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Elevated tumor lactate concentrations predict for an increased risk of metastases in head-and-neck cancer.

Publication ,  Journal Article
Brizel, DM; Schroeder, T; Scher, RL; Walenta, S; Clough, RW; Dewhirst, MW; Mueller-Klieser, W
Published in: Int J Radiat Oncol Biol Phys
October 1, 2001

PURPOSE: Hypoxia shifts the balance of cellular energy production toward glycolysis with lactate generation as a by-product. Quantitative bioluminescence imaging allows for the quantitation of lactate concentrations in individual tumors. We assessed the relationship between pretreatment tumor lactate concentrations and subsequent development of metastatic disease in patients with newly diagnosed head-and-neck cancer. METHODS AND MATERIALS: At the time of biopsy of the primary site, a separate specimen was taken and flash-frozen for subsequent quantitation of lactate concentration using a luciferase bioluminescence technique. The two-dimensional spatial distribution of the bioluminescence intensity within the tissue section was registered directly using a microscope and an imaging photon counting system. Photon intensity was converted to distributions of volume-related tissue concentrations (micromol per gram wet weight). Treatment consisted of either surgery and postoperative radiotherapy or primary radiotherapy, based on presenting disease stage and institutional treatment policies. The subsequent development of metastatic disease constituted the primary clinical endpoint. RESULTS: Biopsies obtained from 40 patients were evaluable in 34. The larynx was the most frequent primary site (n = 25). Other sites included oropharynx (n = 5), hypopharynx (n = 3), and oral cavity (n = 1). Most patients (74%) presented with an advanced stage T3 or T4 primary tumor. Nodal involvement was present in 19 (54%) patients. The median tumor lactate concentration was 7.1 micromol/g. Tumors were classified as having either low or high lactate concentrations according to whether these values were below or above the median. The median follow-up time for surviving patients is 27 months. Two-year actuarial survival was 90% for patients with low-lactate-concentration tumor vs. 35% for patients with high-lactate-concentration primaries (<0.0001). Two-year metastasis-free survival was adversely influenced by high tumor lactate concentrations (90% vs. 25%, p < 0.0001). The median lactate concentration for tumors that subsequently metastasized was 12.9 micromol/g vs. 4.8 micromol/g for patients who remained continuously free of disease (p < 0.005). Lactate concentration was not correlated with presenting T stage or N stage. DISCUSSION: Elevated tumor lactate concentrations are associated with the subsequent development of nodal or distant metastases in head-and-neck cancer patients. This more aggressive malignant phenotype is probably associated with hypoxia-mediated radioresistance and the upregulation of metastasis-associated genes.

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Published In

Int J Radiat Oncol Biol Phys

DOI

ISSN

0360-3016

Publication Date

October 1, 2001

Volume

51

Issue

2

Start / End Page

349 / 353

Location

United States

Related Subject Headings

  • Pharyngeal Neoplasms
  • Oncology & Carcinogenesis
  • Mouth Neoplasms
  • Laryngeal Neoplasms
  • Lactic Acid
  • Humans
  • Head and Neck Neoplasms
  • Follow-Up Studies
  • Cell Hypoxia
  • Carcinoma, Squamous Cell
 

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Brizel, D. M., Schroeder, T., Scher, R. L., Walenta, S., Clough, R. W., Dewhirst, M. W., & Mueller-Klieser, W. (2001). Elevated tumor lactate concentrations predict for an increased risk of metastases in head-and-neck cancer. Int J Radiat Oncol Biol Phys, 51(2), 349–353. https://doi.org/10.1016/s0360-3016(01)01630-3
Brizel, D. M., T. Schroeder, R. L. Scher, S. Walenta, R. W. Clough, M. W. Dewhirst, and W. Mueller-Klieser. “Elevated tumor lactate concentrations predict for an increased risk of metastases in head-and-neck cancer.Int J Radiat Oncol Biol Phys 51, no. 2 (October 1, 2001): 349–53. https://doi.org/10.1016/s0360-3016(01)01630-3.
Brizel DM, Schroeder T, Scher RL, Walenta S, Clough RW, Dewhirst MW, et al. Elevated tumor lactate concentrations predict for an increased risk of metastases in head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2001 Oct 1;51(2):349–53.
Brizel, D. M., et al. “Elevated tumor lactate concentrations predict for an increased risk of metastases in head-and-neck cancer.Int J Radiat Oncol Biol Phys, vol. 51, no. 2, Oct. 2001, pp. 349–53. Pubmed, doi:10.1016/s0360-3016(01)01630-3.
Brizel DM, Schroeder T, Scher RL, Walenta S, Clough RW, Dewhirst MW, Mueller-Klieser W. Elevated tumor lactate concentrations predict for an increased risk of metastases in head-and-neck cancer. Int J Radiat Oncol Biol Phys. 2001 Oct 1;51(2):349–353.
Journal cover image

Published In

Int J Radiat Oncol Biol Phys

DOI

ISSN

0360-3016

Publication Date

October 1, 2001

Volume

51

Issue

2

Start / End Page

349 / 353

Location

United States

Related Subject Headings

  • Pharyngeal Neoplasms
  • Oncology & Carcinogenesis
  • Mouth Neoplasms
  • Laryngeal Neoplasms
  • Lactic Acid
  • Humans
  • Head and Neck Neoplasms
  • Follow-Up Studies
  • Cell Hypoxia
  • Carcinoma, Squamous Cell