Otorhinolaryngeal NeoplasmsNCT02372890
Validation of High-resolution PET/CT for the Pretherapeutic Lymphnode Staging of Head/Neck Cancer
An observational study of Otorhinolaryngeal Neoplasms and Cancer of Head and Neck, run by Insel Gruppe AG, University Hospital Bern at 1 site in Switzerland.
Trial summary
In head and neck squamous cell carcinoma (HNSCC), the presence of lymph node metastases in addition to free resection margins following surgical resection of the primary tumor is an important prognostic factor, and may impact planning of surgery as well as of radiotherapy. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Otorhinolaryngeal Neoplasms, Cancer of Head and Neck
- How many people
- 153 participants
- Where
- 1 siteSwitzerland
- Study dates
- Jul 2012to 31 Dec 2017
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with head and neck squamous cell carcinoma undergoing routine PET/CT staging or restaging and sheduled for neck dissection according to the decision of the interdisziplinary tumor board.
Who may be able to join
- Head and neck squamous cell carcinoma (HNSCC), fulfilling one or more of the following criteria:
- Advanced primary tumor stage (cT3 or cT4)
- Clinical suspicion of neck lymph node metastases
- Cervical lymph node metastases of unknown primary tumor (CUP)
- Tumor recurrence
- Mature adult
- Written informed consent
Who cannot join
- Inoperability
- Histologically verified cervical lymph node metastases of other tumors
Trial locations and contacts
1 site in 1 country.
Switzerland1 site
Dept. of Nuclear Medicine, Bern University Hospital, Bern
Bern, 3010
About this study
In head and neck squamous cell carcinoma (HNSCC), the presence of lymph node metastases in addition to free resection margins following surgical resection of the primary tumor is an important prognostic factor, and may impact planning of surgery as well as of radiotherapy. Until now, imaging modalities including PET/CT and MRI did not allow to exclude especially small lymph node metastases.
Compared to standard whole-body PET/CT acquisition techniques, high-resolution (HR) head and neck PET/CT acquisitions promise improved detection of lymph node metastases in head and neck squamous cell carcinoma (HNSCC). This prospective study aims to determine the sensitivity and specificity of lymph node staging with HR FDG-PET/CT in HNSCC by correlating PET/CT with histopathology after neck dissection. HR PET/CT may have a relevant impact on the therapeutic concept, and the planning and dose prescription of radiotherapy.
Read the detailed description
In head and neck squamous cell carcinoma (HNSCC), the presence of lymph node metastases in addition to free resection margins following surgical resection of the primary tumor is an important prognostic factor, and may impact planning of surgery as well as of radiotherapy. Neck dissection and histopathology are regarded as diagnostic standard procedures to define the lymph node status in patients with HNSCC. Occult lymph node metastases after imaging have been described in up to 46% of patients, e.g. in patients with cancer of the tongue.
Although neck dissection generally has a low rate of intra- and postoperative complications, a small but statistically significant group of patients suffers from surgery-related side effects such as lymphedema, chronic pain syndromes and injury of cranial nerves with paralysis (shoulder lift and mouth angle). Therefore it would be desirable to spare diagnostic neck dissection in patients without macroscopic lymph node metastasis. However, the sensitivity and/or specificity of the non-invasive imaging techniques available up to now, including positron emission tomography (PET) and magnetic resonance imaging (MRI), did not allow to exclude lymph node metastases, which is especially true for small metastases. Therefore, imaging is not able to replace the histological examination of the cervical lymph nodes and have limited impact on the therapeutic concept, the surgical planning and the planning and dose prescription of radiotherapy.
Acquisition techniques and image quality of PET (with the glucose analog F-18-fluorodeoxyglucose (FDG)) and the combined examination with computed tomography (PET/CT) were considerably improved with last generation PET/CT machines. New generation PET/CT machines provide significantly improved image quality and image resolution image, and probably higher sensitivity to detect smaller lesions. However, in the face of an expected increase of detected metabolically active cervical lymph nodes by high-resolution (HR) PET/CT, a diagnostic problem in terms of a potentially increased number of false-positive lymph nodes arises, e. g. due to an inflammatory lymphadenopathy.
