Outcome of rare primary malignant bone sarcoma treated with multimodal therapy: Results from the EUROpean Bone Over 40 Sarcoma Study (EURO‐B.O.S.S.)

Abstract

BackgroundRare primary malignant bone sarcomas (RPMBS) account for 5%–10% of primary high‐grade bone tumors and represent a major treatment challenge. The outcome of patients with RPMBS enrolled in the EUROpean Bone Over 40 Sarcoma Study (EURO‐B.O.S.S) is presented.MethodsInclusion criteria were as follows: age from 41 to 65 years and a diagnosis of high‐grade spindle cell, pleomorphic, or vascular RPMBS. The chemotherapy regimen included doxorubicin 60 mg/m2, ifosfamide 9 g/m2, and cisplatin 90 mg/m2; postoperative methotrexate 8 g/m2 was added in case of a poor histologic response. Version 2.0 of the Common Terminology Criteria for Adverse Events, Kaplan–Meier curves, log‐rank tests, and univariate Cox regression models were used.ResultsIn total, 113 patients were evaluable for analysis. The median patient age was 52 years (range, 40–66 years), and 67 patients were men. Eighty‐eight tumors were categorized as undifferentiated pleomorphic sarcomas (UPS), 20 were categorized as leiomyosarcomas, three were categorized as fibrosarcomas, and two were categorized as angiosarcomas. Eighty‐three of 113 tumors were located in the extremities. Ninety‐five of 113 patients presented with no evidence of metastases. After a median follow‐up of 6.8 years (interquartile range [IQR], 3.5–9.8 years), the 5‐year overall survival rate for patients with localized disease was 68.4% (IQR, 56.9%–77.5%), and it was 71.7% (IQR, 58.1%–81.6%) for patients with UPS and 54.9% (IQR, 29.5%–74.5%) for patients with leiomyosarcoma. Grade III–IV hematologic toxicity was reported in 81% patients; 23% had grade II–III neurotoxicity, and 37.5% had grade I–II nephrotoxicity. Five‐year overall survival was significantly better for patients with localized disease, for patients who obtained surgical complete remission, and when the primary tumor was located in the extremities.ConclusionsThe survival of patients who had RPMBS in the current series was similar to that of age‐matched patients who had high‐grade osteosarcoma treated according to the same protocol. An osteosarcoma‐like chemotherapy may be proposed in patients who have RPMBS.

NTRK rearranged sarcoma of the bone. Role for larotrectinib in the neoadjuvant setting of an ultra-rare tumor: a case report

“…The present case report showed radiological and clinical progression of the disease in a patient with NTRK+ undifferentiated high-grade spindle cell sarcoma treated with chemotherapy, which is a standard for osteosarcoma ( 15 , 16 ) and used in other spindle cell sarcoma of bone ( 17 ). Nonetheless, there was a 40% reduction in maximum SUV ( 25 ).…”

“…Spindle cell sarcoma of the bone is a singular entity of mesenchymal tumors usually treated as high-grade osteosarcoma ( 15 , 17 , 18 ). NTRK-rearranged spindle cell neoplasms have been described in the last WHO classification of soft tissue and bone tumors as an emerging entity, occurring in the soft tissues.…”

What Is the Impact of Multimodal Treatment in Patients with Leiomyosarcoma of Bone? A Multicenter Study of 35 Patients with an Ultra-Rare Tumor Entity

“…As the only prospective, uncontrolled study, Palmerini et al evaluated the use of an osteosarcoma-like chemotherapy regimen, including high-dose methotrexate in the setting of poor histologic response in patients with rare primary malignant bone sarcomas enrolled in the European Over 40 Bone Sarcoma Study (EURO-B.O.S.S; ClinicalTrials.gov number NCT02986503) [12]. The 5-year OS rate for their 20 patients with localized disease of leiomyosarcoma of bone was 54.9% (IQR, 29.5-74.5%), which is slightly lower than the reported 5-year OS rate of 66% for localized high-grade skeletal osteosarcoma from the EURO-B.O.S.S.-group [25], and even lower than the reported 5-year OS rate of 80% in our 15 patients receiving different chemotherapeutical regimens.…”

“…This question cannot be answered conclusively at present. The published evidence does not support the same treatment as for a primary malignant bone tumor and reflects the uncertainty of chemotherapy (CTX) regimens [5,[10][11][12].…”