Efficacy of denosumab treatment for lung metastasis secondary to proximal humerus chondroblastoma.

Chondroblastoma is a rare benign cartilaginous tumor that accounts for approximately 1% of bone tumors, but it can be associated with lung metastasis in extremely rare cases, leading to a poor prognosis and death. Herein, we report the case of a 19-year-old male patient who presented with an aggressive chondroblastoma of the proximal humerus and bilateral lung metastasis. The patient was treated with wide local resection, partial metastasectomy, and denosumab. Denosumab treatment was effective in controlling metastatic progression and preventing local recurrence.

A Rare Coexistence of Hybrid Tumor Low-grade Fibromyxoid Sarcoma/Sclerosing Epithelioid Fibrosarcoma and Hibernoma in the Same Thigh: A Case Report.

Introduction: We encountered a unique case of a patient with two distinct tumors coexisting in the same thigh. To the best of our knowledge, this combination of tumors in the same anatomical region has not been previously described in the literature. Case Report: This case report describes a 38-year-old Caucasian male with a painless mass in his right thigh, which was later diagnosed as a hybrid tumor composed of low-grade fibromyxoid sarcoma and sclerosing epithelioid fibrosarcoma, as well as a second tumor, which was diagnosed as a hibernoma. The patient underwent neoadjuvant chemotherapy and surgical excision, followed by adjuvant radiotherapy and treatment for metastatic recurrence. Conclusion: The rarity of this case highlights the need for interdisciplinary collaboration and further investigations into the behavior and management of hybrid tumors. This case also underscores the importance of an accurate histological diagnosis aided by immunohistochemistry and molecular analyses.

Signature of the vascular tumor microenvironment as a marker of the therapeutic response to doxorubicin in a preclinical model of osteosarcoma.

Predicting a response of osteosarcoma patients to chemotherapy, such as doxorubicin or high-dose methotrexate cocktail, remains a challenge in the clinic. Moreover, the prognostic value of currently used necrosis analysis is debatable. New markers of the therapeutic response or the prognostic response are urgently needed. The microenvironment plays a key role in the vascularization of highly heterogeneous tumors. Using the syngeneic MOS-J mouse model of osteosarcoma, we focused our study on the immunohistochemistry of tumor vascularization in order to identify new vessel markers, and to search for potential markers of the therapeutic response. Endomucin+, CD31+, and α-SMA+-positive elements were quantified in control (n=6) and doxorubicin-treated (n=6) mice in three different intra-tumor locations. We also used co-labeling to assess CD31+/Endomucin+ and CD31+/α-SMA+ co-expression. We identified a central tumor zone with a low vascularization profile for all of these markers. We identified two distinct types of vessels: CD31+/Endomucin+ vessels with a sprouting, neo-angiogenic, interlaced appearance, and CD31+/α-SMA+ vessel with a well-defined, mature structure. Doxorubicin appeared to reduce CD31+ expression in the tumor invasion front. In the doxorubicin-sensitive model, there were four times more CD31+/α-SMA+ elements than in the poorly responsive model. Therefore, we propose a methodology based on immunohistochemistry and multiplexed immunofluorescence to use endomucin as a promising new vascular marker in the osteosarcoma model. Moreover, our results suggest that CD31+/α-SMA+ vessels could be considered to be indicators of vasculature normalization and they may be used as specific markers of a good therapeutic response.

Are spine metastasis survival scoring systems outdated and do they underestimate life expectancy? Caution in surgical recommendation guidance.

