Effect of adjuvant chemotherapy on localized dedifferentiated low-grade osteosarcoma: a systematic review.

PURPOSE: Dedifferentiated low-grade osteosarcomas, which are considered high grade malignancies, can arise from the dedifferentiation of parosteal and low-grade osteosarcomas. Usually, localized dedifferentiated low-grade osteosarcomas are treated by wide resection, and the efficacy of adjuvant chemotherapy is controversial. We conducted a systematic review of studies that investigated the rates of mortality and significant events, such as recurrence and metastases, in localized dedifferentiated low-grade osteosarcoma patients who received wide resection only and in those who received wide resection and (neo-)adjuvant chemotherapy. METHODS: We identified 712 studies through systematic searches of Embase, PubMed, and the Cochrane Central Register of Controlled Trials databases. Of those studies, seven were included in this review and none were randomized controlled trials. In the seven studies, 114 localized dedifferentiated low-grade osteosarcoma patients were examined. RESULTS: Mortality rates of the resection plus chemotherapy (R + C) and the resection only (Ronly) groups were 20.3% and 11.4%, respectively [overall pooled odds ratio, 1.59 (P = 0.662); heterogeneity I2, 0%]. The local recurrence or distant metastasis rate in the R + C group was 36.7% and that in the Ronly group was 28.6% [overall pooled odds ratio, 1.37 (P = 0.484); heterogeneity I2 was 0%]. CONCLUSIONS: Results show a limited efficacy of adjuvant chemotherapy for localized dedifferentiated low-grade osteosarcoma. However, because this was a systematic review of retrospective studies that examined a small number of patients, future randomized controlled trials are needed.

Role of bone marrow adipocytes in bone metastasis development and progression: a systematic review.

Purpose: Bone marrow adipocytes (BMAs) are the most plentiful cells in the bone marrow and function as an endocrine organ by producing fatty acids, cytokines, and adipokines. Consequently, BMAs can interact with tumor cells, influencing both tumor growth and the onset and progression of bone metastasis. This review aims to systematically evaluate the role of BMAs in the development and progression of bone metastasis. Methods: A comprehensive search was conducted on PubMed, Web of Science, and Scopus electronic databases, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement standards, to identify studies published from March 2013 to June 2023. Two independent reviewers assessed and screened the literature, extracted the data, and evaluated the quality of the studies. The body of evidence was evaluated and graded using the ROBINS-I tool for non-randomized studies of interventions and the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) tool for in vivo studies. The results were synthesized using descriptive methods. Results: The search yielded a total of 463 studies, of which 17 studies were included in the final analysis, including 15 preclinical studies and two non-randomized clinical studies. Analysis of preclinical studies revealed that BMAs play a significant role in bone metastasis, particularly in prostate cancer followed by breast and malignant melanoma cancers. BMAs primarily influence cancer cells by inducing a glycolytic phenotype and releasing or upregulating soluble factors, chemokines, cytokines, adipokines, tumor-derived fatty acid-binding protein (FABP), and members of the nuclear receptor superfamily, such as chemokine (C-C motif) ligand 7 (CCL7), C-X-C Motif Chemokine Ligand (CXCL)1, CXCL2, interleukin (IL)-1ß, IL-6, FABP4, and peroxisome proliferator-activated receptor γ (PPARγ). These factors also contribute to adipocyte lipolysis and regulate a pro-inflammatory phenotype in BMAs. However, the number of clinical studies is limited, and definitive conclusions cannot be drawn. Conclusion: The preclinical studies reviewed indicate that BMAs may play a crucial role in bone metastasis in prostate, breast, and malignant melanoma cancers. Nevertheless, further preclinical and clinical studies are needed to better understand the complex role and relationship between BMAs and cancer cells in the bone microenvironment. Targeting BMAs in combination with standard treatments holds promise as a potential therapeutic strategy for bone metastasis.

