NAVIGATORR study
Overview
- Patients aged 18 and over with certain head and neck tumours in the midface, upper jaw or skull base are eligible to participate in the NAVIGATORR study.
- The prerequisite is that the tumour can be removed through surgery and that radiation therapy is planned afterwards.
- The main objective of the NAVIGATORR study is to use a new technique to remove head and neck tumours so precisely that the margins are tumour-free. The data obtained during the operation will also help to plan the subsequent radiotherapy more individually for each patient.
Study status: The study is currently accepting patients (recruitment open).
To cure head and neck tumours at an early stage, the tumour must be completely removed. Experts refer to such a result after surgery as an R0 resection.
To reduce the risk of recurrence, radiation therapy may sometimes be necessary after surgery. Until now, radiation therapists have planned the radiation field and dose based on written surgical and pathology reports. However, this does not allow them to locate the former tumour area and any remaining tumour tissue precisely. To account for the lack of precision, the radiation field is planned to be larger than potentially necessary, and patients receive a higher radiation dose.
This is what researchers hope to achieve with the NAVIGATORR study: To make surgery for head and neck tumours even more precise with the help of a new technique. This allows surgeons to preserve as much healthy tissue as possible and reduce long-term effects or late effects in the head and neck area. This technique also provides information during surgery that enables radiation therapists to create a therapy plan with greater precision.
- You can read more about the goals the scientists are pursuing with the NAVIGATORR study in the section What is the goal of the NAVIGATORR study?
Patients with various head and neck tumours in the midface, upper jaw or skull base can participate in the NAVIGATORR study. These include:
- a specific form of oral cancer known as oral squamous cell carcinoma (OSCC)
- rarer malignant salivary gland tumours such as adenoid cystic carcinoma (ACC), mucoepidermoid carcinoma (MEC) or adenocarcinoma of the salivary gland (AC)
For further eligibility requirements, please refer to the section Who is the study suitable for?.
What is the aim of the NAVIGATORR study?
NAVIGATORR is the abbreviation for the English study title "Multiparametric imaging-based intraoperative navigation for guidance of surgical resection and postoperative radiotherapy in patients with head-and-neck tumours". It describes the surgery and subsequent radiation of head and neck tumours using a new image-guided navigation technique.
Objectives of the NAVIGATORR study
The scientists want to achieve various objectives with the NAVIGATORR study:
- Improve surgical outcomes – Head and neck tumours should be removed more precisely than before using image-guided navigation technology, i.e. without leaving any cancer cells behind. This reduces the risk of recurrence.
- More individualised radiation planning after surgery – Important information can be obtained during surgery using the new technology. This makes it possible to plan subsequent radiation therapy more individually for each patient. As a result, areas with remaining cancer cells can be irradiated more precisely and healthy and sensitive tissue can be better preserved.
- Investigating cell changes after radiation therapy – In the NAVIGATORR study, researchers also want to investigate how healthy body cells change after radiation therapy. To do this, they are conducting various genetic tests on healthy mucosal tissue. This knowledge can help to better understand the side effects of radiation therapy for head and neck tumours and to develop new treatments to counteract them.
- Developing a new follow-up care concept – Researchers want to find out whether additional novel tests, for example on blood samples, can help to better monitor the success of the therapy. The aim is to detect a relapse of the disease earlier than with previous methods and thus enable treatment with the renewed goal of a cure.
Who is the study suitable for?
Patients can participate in the NAVIGATORR study if ALL of the following criteria are met:
- The tumour is located in the midface, upper jaw or skull base: this includes so-called oral squamous cell carcinomas and rarer thyroid tumours (adenocarcinomas, mucoepidermoid carcinomas or adenoid cystic carcinomas).
- The participant is 18 years of age or older.
- The person affected occasionally needs outside help but is largely independent in everyday life. Experts assess this degree of physical impairment using the Karnofsky Performance Status of at least 60% or more.
- Following a multidisciplinary tumour board meeting, the team of doctors recommends surgery to remove the tumour. It is also likely that the surgery will be followed by radiation therapy.
- Women of childbearing age use a reliable method of contraception.
- All participants have been informed about the NAVIGATORR study, understand the content and individual consequences of participation, and have agreed in writing to take part.
Participation in the NAVIGATORR study is not possible if any of the following points apply:
- The patient does not meet the above requirements for the study.
- A patient is pregnant or breastfeeding.
- The patient is already participating in another clinical study.
The NAVIGATORR study is a prospective, multicentre, single-arm feasibility study.
- In a feasibility study, researchers can investigate a treatment method on a smaller group of patients. The NAVIGATORR study aims to further develop the surgical removal of the tumour and subsequent radiation treatment using a new image-guided navigation technique.
- Prospective means that this treatment method is carried out over a specific period of time according to a defined procedure. Researchers then use the collected data to evaluate how effective this new treatment method is compared to the current standard treatment and what consequences and side effects are associated with it.
- In a single-arm study, all participants receive the same treatment.
- Multicentre means that patients can participate in the study at several study centres in Germany.
If there are no obstacles to study participation after the initial examination, the study doctors will explain in detail how the NAVIGATORR study works. Anyone who wishes to participate in the study must then submit a written declaration of consent. Patients can also indicate whether they would like to be informed about any additional hereditary disease risks that may be found.
Once consent has been given, the first examinations as part of the NAVIGATORR study will be carried out. These include, for example, imaging examinations (computed tomography (CT), multiparametric magnetic resonance imaging (mpMRI), and blood tests. The images from these examinations enable the study doctors to plan the operation carefully in advance.
(2) Surgery
A surgeon removes the tumour using an image-guided navigation system, which contains the previously recorded CT and MRI images. This allows surgeons to know with 1 millimetre precision how far they have already removed the tumour.