Until now there are no evidence-based criteria to classify small metabolically active lymph nodes detected by HR PET/CT. Hence, a correlation of PET/CT findings and histopathology of cervical lymph metastases and inflammatory lymph nodes in patients with HNSCC is required to develop diagnostic criteria for HR PET/CT and to exploit the diagnostic potential of HR PET/CT.
Modern concepts of radiotherapy planning for neck lymph node metastases increasingly take into consideration the metabolic and morphological information of PET/CT for target volume definition. Detailed information on the diagnostic performance of HR PET / CT are of importance for the dose prescription of intensity-modulated radiotherapy (IMRT). In radiotherapy side effects depend significantly on the dose and the irradiation volume. Modern radiation techniques, especially IMRT, allow for highly-conformal radiation therapy with steep dose gradients to protect organs such as the salivary glands, and to reduce side effects of radiotherapy. On the other hand modern radiotherapy concepts carry the risk to fail due to non-inclusion of subclinical lymph node metastases in the target volume. HR PET/CT may allow to minimize out-of-field recurrences caused by incorrect target volume contouring or dose prescription. Evidence-based data on the diagnostic accuracy of HR PET/CT with special regard to small lymph node metastases are needed to clarify the potential role of HR PET/CT for radiation treatment planning.
Objective:
- To determine the sensitivity, specificity, accuracy, PPV and NPV of lymph node staging with HR PET/CT in patients with HNSCC
- To determine the sensitivity, specificity, accuracy, PPV and NPV of HR PET/CT for lymph node metastases of different size in patients with HNSCC
- To determine the detection rate of distant metastases by PET/CT in patients with HNSCC
- To develop diagnostic criteria for the multi-modal lymph node staging with HR PET/CT in patients with HNSCC
- To evaluate the potential impact of HR PET/CT on radiation treatment planning
Methods:
Patients with HNSCC are managed according to clinical recommendations of the interdisciplinary tumor board. Elective patients receive selective, modified radical or radical neck dissection of the relevant lymph node region according to clinical routine standards at the Inselspital Bern. The neck dissection must be carried out within a maximum of 6 weeks after the PET / CT examination.
As part of the neck dissection the lymph nodes will be sent to the Institute of Pathology separated by level and side by topographic markers (cranial / caudal, medial / lateral). The histological examination of the removed lymph nodes serves as reference standard for the analysis of PET/CT image data, and calculation of the diagnostic accuracy of HR PET/CT.
Theoretical radiation treatment plans are generated based on conventional imaging, whole-body PET/CT and HR PET/CT protocols to determine the impact of PET/CT.
- Keywords
- Otorhinolaryngeal Neoplasms, Cancer of Head and Neck, Head and Neck Squamous Cell Carcinoma, Positron Emission Tomography, PET/CT, FDG
- Medical subject headings
- Head and Neck Neoplasms, Squamous Cell Carcinoma of Head and Neck
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| All patients | Patients with head and neck squamous cell carcinoma with advanced primary tumor stages (cT3 or cT4), clinical suspicion of cervical lymph node metastases, cervical lymph node metastasis of unknown primary tumor (CUP) or patients with tumor recurrence scheduled for neck dissection. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Diagnostic accuracy (sensitivity, specificity, accuracy, NPV und PPV) of HR PET/CT in comparison to the histopathological reference standard
Measured: At baseline
Secondary outcomes (2)
Diagnostic accuracy (sensitivity, specificity, accuracy, NPV und PPV) of PET/CT according to the size of lymph node metastases
Measured: At baseline
Number of patients where PET/CT results in a change of gross tumor volume (GTV) and/or dose prescription
Measured: At baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2015 (estimated)
- Study startJul 2012
- Primary completion31 Dec 2017
- Study completion31 Dec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Otorhinolaryngeal NeoplasmsStudies of the same condition, open and under way.
