Lolli Jacopo, Tessari Francesca, Berti Franco, Fusella Marco, Fiorentin Davide, Bimbatti Davide, Basso Umberto, Busato Fabio
Radiotherapy Unit, Veneto Institute of Oncology IOV – IRCCS, Padua, Italy.
Department of Radiation Oncology, Abano Terme Hospital, Padua, Italy.
Front Oncol. 2023 Mar 7;13:1136300. doi: 10.3389/fonc.2023.1136300. eCollection 2023.
Radionecrosis is a consequence of SRS (stereotactic radiosurgery) for brain metastases in 34% of cases, and if symptomatic (8%-16%), it requires therapy with corticosteroids and bevacizumab and, less frequently, surgery. Oncological indications are increasing and appropriate stereotactic adapted LINACs (linear accelerators) are becoming more widely available worldwide. Efforts are being made to treat brain radionecrosis in order to relieve symptoms and spare the use of active therapies.
Herein, we describe a 65-year-old female patient presenting with brain radionecrosis 6 months after stereotactic radiotherapy for two brain metastatic lesions. Being symptomatic with headache and slow cognitive-motor function, the patient received corticosteroids. Because of later lung progression, the patient took cabozantinib. An impressive reduction of the two brain radionecrosis areas was seen at the brain MRI 2 months after the initiation of the angiogenic drug.
The high incidence of radionecrosis (2/2 treated lesions) can be interpreted by the combination of SRS and previous ipilimumab that is associated with increased risk of radionecrosis. The molecular mechanisms of brain radionecrosis, and its exact duration in time, are poorly understood. We hypothesize that the antiangiogenic effect of cabozantinib may have had a strong effect in reducing brain radionecrosis areas.
In this clinical case, cabozantinib is associated with a fast and significant volume reduction of brain radionecrosis appearing after SRS and concomitant immunotherapy. This drug seems to show, like bevacizumab, clinical implications not only for its efficacy in systemic disease control but also in reducing brain radionecrosis. More research is needed to evaluate all molecular mechanisms of brain radionecrosis and their interaction with systemic therapies like third-generation TKIs.
放射性坏死是立体定向放射治疗(SRS)治疗脑转移瘤的后果,在34%的病例中出现,若出现症状(8%-16%),则需要使用皮质类固醇和贝伐单抗治疗,较少情况下需进行手术。肿瘤学适应证不断增加,合适的立体定向适配直线加速器(LINAC)在全球范围内越来越普及。人们正在努力治疗脑放射性坏死,以缓解症状并避免使用积极的治疗方法。
在此,我们描述一名65岁女性患者,在对两个脑转移瘤进行立体定向放射治疗6个月后出现脑放射性坏死。患者因头痛和认知运动功能迟缓出现症状,接受了皮质类固醇治疗。由于后来肺部病情进展,患者服用了卡博替尼。在开始使用血管生成药物2个月后的脑部MRI检查中,发现两个脑放射性坏死区域明显缩小。
放射性坏死的高发生率(2/2个治疗病灶)可通过SRS与先前使用的伊匹单抗联合使用来解释,这与放射性坏死风险增加有关。脑放射性坏死的分子机制及其确切持续时间尚不清楚。我们推测卡博替尼的抗血管生成作用可能对减少脑放射性坏死区域有显著效果。
在本临床病例中,卡博替尼与SRS和同步免疫治疗后出现的脑放射性坏死体积快速且显著缩小有关。这种药物似乎不仅在控制全身疾病疗效方面,而且在减少脑放射性坏死方面,都像贝伐单抗一样具有临床意义。需要更多研究来评估脑放射性坏死的所有分子机制及其与第三代酪氨酸激酶抑制剂等全身治疗的相互作用。