Ius Tamara, Somma Teresa, Pasqualetti Francesco, Berardinelli Jacopo, Vitulli Francesca, Caccese Mario, Cella Eugenia, Cenciarelli Carlo, Pozzoli Giacomo, Sconocchia Giuseppe, Zeppieri Marco, Gerardo Caruso, Caffo Maria, Lombardi Giuseppe
Unit of Neurosurgery, Head-Neck and Neurosciences Department, University Hospital of Udine, I-33100 Udine, Italy.
Division of Neurosurgery, Department of Neurosciences, Reproductive and Odontostomatological Sciences, Federico II University, I-80128 Naples, Italy.
Oncol Lett. 2024 Jul 17;28(3):440. doi: 10.3892/ol.2024.14573. eCollection 2024 Sep.
Despite the implementation of multimodal treatments after surgery, glioblastoma (GBM) remains an incurable disease, posing a significant challenge in neuro-oncology. In this clinical setting, local therapy (LT), a developing paradigm, has received significant interest over time due to its potential to overcome the drawbacks of conventional therapy options for GBM. The present review aimed to trace the historical development, highlight contemporary advances and provide insights into the future horizons of LT in GBM management. In compliance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols criteria, a systematic review of the literature on the role of LT in GBM management was conducted. A total of 2,467 potentially relevant articles were found and, after removal of duplicates, 2,007 studies were screened by title and abstract (Cohen's κ coefficient=0.92). Overall, it emerged that 15, 10 and 6 clinical studies explored the clinical efficiency of intraoperative local treatment modalities, local radiotherapy and local immunotherapy, respectively. GBM recurrences occur within 2 cm of the radiation field in 80% of cases, emphasizing the significant influence of local factors on recurrence. This highlights the urgent requirement for LT strategies. In total, three primary reasons have thus led to the development of numerous LT solutions in recent decades: i) Intratumoral implants allow the blood-brain barrier to be bypassed, resulting in limited systemic toxicity; ii) LT facilitates bridging therapy between surgery and standard treatments; and iii) given the complexity of GBM, targeting multiple components of the tumor microenvironment through ligands specific to various elements could have a synergistic effect in treatments. Considering the spatial and temporal heterogeneity of GBM, the disease prognosis could be significantly improved by a combination of therapeutic strategies in the era of precision medicine.
尽管手术后实施了多模式治疗，但胶质母细胞瘤（GBM）仍然是一种无法治愈的疾病，这在神经肿瘤学中构成了重大挑战。在这种临床背景下，局部治疗（LT）作为一种正在发展的模式，随着时间的推移因其克服GBM传统治疗方法缺点的潜力而受到了极大关注。本综述旨在追溯LT的历史发展，突出当代进展，并为GBM管理中LT的未来前景提供见解。按照系统评价和Meta分析方案的首选报告项目标准，对关于LT在GBM管理中的作用的文献进行了系统评价。共发现2467篇潜在相关文章，去除重复项后，通过标题和摘要筛选了2007项研究（科恩κ系数=0.92）。总体而言，分别有15项、10项和6项临床研究探讨了术中局部治疗模式、局部放疗和局部免疫治疗的临床疗效。80%的GBM复发发生在放射野2厘米范围内，这强调了局部因素对复发的重大影响。这突出了对LT策略的迫切需求。近几十年来，总共三个主要原因导致了众多LT解决方案的发展：i）瘤内植入物可以绕过血脑屏障，从而使全身毒性有限；ii）LT有助于手术和标准治疗之间的过渡治疗；iii）鉴于GBM的复杂性，通过针对各种元素的特异性配体靶向肿瘤微环境的多个组成部分在治疗中可能具有协同作用。考虑到GBM的空间和时间异质性，在精准医学时代，通过联合治疗策略可以显著改善疾病预后。