- More trials run by Insel Gruppe AG, University Hospital BernThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 153 participants (actual)
Sponsor and investigators
- Lead sponsor
- Insel Gruppe AG, University Hospital Bern
- Sponsor type
- University, hospital or other
- Collaborators
- University of Bern
- Responsible party
- Sponsor
- Investigators
- Andreas Arnold, Prof. Dr. med., Principal investigator, Insel Gruppe AG, University Hospital Bern
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02372890
- Sponsor's protocol ID
- 277/2014
- Status last verified
- Feb 2019
- First submitted
- 19 Jan 2015
- Last updated
- 27 Feb 2019
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Validation of High-resolution PET/CT for the Pretherapeutic Lymphnode Staging of Head/Neck Cancer
- ClinicalTrials.gov ID
- NCT02372890
- Acronym / sponsor ID
- 277/2014
- Keywords
- Otorhinolaryngeal Neoplasms, Cancer of Head and Neck, Head and Neck Squamous Cell Carcinoma, Positron Emission Tomography, PET/CT, FDG
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 153 participants (actual)
- Lead sponsor
- Insel Gruppe AG, University Hospital BernUniversity, hospital or other
- Collaborators
- University of Bern
- Study start
- Jul 2012
- Primary completion
- 31 Dec 2017 (actual)
- Study completion
- 31 Dec 2017 (actual)
- First posted
- 26 Feb 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In head and neck squamous cell carcinoma (HNSCC), the presence of lymph node metastases in addition to free resection margins following surgical resection of the primary tumor is an important prognostic factor, and may impact planning of surgery as well as of radiotherapy. Until now, imaging modalities including PET/CT and MRI did not allow to exclude especially small lymph node metastases.
Compared to standard whole-body PET/CT acquisition techniques, high-resolution (HR) head and neck PET/CT acquisitions promise improved detection of lymph node metastases in head and neck squamous cell carcinoma (HNSCC). This prospective study aims to determine the sensitivity and specificity of lymph node staging with HR FDG-PET/CT in HNSCC by correlating PET/CT with histopathology after neck dissection. HR PET/CT may have a relevant impact on the therapeutic concept, and the planning and dose prescription of radiotherapy.
Detailed description
In head and neck squamous cell carcinoma (HNSCC), the presence of lymph node metastases in addition to free resection margins following surgical resection of the primary tumor is an important prognostic factor, and may impact planning of surgery as well as of radiotherapy. Neck dissection and histopathology are regarded as diagnostic standard procedures to define the lymph node status in patients with HNSCC. Occult lymph node metastases after imaging have been described in up to 46% of patients, e.g. in patients with cancer of the tongue.
Although neck dissection generally has a low rate of intra- and postoperative complications, a small but statistically significant group of patients suffers from surgery-related side effects such as lymphedema, chronic pain syndromes and injury of cranial nerves with paralysis (shoulder lift and mouth angle). Therefore it would be desirable to spare diagnostic neck dissection in patients without macroscopic lymph node metastasis. However, the sensitivity and/or specificity of the non-invasive imaging techniques available up to now, including positron emission tomography (PET) and magnetic resonance imaging (MRI), did not allow to exclude lymph node metastases, which is especially true for small metastases. Therefore, imaging is not able to replace the histological examination of the cervical lymph nodes and have limited impact on the therapeutic concept, the surgical planning and the planning and dose prescription of radiotherapy.
Acquisition techniques and image quality of PET (with the glucose analog F-18-fluorodeoxyglucose (FDG)) and the combined examination with computed tomography (PET/CT) were considerably improved with last generation PET/CT machines. New generation PET/CT machines provide significantly improved image quality and image resolution image, and probably higher sensitivity to detect smaller lesions. However, in the face of an expected increase of detected metabolically active cervical lymph nodes by high-resolution (HR) PET/CT, a diagnostic problem in terms of a potentially increased number of false-positive lymph nodes arises, e. g. due to an inflammatory lymphadenopathy.
Until now there are no evidence-based criteria to classify small metabolically active lymph nodes detected by HR PET/CT. Hence, a correlation of PET/CT findings and histopathology of cervical lymph metastases and inflammatory lymph nodes in patients with HNSCC is required to develop diagnostic criteria for HR PET/CT and to exploit the diagnostic potential of HR PET/CT.
