Elsevier

Oral Oncology

Volume 49, Issue 1, January 2013, Pages 71-78
Oral Oncology

The role of 18F-FDG PET/CT metabolic tumour volume in predicting survival in patients with metastatic nasopharyngeal carcinoma

https://doi.org/10.1016/j.oraloncology.2012.07.016Get rights and content

Summary

Objectives

To investigate the role of PET-derived imaging markers in predicting metastatic nasopharyngeal carcinoma (NPC) outcomes.

Materials and methods

A total of 56 patients with metastatic NPC were enrolled. Before treatment, all of the participants underwent 18F-FDG PET/CT. The following 18F-FDG PET parameters were assessed: standardised uptake value, metabolic tumour volume (MTV), and total lesion glycolysis. Multivariate Cox proportional hazards models were used to identify the independent predictors of survival.

Results

The multivariate analysis showed that performance status > 1 (P = 0.007), Epstein–Barr virus (EBV) DNA titre > 5000 copies/mL (P = 0.001), and MTV > 110 mL (P = 0.013) were independent risk factors for progression-free survival (PFS). Male sex (P = 0.004), performance status > 1 (P < 0.0001), EBV DNA level > 5000 copies/mL (P < 0.0001), and MTV > 110 mL (P = 0.003) independently predicted overall survival (OS). The 2-year PFS and OS rates of the patients with MTV  110 mL were 23.2% and 43%, respectively, compared with 0% and 9.1%, respectively, for those with MTV > 110 mL. Combining the MTV with the EBV DNA titre allowed further survival stratification by dividing the patients into three groups with distinct PFS (2-year rates = 30.8%, 7.1%, and 0%, P < 0.0001) and OS (2-year rates = 68.4%, 40%, and 0%, P < 0.0001) rates.

Conclusion

The MTV appears to be an independent risk factor in metastatic NPC patients. This factor is complementary to the EBV DNA titre for predicting survival in metastatic NPC.

Introduction

Nasopharyngeal carcinoma (NPC) differs from other cancers of the head and neck in its epidemiology, histopathology, methods of treatment, and failure patterns.1 Despite improvements in locoregional control after applying chemoradiotherapy, distant failure is still the predominant cause of death from NPC.[1], [2], [3]

In contrast to other head and neck cancers, several reports have described patients with metastatic NPC who achieve long-term survival after salvage treatment.[4], [5] Therefore, it is important to define reliable prognostic factors for metastatic NPC and to identify which group of metastatic NPC patients will benefit from salvage treatment. Although the prognostic factors for metastatic NPC have been studied by several investigators,[4], [5], [6] most of the proposed prognostic factors have been limited to clinical characteristics. A more refined prognostic system is desirable, because this could guide the selection of salvage therapies and allow individualisation of treatment.

Glucose metabolism of the tumour has been proved to be associated with the prognosis of the head and neck cancer patients. Many reports in literature indicate standardised uptake value (SUV) on 18F-FDG PET/CT is an important prognostic factor for head and neck malignancy, including NPC.[7], [8], [9], [10] In a previous study, we have shown that combined information of SUV and tumour staging may guide the use of therapy and surveillance protocols to improve disease control of primary NPC patients.9 Recently, other PET semi-quantitative parameters such as metabolic tumour volume (MTV) or total lesion glycolysis (TLG) are becoming a topic of interest in head and neck cancer research.[11], [12], [13], [14] Our recent report has shown that these parameters are important independent risk factors in primary NPC patients.13 Although studies have examined PET/CT imaging as a predictor of treatment outcome in the primary head and neck carcinoma, significantly less is known about how these PET parameter can be used as a prognostic factor in metastatic disease. Furthermore, no report has validated the prognostic value of MTV in patients with metastatic NPC.

In contrast, there is accumulating evidence that supports using blood biomarkers for NPC detection and prognostication. The plasma Epstein–Barr virus (EBV) DNA level is the most validated of these biomarkers.[15], [16], [17] NPC is an EBV-associated cancer, and the EBV genome is present intracellularly in almost every case of primary and metastatic NPC. Several authors have also reported that the plasma EBV DNA level can help predict survival in metastatic/recurrent NPC.[15], [17], [18]

In this study, we sought to investigate the value of PET-derived parameters for predicting metastatic NPC outcomes. We also assessed the potential interactive role of PET parameters and plasma EBV DNA levels.

Section snippets

Study participants

Consecutive metastatic NPC patients admitted to our hospital were eligible for this prospective study. The following inclusion criteria were used for recruitment into the study: (1) biopsy-proven NPC; (2) metastatic disease that was newly diagnosed or had relapsed after a previous local curative treatment and was proven by biopsy or at least two study images; and (3) acceptable internal organ function, including bone marrow function (white blood cell count > 3000/L and platelet count > 75,000/L),

The patients and results of univariate analysis

Between December 2006 and May 2009, 56 eligible patients were included in the study. Table 1 shows the general characteristics of the study participants. Distant metastases were found in bone, lung, liver, distant lymph nodes, and other distant sites. Thirty-five patients had a single metastatic organ site. Of these 35 patients, 14 had metastatic spread to the bone, 10 to the lung, 8 to the liver, and 3 to the distant lymph nodes. The remaining twenty-one patients had metastases to several

Discussion

Among head and neck cancers, NPC has the highest incidence of distant metastasis,1 which has been shown to be the strongest determinant of survival.[25], [26], [27], [28] Studies have indicated that some patients with metastatic NPC can achieve long-term progression-free or overall survival after salvage treatment.[4], [5] However, a reliable prognostic system for these patients is still lacking. Recently, investigators have indicated that the plasma EBV DNA titre is an important biomarker for

Conflict of interest statement

None declared.

