Esophageal Cancer Tissue Banking

Prospective databases have contributed substantially to the advancement of clinical medicine
and surgery. Examples of contributions from databases include an improved understanding of
the treatment and outcome for rare pathologies, the long term outcomes, and incidence of
uncommon complications from more common disease, and the repercussions of infrequently
performed complex procedures. (1-3) Problems identified by database review have led to
improvements in patient care and have guided the planning of numerous prospective studies.
The value of these databases incrementally increases with the number of patients enrolled and
with the length of time the databases have been maintained. Recently databases have been used
to create and test nomograms, which are increasingly being implemented to further refine
patient prognosis and to stratify patients for clinical trials. (4) We anticipate that a
prospective database will become more valuable as we look to the future. Increasingly,
molecular markers are identified which are thought to be important to patient outcome or
treatment response. When linked to pathologic tissues, clinical databases can be used as the
initial test of these newly identified markers and to determine which warrant an independent
prospective review. An independent prospective analysis performed for each marker is costly
and time consuming. A prospective database is more comprehensive, accurate, and ultimately
less time consuming than retrospective review for testing each set of markers as novel
questions arise.

This study will augment a prospective database of patients with esophageal cancer who undergo
investigation and /or surgery at Washington University School of Medicine. This database will
be periodically updated from the patient records and the computerized medical record as
patients continue routine follow-up care. These data will be used to address questions
regarding treatment and/or disease-specific outcomes.

In addition, we seek to acquire, store and analyze tissue and blood samples on these
patients. Samples will be processed and stored at the Tissue Procurement Facility of
Washington University School of Medicine. We will be using this material to support ongoing
efforts to identify serum markers with applications for early diagnosis, prognosis or
treatment efficacy. Markers identified will be linked to the clinical outcomes data as
captured in the database. Using the database, we will be able to link patient and treatment
outcomes to analyses performed on previously collected pathologic specimens or research
specimens and correlate these results with the patients' treatment response and outcome in a
time efficient and cost effective way.

The incidence of esophageal adenocarcinoma is on the rise. This has been a trend that has
been noted over the last decade and has gone hand in hand with a decrease in the incidence of
esophageal squamous cell carcinoma. Overall the number of patients with esophageal cancer
being diagnosed annually in the United States is steadily increasing. Esophageal cancer
afflicts approximately 19,000 patients annually in the United States. Broadly speaking,
esophageal cancer can be diagnosed at an early stage where there is no metastatic disease in
distant organs or at a relatively advanced stage when there is evidence of metastatic disease
in distant organs. Unfortunately patients with metastatic disease can receive only palliative
therapy and survival is quite limited. Stage I - III esophageal cancer is often treated
either by primary surgery or by a combination of preoperative or postoperative chemoradiation
therapy along with surgical resection. For stage I esophageal cancer, surgical resection
usually suffices and patients have upwards of 70-80% five year survival. For patients with
stage III esophageal cancer, the patients usually undergo induction chemoradiation therapy
followed by surgical resection. Induction chemoradiation usually involves two cycles of %
Fluorouracil and cisplatin with 5040 Gy of external beam radiation therapy. This aspect of
treatment has been well standardized (5). For stage II esophageal cancer, surgery forms the
backbone of therapy, however, there is no clear consensus among treating physicians about the
efficacy and role of chemoradiation therapy in these patients.

In patients who undergo chemoradiation therapy prior to surgery for esophageal cancer, it is
noted that 15-30% of patients have had a complete pathologic response to therapy. Thus no
tumor is detected in the resected specimen in these patients. Therefore, theoretically, these
patients have undergone an unnecessary resection. There is currently no way to predict which
patients would have had a pathologic response short of resecting the esophagus and thus
exposing the patients to the significant morbidity and mortality associated with this major
operation.

The most significant impact of next-generation sequencing on cancer genomics has been the
ability to re-sequence, analyze and compare the matched tumor and normal genomes of a single
patient. With the significantly reduced cost of sequencing and tremendously enhanced
throughput, it is now within the realm of possibility to sequence multiple patient samples of
a given cancer type. Genomic analyses over the last few years, with significant contributions
from our own Genome Center at the Washington University in St. Louis, (6-7) have led to
significant advances in understanding the behavior of certain tumors including leukemias and
glioblastoma. Specifically, in acute leukemias, our center has shown that certain genotypes
of the tumor predict favorable or unfavorable outcomes in the patients analyzed. These
findings now have been replicated in at least 3 independent studies of separate AML cohorts.
Our goal with this project would be to develop an understanding of the genomic profile of
esophageal carcinomas and changes with treatment. Furthermore with availability of tissue
both before and after chemoradiation therapy, we would be able to identify changes in the
genome of the malignancy with induction therapy. Also with resection specimens we will be
able to identify which patients have had a significant response to therapy (including
complete pathologic response) and others who have not had a significant response to therapy
or have had progressive disease despite therapy. This may help us in identifying genomic
features of the spectrum of esophageal carcinomas that predict response to therapy after
having had the chance to longitudinally study the disease or the clinical course of the
patients. Specifically this would be achieved by obtaining tissue specimens from the
malignancy prior to any therapy at the time of the initial diagnosis or initial endoscopy for
these patients. Subsequently the patients would undergo routine therapy which would be based
upon their clinical stage of disease. Eventually when patients come back for their definitive
resection, we would be able to access the pathologic profile to assess response to induction
therapy and also to study the genomic profile of the tumor tissue after induction therapy.

A prospective database which would be maintained in the Division of Cardiothoracic Surgery
would be able to link clinical outcomes to processed tissues (pathologic specimens, research
specimens and plasma) enabling higher level correlation studies to be performed. Proper use
of such a resource will aid considerably in our ability to advance our field and care for our
future patients with esophageal cancer.

Our eventual aim with the analyses of the genome of esophageal cancer would be to identify a
patient population that has a complete pathologic response to chemoradiation therapy for
carcinomas of the esophagus. We will be able to identify genomic differences, if any, between
such tumors and other tumors where there is only a partial response/no response/progressive
disease with induction chemoradiation therapy. If analyses are sufficiently predictive and
efficiently dichotomize patients into these categories based upon genomic profiles, this can
be the lead groundwork for a clinical trial where patients with certain specific genomic
profiles would be treated only with chemoradiation therapy for carcinomas of the esophagus,
thus precluding unnecessary surgery with its significant attendant morbidity and mortality.
As we already know, about 15-30% of patients undergoing induction chemoradiation therapy
clinically fall into such a category. The well known morbidity of an esophagectomy includes
significant pulmonary problems, anastomotic leaks, cardiovascular problems, chyle leak,
venous thromboses, amongst other major problems. The rate of morbidity after an esophagectomy
varies from 20-40%. Also there is 3-14 % risk of mortality from esophagectomy. (8-9)
Therefore, a tool that can effectively predict which patients do not require an esophagectomy
for treatment of carcinomas of the esophagus would be extremely useful clinically.

Inclusion Criteria:

- Adults with known or suspected esophageal cancer who are willing and able to give
written informed consent for biospecimen collections.

- Age ≥ 18 years

- Must be willing and able to sign an informed consent document

Exclusion Criteria:

- Pediatric patients