Pathological Validation of Functional Imaging in Head and Neck Squamous Cell Carcinoma

Summary

Chemo-radiotherapy (CRT) is currently the cornerstone in the management of locoregional advanced head and neck cancer (HNC). Optimization of the quality of RT is therefore an important issue, if the investigators want to improve the therapeutic index in HNC. This could be achieved by a more accurate definition of the tumor volume and by identification of radioresistant volumes within the tumor. Recent literature puts in this regard the incorporation of functional imaging (FI) in the RT treatment planning forward as a promising tool.

FI modalities provide an outstanding contrast between tumor and surrounding tissues. This is in contrast to anatomical imaging. Using anatomical imaging in RT treatment planning, sufficient margins need to be placed around the tumor volume in order to compensate for geometric uncertainties. Consequently many surrounding functional structures receive high doses of irradiation, resulting in side effects. It is expected that, using FI in RT treatment planning will make these margins smaller or even unnecessary, which will result in less irradiation of the surrounding tissues. So far only one study has reported a comparison between tumor volume on anatomical (CT and MRI) and FI (PET-CT) modalities with pathological tumor volume. This study showed indeed that the tumor volumes delineated on PET-CT correlated more to tumor volumes defined by pathology and were significantly smaller.

Furthermore, FI provides us with a deeper insight in the tumor's underlying biological activity and microstructure. These techniques can thus help to identify radioresistant subvolumes which might benefit from treatment intensification.

A validation of these FI modalities with pathology is necessary to investigate their true power in tumor delineation and in the identification of radioresistant subvolumes.

Conditions

• Head and Neck Cancer

Interventions

OTHER

A polymerase chain reaction -based hypoxia classifier

Recently, a polymerase chain reaction (PCR) -based hypoxia classifier gene signature was published that can be easily applied. Using this classifier, patients will be divided in hypoxic or non-hypoxic subgroups. These subgroups will be correlated to locoregional control. The hypoxic signature will also be related to parameters on DCE-MRI, DWI and FDG-PET.

OTHER

Functional imaging before treatment.

As part of the standard staging procedure all patients will undergo an MRI of the neck. We will however also take DWI and DCE images at this time point. Parameters of these images will be later on correlated with pathology.

OTHER

Immunohistochemical staining

At 3 levels of the tumour, chosen by the radiologist on the functional imaging modalities, 4µm thick slices will me taken. On each level an immunohistochemical staining will be carried out (GLUT-1, CA-IX, HIF-1alpha, VEGF, KI 67). The result of this staining will be correlated with parameters derived from the functional imaging modalities.

OTHER

MRI of the resection specimen

To account for the shrinkage of the tumour due to fixation, the resection specimen will be placed in a box and scanned with an MRI. From this a shrinkage factor will be calculated using the original pre-treatment MRI.

OTHER

Tumour volume delineation and comparison

On the imaging modalities the tumor volume will be delineated. This will also be done on the resection specimen. Later on the different tumour volumes will be correlated.

Sponsors & Collaborators

• Flemish League Against Cancer

  collaborator OTHER

• Universitaire Ziekenhuizen KU Leuven

  lead OTHER

Principal Investigators

• Sandra Nuyts, PhD MD · Universitaire Ziekenhuizen KU Leuven

Study Design

Allocation

NA

Purpose

OTHER

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2013-03-31

Primary Completion

2015-03-31

Completion

2015-03-31

Countries

• Belgium

Study Locations