Pellerino Alessia, Brastianos Priscilla K, Rudà Roberta, Soffietti Riccardo
Department of Neuro-Oncology, University and City of Health and Science Hospital, 10126 Turin, Italy.
Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02115, USA.
Cancers (Basel). 2021 Jun 9;13(12):2888. doi: 10.3390/cancers13122888.
Leptomeningeal metastases (LM) from solid tumors represent an unmet need of increasing importance due to an early use of MRI for diagnosis and improvement of outcome of some molecular subgroups following targeted agents and immunotherapy. In this review, we first discussed factors limiting the efficacy of targeted agents in LM, such as the molecular divergence between primary tumors and CNS lesions and CNS barriers at the level of the normal brain, brain tumors and CSF. Further, we reviewed pathogenesis and experimental models and modalities, such as MRI (with RANO and ESO/ESMO criteria), CSF cytology and liquid biopsy, to improve diagnosis and monitoring following therapy. Efficacy and limitations of targeted therapies for LM from EGFR-mutant and ALK-rearranged NSCLC, HER2-positive breast cancer and BRAF-mutated melanomas are reported, including the use of intrathecal administration or modification of traditional cytotoxic compounds. The efficacy of checkpoint inhibitors in LM from non-druggable tumors, in particular triple-negative breast cancer, is discussed. Last, we focused on some recent techniques to improve drug delivery.
实体瘤的软脑膜转移（LM）由于早期使用MRI进行诊断以及靶向药物和免疫治疗后某些分子亚组的预后改善，已成为日益重要的未满足需求。在本综述中，我们首先讨论了限制靶向药物在LM中疗效的因素，例如原发性肿瘤与中枢神经系统病变之间的分子差异以及正常脑、脑肿瘤和脑脊液水平的中枢神经系统屏障。此外，我们回顾了发病机制、实验模型和方法，如MRI（采用RANO和ESO/ESMO标准）、脑脊液细胞学检查和液体活检，以改善治疗后的诊断和监测。报告了针对EGFR突变和ALK重排的非小细胞肺癌、HER2阳性乳腺癌和BRAF突变黑色素瘤的LM的靶向治疗的疗效和局限性，包括鞘内给药或传统细胞毒性化合物的改良使用。讨论了检查点抑制剂在不可靶向治疗的肿瘤，特别是三阴性乳腺癌的LM中的疗效。最后，我们重点介绍了一些改善药物递送的最新技术。
