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Restricting carbohydrates to fight head and neck cancer-is this realistic?

Klement RJ - Cancer Biol Med (2014)

Bottom Line: Head and neck cancers (HNCs) are aggressive tumors that typically demonstrate a high glycolytic rate, which results in resistance to cytotoxic therapy and poor prognosis.Dietary restriction of carbohydrates (CHOs) and their replacement with fat, mostly in form of a ketogenic diet (KD), have been suggested to accommodate for both the altered tumor cell metabolism and cancer-associated weight loss.While CHO restriction seems feasible in HNC patients the available evidence indicates that its role may extend beyond fighting malnutrition to fighting HNC itself.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiotherapy and Radiation Oncology, Leopoldina Hospital, Schweinfurt 97421, Germany.

ABSTRACT
Head and neck cancers (HNCs) are aggressive tumors that typically demonstrate a high glycolytic rate, which results in resistance to cytotoxic therapy and poor prognosis. Due to their location these tumors specifically impair food intake and quality of life, so that prevention of weight loss through nutrition support becomes an important treatment goal. Dietary restriction of carbohydrates (CHOs) and their replacement with fat, mostly in form of a ketogenic diet (KD), have been suggested to accommodate for both the altered tumor cell metabolism and cancer-associated weight loss. In this review, I present three specific rationales for CHO restriction and nutritional ketosis as supportive treatment options for the HNC patient. These are (1) targeting the origin and specific aspects of tumor glycolysis; (2) protecting normal tissue from but sensitizing tumor tissue to radiation- and chemotherapy induced cell kill; (3) supporting body and muscle mass maintenance. While most of these benefits of CHO restriction apply to cancer in general, specific aspects of implementation are discussed in relation to HNC patients. While CHO restriction seems feasible in HNC patients the available evidence indicates that its role may extend beyond fighting malnutrition to fighting HNC itself.

No MeSH data available.


Related in: MedlinePlus

Fusion image of a radiotherapy planning CT and FDG-PET scan of a patient with a primary right-sided cT1 cN2b tonsillar squamous cell carcinoma after tonsillectomy. The high FDG uptake of the right lymph node conglomerates is indicative of highly glycolytic metastasis. Note, however, that FDG-PET only measures glucose uptake and conversion into glucose-6-phosphate, and can therefore not discriminate between lactate production or feeding of glycolysis intermediates and end products into the pentose phosphate pathway or citric acid cycle. The high lactate release which can be measured with other techniques such as magnetic resonance spectroscopy is, however, indicated for illustrative purposes since it is characteristic for aggressive metastasis.
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f1: Fusion image of a radiotherapy planning CT and FDG-PET scan of a patient with a primary right-sided cT1 cN2b tonsillar squamous cell carcinoma after tonsillectomy. The high FDG uptake of the right lymph node conglomerates is indicative of highly glycolytic metastasis. Note, however, that FDG-PET only measures glucose uptake and conversion into glucose-6-phosphate, and can therefore not discriminate between lactate production or feeding of glycolysis intermediates and end products into the pentose phosphate pathway or citric acid cycle. The high lactate release which can be measured with other techniques such as magnetic resonance spectroscopy is, however, indicated for illustrative purposes since it is characteristic for aggressive metastasis.

Mentions: The Warburg effect is the basic principle behind molecular imaging using positron emission tomography (PET) with the glucose analog 2-(18F)fluoro-2-deoxy-D-glucose (FDG). FDG is structurally similar to glucose except for the substitution of an OH group by the positron emitter 18F. Similar to glucose it therefore enters the cells through glucose transporters and gets phosphorylated by the enzyme hexokinase. Unlike glucose, however, FDG cannot be further metabolized after phosphorylation to FDG-6-phosphate and stays trapped inside the cell until it decays. The amount of assimilated FDG is quantified by the standardized uptake value (SUV) which expresses the ratio between the measured tissue activity and the injected activity standardized to body weight. In HNC FDG-PET in combination with computer tomography (PET/CT) has shown great benefit for tumor and lymph node staging, detection of an unknown primary tumor, radiation treatment planning, evaluation of therapy response and long-term surveillance20,21 (Figure 1). Furthermore, several studies have found that pretreatment tumor SUV—either as maximal SUV22-25 or combined with tumor volume into a total lesion glycolysis parameter26—is an independent significant predictor of local control, disease free and overall survival rates, while high lymph node SUVs were predictive for distant recurrence at 1 year27. Plasma glucose levels are able to falsify SUVs in highly glycolytic tumors28 which might account for negative results reported in some studies29.


