Is Skeletal Imaging Essential in the Staging Workup for Conventional Chondrosarcoma?

BACKGROUND: Staging of a bone sarcoma before initiating treatment helps orthopaedic oncologists determine the intent of treatment and predicting the prognosis. As per National Comprehensive Cancer Network (NCCN) and European Society for Medical Oncology (ESMO) guidelines, there are no exclusive recommendations for chondrosarcoma staging. They are staged similar to other bone sarcomas even though skeletal metastases are extremely rare in chondrosarcomas. QUESTIONS/PURPOSES: We asked: (1) What proportion of patients with a chondrosarcoma present with detectable only skeletal metastasis? (2) What proportion of patients with chondrosarcoma present with skeletal metastasis with or without concurrent pulmonary metastases? METHODS: Between January 2006 to December 2017, 480 patients with histology-proven chondrosarcomas of the extremity, including clavicle, scapula, spine, and pelvis, presented to our institute. Fifty-three patients were excluded due to incomplete details about their staging. The remaining 427 were retrospectively analyzed and included in this study. Their clinical, radiological, and histopathological details were retrieved from patient files and electronic medical records. Of the 427 patients included, 53 had Grade 1 chondrosarcoma, 330 had Grade 2 chondrosarcoma, and 41 had Grade 3 chondrosarcoma. Grade was not available in three patients. All patients were staged with a thoracic CT scan and bone scan or a whole body fluorodeoxyglucose positron-emission tomography/CT (FDG PET/CT). Patients with a suspected or documented metastasis were reviewed again by an experienced radiologist and a nuclear medicine expert for the purpose of this study. A total of 8% (35 of 427) of patients with chondrosarcoma had isolated lung metastases at the time of initial staging. These included 9% (31 of 330) of patients with Grade 2 chondrosarcomas and 10% (4 of 41) of patients with Grade 3 chondrosarcomas. No patient with a Grade 1 chondrosarcoma had detectable lung metastases. The primary study endpoint was the number of patients who had a diagnosis of skeletal or skeletal and lung metastases as identified by the staging modalities. RESULTS: Three patients with Grade 2 chondrosarcoma had only skeletal metastasis. No patients with Grade 1 or Grade 3 chondrosarcoma had detectable bone metastases. Combined lung and bone metastases were seen in only two patients with Grade 2 chondrosarcoma. CONCLUSIONS: Our study found that the incidence of bony metastasis in conventional chondrosarcomas is extremely low. Considering the present results, we believe skeletal scanning may be overused in current staging algorithms. We do not have survival outcomes to know if detecting these few patients with skeletal lesions at initial presentation would be important in the absence of symptoms, but our data suggest that omitting skeletal imaging from the staging work-up of conventional chondrosarcomas should be considered. It may be reserved for patients with documented pulmonary metastases. LEVEL OF EVIDENCE: Level IV, diagnostic study.

Safety and pharmacokinetics of Withaferin-A in advanced stage high grade osteosarcoma: A phase I trial.

BACKGROUND: Withaferin-A (WA), an active principle obtained from a traditional Indian herb known as Ashwagandha or the Indian ginseng, has been shown to prevent and cure urethane-induced lung tumors in mice, and also inhibit the growth of transplanted sarcoma in mice. OBJECTIVES: In this study, we evaluated the safety and pharmacokinetics of WA in patients with advanced stage high-grade osteosarcoma. METHODS: A phase I dose escalation study was planned using the classical 3 + 3 design (C33D). Dose escalation cohorts comprised of 72, 108, 144 and 216 mg of WA administered in two to four divided doses per day. Three patients were enrolled in each cohort and the last patient was observed for at least 30 days for any dose-limiting toxicity before progressing to a higher cohort. Pharmacokinetic studies were performed using high performance liquid chromatography (HPLC) technique with sensitivity up to 50 ng/ml. Safety evaluation including clinical examination, detailed history of adverse events, Liver Function Tests , Renal Function Tests and complete blood counts were performed at each visit. WA was administered daily till progression. Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 was used for grading adverse events. RESULTS: The formulation used was generally well tolerated. Eleven adverse events of grade 1 or grade 2 severity were observed. No grade 3 or grade 4 adverse events were observed. Elevation of liver enzymes (5/11) and skin rash (2/11) was the most common adverse events. Other adverse effects include fatigue, fever, edema, and diarrhea (one each). None of the patients had detectable levels of WA in circulation. CONCLUSION: The formulation was well tolerated. However, WA appears to have low oral bioavailability. Further studies with improved formulations are warranted.

Pseudoaneurysms Masquerading as Malignant Bone Tumours.

Swelling around the knees can be due to both neoplastic as well as non neoplastic aetiology. One of the rare cause for the same is pseudoaneurysm. Pseudoaneurysms can mimic a bone tumor or a soft tissue sarcoma. Pseudoanuerysms result because of the gradual growth occurring due to constant arterial pressure and development of a reactive fibrous capsule. Inappropriate diagnosis and management of these lesions may result in major morbidity and rarely mortality. We present two cases of pseudoaneurysms around the knees which were misdiagnosed as osteogenic sarcomas. These cases also stress on the importance of multidisciplinary care, in preventing avoidable morbidity, mortality and providing safe and optimal care to the patients.

Giant Cell Tumor Developing in Paget's Disease of Bone: A Case Report with Review of Literature.

INTRODUCTION: Paget's disease of bone (PDB) is a disease of elderly characterized by disorganized bone remodeling. Development of secondary neoplasm in PDB is a known but rare phenomenon. Development of giant cell tumor in PDB (GCT-PDB) is extremely rare, and little is known about its etiopathogenesis and management. We present a case report of such a development with a review of the literature and the role of various new modalities of treatment available in the management of this rare condition. CASE REPORT: A 40-year-old gentleman presented with back pain and on evaluation was diagnosed as a case of polyostotic PDB. He was treated with intravenous bisphosphonates, calcium, and vitamin D supplements. After an asymptomatic period of 3-year, he presented with a gluteal mass involving ilium and sacrum which was confirmed as GCT on biopsy. Serial angioembolization was attempted but mass progressed, so surgery performed with excision and curettage of the lesion. He presented with a local recurrence 2 years later with a large soft tissue component. He was started on denosumab, RANKL inhibitor, with the aim to downstage the lesion. The patient showed a good response after 6 doses with reduction in soft tissue mass followed by which he underwent surgery with partial T-1 internal hemipelvectomy and curettage of sacrum. Currently, the patient is asymptomatic at a follow-up of 15 months. CONCLUSION: GCT-PDB is a rare phenomenon occurring mainly in polyostotic PDB and is associated with more severe manifestations of the disease. The management is challenging and requires multimodality management. Pharmacological agents include use of bisphosphonates and RANK ligand inhibitor - denosumab. Although surgery is the mainstay of treatment for GCT, other modalities of treatment such as RANK ligand inhibitors (denosumab), selective arterial embolization, or radiation therapy has to be used for inoperable cases or where surgery would be functionally too morbid, especially in cases of GCT-PDB where the disease affects more commonly the axial skeleton.