Cancer of the Tongue Clinical Trial
Official title:
Defining a Personalized Hypoxic Radiation Target Through Correlation of Functional F18-FAZA PET Imaging to Pimonidazole-stained 3D Whole-mounted Histological Specimen
In head and neck cancer, areas of tumours with low oxygen supply (called tumour hypoxia) harbour cells that are resistant to radiation and are prone to metastasize. Modern radiotherapy techniques are precise enough to deliver radiation to these small areas and could be used to target these areas to receive higher doses of radiation than the rest of the tumour to overcome resistance. Hypoxia can be "seen" in the body using special imaging such as [F-18]-FAZA-PET ([F-18]-Fluoroazomycin arabinoside positron emission tomography) but it has not been tested as a method for creating radiation treatment targets. As part of regular pathology tumour tissue is sliced extremely thinly (<1/100th of a millimeter) and stained so that individual cells can be seen under a microscope. Immunohistochemistry (IHC) is a special type of "stain" that can specifically highlight hypoxic areas. This method is considered the most accurate way to inspect for the presence of hypoxia. There is not a specific staining target for hypoxia ordinarily, but when patients ingest a substance called pimonidazole-HCl it builds up specifically in hypoxic areas and can be targeted for IHC staining. In this study participants with oral tongue cancer will have a [F-18]-FAZA-PET scan and take a single dose of oral pimonidazole-HCl before having surgery to remove their cancer. The whole tumour will be used to create microscope slides using very thin slices of the tumour. The slices will be stained using IHC to show where the pimonidazole has built up. Digital scans of the slides will be made using a laser scanner. The hypoxia seen on their FAZA-PET scan will be "matched" with hypoxia on the electronic slides to see if the FAZA truly shows where hypoxia is in tumours and if it could be used as a way to plan radiation treatments to deliver more radiation to just those areas.
Modern radiotherapy (RT) now possesses a high level of technical and physical precision that
allows for dose escalation to levels previously considered unsafe (e.g. lung stereotactic
RT). Due to safety concerns, there is considerable interest in the concept of 'dose
painting', where a non-uniform dose is delivered to a biologic target volume where
radioresistance is expected. The hypoxic target volume is likely a major source of cancer
recurrence and can be defined on functional imaging (FAZA-PET). However, the accuracy of
FAZA-PET in defining a hypoxic volume for radiation targeting is not known. Finding a good
correlation between pathology (as a reference standard) to a hypoxic PET target would
provide the foundation for a feasible dose escalation clinical trial in high risk head and
neck cancer that can finally take advantage of all the technical improvements in radiation
delivery.
This study aims to assess the degree to which hypoxia measured by [F-18]-FAZA-PET imaging is
correlated with a reference standard of hypoxia confirmed by pimonidazole targeted
immunohistochemistry using a 3D whole-mount histopathologic approach.
This is a pilot study in the form of a prospective, Phase II, single arm, trial to
investigate the use of IHC methods to validate functional medical imaging on the sub-tumour
level.
Ten patients with biopsy confirmed oral tongue squamous cell carcinoma where surgery is the
intended form of definitive treatment will be approached to participate in the study.
Participants will have received pre-study testing that is standard of care (e.g. biopsy,
complete blood count, serum electrolytes, urinalysis, liver function tests, beta-hCG
testing, etc.) with no incremental testing. Patients will receive a routine MRI and CT. In
addition they will receive a [F-18]-FAZA-PET scan 2-3 days prior to surgery. Within 1 week
of surgery patients will be seen in the pre-anaesthesia clinic for repeat bloodwork and
routine peri-operative assessments. On the day before surgery, in addition to typical
peri-operative activities (e.g. 24 hour solid fast, only consuming clear fluids) the patient
will be instructed to take the prescribed dose of oral pimonidazole-HCl 16-20 hours before
surgery. The patient will be admitted for same day surgery which will be carried out in a
routine fashion, e.g. total removal of tumour plus appropriate margins. For research
purposes, the specimen will be processed differently than routine pathology. Once the
specimen has been completely removed have several external markers applied to its surface to
guide orientation. The specimen will then be embedded in 3.5% agar and placed on ice for 1
hour. The embedded specimen will undergo an MRI (ex-vivo) noting the position of the
specimen in the block using the external markers. The MRI will be a single 5 minute T1
sequence. The specimen is cut from front to back in 3 mm slices and stained for pimonidazole
to show hypoxia as well as typical hematoxylin and eosin staining that will be used for
clinical pathologic assessment. Histology slides will be digitized with a laser scanner at a
resolution of 0.5µm/pixel. The gross tumour and areas of macroscopic hypoxia will be defined
by a pathologist. The histology images will be reconstructed using the external markers and
internal landmarks as well as the ex-vivo MRI and matched (co-registered) to the in vivo
FAZA-PET/CT/MRI tumour volumes.
Despite the available high technical precision of radiation treatment machines, limited
clinical progress has been made in the last 15 years in sub-volume (i.e. less than whole
tumour) targeting because of target uncertainty. With a multidisciplinary,
multi-institutional collaboration, our group will correlate FAZA-PET imaging to a 3D
histological reference to validate (i.e. evaluate accuracy) functional imaging at a
unprecedented level. This invaluable understanding of the biological underpinnings of
commonly used functional imaging could help form the basis of future clinical trials.
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Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT03305302 -
Isolation and Establishment of Gustatory Cell Lines in Patients Operated on for Cancer of the Mobile Tongue - ImmortTasteCELL
|
||
| Active, not recruiting |
NCT03853655 -
Adjuvant Radiotherapy in Early Stage Oral Cancers
|
N/A |