Limb-salvage surgery versus extremity amputation for early-stage bone cancer in the extremities: a population-based study.

Background: Many attempts have been made to induce limb salvage as an alternative to amputation for primary bone cancer in the extremities, but efforts to establish its benefits over amputation yielded inconsistent results with regard to outcomes and functional recovery. This study aimed to investigate the prevalence and therapeutic efficiency of limb-salvage tumor resection in patients with primary bone cancer in the extremities, and to compare it with extremity amputation. Methods: Patients diagnosed with T1-T2/N0/M0 primary bone cancer in the extremities between 2004 and 2019 were retrospectively identified from the Surveillance, Epidemiology, and End Results program database. Cox regression models were used to test for statistical differences between overall survival (OS) and disease-specific survival (DSS). The cumulative mortality rates (CMRs) for non-cancer comorbidities were also estimated. The evidence level in this study was Level IV. Results: A total of 2,852 patients with primary bone cancer in the extremities were included in this study, among which 707 died during the study period. Of the patients, 72.6% and 20.4% underwent limb-salvage resection and extremity amputation, respectively. In patients with T1/T2-stage bone tumors in the extremities, limb-salvage resection was associated with significantly better OS and DSS than extremity amputation (OS: adjusted HR, 0.63; 95% confidence interval [CI], 0.55-0.77; p < 0.001; DSS: adjusted HR, 0.70; 95% CI, 0.58-0.84; p < 0.001). Limb-salvage resection was associated with significantly better OS and DSS than extremity amputation for patients with limb osteosarcoma (OS: adjusted HR, 0.69; 95% CI, 0.55-0.87; p = 0.001; DSS: adjusted HR, 0.73; 95% CI, 0.57-0.94; p = 0.01). Mortality from cardiovascular diseases and external injuries was remarkably declined in primary bone cancer in the extremities patients who underwent limb-salvage resection (cardiovascular diseases, p = 0.005; external injuries, p = 0.009). Conclusion: Limb-salvage resection exhibited excellent oncological superiority for T1/2-stage primary bone tumors in the extremities. We recommend that patients with resectable primary bone tumors in the extremities undergo limb-salvage surgery as the first choice of treatment.

A Systematic Review of the Expression, Signalling and Function of P2 Receptors in Primary Bone Cancer.

Primary bone cancers are rare malignant diseases with significant morbidity and mortality. The treatment regimen relies on a combination of surgery (often involving amputation), chemotherapy and radiotherapy with outcomes dependent on localization of the tumour, grade, size and response to chemotherapy. Both treatment options and survival statistics have remained constant over the past 40 years and alternative therapies need to be explored. Purinergic signalling involving the interaction of extracellular nucleotides with P2 receptors has been investigated in numerous cancers with activation or inhibition a topic of debate. To assess whether purinergic signalling could be a viable target in primary bone cancer a systematic review for relevant primary literature published in PubMed, MEDLINE and Web of Science was performed. Search terms were formulated around three separate distinct topics; expression of P2 receptors in primary bone cancer models, P2 receptor signalling pathways involved and the functional consequences of P2 receptor signalling. Searching identified 30 primary articles after screening and eligibility assessments. This review highlights the diverse expression, signalling pathways and functional roles associated with different P2 receptors in primary bone cancers and provides a systematic summary of which P2 receptors are exciting targets to treat primary bone cancer and its associated symptoms.

Qualitative study exploring patients experiences of being diagnosed and living with primary bone cancer in the UK.

