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Metabolic management of glioblastoma multiforme using standard therapy together with a restricted ketogenic diet: Case Report.

Zuccoli G, Marcello N, Pisanello A, Servadei F, Vaccaro S, Mukherjee P, Seyfried TN - Nutr Metab (Lond) (2010)

Bottom Line: Following incomplete surgical resection, the patient was diagnosed with glioblastoma multiforme expressing hypermethylation of the MGMT gene promoter.The patient was followed using MRI and positron emission tomography with fluoro-deoxy-glucose (FDG-PET).Biomarker changes showed reduced levels of blood glucose and elevated levels of urinary ketones.

View Article: PubMed Central - HTML - PubMed

Affiliation: Radiology Department, Arcispedale Santa Maria Nuova, Reggio E, 42100, Italy. giulio.zuccoli@gmail.com.

ABSTRACT

Background: Management of glioblastoma multiforme (GBM) has been difficult using standard therapy (radiation with temozolomide chemotherapy). The ketogenic diet is used commonly to treat refractory epilepsy in children and, when administered in restricted amounts, can also target energy metabolism in brain tumors. We report the case of a 65-year-old woman who presented with progressive memory loss, chronic headaches, nausea, and a right hemisphere multi-centric tumor seen with magnetic resonance imaging (MRI). Following incomplete surgical resection, the patient was diagnosed with glioblastoma multiforme expressing hypermethylation of the MGMT gene promoter.

Methods: Prior to initiation of the standard therapy, the patient conducted water-only therapeutic fasting and a restricted 4:1 (fat: carbohydrate + protein) ketogenic diet that delivered about 600 kcal/day. The patient also received the restricted ketogenic diet concomitantly during the standard treatment period. The diet was supplemented with vitamins and minerals. Steroid medication (dexamethasone) was removed during the course of the treatment. The patient was followed using MRI and positron emission tomography with fluoro-deoxy-glucose (FDG-PET).

Results: After two months treatment, the patient's body weight was reduced by about 20% and no discernable brain tumor tissue was detected using either FDG-PET or MRI imaging. Biomarker changes showed reduced levels of blood glucose and elevated levels of urinary ketones. MRI evidence of tumor recurrence was found 10 weeks after suspension of strict diet therapy.

Conclusion: This is the first report of confirmed GBM treated with standard therapy together with a restricted ketogenic diet. As rapid regression of GBM is rare in older patients following incomplete surgical resection and standard therapy alone, the response observed in this case could result in part from the action of the calorie restricted ketogenic diet. Further studies are needed to evaluate the efficacy of restricted ketogenic diets, administered alone or together with standard treatment, as a therapy for GBM and possibly other malignant brain tumors.

No MeSH data available.


Related in: MedlinePlus

Brain MRI taken a few days after ending the standard radiotherapy plus concomitant  temozolomide therapy together with KD-CR protocol. No clear evidence of tumor tissue or  associated edema was seen. Arrow indicates porencephaly.
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Figure 4: Brain MRI taken a few days after ending the standard radiotherapy plus concomitant temozolomide therapy together with KD-CR protocol. No clear evidence of tumor tissue or associated edema was seen. Arrow indicates porencephaly.

Mentions: During the concomitant chemotherapy, laboratory tests revealed abnormalities in complete blood count to include leukocytes 2.86 ×1000/mm3, erythrocytes 3.56 million/mm3, hemoglobin 10.5 g/dl, and hematocrit 32%. The patient also developed lymphopenia 0.332 ×1000/mm3. The concomitant treatment was terminated on February 17th. One week later (February 24, 2009), the patient underwent an MRI. No evidence of either the tumor or the associated edema was apparent (Figure 4). Porencephaly was seen in the right frontal region at the tumor site. Ex vacuum enlargement of the right frontal horn and lack of mass effect represented indirect confirmation of tumor regression. Restitutio ad Integrum of the insular lobe, caudate nucleus, and putamen were noted with only minimal damage to the blood brain barrier (Figure 4). On March 3, the patient developed mild hypoproteinemia (5.1 g/dl). This was corrected by increasing dietary protein to about 7 g/day for one month, which returned protein levels to the normal range (6.4 gr/dl). On April 21, the patient underwent positron emission tomography with fluoro-deoxy-glucose (FDG-PET), which included delayed acquisition. No evidence of recurrent disease was detected (Figure 5). An MRI, performed on July 22, was stable over the comparison time from February 24 with no clear evidence of disease recurrence. At that time, the patient weighed 50 kg (110 pounds, BMI 20.0 kg/m2), was in good general health, and had no neurological complications. The patient's Karnofsky performance status was at 100% during the course of the diet. Caloric intake was not strictly followed after July 22. An MRI performed on October 9, 2008 showed tumor recurrence. The patient was then treated with CPT11 (Irinotecan) and bevacizumab (Avastin) therapy. A schematic diagram showing the clinical time course of dietary treatments with dates of MRI and PET is presented in Figure 6.


