Page 8 - Read Online

Cox et al. J Cancer Metastasis Treat 2021;7:25 https://dx.doi.org/10.20517/2394-4722.2021.55 Page 3 of 11

FDG-PET-guided surveillance of the neck
In addition to pre-treatment staging, FDG-PET/CT plays an important diagnostic role in follow-up after
after (C)RT for HNSCC. The main focus of post-therapy FDG-PET is the detection of residual disease in
cervical lymph nodes. Multiple studies confirm that FDG-PET/CT has a high negative predictive value (>
93%) in the evaluation of residual nodal disease after (C)RT [17-20] . However, there are indications that post-
therapy response evaluation with FDG-PET/CT may be less reliable in human papilloma virus (HPV)-
positive HNSCC . FDG-uptake as a result of inflammatory response to irradiation of the neck usually
[19]
declines within weeks, allowing an accurate evaluation at approximately 10-12 weeks after the end of
(C)RT . The PET-NECK trial demonstrated that survival was similar among advanced nodal stage
[21]
HNSCC patients (N2/N3) who underwent PET/CT-guided surveillance 12 weeks after (C)RT, and those
who underwent planned neck dissection. However, PET/CT-guided surveillance resulted in sparing of neck
dissection in 80% of patients . Occasionally, increased FDG-uptake in certain areas of the neck may persist
[22]
for months after (C)RT, without evidence of residual disease . The underlying causes include
[23]
inflammation or ulceration . Correlation with clinical evaluation, anatomical imaging, histopathological
[18]
validation, and discussion within a multidisciplinary board are critical to correctly differentiate persistent
cancer from non-malignant pathology.

FDG-PET/CT-GUIDED RADIOTHERAPY, A NEW ERA
Impact on outcome
The better identification of lymph node metastases by FDG-PET not only has consequences for the
radiotherapy target volume, but also has prognostic implications for HNSCC patients treated with (C)RT.
Defining the nodal target volume based on FDG-PET/CT results in alteration of nodal radiation treatment
in approximately 1 out of 4 patients compared to conventional imaging, with nodal up-staging in 8%-21%
and down-staging in 3%-11% [14,24-27] . Recently, van den Bosch et al. described the clinical impact of target
[28]
volume transformation on radiation treatment outcomes using FDG-PET/CT-based treatment planning.
They retrospectively analysed 633 HNSCC patients treated with definitive (C)RT. In 46% of the patients, a
diagnostic iodine contrast enhanced FDG-PET/CT in treatment position was acquired for radiotherapy
planning. If patients developed a recurrence in the neck after treatment, the exact site of the recurrence was
reconstructed by performing co-registration of the diagnostic images showing the recurrence with the initial
treatment planning scan. It was demonstrated that FDG-PET/CT-assisted radiation treatment planning is
associated with a significantly lower rate of recurrence in the CTV elective-nodal (HR = 0.33; P = 0.026), increased
overall regional control (HR = 0.62; P = 0.027), and higher overall survival (HR = 0.71; P = 0.033), compared
with CT-only radiotherapy planning .
[28]
Target volume transformation
Combining FDG-PET/CT with conventional anatomical imaging significantly improves the detection rate
of lymph node metastases, which has important consequences for radiotherapy target volume and dose
[Figure 1] . Small metastases that remained subclinical in the past can nowadays be detected and thus are
[29]
included in the gross tumor volume (GTV), which is treated to a high dose (≥ 70Gy EQD2).
Consequentially, the GTV covers a larger area and will more often contain small lymph nodes with
relatively low-volume disease. As a result, the CTV elective-nodal harbors less lymph nodes with smaller tumor
load. This “shift” of lymph nodes between target volumes results in a decreased overall tumor burden in the
CTV elective , but also increases the number of nodes with low-volume disease in the GTV.

This nodal target volume transformation imposes changes in radiotherapy dose levels that need to be
prescribed to these volumes. Moreover, this provides a window of opportunity for treatment de-
intensification of the neck in order to decrease treatment-related toxicity without compromising
oncological outcome.