To develop a model that predicts the probability of pathologic complete response to nCRT in esophageal cancer, by integrating diffusion weighted magnetic resonance imaging (DW-MRI) and dynamic contrast enhanced magnetic resonance imaging (DCE-MRI)…
ID
Source
Brief title
Condition
- Malignant and unspecified neoplasms gastrointestinal NEC
- Gastrointestinal neoplasms malignant and unspecified
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
A multiparametric prediction model that predicts the probability of a
pathologic complete response to nCRT in esophageal cancer by integrating DW-MRI
and DCE-MRI in conjunction with 18F-FDG PET-CT scans acquired prior to, during
and after administration of nCRT, as compared to the pathological specimen as
gold standard.
Secondary outcome
• MRI and 18F-FDG PET-CT imaging parameters (including estimated tumor volume,
SUVmean, SUVmax, *SUVmean, *SUVmax, ADC, *ADC and Ktrans values) to assess the
optimal parameters that correlate best with pathological response.
• The presence of residual disease after nCRT according to a radiological
(qualitative) assessment based on T2W-MRI and DW-MRI.
• The estimated post-nCRT T-stage and N-stage, as determined by an expert
radiologist blinded to other imaging results, obtained at the MRI images after
completion of nCRT (MRIpost), will be compared to the pathological TN-stage.
• The diagnostic accuracy of an additional endoscopy and/or endoscopic
ultrasonography (EUS) with biopsies of the primary tumor site, other suspected
lesions and suspected locoregional lymph nodes after completion of nCRT, the
18F-FDG PET/CTpost and the MRIpost, and before surgery (in patients that
provide informed consent for this additional and optional study procedure).
• MRI and 18F-FDG PET-CT imaging parameters (including estimated tumor volume,
SUVmean, SUVmax, *SUVmean, *SUVmax, ADC, *ADC and Ktrans values) to assess
whether these parameters correlate with disease-free and overall survival.
• The presence of, and changes in, ctDNA (circulating tumor DNA) in blood
samples during nCRT as a biomarker for a patients* response to nCRT, the
detection of residual disease after nCRT and disease-free and overall survival
Background summary
For locally advanced esophageal cancer the standard treatment consists of 5
weeks of neoadjuvant chemoradiotherapy (nCRT) followed by surgery. Surgery is
currently performed independent of the response to nCRT and is associated with
substantial morbidity. Prior knowledge of the eventual response to nCRT would
greatly impact on the optimal care for many esophageal cancer patients for two
imperative reasons.
Firstly, it is argued that patients who achieved a pathologic complete response
(pCR, 28-34%) may not have benefitted from surgery. Consequently, proper
identification of pathological complete responders prior to surgery could yield
an organ-preserving regimen avoiding unnecessary toxicity.
Secondly, non-responders are exposed to the side effects of nCRT without
showing any tumor regression. Early identification of the non-responders during
nCRT would be beneficial for this group as ineffective therapy could be
stopped, and for who altered treatment strategies could be explored.
Study objective
To develop a model that predicts the probability of pathologic complete
response to nCRT in esophageal cancer, by integrating diffusion weighted
magnetic resonance imaging (DW-MRI) and dynamic contrast enhanced magnetic
resonance imaging (DCE-MRI) in conjunction with combined 18F-fluorodeoxyglucose
positron emission tomography and computed tomography (18F-FDG PET-CT) scans
acquired prior to, during and after administration of nCRT.
Study design
Multi-center observational study (n=200).
Intervention: In addition to the standard diagnostic work-up for esophageal
cancer that includes a 18F-FDG PET-CT scan at diagnosis and after nCRT, one
18F-FDG PET-CT scans will be performed during nCRT, as well as three MRI scans
(before, during and after nCRT) within fixed time intervals. Furthermore, after
response imaging after nCRT has been performed, but prior to surgery, patients
will undergo (on an opt-out basis) an endoscopy and/or endoscopic
ultrasonography (EUS) with biopsies of the primary tumor site, other suspected
lesions and suspected lymph nodes. Furthermore, blood samples will be collected
at three time points.
Study burden and risks
For study purposes patients will undergo three MRI scans and one 18F-FDG PET-CT
scan, in addition to a pre-nCRT and post-nCRT 18F-FDG PET-CT scan which is
standard of care. During the MRI examinations, an intravenous contrast agent is
administered to the patient. This can lead to mild side effects of headache,
nausea, injection site reaction, disturbed sense of taste and feeling cold. The
use of the contrast agent has a very low risk (<1%) of an allergic reaction to
the contrast medium. The extra 18F-FDG PET-CT exposes the patient to low
radiation dose, which is deemed justified in the study population that receives
41.4 Gy external beam irradiation. Furthermore, on an opt-out basis patients
will undergo an endoscopic assessment after nCRT, which carries a very small
risk of complications, such as esophageal perforation or bleeding (<0.1-1%).
All risks described are considered comparable to the risks associated with
these diagnostic procedures during the initial diagnostic pretreatment work-up.
The additional examinations will be scheduled in combination with standard
diagnostic scans, radiation treatment or standard follow-up appointments. For
the patients included in the study, there is no individual benefit. There are
no risks specifically related to the blood samples that will be collected at
three time points. These will be collected accompanied with regular
venipunctures as much as possible, e.g. with chemotherapy administration or
accompanied with the intravenous cannulas placed for the PET-CT or MRI scans
related to the current study.
Heidelberglaan 100
Utrecht 3584 CX
NL
Heidelberglaan 100
Utrecht 3584 CX
NL
Listed location countries
Age
Inclusion criteria
• Histologically confirmed squamous cell carcinoma or adenocarcinoma of the
esophagus or gastroesophageal junction (i.e. tumors involving both cardia and
esophagus on endoscopy)
• Potentially resectable locally advanced esophageal tumor (cT1b-4a N0-3 M0):
based on standard primary staging by EUS and 18F-FDG PET-CT
• Scheduled to receive neoadjuvant chemoradiotherapy according to the
CROSS-regimen: weekly administration of carboplatin and paclitaxel for 5 weeks
and concurrent radiotherapy (41.4Gy in 23 fractions, 5 days per week) followed
by esophagectomy
• Age > 18 years
• Signed informed consent
Exclusion criteria
• Patients who meet exclusion criteria for MRI
• Patients who meet exclusion criteria for intravenous gadolinium-based
contrast:
o Glomerular Filtration Rate (GFR) of <30 mL/min/1.73m2
o Nephrogenic Systemic Fibrosis (strict contra-indication for gadolinium-based
contrast)
o Known allergy for gadolinium-based contrast
• Patients with a blood plasma glucose concentration >10 mmol/L or poorly
controlled diabetes mellitus
• Irradical endoscopic mucosal resection (EMR) or endoscopic submucosal
dissection (ESD) of primary tumor prior to start of neoadjuvant
chemoradiotherapy
• Pregnant or breast-feeding patients
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 |
|---|---|
| ClinicalTrials.gov | NCT03474341 |
| CCMO | NL62881.041.17 |