The aim of the proposed study is to investigate the accuracy of a liquid biopsy test using ddPCR for HPV DNA in a standardized follow-up setting for the detection of residual disease and/or (early) tumor recurrence in HPV-related oropharyngeal…
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Source
Brief title
Condition
- Other condition
Synonym
Health condition
Hoofd-hals oncologie
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
of HPV DNA detection in blood plasma compared to standard clinical follow-up
(including physical examination, usually with imaging) at 3-4 months
post-treatment for the identification of residual tumor and/or tumor
recurrences.
Secondary outcome
As a secondary parameter, we will evaluate the accuracy of multiple liquid
biopsies over a 2-year follow-up period and assess the correlation between
plasma HPV DNA levels and the development of tumor recurrences over time. In
addition, we will determine the most accurate timing and frequency of blood
collection moments in terms of recurrence prediction. Moreover, we will assess
cost-effectiveness of liquid biopsies as a follow-up strategy. Patient
characteristics that could correlate to HPV DNA plasma levels and may be a
confounder for study results will also be collected, including; plasma HPV DNA
levels at baseline (before treatment), gender, age, comorbidities, smoking
status, alcohol consumption, HPV type, physical status, viral load, and
clinical and pathological tumor characteristics.
Background summary
The incidence of human papillomavirus (HPV)-related head and neck cancer is
increasing worldwide and is expected to rise in coming decades. Typically, this
tumor type is located in the oropharynx. In the Netherlands, the portion of
HPV-related oropharyngeal tumors increased from 5% in 1990 to up to 50% in
recent years. After treatment with (chemo)radiotherapy, follow- up visits are
scheduled to detect possible recurrences in an early stage. Although
HPV-related oropharyngeal cancer generally has a good prognosis, 10-20% of
patients will develop recurrent tumors, mainly within the first 2 years after
treatment. Despite this variation in risk of recurrence and treatment-related
side effects, the current follow-up in The Netherlands is organized according
to a *one-size-fits-all* protocol, consisting of 17 hospital visits, including
physical examination, within the first 5 years. In most centres, response
evaluation is performed using MRI or PET-CT three to four months after the end
of treatment. Recent Dutch studies show that this follow-up shows a 67%
sensitivity and a positive predictive value of 20%, meaning that not all
recurrences are identified and only 1 in 5 suspected recurrences turn out to be
a true relapse. Therefore, this strategy does not seem to be cost-effective,
nor does it fit with the understandings of good quality of care, in which
personal care, adapted to individual needs, preferences, and values is highly
important. Liquid biopsies have emerged as an innovative and promising
diagnostic approach for the surveillance of oncological patients. For
HPV-related oropharyngeal cancer, circulating HPV DNA has shown to be a very
accurate biomarker for residual tumor and (early) recurrences. We expect that
liquid biopsy-based testing will enable earlier and more accurate detection of
recurrent tumors, resulting in improved survival and increased quality of life
for patients.
Study objective
The aim of the proposed study is to investigate the accuracy of a liquid biopsy
test using ddPCR for HPV DNA in a standardized follow-up setting for the
detection of residual disease and/or (early) tumor recurrence in HPV-related
oropharyngeal cancer patients. The accuracy of our liquid biopsy test will be
compared to the current standard follow-up, consisting of hospital visits and
physical examinations. Validation of our liquid biopsy test, using standardized
blood collection moments, is an essential step towards implementation in
clinical practice.
Study design
We propose to conduct a prospective, multicenter study, including patients that
are treated for HPV-related oropharyngeal cancer one of the participating NWHHT
centers. A single-arm study design is chosen, directly comparing the accuracy
of the liquid biopsy test to standard follow-up. Blood samples will be
collected once before start of treatment and at every routine follow-up visit
(every 2-3 months) for the first 2 years after the end of treatment. This
follow-up period is chosen because the vast majority of recurrences present
during the first 2 years after the end of treatment. Blood samples from
inclusion centers will be shipped to the UMCU and MUMC+, where DNA will be
isolated from blood plasma and HPV DNA will be detected using digital droplet
PCR (ddPCR). This is a very sensitive method, which is able to quantify the
presence of HPV DNA, and is already applied for diagnostic purposes in
molecular diagnostics, validated under ISO15189 standards.
Study burden and risks
In the context of this study, participants will undergo a total of 11 blood
collection moments; once before treatment and 10 times during a 2-year
follow-up period after the end of treatment. These blood collection moments are
timed with hospital visits for standard follow-up, so extra hospital visits are
not necessary. Per blood sampling, 30 ml peripheral blood will be drawn
following standard procedures. Participation will have minimal risks for
patients. The withdrawal of venous blood (30 ml) is a regular diagnostic
procedure and will be performed by qualified and experienced doctors and/or
nurses in compliance with the safety guidelines of both hospitals. Blood
collection could causing local pain and bruising. However, this is mostly
harmless and recovers within a few days. Therefore, participation in this study
will lead to minimal time investment without important risks for the health of
the subjects.
Heidelberglaan 100
Utrecht 3584CX
NL
Heidelberglaan 100
Utrecht 3584CX
NL
Listed location countries
Age
Inclusion criteria
In order to be eligible to participate in this study, a subject must meet all
of the following criteria:
- Any age 18 years or older;
- Confirmed diagnosis of HPV-positive squamous cell carcinoma in the oropharynx
(positive for p16 and/or HPV DNA);
- Undergoing curative treatment and follow-up in one of the participating
centers;
- Being able to provide written informed consent;
Exclusion criteria
A potential subject who meets any of the following criteria will be excluded
from participation in this study:
- The presence of distant metastases at diagnosis, except for regional
(cervical) lymph node metastases;
- Any other known HPV-related malignancies (e.g. uterine cervix, anal, penile
carcinomas);
- Unable to provide written informed consent;
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL83769.041.23 |