E, Boas FE, Brown KT, Covey AM, Getrajdman GI, Solomon SB, Kingham PT, Tap WD, Jarnagin WR, Yarmohammadi H
Sarcoma · 2019 · PMID 31565028 · Full text
The aim of this study was to evaluate safety and survival following hepatic artery embolization (HAE) for metastatic solitary fibrous tumor (SFT) in the liver. All patients with SFT metastatic to liver treated with HAE w...
The aim of this study was to evaluate safety and survival following hepatic artery embolization (HAE) for metastatic solitary fibrous tumor (SFT) in the liver. All patients with SFT metastatic to liver treated with HAE were retrospectively analyzed. Tumor response was evaluated using mRECIST. Objective response, overall survival (OS), and progression-free survival (PFS) were evaluated using Kaplan-Meier and multivariate Cox proportional hazard ratio. Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. Twelve patients (6 males and 6 females, mean age: 42.5 ± 13 years; 24-65) were treated with 33 embolizations. Anatomical sites of origin for SFT were the head and neck ( = 6; 50%), pelvis ( = 2), pleura ( = 2), retroperitoneal ( = 1), and thigh ( = 1). The median follow-up from first HAE was 4.5 years (3-7.9). 84% of the patients showed objective response [42% complete response (CR) plus 42% partial response (PR)] to HAE by mRECIST (95% CI, 60-99%). Patients with CR to HAE had significantly higher OS compared to others ( < 0.02). The postembolization median OS was 4 years (95% CI, 2.3-5.2), and mean PFS, for intra- or extrahepatic progression of disease, was 6 months (95%, CI, 3.2-7.1). One patient developed pneumonia/sepsis and died 27 days postembolization, possibly not directly related to embolization. No grade III or IV adverse events were identified in the remaining patients. In conclusion, HAE for metastatic liver SFT is a relatively safe treatment option with high response rate and should be considered as a treatment option for metastatic liver SFT. In our cohort of patients with metastatic SFT to the liver, we observed a median OS of 4 years following HAE. Further studies are needed to confirm the efficacy of HAE.
Corrigendum to "SARC018_SPORE02: Phase II Study of Mocetinostat Administered with Gemcitabine for Patients with Metastatic Leiomyosarcoma with Progression or Relapse following Prior Treatment with Gemcitabine-Containing Therapy".
Choy E, Ballman K, Chen J … +8 more , Dickson MA, Chugh R, George S, Okuno S, Pollock R, Patel RM, Hoering A, Patel S
Sarcoma · 2019 · PMID 31534435 · Full text
[This corrects the article DOI: 10.1155/2018/2068517.].
[This corrects the article DOI: 10.1155/2018/2068517.].
A Retrospective Case Series of Synovial Sarcoma of the Upper Extremity.
Post J, Houdek M, Folpe AL … +2 more , Kakar SK, Wilke BK
Sarcoma · 2019 · PMID 31467480 · Full text
PURPOSE: Previous studies have grouped the treatment of axial and appendicular synovial sarcomas. The purpose of this study was to assess the prognostic variables of upper extremity synovial sarcomas (UESS) and compare t...
PURPOSE: Previous studies have grouped the treatment of axial and appendicular synovial sarcomas. The purpose of this study was to assess the prognostic variables of upper extremity synovial sarcomas (UESS) and compare the outcomes of those who underwent a nononcologic or inadvertent excision prior to definitive resection to those who underwent an initial oncologic resection. METHODS: We reviewed the records of 23 UESS treated with definitive surgery at our institution between 1990 and 2014. There were 13 women and 10 men with a median age of 30 years (6-60) and median follow-up of 63 months (15-248). Prognostic variables, recurrence-free survival (RFS), and overall survival (OS) were then assessed. RESULTS: Fifteen patients (65%) had a prior unplanned excision. Five patients required an amputation to obtain local control of disease. There were 3 observed local recurrences and 2 distant metastases at a median of 45 months from presentation. We found no difference in need for amputation, RFS, or OS between those who had undergone a planned excision and those who had an unplanned excision. CONCLUSION: While we were unable to find a significant difference in outcomes or amputation rates between those who underwent reexcision of a previously unplanned excision and those who underwent an initial planned resection, the high rate of unplanned excision is troubling and should remind practitioners to consider sarcoma in the differential of all upper extremity masses.
Targeting Sporadic and Neurofibromatosis Type 1 (NF1) Related Refractory Malignant Peripheral Nerve Sheath Tumors (MPNST) in a Phase II Study of Everolimus in Combination with Bevacizumab (SARC016).
Widemann BC, Lu Y, Reinke D … +15 more , Okuno SH, Meyer CF, Cote GM, Chugh R, Milhem MM, Hirbe AC, Kim A, Turpin B, Pressey JG, Dombi E, Jayaprakash N, Helman LJ, Onwudiwe N, Cichowski K, Perentesis JP
Sarcoma · 2019 · PMID 31427883 · Full text
PURPOSE: There are no known effective medical treatments for refractory MPNST. Inactivation of the NF1 tumor suppressor in MPNST results in upregulation of mTOR (mammalian target of rapamycin) signaling and angiogenesis,...