Acknowledgements

This work was supported by the National Science Council Grant Nos. 97∼99-2314-B-182A-103-MY3, 100-2314-B-182A-053, 101-2314-B-182A-079, and CMRPG 370081-3 (Chang Gung Memorial Hospital, Taiwan, Republic of China). The authors thank all the members of the Cancer Center, Chang Gung Memorial Hospital, Keelung, for their invaluable help and Yu-Jr Lin in Biostatistical Center for Clinical Research in Chang Gung Memorial Hospital for the statistic consultation.

References (44)

  • S.W. Lee et al.

    Prediction of prognosis using standardized uptake value of 2-[(18)F] fluoro-2-deoxy-d-glucose positron emission tomography for nasopharyngeal carcinomas

    Radiother Oncol

    (2008)
  • J.T. Chang et al.

    Nasopharyngeal carcinoma staging by (18)F-fluorodeoxyglucose positron emission tomography

    Int J Radiat Oncol Biol Phys

    (2005)
  • P. Xie et al.

    Prognostic value of 18F-FDG PET/CT before and after radiotherapy for locally advanced nasopharyngeal carcinoma

    Ann Oncol

    (2010)
  • T.H. La et al.

    Metabolic tumor volume predicts for recurrence and death in head-and-neck cancer

    Int J Radiat Oncol Biol Phys

    (2009)
  • B.B. Ma et al.

    Relationship between pretreatment level of plasma Epstein–Barr virus DNA, tumor burden, and metabolic activity in advanced nasopharyngeal carcinoma

    Int J Radiat Oncol Biol Phys.

    (2006)
  • A. Fandi et al.

    Long-term disease-free survivors in metastatic undifferentiated carcinoma of nasopharyngeal type

    J Clin Oncol

    (2000)
  • P.M. Teo et al.

    Prognosticators determining survival subsequent to distant metastasis from nasopharyngeal carcinoma

    Cancer

    (1996)
  • E.P. Hui et al.

    Lung metastasis alone in nasopharyngeal carcinoma: a relatively favorable prognostic group. A study by the Hong Kong Nasopharyngeal Carcinoma Study Group

    Cancer

    (2004)
  • A.S. Allal et al.

    Standardized uptake value of 2-[(18)F] fluoro-2-deoxy-d-glucose in predicting outcome in head and neck carcinomas treated by radiotherapy with or without chemotherapy

    J Clin Oncol

    (2002)
  • M.K. Chung et al.

    Metabolic tumor volume of [18F]-fluorodeoxyglucose positron emission tomography/computed tomography predicts short-term outcome to radiotherapy with or without chemotherapy in pharyngeal cancer

    Clin Cancer Res

    (2009)
  • Y.M. Seol et al.

    Measurement of tumor volume by PET to evaluate prognosis in patients with head and neck cancer treated by chemo-radiation therapy

    Acta Oncol

    (2010)
  • S.C. Chan et al.

    Clinical utility of 18F-FDG PET parameters in patients with advanced nasopharyngeal carcinoma: predictive role for different survival endpoints and impact on prognostic stratification

    Nucl Med Commun

    (2011)
  • Cited by (38)

    • Pretreatment <sup>18</sup>F-FDG PET/CT texture parameters provide complementary information to Epstein-Barr virus DNA titers in patients with metastatic nasopharyngeal carcinoma

      2020, Oral Oncology
      Citation Excerpt :

      Compared with conventional anatomic imaging, PET/CT provides functional information on tumor glucose metabolism – which may serve as a proxy for the total tumor burden and its biological aggressiveness. Numerous studies have shown that traditional PET-derived parameters – including standardized uptake value (SUV) and metabolic tumor volume (MTV) – predict prognosis in patients with primary NPC [8–17]. However, the question as to whether PET texture analysis – which can detect and quantify local differences in tumor morphology and function – can predict clinical outcomes in this patient group has not been fully elucidated.

    • Management of metastatic nasopharyngeal carcinoma

      2019, Nasopharyngeal Carcinoma: From Etiology to Clinical Practice
    • Hypoxic volume evaluated by <sup>18</sup>F-fluoromisonidazole positron emission tomography (FMISO-PET) may be a prognostic factor in patients with oral squamous cell carcinoma: preliminary analyses

      2018, International Journal of Oral and Maxillofacial Surgery
      Citation Excerpt :

      None of the 17 patients who received preoperative chemotherapy underwent preoperative radiation therapy. Postoperative radiation therapy was administered to five patients (patients 1, 2, 13, 19, and 22); these patients had advanced pT tumours, more than three pathologically positive lymph nodes23, pathological close margins in the primary tumour, or pathological extracapsular invasion of positive lymph nodes24. All 23 patients underwent FMISO-PET CT and FDG-PET CT before surgery, as described previously14.

    • Molecular Imaging and Precision Medicine in Head and Neck Cancer

      2017, PET Clinics
      Citation Excerpt :

      Wang and colleagues44 also investigated the implication of EBV DNA assay and 18F-FDG-PET in the detection of recurrent NPC. Chan and colleagues40 evaluated the role of 18F-FDG-PET/CT in predicting survival in 56 patients with metastatic NPC. EBV DNA titer greater than 5000 copies/mL (P = .001) and MTV greater than 110 mL (P = .013) were found to be independent factors for PFS.

    View all citing articles on Scopus
    f

    These authors contributed equally to this work.

    View full text