Restricting carbohydrates to fight head and neck cancer-is this realistic?

Klement RJ - Cancer Biol Med (2014)

Fusion image of a radiotherapy planning CT and FDG-PET scan of a patient with a primary right-sided cT1 cN2b tonsillar squamous cell carcinoma after tonsillectomy. The high FDG uptake of the right lymph node conglomerates is indicative of highly glycolytic metastasis. Note, however, that FDG-PET only measures glucose uptake and conversion into glucose-6-phosphate, and can therefore not discriminate between lactate production or feeding of glycolysis intermediates and end products into the pentose phosphate pathway or citric acid cycle. The high lactate release which can be measured with other techniques such as magnetic resonance spectroscopy is, however, indicated for illustrative purposes since it is characteristic for aggressive metastasis.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4197426&req=5

f1: Fusion image of a radiotherapy planning CT and FDG-PET scan of a patient with a primary right-sided cT1 cN2b tonsillar squamous cell carcinoma after tonsillectomy. The high FDG uptake of the right lymph node conglomerates is indicative of highly glycolytic metastasis. Note, however, that FDG-PET only measures glucose uptake and conversion into glucose-6-phosphate, and can therefore not discriminate between lactate production or feeding of glycolysis intermediates and end products into the pentose phosphate pathway or citric acid cycle. The high lactate release which can be measured with other techniques such as magnetic resonance spectroscopy is, however, indicated for illustrative purposes since it is characteristic for aggressive metastasis.
Mentions: The Warburg effect is the basic principle behind molecular imaging using positron emission tomography (PET) with the glucose analog 2-(18F)fluoro-2-deoxy-D-glucose (FDG). FDG is structurally similar to glucose except for the substitution of an OH group by the positron emitter 18F. Similar to glucose it therefore enters the cells through glucose transporters and gets phosphorylated by the enzyme hexokinase. Unlike glucose, however, FDG cannot be further metabolized after phosphorylation to FDG-6-phosphate and stays trapped inside the cell until it decays. The amount of assimilated FDG is quantified by the standardized uptake value (SUV) which expresses the ratio between the measured tissue activity and the injected activity standardized to body weight. In HNC FDG-PET in combination with computer tomography (PET/CT) has shown great benefit for tumor and lymph node staging, detection of an unknown primary tumor, radiation treatment planning, evaluation of therapy response and long-term surveillance20,21 (Figure 1). Furthermore, several studies have found that pretreatment tumor SUV—either as maximal SUV22-25 or combined with tumor volume into a total lesion glycolysis parameter26—is an independent significant predictor of local control, disease free and overall survival rates, while high lymph node SUVs were predictive for distant recurrence at 1 year27. Plasma glucose levels are able to falsify SUVs in highly glycolytic tumors28 which might account for negative results reported in some studies29.

Bottom Line: Head and neck cancers (HNCs) are aggressive tumors that typically demonstrate a high glycolytic rate, which results in resistance to cytotoxic therapy and poor prognosis.Dietary restriction of carbohydrates (CHOs) and their replacement with fat, mostly in form of a ketogenic diet (KD), have been suggested to accommodate for both the altered tumor cell metabolism and cancer-associated weight loss.While CHO restriction seems feasible in HNC patients the available evidence indicates that its role may extend beyond fighting malnutrition to fighting HNC itself.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiotherapy and Radiation Oncology, Leopoldina Hospital, Schweinfurt 97421, Germany.

ABSTRACT
Head and neck cancers (HNCs) are aggressive tumors that typically demonstrate a high glycolytic rate, which results in resistance to cytotoxic therapy and poor prognosis. Due to their location these tumors specifically impair food intake and quality of life, so that prevention of weight loss through nutrition support becomes an important treatment goal. Dietary restriction of carbohydrates (CHOs) and their replacement with fat, mostly in form of a ketogenic diet (KD), have been suggested to accommodate for both the altered tumor cell metabolism and cancer-associated weight loss. In this review, I present three specific rationales for CHO restriction and nutritional ketosis as supportive treatment options for the HNC patient. These are (1) targeting the origin and specific aspects of tumor glycolysis; (2) protecting normal tissue from but sensitizing tumor tissue to radiation- and chemotherapy induced cell kill; (3) supporting body and muscle mass maintenance. While most of these benefits of CHO restriction apply to cancer in general, specific aspects of implementation are discussed in relation to HNC patients. While CHO restriction seems feasible in HNC patients the available evidence indicates that its role may extend beyond fighting malnutrition to fighting HNC itself.

No MeSH data available.


Related in: MedlinePlus