Modern concepts of radiotherapy planning for neck lymph node metastases increasingly take into consideration the metabolic and morphological information of PET/CT for target volume definition. Detailed information on the diagnostic performance of HR PET / CT are of importance for the dose prescription of intensity-modulated radiotherapy (IMRT). In radiotherapy side effects depend significantly on the dose and the irradiation volume. Modern radiation techniques, especially IMRT, allow for highly-conformal radiation therapy with steep dose gradients to protect organs such as the salivary glands, and to reduce side effects of radiotherapy. On the other hand modern radiotherapy concepts carry the risk to fail due to non-inclusion of subclinical lymph node metastases in the target volume. HR PET/CT may allow to minimize out-of-field recurrences caused by incorrect target volume contouring or dose prescription. Evidence-based data on the diagnostic accuracy of HR PET/CT with special regard to small lymph node metastases are needed to clarify the potential role of HR PET/CT for radiation treatment planning.
Objective:
- To determine the sensitivity, specificity, accuracy, PPV and NPV of lymph node staging with HR PET/CT in patients with HNSCC
- To determine the sensitivity, specificity, accuracy, PPV and NPV of HR PET/CT for lymph node metastases of different size in patients with HNSCC
- To determine the detection rate of distant metastases by PET/CT in patients with HNSCC
- To develop diagnostic criteria for the multi-modal lymph node staging with HR PET/CT in patients with HNSCC
- To evaluate the potential impact of HR PET/CT on radiation treatment planning
Methods:
Patients with HNSCC are managed according to clinical recommendations of the interdisciplinary tumor board. Elective patients receive selective, modified radical or radical neck dissection of the relevant lymph node region according to clinical routine standards at the Inselspital Bern. The neck dissection must be carried out within a maximum of 6 weeks after the PET / CT examination.
As part of the neck dissection the lymph nodes will be sent to the Institute of Pathology separated by level and side by topographic markers (cranial / caudal, medial / lateral). The histological examination of the removed lymph nodes serves as reference standard for the analysis of PET/CT image data, and calculation of the diagnostic accuracy of HR PET/CT.
Theoretical radiation treatment plans are generated based on conventional imaging, whole-body PET/CT and HR PET/CT protocols to determine the impact of PET/CT.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| All patients | – | –Patients with head and neck squamous cell carcinoma with advanced primary tumor stages (cT3 or cT4), clinical suspicion of cervical lymph node metastases, cervical lymph node metastasis of unknown primary tumor (CUP) or patients with tumor recurrence scheduled for neck dissection. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with head and neck squamous cell carcinoma undergoing routine PET/CT staging or restaging and sheduled for neck dissection according to the decision of the interdisziplinary tumor board.
Key inclusion criteria (7 listed)
- Head and neck squamous cell carcinoma (HNSCC), fulfilling one or more of the following criteria:
- Mature adult
- Written informed consent
Key exclusion criteria (2 listed)
- Inoperability
- Histologically verified cervical lymph node metastases of other tumors
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Diagnostic accuracy (sensitivity, specificity, accuracy, NPV und PPV) of HR PET/CT in comparison to the histopathological reference standard
Time frame: At baseline
2 secondary outcomes
Diagnostic accuracy (sensitivity, specificity, accuracy, NPV und PPV) of PET/CT according to the size of lymph node metastases
Time frame: At baseline
Number of patients where PET/CT results in a change of gross tumor volume (GTV) and/or dose prescription
Time frame: At baseline
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2019.
Related trials for Otorhinolaryngeal Neoplasms
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Andreas Arnold, Prof. Dr. med. principal investigator
Insel Gruppe AG, University Hospital Bern
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Otorhinolaryngeal Neoplasms and Cancer of Head and Neck, run by Insel Gruppe AG, University Hospital Bern at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Diagnostic accuracy (sensitivity, specificity, accuracy, NPV und PPV) of HR PET/CT in comparison to the histopathological reference standard (time frame: At baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Feb 2019.