Safety and feasibility of wide-area trans-epithelial sampling for detecting residual disease after neoadjuvant chemoradiotherapy for esophageal cancer

In the Netherlands, more than 2500 people develop esophageal cancer every year.
Chemotherapy and radiation followed by surgery is the standard treatment for
patients without metastases. In some of the patients, however, the treatment
with chemotherapy and radiation is so effective that the cancer is no longer
detectable in the tissue that is removed during the operation. Surgery may not
be necessary in these patients. The Dutch SANO study is testing whether an
operation after pre-treatment with chemotherapy and radiation can be postponed
in certain cases or perhaps even completely omitted, without compromising the
chance of cure.

After pre-treatment with chemotherapy and radiation, an endoscopy with biopsies
is now used to assess whether there is still residual tumor in the esophagus,
and whether or not surgery is necessary. If the residual tumor in the esophagus
is small and is not visible to the naked eye, then it may be that these
biopsies erroneously missed the residual tumor. For example, there is a risk
that the result of this test will be incorrect and that an operation will be
incorrectly postponed, while there is still a (small) residual tumor in the
esophagus.

The WATS brush may reduce this risk of a false result. WATS is an acronym for:
Wide-Area Transepithelial Sampling. By using a brush, tissue can be taken from
a larger area (Wide-Area) of the esophagus. In addition, the brush is designed
to also sample tissue in a deeper layer of the esophageal wall
(Transepithelial), which may also detect a small tumor residue that is not
located in the most superficial layer of the esophagus.

The objective of this study is to assess the safety and feasibility of WATS for
esophageal sampling after nCRT in patient with esophageal cancer.

Interventional prospective phase I pilot study.

Two WATS procedures will be performed in addition to the established
bite-on-bite biopsies in patients who are undergoing an EGD in the context of a
clinical response evaluation after nCRT (according to the SANO protocol).
First, ten patients without histological proof of resid-ual disease at the
first and second clinical response evaluations (CRE-1 and CRE-2, resp.) will
undergo WATS at the third clinical response evaluation (CRE-3) which is
performed 24-26 weeks after completion of nCRT. At this time, the majority of
patients does not have post-chemoradiotherapy ulceration or erosions any more,
decreasing the risk of complications. If WATS can be safely performed at CRE-3,
another 10 patients without histological proof of residual disease during CRE-1
will undergo WATS during CRE-2 which is performed 12-14 weeks after completion
of nCRT.

The main risk for participating patients is the risk of complications (e.g.
perforation or excessive bleeding) due to performing WATS in an irradiated
esophagus. Prior studies investigating WATS for Barrett*s esophagus (n=18.596)
and studies investigating normal brush sampling (n=67) and bite-on-bite
biopsies (n=123) for patients who underwent nCRT reported no perforations or
excessive bleeding. The current SANO trial (n>500) reported one excessive
bleeding from a gastric ulcer after endoscopy. This bleeding was related to the
endoscopic procedure in time but not causally related to the the bite-on-bite
biopsies (which were taken at a different location). Therefore, the risk of
the present study is considered low.
On the contrary, by performing additional WATS a larger part of the original
tumor area can be covered which potentially increases the chance of detecting
residual disease and therewith decrease the number of false-negative clinical
response evaluations. Early detection of residual disease will result in more
timely and appropriate surgical resection.