RESUMO
Osteosarcoma (OS) is a type of bone cancer that is derived from primitive mesenchymal cells typically affecting children and young adults. The current standard of treatment is a combination of neoadjuvant chemotherapy and surgical resection of the cancerous bone. Post-resection challenges in bone regeneration arise. To determine the appropriate amount of bone to be removed, preoperative imaging techniques such as bone and CT scans are employed. To prevent local recurrence, the current standard of care suggests maintaining bony and soft tissue margins from 3 to 7 cm beyond the tumor. The amount of bone removed in an OS patient leaves too large of a deficit for bone to form on its own and requires reconstruction with metal implants or allografts. Both methods require the bone to heal, either to the implant or across the allograft junction, often in the setting of marrow-killing chemotherapy. Therefore, the issue of bone regeneration within the surgically resected margins remains an important challenge for the patient, family, and treating providers. Mesenchymal stem/stromal cells (MSCs) are potential agents for enhancing bone regeneration post tumor resection. MSCs, used with scaffolds and growth factors, show promise in fostering bone regeneration in OS cases. We spotlight two MSC types-bone marrow-derived (BM-MSCs) and adipose tissue-derived (ASCs)-highlighting their bone regrowth facilitation and immunomodulatory effects on immune cells like macrophages and T cells, enhancing therapeutic outcomes. The objective of this review is two-fold: review work demonstrating any ability of MSCs to target the deranged immune system in the OS microenvironment, and synthesize the available literature on the use of MSCs as a therapeutic option for stimulating bone regrowth in OS patients post bone resection. When it comes to repairing bone defects, both MB-MSCs and ASCs hold great potential for stimulating bone regeneration. Research has showcased their effectiveness in reconstructing bone defects while maintaining a non-tumorigenic role following wide resection of bone tumors, underscoring their capability to enhance bone healing and regeneration following tumor excisions.
RESUMO
Background: Curative treatment of bone sarcoma is primarily based on operative management. The Orthopedic Oncology approach towards this disease has evolved greatly to the breakthrough in systemic treatment options as well as unique implant designs favoring limb salvage over amputations. The purpose of this study was to perform a bibliometric analysis of the top 50 most cited papers related to the orthopedic the approach to bone sarcomas. Methods: We queried the ISI Web of Knowledge database in July 2022. Keywords utilized were: ""Bone Sarcoma" OR "Osteosarcoma" OR "Ewing Sarcoma" OR "Chondrosarcoma" OR "Chordoma". The top 50 articles pertaining to the orthopedic approach to bone sarcoma were included for analysis and included manuscript title, authors, citation count, journal and publication year. Results: The mean number of citations are 187.06 (Range 125-400; SD 67.83). The average citations per year is 10.03 (Range 47.86-3.43; SD 8.05). Many articles were published from 2000 to 2009 (n = 20) and 1990-1999 (n = 13). The majority of the articles were published by institutions within the United States (n = 32). The most common level of evidence was level IV (n = 37). Majority of the articles focused on treatment outcome (n = 22). Conclusion: This study offers a comprehensive review of the most cited literature regarding orthopedic approaches to bony sarcomas. Modern treatment approaches for bone sarcoma has resulted in an increased focus within the literature on achieving disease free survival wide tissue margins. Understanding the trends of available studies allows for physicians and researchers to target and innovate future areas of study.
RESUMO
This study aims to benchmark and analyze the process development and manufacturing costs across the biopharmaceutical drug development cycle and their contribution to overall research and development (R&D) costs. This was achieved with a biopharmaceutical drug development lifecycle cost model that captured the costs, durations, risks and interdependencies of the clinical, process development and manufacturing activities. The budgets needed for process development and manufacturing at each phase of development to ensure a market success each year were estimated. The impact of different clinical success rate profiles on the process development and manufacturing costs at each stage was investigated, with a particular focus on monoclonal antibodies. To ensure a market success each year with an overall clinical success rate (Phase I to approval) of ~12%, the model predicted that a biopharmaceutical company needs to allocate process development and manufacturing budgets in the order of ~$60 M for pre-clinical to Phase II material preparation and ~$70 M for Phase III to regulatory review material preparation. For lower overall clinical success rates of ~4%, which are more indicative of diseases such as Alzheimer's, these values increase to ~$190 M for early-phase and ~$140 Mfor late-phase material preparation; hence, the costs increase 2.5 fold. The costs for process development and manufacturing per market success were predicted to represent 13-17% of the R&D budget from pre-clinical trials to approval. The results of this quantitative structured cost study can be used to aid decision-making during portfolio management and budget planning procedures in biopharmaceutical development.