With the new technology, surgeons can also create tumour resection maps during the operation. These maps mark the exact locations of the tissue samples that they take from the edges of the operation site after removing the tumour.
These digital markings help pathologists who examine the tissue samples for cancer cells and the doctors who plan the radiation treatment following the operation.
(4) Radiation
Based on the data obtained during and after the operation, radiation therapists can carefully plan the subsequent radiation therapy for each individual patient. Through the gathered data they can differentiate between where cancer cells have been found and where they have not. The radiation dose can be adjusted to target any remaining cancer cells more precisely allowing for the best possible preservation of healthy, sensitive tissue.
During the radiation period, there are weekly check-ups as part of the study. These include:
- a physical examination.
- a blood sample.
- an additional blood sample which is taken every two weeks. However, this does not require an extra blood draw as a larger amount of blood is simply taken at once.
A check-up is also scheduled on the last day of radiation therapy.
(5) Follow-up: What happens after the end of treatment
Patients must go to the respective study centre for follow-up examinations. These begin 6 to 8 weeks after the end of radiation therapy and then take place every 3 months. Follow-up care as part of the NAVIGATORR study lasts a total of 2 years.
Standard follow-up care includes:
- a consultation with the doctor, followed by a physical examination.
- an MRI scan of the head/neck area with contrast medium.
- an annual CT scan of the chest/abdominal area.
The follow-up care concept within the NAVIGATORR study also includes:
- additional blood tests.
- 2 questionnaires: Here, patients can provide information about their symptoms and answer questions about their quality of life.
- tissue samples (biopsy): In the Department of Oral and Maxillofacial Surgery at the respective study site, samples of the mucous membrane in the radiation field are taken. The first sample is taken 6 to 8 weeks after the last radiation treatment, the second after 6 months, and the last after 24 months.
These are the possible advantages of participating in the NAVIGATORR study:
- There is a higher chance of safely removing the tumour and performing the subsequent radiotherapy in a more targeted and therefore favourable manner than before. This can reduce long-term and late effects [Glossary] associated with the treatment.
- The medical team monitors the tumour particularly closely with additional, innovative tests on blood samples. This could enable a relapse to be detected earlier than is currently possible.
- In some participants, so-called hereditary changes are found that increase the risk of further cancers. This allows participants and their relatives to seek genetic counselling and possibly take preventive measures.
However, there may also be disadvantages to participating in the NAVIGATORR study:
- The study requires repeated blood draws. Rare risks associated with taking blood include bruising, nerve damage due to a misplaced needle or inflammation at the puncture site.
- After radiation therapy, the researchers take samples from the healthy mucosa during follow-up care. These are usually tissue samples measuring a few millimetres in size, which are removed under local anaesthesia. Possible risks include an allergic reaction to the local anaesthesia, as well as pain and bleeding at the site where the sample was taken. The mucosa usually heals within 7 days.
- Genetic testing can reveal hereditary changes that indicate a higher risk for certain diseases. This risk may also affect family members. However, participants can also decide not to be notified of such results.
- Despite comprehensive data protection and high data security, there is a small residual risk that genetic data could be traced back to the individual if this data falls into the wrong hands.
What costs will participants incur?
Participation in the study is free of charge for patients. However, they will not receive any expense allowance. Travel costs will not be reimbursed as part of the study.
If you have any questions about the financing of the study, please ask the study team, for example, during the informed consent process.
First it is advisable to discuss with your own oncologist whether you are eligible to participate in the study. Your attending physicians are most familiar with your medical condition and can also assess whether you meet the medical criteria for participation.
If the attending physician recommends participation, they will register the patient at one of the participating study centres for a so-called multidisciplinary tumour board. There, doctors from various specialties discuss whether surgery and subsequent radiation therapy are a treatment option for the patient in question.
With the recommendation from the tumour board, the attending physicians can register the patient at the study centre closest to – the patient can also register there themselves. Upon registration, patients receive an appointment at the study centre. Patients should bring all previous findings with them to this appointment.
Further information is available from the study centres.
Scientific publications (selection)
Bittermann G, Wiedenmann N, Voss P, Zimmerer R, Duttenhoefer F, Metzger MC. Marking of tumour resection borders for improved radiation planning facilitates reduction of radiation dose to free flap reconstruction in head and neck cancer surgery. J Craniomaxillofac Surg. 2015 May;43(4):567-73. doi: 10.1016/j.jcms.2015.02.021.
Hinni ML, Ferlito A, Brandwein-Gensler MS, Takes RP, Silver CE, Westra WH, Seethala RR, Rodrigo JP, Corry J, Bradford CR Surgical margins in head and neck cancer: a contemporary review of the . Head Neck. 2013 Sep;35(9):1362-70. doi: 10.1002/hed.23110.
Loree TR, Strong EW. Significance of positive margins in oral cavity squamous carcinoma. Am J Surg. 1990 Oct;160(4):410-4. doi: 10.1016/s0002-9610(05)80555-0.
Feichtinger M, Pau M, Zemann W, Aigner RM, Kärcher H. Intraoperative control of resection margins in advanced head and neck cancer using a 3D-navigation system based on PET/CT image fusion. J Craniomaxillofac Surg. 2010 Dec;38(8):589-94. doi: 10.1016/j.jcms.2010.02.004.
Woolgar JA, Triantafyllou A. A histopathological appraisal of surgical margins in oral and oropharyngeal cancer resection specimens. Oral Oncol. 2005 Nov;41(10):1034-43. doi: 10.1016/j.oraloncology.2005.06.008.
This study description was prepared by authors from the Cancer Information Service, under the direction of Dr. S. Weg-Remers, based on the study documentation.