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生酮代谢疗法联合胶质母细胞瘤标准治疗:一例报告

Ketogenic metabolic therapy in conjunction with standard treatment for glioblastoma: A case report.

作者信息

Phillips Matthew C L, Thotathil Ziad, Dass Prashanth Hari, Ziad Fouzia, Moon Ben G

机构信息

Department of Neurology, Waikato Hospital, Hamilton 3204, New Zealand.

Department of Radiation Oncology, Waikato Hospital, Hamilton 3204, New Zealand.

出版信息

Oncol Lett. 2024 Mar 26;27(5):230. doi: 10.3892/ol.2024.14363. eCollection 2024 May.

Abstract

Glioblastoma (GBM) is the most common primary malignant brain tumour in adults. The standard of care consists of surgical resection and concurrent chemoradiation, followed by adjuvant temozolomide chemotherapy. This protocol is associated with a median survival of 12-15 months, and <5% of patients survive >3 years. Ketogenic metabolic therapy (KMT) targets cancer cell metabolism by restricting glucose availability and evoking differential stress resistance and sensitization, which may augment the standard treatments and lead to therapeutic benefit. The present study reports the case of a 64-year-old woman with isocitrate dehydrogenase (IDH)-wildtype GBM who pursued the standard treatment protocol in conjunction with an intensive, multimodal KMT program for 3 years. The KMT program consisted of a series of prolonged (7-day, fluid-only) fasts, which were specifically timed to maximize the tolerability and efficacy of the standard treatments, combined with a time-restricted ketogenic diet on all other days. During the first and second treatment years the patient sustained a glucose ketone index (GKI) of 1.65 and 2.02, respectively, which coincided with complete clinical improvement, a healthy body-mass index and a high quality of life, with no visible progressive tumour detected on imaging at the end of the second year. In the setting of the death of an immediate family member leading to increased life stress, slightly relaxed KMT adherence, and a higher GKI of 3.20, slow cancer progression occurred during the third year. The adverse effects attributed to KMT were mild. Despite the limitations of this case report, it highlights the feasibility of implementing the standard treatment protocol for GBM in conjunction with an intensive, long-term, multimodal and specifically timed KMT program, the potential therapeutic efficacy of which may depend upon achieving as low a GKI as possible.

摘要

胶质母细胞瘤(GBM)是成人中最常见的原发性恶性脑肿瘤。标准治疗方案包括手术切除和同步放化疗,随后进行辅助替莫唑胺化疗。该方案的中位生存期为12 - 15个月,不到5%的患者生存期超过3年。生酮代谢疗法(KMT)通过限制葡萄糖供应以及引发不同的应激抗性和敏感性来靶向癌细胞代谢,这可能增强标准治疗效果并带来治疗益处。本研究报告了一名64岁异柠檬酸脱氢酶(IDH)野生型GBM女性患者的病例,该患者采用标准治疗方案并结合强化、多模式的KMT计划长达3年。KMT计划包括一系列延长的(7天,仅摄入液体)禁食期,这些禁食期经过特殊安排以最大化标准治疗的耐受性和疗效,同时在其他所有日子采用限时生酮饮食。在治疗的第一年和第二年,患者的葡萄糖酮指数(GKI)分别维持在1.65和2.02,与此同时临床症状完全改善,身体质量指数健康,生活质量高,在第二年结束时影像学检查未发现明显的肿瘤进展。在一名直系家庭成员去世导致生活压力增加、对KMT的依从性稍有放松且GKI升高至3.20的情况下,第三年出现了癌症缓慢进展。归因于KMT的不良反应较轻。尽管本病例报告存在局限性,但它凸显了将GBM的标准治疗方案与强化、长期、多模式且经过特殊安排的KMT计划相结合的可行性,其潜在治疗效果可能取决于尽可能降低GKI。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d4a/10996027/69c0a06a22ba/ol-27-05-14363-g00.jpg

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