Assessment of biological parameters in head and neck cancer based on in vivo distribution of 18 F-FDG-FLT-FMISO-PET/CT images

Abstract

Objective:

Several genetic analyses have identified tumor diversity not only among tumors from different patients (intertumor heterogeneity) but also within individual tumors (intratumor heterogeneity). The aim of this study was to analyze the intratumor heterogeneity and other biological parameters based on in vivo distribution in triple-tracer positron emission tomography with computed tomography (PET/CT) study in patients with newly diagnosed head and neck (H&N) cancer.

Methods:

Thirty-six patients with newly diagnosed H&N cancer were included in the study. Institutional Bioethical Committee approved the study protocol and informed consent was received from every participant. All patients underwent series of 3 PET/CT scans with [¹⁸F]Fluorodeoxyglucose (¹⁸F-FDG-PET), [¹⁸F]Fluorothymidine (¹⁸F-FLT-PET), and [¹⁸F]Fluoromisonidazole (¹⁸F-FMISO-PET) before treatment. Scans were performed on separate days, within a timeframe of 2 weeks. Several PET/CT parameters grading tumor biology including maximum standardized uptake value (SUV_max), total lesion glycolysis (TLG), its equivalent (total hypoxic lesion [TLH] and total proliferative lesion [TLP]), and heterogeneity (area under the curve–cumulative SUV histogram) for the primary tumor were compared.

Results:

All patients showed increased uptake of ¹⁸F-FDG in primary tumor, ranging from 2.29 to 14.89 SUV_max. Respectively, SUV_max values for ¹⁸F-FLT ranged from 0.93 to 16.11 and for ¹⁸F-FMISO 0.36–4.07. Based on 3-year follow-up, we divided patients in terms of survival forecasts (first with good prognosis and second with worse). Higher values of TLG/TLP/TLH and SUV_max were observed in the second group in all 3 tracers (for ¹⁸F-FDG: 167.40 vs 100.32, 11.15 vs 8.95; for ¹⁸F-FLT: 116.61 vs 60.67, 7.09 vs 5.47; for ¹⁸F-FMISO: 37.34 vs 22.30, 1.70 vs 1.61 respectively). Statistically significant differences were shown in SUV_max in ¹⁸F-FDG and ¹⁸F-FLT (P<0.034, P<0.034, respectively; in TLG, P=0.05; TLP, P=0.04; and TLH, P=0.05).

Conclusion:

Our preliminary results suggest worse prognosis in patients with higher heterogeneity values of primary tumor in proliferation and hypoxia images and combination of metabolic and volumetric parameters in TLG and its equivalent and heterogeneity of primary tumor seems to be a prognostic factor.

Keywords

Head and neck heterogeneity positron emission tomography

Get full access to this article

View all access options for this article.

References

Hendrickson

KRG

Philips

Smith

et al. Hypoxia imaging with [F-18] FMISO-PET in head and neck cancer: potential for guiding intensity modulated radiation therapy in overcoming hypoxia-induced treatment resistance. Radiother Oncol 2011; 101: 369–375.

Jassem

Kawecki

Krajewski

et al. Epithelial tumors of the head and neck. In: Recommendations for Diagnostic and Therapeutic Procedures in Malignant Tumors in 2013 [in Polish]. Gdansk: ViaMedica; 2013.

Dandekar

Harrington

Kazi

et al. Challenges in integrating ¹⁸FDG PET-CT into radiotherapy planning of head and neck cancer. Ind J Cancer 2010; 47: 260–266.

Krzakowski

Rutkowski

Jassem

et al. Recommendations on the application of positron emission tomography in oncology [in Polish]. Nowotwory J Oncol 2011; 61: 57.

Almuhaideb

Papathanasiou

Bomanji

¹⁸F-FDG PET/CT imaging in oncology. Ann Saudi Med 2011; 31: 3–13.

Gerlinger

Rowan

Horswell

et al. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 2012; 366: 883–892.

Miles

Ganeshan

Griffiths

et al. Colorectal cancer: texture analysis of portal phase hepatic CT images as a potential marker of survival. Radiology 2009; 250: 444–452.

Ganeshan

Skogen

Pressney

et al. Tumour heterogeneity in oesophageal cancer assessed by CT texture analysis: preliminary evidence of an association with tumour metabolism, stage and survival. Clin Radiol 2012; 67: 157–164.

Larson

Erdi

Akhurst

et al. Tumor treatment response based on visual and quantitative changes in global tumor glycolysis using PET-FDG imaging: the visual response score and the change in total lesion glycolysis. Clin Positron Imaging 1999; 2: 159–171.

10.

Gallamini

Zwarthoed

Borra

Positron emission tomography (PET) in oncology. Cancers 2014; 6: 1821–1889.

11.

Almuhaideb

Papathanasiou

Bomanji

¹⁸F-FDG PET/CT imaging in oncology. Ann Saudi Med 2011; 31: 3–13.

12.

Connell

Corry

Milner

et al. Clinical impact of, and prognostic stratification by, F-18 FDG PET/CT in head and neck mucosal squamous cell carcinoma. Head Neck 2007; 29: 986–995.

13.

Geus-Oei

Oyen

WJ.

Predictive and prognostic value of FDG-PET. Cancer Imaging 2008; 8: 70–80.

14.

Fanti

Mohsen

Luigi

PET-CT Beyond FDG: A Quick Guide to Image Interpretation. Berlin: Springer; 2010.

15.

Hanahan

Weinberg

RA.

Hallmarks of cancer: the next generation. Cell 2011; 144: 646–674.

16.

Mahase

Wernicke

Nori

et al. Current and emerging roles of functional imaging in radiation therapy. Discov Med 2015; 19: 203–211.

17.

Newbold

Powell

PET/CT in radiotherapy planning for head and neck cancer. Front Oncol 2012; 2: 189.

18.

Rajendran

Schwartz

O’Sullivan

et al. Tumor hypoxia imaging with [F-18] fluoromisonidazole positron emission tomography in head and neck cancer. Clin Cancer Res 2006; 12: 5435–5441.

19.

Eschmann

Paulsen

Reimold

et al. Prognostic impact of hypoxia imaging with ¹⁸F-misonidazole PET in non-small cell lung cancer and head and neck cancer before radiotherapy. J Nucl Med 2005; 46: 253–260.

20.

van Velden

Cheebsumon

Yaqub

et al. Evaluation of a cumulative SUV-volume histogram method for parameterizing heterogeneous intratumoral FDG uptake in non-small cell lung cancer PET studies. Eur J Nucl Med Mol Imaging 2011; 38: 1636–1647.

21.

Lee

Ahn

Moon

et al. Comparison of ¹⁸F-FDG, ¹⁸F-FET, ¹⁸F-FLT for differentiation between tumor and inflammation in rats. Nucl Med Biol 2009; 36: 681–686.

22.

Pak

Cheon

Nam

et al. Prognostic value of metabolic tumor volume and total lesion glycolysis in head and neck cancer: a systematic review and meta-analysis. J Nucl Med 2014; 55: 884–890.

23.

Hoeben

Troost

Span

et al. ¹⁸F-FLT PET during radiotherapy or chemoradiotherapy in head and neck squamous cell carcinoma is an early predictor of outcome. J Nucl Med 2013; 54: 532–540.