Metabolic management of glioblastoma multiforme using standard therapy together with a restricted ketogenic diet: Case Report.

Zuccoli G, Marcello N, Pisanello A, Servadei F, Vaccaro S, Mukherjee P, Seyfried TN - Nutr Metab (Lond) (2010)

Brain MRI taken a few days after ending the standard radiotherapy plus concomitant  temozolomide therapy together with KD-CR protocol. No clear evidence of tumor tissue or  associated edema was seen. Arrow indicates porencephaly.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2874558&req=5

Figure 4: Brain MRI taken a few days after ending the standard radiotherapy plus concomitant temozolomide therapy together with KD-CR protocol. No clear evidence of tumor tissue or associated edema was seen. Arrow indicates porencephaly.
Mentions: During the concomitant chemotherapy, laboratory tests revealed abnormalities in complete blood count to include leukocytes 2.86 ×1000/mm3, erythrocytes 3.56 million/mm3, hemoglobin 10.5 g/dl, and hematocrit 32%. The patient also developed lymphopenia 0.332 ×1000/mm3. The concomitant treatment was terminated on February 17th. One week later (February 24, 2009), the patient underwent an MRI. No evidence of either the tumor or the associated edema was apparent (Figure 4). Porencephaly was seen in the right frontal region at the tumor site. Ex vacuum enlargement of the right frontal horn and lack of mass effect represented indirect confirmation of tumor regression. Restitutio ad Integrum of the insular lobe, caudate nucleus, and putamen were noted with only minimal damage to the blood brain barrier (Figure 4). On March 3, the patient developed mild hypoproteinemia (5.1 g/dl). This was corrected by increasing dietary protein to about 7 g/day for one month, which returned protein levels to the normal range (6.4 gr/dl). On April 21, the patient underwent positron emission tomography with fluoro-deoxy-glucose (FDG-PET), which included delayed acquisition. No evidence of recurrent disease was detected (Figure 5). An MRI, performed on July 22, was stable over the comparison time from February 24 with no clear evidence of disease recurrence. At that time, the patient weighed 50 kg (110 pounds, BMI 20.0 kg/m2), was in good general health, and had no neurological complications. The patient's Karnofsky performance status was at 100% during the course of the diet. Caloric intake was not strictly followed after July 22. An MRI performed on October 9, 2008 showed tumor recurrence. The patient was then treated with CPT11 (Irinotecan) and bevacizumab (Avastin) therapy. A schematic diagram showing the clinical time course of dietary treatments with dates of MRI and PET is presented in Figure 6.

Bottom Line: Following incomplete surgical resection, the patient was diagnosed with glioblastoma multiforme expressing hypermethylation of the MGMT gene promoter.The patient was followed using MRI and positron emission tomography with fluoro-deoxy-glucose (FDG-PET).Biomarker changes showed reduced levels of blood glucose and elevated levels of urinary ketones.

View Article: PubMed Central - HTML - PubMed

Affiliation: Radiology Department, Arcispedale Santa Maria Nuova, Reggio E, 42100, Italy. giulio.zuccoli@gmail.com.

ABSTRACT

Background: Management of glioblastoma multiforme (GBM) has been difficult using standard therapy (radiation with temozolomide chemotherapy). The ketogenic diet is used commonly to treat refractory epilepsy in children and, when administered in restricted amounts, can also target energy metabolism in brain tumors. We report the case of a 65-year-old woman who presented with progressive memory loss, chronic headaches, nausea, and a right hemisphere multi-centric tumor seen with magnetic resonance imaging (MRI). Following incomplete surgical resection, the patient was diagnosed with glioblastoma multiforme expressing hypermethylation of the MGMT gene promoter.

Methods: Prior to initiation of the standard therapy, the patient conducted water-only therapeutic fasting and a restricted 4:1 (fat: carbohydrate + protein) ketogenic diet that delivered about 600 kcal/day. The patient also received the restricted ketogenic diet concomitantly during the standard treatment period. The diet was supplemented with vitamins and minerals. Steroid medication (dexamethasone) was removed during the course of the treatment. The patient was followed using MRI and positron emission tomography with fluoro-deoxy-glucose (FDG-PET).

Results: After two months treatment, the patient's body weight was reduced by about 20% and no discernable brain tumor tissue was detected using either FDG-PET or MRI imaging. Biomarker changes showed reduced levels of blood glucose and elevated levels of urinary ketones. MRI evidence of tumor recurrence was found 10 weeks after suspension of strict diet therapy.

Conclusion: This is the first report of confirmed GBM treated with standard therapy together with a restricted ketogenic diet. As rapid regression of GBM is rare in older patients following incomplete surgical resection and standard therapy alone, the response observed in this case could result in part from the action of the calorie restricted ketogenic diet. Further studies are needed to evaluate the efficacy of restricted ketogenic diets, administered alone or together with standard treatment, as a therapy for GBM and possibly other malignant brain tumors.

No MeSH data available.


Related in: MedlinePlus