Clinical Trial Summary
In patients with esophageal cancer (EC) neo-adjuvant chemoradiation (nCRT) followed by
surgery with curative intent leads to objective responses in 45 to 60%, whereas 20-35% of the
patients had no residual tumor (ypT0N0) at pathologic examination. The absolute survival
benefit of response to nCRT is 15%, but still 14% of the patients develop locoregional
failure in the CROSS trial. 18F-fluorodeoxyglucose positron emission tomography with computed
tomography ((FDG-PET-CT) is able to distinct responders from non-responders, but still misses
significant clinical evidence. Whole-body diffusion-weighted imaging (DWI) magnetic resonance
imaging (MRI) has shown potential benefits, which might be enhanced by combining both
methods. PET/CT and DWI-MRI more precisely correlate anatomic and metabolic FDG-avid lesions
and seem to assess post-treatment changes, especially regarding nodal staging. Both
techniques claim an important role in selection of patients with clinical complete response
(cCR) and indirectly with pathologic complete response (pCR) after nCRT. However, the exact
role and complementary effects of both techniques is still unknown.
For appropriate judgment of response, secure standard endoscopic ultrasonography (EUS) with
fine needle aspiration (FNA) / biopsy of potential suspected lesions, both nodal or residual
tumor, seen on PET/CT or DWI/MRI or during EUS will be performed <2 weeks before surgery,
approximately 6-10 weeks after nCRT and compared with the situation at primary staging.
Patients with clinical complete response (cCR) resembling pathologic response (pCR= ypT0N0)
after nCRT may refrain from surgical resection and related morbidity and mortality. However,
patients without early (2wk after commencement) response during nCRT course may not benefit
from nCRT.
DWI-MRI seems effective in pre-treatment prediction of treatment outcome. Apparent diffusion
coefficient (ADC), which indirectly measures tissue density, can be used to determine the
likelihood of tumor response to treatment. High ADC before treatment has shown to predict an
unfavorable response. Tumors with low ADC values on presentation generally respond better to
treatment. An increased ADC in patients during and after nCRT could be used to predict early
pathologic response i.e. discrimination of "responders and non-responders" to nCRT.
DWI-MRI seems effective in pre-treatment prediction of treatment outcome. Tumor hypoxia
mediates chemoradiation resistance, leading to selection of aggressive tumor cell clones with
the capacity to evade tumor microenvironment by increased anaerobic glycolysis and
angiogenesis. Apparent diffusion coefficient (ADC), which indirectly measures tissue density,
can be used to determine the likelihood of tumor response to treatment. High ADC before
treatment has shown to predict an unfavorable response. Tumors with low ADC values on
presentation generally respond better to treatment. An increased ADC in patients during and
after nCRT could be used to predict early pathologic response i.e. discrimination of
"responders and non-responders" to nCRT.
