Comment on 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” published in Clinical Cancer Research 2009;15(18):5861-5866.

With great interest, we read the publication by Chung et al. (1). In 82 pharyngeal cancer patients undergoing (chemo)radiation, the authors studied the prognostic value of a “metabolic tumor volume” (MTV), defined as increased 18FDG-PET uptake in primary tumors and lymph node metastases. Although this concept seems appealing, we feel that comments about the methods are justified.

First, the authors chose a threshold of 2.5 for the standardized uptake value (SUV) for segmentation of the 18FDG-PET images, which is commonly applied in NSCLC. Not only is this threshold arbitrary and protocol dependent (2), but the most appropriate threshold for 18FDG-PET segmentation in head and neck tumors remains to be determined. As opposed to NSCLC, head and neck tumors are surrounded by closely packed tissue consisting of squamous cells, the cell type the tumor originated from, and peritumoral inflammation hampering PET segmentation. In two recent publications, we showed the effect of applying different thresholds, including SUV 2.5, on the segmentation of primary head and neck tumors and cervical lymph nodes and advocated the validation of iterative methods (3, 4). Furthermore, as shown by Nagakawa et al. (5), a threshold of SUV 2.5 is ineffective for the segmentation of metastatic lymph nodes, as 30% of patients had reactive cervical lymph nodes with a maximum SUV of 2.5 or higher.

Second, the authors did not incorporate necrotic areas within the tumor or lymph nodes in the MTVs because they do not consume 18FDG. However, necrotic volumes are often the result of severe hypoxia, a tumor characteristic adversely affecting treatment outcome and prognosis. Thus, although this approach may be legitimate in terms of defining the MTV, these patients should be either excluded from the analysis or analyzed as separate cohort because this confounding characteristic may also influence the correlation of MTVs with short-term outcome.

Third and most importantly, Chung et al. omitted to correlate the gross tumor volumes (GTV) on CT with the MTVs and short-term treatment outcomes in both univariate and multivariate analyses. There is solid evidence that the GTV of the primary tumor and metastatic cervical lymph nodes is one of the most powerful prognostic factors for treatment outcome among patients with advanced-stage disease (6). That is why the anatomic tumor size still forms the basis of the TNM staging system. Consequently, establishing any added value of MTV over anatomic GTV information should have been one of the main goals of the study.

No potential conflicts of interest were disclosed.

1
Chung
MK
,
Jeong
HS
,
Park
SG
, 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
;
15
:
5861
8
.
2
Boellaard
R
,
Oyen
WJ
,
Hoekstra
CJ
, et al
. 
The Netherlands protocol for standardisation and quantification of FDG whole body PET studies in multi-centre trials
.
Eur J Nucl Med Mol Imaging
2008
;
35
:
2320
33
.
3
Schinagl
DA
,
Hoffmann
AL
,
Vogel
WV
, et al
. 
Can FDG-PET assist in radiotherapy target volume definition of metastatic lymph nodes in head-and-neck cancer?
Radiat Oncol
2009
;
91
:
95
100
.
4
Schinagl
DA
,
Vogel
WV
,
Hoffmann
AL
,
van Dalen
JA
,
Oyen
WJ
,
Kaanders
JH
. 
Comparison of five segmentation tools for 18F-fluoro-deoxy-glucose-positron emission tomography-based target volume definition in head and neck cancer
.
Int J Radiat Oncol Biol Phys
2007
;
69
:
1282
9
.
5
Nakagawa
T
,
Yamada
M
,
Suzuki
Y
. 
18F-FDG uptake in reactive neck lymph nodes of oral cancer: relationship to lymphoid follicles
.
J Nucl Med
2008
;
49
:
1053
9
.
6
Chao
KS
,
Ozyigit
G
,
Blanco
AI
, et al
. 
Intensity-modulated radiation therapy for oropharyngeal carcinoma: impact of tumor volume
.
Int J Radiat Oncol Biol Phys
2004
;
59
:
43
50
.