Impact of the COVID-19 on the surgical management of bone and soft tissue sarcoma: A systematic review.

Background: The COVID-19 pandemic had greatly and negatively impacted health services including the management of bone and soft tissue sarcoma. As disease progression is time-sensitive, decision taken by the oncology orthopedic surgeon on performing surgical treatment determines the patient outcome. On the other hand, as the world tried to control the spread of COVID-19 infection, treatment re-prioritization based on urgency level had to be done which consequently affect treatment provision for sarcoma patients. Patient and clinician's concern regarding the outbreak have also inflicted on treatment decision making. A systematic review was thought to be necessary to summarize the changes seen in managing primary malignant bone and soft tissue tumors. Methods: We performed this systematic review in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 Statement. The review protocol had been registered on PROSPERO with submission number CRD42022329430. We included studies which reported primary malignant tumor diagnosis and its surgical intervention from March 11th, 2020 onwards. The main outcome is to report changes implemented by different centers around the world in managing primary malignant bone tumors surgically in response to the pandemic. Three electronic medical databases were scoured and by applying eligibility criteria. Individual authors evaluated the articles' quality and risk of bias using the Newcastle-Ottawa Quality Assessment Scale other instruments developed by JBI of the University of Adelaide. The overall quality assessment of this systematic review was self-evaluated using the AMSTAR (Assessing the Methodological Quality of Systematic Reviews) Checklist. Results: There were 26 studies included in the review with various study designs, conveyed in almost all continents. The outcomes from this review are change in surgery time, change in surgery type, and change in surgery indication in patients with primary bone and soft tissue sarcoma. Surgery timing has been experiencing delay since the pandemic occurred, including delay in the multidisciplinary forum, which were all related to lockdown regulations and travel restrictions. For surgery type, limb amputation was preferred compared to limb-salvage procedures due to shorter duration and simpler reconstruction with better control of malignancy. Meanwhile, the indications for surgical management are still based on the patient's demographics and disease stages. However, some would stall surgery regardless of malignancy infiltration and fracture risks which are indication for amputation. As expected, our meta-analysis showed higher post-surgical mortality in patients with malignant bone and soft tissue sarcoma during the COVID-19 pandemic with odds ratio of 1.14. Conclusion: Surgical management of patients with primary bone and soft tissue sarcoma has seriously been affected due to adjustments to the COVID-19 pandemic. Other than institutional restrictions to contain the infection, patient and clinician's decisions to postpone treatment due to COVID-19 transmission concern were also impactful in treatment course. Delay in surgery timing has caused higher risk of worse surgical outcome during the pandemic, which is aggravated if the patient is infected by COVID-19 as well. As we transition into a post-COVID-19 pandemic period, we expect patients to be more lenient in returning for their treatment but by then disease progression might have taken place, resulting in worse overall prognosis. Limitation to this study were few assumptions made in the synthesis of numerical data and meta-analysis only for changes in surgery time outcome and lack of intervention studies included.

Implantation of bovine hydroxyapatite and secretome with different oxygen concentration may improve massive bone defect regeneration: An experimental study on animal model.

The most widely used biomaterials in the treatment of massive bone defects are allograft bone or metal implants. The current problem is that the availability of allographs is limited and metal implants are very expensive. Mass production of secretome can make bone reconstruction of massive bone defects using a scaffold more effective and efficient. This study aims to prove bone regeneration in massive bone defects using bovine hydroxyapatite reconstruction with normoxic and hypoxic secretome conditions using collagen type 1 (COL1), alkaline phosphate (ALP), osteonectin (ON), and osteopontin (OPN) parameters. This is an in vivo study using male New Zealand white rabbits aged 6-9 months. The research was carried out at the Biomaterials Center-Tissue Bank, Dr. Soetomo Hospital for the manufacturer of bovine hydroxyapatite (BHA) and secretome BM-MSC culture under normoxic and hypoxic conditions, and UNAIR Tropical Disease Institute for implantation in experimental animals. Data analysis was carried out with the one-way ANOVA statistical test and continued with the Post Hoc test LSD statistical test to determine whether or not there were significant differences between groups. There were significant differences between hypoxic to normoxic group and hypoxic to BHA group at day-30 observation using ALP, COL 1, ON, and OPN parameters. Meanwhile, there is only osteonectin parameter has significant difference at day-30 observation. At day-60 observation, only OPN parameter has significant differences between hypoxic to normoxic and hypoxic to BHA group. Between day-30 and day-60 observation, BHA and normoxic groups have a significant difference at all parameters, but in hypoxic group, there are only difference at ALP, COL 1, and ON parameters. Hypoxic condition BM-MSC secretome with BHA composite is superior and could be an option for treating bone defect.

Analysis of prognostic factors in soft tissue sarcoma: Cancer registry from a single tertiary hospital in Indonesia. A retrospective cohort study.

BACKGROUND: Soft tissue sarcoma is one cause of mortality in adult malignancies. This tumor is rare, persistent, and highly-recurrent. Many patients are came in late stage. It is important to identify a prognostic tool that is reliable, easily obtainable, and widely applicable. The aim of this study is to investigate and analyze the prognostic value of clinicopathological and biomarker factors in patients with soft tissue sarcoma. METHODS: This retrospective study extracts data from the musculoskeletal tumor registry from January 2012 to December 2018 in a single tertiary hospital. Eighty patients with diagnosis of soft tissue sarcoma were included. Preoperative modified Glasgow Prognostic Score, Neutrophils/Lymphocytes Ratio, Hemoglobin, serum lactate dehydrogenase data were analyzed along with demographic, clinical, radiological and histopathological data. The relationship between variables on overall survival, distant metastasis, and local recurrence were evaluated using univariate and multivariate Cox regression. RESULTS: On univariate analysis, there was significant relationship between hemoglobin, Neutrophils/Lymphocytes Ratio and modified Glasgow Prognostic Score with overall survival (p = 0.031, HR = 1.99; p = 0.04, HR = 1.129; and p = 0.044, HR = 3.89). A significant relationship was found between age and soft tissue sarcoma stage with distant metastasis (p = 0.046, HR = 1.95; and p = 0.00, HR = 3.22). In addition, we also found significant relationship between surgical margin with local recurrence (p = 0.018, OR = 3.44). However, on multivariate analysis the independent prognostic factor for overall survival was only modified Glasgow Prognostic Score (HR = 2.138; p = 0.011). Stage IIIA (HR = 5.32; p = 0.005) and IIIB (HR = 13.48; p = 0.00) were independent prognostic for distant metastasis. Surgical margin was independently associated with local recurrence (HR = 14.84; p = 0.001). CONCLUSION: Modified Glasgow Prognostic Score can be used as prognostic tool of overall survival in soft tissue sarcoma patients. Moreover, stage of STS and surgical margin can be used as a prognostic factor for distant metastasis and local recurrence of soft tissue sarcoma respectively.