Metabolic activity on [18f]-fluorodeoxyglucose-positron emission tomography/computed tomography and glucose transporter-1 expression might predict clinical outcomes in patients with limited disease small-cell lung cancer who receive concurrent chemoradiation

Clin Lung Cancer. 2014 Mar;15(2):e13-21. doi: 10.1016/j.cllc.2013.09.005. Epub 2013 Nov 14.

Abstract

Background: Limited disease small-cell lung cancer responds well to concurrent chemoradiation therapy (CCRT), but shows high relapse rate and short RFS. We aimed to evaluate tumor metabolic activities measured using FDG-PET as a prognostic factor and analyze its relationships with markers of tumor biologic behavior.

Patients and methods: Forty-one LD-SCLC patients receiving 4 cycles of EP (etoposide 120 mg/m(2), days 1-3; cisplatin 60 mg/m(2), day 1), 2 cycles of EP (etoposide 130 mg/m(2), days 1-3; cisplatin 30 mg/m(2), day 1)-CCRT were enrolled. Maximum standardized uptake value (SUV; SUVmax) of primary tumor was revised with SUV of liver (SUVlivermax). Differences between pre-, posttreatment average SUV uptake of primary tumor, and intrathoracic lymph nodes were presented as ΔSUVliveravg. Thirty-one tumor biopsy specimens were immunostained for GLUT-1, Bcl-2, and HIF-1α.

Results: The median overall survival (OS), and RFS were 13.7 and 10.4 months, respectively. In multivariate analysis, pretreatment lactate dehydrogenase (LDH) and ΔSUVliveravg correlated with RFS (hazard ratio [HR], 2.8, P = .043; HR, 0.3, P = .004). Sex, LDH, objective tumor metabolic response, and SUVlivermax correlated with OS (HR, 12.1, P = .006; HR, 3.7, P = .037; HR, 10.1, P = .008; and HR, 0.2, P = .014, respectively). High GLUT-1 positivity (> 75%), and LDH level (> 400 U/L) correlated with better objective response rate (P = .012) and HIF-1α immunoreactivity score (P = .029).

Conclusion: ΔSUVliveravg and GLUT-1 expression might predict RFS and ORR in patients with LD-SCLC treated with definitive CCRT.

Keywords: Bcl-2; FDG-PET; GLUT-1; HIF-1α; Small-Cell Lung Cancer.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / metabolism
  • Chemoradiotherapy / mortality*
  • Cisplatin / administration & dosage
  • Etoposide / administration & dosage
  • Female
  • Fluorodeoxyglucose F18*
  • Follow-Up Studies
  • Glucose Transporter Type 1 / metabolism*
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Immunoenzyme Techniques
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy
  • Male
  • Middle Aged
  • Multimodal Imaging
  • Neoplasm Staging
  • Positron-Emission Tomography*
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Radiopharmaceuticals
  • Small Cell Lung Carcinoma / metabolism*
  • Small Cell Lung Carcinoma / mortality
  • Small Cell Lung Carcinoma / pathology
  • Small Cell Lung Carcinoma / therapy
  • Survival Rate
  • Tomography, X-Ray Computed*

Substances

  • Biomarkers, Tumor
  • Glucose Transporter Type 1
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Proto-Oncogene Proteins c-bcl-2
  • Radiopharmaceuticals
  • Fluorodeoxyglucose F18
  • Etoposide
  • Cisplatin