OBJECTIVE: Survival scoring systems for spine metastasis (SPM) were designed to help surgical practice. The authors sought to validate the prognostic accuracy of the main preoperative scoring systems for SPM. METHODS: It was hypothesized that true patient survival in SPM was better than that predicted using prognosis scores. To investigate this hypothesis, the authors designed a French national retrospective study of a prospectively collected multicenter database involving 739 patients treated for SPM between 2014 and 2017. RESULTS: In this series, the median survival time for all patients from an SPM diagnosis was 17.03 ± 1.5 months. Sensitivity and specificity were estimated using the area under the curve (AUC). The AUC of Tomita's prognosis score was the lowest and poorest (0.4 ± 0.023, range 0.35-0.44), whereas the AUC of the Tokuhashi score was the highest (0.825). The Lei score presented an AUC of 0.686 ± 0.022 (range 0.64-0.7), and the Rades score showed a weaker AUC (0.583 ± 0.020, range 0.54-0.63). Differences among AUCs were all statistically significant (p < 0.001). The modified Bauer score and the Rades score had the highest rate of agreement in predicting survival, with a weighted Cohen's kappa of 0.54 and 0.41, respectively, indicating a moderate agreement. The revised Tokuhashi and Lei scores had a fair rate of agreement (weighted Cohen's kappa = 0.24 and 0.22, respectively). The van der Linden and Tomita scores demonstrated the worst performance, with only a "slight" rate of agreement (weighted Cohen's kappa = 0.19 and 0.16, respectively) between what was predicted and the actual survival. CONCLUSIONS: The use of prognostic scoring systems in the estimation of survival in patients with SPM has become obsolete and therefore underestimates survival. Surgical treatment decisions should no longer be based on survival estimations alone but must also take into account patient symptoms, spinal instability, and quality of life.

Soft tissue reconstruction after pelvic amputation: The efficacy and reliability of free fillet flap reconstruction.

BACKGROUND: The majority of hindquarter amputation defects can be reconstructed with local anterior or posterior thigh flaps. Less than 5% of soft tissue defects require free flap reconstruction after tumour resection. Lower extremity fillet flap is described for reconstructing such defects, but the majority of publications are case reports or short single institutional series. There is a lack of data regarding the oncological outcomes of this highly selected patient group. METHODS: Three tertiary sarcoma units treated twelve patients with hindquarter amputation or hip disarticulation for oncological indications with a free flap reconstruction of the soft tissue defect. RESULTS: The median age of patients was 60 (range 12-76) years. Bone resection was carried out through the SI-joint in six patients and through the sacrum in five patients, with one patient undergoing hip disarticulation. Nine patients had R0 resection margin and three had R1 resection. The median surgical time and flap ischaemia time was 420 (249-650) and 89 (64-210) min, respectively. Median hospital and ICU stay was 18 (10-42) and 3 (1-8) days, respectively. Median blood loss was 2400 (950-10000) ml. There were three returns to theatre due to vascular compromise, with one total flap loss due to arterial thrombosis. Overall survival was 58% (95%CI 28-91%) both at 1-year and at 3-years. DISCUSSION: Carefully selected patients requiring hindquarter amputation with extensive soft tissue defect necessitating free flap reconstruction can be reconstructed with a lower extremity free fillet flap with low rate of local wound complications. Survival of these patients is similar to that in patients requiring less extensive resection.

Bone microenvironment has an influence on the histological response of osteosarcoma to chemotherapy: retrospective analysis and preclinical modeling.

Osteosarcoma, the most common malignant primary bone tumor, is currently treated with chemotherapy and surgery. The effectiveness of chemotherapy is evaluated by means of histological analysis of tumor necrosis, known as "the Huvos score". However, 25% of the patients initially considered good responders will relapse. In our practice, strong tissue heterogeneity around the residual viable cells of the osteosarcoma is observed, but this is not taken into account by the Huvos score, as it is only an average. The objective is to determine whether heterogeneity in the osteosarcoma's microenvironment can play a role in the histological response to chemotherapy. Two complementary approaches have been developed: (i) the therapeutic response to several monotherapies (ifosfamide, cisplatin, doxorubicin) has been compared to tumor growth and the necrosis levels in different preclinical syngeneic osteosarcoma models, mimicking various microenvironments by injecting the tumor cells into subcutaneous, intra-muscular paratibial, or intra-osseous sites; (ii) a retrospective analysis was performed on patients' osteoblastic osteosarcoma biopsies. Tissue localization mapping of residual live tumor cell colonies was evaluated for potential correlation with overall survival. The results of the preclinical studies showed a difference in tumor growth depending on the osteosarcoma model, with a higher rate in bone sites compared to subcutaneous tumors. For the therapeutic response, a higher response to doxorubicin was observed in the intra-osseous model compared to the intra-muscular model for tumor growth (P = 0.013) and necrosis (P = 0.007). These data strongly suggest that the microenvironment plays a role in how osteosarcoma responds to chemotherapy. The retrospective analysis showed no significant survival difference between residual cell sites, although the soft tissues may be seen as a potential negative factor.