Abstract
Osteosarcoma (OS) is the most common primary bone cancer affecting children and young adults, most often occurring at the metaphysis of long bones. At present, treatment with combinations of surgery and chemotherapy for the localized OS has only brought minuscule improvements in prognosis. In comparison, the advanced, metastatic, or recurrent forms of OS are often non-responsive to chemotherapy, adding to the dire need to develop new and efficient therapies.The question of interest investigated in this systematic review is whether immunotherapy can play a meaningful role in improving the clinical outcomes of children with OS. This article aims to summarize the preclinical and clinical research conducted thus far on potential therapeutic avenues for pediatric OS using immunotherapy, including methods like checkpoint inhibition, adoptive cellular therapy with T-cells, chimeric antigen receptor T (CAR-T), and natural killer (NK) cells. It also highlights the influence of the innate and adaptive immune system on the tumor microenvironment, allowing for OS progression and metastasis.This systematic review contains 27 articles and analyses of multiple clinical trials employing immunotherapeutic drugs to 785 osteosarcoma participants and over 243 pediatric patients. The articles were obtained through PubMed, PubMed Central, and ClinicalTrials.gov and individually assessed for quality using the Assessment of Multiple Systematic Reviews (AMSTAR) checklist and the Cochrane risk-of-bias tool. The reviews reveal that immunotherapy's most significant impact on pediatric OS includes combining immune checkpoint blockers with traditional chemotherapy and surgery. However, due to the bimodal distribution of this aggressive malignancy, these studies cannot precisely estimate the overall effect and any potential life-threatening adverse events following therapy in children. Further research is required to fully assess the impact of these immunotherapies, including more extensive multinational clinical trials to focus on the pediatric population.
Highlights
BackgroundOsteosarcoma (OS), known as osteogenic sarcoma, is one of the most commonly encountered bone malignancies worldwide, occurring in 5% of children globally [1]
Among the 2,391 articles discovered, 223 were from PubMed, 2,035 studies were found in PubMed Central, 92 clinical studies were located through clinicaltrials.gov, and 41 papers were obtained via reference review
We excluded 43 articles by screening for duplicates and removed 1,527 of them after screening for studies based on their eligibility to our inclusion criteria, matching for the age of participants, years of publication, studies performed in humans, completed or ongoing clinical trials, availability of full or open texts, and those published in the English language
Summary
BackgroundOsteosarcoma (OS), known as osteogenic sarcoma, is one of the most commonly encountered bone malignancies worldwide, occurring in 5% of children globally [1]. The outcome of patients with OS was poor, with a survival rate of less than 20% just before the 1970s. Despite surgery and cytotoxic therapy, approximately 30% of patients relapse within five years, with lung and bone metastases being the most prevalent sites of recurrence [4,5]. Metastatic, and recurrent OS continue to experience quite a poor prognosis. The values reflect a stagnant survival rate due to the lack of new treatment strategies, especially in the frontier of pediatric OS [7]. Novel treatments are needed in urgency to improve the outcomes in children with cancer
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