Clinical outcomes of medical treatments for progressive desmoid tumors following active surveillance: a systematic review.

Approximately 80% of desmoid tumors (DTs) show spontaneous regression or disease stabilization during first-line active surveillance. Medical treatment can be considered in cases of disease progression. This systematic review aimed to evaluate the effectiveness and toxicity of each medical treatment by reviewing only the studies that included progressive disease as the inclusion criterion. We searched the EMBASE, PubMed, and CENTRAL databases to identify published studies for progressive DTs. The disease control rates of the medical treatments, such as low-dose chemotherapy with methotrexate plus vinblastine or vinorelbine, imatinib, sorafenib, pazopanib, nilotinib, anlotinib, doxorubicin-based agents, liposomal doxorubicin, hydroxyurea, and oral vinorelbine for progressive DTs were 71-100%, 78-92%, 67-96%, 84%, 88%, 86%, 89-100%, 90-100%, 75%, and 64%, respectively. Low-dose chemotherapy, sorafenib, pazopanib, nilotinib, anlotinib, and liposomal doxorubicin had similar toxicities. Sorafenib and pazopanib were less toxic than imatinib. Doxorubicin-based chemotherapy was associated with the highest toxicity. Hydroxyurea and oral vinorelbine exhibited the lowest toxicity. Stepwise therapy escalation from an initial, less toxic treatment to more toxic agents is recommended for progressive DTs. Sorafenib and pazopanib had limited on-treatment side effects but had the possibility to induce long-term treatment-related side effects. In contrast, low-dose chemotherapy has some on-treatment side effects and is known to have very low long-term toxicity. Thus, for progressive DTs following active surveillance, low-dose chemotherapy is recommended in young patients as long-term side effects are minor, whereas therapies such as sorafenib and pazopanib is recommended for older patients as early side effects are minor.

Epithelioid hemangioendothelioma, an ultra-rare cancer: a consensus paper from the community of experts.

Epithelioid hemangioendothelioma (EHE) is an ultra-rare, translocated, vascular sarcoma. EHE clinical behavior is variable, ranging from that of a low-grade malignancy to that of a high-grade sarcoma and it is marked by a high propensity for systemic involvement. No active systemic agents are currently approved specifically for EHE, which is typically refractory to the antitumor drugs used in sarcomas. The degree of uncertainty in selecting the most appropriate therapy for EHE patients and the lack of guidelines on the clinical management of the disease make the adoption of new treatments inconsistent across the world, resulting in suboptimal outcomes for many EHE patients. To address the shortcoming, a global consensus meeting was organized in December 2020 under the umbrella of the European Society for Medical Oncology (ESMO) involving >80 experts from several disciplines from Europe, North America and Asia, together with a patient representative from the EHE Group, a global, disease-specific patient advocacy group, and Sarcoma Patient EuroNet (SPAEN). The meeting was aimed at defining, by consensus, evidence-based best practices for the optimal approach to primary and metastatic EHE. The consensus achieved during that meeting is the subject of the present publication.

Spontaneous healing of an osteochondroma fracture.

Osteochondroma is the most common benign tumor of bone, usually asymptomatic. Fracture of an osteochondroma is a rare complication and has been recognized as a cause of pain. Treatment of this fracture is controversial and some authors suggest fracture as an indication for surgical excision. We present a case of fractured osteochondroma that healed without complication.

Minimally invasive technique for curettage of chondroblastoma using endoscopic technique.

Chondroblastoma is a rare benign bone tumor. The treatment for chondroblastoma usually consists of curettage of the lesion and packing the tumor cavity with bone grafts or bone cement. However, chondroblastomas are known to recur in 10% to 20% of cases after excision, possibly because the incomplete removal of pathological tissue at surgery. We present a case of chondroblastoma in the distal femur treated by endoscopic curettage, which allowed a complete resection of tumor tissue and a minimal damage of the bone. The patient had relief of symptoms, rapid function restoration and no local recurrence. Endoscopic curettage is a promising new treatment for chondroblastoma. In fact, the extra-articular technique enters the tumor cavity via a tunnel drilled through the medullary canal, allowing to visualize possible residual tumor tissue or defects of the articular surface, without violating the joint and without taking away a much bigger cortical window.

