From Whole-Brain Radiotherapy to Immunotherapy: A Multidisciplinary Approach for Patients with Brain Metastases from NSCLC

Protopapa, Maria; Kouloulias, Vassilis; Nikoloudi, Styliani; Papadimitriou, Christos; Gogalis, Giannis; Zygogianni, Anna

doi:10.1155/2019/3267409

Cited by 12 publications

(9 citation statements)

References 146 publications

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“…The first-line approach to treat BM includes surgery, stereotactic radiosurgery (SRS), and whole-brain radiation therapy (WBRT) [27][28][29]. However, both systemic and intracranial disease control are also possible with the improved systemic therapies that have begun to offer greater potential for specific cancer types and genotypes.…”

Section: Bm Treatmentmentioning

confidence: 99%

Antibodies for the Treatment of Brain Metastases, a Dream or a Reality?

et al. 2020

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The incidence of brain metastases (BM) in cancer patients is increasing. After diagnosis, overall survival (OS) is poor, elicited by the lack of an effective treatment. Monoclonal antibody (mAb)-based therapy has achieved remarkable success in treating both hematologic and non-central-nervous system (CNS) tumors due to their inherent targeting specificity. However, the use of mAbs in the treatment of CNS tumors is restricted by the blood–brain barrier (BBB) that hinders the delivery of either small-molecules drugs (sMDs) or therapeutic proteins (TPs). To overcome this limitation, active research is focused on the development of strategies to deliver TPs and increase their concentration in the brain. Yet, their molecular weight and hydrophilic nature turn this task into a challenge. The use of BBB peptide shuttles is an elegant strategy. They explore either receptor-mediated transcytosis (RMT) or adsorptive-mediated transcytosis (AMT) to cross the BBB. The latter is preferable since it avoids enzymatic degradation, receptor saturation, and competition with natural receptor substrates, which reduces adverse events. Therefore, the combination of mAbs properties (e.g., selectivity and long half-life) with BBB peptide shuttles (e.g., BBB translocation and delivery into the brain) turns the therapeutic conjugate in a valid approach to safely overcome the BBB and efficiently eliminate metastatic brain cells.

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Section: Bm Treatmentmentioning

confidence: 99%

Antibodies for the Treatment of Brain Metastases, a Dream or a Reality?

et al. 2020

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“…Recent advances in imaging, molecular biology, surgery, radiation treatment and systemic therapy considerably expanded therapeutic options available for such patients and, in most of the cases, favorably altered the prognosis. Among recent developments in systemic therapy introduction of immunotherapy for NCCLC influenced standard approach to patients with advanced disease, including those with brain metastases (2,3). Combination of immunotherapy and radiotherapy (RT) became intensively explored considering the potentially beneficial interaction of these modalities.…”

Section: Introductionmentioning

confidence: 99%

Combination of immunotherapy and radiotherapy in the treatment of brain metastases from non-small cell lung cancer

Suwiński¹

2021

J Thorac Dis

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It was commonly assumed in the past that blood-brain barrier could efficiently prohibit penetration of large peptide molecules, such as monoclonal antibodies, including programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors. This belief has been recently revised by studies that demonstrate the presence of functional lymphatic vessels lining the dural sinuses. Furthermore, the activated circulating T cells have been shown to cross the blood-brain barrier. Such observations created strong rationale for attempts of immunotherapy for patients with brain metastases, used either alone or in combination with radiotherapy. The expected benefit from immunotherapy particularly refers to patients without targetable "driver" mutations who are not considered as candidates for novel targeted therapies. Current inference on efficacy and safety of combination of immunotherapy and radiotherapy in the treatment of brain metastases from non-small cell lung cancer (NSCLC) origins, in most, from the retrospective studies. The existing data suggest that use of immune checkpoint inhibitors (ICIs) with brain radiotherapy improves patients outcome, compared to brain radiotherapy alone. The available data also suggest that concurrent use of ICI and stereotactic radiation therapy (SRT) for brain metastases from NSCLC is tolerable and appears more effective than sequential combination of radiotherapy and ICI. Use of steroids appeared detrimental. Since a dependence between the risk of adverse events and type of ICI therapy as well as tumor pathology was found, further studies are required to establish optimal dosage, selection of drugs and sequence of ICI and brain radiotherapy in patients with brain metastases from NSCLC.

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“…In clinical practice, the large sBM, which is hardly separated from GBM, usually comes from the lung cancer. [14,15] The metastases from lung cancer were considered as low perfusion tumor until now. [16] This may explain why the median value and 10th percentile of aCBV could distinguish the two entities.…”

Section: Discussionmentioning

confidence: 99%