PURPOSE: There are no known effective medical treatments for refractory MPNST. Inactivation of the NF1 tumor suppressor in MPNST results in upregulation of mTOR (mammalian target of rapamycin) signaling and angiogenesis, which contributes to disease progression. We conducted a phase II study for patients (pts) with refractory MPNST combining everolimus (10 mg PO once daily) with bevacizumab (10 mg/kg IV every 2 weeks) to determine the clinical benefit rate (CBR) (complete response, partial response (PR), or stable disease (SD) ≥ 4 months). PATIENTS AND METHODS: Patients ≥18 years old with chemotherapy refractory sporadic or NF1 MPNST were eligible. Tumor response was assessed after every 2 cycles (the WHO criteria). A two-stage design targeting a 25% CBR was used: if ≥ 1/15 pts in stage 1 responded, enrollment would be expanded by 10 pts, and if ≥ 4/25 patients had clinical benefit, the combination would be considered active. RESULTS: Twenty-five pts, 17 with NF1 and 8 with sporadic MPNST, enrolled. One of 15 pts in stage 1 had clinical benefit. Of 10 additional pts enrolled, 2 had clinical benefit. The median number of completed cycles was 3 (range 1-16). Adverse events were similar to those known for this combination. CONCLUSION: With a CBR of 12% (3/25), the combination of everolimus and bevacizumab did not reach the study's target response rate and is not considered active in refractory MPNST.
The Fusion Oncogene FUS-CHOP Drives Sarcomagenesis of High-Grade Spindle Cell Sarcomas in Mice.
Chen M, Xu ES, Leisenring NH … +5 more , Cardona DM, Luo L, Ma Y, Ventura A, Kirsch DG
Sarcoma · 2019 · PMID 31427882 · Full text
Myxoid liposarcoma is a malignant soft tissue sarcoma characterized by a pathognomonic t(12;16)(q13;p11) translocation that produces a fusion oncoprotein, FUS-CHOP. This cancer is remarkably sensitive to radiotherapy and...
Myxoid liposarcoma is a malignant soft tissue sarcoma characterized by a pathognomonic t(12;16)(q13;p11) translocation that produces a fusion oncoprotein, FUS-CHOP. This cancer is remarkably sensitive to radiotherapy and exhibits a unique pattern of extrapulmonary metastasis. Here, we report the generation and characterization of a spatially and temporally restricted mouse model of sarcoma driven by FUS-CHOP. Using different Cre drivers in the adipocyte lineage, we initiated tumorigenesis by expressing FUS-CHOP in + mesenchymal progenitor cells. In contrast, expression of FUS-CHOP in more differentiated cells does not form tumors , and early expression of the oncoprotein during embryogenesis is lethal. We also employ electroporation and CRISPR technology to rapidly generate spatially and temporally restricted mouse models of high-grade FUS-CHOP-driven sarcomas for preclinical studies.
Combination Therapy with Disulfiram, Copper, and Doxorubicin for Osteosarcoma: Support for a Novel Drug Repurposing Strategy.
Mandell JB, Lu F, Fisch M … +4 more , Beumer JH, Guo J, Watters RJ, Weiss KR
Sarcoma · 2019 · PMID 31379466 · Full text
Although many cancer cells have significantly higher copper concentrations compared with normal cells and tissues, the role of copper in cancer biology and metastatic disease remains poorly understood. Here, we study the...
Although many cancer cells have significantly higher copper concentrations compared with normal cells and tissues, the role of copper in cancer biology and metastatic disease remains poorly understood. Here, we study the importance of copper in osteosarcoma, which frequently metastasizes to the lungs and is often chemoresistant. K12 and K7M2 are murine OS cells with differing metastatic phenotypes: K7M2 is highly metastatic, whereas K12 is much less so. Intracellular copper levels were determined using atomic absorption. Copper transporters were quantified by qPCR. Cytotoxicity of doxorubicin, disulfiram, and copper(II) chloride was assessed with a cell viability fluorescence stain. Additionally, K7M2 viable cell counts were determined by trypan blue exclusion staining after 72 hours of treatment. Copper levels were found to be significantly higher in K12 OS cells than in K7M2 cells. qPCR showed that K12 cells upregulate the copper influx pump CTR1 and downregulate the copper efflux pump ATP7A compared to K7M2 OS cells. Combination treatment of copper chloride (50 nM) with disulfiram (80 nM) was only cytotoxic to K12 cells. Triple treatment with doxorubicin, disulfiram, and copper displayed potent and durable cytotoxicity of highly metastatic K7M2 cells. We demonstrate here that murine OS cell lines differing in metastatic potential also vary in endogenous copper levels and regulation. Additionally, these differences in copper regulation may contribute to selective cytotoxicity of K12 cells by extremely low doses of copper-potentiated disulfiram. The combination of doxorubicin, disulfiram, and copper should be explored as a therapeutic strategy against OS metastases.
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