Imaging of bone tumors for the musculoskeletal oncologic surgeon.

The appropriate diagnosis and treatment of bone tumors requires close collaboration between different medical specialists. Imaging plays a key role throughout the process. Radiographic detection of a bone tumor is usually not challenging. Accurate diagnosis is often possible from physical examination, history, and standard radiographs. The location of the lesion in the bone and the skeleton, its size and margins, the presence and type of periosteal reaction, and any mineralization all help determine diagnosis. Other imaging modalities contribute to the formation of a diagnosis but are more critical for staging, evaluation of response to treatment, surgical planning, and follow-up.When necessary, biopsy is often radioguided, and should be performed in consultation with the surgeon performing the definitive operative procedure. CT is optimal for characterization of the bone involvement and for evaluation of pulmonary metastases. MRI is highly accurate in determining the intraosseous extent of tumor and for assessing soft tissue, joint, and vascular involvement. FDG-PET imaging is becoming increasingly useful for the staging of tumors, assessing response to neoadjuvant treatment, and detecting relapses.Refinement of these and other imaging modalities and the development of new technologies such as image fusion for computer-navigated bone tumor surgery will help surgeons produce a detailed and reliable preoperative plan, especially in challenging sites such as the pelvis and spine.

Palliative treatments for advanced osteosarcoma.

Advances in diagnostic imaging, interventional radiology, chemotherapy and surgery greatly improved the outcome of patients with osteosarcoma, and made limb salvage possible without compromising survival. In these patients, the prognosis is influenced by the site and resectability of the tumor, prior malignancy, and histological response to preoperative chemotherapy. Unfortunately, the progress has not been as significant in the treatment of advanced osteosarcoma, namely metastatic, recurrent and unresectable tumor. Yet, although advanced and forecasting a dismal prognosis, advanced osteosarcoma is not necessarily untreatable. Aggressive local and medical treatments, including surgical removal of primary and/or metastatic disease are currently available; however, yet, most treatments aim at palliation. Palliative local treatments including isolated limb perfusion, radiation therapy, embolization, chemoembolization, thermal ablation and cryoablation, all have an important role for these patients. The aim of palliative treatments is to achieve a mild response by offering the least discomfort to the patient with the minimum possible complications, and possibly increase of survival.

Selective arterial embolisation for bone tumours: experience of 454 cases.

PURPOSE: The authors present the experience of a single institution with selective arterial embolisation for primary and metastatic bone tumours. MATERIALS AND METHODS: A total of 365 patients were treated with 454 embolisation procedures from December 2002 to April 2010. Embolisation was the primary treatment for benign bone tumours, adjuvant treatment to surgery for benign and malignant bone tumours and palliative treatment for bone sarcomas and metastases. Indications for repeat embolisation included pain or imaging evidence of progressive disease: 105 patients had repeat embolisation at the same location at an interval of 1-3 months; 260 patients had one embolisation, 78 had two and 29 had three or more. In all patients, N-2-butyl cyanoacrylate (NBCA) in 33% lipiodol was the embolic agent used. RESULTS: A total of 419 of the 454 embolisations (93%) were technically successful. In 35 cases, embolisation was not feasible because of poor lesion vascularisation (21 patients with bone metastases and two with aneurysmal bone cysts), origin of the Adamkiewicz artery in the embolisation field (four patients with bone metastases and one with aneurysmal bone cyst), atheromatosis and arteriosclerosis (five patients with bone metastases) and anatomical and technical problems such as small-calibre vessels, many branches and acute vessel angles (two patients with bone metastases). A clinical response was achieved in 406 of the 419 procedures (97%), and no response in 13 procedures in patients with pelvis and sacrum tumours. Complications included postembolisation syndrome in 81 patients (22%), transient paraesthesias in 41 (11%), skin breakdown and subcutaneous necrosis at the shoulder and pelvis in five (1.4%) and paresis of the sciatic nerve in one (0.3%). CONCLUSIONS: We recommend embolisation as primary or palliative treatment or an adjunct to surgery for tumours of variable histology. Strict adherence to the principles of transcatheter embolisation is important. Arteries feeding the tumour and collaterals must be evaluated carefully and catheterised superselectively to protect the normal tissues. NBCA is considered the most appropriate embolic agent for small-vessel occlusion without major complications.

