Santos Juliana Guimaraes, Faria Gisele, Cruz Wanise Da Cruz Souza Da, Fontes Cristina Asvolinsque, Schönthal Axel H, Quirico-Santos Thereza, da Fonseca Clovis O
Departament of Programa de Pós-Graduação em Ciências Médicas, Fluminense Federal University Rio de Janeiro, Brazil.
Departament of Programa de Pós-graduação em Neurologia, Faculdade de Medicina, Fluminense Federal University, Rio de Janeiro, Brazil.
Surg Neurol Int. 2020 Nov 11;11:389. doi: 10.25259/SNI_445_2020. eCollection 2020.
Standard of care for glioblastoma (GB), consisting of cytotoxic chemotherapy, steroids, and high-dose radiation, induces changes in the tumor microenvironment through its effects on glucose availability, which is a determinant for tumor progression (TP). Low-carbohydrate diet (LCD) reduces the glucose levels needed to drive the Warburg effect.
To investigate LCD's effect on GB therapy, we have begun a clinical trial using LCD as an addition to intranasal perillyl alcohol (POH) for recurrent GB (rGB) patients. This study involved 29 individuals and evaluated, over a period of 1 year, the adjuvant effect of LCD associated with POH therapy in terms of toxicity, extent of peritumoral edema, reduced corticosteroid use, seizure frequency, and overall survival. POH group ( = 14) received solely intranasal POH without specific diet regimen, whereas POH/LCD group ( = 15) received intranasal POH in combination with nutritional intervention. Patients' assessment was based on clinical reviews and magnetic resonance data.
In the 1-year follow-up, the POH/LCD group showed a 4.4-fold decrease in the proportion of patients who needed treatment with corticosteroids, as well as a reduction in tumor size and peritumoral edema, as compared to the POH group. While 75% of patients undergoing POH treatment experienced seizures, this fraction was reduced to 56% in the POH/LCD group. A 2.07-fold increase in the proportion of patients with stable disease, along with a 2.8-fold decrease in the proportion of patients with TP, was seen in the POH/LCD group.
The results presented in this study show that the LCD associated with intranasal POH therapy may represent a viable option as adjunctive therapy for rGB to improve survival without compromising patients' quality of life. Prospective cohort studies are needed to confirm these findings and validate the efficacy of this novel therapeutic strategy.
胶质母细胞瘤（GB）的标准治疗方案包括细胞毒性化疗、类固醇和高剂量放疗，通过影响葡萄糖可用性来诱导肿瘤微环境发生变化，而葡萄糖可用性是肿瘤进展（TP）的一个决定因素。低碳水化合物饮食（LCD）可降低驱动瓦伯格效应所需的葡萄糖水平。
为了研究LCD对GB治疗的影响，我们已开始一项临床试验，将LCD作为复发性GB（rGB）患者鼻内使用紫苏醇（POH）治疗的补充。本研究纳入了29名个体，在1年的时间里评估了与POH治疗相关的LCD在毒性、瘤周水肿程度、减少皮质类固醇使用、癫痫发作频率和总生存期方面的辅助作用。POH组（n = 14）仅接受鼻内POH治疗，无特定饮食方案，而POH/LCD组（n = 15）接受鼻内POH联合营养干预。患者评估基于临床检查和磁共振数据。
在1年的随访中，与POH组相比，POH/LCD组需要使用皮质类固醇治疗的患者比例下降了4.4倍，肿瘤大小和瘤周水肿也有所减轻。接受POH治疗的患者中有75%发生癫痫，而在POH/LCD组中这一比例降至56%。POH/LCD组疾病稳定的患者比例增加了2.07倍，TP患者比例下降了2.8倍。
本研究结果表明，与鼻内POH治疗相关的LCD可能是rGB辅助治疗的一个可行选择，可在不影响患者生活质量的情况下提高生存率。需要进行前瞻性队列研究来证实这些发现并验证这种新型治疗策略的疗效。
