Implications of improved diagnostic imaging of small nodal metastases in head and neck cancer: Radiotherapy target volume transformation and dose de-escalation

Abstract

Diagnostic imaging continues to evolve, and now has unprecedented accuracy for detecting small nodal metastasis. This influences the tumor load in elective target volumes and subsequently has consequences for the radiotherapy dose required to control disease in these volumes. Small metastases that used to remain subclinical and were included in elective volumes, will nowadays be detected and included in high-dose volumes. Consequentially, high-dose volumes will more often contain low-volume disease. These target volume transformations lead to changes in the tumor burden in elective and "gross" tumor volumes with implications for the radiotherapy dose prescribed to these volumes. For head and neck tumors, nodal staging has evolved from mere palpation to combinations of high-resolution imaging modalities. A traditional nodal gross tumor volume in the neck typically had a minimum diameter of 10-15 mm, while nowadays much smaller tumor deposits are detected in lymph nodes. However, the current dose levels for elective nodal irradiation were empirically determined in the 1950s, and have not changed since. In this report the radiobiological consequences of target volume transformation caused by modern imaging of the neck are evaluated, and theoretically derived reductions of dose in radiotherapy for head and neck cancer are proposed. The concept of target volume transformation and subsequent strategies for dose adaptation applies to many other tumor types as well. Awareness of this concept may result in new strategies for target definition and selection of dose levels with the aim to provide optimal tumor control with less toxicity.

18F-FDG-PET/CT-based treatment planning for definitive (chemo)radiotherapy in patients with head and neck squamous cell carcinoma improves regional control and survival

“…oropharynx) or HPV-status. The results support the concept of target volume transformation and demonstrate the potential of FDG-PET to guide radiotherapy dose de-escalation in elective neck treatment in HNSCC [3]. In the following section, the concept of target volume transformation will be explicated and illustrated by clinical evidence provided in this paper.…”

“…This 'upgrading' of small nodal metastases from CTV elective-nodal to GTV is defined as target volume transformation ( Fig. 4A) [3]. This is demonstrated in the current analysis by the smaller volume (0.46 cc versus 1.02 cc, p < 0.001) of preexisting lymph nodes on the initial treatment planning CT-scan (at the locations of the CTV elective-nodal recurrences) in patients with FDG-PET/CT-based NTV.…”

“…4. Target volume transformation [3]. (A) Modern multimodality imaging employing FDG-PET has improved the detection threshold of small nodal metastases.…”

“…Abbreviations: FDG-PET = 18Ffluorodeoxy-D-glucose positron emission tomography, CTV = clinical target volume, GTV = gross tumor volume. Reproduced from [3] with permission.…”

“…In a clinically negative neck (cN0) the prevalence of occult metastases ranges between 10% and 35%, depending on the primary tumor site and T-stage [2]. To eradicate potential occult nodal disease, elective irradiation (typically an equivalent dose of 45-50 Gy in 2-Gy fractions) to the clinically uninvolved nodal target volume (CTV elective-nodal ) is performed routinely in definitive (chemo)radiotherapy for HNSCC [2,3].…”