High grade malignant peripheral nerve sheath tumors: outcome of 62 patients with localized disease and review of the literature.

Malignant peripheral nerve sheath tumours (MPNST) are rare sarcomas with one of the poorest prognoses of all the soft tissue sarcomas. Information about adjuvant treatment is scarce and not homogeneous for this diagnosis. We analyzed retrospectively the outcome of patients with localized high grade MPNST admitted to our institute from 1969 to 2008. A review of the literature is also reported. Of 62 evaluable patients, 23 were females and 39 males, median age 39 years (17-71), 22/62 had neurofibromatosis type I. Median follow-up was 54 months (range 12-194). A total of 22/62 are alive; 26 patients had surgery alone, 18 received radiation therapy, 12 received radiation therapy and chemotherapy, and 6 received only adjuvant chemotherapy. The 5-year disease-free survival was 30% and 5-year overall survival was 38%. A positive trend for adjuvant radiation, but not for chemotherapy was observed according to univariate analysis only for disease-free survival and overall survival. Multivariate analysis indicated that primary site, size and surgical margins remained significant for disease-free survival and only site and size were significant for overall survival. New drugs employed successfully in advanced mpNSt should be employed also in the adjuvant setting.

Synovial chondrosarcoma: report of two cases and literature review.

Synovial chondrosarcoma is a rare soft tissue tumor that can arise from a previous synovial chondromatosis or as de novo tumor. The clinical and radiological findings of this malignancy are very similar to those of aggressive synovial chondromatosis. Confusion with other joint pathologies makes the diagnosis of synovial chondrosarcoma difficult in most of the cases. We present one recently diagnosed and treated case of synovial chondrosarcoma. The review of our hospital database revealed one more similar case. In both cases the malignancy arose from a pre-existing synovial chondromatosis. We also present a literature review emphasizing the clinical and histological findings of this rare entity.

Vascular homografts for vessel substitution in skeletal and soft tissue sarcomas of the limbs.

Large vessel involvement by skeletal and soft tissue sarcomas of the extremities does not change the modern limb sparing surgery for those neoplasms. An arterial and, if the vein is open, a venous bypass should always be offered to any patient young or old, with high or low grade sarcoma, because preserving the limb permits quicker rehabilitation, which is particularly useful in the case of a short life expectancy. In 650 cases of skeletal sarcomas, 10 arterial (1.5%) and four venous bypasses were done, all with autologous veins but one in PTFE; we had no problems except a silent arterial occlusion. Of 1000 patients with soft tissue sarcomas, 32 (3%) had vessel involvement permitting limb sparing surgery. The arterial bypass, which is the limb-saving operation, was performed 16 times with a PTFE with one early occlusion and four cases of prosthesis infection, with two amputations despite redo operation with an autologous vein. The more recent 16 cases were, therefore, always done with biological vessel substitution--autologous vein or tissue bank vessel--with only one infection that healed without operation and one case of homograft rupture followed by amputation. Since 1999 in all 13 resected cases with an open vein, we did the arterial and the venous bypass (twice PTFE, six autologous vein, and five bank vessel) with the aim of avoiding postoperative venous hypertension, but only four of the venous bypasses remained open. Venous bypasses are a harmless, but still experimental, procedure.