OBJECTIVE: The aim of this study is to explore the experiences of patients with primary bone cancer. DESIGN: Qualitative study design using semistructured interviews and focus groups. SETTING: Hospitals across the UK and recruitment through UK sarcoma charities and support groups. METHODS: Semistructured telephone/face-to-face interviews and focus groups with a purposive sample of 26 participants. Data were analysed using Framework Analysis. PARTICIPANTS: Patients (n=26) with primary bone cancer aged 13-77 years. The majority were male (69%), white (85%); diagnosed within 4 years (54%); and had lower limb sarcoma (65%). Ten participants had undergone an upper/lower limb amputation (39%). RESULTS: The health-related quality-of-life domains of physical, emotional and social well-being and healthcare professionals' role were the overarching themes of analysis. The physical domain anchored patient experiences. The intensity and length of treatment, the severity of side-effects, the level of disability after surgery and the uncertainty of their prognosis had an impact on patient's self-image, confidence, mood and identity, and caused disruption to various aspects of the patients' social life, including their relationships (emotional and sexual) and participation in work/school and leisure activities. Adaptation was influenced by the way patients dealt with stress and adversity, with some finding a new outlook in life, and others struggling with finding their 'new normal'. Family and friends were the main source of support. Healthcare professional's expertise and support was critical. Rehabilitation services had a considerable role in patient's physical and emotional well-being, but inequitable access to these services was apparent. CONCLUSIONS: This study described the impact of primary bone cancer on patients' well-being and adjustment over time with the identification of influencing factors of better/worse experiences. It showed that impact was felt after end of treatment and affected patients at different life stages. Holistic models of survivorship care are needed.

Socio-economic patterning in early mortality of patients aged 0-49 years diagnosed with primary bone cancer in Great Britain, 1985-2008.

BACKGROUND: Studies have shown marked improvements in survival between 1981 and 2000 for Ewing sarcoma patients but not for osteosarcoma. This study aimed to explore socio-economic patterning in early mortality rates for both tumours. PROCEDURE: The study analysed all 2432 osteosarcoma and 1619 Ewing sarcoma cases, aged 0-49 years, diagnosed in Great Britain 1985-2008 and followed to 31/12/2009. Logistic regression models were used to calculate risk of dying within three months, six months, one year, three years and five years after diagnosis. Associations with Townsend deprivation score and its components were examined at small-area level. Urban/rural status was studied at larger regional level. RESULTS: For osteosarcoma, after age adjustment, mortality at three months, six months and one year was associated with higher area unemployment, OR = 1.05 (95% CI 1.00, 1.10), OR = 1.04 (95% CI 1.01, 1.08) and OR = 1.04 (95% CI 1.02, 1.06) respectively per 1% increase in unemployment. Mortality at six months was associated with greater household non-car ownership, OR = 1.02 (95% CI 1.00, 1.03). For Ewing sarcoma, there were no significant associations between mortality and overall Townsend score, nor its components for any time period. For both tumours increasing mortality was associated with less urban and more remote rural areas. CONCLUSIONS: This study found that for osteosarcoma, early mortality was associated with residence at diagnosis in areas of higher unemployment, suggesting risk of early death may be socio-economically determined. For both tumours, distance from urban centres may lead to greater risk of early death.

A review of the mechanism of action and clinical applications of sorafenib in advanced osteosarcoma.

OBJECTIVE: To summarise the contemporary literature regarding sorafenib and its effectiveness as a novel treatment in advanced osteosarcoma. BACKGROUND: Modern treatment has seen the cure rate of osteosarcoma increase to 65%. However, in patients who do not achieve remission, prognosis is poor, as there are no effective, consensual second line therapies. Sorafenib has emerged as a potentially viable drug to be used in this context. METHOD: A literature review was conducted evaluating articles pertaining to osteosarcoma and sorafenib. DISCUSSION: Clinical studies were prioritised, but preclinical data was also evaluated to elaborate on mechanisms and potential targets for the future. Limitations of the review and data were explored. CONCLUSION: In isolation, sorafenib was shown to only provide brief clinical benefit due to various described mechanisms. However, when combined with other drugs that addressed its weaknesses or other aspects of the pathogenesis of osteosarcoma, it proved to be effective in reducing disease progression in a variety of advanced cases. Further investigation into the use of sorafenib in combination therapy is needed. Specifically, the combination of sorafenib with denosumab has displayed potential to be an effective future treatment for osteosarcoma.